Worlds largest Thymoma Database

Thymoma Database III
Publication Date from 2002/11/01 to 2003/12/31
updated:2006.2.2

START here

thymoma.de

Items 1 - 222 of 222

One page.

1: Ann Hematol. 2004 Jun;83(6):398-400. Epub 2003 Dec 19. Related Articles, Links

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:

Case Reports

PMID: 14689236 [PubMed - indexed for MEDLINE]

2: Blood. 2004 Apr 1;103(7):2705-9. Epub 2003 Dec 4. Related Articles, Links

Erratum in:

Blood. 2004 May 15;103(10):3643.

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]

3: Blood. 2004 Mar 15;103(6):1985-94. Epub 2003 Oct 30. Related Articles, Links: Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.

Laouar Y, Crispe IN, Flavell RA.

Section of Immunobiology, Yale University School of Medicine, 300 Ceda St, CAB S-569, New Haven, CT 06520, USA. richard.flavell@yale.edu

Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.

PMID: 14592827 [PubMed - indexed for MEDLINE]

4: J Biol Chem. 2004 Mar 12;279(11):10476-83. Epub 2003 Dec 18. Related Articles, Links: High incidence of thymic epithelial tumors in E2F2 transgenic mice.

Scheijen B, Bronk M, van der Meer T, De Jong D, Bernards R.

Division of Molecular Carcinogenesis and Center for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands.

In virtually all human tumors, genetic and epigenetic alterations have been found which affect the INK4/-CYCLIN D/RB pathway, which regulates cell cycle entry and exit in normal cells. E2F transcription factors are important downstream components of this pathway, which act by controlling the expression of genes involved in DNA replication and cell cycle progression. To determine whether E2F2 deregulation promotes proliferation and tumorigenesis in vivo, we generated E2F2 transgenic mice, in which the Emu and murine pim1 promoter (pp) direct high expression of E2F2 in thymic epithelial cells. Emu-pp-E2F2 mice start to develop cytokeratin- and ER-TR4-positive cortical thymomas from the age of 20 weeks, and within 1 year, nearly all mice succumb to gross thymic epithelial tumors. General thymic morphology is largely maintained, but T cell development is perturbed in thymomas, with proportionately less CD4(+)CD8(+) double-positive thymocytes. In the first 3 months, E2F2 transgenic thymi exhibit only mild epithelial hyperplasia, and thereafter thymomas arise stochastically, probably following additional mutations. Interestingly, Emu-pp-E2F1 mice do not display cortical thymomas. These data argue that E2F2 promotes unscheduled cell division and oncogenic transformation of thymic epithelial cells.

PMID: 14684733 [PubMed - indexed for MEDLINE]

5: J Biol Chem. 2004 Mar 5;279(10):8895-902. Epub 2003 Dec 18. Related Articles, Links: Formation of HLA-B27 homodimers and their relationship to assembly kinetics.

Antoniou AN, Ford S, Taurog JD, Butcher GW, Powis SJ.

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

The human HLA-B27 class I molecule exhibits a strong association with the inflammatory arthritic disorder ankylosing spondylitis and other related arthropathies. Major histocompatibility complex class I heavy chains normally associate with beta(2)-microglobulin and peptide in the endoplasmic reticulum before transit to the cell surface. However, an unusual characteristic of HLA-B27 is its ability to form heavy chain homodimers through an unpaired cysteine at position 67 in the peptide groove. Homodimers have previously been detected within the ER and at the cell surface, but their mechanism of formation and role in disease remain undefined. Here we demonstrate, in the rat C58 thymoma cell line and in human HeLa cells transfected with HLA-B27, that homodimer formation involves not only cysteine at position 67 but also the conserved structural cysteine at position 164. We also show that homodimer formation can be induced in the non-disease-associated HLA class I allele HLA-A2 by slowing its assembly rate by incubation of cells at 26 degrees C, suggesting that homodimer formation in the endoplasmic reticulum may occur as a result of the slower folding kinetics of HLA-B27. Finally, we report an association between unfolded HLA-B27 molecules and immunoglobulin-binding protein at the cell surface.

PMID: 14684742 [PubMed - indexed for MEDLINE]

6: Int J Cancer. 2003 Dec 10;107(5):868-70. Related Articles, Links

Second primary cancers after thymoma.

Travis LB, Boice JD Jr, Travis WD.

Publication Types:

Letter

PMID: 14566841 [PubMed - indexed for MEDLINE]

7: AJR Am J Roentgenol. 2003 Dec;181(6):1504. Related Articles, Links

Invasive thymoma.

Truong MT, Sabloff BS, Gladish GW, Whitman GJ, Munden RF.

Division of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Publication Types:

Case Reports

PMID: 14627564 [PubMed - indexed for MEDLINE]

8: Am J Pathol. 2003 Dec;163(6):2635-6; author reply 2636. Related Articles, Links

Comment on:

Am J Pathol. 2002 Oct;161(4):1507-13.

Chromosome 6 abnormalities correlated with thymoma progression.

Sasaki H, Fujii Y, Ide N.

Publication Types:

PMID: 14633634 [PubMed - indexed for MEDLINE]

9: Ann Thorac Surg. 2003 Dec;76(6):1866-72; discussion 1872. Related Articles, Links: Long-term outcome after multimodality treatment for stage III thymic tumors.

Venuta F, Rendina EA, Longo F, De Giacomo T, Anile M, Mercadante E, Ventura L, Osti MF, Francioni F, Coloni GF.

Department of Thoracic Surgery, University of Rome "La Sapienza,", Rome, Italy.

BACKGROUND: Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS: Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS: No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS: Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.

PMID: 14667602 [PubMed - indexed for MEDLINE]

10: Ann Thorac Surg. 2003 Dec;76(6):1859-64; discussion 1864-5. Related Articles, Links: Lymphogenous and hematogenous metastasis of thymic epithelial tumors.

Kondo 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: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.

PMID: 14667600 [PubMed - indexed for MEDLINE]

11: Clin Neurol Neurosurg. 2003 Dec;106(1):16-8. Related Articles, Links: Initial predictors of development of pure red cell aplasia in myasthenia gravis after thymectomy.

Suzuki S, Nogawa S, Tanaka K, Koto A, Fukuuchi Y, Kuwana M.

Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Pure red cell aplasia (PRCA) is well known to be concomitant with myasthenia gravis (MG), but it is difficult to predict the development of PRCA in patients with MG. Of 135 patients with MG, four (2.9%) had PRCA. All patients developed PRCA after thymectomy during a period when MG was in remission. The frequencies of thymoma, bulbar involvement and high anti-acetylcholine receptor (AChR) antibody levels were significantly higher in four patients with PRCA. Japanese MG patients with these characteristics at presentation were at significant risk for the development of PRCA after thymectomy.

PMID: 14643910 [PubMed - indexed for MEDLINE]

12: Eur J Cardiothorac Surg. 2003 Dec;24(6):1029. Related Articles, Links

Giant thymoma.

Agarwala S, Millward E, Papagiannopoulos K.

Department of Cardiothoracic Surgery, Leeds General Infirmary, Jubilee Building, Level D, Great George Street, Leeds, West Yorkshire LS1 3EX, UK.

Publication Types:

Case Reports

PMID: 14643825 [PubMed - indexed for MEDLINE]

13: Eur J Surg Oncol. 2003 Dec;29(10):904-7. Related Articles, Links: FHIT mRNA expression in thymoma.

Sasaki H, Yukiue H, Kobayashi Y, Yano M, Fukai I, Fujii Y.

Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp

AIMS: The FHIT gene is located at 3p14.2 a region frequently lost in multiple tumour types. Loss of FHIT expression has been found to occur frequently in multiple tumour types. We wished to investigate that FHIT mRNA levels in a series of thymomas. METHODS: Expression of FHIT messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using a LightCycler in 49 thymomas and 11 adjacent histologically normal thymus samples from patients. RESULTS: FHIT transcripts in tumour samples (28.6+/-35.8) at levels significantly lower than those in normal thymus samples (573.9+/-1028.0, p=0.001). No relationship was seen between FHIT gene expression and age, gender, or pathological thymoma subtypes. FHIT mRNA expression in invasive thymomas (stage II-IV, 34.5+/-39.2) was significantly higher than that in stage I thymomas (20.7+/-29.7, p=0.01). Immunohistochemistry showed that p21 protein positive thymoma had a tendency towards higher FHIT gene expression than in p21 negative thymoma. CONCLUSIONS: Decreased FHIT expression might be seen in early stage thymoma, suggesting that loss of FHIT expression may associate with tumorigenesis of thymoma.

PMID: 14624786 [PubMed - indexed for MEDLINE]

14: Hum Pathol. 2003 Dec;34(12):1253-8. Related Articles, Links: Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organization classification subtype and clinical stage of thymic epithelial tumors.

Takahashi E, Tateyama H, Akatsu H, Fukai I, Yamakawa Y, Fujii Y, Eimoto T.

Department of Pathology, Nagoya City University Medical School, Aichi, Japan.

To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)-MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by immunohistochemistry and in selected 15 cases by in situ hybridization. The tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and 9 type C thymomas according to the World Health Organization histologic classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage IV thymomas according to the Masaoka staging system. In the positive cases, MMPs and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular localization of MMPs detected by immunohistochemistry was almost identical with that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were predominantly expressed in type B3 thymoma and type C thymoma, respectively. Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma. Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical stage. The present study suggests that certain MMPs may play an important role in the tumor progression of different subtypes of thymic epithelial tumors and that MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.

PMID: 14691910 [PubMed - indexed for MEDLINE]

15: Mov Disord. 2003 Dec;18(12):1556-8. Related Articles, Links

Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and CRMP-5 autoantibody.

Samii A, Dahlen DD, Spence AM, Maronian NC, Kraus EE, Lennon VA.

Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. asamii@u.washington.edu

The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5 immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is usually associated with small-cell lung carcinoma or thymoma. We report on details of a movement disorder that followed anti-B-cell therapy in a patient with lymphoma, and was accompanied by CRMP-5 IgG. Copyright 2003 Movement Disorder Society

Publication Types:

PMID: 14673901 [PubMed - indexed for MEDLINE]

16: Vet Dermatol. 2003 Dec;14(6):279-96. Related Articles, Links

Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature.

Turek MM.

School of Veterinary Medicine, Department of Surgical Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA. turekm@svm.vetmed.wisc.edu

Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses associated with internal malignancy. Their recognition can facilitate detection and timely treatment of underlying cancer. More than 30 such disorders have been identified in the human scientific literature, whereas only a few are described in veterinary medicine. This may reflect a lower incidence in animals than in people or may be the result of failure to recognize an association between certain skin lesions and neoplasia. Establishing a relationship between a cutaneous disorder and neoplasia can be difficult unless the skin lesions are rare and almost always associated with a particular tumour type, as is the case for most recognized veterinary paraneoplastic dermatoses. Among these are feline paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis, nodular dermatofibrosis, feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both people and animals.

Publication Types:

Review

PMID: 14678440 [PubMed - indexed for MEDLINE]

17: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Dec;25(6):725-7. Related Articles, Links: [Serum anti-titin antibody in patients with myasthenia gravis]

[Article in Chinese]

Li YF, Zhang JB, Cui LY.

Department of Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.

OBJECTIVE: To study the clinical significance of serum anti-titin antibody level in the diagnosis of myasthenia gravis (MG) with thymoma. METHOD: The serum anti-titin antibody was analysed by ELISA method in 40 cases of health control group, 90 cases of MG, 17 cases of MG with thymoma and 7 cases of no-MG thymoma. The positive rate was compared among these groups. RESULTS: The positive rate of anti-titin antibody was significantly higher in MG with thymoma patients than MG patients (94% and 3%, P < 0.01). According to the Osserman's classification, anti-titin antibody was present mostly in patients (43%) in IV stage, and also present in 2 cases of 7 who with no-MG thymoma. CONCLUSION: Serum anti-titin antibody test is helpful in the diagnosis of MG with thymoma.

PMID: 14714322 [PubMed - indexed for MEDLINE]

18: Ann Allergy Asthma Immunol. 2003 Nov;91(5):501-5. Related Articles, Links

Severe T- and B-cell immune deficiency associated with malignant thymoma.

Yel L, Liao O, Lin F, Gupta S.

Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, California 92697, USA. lyel@uci.edu

BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that generally occurs after the fourth decade of life. Typically, thymic tumors are benign, and gradually developing immunodeficiency consists of hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell ratio due to excessive CD8+ T cells. OBJECTIVE: To report the case of a 32-year-old, white man with an invasive malignant thymoma and profound combined T- and B-cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of circulating B cells, and infection with an unusual organism. METHODS: The patient presented with a superior vena cava syndrome caused by a malignant thymoma. During chemotherapy and radiotherapy, he experienced recurrent episodes of pulmonary infections due to Haemophilus influenza and Serratia marcescens and persistent oral thrush. He was diagnosed as having thymoma and underwent immunological evaluation. RESULTS: Sixteen months after the diagnosis of thymoma, the immunological evaluation revealed profound lymphopenia, eosinopenia, very low counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with negative delayed-type hypersensitivity skin test results. Hypogammaglobulinemia and absent specific antibody responses were associated with a lack of peripheral blood CD19+ B cells. Despite treatment with intravenous immunoglobulin, the patient died of respiratory insufficiency and sepsis secondary to a chronic pulmonary infection. CONCLUSIONS: Malignant thymoma may be associated with severe combined immunodeficiency. A normal CD4+/CD8+ ratio and the absence of peripheral B cells suggest a bone marrow defect that affects both T and B cells in the pathogenesis of this syndrome. Comprehensive immunological evaluation should be performed when thymoma is diagnosed to initiate an early and effective treatment to prevent life-threatening complications.

Publication Types:

Case Reports

PMID: 14692437 [PubMed - indexed for MEDLINE]

19: Ann Thorac Surg. 2003 Nov;76(5):1735-7. Related Articles, Links

Primary intrapulmonary thymoma successfully resected with vascular reconstruction.

Ishibashi H, Takahashi S, Tomoko H, Shibuya J, Suzuki S, Handa M.

Department of Thoracic Surgery, Sendai Kousei Hospital, Sendai, Japan. hishiba@kf6.so-net.ne.jp

Primary intrapulmonary thymomas are defined as intrapulmonary tumors without an associated mediastinal component and are very rare. We report a resected case of primary intrapulmonary thymoma with dissection of mediastinal lymph nodes and vascular reconstruction. Because the tumor directly invaded the right brachiocephalic vein, the vein was reconstructed with a graft, and then adjuvant radiation was performed postoperatively. The tumor was diagnosed as a lymphocyte dominant thymoma and B2 type thymoma in the WHO classification. There has been no evidence of recurrence in 6 years. Complete resection of the tumor with vascular reconstruction and adjuvant radiation should be considered in invasive intrapulmonary thymoma.

Publication Types:

Case Reports

PMID: 14602330 [PubMed - indexed for MEDLINE]

20: Ann Thorac Surg. 2003 Nov;76(5):1643-9; discussion 1649. Related Articles, Links: Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis.

Lopez-Cano M, Ponseti-Bosch JM, Espin-Basany E, Sanchez-Garcia JL, Armengol-Carrasco M.

Department of General Surgery, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain. lopezc@hg.vhebron.es

BACKGROUND: Myasthenia gravis is by far the most common paraneoplastic syndrome of thymomas. There is little information regarding the influence of clinical variables and thymoma-associated factors on biologic development of myasthenia gravis. The aim of the study was to determine independent predictors of clinical outcome in thymoma with myasthenia gravis. METHODS: We studied 108 patients with thymoma-associated myasthenia gravis undergoing removal of the mediastinal mass between 1967 and 2000. Clinical and pathologic variables associated with clinical outcome of myasthenia were assessed by multivariate Cox regression analysis. RESULTS: Patients were followed for a mean period of 10 years (9 months to 33 years). A total of 38 patients died (35.2%), in 14 cases (37%) because of myasthenia gravis and in 6 (16%) because of recurrence of thymoma. With respect to clinical outcome of myasthenia gravis, at the end of the follow-up period, the rate of remission was 16% (n = 17). Of the 91 patients in whom remission was not achieved, 55 had no symptoms with immunosuppressive medication and 36 had symptoms with medication. CONCLUSIONS: In patients with thymoma-associated myasthenia gravis, well-differentiated thymic carcinoma (Muller-Hermelink system), age more than 55 years, and interval from the onset of symptoms to thymectomy of less than 1 year were found to be independent predictors of nonremission of myasthenia gravis after thymectomy.

PMID: 14602301 [PubMed - indexed for MEDLINE]

21: Ann Thorac Surg. 2003 Nov;76(5):1635-41; discussion 1641-2. Related Articles, Links

Comment in:

Ann Thorac Surg. 2004 Dec;78(6):2207; author reply 2207-8.

Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation.

Singhal S, Shrager JB, Rosenthal DI, LiVolsi VA, Kaiser LR.

Section of General Thoracic Surgery, Division of Cardiothoracic Surgery, Department of Surgery, Pennsylvania, Philadelphia, USA.

BACKGROUND: Adjuvant radiation after resection of Masaoka stage II thymoma is widely advocated, but the evidence supporting it is controversial. Studies addressing this issue generally report few patients and lump all patients beyond stage I together in the analysis. METHODS: We retrospectively compared outcomes of stage I and II thymomas treated by resection alone with thymomas treated by resection plus radiation. Histology was re-reviewed to confirm pathologic staging and resection margin status. RESULTS: Between February 1992 and 2002, we performed 167 resections for thymoma. Of these, 70 patients were believed to have tumors in stage IIb or less intraoperatively, and all of these patients underwent complete resection. We reviewed the histopathology of 62 of 70 patients. Thirty thymomas demonstrated less than complete transcapsular microscopic invasion (stage I) and 40 thymomas demonstrated microscopic transcapsular invasion or macroscopic invasion into surrounding fatty tissue (stage II). Forty-seven patients underwent surgery without postoperative mediastinal radiotherapy. Dosages in the 23 radiated patients (3 stage I and 20 stage II) consisted of 45 to 55 Gy. Median follow-up was 70.3 months. Stage II patients who were radiated (n = 20) and those who were not radiated (n = 20) consisted of identical proportions in stages IIa and IIb. Two patients recurred (1 unradiated stage I patient and 1 radiated stage IIb patient). Overall 5-year survival rate was 91%. All who died were free of recurrence at time of death. Log-rank test showed no difference in Kaplan Meier survival curves (p = 0.32) between the radiated and unradiated groups. CONCLUSIONS: These data support the contention that margin-negative surgical resection alone is sufficient treatment for both stages I and II thymoma.

PMID: 14602300 [PubMed - indexed for MEDLINE]

22: Cancer. 2003 Nov 1;98(9):1822-9. Related Articles, Links: Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors.

Sogawa K, Kondo K, Fujino H, Takahashi Y, Miyoshi T, Sakiyama S, Mukai K, Monden Y.

Department of Oncological and Regenerative Surgery, School of Medicine, University of Tokushima, Tokushima, Japan.

BACKGROUND: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma. METHODS: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively). CONCLUSIONS: MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma. Copyright 2003 American Cancer Society.

PMID: 14584061 [PubMed - indexed for MEDLINE]

23: Cell Immunol. 2003 Nov;226(1):1-10. Related Articles, Links: Induction of CD4+ murine natural killer T-like cells by immunization with syngeneic thymoma expressing embryonic alpha-fetoprotein.

Kim Y, Nakagawa Y, Sugiyama H, Shimizu M, Takeshita T, Araki T, Takahashi H.

Department of Microbiology and Immunology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.

In embryo, before the establishment of acquired immunity, a variety of embryonic antigens like alpha-fetoprotein (AFP) are produced and secreted in the sera, which rapidly disappear after the birth. Such embryonic antigens sometimes reappear from various tumor cells and decrease in the case of remission, indicating embryonic antigens may alert immune system to control tumors. In the present study, to examine the evoked immune responses against the tumors expressing embryonic antigen, we administered AFP-gene-transfected EL4 cells into syngeneic C57BL/6 mice and established a killer line against the tumor cells. To our surprise, the killer line was CD4+ NK1.1+, natural killer T (NKT)-like cells and eliminated not only AFP-expressing EL4 but YAC-1 cells. Moreover, the established line uniformly expressed Vbeta11 and secreted IL-4, IL-10, IL-13, and IFN-gamma. In vivo inoculation of the line markedly reduced the tumor growth in SCID mice, suggesting novelty of the NKT-like line for tumor surveillance.

PMID: 14746802 [PubMed - indexed for MEDLINE]

24: Chin Med J (Engl). 2003 Nov;116(11):1723-7. Related Articles, Links

Diffuse panbronchiolitis complicated with thymoma: a report of 2 cases with literature review.

Xie G, Li L, Liu H, Xu K, Zhu Y.

Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China. xgsh62@sina.com

OBJECTIVE: Diffuse panbronchiolitis, a distinct clinical entity of unknown etiology, has been reported originally and primarily in Japanese and rarely in non-Japanese populations. Macrolide therapy is effective for this once dismal disease. Diffuse panbronchiolitis complicated with thymoma is uncommon; only 2 cases have been reported to date. The aims of this study were to describe the clinical profiles, assess the response to macrolide therapy, and to discuss the possible pathogenesis of diffuse panbronchiolitis in this setting. METHODS: The clinical profiles, macrolide therapy response of diffuse panbronchiolitis complicated with encapsulated thymoma in 2 histologically confirmed cases were described and discussed with the 2 cases reported in the literature: one complicated with encapsulated thymoma, another with invasive thymoma. RESULTS: Of the 2 cases, both had negative PPD skin testing and abnormal serum levels of various immunoglobulins, 1 had positive anti-nuclear antibody, but none had elevated cold hemagglutinin titers, and both had an excellent response to macrolide therapy. Of the 2 cases reported in the literature, both had negative PPD or tuberculin skin testing, 1 had severe hypogammaglobulinemia, 1 had elevated IgA, 1 had positive anti-DNA, 1 had elevated cold hemagglutinin titers, but both died of respiratory failure in spite of macrolide therapy in 1 case. CONCLUSIONS: Prognosis for diffuse panbronchiolitis complicated with thymoma may depend on the nature of the thymoma and on the disease course. Macrolide therapy is also effective if administered early in the disease course and if the thymoma is cured. Immunological factors may play an important role in the pathogenesis of diffuse panbronchiolitis in this setting.

Publication Types:

Review

PMID: 14642145 [PubMed - indexed for MEDLINE]

25: Eur J Neurol. 2003 Nov;10(6):707-10. Related Articles, Links

HLA class II genotypes in Mexican Mestizo patients with myasthenia gravis.

Garcia-Ramos G, Tellez-Zenteno JF, Zapata-Zuniga M, Yamamoto-Furusho JK, Ruiz-Morales JA, Villarreal-Garza C, Vargas-Alarcon G, Estanol B, Llorente L, Granados J.

Department of Neurology, Instituo Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico, D.F. garciara@quetzal.innsz.mx

Myasthenia gravis is an autoimmune, heterogeneous disorder, characterized by the presence of antibodies against acetylcholine receptors at the neuromuscular junction. There is a strong evidence that an individual's genetic composition is an important predisposing factor for the development of the disease. To correlate HLA class II genotypes with thymic pathology in Mexican Mestizo patients who had been subjected to thymectomy. HLA class II genes were analyzed in 60 patients and in 99 healthy ethnically matched controls. Thymic hyperplasia, atrophy, thymoma, and normal histology were encountered in 56, 33, 8 and 2% of patients, respectively. HLA-DR11 was significantly increased in patients with thymoma compared with healthy controls (pC = 0.001, OR = 13.35, 95% CI 3.5-51.3), compared with the subgroup of hyperplasia patients (pC = 0.005, OR = 15.5, 95% CI 2.78-95.58) and with the atrophy subgroup (pC = 0.04, OR = 10.5, 95% CI 1.75-70.95). This study provides the evidence of an association between HLA class II alleles with clinical and genetic heterogeneity in myasthenia gravis, particularly in those with thymoma (HLA-DR11).

Publication Types:

Clinical Trial

PMID: 14641517 [PubMed - indexed for MEDLINE]

26: Eur J Neurol. 2003 Nov;10(6):701-6. Related Articles, Links: Disease severity and outcome in thymoma myasthenia gravis: a long-term observation study.

Romi F, Gilhus NE, Varhaug JE, Myking A, Aarli JA.

Department of Neurology, Haukeland University Hospital, Bergen, Norway. fredrik.romi@haukeland.no

Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype and are usually treated by thymectomy. However, the factors that influence MG outcome in thymoma MG patients are not known. In a long-term study, MG severity and treatment was observed in 24 thymoma and 24 non-thymoma MG patients for up to 30 years, and the occurrence of muscle autoantibodies was assayed. The rate of complete stable remission was low and did not differ between the two groups. There was no significant difference in MG severity between thymoma and non-thymoma MG patients at any time during the study. Titin and ryanodine receptor (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four thymoma (all titin and RyR antibody positive) and two non-thymoma (both titin and one RyR antibody positive) MG patients died from MG-related respiratory insufficiency. Seventy percent of thymoma and 75% of non-thymoma MG patients were treated with immunosuppressive drugs. The number of patients who received plasmapheresis did not differ in those who were treated because of acute MG deterioration, irrespective of planned surgery.This study shows equal MG severity and outcome in thymoma and non-thymoma MG, but the presence of RyR antibodies in thymoma MG and titin/RyR in non-thymoma MG indicates a less favorable prognosis.

PMID: 14641516 [PubMed - indexed for MEDLINE]

27: Hokkaido Igaku Zasshi. 2003 Nov;78(6):503-13. Related Articles, Links: [Malignant transformation of epithelial thymoma developed in HTLV-I pX transgenic rat by heterotopic transplantation and its molecular analysis]

[Article in Japanese]

Tsuji T.

Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

PMID: 14672038 [PubMed - indexed for MEDLINE]

28: Hum Pathol. 2003 Nov;34(11):1155-62. Related Articles, Links: Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma.

Pan CC, Chen PC, Chou TY, Chiang H.

Department of Pathology, National Yang-Ming University and Veterans General Hospital, Taipei, Taiwan.

Thymic carcinoma and thymoma are primary neoplasms of the anterior mediastinum that can involve the lung and pleura in advanced stages or, in rare instances, occur as primary pleural tumors. Thus these tumors may be encountered in thoracic and pleural biopsy specimens. Recognizing the immunohistochemical patterns of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma may be helpful in avoiding confusion with malignant mesothelioma and pulmonary carcinoma, both of which are major differential diagnoses in this location. Accordingly, in the present study we examined the expression of calretinin, mesothelin, cytokeratin (CK) 5/6, thrombomodulin, HBME-1, Wilms' tumor-1 (WT-1), Ber-EP4, MOC-31, BG-8, B72.3, carcinoembryonic antigen (CEA), CD15, thyroid transcription factor-1 (TTF-1), p63, and CD5 in 22 thymic carcinomas and 35 thymomas, and compared the results with those of malignant mesothelioma and pulmonary adenocarcinoma. Around 1/3 of thymic carcinomas were positive for calretinin and/or mesothelin. Both thymic carcinomas and thymomas were frequently positive for CK 5/6. Immunoreactivity for HBME-1 was seen in 4 thymic carcinomas and 10 thymomas. Except for 1 thymic carcinoma being positive for WT-1, all other thymic carcinomas and thymomas were negative for WT-1 and thrombomodulin. None of the thymic carcinomas and thymomas expressed TTF-1. More than 70% of the thymic carcinomas were positive for Ber-EP4, BG-8, and CD15. The positive rates of MOC-31, B72.3, and CEA in thymic carcinomas were in the middle between those in mesothelioma and pulmonary adenocarcinoma. All thymic epithelial tumors revealed nuclear immunoreactivity for p63. Nine thymic carcinomas (41%) expressed CD5. We found that a panel of positive p63, negative thrombomodulin, WT-1, and TTF-1 is most discriminatory for thymic epithelial tumors. Other mesothelial (calretinin and mesothelin) and epithelial (Ber-EP4, BG-8, and CD15) markers are less contributory in discerning thymic epithelial tumors due to their overlapping expression with malignant mesothelioma and pulmonary adenocarcinoma. Given the complexity of the staining patterns among the different entities, proper immunohistochemical stainings should be selected and interpreted with caution, and correlated with clinicopathologic findings in the differential diagnoses of thoracic biopsy specimens.

PMID: 14652817 [PubMed - indexed for MEDLINE]

29: J Neuroimmunol. 2003 Nov;144(1-2):143-7. Related Articles, Links: Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients.

van der Pol WL, Jansen MD, Kuks JB, de Baets M, Leppers-van de Straat FG, Wokke JH, van de Winkel JG, van den Berg LH.

Department of Neurology-C3, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. W.L.vanderPol@neuro.azu.nl

Myasthenia gravis (MG) susceptibility is partially determined by allelic heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the humoral and cellular branches of the immune system, and regulate immune responses and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as compared to 239 healthy controls (Pz.Lt;0.01), with a relative increase of the FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9). These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for susceptibility to MG.

PMID: 14597109 [PubMed - indexed for MEDLINE]

30: J Pediatr Hematol Oncol. 2003 Nov;25(11):900-4. Related Articles, Links

Metastatic chondroblastoma with elevated creatine kinase and paraneoplastic neurologic autoimmunity.

Joshi DD, Anderson PM, Matsumoto J, Moir C, Shives T, Unni K, Lennon VA.

Division of Pediatric Hematology/Oncology, Mayo Clinic Rochester, Minnesota 55905, USA.

A 17-year-old girl presented with chondroblastoma of the fibula and pulmonary metastases. Serum creatine kinase (CK) was elevated for a decade preoperatively and fell to near normal after tumor excision. An episode of aseptic meningitis 3 months later led to serologic detection of three antibody markers of paraneoplastic neurologic autoimmunity that in adult patients are characteristic of thymoma and lung carcinoma: muscle-type acetylcholine receptor (AChR) autoantibody (Ab), type 2 Purkinje cell cytoplasmic Ab (PCA-2), and collapsin response-mediator protein-5-IgG (CRMP-5-IgG). Locally recurrent chondroblastoma was excised 1 year later. Serum CK was elevated, CRMP-5-IgG was positive, PCA-2 was lower, and AChR Ab was undetectable. Three years after diagnosis she has stable pulmonary metastases, with elevated CK, higher PCA-2, positive CRMP-5-IgG, and undetectable AChR Ab. The association of metastatic chondroblastoma, elevated CK, and an evolving profile of paraneoplastic autoantibodies reveals a previously unrecognized immunobiologic dimension of chondroblastoma.

Publication Types:

Case Reports

PMID: 14608202 [PubMed - indexed for MEDLINE]

31: Kyobu Geka. 2003 Nov;56(12):1025-8. Related Articles, Links

[Experience with invasive thymoma presenting pleural dissemination]

[Article in Japanese]

Kataoka D, Nonaka M, Yamamoto S, Fukuzumi M, Kunimura T, Kaga E, Kadokura M, Takaba T.

Department of First Surgery, Showa University School of Medicine, Tokyo, Japan.

A 61-year-old man was admitted to Showa University Hospital because of a myasthenia gravis. Chest computed tomography revealed a mediastinal invasive tumor. During surgery, invasion to the pericardium and dissemination on the left visceral pleura and the left diaphragm were observed. Extended thymo-thymectomy and partial resection of the pericardium, left lung, and diaphragm were performed. Incomplete resection was achieved because of the dissemination on the diaphragm. Chemotherapy using ADOC and radiotherapy for mediastinum and left diaphragm were done. Four years after surgery, neither recurrence of the tumor nor myasthenia gravis was observed.

Publication Types:

Case Reports

PMID: 14608927 [PubMed - indexed for MEDLINE]

32: Rev Invest Clin. 2003 Nov-Dec;55(6):629-34. Related Articles, Links

Comment in:

Rev Invest Clin. 2004 Jul-Aug;56(4):528-9; author reply 530.

[Response to thymectomy in patients with thymoma]

[Article in Spanish]

Weder-Cisneros N, Tellez-Zenteno JF, Velasquez-Paz A, Cantu-Brito C, Orozco A, Mimenza-Alvarado A, Garcia-Ramos G.

Departamento de Neurologia, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, DF.

INTRODUCTION: Approximately 10% of patients with myasthenia gravis also have thymomas. The objective of this study was to describe the evolution after the thymectomy in 10 cases of myasthenia gravis associated with thymomas. METHODS: The study was based in a cohort of 132 patients with the diagnosis of myasthenia gravis, that underwent thymectomy between 1987 and 1997, and had at least three years of follow-up. We found 10 cases (7%) of thymomas. We analyzed the following variables: sex, age, associated diseases, disease evolution, Osserman, dose of edrophonium before surgery, steroid use before surgery, types of thymectomy, Osserman after surgery, pathology findings, and evolution. We used descriptive statistics according to the measurement level of the variables. RESULTS: Four (40%) were women and 6 (60%) were men. The antibodies against the acetylcholine receptor were tested in only 5 (50%) patients, and in all of them they were positive. 4 (40%) patients had complications after the thymectomy, being 2 (20%) of them myasthenic crisis, one (10%) pneumonia and another (10%) hemorrhage in the surgical wound. Six (60%) cases had malignant thymomas and 4 (40%) were benign. In the follow-up, 4 (40%) patients had a good clinical response of myasthenia gravis and 6 (60%) had no changes. CONCLUSION: The response to thymectomy was not as good as the response of the vast majority of patients with myasthenia gravis without thymomas. We found a high frequency of malignant thymomas in our patients.

PMID: 15011731 [PubMed - indexed for MEDLINE]

33: Toxicol Lett. 2003 Nov 1;145(1):55-68. Related Articles, Links: TCDD-induced apoptosis in EL-4 cells deficient of the aryl hydrocarbon receptor and down-regulation of IGFBP-6 prevented the apoptotic cell death.

Park JH, Hahn EJ, Kong JH, Cho HJ, Yoon CS, Cheong SW, Oh GS, Youn HJ.

Department of Biology, Changwon National University, #9, Sarim-dong, Changwon, Kyungnam 641-773, South Korea. parkjh@sarim.changwon.ac.kr

Although the potent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well known for its immunosuppressive activity, the mechanisms of its action have been difficult to elucidate, partly because of its inability of exerting its effects in vitro. We previously reported that insulin-like growth factor-binding protein-6 (IGFBP-6) expression in the thymus was increased by TCDD treatment of mice and that the TCDD-up-regulation of the IGFBP-6 gene was also observed with EL-4 mouse thymoma cells. In the present study, we examined the effects of IGFBP-6 on the TCDD-mediated cytotoxicity in EL-4 cells. By stably expressing IGFBP-6 sense or anti-sense mRNA in the EL-4 line of mouse thymoma cells, it was possible to isolate clones in which IGFBP-6 expression was increased or decreased. Clones expressing IGFBP-6 sense mRNA displayed increased sensitivity to cytotoxicity mediated by TCDD, whereas clones expressing IGFBP-6 anti-sense mRNA displayed reduced sensitivity. TCDD-induced DNA fragmentation was less pronounced in clones expressing IGFBP-6 anti-sense mRNA than clones expressing IGFBP-6 sense mRNA or the empty vector. Caspase 3 was activated by TCDD and anti-sense IGFBP-6 expression reduced its activity. Interestingly, the effects of TCDD were exerted without aromatic hydrocarbon (Ah) receptor (AhR). Taken together, the results have shown that IGFBP-6 mediates the immunotoxic effects of TCDD in EL-4 cells in an AhR-independent pathway.

PMID: 12962974 [PubMed - indexed for MEDLINE]

34: Biochim Biophys Acta. 2003 Oct 21;1642(3):149-62. Related Articles, Links: Overexpression of catalase or Bcl-2 delays or prevents alterations in phospholipid metabolism during glucocorticoid-induced apoptosis in WEHI7.2 cells.

Tome ME, Lutz NW, Briehl MM.

Department of Pathology, University of Arizona, PO Box 254043, Tucson, AZ 85724, USA.

Dexamethasone-treated WEHI7.2 mouse thymoma cells readily undergo apoptosis. WEHI7.2 variants that overexpress catalase (CAT38) or Bcl-2 (Hb12) show a delay or lack of apoptosis, respectively, when treated with dexamethasone. This is accompanied by a delay or lack of cytochrome c release from the mitochondria suggesting that alterations in the signaling phase of apoptosis are responsible for the observed resistance. Because membranes are a rich source of signaling molecules, we have used 31P NMR spectroscopy to compare phospholipids and their metabolites in WEHI7.2, CAT38 and Hb12 cells after dexamethasone treatment. Increased lysophosphatidylcholine (lysoPtdC) content accompanied phosphatidylserine (PtdS) externalization in the WEHI7.2 cells. Both changes were delayed in CAT38 cells suggesting phosphatidylcholine (PtdC) metabolites may play a role in steroid-induced apoptotic signaling. The steroid-resistant Hb12 cells showed a dramatic increase in glycerophosphocholine (GPC) content, suggesting increased phospholipid turnover may contribute to the anti-apoptotic mechanism of Bcl-2.

PMID: 14572898 [PubMed - indexed for MEDLINE]

35: N Engl J Med. 2003 Oct 9;349(15):1442. Related Articles, Links

Images in clinical medicine. Spindle-cell thymoma.

Shapira OM, Kasznica JM.

Boston Medical Center, Boston, MA 02118, USA.

Publication Types:

Case Reports

PMID: 14534337 [PubMed - indexed for MEDLINE]

36: Ann Pathol. 2003 Oct;23(5):457-9. Related Articles, Links

[A rare endothoracic tumor]

[Article in French]

Ammar A, Sellami NK, El Hammami S, Horchani H, Kilani T.

Service d'Anatomie et de Cytologie Pathologiques, Hopital Abderrahmen Mami, Ariana. ahlem.ammar@rns.tn

Publication Types:

Case Reports

PMID: 14752394 [PubMed - indexed for MEDLINE]

37: Ann Thorac Surg. 2003 Oct;76(4):1310-1. Related Articles, Links: Thoracoscopic thymectomy using anterior chest wall lifting method.

Ohta M, Hirabayasi H, Okumura M, Minami M, Matsuda H.

Department of General Thoracic Surgery, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan. ohta@surg1.med.osaka-u.ac.jp

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

PMID: 14530043 [PubMed - indexed for MEDLINE]

38: Ann Thorac Surg. 2003 Oct;76(4):1041-5. Related Articles, Links: Thymic carcinoma: involvement of great vessels indicates poor prognosis.

Tseng YL, Wang ST, Wu MH, Lin MY, Lai WW, Cheng FF.

Institute of Clinical Medicine, Taiwan, Tainan, China

BACKGROUND: Thymic carcinoma is a rare, indolent, and invasive cancer. This study investigated the treatment results of thymic carcinoma and clinical prognostic factors. METHODS: From June 1988 to January 2002, 38 patients were enrolled in this study with the diagnosis of thymic carcinoma in the Cheng-Kung University Hospital based on Rosai's and Muller-Hermelink's classification. Clinical and pathologic data were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier, log rank, and Wilcoxon tests. Statistical significance was defined as p < 0.05. RESULTS: Pathology revealed 14 poorly differentiated, 6 moderately differentiated, and 8 well-differentiated squamous cell carcinomas; 8 lymphoepithelioma-like carcinomas; and 2 other carcinomas. Pathologic staging using the Masaoka system included 6 stage II, 23 stage III, and 9 stage IV patients. Six biopsies, five debulkings, and 27 complete resections were performed. All patients were followed from 15 months to 10 years 9 months, with an average of 53.8 months. Median survival time was 81 months, and median recurrence time was 52 months. Eighteen patients are still alive, and 7 are alive with disease. Well-differentiated squamous cell carcinoma had better prognosis than other carcinomas (p = 0.022). Complete resection significantly increased survival rate (p < 0.001). Tumor invasion of the superior vena cava, pulmonary vessels, or aorta were significant predictors for poor prognosis (p = 0.016, 0.002, and 0.002, respectively). CONCLUSIONS: Only patients with thymic carcinoma who underwent complete resection had long-term survival. Prognosis of thymic carcinoma seemed mainly dependent on tumor invasion of the great vessels.

PMID: 14529981 [PubMed - indexed for MEDLINE]

39: Cancer Genet Cytogenet. 2003 Oct 1;146(1):66-9. Related Articles, Links

Deletion (6)(p22p25) is a recurrent anomaly of thymoma: report of a second case and review of the literature.

Herens C, Radermecker M, Servais A, Quatresooz P, Jardon-Jeghers C, Bours V, de Leval L.

Department of Human Genetics, University of Liege, Tour de Pathologie, B23 Sart Tilman, 4000 Liege, Belgium. christian.herens@chu.ulg.ac.be

A patient with type AB thymoma and del(6)(p22p25) as the sole cytogenetic anomaly is described. This is the second report of a del(6)(p22p25) in a thymoma. The same deletion was previously found in association with a type A thymoma. Both patients presented with benign tumors. These data suggest that partial deletion of the short arm of chromosome 6 is a nonrandom change associated with benign thymomas.

Publication Types:

Case Reports

PMID: 14499698 [PubMed - indexed for MEDLINE]

40: Chin Med J (Engl). 2003 Oct;116(10):1578-81. Related Articles, Links: Myasthenia gravis in pediatric and elderly patients.

Liu W, Liu G, Fan Z, Gai X.

Department of Thoracic Surgery, First Hospital, Jilin University, Changchun, China. davidliuw@hotmail.com

OBJECTIVE: To determine whether the clinical and pathologic characteristics and prognoses of myasthenia gravis (MG) patients below 15 years differ from those patients over 50 years after thymectomy. METHODS: We reviewed the registry material of 30 pediatric and 32 elderly MG patients after thymectomy, including their age, sex, clinical classification, pathological types, and prognoses. The Chi-square test or Wilcoxon's rank-sum test was used to determine the statistical differences between the children and elderly groups. RESULTS: No significant difference was seen in sex distribution between the two groups. (Chi-square test, P=0.625), but there were differences in clinical classification: more type I was observed in the pediatric group than in the elderly group, but more type II or III was seen in the elderly group (Wilcoxon's rank-sum test, P<0.001). As to pathological types, the pediatric group was also significantly different from the elderly group (Chi-square test, P<0.01). All of the patients (100%) in the pediatric group had thymus hyperplasia, but in the elderly group more than half (56.26%) were found to have thymoma (benign or malignant). The prognoses after thymectomy were better in the pediatric group than in the elderly group (Wilcoxon's rank-sum test, P<0.001). CONCLUSIONS: Because the prognoses are generally better than those of the elderly patients, we should be careful when operating on pediatric patients of ocular type. The elderly patients tend to receive more aggressive treatment because of more severe generalized types often associated with thymoma and poor prognoses. Both pediatric and elderly patients are seldom associated with other autoimmune disease.

PMID: 14640105 [PubMed - indexed for MEDLINE]

41: Int J Oncol. 2003 Oct;23(4):1231-5. Related Articles, Links: Role of antioxidant genes for the activity of artesunate against tumor cells.

Efferth T, Briehl MM, Tome ME.

Center for Molecular Biology at the University of Heidelberg (ZMBH), 69120 Heidelberg, Germany. thomas.efferth@web.de

The antimalaria drug, artesunate (ART), is very cytotoxic in tumor cell lines. The active moiety of ART is an endoperoxide bridge that generates carbon-centered free radicals and oxidative stress upon cleavage. Oxidative stress appears to be necessary for the antimalarial activity of ART. To test whether antioxidant gene expression affects the ART response in tumor cell lines we compared the baseline antioxidant mRNA gene expression in the 55 human tumor cell line panel from the National Cancer Institute Developmental Therapeutics Program to the ART IC50. Thioredoxin reductase expression showed a significant positive correlation to the ART IC50 and catalase expression was inversely correlated with the ART IC50 (p<0.05). WEHI7.2 mouse thymoma cells selected for resistance to hydrogen peroxide or transfected with thioredoxin, manganese superoxide dismutase, catalase or bcl-2 showed resistance to ART compared to the parental cell line. Taken together these data support a role for oxidative stress in the mechanism of ART action in tumor cells and suggest that antioxidant defenses act in combination to affect the cellular response to ART.

PMID: 12964009 [PubMed - indexed for MEDLINE]

42: Int J Surg Pathol. 2003 Oct;11(4):353-6. Related Articles, Links

Primary intrapulmonary spindle cell thymoma with marked granulomatous reaction: report of a case with review of literature.

Srivastava A, Padilla O, Alroy J, Ucci A, Pilichowska M, Daley B, Wolfe HJ.

Department of Pathology, New England Medical Center, Boston, MA 02111, USA.

Primary intrapulmonary thymoma is a rare lesion with around 20 cases reported so far in the literature. A pure spindle cell morphology in these lesions is rarer still with only a single case recorded to date. We report herein an interesting case of a 47-year-old-man, status post surgical resection and radiotherapy for a squamous cell carcinoma of the floor of mouth, who was being followed up for a radiologic opacity in the right lower lobe of the lung. The lesion remained stable in size for almost 5 years and then an increase in size was noted. A right lower lobectomy was performed with a preoperative suspicion of metastasis. Histologic and immunohistochemical evaluation revealed a primary intrapulmonary spindle cell thymoma that displayed a prominent granulomatous reaction, a phenomenon not described so far in the literature. We discuss the possible embryologic origins and the pitfalls in diagnosis of these rare neoplasms. The remarkable granulomatous response observed in the tumor raises the possibility that similar lesions might conceivably occur in the thymus as well.

Publication Types:

Case Reports

PMID: 14615837 [PubMed - indexed for MEDLINE]

43: J Thorac Cardiovasc Surg. 2003 Oct;126(4):1134-40. Related Articles, Links: Thymoma: a clinicopathologic study based on the new World Health Organization classification.

Nakagawa K, Asamura H, Matsuno Y, Suzuki K, Kondo H, Maeshima A, Miyaoka E, Tsuchiya R.

Divisions of Thoracic Surgery, National Cancer Center Hospital and Research Institute, Tokyo, Japan.

OBJECTIVE: This study explored the relationship between the histologic subtype of thymoma according to the new World Health Organization histologic classification and the clinical findings, as well as the prognostic significance of the classification. METHODS: A total of 130 patients with thymoma, who underwent resection at the National Cancer Center Hospital, Tokyo, from 1962 to 2000, were studied retrospectively. The histologic subtype of thymoma was determined according to the new World Health Organization histologic classification. The stage was also determined according to a modified Masaoka's classification as stage I, II, III, IVa, or IVb. To determine the factors that may affect the prognosis of thymoma, a multivariate analysis with Cox's proportional hazards regression model was performed. RESULTS: The distribution of histologic subtype was type A (n = 18), type AB (n = 56), type B1 (n = 15), type B2 (n = 29), and type B3 (n = 12). A close correlation was seen between the histologic subtype and stage (P =.000). The overall survivals at 5 and 10 years were 92% and 91%, respectively. The 5- and 10-year survivals according to stage were 100% and 100% (stage I, n = 40; stage II, n = 54), 81% and 76% (stage III, n = 25), and 47% and 47% (stage IV, n = 11), respectively. The difference in survival between stage III and stage IV was significant (P =.000). Patients with type A or AB thymoma demonstrated a 100% survival at both 5 and 10 years. Recurrences were seen in 12 patients with complete resection. According to a multivariate analysis, tumor size (P =.001), completeness of resection (P =.002), histologic subtype (P =.011), and stage (P =.00) were significant prognostic factors. CONCLUSION: The World Health Organization histologic classification significantly correlated with the clinical stage. Tumor size, completeness of resection, histologic subtype, and stage predicted the prognosis of thymoma.

PMID: 14566259 [PubMed - indexed for MEDLINE]

44: Jpn J Thorac Cardiovasc Surg. 2003 Oct;51(10):481-7. Related Articles, Links: Increased thymocyte CD4+CD8+ cells and T-cell receptor beta gene rearrangements in thymoma.

Sakuraba M, Motoji T, Nitta S, Mizoguchi H, Ohnuki T.

Department of Surgery I, Tokyo Women's Medical University School of Medicine, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan.

Epithelial cells in thymoma and thymic carcinoma may influence T-cell development in the tumor. In this study, we investigated the cell surface phenotype and T-cell receptor (TCR) gene rearrangement of thymocytes in thymic tumors. TCR rearrangement was observed in all cases of thymoma (A, AB, B1-2). A faint band in each digestion suggested the deletion between D1 to C1 or D1 to J2, and an additional rearrangement band with BamHI suggested the rearrangement between D1 to J1. High percentages of CD1+ cells and CD4+CD8+ (DP) cells were detected in all cases of thymoma (A, AB, B1-2). There are two kinds of cell surface phenotypes increased in populations of thymoma; one is increased DP cells and the other is a relatively low percentage of DP cells accompanied by a relatively high percentage of CD3+CD69+ cells. These findings suggest that thymocytes in thymoma are derived from immature T-cell expansion.

PMID: 14621007 [PubMed - indexed for MEDLINE]

45: N Z Vet J. 2003 Oct;51(5):244-7. Related Articles, Links: Feline paraneoplastic syndrome associated with thymoma.

Smits B, Reid MM.

Alpha Scientific Ltd, PO Box 195, Hamilton, New Zealand. bronwyn-smits@alpha-scientific.co.nz

CASE HISTORY: A 6-year-old, spayed, female, domestic short-haired cat presented with severe erythroderma and scaling skin. She showed disturbed gait and mild behavioural changes. CLINICAL FINDINGS: The cat had a generalised, erythematous, scurfy dermatitis with marked, multifocal crusting and skin thickening. The skin was painful and contracted, which appeared to prevent normal freedom of movement. DIAGNOSIS: The cat was suspected to have a paraneoplastic syndrome. A mediastinal mass was located and histologically confirmed as thymoma. The cat was diagnosed with a thymoma- associated cutaneous paraneoplastic syndrome. CLINICAL RELEVANCE: This is a rare condition with few reports in the literature. The skin changes, both grossly and histologically, were considered to be different from those described in cases of paraneoplastic dermatosis associated with pancreatic neoplasia. The clinical presentation was characteristic and more cases may occur in practice than are recognised. In this case, as in previous reports, the tumour was grossly resectable, which could lead to cure of the clinical condition.

PMID: 16032334 [PubMed]

46: Nervenarzt. 2003 Oct;74(10):888-91. Related Articles, Links

[Polyneuropathy as a sole syndrome in malignant thymoma]

[Article in German]

Schmidt H, Kaboth U, Brinck U, Ratzka P, Rustenbeck H, Nau R.

Klinik fur Neurologie, Georg-August-Universitat, Gottingen. hschmid2@gwdg.de

Up to 40% of patients with malignant thymoma suffer from paraneoplastic symptoms (90% myasthenia, 10% other symptoms). A 55-year-old patient developed ascending symmetrical sensorimotor tetraparesis. A malignant thymoma without metastases was diagnosed 6 months later. Despite thymectomy followed by radiation and high-dose corticosteroid therapy, the polyneuropathy progressed. Six months after onset, the patient was bound to a wheelchair. Immunosuppressive therapy with cyclophosphamide was initiated, leading to marked remission. After ten cycles, the patient was able to walk independently with walking aids. After the sixth and tenth cycle, respectively, attempts to discontinue immunosuppression led to relapse. In several diagnostic workups, however, there was no tumour relapse. After 13 cycles, cyclophosphamide was replaced by immunoglobulins (0.4 g/kg per day i.v. for 5 days/month) due to progressive renal failure. The patient died just before the second course of this treatment. In conclusion, in the differential diagnosis of rapidly progressive polyneuropathy, a malignant thymoma should be considered, even in the absence of myasthenia. Immunosuppression with cyclophosphamide resulted in amelioration of symptoms in this patient.

Publication Types:

Case Reports

PMID: 14551694 [PubMed - indexed for MEDLINE]

47: Nihon Kokyuki Gakkai Zasshi. 2003 Oct;41(10):755-9. Related Articles, Links

[Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report]

[Article in Japanese]

Mochizuki H, Okada T, Yoshizawa H, Suzuki E, Gejyo F.

Department of Respiratory Medicine, Tsuruoka City Shonai Hospital.

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.

Publication Types:

Case Reports

PMID: 14584399 [PubMed - indexed for MEDLINE]

48: Radiat Res. 2003 Oct;160(4):478-87. Related Articles, Links: Generation of reactive oxygen species and radiation response in lymphocytes and tumor cells.

Shankar B, Kumar SS, Sainis KB.

Radiation Biology and Health Sciences Division, Bioscience Group, Bhabha Atomic Research Centre, Modular Laboratories, Trombay, Mumbai 400 085, India.

Several types of lymphoid and myeloid tumor cells are known to be relatively resistant to radiation-induced apoptosis compared to normal lymphocytes. The intracellular generation of reactive oxygen species was measured in irradiated spleen cells from C57BL/6 and BALB/c mice and murine tumor cells (EL-4 and P388) by flow cytometry using dichlorodihydrofluoresceindiacetate and dihydrorhodamine 123 as fluorescent probes. The amount of reactive oxygen species generated per cell was low in the tumor cells compared to spleen cells exposed to 1 to 10 Gy of gamma radiation. This could be due to the higher total antioxidant levels in tumor cells compared to normal cells. Further, the changes in mitochondrial membrane potential and cytoplasmic Ca2+ content were appreciable in lymphocytes even at a dose of 1 Gy. In EL-4 cells, no such changes were observed at any of the doses used. About 65% of spleen cells underwent apoptosis 24 h after 1 Gy irradiation. However, under the same conditions, EL-4 and P388 cells failed to undergo apoptosis, but they accumulated in G2/M phase. Thus the intrinsic radioresistance of tumor cells may be due to a decreased generation of reactive oxygen species after irradiation and down-regulation of the subsequent events leading to apoptosis.

PMID: 12968927 [PubMed - indexed for MEDLINE]

49: Rays. 2003 Oct-Dec;28(4):369-78. Related Articles, Links

Diagnostic imaging and therapy in a case of myasthenia gravis associated with thymic hyperplasia.

Foschi R, Rinaldi P, Meduri A, Campioni P, Pirronti T.

Istituto di Radiologia, Universita Cattolica del S. Cuore, Policlinico A. Gemelli, Roma, Italy.

The diagnostic approach to a patient with myasthenia gravis to verify the presence of thymic hyperplasia/thymoma is presented. The study of the mediastinal region was necessary. Mediastinal MRI showed the presence of a mass. The differential diagnosis between a mediastinal and an extramediastinal lesion is possible with MRI for its high contrast resolution, good spatial resolution and multiplanarity that allow the detection, localization, evaluation of the extent and/or infiltration of adjacent tissues/organs based on the analysis of adipose cleavages and typing in the different pulse sequences of pathologic tissue with contrast enhancement. Definitive diagnosis of thymic hyperplasia was established. Therefore surgery should be essentially associated with the severity of the clinical presentation rather than with thymic hyperplasia.

Publication Types:

Case Reports

PMID: 15152539 [PubMed - indexed for MEDLINE]

50: Rev Med Chir Soc Med Nat Iasi. 2003 Oct-Dec;107(4):881-5. Related Articles, Links

[Morphologic and clinical correlations in medullar thymoma]

[Article in Romanian]

Butcovan D, Tinica G, Sandica E, Diaconescu V, Ivan L, Borza C, Pacuraru L, Pacuraru M, Georgescu GI.

Departamentul de Patologie, Facultatea de Medicina, Universitatea de Medicina si Farmacie Gr.T. Popa Iasi.

The medullar thymoma is a rare and distinctive epithelial thymoma, a thymic tumor characterized histologically by a mixture of spindle epithelial cells and lymphoid cells. We are presenting this tumor to a 68 years old man, admitted at CCI, for a mediastinal tumor, treated by tumorectomy, for revealing the cytological, histological and immunohistochemical characteristic features. The surgical biopsy was prepared by using usual histological techniques and haematoxilin eosin and Van Gieson stainings. We are discussing the relation between the thymoma clinicopathological and prognostic features, resulting a clear correlation between histological type and clinical study. We also pointed the Muller-Hermelink thymoma histological subtypes and their correspondence with OMS histological types, reflecting realistically the thymoma clinical behavior.

Publication Types:

Case Reports

PMID: 14756039 [PubMed - indexed for MEDLINE]

51: AJR Am J Roentgenol. 2003 Sep;181(3):721-4. Related Articles, Links

CT-guided percutaneous ethanol injection of the thymus for treatment of myasthenia gravis.

Wang P, Zuo C, Tian J, Qian Z, Ren F, Shao C, Wang M, Lu T.

Department of Radiology, Changhai Hospital, 174 Changhai Rd., Shanghai, China 200433, USA. lionred98@sohu.com

OBJECTIVE: This study was designed to validate the therapeutic effectiveness of CT-guided percutaneous ethanol injection of the thymus for the treatment of myasthenia gravis. SUBJECTS AND METHODS: The subjects were 45 patients with myasthenia gravis. The diagnosis was determined by the patients' histories, physical findings, neostigmine tests, and morphologic changes. According to the Osserman classification, the 45 patients with myasthenia gravis were classified as stage I (n = 26), stage III (n = 13), and stage IV (n = 6). A 21- or 22-gauge needle was inserted into the thymus under CT guidance, and then ethanol was injected step by step until it was distributed throughout the whole thymoma, the hyperplasia of the thymus, or the normal thymus. The amount of ethanol injected ranged from 2 to 13 mL, with a mean of 7 mL. RESULTS: CT follow-up at 3-4 weeks showed that the thymus or thymoma was completely or mostly necrotized. CT follow-up at 3 months showed that the vertical, transverse, and anteroposterior dimensions of the thymus in all 45 myasthenia gravis patients decreased by 59.2%, 68.6%, and 73.2%, respectively, compared with those before percutaneous ethanol injection treatment. The therapeutic effect was observable clinically 2 days after treatment in 44 patients, including 36 patients who were able to open their eyes after treatment. A 5-year follow-up study showed that the condition markedly improved in 35 patients, improved in nine patients, and failed to improve in one patient who did not respond to the treatment. After treatment, 37 patients presented with low-grade fever (range, 37.3-37.7 degrees C; mean, 37.5 degrees C), which resolved 3 days later without treatment; all 45 patients complained of mild retrosternal pain after ethanol injection. CONCLUSION: The therapeutic effect of CT-guided percutaneous ethanol injection into the thymus of patients with myasthenia gravis is definite. This procedure is safe and has low morbidity. CT-guided percutaneous ethanol injection is a minimally invasive alternative treatment for myasthenia gravis.

Publication Types:

Validation Studies

PMID: 12933467 [PubMed - indexed for MEDLINE]

52: Ann N Y Acad Sci. 2003 Sep;998:509-11. Related Articles, Links: Abnormal single-fiber electromyography in patients not having myasthenia: risk for diagnostic confusion?

Mercelis R.

University Hospital, Antwerp, Belgium. rudy.mercelis@ua.ac.be

PMID: 14592921 [PubMed - indexed for MEDLINE]

53: Ann N Y Acad Sci. 2003 Sep;998:491-3. Related Articles, Links: Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients.

Tellez-Zenteno JF, Remes-Troche JM, Garcia-Ramos G, Estanol B, Garduno-Espinoza J.

Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Delegacion Tlalpan, Mexico. jftellez@quetzal.innsz.mx

PMID: 14592918 [PubMed - indexed for MEDLINE]

54: Ann N Y Acad Sci. 2003 Sep;998:481-90. Related Articles, Links

Thymectomy and antimuscle antibodies in nonthymomatous myasthenia gravis.

Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA.

Department of Neurology, Haukeland University Hospital, N-5021 Bergen, Norway. fredrik.romi@haukeland.no

The clinical effect of thymectomy in early- and late-onset myasthenia gravis (MG) and the correlation to MG severity, pharmacological treatment, and antimuscle antibodies were examined in two series of consecutive acetylcholine receptor (AChR) antibody-positive nonthymoma MG patients. The results indicate a benefit of thymectomy in early-onset MG, but no obvious clinical benefit in late-onset MG. The presence of muscle autoantibodies did not influence the outcome of thymectomy in early-onset MG. In late-onset MG, improvement is least likely in patients with titin and/or RyR antibodies. Thymectomy should always be considered shortly after MG onset in early-onset MG patients and might only be considered in late-onset patients who have early-onset-like immunological characteristics.

Publication Types:

Clinical Trial

PMID: 14592917 [PubMed - indexed for MEDLINE]

55: Ann N Y Acad Sci. 2003 Sep;998:473-80. Related Articles, Links

Development of a thymectomy trial in nonthymomatous myasthenia gravis patients receiving immunosuppressive therapy.

Wolfe GI, Kaminski HJ, Jaretzki A 3rd, Swan A, Newsom-Davis J.

Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas 75390-8897, USA. gil.wolfe@utsouthwestern.edu

Thymectomy has been regularly used in the management of nonthymomatous autoimmune myasthenia gravis (MG), but its benefits have not been established in a randomized, controlled trial. The widespread use of thymectomy in MG patients without thymoma is largely based on retrospective, nonrandomized case series that have produced a consensus that the procedure is sometimes beneficial. Still, the benefits and utilization of thymectomy are actively debated among MG experts. In this paper, we describe the development of a multicenter, international trial to determine whether extended transsternal thymectomy reduces corticosteroid requirements for patients with generalized AChR antibody-positive nonthymomatous MG.

Publication Types:

PMID: 14592916 [PubMed - indexed for MEDLINE]

56: Ann N Y Acad Sci. 2003 Sep;998:424-31. Related Articles, Links: Myasthenia gravis in individuals over 40.

Aarli JA, Romi F, Skeie GO, Gilhus NE.

Department of Neurology, University of Bergen, Bergen, Norway. johan.a.aarli@helse-bergen.no

Myasthenia gravis (MG) in individuals over 40 years of age comprises three groups: early-onset MG with prolonged disease duration, late-onset MG with thymoma, and late-onset of nonthymomatous MG. The clinical features do not differ between the three groups, except that early-onset patients with prolonged disease duration usually have a less severe disease. More than 60% of our MG patients are now more than 50 years of age, often with disease onset after age 40. Although 2 out of the 3 patients in Erb's original description had onset of myasthenic symptoms after age 40, this was apparently infrequent in 1879, when the disease was first identified. Onset of MG after age 40 is now common. For example, in our material, 88/184 (47.8%) had onset of MG after age 40. Eighteen (20.5%) had a thymoma. The female:male ratio in the early-onset group was 2.4:1, whereas it was 1:1.1 among those with onset after age 40. There was no human leukocyte antigen association for MG with thymoma. Antibodies to the acetylcholine receptor were detected in 88% of sera from nonthymomatous MG and in 100% of those with late-onset MG with thymoma. Antibodies to titin were found in sera from 85.7% of MG patients with thymoma (all age groups) and in 58% of nonthymomatous MG with late onset and acetylcholine receptor antibodies. Late-onset, nonthymomatous MG comprises two subgroups, one corresponding to delayed early onset and one immunologically similar to that seen in patients with MG and thymoma.

PMID: 14592910 [PubMed - indexed for MEDLINE]

57: Ann N Y Acad Sci. 2003 Sep;998:413-23. Related Articles, Links: Myasthenia gravis (MG): epidemiological data and prognostic factors.

Mantegazza R, Baggi F, Antozzi C, Confalonieri P, Morandi L, Bernasconi P, Andreetta F, Simoncini O, Campanella A, Beghi E, Cornelio F.

Immunology and Muscular Pathology Unit, National Neurological Institute Carlo Besta, 20133 Milan, Italy. rmantegazza@istituto-besta.it

Data from 756 myasthenic patients were analyzed for diagnostic criteria, clinical aspects, and therapeutic approaches. The patients were followed up at our institution from 1981 to 2001. Clinical evaluation was performed according to the myasthenia gravis score adopted at our clinic. Clinical features of each patient (comprising demographic, clinical, neurophysiological, immunological, radiological, and surgical data, as well as serial myasthenia gravis scores) were filed in a relational database containing more than 7000 records. Clinical efficacy and variables influencing outcome were assessed by life-table methods and Cox proportional hazards regression analysis. Complete stable remission, as defined by the Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, was the end point for good prognosis. Four hundred and ninety-nine patients (66%) were female and 257 (34%) were male. Mean follow-up was 55.1 +/- 48.1 months. Onset of symptoms peaked in the third decade in females, whereas the male distribution was bimodal with peaks in the third and sixth decades. Modality of myasthenia gravis presentation was as follows: ocular, 39.3%; generalized, 28.5%; bulbar, 31.3%; and respiratory, 0.8%. Thymectomy was carried out on 63.7% of our patients by different approaches: (1) transcervical; (2) transsternal; (3) video-thoracoscopic mini-invasive surgery. The last approach has been preferentially used in more recent years and accounted for 62.4% of the thymectomized myasthenia gravis population. Univariate analysis and Kaplan-Meier analysis showed that variables such as sex (female), age at onset (below 40 years), thymectomy, and histological diagnosis of thymic hyperplasia were significantly associated with complete stable remission, whereas on multivariate analysis only age at onset below 40 years and thymectomy were confirmed.

PMID: 14592909 [PubMed - indexed for MEDLINE]

58: Ann N Y Acad Sci. 2003 Sep;998:359-61. Related Articles, Links: Muscle and neuronal autoantibody markers of thymoma: neurological correlations.

Vernino S, Lennon VA.

Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA. verns@mayo.edu

PMID: 14592897 [PubMed - indexed for MEDLINE]

59: Ann N Y Acad Sci. 2003 Sep;998:343-50. Related Articles, Links

Pathogenesis of myositis and myasthenia associated with titin and ryanodine receptor antibodies.

Skeie GO, Romi F, Aarli JA, Bentsen PT, Gilhus NE.

Department of Neurology, University of Bergen, Bergen, Norway. gske@haukeland.no

Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for these antibodies are the Ca(2+) release channel of the sarcoplasmic reticulum, the ryanodine receptor (RyR), and titin, a gigantic filamentous muscle protein essential for muscle structure, function, and development. RyR and titin antibodies are found in MG patients with a thymoma and in a proportion of late-onset MG, and they correlate with severe MG disease. The RyR antibodies recognize a region near the N-terminus important for channel regulation. They inhibit Ca(2+) release from sarcoplasmic reticulum in vitro. There is electrophysiological evidence for a disordered excitation-contraction coupling in MG patients. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy in MG patients. However, so far, there is no direct evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo.

Publication Types:

Review

PMID: 14592894 [PubMed - indexed for MEDLINE]

60: Ann N Y Acad Sci. 2003 Sep;998:278-83. Related Articles, Links: Expression of transforming growth factor-beta1 in thymus of myasthenia gravis patients: correlation with pathological abnormalities.

Bernasconi P, Passerini L, Annoni A, Ubiali F, Marcozzi C, Confalonieri P, Cornelio F, Mantegazza R.

Immunology and Muscular Pathology Unit, Istituto Nazionale Neurologico Carlo Besta, 20133 Milan, Italy. pbernasconi@istituto-besta.it

PMID: 14592886 [PubMed - indexed for MEDLINE]

61: Ann N Y Acad Sci. 2003 Sep;998:270-4. Related Articles, Links: Analysis of SjTREC levels in thymus from MG patients and normal children.

Passerini L, Bernasconi P, Baggi F, Cornelio F, Mantegazza R.

Immunology and Muscular Pathology Unit, Istituto Nazionale Neurologico Carlo Besta, 20133 Milan, Italy.

PMID: 14592884 [PubMed - indexed for MEDLINE]

62: Ann N Y Acad Sci. 2003 Sep;998:257-65. Related Articles, Links

A new model linking intrathymic acetylcholine receptor expression and the pathogenesis of myasthenia gravis.

Levinson AI, Zheng Y, Gaulton G, Moore J, Pletcher CH, Song D, Wheatley LM.

Allergy and Immunology Section, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA. rog@mail.med.upenn.edu

The thymus is thought to play an important role in the pathogenesis of myasthenia gravis (MG), an autoimmune disease characterized by skeletal muscle weakness. However, its role remains a mystery. The studies described represent our efforts to determine how intrathymic expression of the neuromuscular type of acetylcholine receptors (nAChRs) is involved in the immunopathogenesis of MG. We review our work characterizing the expression of the alpha subunit of nAChR (nAChRalpha) in the thymus and advance a new hypothesis that examines the intrathymic expression of this autoantigen in disease pathogenesis.

Publication Types:

Review

PMID: 14592882 [PubMed - indexed for MEDLINE]

63: Ann N Y Acad Sci. 2003 Sep;998:237-56. Related Articles, Links: Scenarios for autoimmunization of T and B cells in myasthenia gravis.

Shiono H, Roxanis I, Zhang W, Sims GP, Meager A, Jacobson LW, Liu JL, Matthews I, Wong YL, Bonifati M, Micklem K, Stott DI, Todd JA, Beeson D, Vincent A, Willcox N.

Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.

We have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy.

PMID: 14592881 [PubMed - indexed for MEDLINE]

64: Ann N Y Acad Sci. 2003 Sep;998:223-36. Related Articles, Links

The role of thymomas in the development of myasthenia gravis.

Marx A, Muller-Hermelink HK, Strobel P.

Institute of Pathology, University of Wurzburg, D-97080 Wurzburg, Germany. path031@mail.uni-wuerzburg.de

Thymic pathology occurs in 80-90% of myasthenia gravis patients. Significant associations between different thymic alterations and clinical findings are discussed. To highlight peculiarities in thymoma-associated myasthenia gravis, we briefly review myasthenia gravis associated with thymic lymphofollicular hyperplasia (TFH) and thymic atrophy.

Publication Types:

Review

PMID: 14592880 [PubMed - indexed for MEDLINE]

65: Ann N Y Acad Sci. 2003 Sep;998:202-10. Related Articles, Links

Autoimmune disorders of neuronal potassium channels.

Newsom-Davis J, Buckley C, Clover L, Hart I, Maddison P, Tuzum E, Vincent A.

Weatherall Institute of Molecular Medicine and Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom. john.newmandavis@btinternet.com

Antibodies to voltage-gated potassium channels (VGKCs) appear likely to be the effector mechanisms in many patients with acquired peripheral nerve hyperexcitability (APNH) syndromes, a group of disorders that include neuromyotonia, cramp-fasciculation syndrome, and Isaacs' syndrome. They may contribute to the associated autonomic changes. Through a central action, they may also be the effector mechanism in those with Morvan's syndrome and in some patients with limbic encephalitis. Evidence supporting this hypothesis includes the increased association of APNH with autoimmune diseases (in particular, myasthenia gravis and thymoma), the response to plasmapheresis, passive transfer of APNH to experimental animals by patients' plasma or immunoglobulins, the action of their serum on VGKC currents studied in vitro, and the presence in many patients of IgG antibodies to VGKCs.

Publication Types:

Review

PMID: 14592877 [PubMed - indexed for MEDLINE]

66: Ann N Y Acad Sci. 2003 Sep;998:178-86. Related Articles, Links

Immunology of paraneoplastic syndromes: overview.

Posner JB.

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. posnerj@mskcc.org

Cancers that cause disturbances of organs or tissues remote from the site of the tumor or its metastases are called paraneoplastic syndromes. The nervous system can be affected at virtually any site, including the neuromuscular junction (e.g., Lambert-Eaton myasthenic syndrome, myasthenia gravis). Paraneoplastic syndromes affecting the central nervous system are characterized by (1) high titers of antibodies that react with both the cancer and the affected portion of the nervous system, (2) specifically reacting T cells in the blood and cerebrospinal fluid, and (3) autopsy evidence of neuronal destruction, inflammatory infiltrates, and antibody penetration. Clinically, paraneoplastic syndromes affecting the central nervous system are usually subacute in onset, rapid in evolution, and cause severe damage, but generally stabilize after several months with or without treatment. Immune suppression does not appear to be particularly effective in treating these disorders. Treatment of the underlying cancer sometimes ameliorates symptoms.

Publication Types:

Review

PMID: 14592873 [PubMed - indexed for MEDLINE]

67: Ann Thorac Surg. 2003 Sep;76(3):878-84; discussion 884-5. Related Articles, Links: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.

Kondo 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: Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures. METHODS: We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery. RESULTS: Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma. CONCLUSIONS: Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.

PMID: 12963221 [PubMed - indexed for MEDLINE]

68: Arch Pathol Lab Med. 2003 Sep;127(9):e378-81. Related Articles, Links

Ectopic hamartomatous thymoma: a case report showing CD99+ lymphocytes and a low proliferation index.

Lee SN, Cho MS, Koo H, Han WS.

Department of Pathology, Medical College, Ewha Womans University, Seoul, South Korea.

Ectopic hamartomatous thymoma is a rare benign tumor that consists of spindle, epithelial, and adipose cell elements. We present a case of this lesion arising in the supraclavicular region of a 59-year-old man, including the characteristic immunohistochemical and ultrastructural findings. DNA flow cytometry revealed diploidy with a low proliferation index (6.73%). The tumor contained CD99+ lymphocytes; CD99 (MIC2) can serve as a useful marker of immature T cells. These findings suggest that ectopic hamartomatous thymoma may develop from the third branchial pouch or thymic anlage.

Publication Types:

Case Reports

PMID: 12946212 [PubMed - indexed for MEDLINE]

69: Aust Vet J. 2003 Sep;81(9):543-6. Related Articles, Links

Acquired myasthenia gravis associated with a non-invasive thymic carcinoma in a dog.

Stenner VJ, Parry BW, Holloway SA.

Department of Veterinary Clinic and Hospital, The University of Melbourne, 250 Princes Highway, Werribee, Victoria 3030. vstenner@powerup.com.au

An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma.

Publication Types:

Case Reports

PMID: 15086092 [PubMed - indexed for MEDLINE]

70: Bull Exp Biol Med. 2003 Sep;136(3):283-5. Related Articles, Links: Study of total lipid peroxidation and antioxidant activity in pulmonary and mediastinal malignant and benign tumor tissue.

Korotkina RN, Spiridonova OV, Matskevich GN, Kucheinik ASh, Kunitsyn AG, Vishnevskii AA, Karelin AA.

Clinical Biochemical Laboratory and Department of Thoracal Surgery, A. V. Vishnevskii Institute of Surgery, Russian Academy of Sciences, Moscow.

Total lipid peroxidation and antioxidant activity were studied in pulmonary and mediastinal malignant and benign neoplasms. In malignant tumors total lipid peroxidation increased and antioxidant activity decreased; the intensity of these shifts depended on histological characteristics and degree of malignancy: the most pronounced changes were observed in thymoma and adenocarcinoma tissues and minimum changes were found in bronchoalveolar carcinoma tissue.

PMID: 14666195 [PubMed - indexed for MEDLINE]

71: Cancer Sci. 2003 Sep;94(9):809-13. Related Articles, Links: Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage.

Sasaki H, Ide N, Sendo F, Takeda Y, Adachi M, Fukai I, Fujii Y.

Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan. hisasaki@kch.hosp.go.jp

Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early- (stage I or II) and late- (stage IVa) stage thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 48 thymoma patients and sandwich ELISA for 33 thymoma patients. Using both methods, a candidate gene was identified which was overexpressed in stage IV thymoma. This was a known glycosylphosphatidyl inositol (GPI)-anchored protein (GPI-80), which is highly homologous with Vanin-1, a mouse thymus homing protein. Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA. The combined use of oligonucleotide microarray, real-time RT-PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma.

PMID: 12967480 [PubMed - indexed for MEDLINE]

72: J Comput Assist Tomogr. 2003 Sep-Oct;27(5):714-23. Related Articles, Links

Cystic tumors in the anterior mediastinum. Radiologic-pathological correlation.

Kim JH, Goo JM, Lee HJ, Chung MJ, Jung SI, Lim KY, Lee MW, Im JG.

Department of Radiology, Seoul National University College of Medicine, Korea.

Anterior mediastinal neoplasms comprise a diverse group of tumors and occasionally manifest as a cystic lesion. We retrospectively reviewed computed tomography (CT) scans in 46 patients with pathologically proved cystic anterior mediastinal tumors. We categorize them into a pure cystic mass and a cystic tumor with a solid portion. In this pictorial essay, the radiologic appearances of cystic anterior mediastinal tumors are described with CT and illustrated with their gross and histopathological findings on resected specimen.

Publication Types:

Review

PMID: 14501362 [PubMed - indexed for MEDLINE]

73: J Immunol. 2003 Sep 1;171(5):2296-304. Related Articles, Links: Surface expression of Notch1 on thymocytes: correlation with the double-negative to double-positive transition.

Huang EY, Gallegos AM, Richards SM, Lehar SM, Bevan MJ.

Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

Notch1 plays a critical role in regulating T lineage commitment during the differentiation of lymphoid precursors. The physiological relevance of Notch1 signaling during subsequent stages of T cell differentiation has been more controversial. This is due in part to conflicting data from studies examining the overexpression or targeted deletion of Notch1 and to difficulties in distinguishing between the activities of multiple Notch family members and their ligands, which are expressed in the thymus. We employed a polyclonal antiserum against the extracellular domain of Notch1 to study surface expression during thymopoiesis. We found high levels of Notch1 on the cell surface only on double negative (DN) stage 2 through the immature single-positive stage of thymocyte development, before the double-positive (DP) stage. The Notch signaling pathway, as read out by Deltex1 expression levels, is highly active in DN thymocytes. When an active Notch1 transgene, Notch1IC, is exogenously introduced into thymocytes of recombinase-activating gene 2-deficient mice, it promotes proliferation and development to the DP stage following anti-CD3 treatment without apparently affecting the intensity of pre-TCR signaling. In addition, a stromal cell line expressing the Notch ligand, Delta-like-1, promotes the in vitro expansion of wild-type DN3 thymocytes in vitro. Consistent with other recent reports, these data suggest a role for Notch1 during the DN to DP stage of thymocyte maturation and suggest a cellular mechanism by which Notch1IC oncogenes could contribute to thymoma development and maintenance.

PMID: 12928374 [PubMed - indexed for MEDLINE]

74: Jpn J Thorac Cardiovasc Surg. 2003 Sep;51(9):442-4. Related Articles, Links

Hemangioma in the anterior mediastinum.

Nishikawa H, Osaki T, Tajima Y, Yoshimatsu T, Nagashima A, Yasumoto K.

Department of Chest Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Fukuoka, Japan.

Anterior mediastinal hemangiomas are very rare neoplasms in mediastinal tumors. A 58-year-old woman was revealed to have a mass measuring 4 x 3 cm in size in the anterior mediastinum with calcification on computed tomography. It was initially suspected to be a thymoma. We performed tumor extirpation in November 1998. The tumor was close to the thymus and slightly adhered to the superior vena cava, ascending aorta and right phrenic nerve, however, it did not invade any surrounding organs. Histopathologically, it was diagnosed to be a venous type hemangioma composed of vessels covered by smooth muscle and a cavernous type hemangioma composed of dilated vessels covered by one layer of endothelial cells.

Publication Types:

Case Reports

PMID: 14529162 [PubMed - indexed for MEDLINE]

75: Rev Pneumol Clin. 2003 Sep;59(4):213-5. Related Articles, Links

[Thymoma and autoimmune thyroiditis. A case report]

[Article in French]

Brinkane A, Bellamy J, Leroy-Terquem E, Levy R.

Service de Medecine Interne, Centre Hospitalier Intercommunal de Meulan-Les Mureaux, 1, rue du Fort, 78250 Meulan. abrinkane@hotmail.com

We report an association between a thymus tumor and autoimmune thyroiditis. This association is probably related to loss of immune control secondary to loss of thymus integrity. A 48-year-old woman was hospitalized for thoracic pain. Her past history included thyroiditis treated by L-thyroxin for two years. The chest x-ray demonstrated a mediastinal opacity which was confirmed by computed tomography. Surgical resection was performed and histological analysis of the surgical specimen confirmed the diagnosis of lympho-epithelial thymoma. Thyroid immunity tests demonstrated the presence of anti-peroxidase antibodies confirming the diagnosis of Hashimoto's thyroiditis. Chest x-ray and CT-scan are indicated in patients with autoimmune thyroiditis to search for a thymic mass. Conversely, search for autoimmune thyroiditis is warranted in patients with an identified thymic mass.

Publication Types:

Case Reports

PMID: 14699299 [PubMed - indexed for MEDLINE]

76: Rinsho Shinkeigaku. 2003 Sep;43(9):544-7. Related Articles, Links

[A case of thymoma-associated myasthenia gravis with antibodies against interferon-alpha--a clinico-immunological follow up of the symptoms and its titer]

[Article in Japanese]

Nakamori M, Matsumura T, Saito T, Kunitomi A, Iyama A, Nozaki S, Fujimura H, Shinno S.

Department of Neurology, Osaka University Graduate School of Medicine.

A 73-year-old woman developed myasthenia gravis (MG) with thymoma. She had a very high level of serum antibodies against interferon-alfa (IFN-alpha). We observed the changes to her clinical symptoms and titer of the antibody during therapeutic course. Although she underwent thymectomy, intravenous methylprednisolone therapy, and oral tacrolimus administration, MG symptoms of the patient were not significantly improved and the antibody titer remained at a high level. IFN-alpha is a potent immunomodulating cytokine that regulates MHC class II expression on antigen presenting cells and activities of NK cells, B cells, and helper/suppressor T cells. This case suggests that IFN-alpha related immunological perturbation participates in the pathogenesis of thymoma-associated myasthenia gravis.

Publication Types:

Case Reports

PMID: 14727560 [PubMed - indexed for MEDLINE]

77: Surg Endosc. 2003 Sep;17(9):1496. Epub 2003 Jun 19. Related Articles, Links

First report on sequential totally endoscopic thymomectomy and adrenalectomy using computer-enhanced telemanipulation.

Khan MF, Binder J, Dogan S, Bentas W, Aybek T, Wimmer-Greinecker G.

Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany. fawad@gmx.de

BACKGROUND: Laparoscopic adrenalectomy is considered the standard method for removal of benign adrenal tumors, regardless of hormone activity. Minimally invasive surgery for thymomectomy aims at limited approaches, avoiding complete sternotomy or large thoracotomy. METHODS: We report on a case in which totally endoscopic thymomectomy and adrenal gland resection were performed sequentially using a computer-enhanced telemanipulation system within 3 weeks. RESULTS: Operating time was 4.5 h for totally endoscopic adrenalectomy and 1.5 h for totally endoscopic thymomectomy. The patient was transferred to the normal ward on the day of operation after either procedure and had an uneventful recovery. Pathology yielded no malignancy in both cases. CONCLUSION: This report demonstrates the safety and feasibility of various totally endoscopic procedures performed sequentially.

Publication Types:

Case Reports

PMID: 12811659 [PubMed - indexed for MEDLINE]

78: Tumour Biol. 2003 Sep-Oct;24(5):271-4. Related Articles, Links: Cten mRNA expression is correlated with tumor progression in thymoma.

Sasaki H, Yukiue H, Kobayashi Y, Fukai I, Fujii Y.

Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.Nagoya-cu.ac.jp

Cten is a recently isolated gene which has homology with tensin, suggesting that it is a focal adhesion molecule. Tensin family proteins play an important role in cell motility. We attempted to determine the influence of cten expression on clinicopathological features in patients with thymoma who had undergone surgery. Expression of cten messenger RNA was evaluated by reverse-transcription polymerase chain reaction in 45 thymoma samples using a LightCycler. There was no relationship between cten/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression and age, gender or pathological subtypes. However, cten/GAPDH expression was significantly higher in stage IV thymoma (5.463 +/- 7.730) when compared to stage I thymoma (0.905 +/- 0.811; p = 0.0187). Cten/GAPDH mRNA expression was correlated with evidence of tumor progression in thymoma. Consequently, cell motility or migration might play a role in progression of thymoma. Copyright 2003 S. Karger AG, Basel

PMID: 15001839 [PubMed - indexed for MEDLINE]

79: Vet Res Commun. 2003 Sep;27 Suppl 1:715-8. Related Articles, Links

Acquired canine myasthenia gravis associated with thymoma: histological features and immunohistochemical localization of HLA type II and IgG.

Paciello O, Maiolino P, Navas L, Papparell S.

Department of Pathology and Animal Health, Section of Pathologic Anatomy, Faculty of Veterinary Medicine, University Federico II Naples, Italy. paciello@unina.it

Publication Types:

Case Reports

PMID: 14535505 [PubMed - indexed for MEDLINE]

80: West Indian Med J. 2003 Sep;52(3):213-8. Related Articles, Links: Thymic surgery in Jamaica 1992-2000.

Ramphal PS, Irvine RW, Mitchell DI, Scarlett M, McGaw CD, Fletcher PR, Spencer HW.

Department of Surgery, Radiology, Anaesthesia and Intensive Care, University Hospital of the West Indies, Kingston 7, Jamaica, West Indies. pabloram@cwjamaica.com

The treatment for thymic tumours and/or myaesthenia gravis (MG) includes thymectomy. Controversy exists as to the optimal timing and operative approach to thymectomy. At the University Hospital of the West Indies, Kingston, Jamaica, the results of thymic surgery during the period 1992 to 2000 were studied retrospectively. There were 26 patients operated on, 17 females and nine males. Twenty-three underwent thymectomy to treat MG, and three to remove a thymoma. The average age for females was 30.7 years, and 25.1 years for males. Average duration of symptoms prior to surgery was 16 months (all patients), and the interval between diagnosis and referral averaged 2.6 months. All patients underwent thymectomy via median sternotomy with a cervical extension of the incision if required. A policy of phrenic nerve preservation, even if residual tumour was left behind, was followed. Patients with thymomas were given post-operative radiotherapy. Chemotherapy was not given to any patient. The medium and long term results of thymic surgery in a developing country are presented. The results are within international norms, although the small patient population makes statistical analysis difficult. There appears to be no need to change current practice, despite the reported efficacy of less invasive approaches to thymic surgery.

PMID: 14649102 [PubMed - indexed for MEDLINE]

81: J Immunol. 2003 Aug 15;171(4):1909-17. Related Articles, Links: Potential role of NKG2D/MHC class I-related chain A interaction in intrathymic maturation of single-positive CD8 T cells.

Hue S, Monteiro RC, Berrih-Aknin S, Caillat-Zucman S.

Laboratory of Immunology, Hopital Necker, Paris, France.

The nonclassical MHC class I molecule MHC class I-related chain A (MICA) interacts with the NKG2D receptor expressed at the surface of most peripheral CD8 T cells, gammadelta T cells, and NK cells. We investigated the role of MICA-NKG2D interactions in the selection or maturation of the T cell repertoire within the thymus using MICA tetramers and anti-MICA mAbs. MICA tetramers identified a small population of late stage CD8 single-positive, CD45RA(+) CD62L(+) CCR7(+) CD69(-) thymocytes, a phenotype compatible with that of fully mature CD8(+) cells ready to emigrate to the periphery as naive cells. MICA molecules were expressed in the outer layer of Hassal's corpuscles within the medulla of normal thymus. In thymomas, an overexpression of MICA in cortical and medullar epithelial cells was observed. This was associated with a decreased percentage of NKG2D-positive thymocytes, which expressed a less mature phenotype than in normal thymus. These results indicate that CD8(+) thymocytes up-regulate NKG2D as they complete their developmental program before leaving the thymic medulla to seed the periphery, and identify NKG2D as a potential regulator of the developmental processes in T cells that are essential for immune homeostasis.

PMID: 12902493 [PubMed - indexed for MEDLINE]

82: Am J Clin Oncol. 2003 Aug;26(4):366-8. Related Articles, Links

Retrovesical soft-tissue metastasis of malignant thymoma: case report.

Tas F, Agan M, Tenekeci N, Topuz E.

Institute of Oncology, Istanbul Medical Faculty, University of Istanbul, Istanbul, Turkey.

Malignant thymomas are usually confined to the mediastinum at the time of diagnosis and follow-up. Distant metastasis is distinctly rare. This is the first clinical case report of a thoracic malignant thymoma with distant soft-tissue metastasis that involves the retrovesical area to include the seminal vesicle.

Publication Types:

Case Reports

PMID: 12902887 [PubMed - indexed for MEDLINE]

83: Chin Med J (Engl). 2003 Aug;116(8):1187-90. Related Articles, Links: Diagnosis, treatment and prognosis of thymoma: an analysis of 116 cases.

Wang Y, Sun Y, Zhang J, Zhou N, Liu Y, Li X, Xu Y.

Department of Thoracic Surgery, General Hospital of People's Liberation Army, Beijing 100853, China.

OBJECTIVE: To study the diagnosis and treatment of thymoma and to assess its prognostic factors. METHODS: The clinical data of 116 patients with thymoma were collected. A retrospective analysis was performed, by comparing the survival rate calculated by the Kaplan-Meier method with the rate of recurrence or metastasis. RESULTS: The standard posteroanterior and lateral chest radiographs were reliable means of detection of most thymomas. Myasthenia gravis was the most commonly paraneoplastic disease (25.0%, 29/116). The extensive radical resection was beneficial for reducing the rate of recurrence of stage I or stage II thymomas (chi(2) = 4.941, P = 0.0219). The survival time could be prolonged by postoperative radiotherapy and chemotherapy. There was a strong correlation between the clinical stage and the histological classification (according to MH classification), through which the invasive behavior of thymoma could be predicted (chi(2) = 19.76, P = 0.007, RR = 1.47). The 3- 5- and 10-year survival rates were 81.2%, 67.9%, and 40.5%, respectively. Statistical analysis showed a significant negative correlation between the stage and the survival rate (chi(2) = 29.73, P = 0.0000, RR = 0.15). CONCLUSION: The prognosis of thymoma depends mainly on the histological classification, clinical stage and multimodality treatment rather than on the paraneoplastic diseases.

PMID: 12935408 [PubMed - indexed for MEDLINE]

84: Eur J Cardiothorac Surg. 2003 Aug;24(2):331-3. Related Articles, Links

Extended operation for invasive thymoma with intracaval and intracardiac extension.

Funakoshi Y, Ohta M, Maeda H, Matsuda H.

Department of Surgery, E1, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.

Two cases of invasive thymoma with intracaval and intracardiac extension into the right atrium are reported. Radical excisions and reconstructions of the superior vena cava (SVC) requiring extracorporeal circulation were performed. Invasive thymoma with this growth pattern is extremely rare, and patients with SVC obstruction should be evaluated for the resection of tumors and reconstruction of the SVC.

Publication Types:

Case Reports

PMID: 12895640 [PubMed - indexed for MEDLINE]

85: Histopathology. 2003 Aug;43(2):165-72. Related Articles, Links: Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours.

Pan CC, Chen PC, Wang LS, Lee JY, Chiang H.

Department of Pathology, National Yang-Ming University, and Veterans General Hospital-Taipei, Taiwan. ccpan@vghtpe.gov.tw

AIMS: To correlate the expression of a series of apoptotic and oncogene markers (including p53, Bcl-2, BAX, Bcl-XL, p21WAF,1/CIP1, cyclin D1, HER-2/neu) in thymic epithelial tumours with histological type, stage and resectability and to determine whether the information on HER-2/neu would be valuable in identifying patients who are eligible for anti-HER-2/neu treatment. METHODS AND RESULTS: Immunohistochemical stains were performed on 16 cases of non-neoplastic thymus, 63 thymomas and 17 thymic carcinomas. Fluorescence in-situ hybridization (FISH) for HER2 was performed to validate the gene amplification. Eighteen thymomas were positive for p53 and 14 of them were low-expressors, with positive cells below 10%. All thymic carcinomas revealed over-expression of p53 with positive cells either between 10% and 50% or >50%. The expression of p53 correlated with histological type and stage in thymoma. In both thymoma and thymic carcinoma, there was a statistically significant correlation between p53 status and resectability, with low expressors having a higher likelihood of being resectable. Thymic carcinomas, regardless of the histological subtypes, uniformly expressed Bcl-2, while thymomas showed no or only weak cytoplasmic immunoreactivity. Most thymomas and thymic carcinomas were negative for Bcl-XL, p21WAF,1/CIP1 and cyclin D1. The expression of BAX was inconsistent among different histological types. Nine thymic carcinomas revealed membranous positivity for HER-2/neu, but no HER2 gene amplification could be demonstrated by FISH in any of the cases. CONCLUSIONS: p53 and Bcl-2 are more implicated in the development of thymic carcinoma than thymoma. The higher level of p53 expression and the strong immunopositive pattern of Bcl-2 in thymic carcinomas have potential value in the differential diagnosis and prediction of aggressiveness and resectability. On account of the absence of HER2 amplification, patients would probably not benefit from anti-HER-2/neu treatment.

PMID: 12877732 [PubMed - indexed for MEDLINE]

86: Int Immunol. 2003 Aug;15(8):903-13. Related Articles, Links: Spontaneous production of anti-IFN-alpha and anti-IL-12 autoantibodies by thymoma cells from myasthenia gravis patients suggests autoimmunization in the tumor.

Shiono H, Wong YL, Matthews I, Liu JL, Zhang W, Sims G, Meager A, Beeson D, Vincent A, Willcox N.

Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Myasthenia gravis (MG) is mediated by autoantibodies to the acetylcholine receptor (AChR), expressed in muscle and rare thymic myoid cells. Most early-onset cases show thymic lymph node-type infiltrates, including pre-activated plasma cells spontaneously producing anti-AChR antibodies. Since these are not evident in the associated thymomas found in another 10% of MG patients, AChR-specific B cells must be autosensitized elsewhere. Unexpectedly, at diagnosis, >70% of MG/thymoma patients also have high-titer neutralizing autoantibodies to IFN-alpha, and >50% to IL-12; moreover, titers increase strikingly if the thymomas recur, indicating a closer tumor relationship than for anti-AChR. To investigate this, we have measured autoantibody production by cells cultured from thymomas, any available thymic remnants and blood, with or without the B cell stimulant pokeweed mitogen (PWM). To check autoantibody specificity and clonal origins, we isolated Fabs from two combinatorial libraries from producer thymus/thymoma cells. Surprisingly, thymoma cells spontaneously produced antibodies to IFN-alpha and/or IL-12 in >40% of seropositive cases, showing typical plasma cell behavior, whereas they produced anti-AChR only after PWM stimulation. We isolated 15 combinatorial Fabs to IFN-alpha (versus only one to AChR). Their strong binding in radio-immunoprecipitation and Western blots implies high affinities. The four Fabs tested neutralized anti-viral actions of IFN-alpha. The diverse V genes clearly showed ongoing antigen-driven selection. These results imply pre-activation in situ by native IFN-alpha/IL-12 expressed within a 'dangerous' tumor microenvironment. With these molecules, it should be easier to identify provoking cell type(s) that may give novel additional clues to autoimmunization against T-cell epitopes from the more complex AChR.

PMID: 12882828 [PubMed - indexed for MEDLINE]

87: Kyobu Geka. 2003 Aug;56(9):801-5. Related Articles, Links

[Spontaneous regression of thymoma; report of a case]

[Article in Japanese]

Ishibashi H, Ashino Y, Niikawa H, Hosaka T, Hasumi T, Shibuya J, Suzuki S, Handa M.

Department of Surgery, Sendai Kousei Hospital, Sendai, Japan.

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.

Publication Types:

PMID: 12931595 [PubMed - indexed for MEDLINE]

88: Nephrol Dial Transplant. 2003 Aug;18 Suppl 6:vi64-7. Related Articles, Links

Secondary focal glomerulosclerosis not due to HIV.

Mallick N.

Department of Renal Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. np.mallick@ntlworld.com

The idiopathic and familial forms of focal glomerulosclerosis, and the similar lesion that occurs in association with HIV infection, are dealt with elsewhere in this supplement. This article highlights conditions where FSGS develops, apparently, as a phenomenon secondary to another defined pathology. It may occur in a setting of normal renal mass associated with (i) an immunological aberration such as thymoma, or (ii) in a non-immunological setting associated with increased intra-glomerular pressure or deposition of inappropriate material. FSGS may also be found (iii) in association with a reduced renal mass that may, for example, follow an ischaemic renal insult. The pathogenetic mechanism(s) involved remain unclear.

Publication Types:

Review

PMID: 12953045 [PubMed - indexed for MEDLINE]

89: Pathology. 2003 Aug;35(4):349-51. Related Articles, Links

Hodgkin's disease associated cholestasis in a man with thymoma.

Opeskin K, Burke M, McCaffrey G, Nandurkar H.

Publication Types:

PMID: 12959773 [PubMed - indexed for MEDLINE]

90: Rinsho Shinkeigaku. 2003 Aug;43(8):500-2. Related Articles, Links

[Blepharospasm in a patient with thymoma and positive anti-acetylcholine receptor antibody]

[Article in Japanese]

Tsuda H, Kamei S, Mizutani T, Saito N, Ishikawa H, Omori K.

Division of Neurology, Department of Medicine, Nihon University School of Medicine.

We report a rare case of a 70-year-old woman diagnosed as having blepharospasm with positive anti-acetylcholine receptor antibody. Blepharospasm developed in November, 2000, and increased in frequency, and worsened toward the evening. She complained of difficulty in her eyelid opening from October, 2002. Neurological examinations revealed blepharospasm and mild ptosis in both eyes. Tensilon test was negative. Waning and waxing were not detected in bilateral orbicularis oculi muscles by Harvey-Masland test. However, anti-acetylcholine receptor antibody was positive and thymoma in the anterior mediastinum was also found by the computed tomography of the chest. After the thymectomy, frequency of blepharospasm decreased. When blepharospasm worsened toward the evening, the co-existence of myasthenia gravis should be borne in mind.

Publication Types:

Case Reports

PMID: 14658404 [PubMed - indexed for MEDLINE]

91: Rinsho Shinkeigaku. 2003 Aug;43(8):496-9. Related Articles, Links

[A patient with giant cell myocarditis and myositis associated with thymoma and myasthenia gravis]

[Article in Japanese]

Sato H, Iwasaki E, Nogawa S, Suzuki S, Amano T, Fukuuchi Y, Shimoda M, Okada Y.

Department of Neurology, School of Medicine, Keio University.

We report a 62-year-old man with giant cell myocarditis and myositis associated with thymoma and myasthenia gravis (MG). He was diagnosed as having MG and invasive thymoma at the age of 45. After he had a myasthenic crisis at the age of 61, tacrolimus was indicated in order to improve his neurological symptoms, in addition to glucocorticoid. Three months later, he was readmitted to our hospital complaining of general fatigue and dyspnea. Serum level of creatine phosphokinase (9,835IU/L) and myocardium-derived troponin T (3.24 ng/mL) were elevated, and the ECG showed atrioventricular dissociation and accelerated idioventricular rhythm. In spite of glucocorticoid pulse therapies and high-dose immunoglobulin therapies, he died of cardiac failure within a few days. Autopsy was done, and histological examination of the myocardium and the skeletal muscle showed massive necrosis with infiltration of inflammatory cells including giant cells. These findings constituted giant cell myocarditis and myositis. Although it has been suggested that myocardial disorders can often occur in patients with thymoma and/or MG, the mechanism involved is still unknown. This report may provide new knowledge about the pathophysiology of giant cell myocarditis and myositis associated with thymoma and MG.

Publication Types:

Case Reports

PMID: 14658403 [PubMed - indexed for MEDLINE]

92: Rofo. 2003 Aug;175(8):1138-40. Related Articles, Links

[Pleural metastases of malignant thymoma: differential pleural mesothelioma diagnosis]

[Article in German]

Paquin A, Brochhagen HG, Lackner K.

Publication Types:

Case Reports

PMID: 12886485 [PubMed - indexed for MEDLINE]

93: Virchows Arch. 2003 Aug;443(2):175-83. Epub 2003 Jul 8. Related Articles, Links: Constitutive expression of DeltaN-p63alpha isoform in human thymus and thymic epithelial tumours.

Chilosi M, Zamo A, Brighenti A, Malpeli G, Montagna L, Piccoli P, Pedron S, Lestani M, Inghirami G, Scarpa A, Doglioni C, Menestrina F.

Department of Pathology, University of Verona, Policlinico G.B.Rossi, 37134 Verona, Italy. marco.chilosi@univr.it

p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8).

PMID: 12851817 [PubMed - indexed for MEDLINE]

94: BMC Cancer. 2003 Jul 28;3:21. Related Articles, Links: Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment.

Bathe OF, Dalyot-Herman N, Malek TR.

Department of Surgery, University of Calgary, Calgary, AB, Canada. bathe@ucalgary.ca

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21-28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer.

PMID: 12882650 [PubMed - indexed for MEDLINE]

95: Circulation. 2003 Jul 15;108(2):245-6. Related Articles, Links

Images in cardiovascular medicine. Pulmonary artery: stuck between a rock and a hard place.

Grothues F, Welte T, Huth C, Klein HU.

Department of Cardiology, Angiology, and Pneumology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. frank.grothues@medizin.uni-magdeburg.de

Publication Types:

Case Reports

PMID: 12860893 [PubMed - indexed for MEDLINE]

96: Cancer Res. 2003 Jul 1;63(13):3708-15. Related Articles, Links: Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas.

Inoue M, Starostik P, Zettl A, Strobel P, Schwarz S, Scaravilli F, Henry K, Willcox N, Muller-Hermelink HK, Marx A.

Institute of Pathology, University of Wurzburg, D-97080 Wurzburg, Germany.

Thymomas are thymic epithelial tumors. Because most of them are rich in nonneoplastic T-cells, recurrent genetic aberrations have been reported only in the rare, lymphocyte-poor WHO types A, B3, and C. We have now investigated virtually the whole spectrum of thymomas, including the commoner types AB and B2, microdissecting or culturing neoplastic cells from these lymphocyte-rich thymomas and applying 41 microsatellite markers covering 17 loci on 10 chromosomes. In 28 cases, comparative genomic hybridization data were available. Apart from type A, there was striking heterogeneity between thymomas. Allelic imbalances were seen in 87.3% of the 55 cases, and MSI in 9.9%. Losses of heterozygosity (LOHs) were much the commonest aberration. Overall, they were most prevalent at four regions on chromosome 6. Aberrations elsewhere, affecting mainly 8p11.21 and 7p15.3, suggested a cortical footprint because they recurred only in the thymopoietically active type AB and B thymomas. LOHs were also seen at the adenomatous polyposis coli (APC) locus (5q21-22) in subsets of these thymomas, whereas combined LOHs at the APC, retinoblastoma (13q14.3), and p53 (17p13.1) loci were confined to a subset of B3 thymomas that had possibly evolved from APC-hemizygous B2 thymomas by tumor progression; indeed, thymomas combing B2 plus B3 features are common. Notably, some AB and B thymomas shared LOHs despite their nonoverlapping morphology and different clinical behavior. Finally, allelic imbalances at 8p11.21 and 16q22.1 (CDH1) were significantly more frequent in stage IV metastatic thymomas. We conclude that the WHO-defined histological thymoma types generally segregate with characteristic genetic features, type A thymomas being the most homogeneous. Many findings support the view that B2 and B3 thymomas form a continuum, with evidence of tumor progression. However, other findings imply that types A and AB are biologically distinct from the others, any potential invasiveness being severely restricted by a medullary commitment in the precursor cell undergoing neoplastic transformation.

PMID: 12839963 [PubMed - indexed for MEDLINE]

97: Clin Med Res. 2003 Jul;1(3):227-32. Related Articles, Links

Thymoma and multiple malignancies: a case of five synchronous neoplasms and literature review.

Welsh JS, Thurman SA, Howard SP.

Department of Human Oncology, University of Wisconsin School of Medicine, Madison, Wisconsin 53792, USA. welsh@humonc.wisc.edu

The presence of five discrete synchronous or metachronous primary neoplasms in a single patient is an extremely rare event. This is a report of a patient with a malignant (invasive) thymoma and four other independent primary neoplasms including: gliosarcoma, papillary thyroid cancer, meningioma and metastatic adenocarcinoma of the colon, found synchronously at autopsy. Thymoma patients appear to have an inherent predisposition towards developing additional neoplasms. Other than the thymoma, the presented patient had no obvious risk factors for neoplasia. This case provides evidence for an unusual syndrome of thymoma and multiple primary neoplasms. Further research is required to elucidate the mechanism of this association. Meanwhile, heightened awareness of this association may allow earlier detection and treatment of additional cancers in patients with a history of thymoma.

Publication Types:

PMID: 15931312 [PubMed - indexed for MEDLINE]

98: Hum Pathol. 2003 Jul;34(7):717-9. Related Articles, Links

Invasive thymoma with paraneoplastic retinopathy.

Yamada G, Ohguro H, Aketa K, Itoh T, Shijubo N, Takahashi H, Fujiwara O, Satoh M, Ohtsuka K, Abe S.

Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.

A 60-year-old man was admitted for progressive visual loss in both eyes. He was diagnosed with retinopathy and chest computed tomography revealed an invasive thymoma. In western blot analysis, serum autoantibodies against recoverin, photoreceptor-specific calcium-binding protein, and heat shock cognate protein 70 which were identified as the cause of cancer-associated retinopathy (CAR). Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case.

Publication Types:

Case Reports

PMID: 12874770 [PubMed - indexed for MEDLINE]

99: Indian J Pathol Microbiol. 2003 Jul;46(3):405-8. Related Articles, Links

Pure red cell aplasia--report of 11 cases from eastern Nepal.

Sinha AK, Agarwal A, Lakhey M, Ansari J, Rani S.

Department of Pathology, B. P. Koirala Institute of Health Sciences, Dharan, Nepal. arvindak1969@yahoo.com

There were eleven cases of pure red cell aplasia diagnosed over a period of 2 years (January 2000-December 2001). All the patients had anemia with pallor and weakness being the presenting complaints. Hematological profile depicted normocytic normochromic anemia, reticulocytopenia and marked paucity of erythroid precursors on bone marrow aspiration and biopsy studies. In the present study, one case was of congenital pure red cell aplasia, in one other case of pyrexia of unknown origin, no definitive diagnosis could be made. Other associated diseases seen with pure red cell aplasia were thymoma, septicemia, protein energy malnutrition, non-Hodgkin's lymphoma, juvenile rheumatoid arthritis, acute myeloid leukemia, tuberculosis and hepatitis C. The association of pure red cell aplasia with haematologic malignancies is rare. There are very few case reports on pure red cell aplasia with hepatitis C.

Publication Types:

Case Reports

PMID: 15025285 [PubMed - indexed for MEDLINE]

100: Indian J Pathol Microbiol. 2003 Jul;46(3):378-81. Related Articles, Links: Clinicopathological study of thymomas--correlation of histologic subtype to myasthenia gravis and prognosis.

Sundaram C, Rajagopal P, Rakshak AD, Omprakash G, Das SM, Murthy JM.

Department of Pathology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad. challa_sundaram@yahoo.com

Thymoma is the most common primary tumor of anterior superior mediastinum. Sixty cases of thymomas over a 12 year period were analysed and the histologic subtype, according to Marino and Muller-Hermilink, classification was correlated with presence or absence of myasthenia gravis (MG) and capsular invasion. Thirty four patients had myasthenia gravis associated with thymoma and there was one case of pure red cell aplasia. There were 3 (1) predominantly cortical, 28 (20) cortical, 12 (9) mixed, 16 (4) medullary thymomas and 1 (0) thymic carcinoma (Figures in parenthesis indicate number of cases associated with MG). Capsular invasion was seen in 25 cases. Association with myasthenia gravis and capsular invasion were seen predominantly in cortical and mixed thymomas which were also associated with aggressive behaviour.

PMID: 15025278 [PubMed - indexed for MEDLINE]

101: Int J Cancer. 2003 Jul 1;105(4):546-51. Related Articles, Links

Comment in:

Int J Cancer. 2004 Jan 10;108(2):327.

Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies.

Engels EA, Pfeiffer RM.

Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, MD 20892, USA. engelse@exchange.nih.gov

The cause of thymoma is unknown. No population-based study has described demographic patterns of thymoma incidence. Previous reports have linked thymoma with diverse subsequent malignancies, but these associations are uncertain. We used Surveillance, Epidemiology and End Results (SEER) data to study the incidence of malignant thymoma by sex, age and race in the United States (1973-1998). Incidence was modeled with joinpoint regression (for age) and Poisson regression. We also used SEER data to compare malignancies following thymoma diagnosis with those expected from general population rates, calculating the standardized incidence ratio (SIR, observed/expected cases) to measure risk. The overall incidence of malignant thymoma was 0.15 per 100000 person-years (849 cases). Thymoma incidence increased into the 8th decade of age and then decreased. Incidence was higher in males than females (p=0.007) and was highest among Asians/Pacific Islanders (0.49 per 100000 person-years). Following thymoma, there were 66 malignancies (SIR 1.5, 95%CI 1.2-1.9). The most notable excess risk for subsequent malignancy was for non-Hodgkin's lymphoma (B immunophenotype) where the SIR was 4.7 (95%CI 1.9-9.6, 7 cases). There were also excess digestive system cancers (SIR 1.8, 95%CI 1.1-2.9) and soft tissue sarcomas (SIR 11.1, 1.3-40.1). No other cancers were increased after thymoma. In conclusion, malignant thymoma is extremely rare. The peak in late adulthood deserves further study. Variation in incidence by race suggests a role for genetic factors. Our study did not demonstrate broadly increased risk for malignancies following thymoma. Copyright 2003 Wiley-Liss, Inc.

PMID: 12712448 [PubMed - indexed for MEDLINE]

102: Int J Cancer. 2003 Jul 1;105(4):494-8. Related Articles, Links: Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka.

Penzel R, Hoegel J, Schmitz W, Blaeker H, Morresi-Hauf A, Aulmann S, Hecker E, Mechtersheimer G, Otto HF, Rieker RJ.

Department of Pathology, University of Heidelberg, Heidelberg, Germany.

Using comparative genomic hybridisation, we investigated chromosomal imbalances in 28 cases of thymic epithelial neoplasms including type A, B2, B3, the A component of type AB and different subtypes of type C thymoma. To identify different patterns of chromosomal aberrations associated with the biological behaviour and the histological diversity of thymomas, a hierarchical cluster analysis of 65 cases was performed. The here-reported Comparative Genomic Hybridisation (CGH) data (28 cases) of partly uninvestigated tumour subtypes were pooled with previously published data of chromosomal imbalances of 37 thymomas (Zettl et al. [Am J Pathol 2000;157:257-66]). The analysis of 278 chromosomal subbands yielded 2 main clusters. The first main cluster was characterised by gains of the chromosomal arm 1q, consisted only of type C and B3 thymomas and was further subdivided into 2 subgroups. To the first subgroup only thymomas were attributed, which, in addition to gains of the chromosomal arm 1q, showed losses on 6q and 16q, whereas tumours belonging to the second subgroup exhibited no further recurrent chromosomal alterations. The second main cluster was formed by a heterogeneous group of thymoma types (types A, AB, B2, B3 and C), showing no specific pattern of chromosomal imbalances. In 19 thymomas, no chromosomal imbalances could be detected (3 type B2 and 5 type A thymomas of our study as well as 11 type A thymomas investigated by Zettl et al., Am J Pathol 2000;157:257-66). Chromosomal imbalances were more frequent in type C thymomas than in other subtypes. The distribution of tumour stages according to Masaoka (p = 0.003) and the World Health Organisation (WHO) classification (p < 0.0001) was significantly different in the clusters and subgroups obtained. The groups reflect the staging system and the WHO classification and show that type B3 and type C carcinomas have a strong relationship concerning their chromosomal imbalances. Furthermore, chromosomal imbalances detected in some type A thymomas might be responsible for the aggressive behaviour described in a few cases of this thymoma subtype. Copyright 2003 Wiley-Liss, Inc.

PMID: 12712440 [PubMed - indexed for MEDLINE]

103: J Am Coll Surg. 2003 Jul;197(1):88-96. Related Articles, Links: What's new in general thoracic surgery.

Naunheim KS.

Division of Cardiothoracic Surgery, St. Louis University Health Sciences Center, MO 63110, USA.

PMID: 12831929 [PubMed - indexed for MEDLINE]

104: Kathmandu Univ Med J (KUMJ). 2003 Jul-Sep;1(3):193-6. Related Articles, Links

A typical case of Myasthenia Gravis.

Poudel M, Angel GM, Neopane A, Karki DB.

Department of Internal Medicine, Kathmandu Medical College, Sinamangal. poudel_mahendra@hotmail.com

Publication Types:

Case Reports

PMID: 16388230 [PubMed - indexed for MEDLINE]

105: Mol Cancer Res. 2003 Jul;1(9):682-9. Related Articles, Links: Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis.

Nonn L, Berggren M, Powis G.

Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-5024, USA.

Peroxiredoxin-3 (Prdx3) is a mitochondrial member of the antioxidant family of thioredoxin peroxidases that uses mitochondrial thioredoxin-2 (Trx2) as a source of reducing equivalents to scavenge hydrogen peroxide (H(2)O(2)). Low levels of H(2)O(2) produced by the mitochondria regulate physiological processes, including cell proliferation, while high levels of H(2)O(2) are toxic to the cell and cause apoptosis. WEHI7.2 thymoma cells with stable overexpression of Prdx3 displayed decreased levels of cellular H(2)O(2) and decreased cell proliferation without a change in basal levels of apoptosis. Prdx3-transfected cells showed a marked resistance to hypoxia-induced H(2)O(2) formation and apoptosis. Prdx3 overexpression also protected the cells against apoptosis caused by H(2)O(2), t-butylhydroperoxide, and the anticancer drug imexon, but not by dexamethasone. Thus, mitochondrial Prdx3 is an important cellular antioxidant that regulates physiological levels of H(2)O(2), leading to decreased cell growth while protecting cells from the apoptosis-inducing effects of high levels of H(2)O(2).

PMID: 12861054 [PubMed - indexed for MEDLINE]

106: Mol Immunol. 2003 Jul;39(17-18):1115-9. Related Articles, Links: Results of radiation therapy for thymoma based on a review of 27 patients.

Akoum R, Brihi E, Chammas S, Abigerges D.

Department of Medical Oncology, Rizk Hospital, Beirut, Lebanon. rakoum@yahoo.com

BACKGROUND: Radiotherapy has a well recognized role as an adjuvant treatment to surgery in thymoma and remains the only available treatment, with or without chemotherapy, in unresectable tumors. OBJECTIVE: Our objective is to assess the factors predicting the outcome and the pattern of survival in patients with thymoma treated by radiotherapy in our institution. METHODS: Between February 1989 and October 2000, 27 patients underwent radiotherapy for thymoma and were reviewed retrospectively. A follow-up could be obtained on all 27 patients. The parameters assessed were: age, sex, stage, presenting Myasthenia gravis, resectability, treatment modalities and survival. The total radiation dose to the tumor area in the adjuvant setting was 40-60 Gy and in the curative setting: 50-70 Gy. RESULTS: The median follow-up time of the 18 living patients was 74 months (range: 8-144 months). According to the Masaoka classification, there were 8 stage IV, 14 stage III and 5 stage II patients (three patients had relapsed tumors). There were 15 males and 12 females with a median age of 56 years. Ten patients had Myasthenia gravis at the time of presentation, two patients had pure red cell aplasia. Eighteen patients had dyspnea or superior vena caval syndrome (six of them). And five patients had only mild chest discomfort. Sixteen patients had complete surgical resection and 11 patients had partial resection (5) or only biopsy (6). Ten of them received a mean of three courses of chemotherapy with Cisplatin, Doxorubicin, and Cyclophosphamide (CAP). The overall 5 and 10 years survival rates were 65 and 47%, respectively. The 5 years survival rate for patients with complete resection was 81% compared to 44% for patients with partial resection or biopsy (P=0.01). Patients with Myasthenia had a 5 years survival of 71% compared to 53% for non-myasthenic patients. All patients with Myasthenia had complete surgical resection. Age, sex, presence of anemia, or superior vena caval syndrome were not adverse prognostic factors. There was no difference in terms of survival between relapsed and newly diagnosed tumors or between debulking surgery and biopsy. The 2 years survival for the four patients non-responders to chemotherapy was 0% while the 5 years survival for the responders was 71% (P=0.005). CONCLUSION: Resectability and response to chemotherapy for unresectable patients seem to be factors that predict the outcome in thymoma. Myasthenia gravis appears to be important in detecting the tumor when it is still resectable.

PMID: 12835088 [PubMed - indexed for MEDLINE]

107: Surgery. 2003 Jul;134(1):108-9. Related Articles, Links

Comment on:

Surgery. 2003 Feb;133(2):226-7.

Reply to "Transverse sternal approach for thymectomy".

Toniato A, Zuin A.

Publication Types:

PMID: 12874595 [PubMed - indexed for MEDLINE]

108: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7971-6. Epub 2003 Jun 10. Related Articles, Links: A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses.

Bartfai T, Behrens MM, Gaidarova S, Pemberton J, Shivanyuk A, Rebek J Jr.

Department of Neuropharmacology, The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. tbartfai@scripps.edu

Toll-like receptors (TLRs) and the type I IL-1 receptor (IL-1RI) are key components of the innate immune system activated by microbial infections and inflammation. The signaling cascade from agonist-occupied TLRs and IL-1Rs involves recruitment of the small cytosolic adapter protein MyD88 that binds to IL-1RI via homotypic interactions mediated by Toll/IL-1R/resistance (TIR) domains. Dominant negative forms and null mutations of MyD88 have recently been shown to preclude bacterial product or IL-1-mediated activation of NF-kappaB pathways, demonstrating that MyD88 is an essential component of the Toll receptor signaling. Here, we report the synthesis and pharmacological effects of a low molecular weight MyD88 mimic, hydrocinnamoyl-l-valyl pyrrolidine (compound 4a), modeled on a tripeptide sequence of the BB-loop [(F/Y)-(V/L/I)-(P/G)] of the TIR domain. Results are presented showing that compound 4a interferes with the interactions between mouse MyD88 and IL-1RI at the TIR domains. Compound 4a inhibited IL-1beta-induced phosphorylation of the mitogen-activated protein kinase p38 in EL4 thymoma cells and in freshly isolated murine lymphocytes in a concentration-dependent manner. In vivo, compound 4a produced a significant attenuation of the IL-1beta-induced fever response (200 mg/kg, i.p.). Inhibition of the TIR domain-mediated MyD88/IL1-RI interaction by a low molecular weight, cell-penetrating TIR domain mimic suggests an intracellular site for antiinflammatory drug action.

PMID: 12799462 [PubMed - indexed for MEDLINE]

109: Br J Cancer. 2003 Jun 16;88(12):1839-43. Related Articles, Links

Long-term results of intrathoracic chemohyperthermia (ITCH) for the treatment of pleural malignancies.

Monneuse O, Beaujard AC, Guibert B, Gilly FN, Mulsant P, Carry PY, Benoit M, Glehen O.

EA 'Ciblage Therapeutique en Oncologie, Universite Lyon 1, Faculte Lyon Sud, 69310, Oullins, France.

There is no standard treatment for patients with pleural malignancies. The aim of this prospective study was to investigate the toxicity and long-term results of a multimodality treatment consisting of surgery and intrathoracic chemohyperthermia (ITCH) for the treatment of patients with pleural malignancies. From January 1990 to August 2000, 24 patients with mesothelioma (n=17), fibrosarcoma (n=3), pleural adenocarcinoma (n=3) and thymoma (n=1) were included. The mesothelioma stages were T1 or T2 in 10 cases, and T3 or T4 in seven cases. After cytoreductive surgery, ITCH was carried out for over 60 min, at inflow temperatures less than 45 degrees C, either with mitomycin C (n=7) or cisplatin (n=5) or both (n=12). One patient died from major thoracic air leaks after major decortication and pleurectomy. Seven patients had complications, one pleural clotting necessitating reoperation. After a median follow-up of 89 months, the overall 1-year and 5-year survival rates were 74 and 27%, respectively. For T1 and T2 mesothelioma patients, the median survival was 41.3 months, and for T3 and T4 tumours, it was 4.5 months (P=0.001). The fibrosarcoma patients are alive with no evidence of recurrence at 24, 43 and 54 months. In the conclusion, the combination of surgery with ITCH with mitomycin and/or cisplatin is relatively safe. This procedure may offer unexpected long-term survival in a selected group of patients (T1 and T2 mesothelioma patients and fibrosarcoma patients).

Publication Types:

Clinical Trial

PMID: 12799624 [PubMed - indexed for MEDLINE]

110: Cancer Res. 2003 Jun 15;63(12):3281-8. Related Articles, Links: Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade.

Davila E, Kennedy R, Celis E.

Department of Immunology, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905, USA.

Although peptide immunization often leads to the induction of strong T-cell responses, it is seldom effective against established tumors. One possibility is that these T-cell responses are not strong enough or do not last sufficiently long to have an effect in tumor eradication. Here, we examined the role of synthetic oligodeoxynucleotide (ODN) adjuvants containing unmethylated cytosine-guanine motifs (CpG-ODN) and CTLA-4 blockade in enhancing the antitumor effectiveness of peptide vaccines intended to elicit CTL responses. The results show that combination immunotherapy consisting of vaccination with a synthetic peptide corresponding to an immunodominant CTL epitope derived from tyrosinase-related protein-2 administered with CpG-ODN adjuvant and followed by systemic injection of anti-CTLA-4 antibodies increased the survival of mice against the poorly immunogenic B16 melanoma. Interestingly, whereas this combination therapy was effective when administered to tumor-bearing mice (therapeutic protocol), it had no significant effect when applied in the prophylactic mode (i.e., before the tumor challenge). Moreover, the antitumor effect of the combination immunotherapy required the participation of CD4+ and CD8+ T lymphocytes and was accompanied by the induction of antitumor CD4+ T-cell responses. The overall results suggest that peptide vaccination of tumor-bearing mice, applied in combination with a strong adjuvant and CTLA-4 blockade, is capable of eliciting durable antitumor T cell responses that provide survival benefit. These findings bear clinical significance for the design of peptide-based therapeutic vaccines for human cancer patients.

PMID: 12810660 [PubMed - indexed for MEDLINE]

111: J Immunol. 2003 Jun 15;170(12):5834-41. Related Articles, Links: Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1 signaling pathways involved in T cell development.

Yun TJ, Bevan MJ.

IDEC Pharmaceuticals, San Diego, CA 92121, USA.

We have characterized the function of Notch-regulated ankyrin-repeat protein (Nrarp) in mouse cell lines and in hematopoietic stem cells (HSCs). Nrarp overexpression is able to block Notch-induced activation of CBF-1. In AKR1010 thymoma cells, Nrarp overexpression blocks CBF-1-dependent transcriptional activation of Notch-responsive genes and inhibits phenotypic changes associated with Notch activation. Enforced expression of Nrarp in mouse HSCs results in a profound block in T lineage commitment and progression through early stages of thymocyte maturation. In contrast, Deltex-1 overexpression in HSCs can also block T lineage commitment but not progression through the early double negative stages of thymocyte maturation. The different effects of Deltex-1 and Nrarp overexpression suggest that alternate Notch signaling pathways mediate T vs B lineage commitment and thymocyte maturation.

PMID: 12794108 [PubMed - indexed for MEDLINE]

112: Vaccine. 2003 Jun 2;21(19-20):2318-28. Related Articles, Links: Mechanisms of enhanced antigen-specific T cell response following vaccination with a novel peptide-based cancer vaccine and systemic interleukin-2 (IL-2).

Nguyen CL, Salem ML, Rubinstein MP, Demcheva M, Vournakis JN, Cole DJ, Gillanders WE.

Department of Surgery, Section of Surgical Oncology, Medical University of South Carolina, Room 420P, 96 Jonathan Lucas Street, PO Box 250613, Charleston, SC 29425, USA.

Systemic interleukin-2 (IL-2) therapy has been shown to enhance the clinical efficacy of peptide-based cancer vaccines. However, the mechanisms involved in this complex response remain poorly defined. IL-2 is known to be a potent T cell growth factor, but recent studies suggest that IL-2 is also involved in the regulation of T cell immune responses by increasing the susceptibility of proliferating T cells to apoptosis. Using an adoptive transfer model, we demonstrate that the administration of systemic IL-2 significantly enhances the primary and memory immune responses following peptide-based vaccination. In order to define the mechanisms of IL-2 therapy on the antigen-specific T cell response, the kinetics of T cell proliferation, apoptosis, and trafficking were explored. Systemic IL-2 therapy did not appear to alter the kinetics of T cell proliferation immediately following vaccination, but did prolong the proliferative response. Furthermore, IL-2 therapy did not significantly influence apoptosis of proliferating T cells. Such therapy did, however, potentiate L-selectin (CD62L) downregulation on activated antigen-specific T cells, and altered their trafficking confirming their potential therapeutic value. Our findings support the use of systemic IL-2 following peptide-based vaccination, and suggest that IL-2 therapy enhances the primary and memory immune responses by prolonging the proliferative response and altering the trafficking of antigen-specific T cells.

PMID: 12744862 [PubMed - indexed for MEDLINE]

113: Ann Allergy Asthma Immunol. 2003 Jun;90(6):595-8. Related Articles, Links

Implications of persistent cough in a 3-year-old female.

Khan AI, Giusti R, Murali M, Silverman B, Schneider A.

Department of Allergy and Immunology, Long Island College Hospital, Brooklyn, New York 11201, USA. ak57@drexel.edu

Publication Types:

PMID: 12839315 [PubMed - indexed for MEDLINE]

114: Ann Hematol. 2003 Jun;82(6):343-7. Epub 2003 Apr 25. Related Articles, Links: B-cell lymphopenia and hypogammaglobulinemia in thymoma patients.

Montella L, Masci AM, Merkabaoui G, Perna F, Vitiello L, Racioppi L, Palmieri G.

Molecular and Clinical Oncology and Endocrinology Department, Faculty of Medicine, University Federico II, via Pansini 5, 80131, Naples, Italy.

Thymic tumors represent a unique neoplastic disease associated with various immune-mediated syndromes. Immune impairment is generically recognized to be associated with thymoma. Hypogammaglobulinemia and recurrent pulmonary infections in thymoma patients define Good's syndrome. Apart from sporadic reports focusing on this topic, there is still a lack of knowledge on immune assessment and clinical sequelae in thymoma patients. The present study was performed to evaluate immunoglobulin levels, CD19(+) B lymphocytes, and CD3(+) T lymphocytes in a large series of thymoma patients from a single institution. The occurrence of recurrent severe infections was related to immunological findings to identify the possible correlation with the immunodeficiency status. Eighteen patients (eight males, ten females, mean age: 56 years, range: 19-75) with a pathological diagnosis of thymic tumor were studied. Six patients suffered from clinical recurrent pulmonary infections. Blood samples were collected to measure serum immunoglobulins and analyze immunophenotype. Low T lymphocyte number was found in 22% of the patients. T lymphocytosis was present in one patient. Panhypogammaglobulinemia was found in 4 of 18 patients (22%). Conversely B lymphopenia was a frequent finding in this series of thymoma patients (9 of 18, 50%). Five of six patients (83%) with recurrent infections had B lymphopenia, while only two (33%) had panhypogammaglobulinemia. B lymphopenia often occurred in this series of thymoma patients and was related to susceptibility to recurrent infections more than hypogammaglobulinemia. Therefore, immunophenotype has to be monitored in follow-up of thymoma patients because it may reveal significant abnormalities.

PMID: 12715206 [PubMed - indexed for MEDLINE]

115: G Chir. 2003 Jun-Jul;24(6-7):255-8. Related Articles, Links

[Role of thymectomy in the treatment of myasthenia gravis: considerations and personal cases]

[Article in Italian]

Pavia R, Mondello B, Monaco F, Pavone A, Micali V, Barresi P, Mule V, Familiani D, La Rocca A, Monaco M.

Azienda Ospedaliera Universitaria G. Martino Dipartimento di Scienze Cardiovascolari e Toraciche Cattedra di Chirurgia toracica, Universita degli Studi di Messina.

The therapeutic impact of thymectomy on the clinical course of myasthenia gravis is still very controversial. In fact, while nowadays the surgical approach is widely adopted for thymomas, its role is still debatable in patients suffering from myasthenia gravis. The surgical approach of choice for total thymectomy is represented by median sternotomy. Other surgical methodologies include cervical access and partial sternotomy. All these approaches have shown excellent results in the exeresis of the thymus. More recently video-assisted thoracoscopic thymectomy has been proposed as a less invasive and similarly effective technique for the removal of this organ and the treatment of myasthenia gravis. Aim of the present study is to report Author's experience with thymectomy, emphasizing the data available in the international literature on the surgical mortality, complications and aesthetical results of the different surgical accesses.

Publication Types:

PMID: 14569924 [PubMed - indexed for MEDLINE]

116: J Exp Clin Cancer Res. 2003 Jun;22(2):341-2. Related Articles, Links

Philadelphia negative, Bcr-Abl positive chronic myeloid leukemia associated with pure red cell aplasia.

Karti S, Yilmaz M, Sonmez M, Akdogan R, Ersoz S, Ucar F, Ovali E.

Dept. of Internal Medicine, Division of Hematology, Karadeniz Technical University, School of Medicine, Trabzon, Turkey. samikarti@yahoo.com

Pure red cell aplasia (PRCA) is a rare disorder which is associated with thymoma, viral infections and autoimmune diseases. A few cases of PRCA during the clinical course of CML have been reported and these usually terminate in blastic crisis and death, suggesting a poor prognosis. However, only one case of Philedelphia chromosome negative, Bcr-Abl positive CML associated with PRCA has been reported. Here, we present a second case report of a Philedelphia negative, Bcr-Abl positive CML associated with PRCA who was unresponsive to all the chemotherapeutic regimens. We conclude that the present case supports the idea that the development of PRCA in the course of CML may be a bad prognostic sign.

Publication Types:

Case Reports

PMID: 12866588 [PubMed - indexed for MEDLINE]

117: J Neuroimmunol. 2003 Jun;139(1-2):102-8. Related Articles, Links: Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on the IFN-gamma responses of healthy CD4+ T cells.

Zhang W, Liu JL, Meager A, Newsom-Davis J, Willcox N.

Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, OX3 9DS, Oxford, UK.

In humans, interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) normally favor IFN-gamma-producing "Th1" T cell responses. Myasthenia gravis (MG) patients with thymomas frequently have high-titer neutralizing autoantibodies against these cytokines, but not against IFN-gamma. Because they occasionally develop intractable (even fatal) infections, we have tested effects of their sera on the generation of IFN-gamma responses by healthy adult T cells to autologous lipopolysaccharide (LPS)-treated dendritic cells (DC). Anti-IL-12(+) sera consistently reduced IFN-gamma responses substantially, whether assessed by intracellular staining or ELISA. Therefore, thymoma patients with intractable infections might benefit from cautious IFN-gamma therapy. We discuss wider implications of the surprising rarity of clear clinical hazards-or benefits-of these autoantibodies.

PMID: 12799027 [PubMed - indexed for MEDLINE]

118: J Neurol. 2003 Jun;250(6):698-701. Related Articles, Links: The epidemiology of myasthenia gravis, Lambert-Eaton myasthenic syndrome and their associated tumours in the northern part of the province of South Holland.

Wirtz PW, Nijnuis MG, Sotodeh M, Willems LN, Brahim JJ, Putter H, Wintzen AR, Verschuuren JJ; Dutch Myasthenia Study Group.

Department of Neurology, J3R-166, Leiden University Medical Centre, P. O. Box 9600, The Netherlands. pwwirtz@lumc.nl

We studied the epidemiology of myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS), and their association with small cell lung carcinoma (SCLC) and thymoma, in a well defined region of the Netherlands. Available data on all the patients with MG, LEMS, thymoma or SCLC living between 1 January 1990 and 31 December 1999 in the northern region of South Holland, with a population of 1.7 million inhabitants, were evaluated. A total of 202 patients with MG (20 with thymoma) and ten patients with LEMS (seven with SCLC) were identified. LEMS was 46 times less prevalent (2.32 x 10(-6)) than MG (106.1 x 10(-6)), whereas the annual incidence rate of LEMS was 14 times lower (0.48 x 10(-6)) than of MG (6.48 x 10(-6)), reflecting the poor survival of LEMS patients with SCLC. SCLC was diagnosed in 1593 patients, seven (0.44 %) of whom developed LEMS. Mean age at diagnosis of SCLC was significantly lower in SCLC patients with LEMS (p = 0.006). A thymoma was diagnosed in 32 patients, of whom the ten patients with MG (31 %) had a younger age at diagnosis of thymoma than the patients without MG (p = 0.27). This study confirms the increasing prevalence of MG over the last few decades as reported by others, and underscores the relative rarity of LEMS. The frequency of LEMS in our patients with SCLC was lower than reported in previous studies. In patients with a SCLC or thymoma, the tumour was diagnosed at younger age in those who had the associated myasthenic syndrome.

PMID: 12796832 [PubMed - indexed for MEDLINE]

119: Kyobu Geka. 2003 Jun;56(6):448-51. Related Articles, Links

[Needle tract implantation of thymoma after transthoracic needle biopsy]

[Article in Japanese]

Fujiwara K, Matsumura A, Tanaka H, Ohmori K, Yamamoto S, Iuchi K.

Department of Surgery, National Kinki-chuou Hospital, Sakai, Japan.

A 53-year-old man was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under ultrasonic examination. The histopathological diagnosis was thymoma and thymo-thymectomy was performed. The tumor recurred in the right anterior chest wall 10 years later. It is suggested that the thymoma tissue had been implanted in the needle tract. To our knowledge, this is the 2nd reported case of thymoma which has been implanted in the needle tract.

Publication Types:

Case Reports

PMID: 12795148 [PubMed - indexed for MEDLINE]

120: Nihon Kokyuki Gakkai Zasshi. 2003 Jun;41(6):421-5. Related Articles, Links

[Hypogammaglobulinemia associated with thymoma (Good syndrome) similar to diffuse panbronchiolitis]

[Article in Japanese]

Tsuburai T, Ikehara K, Suzuki S, Shinohara T, Mishima W, Tagawa A, Itou M, Miyazawa N, Nishiyama H, Shoji A, Suzuki M, Matsuse T, Ishigatsubo Y.

First Department of Internal Medicine, Yokohama City University School of Medicine.

A 65-year-old woman complained of dyspnea and a productive cough after surgical treatment and irradiation therapy for thymoma. Chest radiography and high-resolution computed tomography showed small nodules in centrilobular lesions in all of both lung fields, but predominantly in the lower fields. In addition, blood tests showed hypogammaglobulinemia. Chronic sinusitis, mild hypoxemia, severe obstructive impairment and the pathological findings of bronchiolitis led to a diagnosis of sinobronchial syndrome caused by Good syndrome. Treatment with oral erythromycin 600 mg/day was started. After 6 months, the patient improved both clinically and radiologically. Low-dose, long-term treatment with erythromycin was effective against sinobronchial syndrome caused by Good syndrome.

Publication Types:

Case Reports

PMID: 12833850 [PubMed - indexed for MEDLINE]

121: Radiother Oncol. 2003 Jun;67(3):265-74. Related Articles, Links

Dose-volume analysis of lung complications in the radiation treatment of malignant thymoma: a retrospective review.

Moiseenko V, Craig T, Bezjak A, Van Dyk J.

London Regional Cancer Centre, Ontario, London, Canada.

BACKGROUND AND PURPOSE: Radiation pneumonitis and fibrosis are limiting factors in radiation treatment (RT) of thoracic tumors. The objectives of this study were to quantify the influence of irradiated lung volume and dose on lung response, and to evaluate the influence of other prognostic factors. MATERIAL AND METHODS: Treatment histories of 55 thymoma patients were evaluated retrospectively for radiation pneumonitis and fibrosis. Complications were scored as pneumonitis if observed within 6 months of completion of RT, and as fibrosis if observed after 6 months. Complications were classified as 'all pneumonitis' and 'all fibrosis' if a patient either showed symptoms (such as chronic cough and dyspnea) or radiographic changes in lung. The second group scored as 'symptomatic pneumonitis' and 'symptomatic fibrosis' consisted of patients that exhibited clinical symptoms. Dose-volume data were estimated using representative anatomies combined with available individual dose data. The Lyman NTCP model was used to assess the dependence of lung complication incidence on dose and volume. RESULTS: The derived values of the parameters governing dose-volume dependence for symptomatic complications agreed with currently accepted and recently published values within the margins of error. Dose-response curves for complications that included radiographic changes were less steep than for symptomatic complications. The volume dependence for symptomatic fibrosis was more pronounced compared to all fibrosis. A strong correlation was observed between developing pneumonitis and developing fibrosis. CONCLUSIONS: The long survival allowed the assessment of lung complication data in thymoma patients for both acute and late response. Mean dose in lung strongly correlated with lung complications that manifest clinically. The determination of the dose-volume dependence is affected by the choice of endpoints (i.e. whether complications are scored based on clinical symptoms or radiographic changes not accompanied by clinical symptoms).

Publication Types:

Evaluation Studies

PMID: 12865174 [PubMed - indexed for MEDLINE]

122: Rinsho Shinkeigaku. 2003 Jun;43(6):322-6. Related Articles, Links

[Head retraction reflex-like movements with severe bulbar symptoms in a patient with stiff-person syndrome]

[Article in Japanese]

Atsumi M, Chimoto Y, Nishikawa S, Mineta H, Nakasaka Y, Nishimoto K, Tanaka H, Kitaguchi M.

Department of Neurology, Baba Memorial Hospital.

A 57-year-old woman developed muscular stiffness and painful cramps, which were relieved by administration of dantrolene sodium. Her serum level of antibodies to glutamic acid decarboxylase (GAD) was markedly elevated and continuous muscular activities were observed on resting surface EMG. These features were compatible with those in stiff-person syndrome (SPS). She was found to have thymoma on CT scan. Immediately after thymomectomy, which was histologically diagnosed as a benign hyperplasia, she developed head retraction reflex-like movements evoked by sensory stimulation to the face, which were followed by severe bulbar symptoms with dysphagia and respiratory arrest. Postoperative myasthenia gravis was excluded clinically. While somatosensory evoked EMG on splenius muscle initially showed biphasic responses with latency of 15 msec and 55 msec, respectively after oral angle non-painful electric stimulation, the late potential phase disappeared after the patient recovered from bulbar symptoms. This suggests that head retraction reflex-like movements of this patient reflected the attenuation of inhibitory potentials from the brainstem.

Publication Types:

Case Reports

PMID: 14503349 [PubMed - indexed for MEDLINE]

123: Semin Neurol. 2003 Jun;23(2):191-8. Related Articles, Links

Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome.

Newsom-Davis J.

Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom.

Myasthenia gravis (MG) is a heterogeneous disorder, a fact that needs to be kept in mind when considering treatment. Most patients benefit from pyridostigmine. In nonthymomatous ocular MG, prednisolone is often effective. Thymectomy is indicated for thymoma and is an option for acetylcholine receptor antibody-positive patients with generalized weakness developing under the age of 45 years. In older patients and in those failing to respond to thymectomy, prednisone alone or combined with azathioprine is the treatment of choice. Mycophenolate mofetil is an option in those intolerant of azathioprine. Lambert-Eaton myasthenic syndrome (LEMS) can exist in paraneoplastic (P-) and nonparaneoplastic (NP-) forms. Most patients benefit from 3,4-diaminopyridine. In P-LEMS, treatment of the tumor often results in neurological improvement. In both forms, prednisone alone is an option or combined with azathioprine in NP-LEMS. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.

Publication Types:

Review

PMID: 12894384 [PubMed - indexed for MEDLINE]

124: Chir Ital. 2003 May-Jun;55(3):379-84. Related Articles, Links: Diagnosis of anterior mediastinal masses with ultrasonically guided core needle biopsy.

Annessi V, Paci M, De Franco S, Cavazza A, Ferrari G, Ricchetti T, Sgarbi G.

1st Department of Surgery, Division of Thoracic Surgery, Santa Maria Nuova Hospital, Viale Risorgimento 80, 42100 Reggio Emilia.

The various techniques used to perform percutaneous guided biopsies of mediastinal masses have already been amply described, with particular attention to the type of needle used. In this study our experience with mediastinal transthoracic core needle biopsy has been compared with reported descriptions of ultrasonically guided fine needle aspiration to determine which is better and the respective influence on pathological diagnosis. Between January 1998 and July 2002, 47 patients underwent anterior mediastinal core needle biopsy with ultrasonic guidance. An accurate diagnosis was achieved in all patients, with 100% sensitivity and specificity. In all patients with lymphoma and thymoma it proved possible to establish the histological type. Two cases of pneumothorax were seen with pleural drainage and a 5-day hospital stay required in one of the cases. The remaining 45 patients were treated as outpatients and were discharged within 4 hours of the procedure. Ultrasonically guided percutaneous needle biopsy is a safe procedure; fine needle aspiration usually suffices for solid malignant lesions while a core needle biopsy should be performed when lymphoma or thymoma masses are suspected in order to obtain larger specimens for a precise histological diagnosis. The core needle procedure avoids repetition of unsuccessful fine- needle aspirations and reduces the number of mediastinoscopies and videothoracoscopies carried out for diagnostic purposes.

PMID: 12872573 [PubMed - indexed for MEDLINE]

125: Clin Biochem. 2003 May;36(3):171-6. Related Articles, Links: A homozygous and a heterozygous defect of the winged helix DNA-binding domain of the fork head (FH) gene in tailless and tailed rat siblings: resultant lymphocyte-rich thymoma connected with renal tubule amyloid beta (Abeta) deposits.

Nakatsuji T.

Department of Transfusion, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan. nh80415@hama-med.ac.jp

OBJECTIVE: To investigate the cause of thymoma connected with renal amyloid beta (Abeta) overproduction. DESIGN AND METHODS: Pathologic, immune-fluorescence analyses, flow cytometry (FCM) analyses, polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR were applied for tailless and tailed Lewis/Sea rat siblings at the age of 6 months. RESULTS: A homozygous defect of the winged helix DNA-binding domain of the fork head (FH) gene was detected in the RT-PCR of the tailless rat kidney and liver. Lymphocyte-rich thymoma was found in both rats, but was more prominent in the tailless rat. FCM showed that CD4+ and CD8a+ cells constituted of more than 90% of the thymus lymphocytes in both rats. Abeta deposits in the renal tubules of both rats were shown by positive staining with antihuman Abeta (11-28) antibody (Ab) together with the activation of the kidney presenilin (PSEN) genes. The mRNA level of transthyretin (TTR) was suppressed moderately with age by the homozygous FH1 gene defect. CONCLUSIONS: Both homozygous and heterozygous defects of the DNA-binding domain of the FH gene caused lymphocyte-rich thymoma and renal Abeta overproduction.

PMID: 12726924 [PubMed - indexed for MEDLINE]

126: Eur J Gastroenterol Hepatol. 2003 May;15(5):565-9. Related Articles, Links

Full-blown graft-versus-host disease presenting with skin manifestations, jaundice and diarrhoea: an unusual paraneoplastic phenomenon of a thymoma.

Sleijfer S, Kaptein A, Versteegh MI, Hegt VN, Snels DG, van Tilburg AJ.

Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.

We describe a patient who presented with chronic diarrhoea, skin lesions and jaundice. Based on histopathological examinations of the affected organs combined with the clinical features, it appeared that the patient fulfilled the criteria for graft-versus-host disease (GVHD). GVHD occurs especially after allogeneic stem cell transplantation and sometimes after organ transplantations. However, this patient had never undergone such a procedure. Further examination revealed that the patient also suffered from a thymoma, which was concluded to be the cause of GVHD. Unfortunately, the patient died after resection of the thymoma. This patient is probably the second case with thymoma and full-blown GVHD and shows that GVHD can occur in the absence of a previous transplantation.

Publication Types:

Case Reports

PMID: 12702918 [PubMed - indexed for MEDLINE]

127: Gan To Kagaku Ryoho. 2003 May;30(5):595-8. Related Articles, Links: [The diagnosis and treatment of the thymic carcinoma]

[Article in Japanese]

Moriyama H, Nishimura Y, Kuwabara K, Hishima T, Moriyama S.

Department of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkamagome, Bunkyo-ku, Tokyo 113-8677, Japan.

Thymic carcinoma was indistinct for criteria of clinicopathological diagnosis. Recently it gets easier to diagnose thymic carcinoma, because of progression of WHO classification and immunohistochemical technique. Commonly, patients are men and in sixties. Common symptoms are chest pain and dyspnea. Most cases are advanced, over Stage III of the Masaoka's classification. Combined therapies e.g. operation, chemotherapy and radiation were done, but complete resection is difficult. Prognosis is poor, the 3- and 5-year survival is 48.7% and 40.6%.

PMID: 12795088 [PubMed - indexed for MEDLINE]

128: J Clin Endocrinol Metab. 2003 May;88(5):2309-17. Related Articles, Links: Sex steroid hormone receptors in human thymoma.

Ishibashi H, Suzuki T, Suzuki S, Moriya T, Kaneko C, Takizawa T, Sunamori M, Handa M, Kondo T, Sasano H.

Department of Pathology, Tohoku University School of Medicine, Sendai, Miyagi, Japan. hishiba@kf6.so-net.ne.jp

In this study we examined the immunohistochemical localization of sex steroid receptors for estrogen alpha (ER alpha) and ER beta, progesterone-A (PR-A) and PR-B, and androgen (AR) in human thymoma (n = 132) and correlated these findings with various clinicopathological parameters. We used RT-PCR and real-time PCR to further study the expression of these receptors in 20 thymoma cases. Immunoreactivity for all sex steroid receptors was detected in the nuclei of thymoma epithelial cells. The percentage of immunopositive cases and the H-score values for each receptor (mean +/- SD) were: ER alpha, 66% and 85.8 +/- 80.2; ER beta, 7% and 7.2 +/- 8.7; PR-A, 4% and 2.7 +/- 4.9; PR-B, 49% and 55.8 +/- 68.3; and AR, 15% and 14.1 +/- 11.7, respectively. The results of real-time PCR were consistent with those of immunohistochemistry, especially results for ER alpha, PR-B, and AR. A significant positive correlation was detected between immunoreactivity for ER alpha and PR-B. ER alpha immunoreactivity was inversely correlated with tumor size, clinical stage, WHO classification, and Ki-67 labeling index. In addition, the status of ER alpha immunoreactivity was significantly associated with a better clinical outcome in thymoma patients. Results from our study suggest that estrogens may inhibit thymoma growth via ER alpha, and that ER alpha immunoreactivity may act as a prognostic factor in human thymoma.

PMID: 12727990 [PubMed - indexed for MEDLINE]

129: J Surg Oncol. 2003 May;83(1):24-30. Related Articles, Links: Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution.

Takeda S, Miyoshi S, Akashi A, Ohta M, Minami M, Okumura M, Masaoka A,