Thymoma Database IV
Publication Date from 2004/01/01 to 2004/12/31
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Items 1 - 193 of 193
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1: Cell Signal. 2005 Aug;17(8):961-73. Epub 2004 Dec 24. Related Articles, Links
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CD44v6 promotes proliferation by persisting activation of MAP kinases.

Marhaba R, Bourouba M, Zoller M.

Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg.

CD44v6 is transiently expressed during T cell activation, and constitutively CD44v4-v7 expressing transgenic T cells show accelerated responses towards nominal antigens. The underlying mechanism is unknown. The mouse thymoma EL4 was transfected with CD44 standard isoform (CD44s) or CD44v6 cDNA (EL4-s, EL4-v6). Only EL4-v6 cells proliferated at an over 10-fold higher rate than untransfected cells, displayed up-regulated expression of CD69, CD25, and IL-2, and were protected from apoptosis by CD44v6 cross-linking. In the absence of any stimulus, ERK1/2 was partly phosphorylated, and phosphorylation was significantly increased by CD44v6 cross-linking. The same accounted for JNK, c-jun, and IkappaBalpha. Moreover, NF-kappaB was partly translocated into the nucleus. Instead, CD44s cross-linking induced ERK1/2, JNK, c-jun, and IkappaBalpha phosphorylation only in the context of TCR engagement. No selectively CD44v6 associated transmembrane proteins were uncovered in EL4 cells. However, CD44v6, as opposed to CD44s, did not colocalise with the TCR/CD3 complex after CD3 cross-linking. Furthermore, a CD44-associated 85-kDa protein became hypophosphorylated only after CD44v6 cross-linking. Threonine hypophosphorylation of this protein coincided with the activation of MAP and SAP kinases, which was prohibited in the presence of a phosphatase inhibitor. Thus, CD44v6, distinct to CD44s, stimulates autonomously growth and IL-2 secretion of a thymoma line and rescues cells from apoptosis.

PMID: 15894169 [PubMed - indexed for MEDLINE]
2: Autoimmun Rev. 2005 Jun;4(5):264-9. Epub 2004 Nov 13. Related Articles, Links
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Intravenous immunoglobulins in autoimmune- or parvovirus B19-mediated pure red-cell aplasia.

Mouthon L, Guillevin L, Tellier Z.

Department of Internal Medicine, Hopital Cochin, Assistance Publique-Hopitaux de Paris and Universite Paris V, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France. luc.mouthon@cch.ap-hop-paris.fr

Pure red-cell aplasia (PRCA) is defined as the absence of mature erythroid precursors in a bone marrow that otherwise exhibit normal cellularity. Acquired PRCA may occur in association with neoplasms (such as lymphoproliferative disorders), thymoma, autoimmune disorders, pregnancy, or as a consequence of chronic human parvovirus B19 (B19) infection in an immunologically incompetent host. PRCA may also develop after exposure to drugs (erythropoietin or tacrolimus). PRCA of autoimmune origin was first treated successfully with intravenous immunoglobulins (IVIg) more than 20 years ago. Since then, B19-associated PRCA in solid-organ transplant recipients and in human immunodeficiency virus (HIV)-infected patients has also been successfully treated with IVIg. Routine maintenance therapy is probably not indicated in HIV-infected patients with CD4+ counts above 300/microL, whereas repeated infusions might be necessary if CD4+ count is below 80.

Publication Types:
PMID: 15990072 [PubMed - indexed for MEDLINE]
3: Biol Reprod. 2005 Feb;72(2):384-92. Epub 2004 Sep 22. Related Articles, Links
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Changes in intracellular distribution and activity of protein phosphatase PP1gamma2 and its regulating proteins in spermatozoa lacking AKAP4.

Huang Z, Somanath PR, Chakrabarti R, Eddy EM, Vijayaraghavan S.

Department of Biological Sciences, Kent State University, Kent, Ohio 44242, USA. zhuang1@kent.edu

The second messenger cAMP mediates its intracellular effects in spermatozoa through cAMP-dependent kinase (PKA, formally known as PRKACA). The intracellular organization of PKA in spermatozoa is controlled through its association with A-kinase-anchoring proteins (AKAPs). AKAP4 (A kinase [PRKA] anchor protein 4; also called fibrous sheath component 1 or AKAP 82) is sperm specific and the major fibrous sheath protein of the principal piece of the sperm flagellum. Presumably, AKAP4 recruits PKA to the fibrous sheath and facilitates local phosphorylation to regulate flagellar function. It is also proposed to act as a scaffolding protein for signaling proteins and proteins involved in metabolism. Akap4 gene knockout mice are infertile due to the lack of sperm motility. The fibrous sheath is disrupted in spermatozoa from mutant mice. In this article, we used Akap4 gene knockout mice to study the effect of fibrous sheath disruption on the presence, subcellular distribution, and/or activity changes of PKA catalytic and regulatory subunits, sperm flagellum proteins PP1gamma2 (protein phosphatase 1, catalytic subunit, gamma isoform, formally known as PPP1CC), GSK-3 (glycogen synthase kinase-3), SP17 (sperm autoantigenic protein 17, formally known as SPA17), and other signaling proteins. There were no changes in the presence and subcellular distribution for PP1gamma2, GSK-3, hsp90 (heat shock protein 1, alpha, formally known as HSPCA), sds22 (protein phosphatase 1, regulatory [inhibitor] subunit 7, formally known as PPP1R7), 14-3-3 protein (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein), and PKB (thymoma viral proto-oncogene, also known as AKT) in mutant mice. However, the subcellular distributions for PKA catalytic subunit and regulatory subunits, PI 3-kinase (phosphatidylinositol 3-kinase), and SP17 were disrupted in mutant mice. Furthermore, there was a significant change in the activity and phosphorylation of PP1gamma2 in mutant compared with wild-type spermatozoa. These studies have identified potentially significant new roles for the fibrous sheath in regulating the activity and function of key signaling enzymes.

PMID: 15385410 [PubMed - indexed for MEDLINE]
4: Virchows Arch. 2005 Feb;446(2):185-8. Epub 2004 Dec 11. Related Articles, Links
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Pericardial ectopic thymoma.

Azoulay S, Adem C, Gatineau M, Finet JF, Bakdach H, Regnard JF, Capron F.

Service d'Anatomie pathologique, Groupe Hospitalier de la Pitie-salpetriere, 47-83 Bd de l'Hopital, 75013 , Paris, France.

Primary intrapericardial thymoma is an unusual localization. We report a case of a patient with an isolated and primary pericardial thymoma. This 72-year-old woman presented with dyspnea, dysphony and myalgia. The radiological evaluation revealed an intrapericardial mass. Surgical exploration showed a hemorrhagic and infiltrative tumor in the pericardial sac, while the mediastinum was free of tumor. Surgical biopsies and, later, an ablation of pericardial mass were done. The tumor was a thymoma, composed of large epithelial cells and immature T lymphocytes and was classified B2 according to the World Health Organization classification (1999). Clinically, a myasthenia gravis was revealed. We discuss the few cases reported in the literature.

Publication Types:
PMID: 15735980 [PubMed - indexed for MEDLINE]
5: Ann Neurol. 2004 Dec;56(6):901-4. Related Articles, Links
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Selective loss of regulatory T cells in thymomas.

Strobel P, Rosenwald A, Beyersdorf N, Kerkau T, Elert O, Murumagi A, Sillanpaa N, Peterson P, Hummel V, Rieckmann P, Burek C, Schalke B, Nix W, Kiefer R, Muller-Hermelink HK, Marx A.

Institute of Pathology, University of Wurzburg, Wurzburg, Germany. philipp.stroebel@mail.uni-wuerzberg.de

Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We investigated the generation of T cells with a regulatory phenotype (T(R)) in thymomas with and without associated MG. In patients with MG(+) thymomas, maturation and export of T(R) cells but not of other T-cell subsets was significantly reduced. We conclude that imbalance between effector and regulatory T cells in thymomas may be involved in modulation of onset and/or severity of MG.

PMID: 15562414 [PubMed - indexed for MEDLINE]
6: Ann Thorac Cardiovasc Surg. 2004 Dec;10(6):321-3. Related Articles, Links
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Thymoma.

Sumiyama Y, Yoshida Y.

Publication Types:
PMID: 15658902 [PubMed - in process]
7: Ann Thorac Surg. 2004 Dec;78(6):2207; author reply 2207-8. Related Articles, Links
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Comment on:
Time to move beyond retrospective analyses for thymic neoplasms and conduct a prospective multi-institutional clinical trial.

Thomas CR Jr.

Publication Types:
PMID: 15561080 [PubMed - indexed for MEDLINE]
8: Bull Cancer. 2004 Dec;91(12):928-40. Related Articles, Links
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[Expression of the p56lck by colon tumors: a marker of their invasive capacity?]

[Article in French]

Rouer E.

Inserm U536, 17 rue du Fer-a-Moulin, 75005 Paris. Evelyne.Rouer@fer-a-moulin.inserm.fr

Since its discovery in murine thymoma in 1982, the p56lck (lymphocyte cellular kinase) has been shown to be a pivotal enzyme to both maturation of thymocytes and activation and proliferation of peripheral lymphocytes. The p56lck sequence appeared highly homologous to that of the oncogene p60c-src as did its exon-intron organisation. These data have suggested the lck gene originates from the ancestral src gene by the exon-shuffling mechanism. However, and in spite of this relationship with the p60src oncogene which is often implicated in human cancers, p56lck does not appear involved in lymphoproliferative diseases, either by overexpression or activating mutations. Nevertheless, its aberrant expression has been reported in some carcinomas (colon, lung and mammary). This unexpected expression of a lymphoid-specific protein in solid tumors remained enigmatic until recent studies. In this review, we report these data and explain the possible mechanisms which could lead to the p56lck ectopic expression. We also discuss of signalling pathways which could be affected by the abnormal presence of the p56lck in these tumoral epithelial cells. In particular, we indicate that p56lck could favor metastases by facilitating loss of cell adhesion.

Publication Types:
PMID: 15634634 [PubMed - indexed for MEDLINE]
9: Chemotherapy. 2004 Dec;50(6):279-82. Epub 2004 Dec 8. Related Articles, Links
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Efficacy of docetaxel as a second-line chemotherapy for thymic carcinoma.

Oguri T, Achiwa H, Kato D, Maeda H, Niimi T, Sato S, Ueda R.

Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Thymic carcinoma is a rare and aggressive tumor, and the efficacy of second-line chemotherapy is still unclear. Here, we reported a case of thymic carcinoma that responded well to the administration of docetaxel alone as a second-line chemotherapy. A 64-year-old woman was diagnosed with thymic carcinoma (squamous cell type) with bone metastasis, and she, therefore, received nedaplatin combined with etoposide and ifosfamide. She responded partially, after which she received irradiation for bone metastasis. Two months after chemotherapy, the thymic carcinoma exhibited gradual regrowth and she experienced shoulder pain. We treated this with docetaxel alone (60 mg/m2 every 4 weeks). After three courses of docetaxel, we observed a partial response and her shoulder pain disappeared. This case demonstrated that docetaxel is effective as a second-line chemotherapy for thymic carcinoma. 2004 S. Karger AG, Basel.

Publication Types:
PMID: 15608443 [PubMed - indexed for MEDLINE]
10: Clin Infect Dis. 2004 Dec 1;39(11):1740-1. Related Articles, Links
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Fatal pneumocystis pneumonia with good syndrome and pure red cell aplasia.

Jian L, Bin D, Haiyun W.

Publication Types:
PMID: 15578389 [PubMed - indexed for MEDLINE]
11: J Cardiovasc Surg (Torino). 2004 Dec;45(6):585-7. Related Articles, Links

Synchronous independent bifocal orthotopic thymomas. A case report.

Nonami Y, Moriki T.

Department of Surgery II, Kochi Medical School, Kohasu Nankoku, Kochi 783-8505, Japan. nonamiy@med.kochi-ms.ac.jp

A case of synchronous multiple thymomas is reported. The patient was an 81-year-old woman with 2 separate thymomas in the anterior mediastinum. A histological study revealed that both thymomas consisted of dense lymphocyte infiltration in the stroma and a small number of polygonal epithelial tumor cells with clear nuclei and distinct nucleoli. Immunohistochemical staining using the antibodies to 2 antigens, bcl-2, and MIB-1 showed identical staining patterns. In spite of these findings, we considered their origin to be synchronous multicentric development rather than intra-thymic metastasis, based on the non-invasive nature of these tumors.

Publication Types:
PMID: 15746641 [PubMed - indexed for MEDLINE]
12: J Small Anim Pract. 2004 Dec;45(12):589, 626-8. Related Articles, Links

What is your diagnosis? Thymoma.

Mellanby RJ, Mellor PJ, Herrtage ME.

Queen's Veterinary School Hospital, University of Cambridge, Madingley Road, Cambridge.

Publication Types:
PMID: 15600268 [PubMed - indexed for MEDLINE]
13: Kyobu Geka. 2004 Dec;57(13):1229-32. Related Articles, Links

[A constrictive pericarditis on oral steroid and immunosuppressant treated with bilateral anterolateral thoracotomy; report of a case]

[Article in Japanese]

Suzuki E, Kotoh K, Fukahara K, Doi T, Misaki T.

Department of Surgery I, Toyama Medical and Pharmaceutical University, Toyama, Japan.

A successful case of pericardiectomy without median sternotomy for an immunosuppressive 59-year-old man with constrictive pericarditis (CP) was reported. He had a history of invasive thymoma, myasthenia gravis and pure red cell aplasia, and he was on oral steroid and immunosuppressant. Pericardiectomy was performed by the approach of bilateral anterolateral thoracotomy to avoid troubles due to median sternotomy under immunosuppression, and there was no postoperative infection such as mediastinitis. Bilateral anterolateral thoracotomy was considered to be useful for immunosuppressive cases.

Publication Types:
PMID: 15609663 [PubMed - indexed for MEDLINE]
14: Magy Seb. 2004 Dec;57(6):311-9. Related Articles, Links

[Surgery of the thymus]

[Article in Hungarian]

Kas J, Besznyak I, Kocsis A, Major L, Saortay S, Svastics E.

Budai MAV Korhaz, Sebeszet, Budapest. kasaczel@axelero.hu

On the occasion of the 50th anniversary of Gyula Sebesteny's death, an overview was prepared on the surgery of the thymic gland that was closely connected to his thoracic surgical activity. His results with thymectomy in myasthenia gravis were published as the second study on this topic in Europe and the first in Hungary. The early thymic surgery was based on pathological observations. Myasthenia gravis, a well-known disease for long, occurred frequently with pathological lesions of the thymus. Autopsies suggested potential causative relationship. The early period of thymic surgery was characterised by sporadic interventions and high mortality. The new period of the thymic surgery started with the American Blalock's 20 operations, and accomplished by the operative activity of Keynes including 281 thymectomies. They were followed by many European, American and Asian surgeons. Even today, there are many hotly debated topics, like indication and type of operation, prognostic factors, perioperative care, diagnosis, treatment and pathology of the thymic tumor. With fine-tuning the indication, the development of operation techniques, neurology, anaesthesiology and intensive care, imaging techniques and oncology and with introduction of new drugs the early and late results are improving. Thanks to Dr. Sebesteny, Hungarian thoracic surgeons joined early the international thoracic surgical activities. Currently in Hungary there are two major centers for myasthenia gravis surgery, and all important thoracic surgical departments in the country treat thymic tumor cases.

Publication Types:
PMID: 15803873 [PubMed - indexed for MEDLINE]
15: Neurol India. 2004 Dec;52(4):453-6. Related Articles, Links
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Myasthenic crisis: a retrospective study.

Panda S, Goyal V, Behari M, Singh S, Srivastava T.

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.

BACKGROUND AND OBJECTIVE: Myasthenic crisis (MC) is one of the important and common complications in the natural history of myasthenia gravis (MG). MC can be precipitated by multiple factors including deficiency or excess of the acetylcholinesterase inhibitors (AChEI). Any episode of MC is an emergency requiring aggressive therapy. We studied the demographic, clinical and treatment-related characteristics of patients who developed MC. MATERIALS AND METHODS: A retrospective study was conducted in patients with MC admitted during a 31-month period from February 1999 to August 2001, at a tertiary care center in India. RESULTS: Eleven patients (9.69% of the total 114 patients with MG) were admitted with 12 episodes of MC. Mean age at presentation was 39.83 + 13.18 years with male predominance. Seven patients had undergone thymectomy previously; of which 2 had postoperative MC. Six patients had thymoma. Steroid or cholinesterase inhibitor withdrawal and infections were the commonest precipitating factors for MC. Patients required ventilatory support for median 14 days. They responded to low volume of plasma exchange (PE) (mean 854 ml / day with mean 6.5 cycles per patient). CONCLUSIONS: This report highlights that the subset of Indian patients with MG who are at risk to develop MC belong to the 3rd and 4th decade, have bulbar symptoms at presentation and are associated with thymoma. Patients with MC should have judicious drug adjustments under supervision and should be treated aggressively during impending MC.

PMID: 15626832 [PubMed - indexed for MEDLINE]
16: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 Dec;21(6):574-8. Related Articles, Links

[Studies on the genetic pathogenesis of myasthenia gravis caused by CTLA-4 gene polymorphism.]

[Article in Chinese]

Mao HT, Wang XB, Zhang L, Gu HT.

Institute of Basic Medical Research, Shandong Academy of Medical Sciences, Jinan, Shandong, 250062 P. R. China.

OBJECTIVE: To study the genetic pathogenesis of myasthenia gravis (MG) caused by cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms and regulation function of transcription factor. METHODS: ELISA assay was used to determine the expression level of serum sCTLA-4 in MG. Four single nucleotide polymorphisms (SNPs) of CTLA-4 at exon 1 +49, promoter -318, -1661, -1772 were analyzed by restriction fragment length polymorphism (RFLP). Transcription factor nuclear factor 1(NF-1) and c/EBPbeta binding site were confirmed by chromatin immunoprecipitation(CHIP) assay. RESULTS: It was found that the frequencies of the GG+49 genotype and G+49 allele are higher in MG patients with thymoma than those in patients of thymic hyperplasia and normal thymus subgroups. T/C-318 is not correlated with MG. The frequency of CT-1772 genotype is significantly higher in MG patients, especially in MG patients with thymoma, when compared with that in healthy controls. Meanwhile, the frequency of the G-1661 allele and GG-1661 genotype is lower in MG patients. Linkage disequilibrium (LD) between each SNPs in promoter -1772, -1661, -318 and coding sequence 1 (CDS 1) +49 is apparent. sCTLA-4 levels in patients' sera are correlated with the haplotype and genotype. T/C-1772 and A/G-1661 SNPs change the sequence of transcription factor NF-1 and c/EBPbeta binding sites. DNA variants lose site-specific binding activity of transcription factor regulated by lectin ConA and PHA. CONCLUSION: There are strong positive linkages among four SNPs. C/T-1772 and A/G-1661 polymorphisms can result in inefficient transcription of CTLA-4 gene. T>C-1772 mutation also affects gene splicing. These SNPs may constitute a factor of susceptibility to disease.

PMID: 15583985 [PubMed - indexed for MEDLINE]
17: Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1113-9. Related Articles, Links
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Comment in:
Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.

Zhu G, He S, Fu X, Jiang G, Liu T.

Department of Radiation Oncology, Cancer Hospital of Fudan University, Shanghai, China.

PURPOSE: To assess the factors that predict local control and survival in patients with thymoma treated with adjuvant radiotherapy (RT) and suggest strategies for optimizing adjuvant RT. METHODS AND MATERIALS: The study population comprised 47 patients with noninvasive thymoma and 128 patients with invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169 patients; 25 patients also received adjuvant chemotherapy. The clinical factors (age, histologic features, stage, presence of myasthenia gravis) and therapeutic factors (extent of operation, irradiation dose, and field size) were retrospectively recorded and accessed using multivariate analysis. RESULTS: The overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2 patients had a relapse in the noninvasive group. None died of thymoma during the study period. The patients with invasive disease had a 5- and 10-year disease-free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic failures, 14 extrathoracic failures, and 8 combined failures. The univariate and multivariate analyses showed that Mosaoka stage and extent of resection were the important prognostic factors for patient with invasive thymoma. The 5-year survival rate and local control rate was 96% and 96% for Stage II, 77.8% and 56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage IVb (p < 0.0001 among different stage groups), respectively. The 5-year local control rate in patients with the tumor bed irradiated was 68.2%, comparable to the group treated with an extended RT field (66.6%). Age, histopathologic findings, radiation dose, and presence of myasthenia gravis were not statistically significant prognostic factors. CONCLUSION: Disease stage and extent of resection affected the prognosis of invasive thymoma patients. Extending the radiation field prophylactically was not associated with greater local control and is of questionable value for patients with invasive thymoma.

PMID: 15519782 [PubMed - indexed for MEDLINE]
18: Anticancer Res. 2004 Nov-Dec;24(6):4113-9. Related Articles, Links

Masaoka staging is of prognostic relevance in type B3 / C thymomas.

Luebke T, Beckurts KT, Wickenhauser C, Schneider P, Hoelscher AH, Moenig SP.

Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany.

BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index (LI) with the Masaoka classification and the new WHO-classification in type B3 / C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas were evaluated, and archived specimens were histologically reclassified according to Masaoka staging, the new WHO classification and the Ki-67 LI in a retrospective analysis. RESULTS: Four patients presented with Masaoka stage II disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3 WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C). The statistical analysis revealed a significant correlation between Masaoka staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in patients with type B3 / C thymoma whereas WHO-classification did not (p = 0.3266). Between survivors and non-survivors there was no statistically significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study indicated that the Masaoka staging system is of prognostic relevance in type B3 / C thymomas.

PMID: 15736461 [PubMed - indexed for MEDLINE]
19: Biol Psychiatry. 2004 Nov 1;56(9):698-700. Related Articles, Links
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Association of AKT1 with schizophrenia confirmed in a Japanese population.

Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y, Inada T, Ozaki N.

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

BACKGROUND: Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test. METHODS: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP. RESULTS: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association. CONCLUSIONS: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.

PMID: 15522255 [PubMed - indexed for MEDLINE]
20: Clin Cancer Res. 2004 Nov 1;10(21):7270-5. Related Articles, Links
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Autoantibody profiles and neurological correlations of thymoma.

Vernino S, Lennon VA.

Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

PURPOSE: Determine muscle and neuronal autoantibody frequencies in patients with thymoma, with and without paraneoplastic neurological accompaniments. EXPERIMENTAL DESIGN: Analysis of IgG autoantibodies in stored serum collected between 1985 and 2003 from 201 patients with histologically diagnosed thymoma (including six with thymic carcinoma). Contemporary assays quantitated antibodies reactive with muscle and neuronal cation channels, muscle sarcomeric proteins and neuronal cytoplasmic, and nuclear proteins. RESULTS: Neurological diagnoses included myasthenia gravis (MG), myositis, encephalitis, neuromuscular hyperexcitability, autonomic neuropathy, and subacute hearing loss, a previously unrecognized accompaniment of thymoma. Muscle acetylcholine receptor (AChR) binding antibodies were found in all patients with a diagnosis of MG. Muscle autoantibodies (AChR-binding, AChR-modulating, or striational) were also found in 59% of patients without any neurological disorder. One or more neuronal autoantibodies were found in 41% of patients without any neurological disorder, 43% of patients with MG only, and 78% of patients with other neurological disorders. Neuronal autoantibody specificities were, in descending order of frequency, as follows: glutamic acid decarboxylase, voltage-gated potassium channel, collapsin response-mediator protein-5, ganglionic AChR, and antineuronal nuclear antibody-type 1 (ANNA-1). CONCLUSIONS: Neuronal autoantibodies complement skeletal muscle autoantibodies as serological markers of thymoma in patients with and without clinical evidence of a neurological disorder. The high prevalence of glutamic acid decarboxylase autoantibody, not previously considered a paraneoplastic marker, justifies its consideration as a marker of thymoma-related neurological autoimmunity. Serological evaluation of a patient's profile of neuronal and muscle autoantibodies may aid in preoperative identification of an indeterminate mediastinal mass.

PMID: 15534101 [PubMed - indexed for MEDLINE]
21: J Gastroenterol Hepatol. 2004 Nov;19(11):1324-7. Related Articles, Links
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Autoimmune cholangitis in a patient with thymoma.

Kim JH, Kim BH, Kim YW, Park JC, Jung YH, Lee BO, Han YS, Dong SH, Kim HJ, Chang YW, Lee JI, Chang R.

Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea.

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritis, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.

Publication Types:
PMID: 15482546 [PubMed - indexed for MEDLINE]
22: J Med Assoc Thai. 2004 Nov;87(11):1304-10. Related Articles, Links

Outcome after transsternal radical thymectomy for myasthenia gravis: 14-year review at Ratchaburi Hospital.

Glinjongol C, Paiboonpol S.

Division of Thoracic Surgery, Department of Surgery, Ratchaburi Hospital, Ratchaburi 70000, Thailand.

OBJECTIVE: To determine predictability factors, clinical features and outcome in the patients after transsternal radical thymectomy (TRT) for Myasthenia Gravis (MG). METHOD: A 14-year retrospective review (1990-2004) and analysis of medical data on 32 patients with MG who underwent TRT. Two patients were lost to follow-up. Preoperative medication included anticholinesterase drugs and steroids. Plasmaphereses were used in 2 cases before operation. The modified Osserman clinical classification (Table 1) was used to define disease severity. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Using univariate analysis, sex, age, onset, Osserman class and pathology correlated with outcome and statistical significance is defined as P < 0.05. RESULTS: Among the 30 patients in the present study with MG who underwent TRT women comprised 70% (21 of 30 patients), and mean age was 42.87 +/- 12.16 year (19-65 years). The preoperative duration of the disease ranged from 0.5 to 120 months (mean = 25.72 +/- 30.68 months). Clinical statuses of patients as assessed on initial evaluation were 13 patients (43.3%) were in class IIA, 6 (20%) in class IIB, and 11 (36.7%) in class III. (Table 2) The histology of thymus glands consisted of hyperplasia in 22 patients, normal in 2, atrophic thymus in 3, thymomas in 3, (2 were malignant thymomas). Hospital mortality was 0, but 9-month mortality was 3.33% (1 of 30 patients). The mean follow-up period was 41.80 +/- 53.89 months. Complete remission (A) was achieved in 40% of patients (12 of 30), and marked improvement (B) of MG in 40% (12 of 30), for a total benefit rate of 80%. 6.7% (2 of 30) were unchanged (C), 10% (3 of 30) were worse (D) and 3.3% died because of MG (E). Using univariate analysis on sex, clinical status by Osseman classification, and histopathology correlated significantly with outcome (P < 0. 05); 95.2% of women (20 of 21) benefited from the procedure, versus 44.4% of men (4 of 9). 100% (19 of 19) of patients in class IIA and IIB benefited from the procedure, versus 45.5% (4 of 9) of patients in class III. All patients with thymoma presented a less favorable outcome (deteriorated in 2, and died in 1) versus 11.1% (3 of 24) of patients without thymomas were deteriorated. CONCLUSION: The remission and improvement in 80% of patients suggested that adequate thymic tissue were removed with radical thymectomy. Female, absence of thymoma, thymic hyperplasia, patients in class IIA, and IIB (non-respiratory involvement) are favorable predictability prognostic factors.

PMID: 15825704 [PubMed - indexed for MEDLINE]
23: Neuroepidemiology. 2004 Nov-Dec;23(6):281-4. Epub 2004 Aug 5. Related Articles, Links
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Incidence of myasthenia gravis in the province of Ferrara: a community-based study.

Casetta I, Fallica E, Govoni V, Azzini C, Tola M, Granieri E.

Sezione di Clinica Neurologica, Dipartimento di Discipline Medico Chirurgiche della Comunicazione e del Comportamento, and Centro di Neuroscienze, Universita degli Studi di Ferrara, Ferrara, Italy. cti@dns.unife.it

BACKGROUND: The reported annual incidence of myasthenia gravis (MG) ranges from 0.25 to 15 per million. The sex- and age-related pattern of disease incidence is still debated. METHODS: An intensive descriptive study was performed in the province of Ferrara (mean population 360,950 people) over the period 1985 through 2000. RESULTS: The average crude annual incidence rate was 2 per 100,000. We confirm a female preponderance in the total population, particularly in the youngest age groups. CONCLUSIONS: We observed an early increase in incidence in females, partly due to thymoma-associated MG, while MG without thymoma showed increasing incidence with age nonsignificantly different in the two sexes. 2004 S. Karger AG, Basel

PMID: 15297794 [PubMed - indexed for MEDLINE]
24: Vet Radiol Ultrasound. 2004 Nov-Dec;45(6):542-6. Related Articles, Links

Computed tomographic evaluation of canine and feline mediastinal masses in 14 patients.

Yoon J, Feeney DA, Cronk DE, Anderson KL, Ziegler LE.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, C339 Veterinary Teaching Hospital, 1352 Boyd Avenue, St Paul, MN 55108, USA.

A 15-year retrospective analysis of histologically proven canine and feline mediastinal malignancies at the University of Minnesota was conducted to identify patients imaged by computed tomography (CT). The goal of the study was to characterize the CT appearance, to determine if there were any tumor type-specific appearances, and to clarify the role of CT in patients with mediastinal masses. Fourteen patients meeting these criteria were available for evaluation. The masses were characterized based on the presence or absence of contrast enhancement, internal architecture, size, extent of local invasion, the presence of pleural fluid, and the presence of regional vascular invasion. Within the limits of this study and the histopathologic information available, there appeared to be no clinically exploitable relationship between the CT appearance and the histologic characterization of the mass. However, CT does provide reasonably accurate local staging information.

Publication Types:
PMID: 15605846 [PubMed - indexed for MEDLINE]
25: J Am Vet Med Assoc. 2004 Oct 15;225(8):1205-10, 1196. Related Articles, Links

Use of a jugular vein autograft for reconstruction of the cranial vena cava in a dog with invasive thymoma and cranial vena cava syndrome.

Holsworth IG, Kyles AE, Bailiff NL, Hopper K, Long C, Ilkiw JE.

Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

A spayed female dog was evaluated because of edema of the ventral cervical region, lethargy, cough, and reduced exercise tolerance. Invasive thymoma and cranial vena cava syndrome were diagnosed by use of ultrasound-guided fine-needle biopsy and contrast-enhanced helical computed tomography. Resection of the cranial vena cava and an autogenous jugular vein graft were used for restoration of normal venous return to the right atrium and alleviation of the cranial vena cava syndrome.

Publication Types:
PMID: 15521441 [PubMed - indexed for MEDLINE]
26: J Neurol Sci. 2004 Oct 15;225(1-2):27-31. Related Articles, Links
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High frequency of allergic conjunctivitis in myasthenia gravis without thymoma.

Murai H, Osoegawa M, Ochi H, Kira J.

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. hmurai@neuro.med.kyushu-u.ac.jp

OBJECTIVES: To investigate the frequency of allergic disorders in myasthenia gravis (MG) patients and characterize the features of MG associated with allergic disorders. METHODS: Frequencies of past and present common allergic disorders in 160 MG patients who visited the Department of Neurology, Kyushu University Hospital from April 2000 to July 2003 and in 81 neurological normal controls were studied. RESULTS: Among various allergic disorders, the frequency of allergic conjunctivitis (AC) was significantly higher in MG patients (39/160, 24.4%, p(corr)=0.0112), especially with MG without thymoma (36/123, 29.3%, p(corr)=0.0016), in comparison to the controls (6/81, 7.4%). MG patients with AC showed a significantly higher rate of seronegative MG (43.6% vs. 17.4%, p=0.008) and a higher tendency of ocular MG (43.6% vs. 28.1%, p=0.071). Moreover, MG with AC had significantly lower anti-acetylcholine receptor antibody titers (median 6.8 nmol/l vs. median 23.6 nmol/l, p=0.0359) as well as a lower rate of coexisting thymoma (7.7% vs. 17.4%, p=0.016). The incidence of myasthenic crisis was also lower in MG with AC than without AC, yet the difference was not significant (7.7% vs. 15.7%). CONCLUSION: There was a significant association of AC with MG especially for ocular or seronegative MG in cases without thymoma.

PMID: 15465082 [PubMed - indexed for MEDLINE]
27: Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E686-95. Epub 2004 May 27. Related Articles, Links
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Cold-induced PGC-1alpha expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway.

Oliveira RL, Ueno M, de Souza CT, Pereira-da-Silva M, Gasparetti AL, Bezzera RM, Alberici LC, Vercesi AE, Saad MJ, Velloso LA.

Department of Internal Medicine, State University of Campinas, SP 13083-970, Brazil.

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) participates in control of expression of genes involved in adaptive thermogenesis, muscle fiber type differentiation, and fuel homeostasis. The objective of the present study was to evaluate the participation of cold-induced PGC-1alpha expression in muscle fiber type-specific activity of proteins that belong to the insulin-signaling pathway. Rats were exposed to 4 degrees C for 4 days and acutely treated with insulin in the presence or absence of an antisense oligonucleotide to PGC-1alpha. Cold exposure promoted a significant increase of PGC-1alpha and uncoupling protein-3 protein expression in type I and type II fibers of gastrocnemius muscle. In addition, cold exposure led to higher glucose uptake during a hyperinsulinemic clamp, which was accompanied by higher expression and membrane localization of GLUT4 in both muscle fiber types. Cold exposure promoted significantly lower insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and Ser473 phosphorylation of acute transforming retrovirus thymoma (Akt) and an insulin-independent increase of Thr172 phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). Inhibition of PGC-1alpha expression in cold-exposed rats by antisense oligonucleotide treatment diminished glucose clearance rates during a hyperinsulinemic clamp and reduced expression and membrane localization of GLUT4. Reduction of PGC-1alpha expression resulted in no modification of insulin-induced tyrosine phosphorylation of the IR and Ser473 phosphorylation of Akt. Finally, reduction of PGC-1alpha resulted in lower Thr172 phosphorylation of AMPK. Thus cold-induced hyperexpression of PGC-1alpha participates in control of skeletal muscle glucose uptake through a mechanism that controls GLUT4 expression and subcellular localization independent of the IR and Akt activities but dependent on AMPK.

PMID: 15165993 [PubMed - indexed for MEDLINE]
28: Am J Surg Pathol. 2004 Oct;28(10):1360-70. Related Articles, Links
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Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor.

Fetsch JF, Laskin WB, Michal M, Remotti F, Heffner D, Ellis G, Furlong M, Miettinen M.

Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. FETSCH@afip.osd.mil

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males. Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years. Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), alpha-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of > or =3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best. Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.

PMID: 15371953 [PubMed - indexed for MEDLINE]
29: Brain. 2004 Oct;127(Pt 10):2331-8. Epub 2004 Sep 10. Related Articles, Links
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FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes.

Younes-Mhenni S, Janier MF, Cinotti L, Antoine JC, Tronc F, Cottin V, Ternamian PJ, Trouillas P, Honnorat J.

Neurology B, Hopital Pierre Wertheimer, Universite Claude Bernard, Lyon, France.

To determine the usefulness of [18F]fluorodeoxyglucose (FDG) whole body FDG-PET in the diagnosis of tumours in patients with paraneoplastic neurological syndromes (PNS), we prospectively studied 20 patients with paraneoplastic antibodies in whom conventional imaging gave negative or inconclusive results for the presence of tumour. All 20 patients had neurological manifestations compatible with PNS and well-characterized paraneoplastic antibodies (12 anti-Hu, one anti-Hu and anti-CV2, one anti-CV2, four anti-Yo, one anti-Ri and one anti-amphiphysin). The mean delay between the onset of neurological symptoms and FDG-PET was 10 months (range 1-54). In these 20 patients, abnormal uptake was demonstrated in 18 patients, with some patients having abnormal signal in several areas. We observed abnormal uptake in the mediastinum (13 cases), lung (two cases), breast (two cases), parotid gland (one case), or the cervical, supraclavicular or axillary lymph nodes (seven cases). Following FDG-PET, the histological diagnosis of the tumour was made in 14 patients (small cell lung carcinoma in eight cases, breast adenocarcinoma in two, lung adenocarcinoma in two, axillary metastasis of ovary carcinoma in one, and malignant thymoma in one). Two other patients with abnormal FDG uptake showed radiological evidence of lung cancer, but a histological diagnosis could not be obtained. In two other patients, initial FDG-PET showed abnormal FDG uptake that was not confirmed a few months later by repeat FDG-PET. In the two patients with negative FDG-PET, peritoneal carcinomatosis was diagnosed in one and no tumour was found in the other. In our series, the sensitivity of FDG-PET for tumour detection was >83% demonstrating a clear role of this technique in the management of patients with PNS. However, in our series, the specificity of FDG uptake was only 25% due to unexplained abnormal FDG uptake in three patients and in abnormal FDG uptake due to a benign tumour in one patient. Over the study period, we saw 73 other patients with PNS and paraneoplastic antibodies. A tumour was demonstrated in 71 out of 73 by conventional techniques. Since false-positive and false-negative results are possible with FDG-PET and in most patients with PNS, the tumour is demonstrated by conventional techniques, we believe that FDG-PET should be reserved, at the moment, for patients with well-defined PNS antibodies when conventional imaging fails to identify a tumour or when lesions are difficult to biopsy.

PMID: 15361417 [PubMed - indexed for MEDLINE]
30: Cancer Chemother Pharmacol. 2004 Oct;54(4):308-14. Epub 2004 Jun 4. Related Articles, Links
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Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors.

Tran HT, Blumenschein GR Jr, Lu C, Meyers CA, Papadimitrakopoulou V, Fossella FV, Zinner R, Madden T, Smythe LG, Puduvalli VK, Munden R, Truong M, Herbst RS.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 432, Houston, TX 77030, USA. htran@mdanderson.org

PURPOSE: Preclinical studies have demonstrated a synergistic effect with the angiogenesis inhibitor TNP-470 and several cytotoxic agents. A recent clinical trial with the combination of paclitaxel and TNP-470 has shown promising effects. The present study was designed to determine the toxicity and pharmacokinetics of carboplatin in combination with TNP-470 in comparison with the doublet regimen of paclitaxel and carboplatin in patients with solid tumors. EXPERIMENTAL DESIGN: Enrolled in the study were 17 patients with lung (11), head/neck (3), sarcoma (2) and thymoma (1). The patients received intravenous paclitaxel and carboplatin on day 1 followed by TNP-470 (60 mg/m(2) i.v. over 1 h administered thrice weekly on Monday, Wednesday, and Friday). Each cycle of therapy consisted of 3 weeks. The initial cohort of three patients received carboplatin at AUC 5 mg/ml x min. No dose-limiting toxic effects occurred, thus the subsequent cohort received carboplatin at AUC 6 mg/ml x min. In addition to toxicity, the pharmacokinetics of carboplatin were evaluated, and tumor response and patient survival rates were assessed. RESULTS: The administered regimen of paclitaxel (225 mg/m(2) i.v. over 3 h) and carboplatin (AUC 6 mg/ml x min i.v. over 1 h) on day 1 followed by TNP-470 (60 mg/m(2) i.v. over 1 h administered thrice weekly on Monday, Wednesday, and Friday) was defined as both the maximum tolerated and optimal dose. Hematological toxic effects were similar to those expected with the chemotherapy doublet. All neurocognitive impairments were graded as mild to moderate and reversed after discontinuation of TNP-470 administration. No alterations in the pharmacokinetic disposition of carboplatin were noted. Overall, the median survival duration was 297 days. Four patients (24%) had a partial response, and eight (47%) had stable disease. CONCLUSIONS: The combination of TNP-470, paclitaxel, and carboplatin is a reasonably well tolerated regimen. Further randomized studies of TNP-470 with this doublet regimen are now warranted for non-small-cell lung carcinoma and other solid tumors.

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PMID: 15184994 [PubMed - indexed for MEDLINE]
31: Int J Surg Pathol. 2004 Oct;12(4):395-400. Related Articles, Links

KI-67 antigen expression predicts survival and correlates with histologic subtype in the WHO classification of thymic epithelial tumors.

Comin CE, Messerini L, Novelli L, Boddi V, Dini S.

Dipartimento di Patologia Umana ed Oncologia, Universita degli Studi di Firenze, Italy.

We performed an immunohistochemical study with monoclonal antibodies to Ki-67 antigen and p53 protein on 45 cases of thymic epithelial tumors classified according to the recent World Health Organization (WHO) classification system to evaluate whether there is correlation between the expression of these markers and prognosis, histologic subtype, and myasthenia gravis (MG). We also correlated histologic subtype with sex, age, MG, and survival. Ki-67 and p53 labeling indices (LIs) were expressed as a percentage of positive nuclear immunostaining by counting 1,000 epithelial tumor cells. Statistically significant differences were found between Ki-67 LI and survival (p = 0.007), whereas the prognostic implication of p53 could not be demonstrated, although there appeared a trend that patients with tumors of higher LIs had worse survival. Significant correlations were also found between Ki-67 (p < 0.0005) and p53 (p < 0.0005) LIs and histologic subtypes. No correlation was found between these parameters and MG. Histologic subtypes of the WHO classification also correlated with survival (p = 0.01), whereas no correlation was found with sex, age, and MG. In conclusion, our results indicate that the proliferative activity, assessed by Ki-67 LI, and the histologic pattern, according to WHO classification system, seems to represent reliable parameters in the prognosis of thymic epithelial tumors.

PMID: 15494865 [PubMed - indexed for MEDLINE]
32: J Neurol Neurosurg Psychiatry. 2004 Oct;75(10):1504-5. Related Articles, Links
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Sub-acute presentation of Morvan's syndrome after thymectomy.

Cottrell DA, Blackmore KJ, Fawcett PR, Birchall D, Vincent A, Barnard S, Walls TJ.

Publication Types:
PMID: 15377711 [PubMed - indexed for MEDLINE]
33: J Pediatr Hematol Oncol. 2004 Oct;26(10):681-5. Related Articles, Links
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Thymoma in children: report of two cases and review of literature.

Dhall G, Ginsburg HB, Bodenstein L, Fefferman NR, Greco MA, Chang MW, Gardner S.

Division of Pediatric Hematology-Oncology, St. Peter's University Hospital, New Brunswick, NJ 08903-0591, USA. gdhall@saintpetersuh.com

Thymoma is an uncommon tumor of childhood. Stage of the tumor is an independent prognostic factor for survival. Surgery is the treatment of choice for stage I and stage II tumors. Chemotherapy is reserved for patients with refractory or metastatic disease. Thymomas are moderately radiosensitive. However, radiation therapy is not an attractive option for children due to its side-effects on developing organs. The authors describe 2 children with completely encapsulated thymoma who were successfully treated with surgery alone. Both patients remain free of disease 3 years after surgery. One of the patients also has nevus sebaceous. The authors also discuss the possible association between the two disease entities.

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PMID: 15454843 [PubMed - indexed for MEDLINE]
34: J Pediatr Surg. 2004 Oct;39(10):1565-7. Related Articles, Links
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Tumor recurrence at thoracostomy tube insertion sites: a report of two pediatric cases.

Hayes-Jordan AA, Daw NC, Furman WL, Hoffer FA, Shochat SJ.

Department of Surgery, Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Recurrence of thoracic malignant tumors at port sites used for thoracoscopic procedures in adults have been described. However, there are no reports of tumor recurrence at thoracostomy tube or thoracoscopic trocar insertion sites after operation for thoracic malignancies in children. The authors report 2 cases of tumor recurrence at thoracostomy tube insertion sites after intraoperative gross spillage of pleuropulmonary blastoma and malignant epithelial thymoma and discuss approaches that may potentially prevent this devastating complication.

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PMID: 15486906 [PubMed - indexed for MEDLINE]
35: Jpn J Clin Oncol. 2004 Oct;34(10):630-3. Related Articles, Links
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Pulmonary metastasis 12 years after resection of thymoma with microscopic capsule invasion.

Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Orikasa H, Yamazaki K.

Department of Thoracic Surgery, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo 108-0073, Japan. hnomori@qk9.so-net.ne.jp

We report on a 50-year-old female who developed pulmonary metastasis 12 years following the resection of a thymoma with microscopic capsular invasion. The patient was found to have a mediastinal mass at the age of 18 years; however, she refused to undergo surgery. At the age of 38 years, the patient underwent surgery for resection of the tumor; it was diagnosed as a macroscopically encapsulated thymoma with microscopic capsular invasion. Multiple pulmonary metastases occurred 12 years following the resection of the tumor; all the metastatic masses were resected. Although the patient suffered from myasthenia gravis 4 months following the resection of pulmonary metastases, she remains free of myasthenia gravis with no recurrence of tumor at 2 years post-surgery. Long-term follow-up is essential for the detection of recurrence after resection of a thymoma with microscopic capsular invasion, and surgery could be the best treatment for distant metastasis in case of resectable lesions.

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PMID: 15591463 [PubMed - indexed for MEDLINE]
36: Kyobu Geka. 2004 Oct;57(11):1070-3. Related Articles, Links

[Mediastinal seminoma difficult to differentiate from thymoma through preoperative biopsy; report of a case]

[Article in Japanese]

Ito S, Isowa N, Kikuchi R, Hasegawa S, Inui K, Wada H.

Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

A case of a 36-year-old male patient with mediastinal seminoma is presented. He consulted a physician with a complaint of back pain and an abnormal shadow was detected on chest X-ray. Chest computed tomography (CT) scan revealed a pulmonary nodule and an anteriormediastinal mass. Preoperative percutaneous needle biopsy suggested that the tumor was similar to thymoma. Complete surgical excision of the mediastinal mass was performed. Immunohistochemical studies showed positive staining of the tumor cells with placental alkaline phosphatase. The final diagnosis was seminoma. Additional postoperative chemotherapy (cisplatin + etoposide) was done. He is alive and well 34 months after the operation.

Publication Types:
PMID: 15510825 [PubMed - indexed for MEDLINE]
37: Kyobu Geka. 2004 Oct;57(11):1000-4. Related Articles, Links

[Extrapleural pneumonectomy for thoracic malignancies]

[Article in Japanese]

Yokoi K, Matsuguma H, Nakahara R.

Division of General Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Extrapleural pneumonectomy has been used by thoracic surgeons in the treatment of malignant pleural mesothelioma as well as other pleural diseases, such as tuberculous empyema. Recently, this operative procedure has been also sporadically applied for the treatment of carcinomatous pleuritis of lung cancer and/or invasive thymoma in some institutions. We performed this operation in 24 patients with thoracic malignancy: 15 patients with carcinomatous pleuritis of primary lung adenocarcinoma (6 patients with T4N0 disease, 2 with T4N1, and 7 with T4N2), 3 patients with stage IV a thymoma, and 6 patients with malignant pleural mesothelioma (2 patients with stage II disease, 3 with stage III, and 1 with stage IV). All patients survived the operation and were discharged from the hospital. Major complications were intrathoracic hemorrhage and empyema in 2 patients each. The median survival time and 5-year survival rate of lung cancer patients were 34 months and 45.5%, respectively. All patients with thymoma are alive now without disease 9 to 133 months after operation. All patients with malignant pleural mesothelioma except 1, who lately underwent this treatment, died of disease from 15 to 27 months after surgery. Our results indicate that carefully selected patients with carcinomatous pleuritis of lung cancer and thymoma may be candidates for extrapleural pneumonectomy for cure. Nevertheless, the ultimate value of this surgical treatment should be ascertained in a prospective study with a large number of patients.

PMID: 15510811 [PubMed - indexed for MEDLINE]
38: Sarcoidosis Vasc Diffuse Lung Dis. 2004 Oct;21(3):232-6. Related Articles, Links

Thymus tuberculosis poorly responding to anti-mycobacterial therapy in a young girl with primary infection.

Sacco O, Gambini C, Aicardi M, Silvestri M, Rossi UG, Toma P, Mattioli G, Jasonni V, Rossi GA.

G Gaslini, Institute and University of Genoa, Genoa, Italy.

Tuberculous infection of the thymus is a rare condition, previously described only in young adults. A case of a young girl with primary pulmonary tuberculosis, hilar and mediastinal lymph node enlargement and a partially necrotic mass in antero-superior mediastinum is described. Treatment with three anti-mycobacterial drugs was started, effective in markedly reducing all the intrathoracic abnormalities with the exception of the antero-superior mediastinal mass. Since the radiographic and ultrasonographic appearance of the thymus tuberculous infection may be indistinguishable from other serious conditions, including lymphoma and thymoma, a diagnostic procedure was performed. Evaluation of the resected specimen showed foci of caseation and multiple granulomas with extensive central necrosis within the thymic tissue.

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PMID: 15554081 [PubMed - indexed for MEDLINE]
39: Surg Endosc. 2004 Oct;18(10):1535-8. Epub 2004 Aug 26. Related Articles, Links
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Video-assisted transcervical thymectomy.

Bramis J, Diamantis T, Tsigris C, Pikoulis E, Papaconstantinou I, Nikolaou A, Leonardou P, Bastounis E.

First Surgical Department, Athens University, Medical School, Laikon Hospital, Athens, Greece.

BACKGROUND: The optimal surgical approach for complete removal of the thymus gland has long been debated. In this report, the excision of the entire gland through a transcervical incision using video-assisted techniques is described. METHODS: Ten patients, including one with thymoma and myasthenia gravis, underwent surgery via the transcervical approach. After standard dissection up to the level of the innominate vein and ligation of the thymic vessels, a laparoscope was inserted into the mediastinum. In the patient with thymoma, the operation was completed by a small incision in the third intercostal space. RESULTS: No perioperative mortality or long-term morbitity was observed. The mean hospital stay was 69.6 h. After a mean follow-up period of 63.8 months, eight patients displayed complete remission, whereas one continued to receive minimal medication. The patient with thymoma showed considerable improvement, but remained on same medical regimen No complications were seen throughout the study. CONCLUSION: Video-assisted thymectomy improves effectiveness of the transcervical approach for thymectomy with a minimum of trauma and excellent results.

PMID: 15791384 [PubMed - in process]
40: J Neurol Sci. 2004 Sep 15;224(1-2):93-5. Related Articles, Links
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Myasthenia gravis with thymus hyperplasia and pure red cell aplasia.

Suto Y, Araga S, Sakuma K, Nakano T, Ishiga K, Tajima F, Kowa H, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan.

A case of myasthenia gravis (MG) with thymus hyperplasia and pure red cell aplasia (PRCA) is reported. A 57-year-old woman was diagnosed as having MG and was treated with thymectomy 26 years ago. The histology of the resected thymus was thymic lymphoid follicular hyperplasia. She developed rapidly progressive anemia and a bone marrow examination revealed PRCA. Her hematological results improved with oral administration of cyclosporine A. Cases of MG, thymoma and PRCA have been reported in the literature. We report the first case of MG without thymoma and PRCA.

Publication Types:
PMID: 15450777 [PubMed - indexed for MEDLINE]
41: BMC Neurol. 2004 Sep 11;4:12. Related Articles, Links
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Frequency of myasthenic crisis in relation to thymectomy in generalized myasthenia gravis: a 17-year experience.

Soleimani A, Moayyeri A, Akhondzadeh S, Sadatsafavi M, Shalmani HT, Soltanzadeh A.

Division of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. asoleimani@ddrcir.org

BACKGROUND: Myasthenic crisis is the most serious life-threatening event in generalized myasthenia gravis (MG) patients. The objective of this study was to assess the long-term impact of thymectomy on rate and severity of these attacks in Iranian patients. METHODS: We reviewed the clinical records from 272 myasthenic patients diagnosed and treated in our neurology clinic during 1985 to 2002. Fifty-three patients were excluded because of unconfirmed diagnosis, ocular form of MG, contraindication to surgery, concomitant diseases and loss to follow-up. The Osserman classification was used to assess the initial severity of the disease. Frequency and severity of the attacks were compared between two groups with appropriate statistical tests according to the nature of variables. Multivariate logistic regression analysis was used to assess the predictors of myasthenic crisis in the group of patients without thymoma. RESULTS: 110 patients were in thymectomy group and the other 109 patients were on medical therapy. These two groups had no significant differences with respect to age at onset, gender, Osserman score in baseline and follow up period. 62 patients (28.3% of all 219 patients) had reported 89 attacks of myasthenic crisis. 20 patients of 62 (32%) were in thymectomy group and 42 (68%) were in the other group. There was significant difference between the two groups in number of patients with crisis (P = 0.001; odds ratio = 2.8 with 95% CI of 1.5 to 5.2). In addition, these attacks were more severe in group of non-thymectomized patients as the duration of ICU admission was longer and they needed more ventilatory support during their attacks. Regression model showed thymectomy and lower age at onset as two predictors of decrement in myasthenic crisis rate in non-thymomatous MG patients. CONCLUSIONS: It is suggested that frequency and severity of myasthenic attacks as important endpoints in evaluation of MG patients. Thymectomy seems to have a preventive role on rate and severity of these attacks.

PMID: 15361260 [PubMed - indexed for MEDLINE]
42: Lancet. 2004 Sep 11-17;364(9438):936. Related Articles, Links
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History of thymoma and yellow fever vaccination.

Barwick R; Eidex for the Yellow Fever Vaccine Safety Working Group.

Publication Types:
PMID: 15364184 [PubMed - indexed for MEDLINE]
43: Ann Thorac Surg. 2004 Sep;78(3):1024-30. Related Articles, Links
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Surgical management of thoracic malignancies invading the heart or great vessels.

Park BJ, Bacchetta M, Bains MS, Downey RJ, Flores R, Rusch VW, Girardi LN.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. parkb@mskcc.org

BACKGROUND: Surgical resection of thoracic malignancies involving either the heart or great vessels is uncommonly performed because of the potential morbidity and mortality for an unknown probability of significant palliation or cure. We reviewed our experience of 10 patients treated surgically, either primarily or as a component of multimodality therapy, to assess feasibility and results. METHODS: A retrospective review of the results in 10 patients who underwent resection of thoracic malignancies that included either great vessel or the heart was conducted. RESULTS: Histologic diagnoses included soft tissue sarcoma (n = 7), squamous cell carcinoma (n = 1), malignant thymoma (n = 1), and mediastinal teratoma (n = 1). Three patients underwent induction chemotherapy. Cardiopulmonary bypass was used in 7 patients. Structures resected included superior vena cava (n = 5), left atrium (n = 4), right atrium (n = 2), descending aorta (n = 1), and main pulmonary artery (n = 1). Concomitant anatomic pulmonary resections were performed in 3 patients. Seven patients had an R0 or R1 resection. There were no perioperative deaths. All symptomatic patients had immediate and sustained palliation of their presenting symptoms. The median length of stay was 6 days (range, 4 to 43 days). Six patients underwent postoperative systemic therapy. The overall median survival was 21.7 months (range, 3.2 to 69 months) and was 33.3 months (range, 3.7 to 69 months) for patients who had an R0 or R1 resection. CONCLUSIONS: Resection of the heart and great vessels involved by thoracic malignancies can be performed with acceptable morbidity and mortality and results in significant palliation and, in some cases, prolonged survival.

PMID: 15337042 [PubMed - indexed for MEDLINE]
44: Ann Thorac Surg. 2004 Sep;78(3):992-7; discussion 997-8. Related Articles, Links
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Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification.

Park MS, Chung KY, Kim KD, Yang WI, Chung JH, Kim YS, Chang J, Kim JH, Kim SK, Kim SK.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

BACKGROUND: The aim of this study was to document the prognosis of thymic epithelial tumors (TETs) according to new the World Health Organization (WHO) classification. METHODS: We retrospectively reviewed 150 patients with TETs that were confirmed pathologically during 11 years (from 1992 to 2002) in Severance Hospital, Seoul, Korea. RESULTS: TETs were classified as type A, AB, B1, B2, B3, or C, tumors and these represented 7 (4.7%), 26 (17.3%), 13 (8.7%), 45 (30.0%), 26 (17.3%), and 33 (22.0%) cases, and the 5-year survival rates were 100%, 93%, 89%, 82%, 71%, and 23%, respectively. Their Masaoka stages were I, II, III, IVa, and IVb, with 53 (35.3%), 39 (26.0%), 20 (13.3%), 22 (14.7%), and 16 (10.7%) cases. Tumor invasiveness, recurrence, completeness of resection, and tumor-related death were more frequent in types AB, B2, B3, and C than in types A and B1. Multivariate analysis showed that Masaoka stage (p < 0.001) and the WHO classification (p = 0.019) were significant independent prognostic factors. CONCLUSIONS: The WHO classification is associated with tumor invasiveness, recurrence, completeness of resection, and tumor-related death, and has good correlation with Masaoka stage. The WHO histologic subtypes are an independently significant prognostic factor with respect to survival in our multivariate analysis. Types AB, B2, B3, and C showed invasive behaviors and R1 or R2 resections were frequently performed. Postoperative adjuvant radiotherapy was effective, but long-term follow-up is recommended because of decreased survival after 5 years following operation. The WHO classification may be helpful in clinical practice for the assessment and treatment of TET patients.

PMID: 15337034 [PubMed - indexed for MEDLINE]
45: Anticancer Res. 2004 Sep-Oct;24(5C):3379-86. Related Articles, Links

Tumor cell-specific transcription of a murine histocompatibility class Ib Q5 gene.

Noguchi K, Kuwada E, Goto S, Egawa K.

Institute of Molecular Immunology, Medinet, Tamagawadai, Setagaya-ku, Tokyo 158-0096 and 2Seta Clinic, 4-20-18 Seta, Setagayaku, Tokyo 158-0095, Japan. noguchi@j-immunother.com

BACKGROUND: We previously reported that the Q5 gene product (Q5 antigen) was expressed on the surface of various tumor cells derived from H-2k (Qa-2-) mice. The Q5 antigen has tumor-protective antigenicity in the syngeneic mice. MATERIALS AND METHODS: Transcripts of the Qa region genes were analyzed by the RT-PCR method. Cell fractionation was performed with the MACS method and the phenotypes were estimated by flow cytometry analysis. RESULTS: Transcripts of Q5 were produced by all tumor cell lines. The Q5 transcription was detected only in thymocytes and PBMCs of H-2k (AKR and C3H/He) mice. The phenotype of the PBMCs in which Q5 transcription takes place seems to be, at least partly, CD3-48 cells that might be related to CD3-4-8- spontaneous thymoma cells derived from an H-2k mouse. CONCLUSION: The expression of Q5 in tumor cells in general is a result of a change of transcriptional regulation associated with malignant transformation.

PMID: 15515435 [PubMed - indexed for MEDLINE]
46: Eur J Surg Oncol. 2004 Sep;30(7):776-80. Related Articles, Links
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Experience with video-assisted surgery for suspected mediastinal tumours.

Chetty GK, Khan OA, Onyeaka CV, Ahmad F, Rajesh PB, Waller DA.

Department of Thoracic Surgery, Glenfield Hospital, Leicester LE3 9QP, UK.

AIM: To assess the therapeutic feasibility of video-assisted thoracoscopic surgery (VATS) in the excision of suspected mediastinal tumours. METHODS: The case notes of 24 consecutive patients referred to a single surgeon between 1997 and 2002 for excision of suspected mediastinal tumours were reviewed. The operative, post-operative and pathological characteristics of patients treated thoracoscopically and by open procedure were analysed. RESULTS: Thirteen of 24 patients underwent thoracoscopic excision. The mean age of the two groups was similar as was the mean operating time and duration of chest drainage. However, patients in the thoracoscopic group had less chest drainage, less pain and a shorter hospital stay. CONCLUSIONS: Video-assisted thoracoscopic excision of mediastinal tumours is a safe and technically feasible procedure and may offer significant post-operative advantages over open procedures.

Publication Types:
PMID: 15296993 [PubMed - indexed for MEDLINE]
47: J Dtsch Dermatol Ges. 2004 Sep;2(9):797-800. Related Articles, Links

[Grouped blisters and mediastinal tumor in a 50-year-old woman]

[Article in German]

Hehn J, Herzog S, Gesierich A, Zillikens D, Rose C.

Universitats-Hautklinik Wurzburg.

Publication Types:
PMID: 16279225 [PubMed - indexed for MEDLINE]
48: J Neurosci Res. 2004 Sep 1;77(5):670-80. Related Articles, Links
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T-cell hybridoma specific for myelin oligodendrocyte glycoprotein-35-55 peptide produced from HLA-DRB1*1501-transgenic mice.

Chou YK, Culbertson N, Rich C, LaTocha D, Buenafe AC, Huan J, Link J, Wands JM, Born WK, Offner H, Bourdette DN, Burrows GG, Vandenbark AA.

Neuroimmunology Research and Tykeson Multiple Sclerosis Research Laboratory, Veterans Affairs Medical Center, and Oregon Health and Science University, Portland, Oregon 97239, USA. chouy@ohsu.edu

The goal of this study was to establish an unlimited and standardized source of humanized myelin peptide-specific T cells for in vitro testing of biological function. Thus, we perpetuated myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-specific T cells obtained from immunized HLA-DRB1*1501-transgenic (Tg) mice by somatic fusions with BW5147 thymoma cells or BW5147 T-cell receptor (TCR) alpha(-)beta(-) variant (BW5147 variant) cells. The resulting T-cell hybridomas responded strongly to both mouse MOG-35-55 (42S) and human MOG-35-55 peptide (42P), regardless of which peptide was used for initial immunization, and were DRB1*1501 restricted. The MOG-35-55-reactive T-cell hybridomas were CD3(+)CD4(+)CD8(-) and expressed intracellular Th1 cytokines upon concanavalin A stimulation. Clones from either human MOG-35-55- or mouse MOG-35-55-selected hybridomas uniquely expressed the TCR BV8 gene in combination with AV17 and AV11 genes. V gene analyses confirmed the expression of TCR AV1, AV11, AV16, BV1, and BV5 gene segments in the widely used fusion partner BW5147 and demonstrated deletion of TCR AV1, AV11, and BV1 in the BW5147 variant. T-cell hybridomas were positively stained with anti-TCR beta-chain antibody on the cell surface, whereas neither BW5147 nor its variant had positive TCR surface expression. For functional application, we found that a monomeric form of the human HLA-DR2-derived recombinant T-cell receptor ligand (RTL) covalently linked to human MOG-35-55 peptide specifically inhibited proliferation of a hybridoma clone selected with human MOG-35-55 but not a different hybridoma clone selected with myelin basic protein. The RTL-induced inhibition in vitro of the human MOG-35-55 peptide-specific hybridoma reflected the ability of the RTL to inhibit experimental autoimmune encephalomyelitis induced by human MOG-35-55 peptide in HLA-DR2 transgenic mice. Thus, the MOG-35-55 peptide-specific T-cell hybridoma from DR2-Tg mice represents a novel humanized T-cell reagent useful for standardized biological screening of both DR2-restricted stimulation and RTL-dependent inhibition of response to human MOG-35-55 peptide.

PMID: 15352213 [PubMed - indexed for MEDLINE]
49: J Zoo Wildl Med. 2004 Sep;35(3):409-11. Related Articles, Links

Myasthenia gravis in a polar bear (Ursus maritimus).

Kenny DE, Baier J, Knightly F, Steinheimer D, Getzy DM, Shelton GD.

Denver Zoological Gardens, City Park, E. 2300 Steele Street, Denver, Colorado 80205-4899, USA.

A 14.6-yr-old, female, multiparous polar bear (Ursus maritimus) acutely developed an apparent hind limb weakness. Physical examination and diagnostic tests including a hemogram, serum biochemistry, electrolytes, radiographs, and myelogram did not provide a definitive diagnosis. No improvement in condition was noted during 4 days of supportive care, and the bear was euthanized. An ovoid mass was present in the anterior mediastinum, and a thymoma was confirmed histologically. Compared with control polar bears, elevated serum acetylcholine receptor (AChR) antibodies (0.13 +/- 0.06 nmol/L vs. 0.86 nmol/L) were detected by immunoprecipitation radioimmunoassay, which is consistent with myasthenia gravis (MG) in other species. Although the AChR antibody test has not been validated in the polar bear, we are confident in the postmortem diagnosis of MG, which is commonly associated with thymoma in other species.

Publication Types:
PMID: 15526902 [PubMed - indexed for MEDLINE]
50: Korean J Intern Med. 2004 Sep;19(3):193-5. Related Articles, Links

Myelodysplastic syndrome with erythroid aplasia following pure red cell aplasia.

Kim HD, Kim KW, Park SY, Ko HJ, An YY, Shin SY, Jang JY.

Department of Internal Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Myelodysplastic syndrome (MDS) with erythroid aplasia is a very rare disorder that has not been clearly defined. We experienced a case of pure red cell aplasia (PRCA), which evolved to MDS with erythroid aplasia. A 59-year-old male with transfusion-dependent PRCA was referred to our hospital for an evaluation of newly developed thrombocytopenia. Two years ago, PRCA was diagnosed by the laboratory findings and a bone marrow examination, which showed no evidence of any myelodysplastic features and thymoma. Upon admission, the bone marrow findings showed marked hypercellularity. with numerous dysplastic features in the three lineages including erythroid hypoplasia. These findings were compatible with a diagnosis of MDS with red cell aplasia. It is very interesting that the PRCA evolved to MDS with red cell aplasia, which strongly suggests an autoimmune mechanism for the development of MDS.

Publication Types:
PMID: 15481612 [PubMed - indexed for MEDLINE]
51: Leuk Lymphoma. 2004 Sep;45(9):1913-8. Related Articles, Links
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Multiple myeloma in a patient with systemic lupus erythematosus, myasthenia gravis and non-familial diffuse palmoplantar keratoderma.

Urbanska-Rys H, Robak E, Kordek R, Bartkowiak J, Rieske P, Wozniacka A, Smolewski P, Robak T.

Department of Haematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-513 Lodz Pabianicka st. 62, Poland.

The coexistence of autoimmune diseases and malignancies including lymphoproliferative diseases is often reported in the literature. Here we report an unusual case with two autoimmune diseases--myasthenia gravis (MG) and systemic lupus erythematosus (SLE) associated with unique palmoplantar keratoderma (PK) which preceded the development of multiple myeloma (MM) for twenty and seven years respectively. MG associated with non-malignant thymoma developed in 1981 and was successfully treated with thymectomy and physostigmine. Thirteen years later SLE was diagnosed and until now it is also accompanied by skin lesions corresponding to non-familial, diffuse palmoplantar keratoderma which is resistant to treatment. In 2001 the patient revealed inguinal and abdominal lymphadenopathy first diagnosed as extramedullary plasmacytoma and then as multiple myeloma on the basis of bone marrow infiltration and monoclonal gammopathy. Therapy with VAD regimen achieved complete remission of the MM and significant improvement of the skin changes lasting for six months. We failed to collect sufficient numbers of CD 34+ cells for peripheral blood stem cell transplantation. Now the malignancy is in partial remission after CHOP therapy and the skin lesions have returned to their initial status. To our knowledge, this is the first case to be reported with coexistence of these four diseases. Copyright 2004 Taylor and Francis Ltd

Publication Types:
PMID: 15223654 [PubMed - indexed for MEDLINE]
52: Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):608-10. Related Articles, Links

[Diffuse panbronchiolitis complicated by thymoma: a case report and a review of literature]

[Article in Chinese]

Zhang D, Wang CH, Li Q.

Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

OBJECTIVE: To highlight the characteristics of diffuse panbronchiolitis (DPB). METHOD: One patient with DPB confirmed by thorocoscopic biopsy was described and relevant literatures were reviewed. RESULTS: DPB is a chronic lower respiratory tract disease common in Japanese, rare in China, characterized by infiltration of inflammatory cells around bronchioles. Although the etiology and precise mechanisms are under investigation, it is commonly hypothesized that heredity and immunity have a major role in DPB. Symptoms include cough, expectoration, and dyspnea after exercises. Pseudomonas aeruginosa is isolated from sputum in some cases. If left untreated, DPB progresses rapidly and has a poor prognosis if respiratory failure occurs. CONCLUSIONS: DPB should be included in the differential diagnosis of bilateral multiple pulmonary nodular shadows. Long-term, low-dose macrolide therapy may improve the prognosis through an anti-inflammatory effect.

Publication Types:
PMID: 15498273 [PubMed - indexed for MEDLINE]
53: Zhonghua Nei Ke Za Zhi. 2004 Sep;43(9):657-60. Related Articles, Links

[Influence factors on diagnosis and prognosis of thymoma: analysis of 135 cases.]

[Article in Chinese]

Tian XL, Zhu YJ.

Department of Respiratory Disease, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

OBJECTIVE: To investigate the clinical features and prognostic factors of thymoma. METHODS: 135 patients with a diagnosis of thymoma or thymic carcinoma were identified in Peking Union Medical University Hospital from Jan, 1990 to Feb, 2003. Their clinical presentation and prognostic factors were analyzed. RESULTS: Of the 135 patients, 21 (15.6%) were asymptomatic and 66 (48.9%) presented symptoms consistent with myasthenia gravis. Venous obstruction, male gender and longer disease course appeared to be the predisposing factors of malignancy (chi(2) = 8.373, P = 0.004; chi(2) = 6.125, P = 0.013; U = 1691.5, P = 0.013 respectively). Calcification and necrosis on radiological findings did not differentiate thymoma from thymic carcinoma. Tumor recurrence was related to the Masaoka stage and the course of disease by logistic method [Exp(b) = 1.050, 6.728, P = 0.038, 0.003]. The recurrence rate was 2.7% in stage I, 11.1% in stage II, 30.4% in stage III, and 83.3% in stage IV. CONCLUSIONS: Thymoma has a variable clinical manifestation. Clinical outcome is correlated with Masaoka stage and early tumor resection. Radiographic findings are not reliable in the differentiation of benign tumor from malignancy.

PMID: 15500776 [PubMed - in process]
54: Virology. 2004 Aug 15;326(1):29-40. Related Articles, Links
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Unique three-repeat sequences containing FVa, LVb/C4, and CORE motifs in LTR-U3 of Friend murine leukemia virus clone A8 accelerate the induction of thymoma in rat.

Takase-Yoden S, Watanabe R.

Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan. takase@t.soka.ac.jp

Friend murine leukemia virus (Fr-MLV) clone A8 causes thymoma 7 weeks postinfection in rats with a more rapid progression than clone 57. The U3 region of A8-LTR contains a unique structure of enhancer motifs consisting of three repeats of a 38-bp sequence containing FVa, LVb/C4, and CORE motifs. Replacement or deletion of the 38-bp sequence in the A8-U3 resulted in a marked reduction in tumorigenicity. Furthermore, the virus with 57-U3 gained high tumorigenicity after construction of the three 38-bp repeats in the U3 region. These findings indicated that the repeats of the 38-bp sequence of A8-LTR are essential for the rapid induction of thymoma. Interestingly, the repeat of the 38-bp sequence did not accelerate the amount of integrated viral DNA in the thymus during the early phase of infection, although it contributed to higher production of infectious virus. Thus, it was demonstrated that the ability to induce thymoma, which correlates with virus titer in the thymus, is not determined by the rate of viral DNA integration into the host genome.

PMID: 15262492 [PubMed - indexed for MEDLINE]
55: J Biol Chem. 2004 Aug 13;279(33):34373-9. Epub 2004 Jun 8. Related Articles, Links
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Nitric oxide inhibits glucocorticoid-induced apoptosis of thymocytes by repressing the SRG3 expression.

Jeong SM, Lee KY, Shin D, Chung H, Jeon SH, Seong RH.

School of Biological Sciences and Institute of Molecular Biology & Genetics, Seoul National University, Seoul 151-742, Korea.

Nitric oxide (NO) plays many roles in the immune system. It has been known that NO rescues thymocytes from glucocorticoid (GC)-induced apoptosis. However, the downstream target of NO in the protection from GC-induced thymocyte apoptosis has yet to be identified. We previously reported that GC sensitivity of developing thymocytes is dependent on the expression level of SRG3. In the present report, we found that NO repressed the SRG3 expression in both primary thymocytes and 16610D9 thymoma cells. Specifically, NO down-regulated the transcription of SRG3 via the inactivation of the transcription factor Sp1 DNA-binding activity to the SRG3 promoter. In addition, overexpression of SRG3 by a heterologous promoter reduced NO-mediated rescue of thymocytes from GC-induced apoptosis. These observations strongly suggest that NO may be involved in protecting immature thymocytes from GC-induced apoptosis by repressing the SRG3 expression in thymus.

PMID: 15187086 [PubMed - indexed for MEDLINE]
56: AJR Am J Roentgenol. 2004 Aug;183(2):283-9. Related Articles, Links
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Does CT of thymic epithelial tumors enable us to differentiate histologic subtypes and predict prognosis?

Jeong YJ, Lee KS, Kim J, Shim YM, Han J, Kwon OJ.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.

OBJECTIVE: The aims of our study were to describe the CT findings of thymic epithelial tumors and to correlate these findings with the histopathologic subtypes and prognosis. MATERIALS AND METHODS: The CT findings of thymic epithelial tumors were analyzed in 91 patients who had undergone surgery between May 1995 and June 2002. Two observers, who were unaware of the histopathologic classification made in accordance with World Health Organization (WHO) recommendations and the prognosis of the tumors, retrospectively reviewed the initial CT findings in terms of the contours and shapes of the tumors and the presence of necrosis, calcification, mediastinal fat or great vessel invasion, pleural seeding, contrast enhancement, and lymph node enlargement. These findings were compared with the simplified subgroups of WHO histologic classification (low-risk thymomas [types A, AB, and B1], high-risk thymomas [types B2 and B3], and thymic carcinomas [type C]) and with postoperative recurrence. RESULTS: The study found 31 low-risk thymomas (eight type A, 16 type AB, and seven type B1 tumors), 45 high-risk thymomas (25 type B2 and 20 type B3), and 15 thymic carcinomas (type C). Lobulated contour was more often seen in high-risk thymomas (26/45, 58%; p = 0.0456) and thymic carcinomas (10/15, 67%; p = 0.033) than in low-risk thymomas (9/31, 29%). Mediastinal fat invasion was more often seen in thymic carcinomas (5/15, 33%; p = 0.0133) than in low-risk thymomas (1/31, 3%). Great vessel invasion was seen only in thymic carcinomas (2/15, 13%; p = 0.0244). Tumors with a lobulated or irregular contour, an oval shape, mediastinal fat or great vessel invasion, and pleural seeding showed significantly more frequent recurrence and metastasis (all, p < 0.05). CONCLUSION: Although CT is of limited value in differentiating histologic subtypes according to the WHO classification, CT findings may serve as predictors of postoperative recurrence or metastasis for the thymic epithelial tumors.

PMID: 15269013 [PubMed - indexed for MEDLINE]
57: Ann Thorac Surg. 2004 Aug;78(2):411-6. Related Articles, Links
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Atypical thymoma: a report of seven patients.

Baran JL, Magro CM, King MA, Williams TE Jr, Ross P Jr.

School of Medicine and Public Health, Ohio State University, Columbus, OH 43210, USA.

BACKGROUND: Most thymic neoplasms fall under the designation of thymoma, consisting of well-differentiated epithelial cells, resembling normal thymus. At the opposite spectrum are thymic carcinomas; the cell of origin while similar is malignant. Recently a third category of thymic neoplasms, atypical thymomas, has been recognized representing thymic neoplasms manifesting atypia although without overt cytomorphologic criteria of malignancy. METHODS: Seven patients with a diagnosis of atypical thymoma were encountered over a 6-year period from the patient files of the cardiothoracic division of The Ohio State Medical Center. RESULTS: In all patients there was gross or light microscopic invasive disease with involvement of the capsule, phrenic nerve, diaphragm, chest wall, and lung. Surgical extirpation/de-bulking along with radiation therapy in six and chemotherapy in one led to complete disease regression. Intrathoracic recurrences developed in 4 involving lung, pleura, chest wall and diaphragm. All patients are well. CONCLUSIONS: Atypical thymomas are locally aggressive tumors with a high incidence of intrathoracic recurrence; extrathoracic spread is not seen. Our study corroborates other reports that death attributable to atypical thymoma is uncommon.

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PMID: 15276487 [PubMed - indexed for MEDLINE]
58: Cancer Res. 2004 Aug 1;64(15):5059-62. Related Articles, Links
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Uric acid promotes tumor immune rejection.

Hu DE, Moore AM, Thomsen LL, Brindle KM.

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.

Uric acid released from dying cells has been shown recently to act as a danger signal for the immune system, stimulating dendritic cell maturation and enhancing T-cell responses to foreign antigens. Stimulation of dendritic cell maturation by uric acid has been proposed as a mechanism by which the immune system could generate responses against tumors. We show here that uric acid levels are elevated in tumors undergoing immune rejection and that the inhibition of uric acid production, by systemic administration of allopurinol, or the removal of uric acid, by administration of uricase, delayed tumor immune rejection, whereas subcutaneous administration of crystalline uric acid enhanced the rejection process.

PMID: 15289304 [PubMed - indexed for MEDLINE]
59: Eur J Cardiothorac Surg. 2004 Aug;26(2):412-8. Related Articles, Links
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Long-term survival and prognostic factors in thymic epithelial tumours.

Rea F, Marulli G, Girardi R, Bortolotti L, Favaretto A, Galligioni A, Sartori F.

Thoracic Surgery, University of Padua, via Giustiniani, 2, 35128 Padua, Italy. federico.rea@unipd.it

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

PMID: 15296907 [PubMed - indexed for MEDLINE]
60: Eur J Cardiothorac Surg. 2004 Aug;26(2):407-11. Related Articles, Links
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Safety for preoperative use of steroids for transsternal thymectomy in myasthenia gravis.

Zielinski M, Kuzdzal J, Staniec B, Harazda M, Nabialek T, Pankowski J, Szlubowski A, Medon J.

Department of Thoracic Surgery, Pulmonary Hospital, Zakopane, ul. Gladkie 1, 34-500 Zakopane, Poland. marcinz@mp.pl

OBJECTIVE: Effects of preoperative steroids on morbidity and mortality after transsternal thymectomy are analyzed. METHODS: There were 620 transsternal thymectomies for myasthenia gravis performed in the period 1973-2002. There were 547 patients with nonthymomatous myasthenia, including 17 patients submitted to repeated thymectomy (rethymectomy) and 46 patients with thymoma. There were 522 upper median sternotomies performed in the period 1973-1997 and 98 complete median sternotomies performed in the period 1998-2002 (74 patients without thymoma, 7 thymomas and 17 rethymectomies). One hundred and seventeen of these 620 patients were taking steroids preoperatively. The impact of steroids use on postoperative respiratory insufficiency (ventilator), need for tracheostomy, superficial wound dehiscence, superficial wound suppuration, sternal dehiscence and mortality was analyzed. RESULTS: The rate of morbidity and mortality in the steroids and the no-steroids groups included respiratory insufficiency necessitating the use of a ventilator in 46/503 patients from the no-steroids group (9.1%) and 8/117 patients from the steroids group (6.8%; P = 0.4260), need for tracheostomy in 14/503 patients from the no-steroids group (2.8%) and 3/117 patients from the steroids group (2.6%; P = 9054). Complications with wound healing (including sternal dehiscence, superficial wound dehiscence and superficial wound suppuration) occurred in 47/503 (9.3%) patients from the no-steroids group and in 1/117 (0.9%) patient from the steroids group (P = 0.0023) The overall complications rate was 30.6% (154/503) in the no-steroids group and 11.1% (13/117) in the steroids group (P = 0.0001). Mortality rate in the no-steroids group was 0.4% (2/503 patients) and none in the steroids group. Morbidity in patients with complete sternotomy was low, respiratory insufficiency in three patients (3.1%), and superficial wound suppuration in one patient (1.0%), no other morbidity and no mortality. Changing morbidity in periods 1973-1980, 1981-1990 and 1991-2002 is analyzed. CONCLUSIONS: Preoperative use of steroids for transsternal thymectomy in patients with myasthenia gravis had no negative impact on morbidity and mortality, conversely, the results in patients taking steroids were better, with significant difference of results regarding the overall complication rates and the overall complication rates of wound healing.

PMID: 15296906 [PubMed - indexed for MEDLINE]
61: Eur J Cardiothorac Surg. 2004 Aug;26(2):401-6. Related Articles, Links
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Thymic carcinoma. Clinical institutional experience with 15 patients.

Takeda S, Sawabata N, Inoue M, Koma M, Maeda H, Hirano H.

Department of Thoracic Surgery, Toneyama National Hospital, Toneyama 5-1-1, Toyonaka City, Osaka 560-8552, Japan. stakeda@toneyama.hosp.go.jp

OBJECTIVE: We retrospectively evaluated 15 patients with thymic carcinoma treated with various modalities and investigated overall management of this disease. METHODS: From 1983 to 2003, we treated 15 patients with thymic carcinoma (12 squamous cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma). According to Masaoka's staging system, they consisted of 2 at stage II, 5 at stage III, 4 at stage IVa and 4 at stage IVb. RESULTS: Ten patients were histologically diagnosed preoperatively, and 5 patients underwent an exploratory procedure under the diagnosis of thymoma or benign teratoma. Complete resection was performed in 9 patients (2 stage II, 5 stage III and 2 stage IVa), which included 4 patients who received induction therapy, 4 who received postoperative radiation therapy, and 1 who received postoperative chemotherapy. Six patients with unresectable tumors were treated by irradiation (40-60 Gy) with or without chemotherapy. The median survival was 13 months for patients without resection, and 57 months for patients with a complete resection. Total 3-year and 5-year survival rates were 51.9 and 39.0%, respectively. CONCLUSIONS: We concluded that a complete resection is mainstay of therapy when possible, but chemoradiation therapy being potential benefit in the management of thymic carcinoma. However, considering the high prevalence of advanced stage patients, to establish the effective regimen of induction therapy in the additional multicenter trials should be mandatory.

Publication Types:
PMID: 15296905 [PubMed - indexed for MEDLINE]
62: Histopathology. 2004 Aug;45(2):202-4. Related Articles, Links
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'Ectopic' ectopic hamartomatous thymoma.

Kazakov DV, Mukensnabl P, Hes O, Michal M.

Publication Types:
PMID: 15279645 [PubMed - indexed for MEDLINE]
63: J Autoimmun. 2004 Aug;23(1):63-73. Related Articles, Links
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Characterization of the immunoreactivity of anti-interferon alpha antibodies in myasthenia gravis patients. Epitope mapping.

Bello-Rivero I, Cervantes M, Torres Y, Ferrero J, Rodriguez E, Perez J, Garcia I, Diaz G, Lopez-Saura P.

Centro de Investigaciones Biologicas, Clinical Trials Division, P.O. Box 6332, La Habana, Cuba. iraldo.bello@cigb.edu.cu

Cytokines, such as interferons (IFN), underlie many immunological functions and are increasingly implicated in disease-related symptoms and pathology. In order to study the potential roles of IFN alpha and its antagonists in autoimmune phenomena, the sera from 89 patients (aged 15-95 years, 65 females) diagnosed as having myasthenia gravis (MG) (2 months to 34 years duration) were tested for the presence of natural anti-IFN alpha-2b auto-antibodies. Sera were screened for anti-IFN alpha-2b by a sandwich-type enzyme immunoassay system. Ten (11.2%) and 6 (6.7%) sera were identified that contained positive-competing and non-competing anti-IFN alpha-2b auto-antibodies, respectively. The MG sera were further analyzed by immunobloting against reduced IFN alpha-2b and for neutralizing anti-IFN alpha activity in an antiviral assay cells system. From tested EIA positive-competing sera, 5 were shown to be positive by immunoblot and 6 sera were found to contain neutralizing anti-IFN alpha-2b. Four of the 6 neutralizing anti-IFN alpha-2b sera came from patients with thymoma-associated MG. The sera were studied for linear epitope recognition on the IFN alpha-2b molecule by a solid phase binding assay, in which overlapping peptides homologous with the entire IFN alpha-2b sequence were separately synthesized on a nitrocellulose sheet. Peptides number 2 (residues 8-21), 3 (15-28), 6 (33-46), 10 (63-76), 15 (98-112), and 21 (141-154) were immunoreactive. Peptide 21 was apparently associated with antiviral activity, although peptide 21 has not been previously described as an immunogenic determinant on the IFN alpha-2b molecule. These results indicate that neutralizing anti-IFN alpha-2b is often present in MG, particularly in cases of thymoma-associated MG, and recognize a variety of epitopes on the IFN alpha-2b molecule, including those involved in its biological activity. Two groups of IFN epitopes were described associated with patient's age but not with diseases evolution. Copyright 2004 Elsevier Ltd.

PMID: 15236754 [PubMed - indexed for MEDLINE]
64: J Clin Neurosci. 2004 Aug;11(6):610-3. Related Articles, Links
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Comparative study of pre-operative thymic imaging and pathology in patients with myasthenia gravis.

Yasukawa Y, Yoshikawa H, Iwasa K, Yamada M, Takamori M.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8640, Japan.

The objective of our study is to compare the diagnostic significance of mediastinal CT and (201)Tl-single-photon emission computed tomography (SPECT) with thymic histology in patients with myasthenia gravis (MG). The subjects were 30 patients with MG who were scheduled to receive thymectomy. They did not receive immunosuppressive therapy. The mediastinal CT and (201)Tl-SPECT were performed before the thymectomy. As a consequence, 9 patients had thymoma, 11 had lymphoid follicular hyperplasia (LFH), and 10 had normal thymus on histologic examination after thymectomy. Retrospectively, CT diagnosed the histology of all 9 patients with thymoma, and 5 of 11 with LFH. (201)Tl-SPECT could detect abnormal accumulations in only 6 of 9 cases of thymoma, and 6 of 11 cases of LFH. (201)Tl-SPECT could not distinguish thymoma from LFH. We conclude that a CT study is recommended as an essential study for the detection of thymic abnormalities in pre-operative patients with MG.

PMID: 15261231 [PubMed - in process]
65: J Neurol. 2004 Aug;251(8):1006-11. Related Articles, Links
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The significance of titin antibodies in myasthenia gravis--correlation with thymoma and severity of myasthenia gravis.

Chen XJ, Qiao J, Xiao BG, Lu CZ.

Institute of Neurology, Fudan University, 12 Wulumuqi Zhong Road, 200040, Shanghai, China.

Myasthenia gravis (MG) is caused by autoantibodies to acetylcholine receptors (AChR). Non-AChR muscle autoantibodies, such as titin antibodies, are present in sera of many MG patients. To study the correlation between titin antibodies and the features of MG, the cDNA segment encoding MGT-30 was amplified and sequenced. The cloned MGT-30 cDNA was expressed in vector pET-30a, and then transfected into E.coli. BL21. We examined titin antibodies in sera of 265 normal subjects, 154 MG patients with different thymic pathology and 48 patients with other neurological diseases. Titin antibodies occurred more frequently in MGT, especially in MG with epithelial predominant-thymoma, and were correlated with the severity of disease. The levels of titin antibodies were reduced 6 months after thymectomy. The specificity of titin antibodies for the detection of thymoma was higher than that of CT examination in MG with thymoma. These results suggest that titin antibodies could be useful in both diagnosis and follow-up of MG patients with thymoma.

PMID: 15316806 [PubMed - indexed for MEDLINE]
66: Kyobu Geka. 2004 Aug;57(9):905-9. Related Articles, Links

[Thymothymectomy for the thymoma with pure red cell aplasia; report of a case]

[Article in Japanese]

Ayabe T, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Ninomiya H, Onitsuka T.

Department of Second Surgery, Miyazaki Medical College, Miyazaki, Japan.

We report a case of thymothymectomy for the thymoma with pure red cell aplasia (PRCA). A 31-year-old male with a general fatigue had a severe anemia (hemoglobin 3.1 g/dl) since November 1997. By the bone marrow examination, PRCA was diagnosed and treated with blood transfusion and immunosuppressive drug (cyclosporin: CYA) administration but anemia had not been improved. The chest computed tomography displayed a 3 cm in a diameter of thymoma located in the anterior mediastinum. The extended thymothymectomy had been performed in February 1998, pathological detection disclosed Masaoka classification stage I, type AB was diagnosed due to the World Health Organization (WHO) classification. PRCA had not obtained an immediate remission during the postoperative-early term, while, adjuvant therapy (CYA 300 mg/day) has been continued and it brought a complete remission of PRCA in August 2001 (after the postoperative 3 years and 6 months later). Conclusions: Even though only thymothymectomy for thymoma with PRCA showed no effectiveness for the postoperative-early remission of PRCA, however, the combination of thymectomy and the postoperative adjuvant therapy (CYA) should bring a better outcome, and the continuous follow-up would be required for a long postoperative term.

Publication Types:
PMID: 15366581 [PubMed - indexed for MEDLINE]
67: J Immunol. 2004 Jul 15;173(2):900-9. Related Articles, Links
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IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21.

Moroz A, Eppolito C, Li Q, Tao J, Clegg CH, Shrikant PA.

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Cytokines that use the common receptor gamma-chain for regulating CD8(+) T cell responses to Ag include IL-2, IL-15, and the recently identified IL-21. The ability of these cytokines to regulate antitumor activity in mice has generated considerable interest in understanding their mode of action. In this study we compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21-treated mice. By monitoring both endogenous and adoptively transferred tumor Ag-specific CD8(+) T cells, it was determined that IL-21 activities overlap with those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal expansion. However, unlike IL-2 treatment, which induces activation-induced cell death, IL-21 sustained CD8(+) T cell numbers long term as a result of increased survival, an effect often attributed to IL-15. These findings indicate that the mechanisms used by IL-21 to promote CD8(+) T cell responses offer unique opportunities for its use in malignant diseases and infections.

PMID: 15240677 [PubMed - indexed for MEDLINE]
68: Ann Thorac Surg. 2004 Jul;78(1):259-65; discussion 265-6. Related Articles, Links
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Early experience with robot-assisted surgery for mediastinal masses.

Bodner J, Wykypiel H, Greiner A, Kirchmayr W, Freund MC, Margreiter R, Schmid T.

Department of General and Transplant Surgery, Innsbruck University Hospital, Innsbruck, Austria.

BACKGROUND: We report the experience of a single institution with the minimally invasive resection of mediastinal masses using the da Vinci robotic surgical system. METHODS: From August 2001 to June 2003, 14 patients (5 men and 9 women aged from 21 to 77 years) with mediastinal masses were operated on minimally invasively with the da Vinci robotic system. This consisted of 9 thymectomies (6 thymomas, 2 nonatrophic thymic glands, 1 thymic cyst), 3 resections of paravertebral neurinomas, 1 ectopic mediastinal parathyroidectomy, and 1 resection of a lymphangioma. RESULTS: Complete, extended thymectomy was accomplished in all 9 cases, proven by examination of the thymic bed and resected specimen. In 1 patient with an hourglass-shaped neurinoma, conversion to an open procedure was necessary because the excessive size of the tumor limited vision. The median overall operation time was 166 minutes (range, 61 to 182) including 110 minutes (range, 46 to 142) for the robotic act. There were no intraoperative complications or surgical mortality. CONCLUSIONS: These preliminary results of our series suggest that application of the da Vinci robotic surgical system for resection of selected mediastinal masses is technically feasible and safe. It provides an alternative to open approaches and "conventional" thoracoscopy. Nevertheless, this new technique requires further investigation in larger series and longer follow-up.

Publication Types:
PMID: 15223439 [PubMed - indexed for MEDLINE]
69: Ann Thorac Surg. 2004 Jul;78(1):253-8. Related Articles, Links
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Comparison of late results of basic transsternal and extended transsternal thymectomies in the treatment of myasthenia gravis.

Zielinski M, Kuzdzal J, Szlubowski A, Soja J.

Department of Thoracic Surgery, Pulmonary Hospital, Zakopane, Poland. marcinz@mp.pl

BACKGROUND: The influence of the technique of thymectomy on late results in the treatment of myasthenia gravis remains controversial. METHODS: Results of 60 basic transsternal thymectomies and 58 extended transsternal thymectomies were compared. Both positive results (complete remissions or improvement) and negative results (no improvement, deterioration, or death from myasthenia) were analyzed. RESULTS: There were no differences between both groups according to patient's characteristics and postoperative complications rate. Ectopic foci of the thymic tissue were discovered in the fat of the neck and the mediastinum in 56.9% of patients from the extended thymectomy group. The foci occurred in all areas of dissection of the neck and the mediastinum. Complete remission rates in the basic thymectomy group were 8.3%, 11.7%, 15.0%, 16.7%, 20.0%, and 21.7% after 1, 2, 3, 4, 5, and 6 years of follow-up, respectively, and 29.3%, 37.9%, 41.4%. and 46.6% after 1, 2, 3, and 4 years, respectively, in the extended thymectomy group. The differences between both groups after 1, 2, 3, and 4 years were statistically significant (p = 0.0093, p = 0.0013, p = 0.0018, and p = 0.0007, respectively). Negative results were noted in 23.3% of patients in the basic thymectomy group and in 6.9% of patients in the extended thymectomy group (p = 0.0613). No other factors had any influence on the results. CONCLUSIONS: Late results, both positive and negative, were considerably better in the extended thymectomy group. The difference can be explained by the removal of ectopic foci of the thymic tissue from the neck and the mediastinum in these patients.

Publication Types:
PMID: 15223438 [PubMed - indexed for MEDLINE]
70: Chang Gung Med J. 2004 Jul;27(7):515-22. Related Articles, Links

Concurrent chemoradiotherapy for unresectable thymic carcinoma.

Chen YY, Huang CH, Tang Y, Eng HL.

Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan 833, ROC.

BACKGROUND: Thymic carcinoma is a rare anterior mediastinal neoplasm. It is more invasive and has a poorer prognosis than ordinary thymoma. Complete curative resection is frequently impossible to achieve because of extensive invasion or metastasis at diagnosis. The role of systemic chemotherapy and the optimal regimen in thymic carcinoma remain uncertain. We report our experience with 16 patients with unresectable thymic carcinoma who underwent concurrent chemoradiotherapy. METHODS: Between July 1989 and July 2003, 29 patients were diagnosed with unresectable thymic carcinoma at our hospital. Sixteen of the 29 patients were treated with concurrent chemoradiotherapy. There were 10 men and 6 women whose ages ranged from 45 to 66 years old. Chemotherapy regimens consisted of either (A) cisplatin plus 5-fluorouracil or (B) doxorubicin, cisplatin, vincristine and cyclophosphamide every 4 weeks for at least 2 cycles. Radiotherapy was given concurrently and ranged from 34.2 to 70 Gy. RESULTS: There were 4 (25.0%) patients with complete responses, 4 (25.0%) with partial responses, 6 (37.5%) with stable disease and 2 (12.5%) with progressive disease. The overall response rate was 50%. The median follow-up was 64 months, and the median survival was 82 months. The overall cumulative survival rates at 1, 2, 3, and 5 years were 93.8%, 81.3%, 74.5%, and 67.7%, respectively. The most common side effects were Grade I/II toxicity, including vomiting, fatigue, and esophagitis. All patients experienced radiation pneumonitis. No life-threatening side effects were noted. CONCLUSIONS: Concurrent chemoradiotherapy seems effective for unresectable thymic carcinoma. Our experience, although preliminary, is encouraging and merits conducting a randomized trial to determine the impact of concurrent chemoradiotherapy on unresectable thymic carcinoma.

PMID: 15508874 [PubMed - indexed for MEDLINE]
71: Clin Exp Dermatol. 2004 Jul;29(4):430-2. Related Articles, Links
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Acrokeratosis paraneoplastica associated with recurrent metastatic thymic carcinoma.

Chave TA, Bamford WM, Harman KE.

Publication Types:
PMID: 15245552 [PubMed - indexed for MEDLINE]
72: Clin Lung Cancer. 2004 Jul;6(1):28-32. Related Articles, Links
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Thymoma and thymic carcinoma: therapeutic approaches.

Kurup A, Loehrer PJ Sr.

Department of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.

Thymomas and thymic carcinomas, which are rare epithelial tumors arising from the thymus gland, are the most common tumors of the anterior mediastinum. Thymomas are generally encapsulated, slow-growing tumors that have a "bland" histologic appearance. Thymic carcinomas possess more overtly malignant histologic features than thymomas and are more likely to present as invasive or disseminated disease. Surgery is the treatment of choice for localized thymic tumors, with complete resection being the most important prognostic factor. Complete resection also improves survival in locally invasive thymic tumors. Adjuvant postoperative radiation therapy may improve the outcome in patients with invasive disease, although the data are conflicting. Multimodal regimens, including neoadjuvant combination chemotherapy, surgery, and/or postoperative radiation therapy, are recommended for patients with advanced thymomas and thymic carcinomas. Use of octreotide plus prednisone has produced responses in thymomas, but the dosing and schedule have not been clearly defined. Prospective studies have been limited, and, as such, enrollment in clinical trials is encouraged.

Publication Types:
PMID: 15310414 [PubMed - indexed for MEDLINE]
73: Hum Immunol. 2004 Jul;65(7):752-7. Related Articles, Links
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HLA genotypes in Turkish patients with myasthenia gravis: comparison with multiple sclerosis patients on the basis of clinical subtypes and demographic features.

Donmez B, Ozakbas S, Oktem MA, Gedizlioglu M, Coker I, Genc A, Idiman E.

Department of Neurology, Dokuz Eylul University, Izmir, Turkey.

The nature and intensity of the association of myasthenia gravis (MG) with distinct human leukocyte antigens (HLA) haplotypes differ between ethnic populations. The aims of the present study were to examine the relationship between HLA class I and II haplotypes and MG; to show the HLA associations with various MG subsets; and to investigate the association between MG and clinical subgroups of multiple sclerosis (MS) regarding HLA haplotypes. A total of 66 patients with MG were enrolled onto the study. The mean age at onset was 42.01 years. A total of 122 clinically definite MS patients and 188 healthy subjects were examined as control groups. The present study clearly showed associations with HLA-DR3, -B8, -A1, and -A2 in MG. In patients with early-onset MG, associations with HLA-DR3, -B8, and -A2 were stronger. When compared with MS, in the MG group, there was still a strong association with -B8, -DR3, and -A1. In subgroup analysis, there was no difference between MG and primary progressive MS patients. On the basis of the presence of anti-AChR antibodies, there was a statistically significant association with HLA-DR3. On the basis of presence of thymoma, no HLA allele showed clear associations in MG patients with thymoma. This is the first study to examine the relationship between HLA haplotypes and MG in the Turkish population and to compare MG with another autoimmune disease, MS, on the basis of the HLA haplotypes. Further investigations with a larger population are required to explain this finding.

PMID: 15301866 [PubMed - indexed for MEDLINE]
74: Indian J Gastroenterol. 2004 Jul-Aug;23(4):152-3. Related Articles, Links
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Good's syndrome: an unusual cause of chronic diarrhea.

Khanna S, Kumar A, Tandon R.

Department of Gastroenterology, Pushpawati Singhania Research Institute for Liver, Renal and Digestive Diseases, Shiekh Sarai-Phase II, New Delhi-110 019, India. khannasudeep@hotmail.com

A 50-year-old man presented with recurrent episodes of pulmonary infections over a period of 5 years, chronic small bowel diarrhea and weight loss of 6 months' duration. On evaluation he was found to have a thymoma, intestinal infection with giardia, oral candidiasis, and low immunoglobin levels. He was diagnosed to have Good's syndrome. The patient refused further management.

Publication Types:
PMID: 15333980 [PubMed - indexed for MEDLINE]
75: Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):654-64. Related Articles, Links
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Thymic carcinoma: state of the art review.

Eng TY, Fuller CD, Jagirdar J, Bains Y, Thomas CR Jr.

Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, 78284-7800, USA. tyeng@pol.net

Thymic carcinoma is a rare neoplasm with distinct clinical and pathological characteristics. The prognosis is often poor with an aggressive course that belies its numerical rarity. Potentially prognostic factors for survival include histopathologic grade, clinical stage, and resectability of the tumor. Five-year survival rates for all patients are approximately 30-50%, with a significant survival time differential between low-grade and high-grade neoplasms. Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. At present, a multimodality approach involving aggressive surgical resection, platinum-based combination chemotherapeutic interventions, and radiotherapy represent the preferred therapeutic approach. Though our knowledge remains somewhat speculative at present, several scientific, technological and therapeutic innovations may have a potentially significant impact on the future of this disease.

Publication Types:
PMID: 15183468 [PubMed - indexed for MEDLINE]
76: J Immunol. 2004 Jul 1;173(1):222-9. Related Articles, Links
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Antigen distribution drives programmed antitumor CD8 cell migration and determines its efficiency.

Boissonnas A, Combadiere C, Lavergne E, Maho M, Blanc C, Debre P, Combadiere B.

Laboratoire d'Immunologie Cellulaire, Institut National de la Sante et de la Recherche Medicale, Unite 543, Faculte de Medecine Pitie-Salpetriere, 91 Boulevard de l'Hopital, 75634 Paris cedex 13, France.

Understanding both the role of tumor Ag in CD8 cell differentiation and the reasons that CD8 cells may work inefficiently is crucial for therapeutic approaches in cancer. We studied OT-1 CD8 cell responses in vivo in a differential Ag-distribution model that used EG-7, the EL-4 thymoma transfected with OVA. On their initial Ag encounter, OT-1 CD8 cells underwent programmed expansion in the lymph nodes, where they acquired the ability to migrate to the encapsulated tumor site after > or =4 divisions, without continuous antigenic stimulation. This short antigenic stimulation was sufficient to induce the migration differentiation program, which included modulation of chemokine receptor mRNA expression and down-regulation of CD62L. Moreover, Ag quantity determined the behavior of the OT-1 CD8 cells, including their effector functions and sensitivity to apoptosis. Thus, the initial Ag encounter drives the programmed cell migration potencies, but neither effector functions nor cell death can occur without continuous TCR triggering.

PMID: 15210778 [PubMed - indexed for MEDLINE]
77: J Thorac Imaging. 2004 Jul;19(3):192-5. Related Articles, Links
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Thymic masses of the middle mediastinum: report of 2 cases and review of the literature.

Minniti S, Valentini M, Pinali L, Malago R, Lestani M, Procacci C.

Department of Radiology, University of Verona, Italy. procacci@univr.it

Although thymic lesions are relatively common causes of anterior mediastinal masses, they can rarely arise in other mediastinal compartments, as it is well recognized that thymic tissue can lie in ectopic intrathoracic locations. A thymic mass within the middle mediastinum has rarely been reported, with only a single case of a thymic cyst described and no reports of a middle mediastinal thymoma. We report 2 thymic masses (1 thymoma and 1 thymic cyst) found to arise in the middle mediastinum.

Publication Types:
PMID: 15273616 [PubMed - indexed for MEDLINE]
78: Jpn J Thorac Cardiovasc Surg. 2004 Jul;52(7):345-8. Related Articles, Links

Triad of thymoma, myasthenia gravis and pure red cell aplasia combined with Sjogren's syndrome.

Fujiu K, Kanno R, Shio Y, Ohsugi J, Nozawa Y, Gotoh M.

First Department of Surgery, Fukushima Medical University, Hikarigaoka, Fukushima, Japan.

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sjogren's syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sjogren's syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.

Publication Types:
PMID: 15296032 [PubMed - indexed for MEDLINE]
79: Nihon Kokyuki Gakkai Zasshi. 2004 Jul;42(7):660-4. Related Articles, Links

[Six cases of thymic carcinoma: a clinical review]

[Article in Japanese]

Takemura Y, Yuba T, Kono K, Hosogi K, Osugi S, Kuwahara H, Nagata K, Harada H, Yokomura I, Iwasaki Y.

Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto-city, Japan.

Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.

Publication Types:
PMID: 15357270 [PubMed - indexed for MEDLINE]
80: Nihon Kokyuki Gakkai Zasshi. 2004 Jul;42(7):634-9. Related Articles, Links

[Thymic carcinoma. A clinicopathological study of seven patients]

[Article in Japanese]

Mochizuki T, Numata T, Kimura A, Onodera R, Kojima A, Kotajima F, Satou T, Tai H, Satou S, Akiba N, Yosimura K, Ito H, Oka T.

Division of Respiratory Disease, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minatoku, Tokyo 105-8461, Japan.

The treatment of seven cases of thymic carcinoma is reported. According to the Masaoka classification of the disease, there were five cases of stage III and two of stage IVb. Five were identified histopathologically as squamous cell carcinoma, one as undifferentiated carcinoma, and one as small cell neuroendocrine carcinoma. Surgery was performed during the course of chemotherapy and radiotherapy in 5 cases, and in 2, the organs infiltrated by neoplastic cells were partially excised together. Radiotherapy was performed as adjuvant therapy in one case of partial excision. In another case, after six years of chemotherapy and radiotherapy that yielded a partial response (PR), cancerous infiltration of the chest wall occurred, and partial removal of the chest wall became necessary. After the remaining case showed a PR to chemotherapy, complete macroscopic excision of the tumor was undertaken, but mediastinal lymph gland metastasis was present, and so radiotherapy was also initiated. In two cases, surgery was not performed. One of these was treated with chemotherapy alone, the other, only with radiotherapy. The mean survival period of the five patients who died as a result of their tumors was 44.8 months. One of the two who survived for over four years had squamous cell carcinoma, the other, undifferentiated carcinoma. The case of small cell neuroendocrine carcinoma was assessed as having a PR, and so complete extraction of the thymic neoplasm was carried out, and followed with radiotherapy. This patient is still alive.

PMID: 15357265 [PubMed - indexed for MEDLINE]
81: Rev Invest Clin. 2004 Jul-Aug;56(4):528-9; author reply 530. Related Articles, Links

Comment on:
[Response to thymectomy in patients with thymoma and myasthenia gravis]

[Article in Spanish]

Santillan-Doherty P.

Publication Types:
PMID: 15587300 [PubMed - indexed for MEDLINE]
82: Tunis Med. 2004 Jul;82(7):698-700. Related Articles, Links

[Hypertrophic osteoarthropathy revealing a malignant thymoma in a child]

[Article in French]

Aloui N, Mrad S, Bellagha I, Barsaoui S, Hammou A.

Service de radiologie, Hopital d'enfants de Tunis.

Association of hypertrophic osteoarthropathy and malignant thymoma is very rare in children. Authors report a case of a 14 year old girl followed for rheumatic fever since she was 8 years old. She was explored for arthralgia. The exam showed hippocratic fingers, soft tissues hypertrophy of lower limbs and dyspnoea. Plain radiography had demonstrated symmetrical ossifying periostisis in tubular bones of lower limbs evocating hypertrophic osteoarthropathy diagnosis. Chest radiography has demonstrated bilobate anterior mediastinal mass. Ultrasonography and MRI revealed a voluminous anterior mediastinal mass with cystic and fleshy components. Thymic adenocarcinoma diagnosis was made by surgical biopsy.

Publication Types:
PMID: 15552030 [PubMed - indexed for MEDLINE]
83: Vet Pathol. 2004 Jul;41(4):429-33. Related Articles, Links
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Thymoma-associated exfoliative dermatitis in cats.

Rottenberg S, von Tscharner C, Roosje PJ.

Interdisciplinary Dermatology Unit, Institute of Animal Pathology, Vet-Suisse Faculty Bern, Langgassstrasse 122, CH-3001 Bern, Switzerland.

Five cases of exfoliative dermatitis in cats were presented from 1996 to 2002 in which a feline thymoma was found by postmortem or postsurgical examination. Besides abundant exfoliation of keratin squames and layers, the histologic picture of the skin revealed a similar pattern of interface dermatitis with predominantly CD3+ lymphocytes and fewer mast cells and plasma cells. In the epidermal basal layer a hydropic degeneration of keratinocytes was present. In all cases an infundibular lymphocytic mural folliculitis and absence of or drastic decrease in the number of sebaceous glands occurred. In addition to the so far described cell-poor type, we also found examples of a cell-rich skin lesion. Together with the clinical observation of generalized exfoliative dermatitis, the histologic pattern of this dermatitis was suggestive of an underlying thymoma. The pathogenesis of this skin disease in association with thymic neoplasia remains obscure, and our results contradict the hypothesis of production of autoantibodies that cross-react with epithelial antigens. The morphology of the thymomas and CD3 expression of the thymocytes varied and did not seem to have an impact on the dermal lesions.

Publication Types:
PMID: 15232147 [PubMed - indexed for MEDLINE]
84: Vet Pathol. 2004 Jul;41(4):346-52. Related Articles, Links
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Comparative morphologic and immunohistochemical investigation of spontaneously occurring thymomas in a colony of European hamsters.

Brandes K, Fend F, Monecke S, Teifke JP, Breuer W, Hermanns W.

Institute of Veterinary Pathology, Ludwig-Maximilians-University Muenchen, Munich, Germany. brandes@patho.vetmed.uni-muenchen.de

This study documents the characteristics of a large series of spontaneously occurring thymomas in a laboratory colony of European hamsters (Cricetus cricetus). Thymomas are rare organotypic neoplasms originating from the thymic epithelial compartment. Because the hamster thymomas largely resembled their human counterparts, the recent World Health Organization (WHO) classification of human thymic epithelial tumors was used. Forty hamsters of both sexes aged 3-29 months were examined macroscopically and histologically. In 22 (55%) of the 40 animals, necropsy revealed enormous whitish masses in the anterior mediastinum, with a diameter ranging from 0.5 to 4.5 cm and a lobulated structure. The anatomy of the thymus region was normal in the remaining 18 hamsters. Histologically, the tumors presented as thymuslike organoid structures with areas of medullary and cortical differentiation and a predominance of lymphoid cells. A network of epithelial cells in the cortical areas, demonstrated immunohistochemically with a cross-reactive antibody against pancytokeratin, supported the diagnosis of thymoma. Cortical lymphocytes showed positive staining with cross-reacting antibodies against CD3 and terminal deoxynucleotidyl transferase, characteristic of immature T cells. On the basis of these findings, the tumors were classified as B1 thymomas, in some cases with AB or B2 components, according to the new WHO classification for human thymic epithelial tumors.

PMID: 15232134 [PubMed - indexed for MEDLINE]
85: N Engl J Med. 2004 Jun 17;350(25):2625-6. Related Articles, Links

Thymic carcinoma with overexpression of mutated KIT and the response to imatinib.

Strobel P, Hartmann M, Jakob A, Mikesch K, Brink I, Dirnhofer S, Marx A.

Publication Types:
PMID: 15201427 [PubMed - indexed for MEDLINE]
86: Neurology. 2004 Jun 8;62(11):2132-3. Related Articles, Links
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Comment in:
MuSK antibodies in AChR Ab-seropositive MG vs AChR Ab-seronegative MG.

Ohta K, Shigemoto K, Kubo S, Maruyama N, Abe Y, Ueda N, Ohta M.

Clinical Research Center, Utano National Hospital, Kyoto, Japan. mohta@kobepharma-u.ac.jp

PMID: 15184636 [PubMed - indexed for MEDLINE]
87: Vaccine. 2004 Jun 2;22(17-18):2316-27. Related Articles, Links
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The apoptotic and necrotic effects of tomatine adjuvant.

Yang YW, Wu CA, Morrow WJ.

School of Pharmacy, College of Medicine, National Taiwan University, 1, Jen-Ai Road, Section 1, Taipei 100, Taiwan. ywyang@ha.mc.ntu.edu.tw

Tomatine adjuvant, consisting of tomatine, n-octyl-beta-d-glucopyranoside (OGP), phosphatidylethanolamine and cholesterol is unique in that when combined with soluble protein antigen it elicits a cytotoxic T lymphocyte (CTL) response in immunized animals. The mechanisms underlying this property are unknown. In an attempt to understand how tomatine activates cellular immunity, we examined its potential to induce apoptosis. Thus in the present study, cell death of EL4 thymoma cells induced by whole adjuvant and the surface-active components in the formulation was examined. Cytotoxicity was monitored using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and lactate dehydrogenase release assays, apoptosis and necrosis were quantified by flow cytometry using Annexin V and propidium iodide staining, and morphology was examined by Hoechst 33342 staining. Flow cytometric analysis demonstrated the appearance of the sub-G1 phase in cells treated with these agents and Annexin V/PI staining showed that all three agents induced both apoptosis and necrosis in EL4 cells in a concentration-dependent manner. Tomatine was effective at much lower concentrations than OGP, suggesting that the majority of the effect of whole adjuvant could be attributed to this component. Microscopic examination of EL4 cells after treatment with these agents revealed morphological features of apoptosis, including chromatin condensation and DNA fragmentation. Pretreatment with zVAD-fmk did not block cell death induced by these agents, showing that tomatine adjuvant-induced EL4 cell apoptosis is caspase-independent.

PMID: 15149791 [PubMed - indexed for MEDLINE]
88: Am J Clin Oncol. 2004 Jun;27(3):236-46. Related Articles, Links
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Treatment of thymoma: a comparative study between Thailand and the United States and a review of the literature.

Sunpaweravong P, Kelly K.

Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand. patrapim@hotmail.com

This article provides a unique perspective on thymoma by describing the clinical scenarios from 2 diverse patient populations followed by an update. A comparative chart review was conducted on patients diagnosed at 2 university-based hospitals, 1 in the United States and 1 in Thailand. A comprehensive review of the literature was then performed through MEDLINE for articles between 1980 and 2002. During the last 23 years, charts from 16 patients at each institution were available for review. The most common presenting symptoms were myasthenia gravis (47%), dyspnea (25%), and chest discomfort (19%) and are similar to those reported in the literature. The primary treatment of stages I-III disease included surgery with or without radiation. Trimodality therapy with surgery, radiotherapy, and chemotherapy was pursued in 43% of patients with stage IV disease in the United States, whereas no patients from Thailand underwent this regimen. Median overall survivals were 124 and 76 months in the Thai and the US groups, respectively (P = 0.76). No major differences in the clinical features were observed between the 2 institutions, although a trend toward more advanced disease was seen in the United States. Surgery and radiation remain the backbone of treatment, but the role for chemotherapy is increasing.

Publication Types:
PMID: 15170141 [PubMed - indexed for MEDLINE]
89: Am J Clin Pathol. 2004 Jun;121(6):867-71. Related Articles, Links
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"Ancient" (sclerosing) thymomas: a clinicopathologic study of 10 cases.

Moran CA, Suster S.

Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

We present 10 cases of "ancient" (sclerosing) thymomas in 4 women and 6 men (age range, 34-73 years; mean, 53.5 years). Clinically, 4 patients had a history of shortness of breath and chest pain of several weeks' duration, 1 had a history of myasthenia gravis, and 5 were asymptomatic (anterior mediastinal masses discovered on routine chest radiographs). All underwent complete surgical resection of the anterior mediastinal mass. The tumors were light tan and solid, without areas of hemorrhage or necrosis, and 5 to 10 cm in greatest diameter. Extensive areas of hyalinized fibroconnective tissue constituting about 85% to 90% of the tumor mass was the main tumor feature. Focal areas of conventional thymoma also were present in all tumors. Follow-up information was obtained for 8 patients. Of these 8 patients, 6 died, all of unrelated causes (congestive heart failure, renal insufficiency, and pulmonary edema), and 2 were alive 1 and 6 years after surgical resection. The present cases highlight an important histopathologic feature of thymomas, which can pose problems in diagnosis, namely when dealing with small mediastinoscopic biopsy specimens.

PMID: 15198359 [PubMed - indexed for MEDLINE]
90: Ann Hematol. 2004 Jun;83(6):398-400. Epub 2003 Dec 19. Related Articles, Links
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Remission induced by Campath-1H for thymoma-associated agranulocytosis.

Alvares CL, Svasti-Salee D, Rowley M, Gordon-Smith EC, Marsh JC.

Department of Haematology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK.

Thymoma-associated agranulocytosis is a rare but almost universally fatal condition. Reports to date have described several immunosuppressive therapies including steroids, cyclophosphamide and vincristine as adjuvants to thymectomy, in an effort to improve neutropenia. We report the response to the monoclonal antibody Campath-1H of a patient with a thymoma and associated agranulocytosis with complete absence of bone marrow granulocyte precursors, which had failed to respond to thymectomy. Treatment with Campath-1H resulted in complete responses of promising durability sustained with the addition of cyclosporin and mycophenolate mofetil as maintenance therapy.

Publication Types:
PMID: 14689236 [PubMed - indexed for MEDLINE]
91: Ann Thorac Surg. 2004 Jun;77(6):2209-10. Related Articles, Links
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Noninvasive thymoma in the middle mediastinum.

Kanzaki M, Oyama K, Ikeda T, Yoshida T, Murasugi M, Onuki T.

Department of Surgery I, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan. kanzaki@chi.twmu.ac.jp

We present a rare case of thymoma that developed entirely in the middle mediastinum. A 60-year-old woman was referred to our hospital with a mediastinal mass. The mass was located in the visceral compartment of Shields' mediastinal classification. Intraoperative pathologic evaluation revealed a thymoma, whereupon total thymectomy was performed. The postoperative course was uncomplicated and the patient received no postoperative adjuvant radiotherapy.

Publication Types:
PMID: 15172308 [PubMed - indexed for MEDLINE]
92: Br J Cancer. 2004 Jun 1;90(11):2181-5. Related Articles, Links
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Absence of human T-cell lymphotropic virus type I and human foamy virus in thymoma.

Li H, Loehrer PJ Sr, Hisada M, Henley J, Whitby D, Engels EA.

Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, 6120 Executive Blvd., EPS 8010, Rockville, MD 20892, USA.

The cause of thymoma, a rare malignancy of thymic epithelial cells, is unknown. Recent studies have reported the detection of DNA from human T-cell lymphotropic virus type I (HTLV-I) and human foamy virus (HFV) in small numbers of thymoma tumours, suggesting an aetiologic role for these retroviruses. In the present study, we evaluated 21 US thymoma patients and 20 patients with other cancers for evidence of infection with these viruses. We used the polymerase chain reaction to attempt to amplify viral DNA from tumour tissues, using primers from the pol and tax (HTLV-I) and gag and bel1 (HFV) regions. In these experiments, we did not detect HTLV-I or HFV DNA sequences in any thymoma or control tissues, despite adequate sensitivity of our assays (one HTLV-I copy per 25 000 cells, one HFV copy per 7500 cells). Additionally, none of 14 thymoma patients evaluated serologically for HTLV I/II infection was positive by enzyme-linked immunoassay (ELISA), while five (36%) had indeterminate Western blot reactivity. In comparison, one of 20 US blood donors was HTLV-I/II ELISA positive, and nine (45%) donors, including the ELISA-positive donor, had indeterminate Western blot reactivity. Western blot patterns varied across individuals and consisted mostly of weak reactivity. In conclusion, we did not find evidence for the presence of HTLV-I or HFV in US thymoma patients.

PMID: 15150553 [PubMed - indexed for MEDLINE]
93: Clin Nucl Med. 2004 Jun;29(6):390-1. Related Articles, Links
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Increased tc-99m tetrofosmin uptake in a mediastinal tumor during myocardial perfusion imaging.

Vijayakumar V, Soloff E, Rahman AM.

Nuclear Medicine Section, Department of Radiology, University of Texas Medical Branch, Galveston, Texas 77555-0793, USA. vavijaya@utmb.edu

Publication Types:
PMID: 15166893 [PubMed - indexed for MEDLINE]
94: Clin Rheumatol. 2004 Jun;23(3):262-5. Epub 2004 Mar 24. Related Articles, Links
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Efficacy of tacrolimus in treatment of polymyositis associated with myasthenia gravis.

Shimojima Y, Gono T, Yamamoto K, Hoshi K, Matsuda M, Yoshida K, Ikeda S.

Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621 Matsumoto, Japan.

We report a patient with polymyositis (PM) associated with myasthenia gravis (MG). Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. Oral tacrolimus was therefore tried, and produced an improvement in muscular symptoms in association with normalization of myogenic enzymes. PM associated with MG as in this patient might be the best indication for tacrolimus, considering its efficacy in MG, but this drug should also be actively considered as a therapeutic option in refractory cases of PM alone, particularly when either corticosteroids or other immunosuppressive agents are not usable.

PMID: 15168159 [PubMed - indexed for MEDLINE]
95: Haematologica. 2004 Jun 1;89(6 Suppl):ECR17. Related Articles, Links
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Successful treatment of pure red cell aplasia with cyclosporin A and erythropoietin after thymectomy in a 88-year old woman.

Maeda T, Shiokawa S, Yoshikawa Y, Hiroyama T, Nakajima Y, Muta H, Nakayama M, Nakazaki Y, Akizuki S, Shimizu K, Mutoh T, Somada S, Kurita R, Shiratsuchi M, Makino N, Nishimura J, Tani K.

Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Shin-Beppu Hospital. maedat@beppu.kyushu-u.ac.jp <maedat@beppu.kyushu-u.ac.jp>

An 88-year old Japanese female with pure red cell aplasia was treated safely and effectively by a combination of thymectomy, cyclosporin A, and erythropoietin. The thymoma was histologically classified as lymphocytic type or cortical type, which are uncommon in cases of a thymoma accompanied by pure red cell aplasia. Immunohistochemical analysis of the thymoma and bone marrow revealed a predominance of CD8(+) cells. Thymectomy alone was ineffective, but cyclosporin A treatment subsequent to thymectomy was safe and effective and resulted in the disappearance of a Vbeta12 bearing T-cell clone in the bone marrow. Additional treatment with erythropoietin enhanced the effects of cyclosporin A and restored the patient's hemoglobin to normal levels. The beneficial effect of cyclosporin A may be attributed not to a broad immunomodulatory effect, but to a local effect on a limited T-cell subset.

PMID: 15194553 [PubMed - in process]
96: Heart Lung Circ. 2004 Jun;13(2):191-4. Related Articles, Links
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Thymoma presenting with infarction.

Gray KM, Windsor M.

The Prince Charles Hospital, Rode Road, Chermside, Qld, Australia. martint@bigpond.net.au

Thymomas are the most common tumours of the anterior mediastinum with most patients presenting incidentally. We present a case of thymoma presenting with sudden onset severe chest pain and raised plasma aminotransaminases secondarily to spontaneous infarction. We discuss the presence of these aminotransaminases in this highly unusual presentation of thymoma and believe our case demonstrates the inherent limitations of plasma enzymes due to their lack of specificity and sensitivity.

PMID: 16352194 [PubMed]
97: J Exp Clin Cancer Res. 2004 Jun;23(2):343-4. Related Articles, Links

Myasthenic crisis following cisplatin chemotherapy in a patient with malignant thymoma.

Solak Y, Dikbas O, Altundag K, Guler N, Ozisik Y.

Dept of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

Malignant thymomas are associated with numerous autoimmune disorders including myasthenia gravis. Myastenia gravis is characterized by antibodies against the acetylcholine receptors located on the neuromuscular junction of the skeletal muscle. We present a case with malignant thymoma who developed myasthenia crisis while he was treated with cisplatin chemotherapy.

Publication Types:
PMID: 15354421 [PubMed - indexed for MEDLINE]
98: J Fish Dis. 2004 Jun;27(6):369-73. Related Articles, Links
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Epithelio-reticular cell thymoma in carp, Cyprinus carpio L: an ultrastructural study.

Romano LA, Marozzi VA.

Aquatic Biopathology Center, Bar-Ilan University, Buenos Aires, Argentina. cbadrromano@infovia.com.ar

Publication Types:
PMID: 15189377 [PubMed - indexed for MEDLINE]
99: J Vet Med Sci. 2004 Jun;66(6):713-5. Related Articles, Links
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Thymoma in a dog with a part of granular cell proliferation and concurrent lymphoma cells.

Fukuoka A, Nakayama H, Nakayama Y, Yasoshima A, Uetsuka K, Fujino Y, Tsujimoto H, Doi K.

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.

A 12-year-old male Shiba dog showed anemia and the swelling of systemic lymph nodes. X-ray and post mortal examinations revealed a anterior mediastinal mass. Histologically, the tumor mass consisted of four different elements; cord-like proliferation of cuboidal epithelial cells, tubular or cystic structures lined with ciliated epithelial cells, proliferation of large round-shaped epithelial cells with PAS-slightly positive granular cytoplasm, and diffuse proliferation of neoplastic lymphocytes. Epithelial cells in cord-like or cystic structures were strongly positive for cytokeratin. Granular or foamy cells were negative for all markers examined and had myelin-like bodies in the cytoplasm by electron microscopy. The neoplastic lymphocytes in the tumor mass were considered being derived from concurrent multicentric lymphoma. Based on these findings, the present case was diagnosed as thymoma with a part of granular cell proliferation and concurrent lymphoma cells.

Publication Types:
PMID: 15240949 [PubMed - indexed for MEDLINE]
100: Lung Cancer. 2004 Jun;44(3):369-79. Related Articles, Links
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Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report.

Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM.

Department of Thoracic/Head and Neck Medical Oncology, Thoracic/Cardiovascular Surgery, Radiation Therapy, Pathology, Radiology, and Biostatistics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. edkim@mdanderson.org

PURPOSE: To evaluate tumor resectability after induction chemotherapy and to determine disease-free and overall survival rates of patients with locally advanced unresectable thymoma that received a multimodal treatment regimen. PATIENTS AND METHODS: Twenty-two patients (9 men, 13 women) with histologically confirmed invasive thymoma were treated with a multidisciplinary regimen consisting of three courses of induction chemotherapy, surgical resection, and radiation therapy, followed by three courses of consolidation chemotherapy. The median age was 47 years (range, 25-70). Eleven patients had stage III disease, 10 patients, stage IVA, and one patient, IVB. The most common histologic type was lymphocytic. Induction chemotherapy consisted of 500 mg/m(2) of cyclophosphamide on day 1; doxorubicin (20 mg/m(2) per day) on days 1-3 via continuous infusion (a total of 60 mg/m(2)); cisplatin (30 mg/m(2) per day) on days 1-3 (a total of 90 mg/m(2)); and prednisone (100 mg per day) on days 1-5. This cycle was repeated three times at 3-4-week intervals. Patients then underwent surgery for tumor resection and received radiotherapy. Consolidation chemotherapy given at 80% of the induction chemotherapy doses of cyclophosphamide, doxorubicin, and cisplatin and 100% of the dose of prednisone was then repeated every 3-4 weeks for a total of three courses. RESULTS: Induction chemotherapy produced major responses in 17 (77%) of the 22 patients including 3 (14%) complete responses (CR) and 14 (63%) partial responses (PR). Twenty-one patients underwent surgical exploration: 16 (76%) had complete resection and 5 (24%) had incomplete resection; one patient refused surgery. All 22 patients received radiation therapy. Nineteen of 22 patients completed the planned therapy, and all but one had completed consolidation chemotherapy at the time of analysis. With a median follow-up time of 50.3 months, 18 of the 19 patients who completed the multidisciplinary approach were disease-free. Of the 22 patients originally registered, 20 were alive at the time of analysis (one patient died of endocarditis, and one died of recurrent disease). The overall survival rate was 95% at 5 years (95% confidence interval (CI), 0.87-1.0) and 79% at 7 years (95% CI, 0.55-1.0). The progression-free survival rates were 77% at 5 years (95% CI, 0.58-1.0) and 77% at 7 years (95% CI, 0.58-1.0). The major side effect from induction and consolidation chemotherapy was myelosuppression. Nine patients experienced grade III/IV neutropenia, which included neutropenic fever in two patients, and grade III thrombocytopenia in two patients. The most common nonhematologic side effects were fatigue, nausea and vomiting, and decreased appetite. One patient experienced acute respiratory distress syndrome after surgical resection and required a prolonged hospitalization. No patients developed cardiac toxic effects, and no surgical mortality occurred. CONCLUSIONS: The use of induction chemotherapy to optimize surgical resectability of thymoma followed by radiation therapy and consolidation chemotherapy lead to good control of residual disease and high overall survival rates. We believe that this combined multidisciplinary approach prolongs lives and may cure locally advanced unresectable malignant thymomas. Future prospective multi-institutional studies are needed to further verify or define the best treatment for this patient population.

Publication Types:
PMID: 15140551 [PubMed - indexed for MEDLINE]
101: Neurology. 2004 May 25;62(10):1894-6. Related Articles, Links
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Anti-ryanodine receptor antibodies and FK506 in myasthenia gravis.

Takamori M, Motomura M, Kawaguchi N, Nemoto Y, Hattori T, Yoshikawa H, Otsuka K.

Neurological Center, Kanazawa-Nishi Hospital, Kanazawa, Japan. t-kiyomi@guitar.ocn.ne.jp

Anti-ryanodine receptor (RyR) antibodies were measured in sera from 33 myasthenia gravis (MG) patients using three peptides from the human RyR1 sequence, two C-terminal peptides included in the functional calcium release channel, and an N-terminal peptide implicated in ion-conduction. Antibodies were more frequently positive against the two C-terminal peptides, particularly in thymoma-associated MG. In a preliminary open trial with FK506, immunosuppressant and enhancer of RyR-related sarcoplasmic calcium release, the authors observed the sustained benefits in anti-RyR-positive MG patients.

Publication Types:
PMID: 15159506 [PubMed - indexed for MEDLINE]
102: J Biol Chem. 2004 May 21;279(21):21903-15. Epub 2004 Mar 11. Related Articles, Links
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T cell receptor signaling inhibits glucocorticoid-induced apoptosis by repressing the SRG3 expression via Ras activation.

Ko M, Jang J, Ahn J, Lee K, Chung H, Jeon SH, Seong RH.

School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742.

Activation of T cell antigen receptor (TCR) signaling inhibits glucocorticoid (GC)-induced apoptosis of T cells. However, the detailed mechanism regarding how activated T cells are protected from GC-induced apoptosis is unclear. Previously, we have shown that the expression level of SRG3, a murine homolog of BAF155 in humans, correlated well with the GC sensitivity of T cells either in vitro or in vivo. Intriguingly, the expression of SRG3 decreased upon positive selection in the thymus. Here we have shown that TCR signaling inhibits the SRG3 expression via Ras activation and thereby renders primary thymocytes and some thymoma cells resistant to GC-mediated apoptosis. By using pharmacological inhibitors, we have shown that Ras-mediated down-regulation of the SRG3 gene expression is mediated by MEK/ERK and phosphatidylinositol 3-kinase pathways. Moreover, TCR signals repressed the SRG3 transcription through the putative binding sites for E proteins and Ets family transcription factors in the proximal region of the SRG3 promoter. Introduction of mutations in these elements rendered the SRG3 promoter immune to the Ras or TCR signals. Taken together, these observations suggest that TCR signals result in GC desensitization in immature T cells by repressing SRG3 gene expression via Ras activation.

PMID: 15016814 [PubMed - indexed for MEDLINE]
103: Zhonghua Wai Ke Za Zhi. 2004 May 7;42(9):540-2. Related Articles, Links

[Myasthenia gravis occurring after resection of thymoma]

[Article in Chinese]

Li J, Zhang DC, Wang LJ, Zhang DW, Zhang RG.

Department of Thoracic Surgery, Cancer Hospital (Institute), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China.

OBJECTIVE: The aim of this study was to analyses the clinicopathologic features of the patient with myasthenia gravis (MG) occurring after resection of thymoma. METHODS: 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 hadn't 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. RESULTS: (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, unknow in 1. According to Osserman's classification of MG, grade I in 7, IIa in 4, IIb in 3, III in 1. The MG onseting 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. CONCLUSIONS: The factors including the operation, relatively using overdose relaxometric 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.

PMID: 15196367 [PubMed - in process]
104: Zhonghua Wai Ke Za Zhi. 2004 May 7;42(9):536-9. Related Articles, Links

[Clinical characteristics and outcome of myasthenia gravis with and without thymoma after operation]

[Article in Chinese]

Wang RW, Jiang YG, Xue ZQ, Zhao YP, Ma Z.

Center of Thoracic Surgery of PLA, Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China.

OBJECTIVE: To explore the clinical characteristics and outcome of myasthenia gravis with and without thymoma after operation. METHODS: Two hundred and forty-three patients with myasthenia gravis surgically treated in our department from 1978 to 2003 were studied retrospectively. The clinical characteristics, complication, remission and survival were compared between myasthenia gravis with and without thymoma. RESULTS: The patients of myasthenia gravis with thymoma were significantly older (t = 6.138, P = 0.000), had shorter duration of symptom (t = 3.783, P = 0.000), and also had higher myasthenia crisis rates after operation (chi(2) = 64.77, P = 0.000) than those of myasthenia gravis without thymoma. No differences of Osserman classification was found between the two groups (chi(2) = 7.678, P = 0.104). The complete remission rates and partial remission rates of myasthenia gravis with thymoma were significantly lower than those of myasthenia gravis without thymoma at 1 and 3 years (P = 0.049, P = 0.000; P = 0.015, P = 0.010), but no differences at 5 year (P = 0.457; P = 0.699). The survival rates of MG with thymoma were lower than that of MG without thymoma (Log-rank = 18.58, P = 0.000). CONCLUSIONS: The clinical characteristics are different between myasthenia gravis with and without thymoma. The remission of symptom of myasthenia gravis with thymoma is worse than that of myasthenia gravis without thymoma in the near future, but is similar in the long future. The death rates of MG with thymoma is significantly higher than that of MG without thymoma.

PMID: 15196366 [PubMed - in process]
105: Ann Thorac Surg. 2004 May;77(5):1878; author reply 1878. Related Articles, Links
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Comment on:
Video-assisted extended thymectomy in patients with thymoma by lifting the sternum: is it safe?

Aubert A, Chaffanjon P, Brichon PY.

Publication Types:
PMID: 15111222 [PubMed - indexed for MEDLINE]
106: Ann Thorac Surg. 2004 May;77(5):1860-9. Related Articles, Links
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Thymic tumors.

Detterbeck FC, Parsons AM.

Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7065, USA. fdetter@med.unc.edu

Thymic tumors include thymic carcinoma, which exhibit aggressive behavior, and thymomas, which manifest a more indolent course. Complete resection is the mainstay of treatment, and there appears to be little benefit to partial resection. Postoperative radiotherapy may be useful in incompletely resected patients. Preoperative chemotherapy appears to increase the rate of complete resection and survival of patients with a stage III or IVa thymoma and should strongly be considered in such cases.

Publication Types:
PMID: 15111216 [PubMed - indexed for MEDLINE]
107: Bull Exp Biol Med. 2004 May;137(5):493-8. Related Articles, Links

Cross reactivity of T cell receptor on memory CD8+ cells isolated after immunization with allogeneic tumor cells.

Pobezinskaya EL, Pobezinskii LA, Silaeva YY, Anfalova TV, Khromykh LM, Tereshchenko TS, Zvezdova ES, Kazanskii DB.

N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow.

Experiments on mice deficient in expression of class I major histocompatibility complex molecules showed that memory CD8+ cells recognizing the alloantigen by the direct allogeneic recognition mechanism selectively proliferated in response to heated allogeneic cells. Adoptive transfer of memory cells from mice expressing green fluorescent protein transgene to wild-type animals showed for the first time that long-living memory cells suppress the response of naive T cells and abolish their involvement in the pool of memory cells. The pool of long-living memory T cells was obtained in vitro with heated allogeneic stimulators. Apart from immunizing alloantigen, this clone recognized foreign molecules of the major histocompatibility complex. Cloning and sequencing of rearranged regions in memory T cells showed that two alpha-chains and one functional beta-chain are rearranged in cells of this pool. Only one alpha-chain was capable of forming protein product, which determines expression of only one form of T cell receptor. Experimental data directly confirm the hypothesis about degeneracy of recognition of allelic products of major histocompatibility complex molecules by T cell receptors. Suppression of the response of naive cells by memory cells probably underlies a previously unknown type of polarization of the immune response and determines clonal dominance and peripheral selection of T lymphocytes.

PMID: 15455127 [PubMed - indexed for MEDLINE]
108: Kyobu Geka. 2004 May;57(5):410-2. Related Articles, Links

[Thymic carcinoma incidentally detected on routine chest computed tomography; report of a case]

[Article in Japanese]

Shundo Y, Kita Y, Nogimura H, Ida M, Neyatani H.

Department of Thoracic Surgery, Haibara General Hospital, Shizuoka, Japan.

We reported a case of thymic carcinoma. A 61-year-old man was admitted to evaluate an abnormal shadow of lung field by chest X-ray. Routine chest computed tomography (CT) showed no abnormal findings on the lung field, but thymic tumor was incidentally detected. We suspected thymoma, performed a mediansternotomy and thymectomy with partial resection of pericardium. Pathological findings diagnosed undifferentiated carcinoma (large cell type) of thymus, the patient underwent radiation therapy of the mediastinum at a total dosage of 50 Gy and chemotherapy [cisplatin (CDDP) + vinorelbine ditartrate + mitomycin C (MMC)]. He has been doing well without recurrence for 2 years after the operation.

Publication Types:
PMID: 15151046 [PubMed - indexed for MEDLINE]
109: Kyobu Geka. 2004 May;57(5):347-50; discussion 350-2. Related Articles, Links

[Stenting in obstruction of superior vena cava; clinical experience with the self-expanding endovascular prosthesis]

[Article in Japanese]

Kanzaki M, Sakuraba M, Kuwata H, Ikeda T, Oyama K, Mae M, Murasugi M, Miyano H, Wachi N, Kikkawa T, Aoshima H, Onuki T.

Department of Surgery I, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.

From August 1997 to December 2002, 14 consecutive patients with superior vena cava syndrome with the self-expanding endovascular prosthesis. Diagnoses were adenocarcinoma in 6, small cell carcinoma in 4, squamous cell carcinoma in 1, metastatic lung cancer in 2, and invasive thymoma in 1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured on their admission and perioperative period. Expecting only 1 patient complete symptomatically relieved within 3 days of stent implantation. Superior vena cava pressure or radial pressure of the stent was sufficient to relieve obstruction. Preoperative ANP level were normal, BNP level were increased. Postoperatively both ANP level and BNP level were slightly increased under intravenous dopamine hydrochloride. Implantation of the self-expanding stent endovascular prosthesis for superior vena cava syndrome provides rapid symptomatic relief and improves the patient's quality of life.

PMID: 15151030 [PubMed - indexed for MEDLINE]
110: Rev Neurol (Paris). 2004 May;160(5 Pt 2):S85-9. Related Articles, Links
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Neuromyotonia.

Newsom-Davis J.

Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK. john.newsomdavis@btinternet.com

There is increasing evidence that autoimmunity is implicated in the pathogenesis of peripheral nerve hyperexcitability (neuromyotonia, NMT and Cramp-fasciculation syndrome C-FS ) and in Maladie de Morvan in which CNS features are also present. All three conditions can associate with thymoma, myasthenia gravis and other autoimmune disorders, and can often respond to plasma exchange. In NMT, patient's plasma or IgG can transfer the electrophysiological features to mice, and can reduce voltage-gated potassium channel currents in vitro. Antibodies to voltage-gated potassium channels can be detected in the serum of many patients who have peripheral nerve hyperexcitability, and also in those with Maladie de Morvan. These latter patients have clinical features similar to limbic encephalitis in which VGKC antibodies can also occur. Thus neuromyotonia, cramp-fasciculation syndrome and Maladie de Morvan can occur as antibody-mediated autoimmune ion channelopathies like myasthenia gravis and the Lambert-Eaton myasthenic syndrome. These discoveries should aid diagnosis and offer new approaches to treatment.

Publication Types:
PMID: 15269665 [PubMed - indexed for MEDLINE]
111: Surg Endosc. 2004 May;18(5):843-6. Epub 2004 Apr 6. Related Articles, Links
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Infrasternal mediastinoscopic surgery for anterior mediastinal masses.

Uchiyama A, Shimizu S, Murai H, Ohshima A, Konomi H, Ogura Y, Ishikawa N, Yamashita H, Matsumoto S, Kuroki S, Tanaka M.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Fukuoka, Japan. kyukou@pmet.or.jp

BACKGROUND: Infrasternal mediastinoscopic surgery is a new alternative to the thoracoscopic approach for patients with anterior mediastinal masses. METHODS: We applied this technique to 18 thymectomies, one thymomectomy, and one cystectomy in a total of 20 patients with anterior mediastinal masses and then assessed the surgical results. RESULTS: Infrasternal mediastinoscopic surgery was accomplished in 18 of the 20 patients (90%). The pathological diagnoses included 13 Masaoka stage I thymomas, one stage II thymoma, two stage III thymomas, one thymic cyst, one pericardial cyst, one thymic granuloma, and one mature teratoma. Two patients with stage III thymoma required conversion to sternotomy, one for invasion into the innominate vein and the other for invasion into the pericardium. There was no surgically related mortality or complications in any patients. CONCLUSION: Infrasternal mediastinoscopic surgery is safe and feasible for stage I thymoma and other benign tumors in the anterior mediastinum.

PMID: 14755356 [PubMed - indexed for MEDLINE]
112: J Biol Chem. 2004 Apr 23;279(17):16918-26. Epub 2004 Feb 3. Related Articles, Links
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The Pro-451 to Leu polymorphism within the C-terminal tail of P2X7 receptor impairs cell death but not phospholipase D activation in murine thymocytes.

Le Stunff H, Auger R, Kanellopoulos J, Raymond MN.

Laboratoire d'activation Cellulaire et Transduction des Signaux, Institut de Biochimie et de Biophysique Moleculaire et Cellulaire, UMR 8619 CNRS, Batiment 430, Universite Paris-Sud, 91405 Orsay Cedex, France.

The P2X family of ATP receptors (P2XR) are ligandgated channels that have been proposed to regulate cell death of immature thymocytes. However, the nature of the P2XR subtype involved has been controversial until recently. In agreement with previous studies, we found that extracellular ATP (ATPe) induces a caspase-dependent apoptosis of BALB/c thymocytes, as observed by DNA fragmentation. Additionally, ATPe induces a predominant caspase-independent thymocytes lysis characterized by plasma membrane disruption. Both responses to ATPe can be induced by a potent P2X7R agonist, benzoylbenzoyl-ATP, whereas P2X7R antagonists, oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, inhibited the effect of ATPe. These results are further supported by observations where disruption of the P2X7R gene (P2X7R(-/-) mice) completely abolishes thymocytes death induced by ATPe. Interestingly, the natural P451L mutation in the C-terminal tail of P2X7R present in C57BL/6 mice, which impairs ATPe-dependent pore formation in T lymphocytes, significantly reduces thymocytes death triggered by ATPe. Furthermore, we found that P2X7R from BW5147 thymoma cells also harbors this point mutation, accounting for their insensitivity to ATPe-induced cell death. Concentrations of ATPe effective in inducing cell death also increase phosphatidylcholine-hydrolyzing phospholipase D (PC-PLD) activity in BALB/c thymocytes through the stimulation of P2X7R. However, in contrast to ATPe-induced cell death, PC-PLD activation is totally Ca(2+)-dependent. Moreover, the stimulation of PC-PLD by ATPe is not affected by the P451L mutation present in C57BL/6 thymocytes and BW5147 cells, suggesting that cell death and PC-PLD activity are regulated through distinct domains of the P2X7R. Finally, the inhibition of ATPe-induced PC-PLD stimulation does not affect thymocytes death. Altogether, these data suggest that P2X7R-induced thymocytes death is independent of the stimulation of PC-PLD activity.

PMID: 14761980 [PubMed - indexed for MEDLINE]
113: J Biol Chem. 2004 Apr 16;279(16):16077-82. Epub 2004 Feb 4. Related Articles, Links
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Competition for access to the rat major histocompatibility complex class I peptide-loading complex reveals optimization of peptide cargo in the absence of transporter associated with antigen processing (TAP) association.

Ford S, Antoniou A, Butcher GW, Powis SJ.

Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.

Major histocompatibility complex (MHC) class I molecules load peptides in the endoplasmic reticulum in a process during which the peptide cargo is normally optimized in favor of stable MHC-peptide interactions. A dynamic multimolecular assembly termed the peptide-loading complex (PLC) participates in this process and is composed of MHC class I molecules, calreticulin, ERp57, and tapasin bound to the transporter associated with antigen processing (TAP) peptide transporter. We have exploited the observation that the rat MHC class I allele RT1-Aa, when expressed in the rat C58 thymoma cell line, effectively competes and prevents the endogenous RT1-Au molecule from associating with TAP. However, stable RT1-Au molecules are assembled efficiently in competition with RT1-Aa, demonstrating that cargo optimization can occur in the absence of TAP association. Defined mutants of RT1-Aa, which do not allow formation of the PLC, fail to become thermostable in C58 cells. Wild-type RT1-Aa, which does allow PLC formation, also fails to become thermostable in this cell line, which carries the rat TAPB transporter that supplies peptides incompatible for RT1-Aa binding. Full optimization of RT1-Aa requires the presence of the TAP2A allele, which is capable of supplying suitable peptides. Thus, formation of the PLC alone is not sufficient for optimization of the MHC class I peptide cargo.

PMID: 14764587 [PubMed - indexed for MEDLINE]
114: J Biol Chem. 2004 Apr 16;279(16):15743-51. Epub 2004 Jan 23. Related Articles, Links
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Subcellular localization and targeting of N-acetylglucosaminyl phosphatidylinositol de-N-acetylase, the second enzyme in the glycosylphosphatidylinositol biosynthetic pathway.

Pottekat A, Menon AK.

Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.

The second step in glycosylphosphatidylinositol biosynthesis is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) catalyzed by N-acetylglucosaminylphosphatidylinositol deacetylase (PIG-L). Previous studies of mouse thymoma cells showed that GlcNAc-PI de-N-acetylase activity is localized to the endoplasmic reticulum (ER) but enriched in a mitochondria-associated ER membrane (MAM) domain. Because PIG-L has no readily identifiable ER sorting determinants, we were interested in learning how PIG-L is localized to the ER and possibly enriched in MAM. We used HeLa cells transiently or stably expressing epitope-tagged PIG-L variants or chimeric constructs composed of elements of PIG-L fused to Tac antigen, a cell surface protein. We first analyzed the subcellular distribution of PIG-L and Glc-NAc-PI-de-N-acetylase activity and then studied the localization of Tac-PIG-L chimeras to identify sequence elements in PIG-L responsible for its subcellular localization. We show that human PIG-L is a type I membrane protein with a large cytoplasmic domain and that, unlike the result with mouse thymoma cells, both PIG-L and GlcNAc-PI-de-N-acetylase activity are uniformly distributed between ER and MAM in HeLa cells. Analyses of a series of Tac-PIG-L chimeras indicated that PIG-L contains two ER localization signals, an independent retention signal located between residues 60 and 88 of its cytoplasmic domain and another weak signal in the luminal and transmembrane domains that functions autonomously in the presence of membrane proximal residues of the cytoplasmic domain that themselves lack any retention information. We conclude that PIG-L, like a number of other ER membrane proteins, is retained in the ER through a multi-component localization signal rather than a discrete sorting motif.

PMID: 14742432 [PubMed - indexed for MEDLINE]
115: Exp Cell Res. 2004 Apr 15;295(1):91-101. Related Articles, Links
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Changes in protein expression in p53 deleted spontaneous thymic lymphomas.

Honore B, Vorum H, Pedersen AE, Buus S, Claesson MH.

Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark. bh@biokemi.au.dk

By the use of high-resolution two-dimensional gel electrophoresis and computerized image analysis we investigated and compared the expression of cellular proteins from p53 positive (+/+) mouse thymocytes, p53-/- thymocytes before neoplastic transformation, and from cell lines derived from two spontaneous p53-/- thymic lymphomas, SM5 and SM7. A total of around 1500 proteins were detected on individual gels. Only changes in protein expression by a factor of 2 or more were considered. In the thymic lymphoma cells 3-5% of the proteins were found to be differentially regulated when compared with the protein expression in p53+/+ and p53-/- thymocytes. Only a minority (13 proteins) of the quantitatively changed proteins were common for the two thymic lymphoma cell lines, suggesting that the p53 deficiency mainly results in genetic dysfunctions which are individual for a given tumor. Two of the detected proteins increased their expression levels by more than 10 times from the p53+/+ to the p53-/- thymocytes and these high expression levels were also found in thymic lymphomas. The two proteins were identified by mass spectrometry as acidic ribosomal phosphoprotein P0 and a 33-kDa protein with a primary structure containing motifs of the glyoxalase-bleomycin resistance protein family (MDR) as deduced from the cDNA.

PMID: 15051493 [PubMed - indexed for MEDLINE]
116: J Clin Oncol. 2004 Apr 15;22(8):1501-9. Related Articles, Links
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Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

Strobel P, Bauer A, Puppe B, Kraushaar T, Krein A, Toyka K, Gold R, Semik M, Kiefer R, Nix W, Schalke B, Muller-Hermelink HK, Marx A.

Institute of Pathology, University of Wurzburg, Josef-Schneider-Strasse 2, D-97080 Wurzburg, Germany. path036@mail.uni-wuerzburg.de

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.

PMID: 15084623 [PubMed - indexed for MEDLINE]
117: J Biol Chem. 2004 Apr 9;279(15):15142-52. Epub 2004 Jan 22. Related Articles, Links
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Neuronal calcium sensor protein visinin-like protein-3 interacts with microsomal cytochrome b5 in a Ca2+-dependent manner.

Oikawa K, Kimura S, Aoki N, Atsuta Y, Takiyama Y, Nagato T, Yanai M, Kobayashi H, Sato K, Sasajima T, Tateno M.

Department of Pathology, School of Nursing, Asahikawa Medical College, Midorigaoka Higashi 2-1, Asahikawa, Hokkaido 078-8510, Japan.

Visinin-like protein-3, which is one of the neuronal calcium sensors, has been shown to be mainly expressed in cerebellar Purkinje cells, but cellular function of this protein has not yet been elucidated. We examined the tissue distribution of murine visinin-like protein-3 transcripts using real-time reverse transcription-PCR. Visinin-like protein-3 mRNA was found to be expressed in peripheral tissues. Particularly, the expression of the transcript in the thymus was significantly higher than in other peripheral tissues. In addition, B6RVTC1 thymoma cells robustly expressed visinin-like protein-3 mRNA. To identify a target protein of visinin-like protein-3, we performed a pull-down experiment using glutathione S-transferase-tagged visinin-like protein-3 and two-dimensional electrophoresis. We demonstrated that microsomal cytochrome b(5) was a Ca(2+)-dependent binding partner of visinin-like protein-3. In a co-immunoprecipitation experiment, it was observed that hippocalcin, as well as visinin-like protein-3, could interact with cytochrome b(5). Furthermore, we confirmed that the sequence Val(114)-Tyr(127) at the C-terminal tail of cytochrome b(5) is the minimal structural requirement for binding to visinin-like protein-3. In addition, the loop His(19)-His(25) at the N terminus of visinin-like protein-3 is essential for binding to cytochrome b(5). Microsomal cytochrome b(5) was also shown to be a potential activator of cytochrome P450. The present findings raise the possibility that visinin-like protein-3 may link Ca(2+) signaling to the machinery of microsomal monooxygenase complex composed of cytochrome b(5), cytochrome P450, and some reductases. This report provides the first evidence of an interaction between visinin-like protein-3 and microsomal cytochrome b(5).

PMID: 14739275 [PubMed - indexed for MEDLINE]
118: Ann Oncol. 2004 Apr;15(4):692-3. Related Articles, Links
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Extrathymic malignancies in patients with thymoma.

Evoli A, Punzi C, Marsili F, Di Schino C, Cesario A, Galetta D, Margaritora S, Granone P.

Publication Types:
PMID: 15033685 [PubMed - indexed for MEDLINE]
119: Ann Pathol. 2004 Apr;24(2):176-8. Related Articles, Links
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[Ectopic hamartomatous thymoma: a case report and review of the literature]

[Article in French]

de Saint Aubain Somerhausen N, Richard C, Priollet D, Dequanter D.

Service d'Anatomie Pathologique, Institut Jules Bordet, bruxelles. nicolas.desaintaubain@skynet.be

We report a case of a rare tumor of the head and neck: ectopic hamartomatous thymoma. The tumor involved the sus-clavicular area of a 48 year-old male. Ectopic hamartomatous thymoma exclusively occurs in the sus-scapular region. Histologically, it is characterized by the association of spindle-cell fascicles, epithelial solid or cystic structures and foci of mature adipose tIssue. Spindle cells express diffusely cytokeratins. The differential diagnosis of ectopic hamartomatous thymoma includes mixed tumor of salivary glands, biphasic synovial sarcoma and sarcomatoid carcinoma. Ectopic hamartomatous thymoma is a benign tumor which does not recur after complete excision.

Publication Types:
PMID: 15220838 [PubMed - indexed for MEDLINE]
120: Ann Thorac Surg. 2004 Apr;77(4):1183-8. Related Articles, Links
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WHO histologic classification is a prognostic indicator in thymoma.

Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, Miyoshi T, Sakiyama S, Mukai K, Monden Y.

Department of Oncological and Regenerative Surgery, School of Medicine, University of Tokushima, Tokushima, Japan. kondo@clin.med.tokushima-u.ac.jp

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

PMID: 15063231 [PubMed - indexed for MEDLINE]
121: Arch Pathol Lab Med. 2004 Apr;128(4):452-5. Related Articles, Links
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Giant cell tumor of rib masquerading as thymoma: a diagnostic pitfall in needle core biopsy of the mediastinum.

Volmar KE, Sporn TA, Toloza EM, Martinez S, Dodd LG, Xie HB.

Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. kevolmar@yahoo.com

Giant cell tumor of bone is rarely seen in the rib, where it may present as a mediastinal mass. The diagnosis of giant cell tumor of bone is generally straightforward by fine-needle aspiration or needle core biopsy, but sampling problems may lead to confusion with other neoplasms or inflammatory processes. Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass in a 36-year-old man. Because of inadequate sampling and inaccurate clinical information, the tumor was initially mistaken for thymoma. When the mass failed to respond to conventional chemotherapy, additional tissue was obtained and a giant cell tumor was diagnosed. Consequently, definitive therapy was delayed. The case illustrates an important diagnostic pitfall in the biopsy of mediastinal masses.

Publication Types:
PMID: 15043459 [PubMed - indexed for MEDLINE]
122: Blood. 2004 Apr 1;103(7):2705-9. Epub 2003 Dec 4. Related Articles, Links
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Erratum in:
IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-gamma response that is regulated by CD8+ T cells.

Sayeh E, Sterling K, Speck E, Freedman J, Semple JW.

Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, University of Toronto, ON, Canada.

The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P<.001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2 (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type mice, platelet transfusions into CD8-depleted mice stimulated enhanced intracellular interferon (IFN)-gamma production by CD4- lymphocytes within 24 hours after the first transfusion. The early IFN-gamma response correlated with nitric oxide-dependent splenic cytotoxicity (P<.001). In asialo ganglioside monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the IFN-gamma production, splenic cytotoxicity, and IgG antidonor antibody response were significantly suppressed. These results demonstrate that IgG antiplatelet immunity is dependent on an early NK cell-derived IFN-gamma response that is negatively regulated by CD8+ T cells and suggest that targeting innate NK cell responses may significantly reduce platelet alloimmunization.

PMID: 14656873 [PubMed - indexed for MEDLINE]
123: Cir Pediatr. 2004 Apr;17(2):55-7. Related Articles, Links

[Thoracoscopic thymectomy]

[Article in Spanish]

Tarrado X, Ribo JM, Sepulveda JA, Castanon M, Morales L.

Servicio de Cirugia Pediatrica, Unidad Integrada, Hospital Sant Joan de Deu/Hospital Clinic, Barcelona. anabosque@hsjdbcn.es

BACKGROUND/PURPOSE: The use of videothoracoscopy in thoracic pediatric pathology has been progressively accepted in different diagnostic and therapeutic procedures along last decade. The aim of this work is to analyze our initial experience in thymectomy through this approach. PATIENTS AND METHODS: We have used the thoracoscopic approach in the last two cases of thymus pathology with surgical indication. Case 1: 9 year-old patient recently diagnosed on myasthenia gravis and several hospital admissions because of clinical worsening. Case 2: 9 year-old patient with a 7x8x3.5 cm. cervico-mediastinal tumour. Final diagnosis: Multilocular cystic thymoma. In both cases we used right approach in lateral decubitus, and the harmonic scalpel. RESULTS: Mean operating time was 125 minutes. No procedure-related complications. They were discharged on the 6th and 4th postoperative day. After 6 and 7 month follow-up, no incidences have been found, and case 1 has shown a sympthomatic improvement and a decrease in drug dosage. CONCLUSIONS: Thoracoscopy is a good alternative in thymus approach. Its cosmetic and recovery advantages upon transcervical and transsternal are obvious. Despite our very initial experience, we believe that this approach at least equals classic ones in the ability to resect the whole thymus.

Publication Types:
PMID: 15285584 [PubMed - indexed for MEDLINE]
124: Endocr J. 2004 Apr;51(2):237-41. Related Articles, Links
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A case of malignant thymoma mimicking thyroid carcinoma: a pitfall in fine-needle aspiration.

Matsuura B, Tokunaga H, Miyake T, Utsunomiya S, Minami H, Onji M.

The Third Department of Internal Medicine, Ehime University School of Medicine, Japan.

A case of malignant thymoma presenting as an anterior neck mass is reported. The tumor extended from the thyroid gland to the superior mediastinum. It did not accumulate Tc-99m pertechnetate, but continued to accumulate Tl-201 at the late phase. A fine-needle aspiration cytology from the