Thymoma Database 2007

1: Biomaterials. 2008 Mar;29(7):917-924. Epub 2007 Nov 26. Related Articles, Links: The effect of covalent cross-links between the membrane components of microcapsules on the dissemination of encapsulated malignant cells.

Dusseault J, Langlois G, Meunier MC, Ménard M, Perreault C, Hallé JP.

Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, 5415 boul. de l’Assomption, Montréal, Québec, Canada H1T 2M4.

Stem cells and immortalized cells have considerable therapeutic potential but present risks of malignant transformation. Cell microencapsulation allows transplantation without immunosuppression. We have developed a method for microencapsulating living cells within covalently cross-linked membranes that are chemically and mechanically extremely resistant. We provide herein direct evidence that these microcapsules can prevent malignant cell dissemination. When 20,000 or more nonencapsulated EL-4 thymoma cells were implanted intraperitoneally in mice, all recipients died with widespread metastasis within 26.3+/-1.0 days. All recipients of 250,000 EL-4 cells microencapsulated in covalently cross-linked membranes were living and disease-free, 150 days post-implantation. Encapsulation in standard microcapsules only slightly delayed the recipient death. Pancreatic islets transplanted using either type of microcapsule presented similar survival. We conclude that microencapsulation in covalently cross-linked membranes prevents malignant cell dissemination.

PMID: 18035411 [PubMed - as supplied by publisher]

2: Cancer Immunol Immunother. 2008 Feb;57(2):227-32. Epub 2007 Jul 27. Related Articles, Links: CRMP5 antibodies in patients with small-cell lung cancer or thymoma.

Monstad SE, Drivsholm L, Skeie GO, Aarseth JH, Vedeler CA.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

The collapsin response mediator protein 5 (CRMP5) antibody is usually associated with paraneoplastic neurological syndrome (PNS) and small-cell lung cancer (SCLC) or thymoma. The objective of this study was to assess the frequency of CRMP5 antibodies in patients with such tumours and to see if the presence of antibodies was associated with prognosis in these cancers. A multi-well adapted immunoprecipitation assay using radiolabelled recombinant CRMP5 protein, produced by coupled in vitro transcription/translation, was used for the detection of CRMP5 antibodies. Sera from 200 patients with SCLC, 73 patients with thymoma and myasthenia gravis (MG) and from 300 healthy blood donors were examined for CRMP5 antibodies. Positive sera were also examined by immunofluorescence and immune blots. The serological results were compared with disease severity of the patients with thymoma or SCLC. CRMP5 antibodies were detected in 10/200 (5%) of the SCLC, 9/73 (12%) of the thymomas and in 2/300 (0.6%) of the healthy controls by immunoprecipitation. The antibodies were less frequently detected by immunofluorescence or immune blots. There was no significant correlation between CRMP5 antibodies and disease severity. CRMP5 antibodies are more than twice as frequent, and the antibody levels are higher in patients with thymoma and MG than in patients with SCLC. The antibodies are correlated to these tumours, but not to disease severity.

PMID: 17657489 [PubMed - in process]

3: Biol Reprod. 2008 Jan;78(1):143-50. Epub 2007 Sep 26. Related Articles, Links: Activation of multiple signaling pathways is critical for fibroblast growth factor 2- and vascular endothelial growth factor-stimulated ovine fetoplacental endothelial cell proliferation.

Zheng J, Wen Y, Song Y, Wang K, Chen DB, Magness RR.

Department of Reproductive Medicine, Division of Maternal-Fetal Medicine, University of California, San Diego, California 92093.

Fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) are two key regulators of placental angiogenesis. The potent vasodilator nitric oxide (NO) could also act as a key mediator of FGF2- and VEGF-induced angiogenesis. However, the postreceptor signaling pathways governing these FGF2- and VEGF-induced placental angiogenic responses are poorly understood. In this study, we assessed the role of endogenous NO, mitogen-activated protein kinase 3/1 (MAPK3/1), and v-akt murine thymoma viral oncogene homolog 1 (AKT1) in FGF2- and VEGF-stimulated proliferation of ovine fetoplacental endothelial (OFPAE) cells. Both FGF2 and VEGF time-dependently stimulated (P < 0.05) NO production and activated AKT1. Both FGF2- and VEGF-stimulated cell proliferation was dose-dependently inhibited (P < 0.05) by N(G)-monomethyl-l-arginine (l-NMMA; an NO synthase inhibitor), PD98059 (a selective MAPK3/1 kinase 1 and 2 [MAP2K1/2] inhibitor), or LY294002 (a selective phosphatidylinositol 3 kinase [PI3K] inhibitor) but not by phenyl-4,4,5,5 tetramethylimidazoline-1-oxyl 3-oxide (PTIO, a potent extracellular NO scavenger). At the maximal inhibitory dose without cytotoxicity, PD98059 and LY294002 completely inhibited VEGF-induced cell proliferation but only partially attenuated (P < 0.05) FGF2-induced cell proliferation. PD98059 and LY294002 also inhibited (P < 0.05) FGF2- and VEGF-induced phosphorylation of MAPK3/1 and AKT1, respectively. l-NMMA did not significantly affect FGF2- and VEGF-induced phosphorylation of either MAPK3/1 or AKT1. Thus, in OFPAE cells, both FGF2- and VEGF-stimulated cell proliferation is partly mediated via NO as an intracellular and downstream signal of MAPK3/1 and AKT1 activation. Moreover, activation of both MAP2K1/2/MAPK3/1 and PI3K/AKT1 pathways is critical for FGF2-stimulated cell proliferation, whereas activation of either one pathway is sufficient for mediating the VEGF-induced maximal cell proliferation, indicating that these two kinase pathways differentially mediate the FGF2- and VEGF-stimulated OFPAE cell proliferation.

PMID: 17901071 [PubMed - in process]

4: Clin Imaging. 2008 Jan-Feb;32(1):54-7. Related Articles: Nodular thymic lymphoid follicular hyperplasia mimicking thymoma.

Nakagawa M, Hara M, Itoh M, Shibamoto Y.

Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

In this report, we describe a case of thymic lymphoid follicular hyperplasia that was incidentally found as a small thymic nodule in the health screening program including a low-dose chest CT. The CT and MRI findings of the nodule were similar to those of thymoma, and it was difficult to differentiate the lesion from thymoma.

PMID: 18164397 [PubMed - in process]

5: Ann N Y Acad Sci. 2007 Dec 20 [Epub ahead of print] Related Articles, Links: Tacrolimus for Myasthenia Gravis: A Clinical Study of 212 Patients.

Ponseti JM, Gamez J, Azem J, Manuel LC, Vilallonga R, Armengol M.

Surgery, Hospital General Universitari Vall d'Hebron, P. Vall d'Hebron, 119-129, Barcelona, 08035, Spain.

Tacrolimus is a macrolide T-cell immunomodulator the use of which in patients myasthenia gravis (MG) is supported by its effect on muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing in muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking its export mechanism), and also increasing apoptosis of T cells. We here report the results of low dose tacrolimus (0.1 mg/kg/day) in 212 MG patients. There were 110 thymectomyzed, cyclosporine- and prednisone-dependent patients, 68 thymectomyzed starting tacrolimus early postoperatively (24 h after operation), and 34 patients with non-thymomatous generalized MG over 60 years or in whom thymectomy was contraindicated. The mean follow-up was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. AChR antibodies decreased significantly from a mean of 33.5 nmol/L at baseline to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn due to major adverse effects. Our results suggest than low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.

PMID: 18096852 [PubMed - as supplied by publisher]

6: Virchows Arch. 2007 Dec 20 [Epub ahead of print] Related Articles, Links: Thymoma with ganglioneuroblastomatous component: case report.

Kashiwabara K, Ikota H, Tanaka S, Ohta C, Yajima T, Endoh H, Yamaki E, Kuwano H, Nakajima T.

Department of Clinical Pathology, Saiseikai Maebashi Hospital, 564-1 Kamishinden-machi, Maebashi, Gunma, 371-0821, Japan, ke-kashiwabara@maebashi.saiseikai.or.jp.

A mediastinal tumor in a 49-year-old woman with myasthenia gravis is reported. The tumor was well-demarcated and located in the supero-anterior mediastinum. Microscopically, the tumor consisted of thymic and neuroblastic tumor components, the latter of which consisted of immature and maturing neuronal cells, abundant neuropils, and Schwannian stroma. The two components intermingled with each other inside the tumor capsule. The tumor was diagnosed as thymoma with a ganglioneuroblastomatous component. The coexistence of epithelial and neuronal tissues in the thymic neoplasm is extremely rare.

PMID: 18094997 [PubMed - as supplied by publisher]

7: Cancer. 2007 Dec 15;110(12):2747-55. Related Articles, Links: Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA-87 and LALA-94 trials.

Tavernier E, Le QH, de Botton S, Dhédin N, Bulabois CE, Reman O, Vey N, Lhéritier V, Dombret H, Thomas X.

Hôpital Nord, Saint-Etienne, France.

BACKGROUND.: Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). Although treatment intensity and outcome were not comparable, with improvements in survival it is important to evaluate the rate and the type of second neoplasms in adults with ALL. METHODS.: The data from the GET-LALA group were analyzed. A cohort of 1494 patients, aged 15 to 60 years and enrolled in 2 successive multicenter protocols between 1987 and 2002, was observed to determine the incidence of second neoplasms and associated risk factors. The median follow-up from diagnosis was 6 years. RESULTS.: By February 2005 secondary or concomitant neoplasms were documented in 23 patients, including 9 acute myeloid leukemias (AML) or myelodysplasias (MDS), 4 non-Hodgkin lymphomas (NHL), 5 skin tumors, and 5 other solid tumors (1 lung cancer, 1 tongue carcinoma, 1 thymoma, 1 condrosarcoma, 1 histiocytosis). Neoplasms developed 0.5 to 13.8 years (median, 4.5 years) after the diagnosis of ALL. There were 22 patients in first remission and 1 was in second remission. The overall cumulative risk of secondary neoplasms was 2.1% at 5 years, 4.9% at 10 years, and 9.4% at 15 years. The cumulative risk of developing a second hematologic malignancy was 1.8% at 5 years, 2.2% at 10 years, 3.3% at 18 years; that of developing a solid tumor was 0.2% at 5 years, 2.8% at 10 years, 6.2% at 15 years. The development of secondary neoplasm was not associated with the use of any specific cytotoxic agent. However, the risk of skin tumor increased with radiation dose and transplantation (P = .01). Overall survival (OS) after the diagnosis of a second malignant neoplasm was 55% at 10 years. However, the median OS in patients developing AML/MDS was 5.7 months. CONCLUSIONS.: The data document that adult ALL survivors are at an increased risk of later malignancy. The risk of secondary or concomitant neoplasm appeared higher than that of childhood ALL previously reported in the literature. Considering the low survival rate of this large unselected adult ALL cohort (32% at 10 years) as compared with that observed in childhood ALL, the risk of second malignancy remains underestimated. Larger series with long-term follow-up are necessary, as well as methods of screening and identification of patients at increased risk. Cancer 2007. (c) 2007 American Cancer Society.

PMID: 17963265 [PubMed - in process]

8: Cell Immunol. 2007 Dec 13 [Epub ahead of print] Related Articles, Links: Cyclophilin A produced by thymocytes regulates the migration of murine bone marrow cells.

Khromykh LM, Kulikova NL, Anfalova TV, Muranova TA, Abramov VM, Vasiliev AM, Khlebnikov VS, Kazansky DB.

Laboratory of Regulatory Mechanisms in Immunity, Carcinogenesis Institute State Institution Russian N.N. Blokhin Cancer Research Center Russian Academy of Medical Sciences, Kashirskoe shosse 24, 115478 Moscow, Russia.

Supernatant obtained from high dose hydrocortisone resistant thymocytes can induce migration of the bone marrow cell precursors to the periphery. This biological activity depends on the presence of the 18kDa protein, whose amino acid sequence fits with the sequence of the secretory form of murine cyclophilin A (SP-18). Cyclophilin A isolated from the supernatant of the cortisone-resistant thymoma EL-4 shows its characteristic functional features as it demonstrates isomerase activity and binds with cyclosporine A. The cyclophilin A obtained manifests chemotactic activity that regulates migration of bone marrow cell precursors of neutrophils, T-, B- and dendritic cells.

PMID: 18082675 [PubMed - as supplied by publisher]

9: Chirurg. 2007 Dec 7 [Epub ahead of print] Related Articles, Links: [Surgery of mediastinal tumors.]

[Article in German]

Stremmel C, Passlick B.

Abteilung für Thoraxchirurgie, Universitätsklinikum Freiburg, Hugstetter Straße 55, 79106, Freiburg, Deutschland, christian.stremmel@uniklinik-freiburg.de.

Thymomas, lymphomas, and germ cell tumors are the most frequent lesions of the anterior mediastinum, whereas endodermal (bronchogenic) cysts and lymphomas are the most frequent lesions of the middle mediastinum. In the posterior mediastinum, neurogenic tumors and soft-tissue sarcomas are the most frequent. Depending on tumor location, mediastinoscopy, mediastinotomy, and thoracoscopy are the preferred diagnostic methods. Surgical treatment of thymoma is the gold standard, and median sternotomy is the most frequently applied approach. The decisive prognostic and therapeutic criteria are Masaoka staging, WHO classification, and R0 status. Thoracoscopy should be performed only in patients with myasthenia gravis and with very small tumors. Surgical treatment is highly recommended in patients with locally recurrent tumors. The importance of surgical treatment of germ cell tumors is determined by a negative concentration of beta-HCG and alpha-fetoprotein and in cases of residual tumor after chemotherapy. Bronchogenic cysts always require resection because of their high complication rate (66%) after conservative treatment. In these cases complete resection is necessary due to the probability of recurrence. Ninety-eight percent of neurogenic tumors in adults are benign and usually resected via thoracoscopy or thoracotomy, depending on location and size.

PMID: 18058077 [PubMed - as supplied by publisher]

10: Interact Cardiovasc Thorac Surg. 2007 Dec 6 [Epub ahead of print]
Related Articles, Links: Thymoma accompanied by lichen planus.

Hayashi A, Shiono H, Okumura M.

Osaka University Graduate School of Medicine, Japan.

Thymomas are associated at a high frequency with paraneoplastic autoimmune diseases. We treated a 64-year-old male with a thymoma, who also had lichen planus. The tumor was resected and diagnosed as thymoma, however, the symptoms associated with lichen planus did not subside and persisted. A preoperative examination showed an elevated serum level of squamous cell carcinoma antigen, which gradually decreased to normal after surgery. The findings of this case are interesting for understanding the correlation between a thymoma and autoimmune abnormalities. Keywords: Thymoma; Lichen planus; Thymectomy; Immunology.

PMID: 18063606 [PubMed - as supplied by publisher]

11: Ann Thorac Surg. 2007 Dec;84(6):2095-7.
Related Articles, Links

Good syndrome coexisting with leukopenia.

Ohuchi M, Inoue S, Hanaoka J, Igarashi T, Tezuka N, Ozaki Y, Teramoto K.

Department of Thoracic Surgery, National Hospital Organization Shiga Hospital, Shiga, Japan. iky10@shiga-hp.jp

A 61-year-old man was admitted to our hospital for further examinations of a mediastinal mass. He had underwent an extended thymothymectomy, and had a tumor that was diagnosed as a type B1 thymoma, according to the World Health Organization. One year after surgery he was admitted again for recurrent diarrhea and pneumonia. Laboratory data revealed severe hypogammaglobulinemia with leukopenia. He was diagnosed with Good syndrome with leukopenia. Regular gamma globulin and figrastim injections were successful in keeping the patient symptom free. The prognosis of patients with Good syndrome and leukopenia is very poor; therefore, immediate diagnosis is important. The development of infectious diseases in a patient with thymoma or after the resection of thymoma mandates early and comprehensive immunologic investigation.

Publication Types:

Case Reports

PMID: 18036947 [PubMed - indexed for MEDLINE]

12: Clin Neurol Neurosurg. 2007 Dec;109(10):858-61. Epub 2007 Sep 27.
Related Articles, Links

Effects of thymectomy on late-onset myasthenia gravis without thymoma.

Kawaguchi N, Kuwabara S, Nemoto Y, Fukutake T, Arimura K, Osame M, Hattori T.

Department of Neurology, Chiba University, Graduate School of Medicine, 1-8-1 Inohna, Chuo-ku, Chiba 260-8670, Japan. kawaguchi@faculty.chiba-u.jp

OBJECTIVES: This study aims to investigate whether thymectomy is beneficial for late-onset (>50 years) myasthenia gravis patients with no thymoma, particularly for those with mild generalized weakness. PATIENTS AND METHODS: A total of 34 patients were included in the study. The clinical course and long-term outcomes over 2 years were reviewed in 20 patients who underwent thymectomy and in 14 without thymectomy. RESULTS: Of the 34 patients, 20 (59%) underwent thymectomy. Thymectomized patients had more severe disability at entry than non-thymectomized patients, but outcome measures did not significantly differ between the two patient groups. Moreover, subgroup analyses including 22 patients with mild generalized weakness at entry showed that the thymectomized group (n=10) showed a greater percentage of clinical remission (no symptoms; 50% versus 17%; p=0.11) and a lower frequency of the presence of generalized symptoms (30% versus 75%; p<0.05) than the non-thymectomized group (n=12) at the end of follow-up (means 9.6 years after onset). CONCLUSIONS: Thymectomy is a potentially effective treatment for late onset, non-thymomatous patients with mild generalized myasthenia gravis.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17904281 [PubMed - in process]

13: Clin Nucl Med. 2007 Dec;32(12):920-6.
Related Articles, Links: Unusual extracardiac findings detected on myocardial perfusion single photon emission computed tomography studies with Tc-99m sestamibi.

Gedik GK, Ergün EL, Aslan M, Caner B.

Department of Nuclear Medicine, School of Medicine, Hacettepe University, Ankara, Turkey. goncakara@yahoo.com

The authors describe the incidence and various uptake patterns of Tc-99m sestamibi (MIBI) in the extracardiac area due to unusual causes on myocardial perfusion single photon emission computed tomography (SPECT) studies. Seven patients are presented in whom incidental extracardiac findings were observed during the interpretation of the raw data besides the routine evaluation of myocardial reconstructed SPECT slices. These 7 patients were detected out of 582 consecutive patients (1.2%) who had myocardial perfusion SPECT with Tc-99m MIBI. The findings on the raw data led to additional reconstruction of thoracic SPECT images and eventually detailed examination of the extracardiac area. Two of the patients underwent surgery because of incidental extracardiac findings (thymoma and multinodular goiter) on cardiac scintigraphy. Other causes of increased extracardiac activity were the intestine protruded through the left hemithorax, uptake in the pulmonary arterial wall, and pulmonary interstitial fibrosis due to sarcoidosis. The reasons for decreased Tc-99m MIBI accumulation in the extracardiac area in the 2 other patients were significantly dilated pulmonary arteries and hydatic cyst, which were not defined before to our knowledge. Familiarity with the normal biodistribution and variable uptake patterns in the raw images becomes necessary during the interpretation of myocardial SPECT in order not to miss very unusual incidental extracardiac uptake or information that could lead to alteration in patient management. Potential underlying mechanisms of extracardiac Tc-99m MIBI accumulation are discussed, and the literature about noncardiac Tc-99m MIBI findings detected on myocardial perfusion SPECT studies was reviewed.

PMID: 18030041 [PubMed - in process]

14: Endocrinology. 2007 Dec;148(12):5933-42. Epub 2007 Sep 6.
Related Articles, Links

Role of insulin receptor substrate-1 serine 307 phosphorylation and adiponectin in adipose tissue insulin resistance in late pregnancy.

Sevillano J, de Castro J, Bocos C, Herrera E, Ramos MP.

Facultad de Farmacia, Universidad CEU-San Pablo, Crta. Boadilla Km 5, 3, Madrid, Spain.

Insulin resistance is a hallmark of late pregnancy both in human and rat. Adipose tissue is one of the tissues that most actively contributes to this reduced insulin sensitivity. The aim of the present study was to characterize the molecular mechanisms of insulin resistance in adipose tissue at late pregnancy. To this end, we analyzed the insulin signaling cascade in lumbar adipose tissue of nonpregnant and pregnant (d 20) rats both under basal and insulin-stimulated conditions. We found that the levels of relevant signaling proteins, such as insulin receptor (IR), IR substrate-1 (IRS-1), phosphatidylinositol 3-kinase, 3-phosphoinositide-dependent kinase-1, ERK1/2, and phosphatase and tensin homolog (PTEN) did not change at late pregnancy. However, insulin-stimulated tyrosine phosphorylation of both IR and IRS-1 were significantly decreased, coincident with decreased IRS-1/p85 association and impaired phosphorylation of AKR mouse thymoma viral protooncogene (Akt) and ERK1/2. This impaired activation of IRS-1 occurred together with an increase of IRS-1 phosphorylation at serine 307 and a decrease in adiponectin levels. To corroborate the role of IRS-1 in adipose tissue insulin resistance during pregnancy, we treated pregnant rats with the antidiabetic drug englitazone. Englitazone improved glucose tolerance, and this pharmacological reversal of insulin resistance was paralleled by an increase of adiponectin levels in adipose tissue as well as by a reduction of IRS-1 serine phosphorylation. Furthermore, the impaired insulin-stimulated tyrosine phosphorylation of IRS-1 in adipose tissue of pregnant animals could be restored ex vivo by treating isolated adipocytes with adiponectin. Together, our findings support a role for adiponectin and serine phosphorylation of IRS-1 in the modulation of insulin resistance in adipose tissue at late pregnancy.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17823255 [PubMed - in process]

15: Eur J Cardiothorac Surg. 2007 Dec;32(6):848-51. Epub 2007 Oct 29.
Related Articles, Links: Thoracoscopic resection of bulky intrathoracic benign lesions.

Gossot D, Izquierdo RR, Girard P, Stern JB, Magdeleinat P.

Thoracic Department, Institut Mutualiste Montsouris, 42 Bd Jourdan, F-75014 Paris, France. dominique.gossot@imm.fr

BACKGROUND: Video-assisted thoracic surgery (VATS) is used for the diagnosis and treatment of some mediastinal lesions. However, large-size tumours are usually approached by thoracotomy or sternotomy. We report our experience of a full thoracoscopic approach for bulky intrathoracic lesions. METHODS: From November 2002 to March 2007, 14 patients with a bulky intrathoracic mass were referred for resection. The study group consisted of eight females and six males with a mean age of 44 years (range: 13-74). We defined as bulky a mass with a minimal cross-sectional diameter equal to or larger than 50 mm, as measured on the specimen by the pathologist. RESULTS: Thoracoscopic resection was completed in all patients. In 4 cases, the mass originated from the pleura, and in 10 cases from the mediastinum. The larger diameter of the lesion ranged from 50 mm to 160 mm, with a median of 90.2 mm. Operative time, calculated from insertion of the first trocar to skin closure, ranged from 40 to 190 min (mean: 102). Mean chest drain duration was 2.1 days (range: 1-4 days) and the mean hospital stay was 4.3 days (range: 3-11 days). There were no major postoperative complications. The final pathological diagnoses were the following: solitary fibrous tumours of the pleura (4), benign thymic cysts (2), teratomas (2), bronchogenic cyst (1), benign thymoma (1), pleuropericardial cyst (1) and benign neurogenic tumours (3). CONCLUSIONS: With experience and use of appropriate instrumentation, resection of bulky intrathoracic lesions by thoracoscopy is feasible and safe. It should be considered as a reliable alternate for tumours that are benign and most often asymptomatic.

PMID: 17913504 [PubMed - in process]

16: Eur J Surg Oncol. 2007 Dec;33(10):1137-41. Epub 2007 Apr 17.
Related Articles, Links

Primary intrapulmonary thymoma: a systematic review.

Myers PO, Kritikos N, Bongiovanni M, Triponez F, Collaud S, Pache JC, Robert JH.

Department of Cardiovascular Surgery, University Hospitals of Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. patrick.myers@hcuge.ch

AIM: This article reviews the literature on the clinical features, diagnosis and management of primary intrapulmonary thymoma. METHODS: Medline, Embase and Cochrane Library searches were performed on all relevant Anglo-Saxon language articles. The search words included "primary pulmonary thymoma" and "intrapulmonary thymoma". Secondary references were obtained from key articles. Prognostic and treatment strategies were analyzed by the Kaplan-Meier method, comparisons between curves were made using log rank test. RESULTS: The searches yielded 25 cases of primary intrapulmonary thymoma. Median follow-up was 9 months (1 day to 13 years). At follow-up, 14 patients were tumor free, one patient had a local recurrence 8 years after radiotherapy, one patient responded favorably to radiotherapy, six patients died and three patients were lost to follow-up. The presence of a paraneoplastic syndrome decreased survival (P=0.02), however, histological subgroup (P=0.216), clinical stage (P=0.63) and tumor size (P=0.288) did not affect survival. Survival in surgically managed patients was significantly better than in conservatively managed patients (P=0.039). Adjuvant radiotherapy did not provide any benefit (P=0.4). CONCLUSION: Complete resection of primary intrapulmonary thymomas appears sufficient in non-malignant tumors. Because of the risk of late local recurrence, long-term regular clinical follow-up is warranted.

Publication Types:

Review

PMID: 17442530 [PubMed - indexed for MEDLINE]

17: Gen Thorac Cardiovasc Surg. 2007 Dec;55(12):515-7. Epub 2007 Dec 11.
Related Articles, Links: Thymoma with spontaneous regression and disappearance of pleural effusion.

Okagawa T, Uchida T, Suyama M.

Department of Chest Surgery, Aichi Cancer Center, Aichi Hospital, 18 Kuriyado, Kake-machi, Okazaki, Aichi, 444-0011, Japan, tokagwa@acc-aichi.com.

A 31-year-old woman was admitted to our hospital with sudden onset of chest pain. Chest radiography and computed tomography (CT) on admission showed an anterior mediastinal tumor with left pleural effusion, which was diagnosed as an inoperable malignant mediastinal tumor. However, 3 weeks after admission CT showed that the tumor was diminishing and the pleural effusion had disappeared without any treatment. CT-guided needle biopsy was performed, but diagnosis was impossible because most of the specimen was necrotic. A biopsy during video-assisted thoracic surgery was then performed. The intraoperative finding showed that the tumor was round, well mobilized, and did not invade adjacent structures. It was then assumed to be a benign teratoma that had been ruptured into the thoracic cavity. The operation was converted to a thoracotomy to resect it, but it could not be completely resected because of inflammatory adhesions to the mediastinum. Two months later, total thymectomy was performed through a median sternotomy because the tumor was pathologically diagnosed as a thymoma.

PMID: 18066646 [PubMed - in process]

18: Heart Lung Circ. 2007 Dec;16(6):462-4. Epub 2007 Apr 10.
Related Articles, Links: Superior vena cava obstruction by tumour thrombus in invasive thymoma: diagnosis and surgical management.

Konstantinov IE, Saxena P, Koniuszko M, Ghosh S, Low VH, Khor TS, Naran A, Newman MA.

Department of Cardiothoracic Surgery, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.

Thymomas are common mediastinal tumours. We report a rare case of thymoma invasion into the superior vena cava with resultant venous obstruction. The tumour was resected. The superior vena cava and left brachiochephalic vein were reconstructed with autologous pericardial patch.

PMID: 17428732 [PubMed - in process]

19: J Cardiothorac Vasc Anesth. 2007 Dec;21(6):867-9. Epub 2007 Jan 25.
Related Articles, Links: Peripheral cardiopulmonary bypass-assisted thymoma resection.

Soon JL, Poopalalingam R, Lim CH, Koong HN, Agasthian T.

Department of Cardiothoracic Surgery, National Heart Centre, Singapore.

PMID: 18068069 [PubMed - in process]

20: J Thorac Cardiovasc Surg. 2007 Dec;134(6):1477-83; discussion 1483-4. Epub 2007 Oct 26.
Related Articles, Links: Feasibility of multimodality therapy including extended resections in stage IVA thymoma.

Huang J, Rizk NP, Travis WD, Seshan VE, Bains MS, Dycoco J, Downey RJ, Flores RM, Park BJ, Rusch VW.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

OBJECTIVE: Extended resections for advanced-stage thymomas are not commonly performed because of the potential morbidity in the face of unclear survival or palliative benefit. We reviewed our experience with multimodality treatment for Masaoka stage IVA thymomas for feasibility and outcomes. METHODS: We conducted a retrospective review of a single-institution surgical database. Data included patient demographics, preoperative staging and treatment, perioperative events, pathologic findings, and postoperative outcomes. RESULTS: During the period from 1996 to 2006, 18 patients who had Masaoka stage IVA thymoma underwent surgical resection. All patients received preoperative chemotherapy. Four patients with extensive pleural involvement underwent concomitant extrapleural pneumonectomy and postoperative hemithoracic radiation. Complete resection was achieved in 12 (67%) patients. There was no operative mortality. With a median follow-up of 32.2 months (range 1.4-129.9 months), 3-year, 5-year, and 10-year survivals were 91%, 78%, and 65%, respectively, and median survival has not yet been reached. CONCLUSION: Multimodality therapy including extended surgical resection can be performed in select patients with stage IVA thymoma with low morbidity and mortality and can result in excellent long-term survival.

PMID: 18023668 [PubMed - indexed for MEDLINE]

21: J Thorac Oncol. 2007 Dec;2(12):1130-2.
Related Articles, Links: Thymoma-associated graft-versus-host disease-like erythroderma.

Nakagiri T, Okumura M, Inoue M, Minami M, Kiyohara E, Umegaki N, Nakamura T, Tomita Y, Katayama I, Aozasa K.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.

We report a 40-year-old woman with recurrent thymoma associated with myasthenia gravis, in whom an unusual form of erythroderma developed. A histological examination revealed a graft-versus-host disease (GVHD)-like reaction. After high-dose steroid therapy, the metastatic thymoma lesion in the abdominal cavity was reduced in size from 9.5 x 6 x 7.5 cm to 4 x 3 x 1 cm in diameter. Nevertheless, the GVHD-like erythroderma become aggravated, her condition worsened, and the patient finally suffered from respiratory failure and died of sepsis. A GVHD-like reaction may be a rare presentation of thymoma-associated immunological disorders such as myasthenia gravis or pure red cell aplasia. Herein, we discuss the present case and review pertinent reports of thymoma cases associated with GVHD.

PMID: 18090589 [PubMed - in process]

22: Neuromuscul Disord. 2007 Dec;17(11-12):935-42. Epub 2007 Jul 24.
Related Articles, Links: Muscle lymphocytic infiltrates in thymoma-associated myasthenia gravis are phenotypically different from those in polymyositis.

Zamecnik J, Vesely D, Jakubicka B, Simkova L, Pitha J, Schutzner J, Mazanec R, Vogel H.

Department of Pathology and Molecular Medicine, Charles University, 2nd Medical Faculty and Faculty Hospital Motol, V Uvalu 84, 150 06 Prague, Czech Republic.

The aim of the study is to provide evidence that the lymphocytic infiltration of myasthenia gravis (MG) muscle do not represent a true autoimmune myositis, rather an infiltration by naive lymphocytes derived from lymphocyte-rich thymomas. Muscle biopsies from 179 patients with pure MG, 6 thymoma patients without MG and 15 patients with definite polymyositis were analyzed. In 18 patients with MG (all associated with lymphocyte-rich thymomas) and in two thymoma patients without MG, lymphocytic infiltrates were identified in muscles. By use of immunohistochemistry, we demonstrated that the lymphocytes in MG differ from those in polymyositis, being mature but in contrast to polymyositis naive CD45RA+ T lymphocytes. We suggest that the lymphocytic infiltrates in patients with MG and thymoma represent an infiltration of muscle by thymoma-derived mature but naive T cells. The finding of CD8+CD45RA+ lymphocytes in muscle may signify an underlying thymoma and should not be misdiagnosed as polymyositis.

PMID: 17651972 [PubMed - in process]

23: Pediatr Blood Cancer. 2007 Dec;49(7):1004-7.
Related Articles, Links

Thymic carcinoma in a child with HIV infection.

McDonald M, McLean T, Belhorn T, Smith SV, Fordham LA, Woods C, Blatt J.

Division of Pediatric Hematology-Oncology, The University of North Carolina, Chapel Hill, North Carolina 27599-7220, USA.

HIV infection predisposes to cancer during childhood. In addition to the AIDS-defining non-Hodgkin lymphoma (NHL) and Kaposi sarcoma, a range of other lymphoid malignancies and solid tumors have been described. We report the first case of an HIV-positive child with thymic carcinoma in the setting of regressing thymic cysts. The tumor expressed CKIT but failed to respond to imatinab mesylate after a transient response to multiagent chemotherapy. This case extends the spectrum of pediatric malignancy in the setting of HIV and suggests that patients with presumed benign thymic cysts require ongoing surveillance. 2007 Wiley-Liss, Inc

Publication Types:

Case Reports

PMID: 16317759 [PubMed - indexed for MEDLINE]

24: Immunol Lett. 2007 Nov 30;114(1):31-7. Epub 2007 Sep 29.
Related Articles, Links: Graft-versus-host-like disease complicating thymoma: lack of AIRE expression as a cause of non-hereditary autoimmunity?

Offerhaus GJ, Schipper ME, Lazenby AJ, Montgomery E, Morsink FH, Bende RJ, Musler AR, van Lier RA, van Noesel CJ.

Department of Pathology, University Medical Center Utrecht, The Netherlands.

Three patients with graft-versus-host-like enterocolonopathy are reported. Their history was remarkable for thymoma and other autoimmune manifestations such as thrombocytopenia, red cell aplasia, interface dermatitis, Sjogren sialadenits, vanishing bile ducts and rheumatoid arthritis. In all patients, microsatellite analysis showed the autologous nature of the lymphocytes in the affected organs ruling out GVHD. In search for mechanisms that could mediate loss of tolerance to self-antigens we found in a panel of thymomas, including those of the three patients, a complete lack of autoimmune regulator (AIRE) and minimal expression of the transcription factor FOXP3 in the intra-tumoral T cells. AIRE is a recently discovered transcription factor which plays a key role in the maintenance of central tolerance and is mutated in the autosomal recessive autoimmune polyendocrinopathy syndrome APS-1. Our observations indicate that thymoma-related autoimmunity can potentially be elicited by an incomplete deletion of 'self'-specific T cells in concert with an insufficient formation of natural Tregs.

PMID: 17928069 [PubMed - in process]

25: Mol Cell Biol. 2007 Nov 26 [Epub ahead of print]
Related Articles, Links: Differential chromatin looping regulates CD4 expression in immature thymocytes.

Jiang H, Peterlin BM.

Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, CA, 94143.

Runx1 binds the silencer and represses CD4 transcription in immature thymocytes. In this study, using looping-ChIP and 3C, we demonstrated that interactions between Runx1 and P-TEFb appose the silencer and enhancer in CD4-negative thymoma cells and double negative immature thymocytes. This chromatin loop decoys P-TEFb away from the promoter thus preventing RNA polymerase II from elongating on the CD4 gene. In the absence of Runx1 on the silencer, P-TEFb interacts with the transcription complex, forming a different chromatin loop between the enhancer and promoter, which leads to the expression of the CD4 gene in CD4-positive hybridoma cells and double positive thymocytes. Moreover, the knockdown of CycT1 from P-TEFb abolishes both of these chromatin loops. Finally, the selective removal and restoration of Runx1 causes rapid interchanges between these chromatin loops, which reveals the plasticity of this regulatory circuit. Thus, differential looping and decoying P-TEFb away from the promoter mediate active repression of the CD4 gene during thymocyte development.

PMID: 18039856 [PubMed - as supplied by publisher]

26: Spine J. 2007 Nov 21 [Epub ahead of print]
Related Articles, Links: Metastasis of carcinoid to the arch of the axis in a multiple endocrine neoplasia patient: a case report.

Tanabe M, Akatsuka K, Umeda S, Shomori K, Taniura S, Okamoto H, Kamitani H, Watanabe T.

Department of Neurosurgery, Gamma-Knife Center, Takashima Hospital, Yonago 6830826, Japan; Department of Neurosurgery, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago 6838504, Japan.

BACKGROUND CONTEXT: Carcinoid tumors eventually metastasize to the spine, and epidural spinal cord compression is a relatively frequent neurologic complication of carcinoid. However, a case of multiple endocrine neoplasia type 1 (MEN1) presenting with spinal cord compression as a result of a metastatic carcinoid tumor has not been reported previously. PURPOSE: To report an extremely rare case of MEN1 presenting with spinal cord compression by metastatic carcinoid tumor. STUDY DESIGN: Case report. METHODS: A 51-year-old man, with a past history of thymoma, insulinoma, and gastric carcinoid presented with neck pain. Neuroradiological examination revealed that a tumor around the arch of the axis compressed the spinal cord with osteoblastic changes. RESULTS: After hemilaminectomy of the axis and removal of the tumor followed by irradiation, the patient returned to his previous job. Histological examination confirmed metastatic carcinoid tumor. CONCLUSIONS: Spinal metastasis of carcinoid tumor occurred in a multiple endocrine neoplasia patient, and it is significant to note that carcinoid metastasis is one of differential diagnoses for osteoblastic lesions.

PMID: 18037349 [PubMed - as supplied by publisher]

27: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18660-5. Epub 2007 Nov 14.
Related Articles, Links

IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells.

Ali S, Huber M, Kollewe C, Bischoff SC, Falk W, Martin MU.

Immunology FB08, Justus-Liebig-University Giessen, Winchesterstrasse 2, D-35394 Giessen, Germany.

Lack of the IL-1 receptor accessory protein (IL-1RAcP) abrogates responses to IL-33 and IL-1 in the mouse thymoma clone EL-4 D6/76 cells. Reconstitution with full-length IL-1RAcP is sufficient to restore responsiveness to IL-33 and IL-1. IL-33 activates IL-1 receptor-associated kinase-1, cJun-N-terminal kinase, and the NF-kappaB pathway in an IL-1RAcP-dependent manner and results in IL-2 release. IL-33 is able to induce the release of proinflammatory cytokines in bone marrow-derived (BMD) mast cells, indicating that IL-33 may have a proinflammatory potential like its relatives IL-1 and IL-18, in addition to its Th2-skewing properties in the adaptive response described previously. Blocking of murine IL-1RAcP with the neutralizing antibody 4C5 inhibits response of mouse thymoma cells and BMD mast cells to IL-33. The interaction of either membrane-bound or soluble forms of IL-1RAcP and IL-33Ralpha-chain depends on the presence of IL-33, as demonstrated by coimmunoprecipitation assays. These data demonstrate that IL-1RAcP is indispensable for IL-33 signaling. Furthermore, they suggest that IL-1RAcP is used by more than one alpha-chain of the IL-1 receptor family and thus may resemble a common beta-chain of that family.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 18003919 [PubMed - in process]

28: Eur J Radiol. 2007 Nov 17 [Epub ahead of print]
Related Articles, Links: Anterior mediastinal tumors: Diagnostic accuracy of CT and MRI.

Tomiyama N, Honda O, Tsubamoto M, Inoue A, Sumikawa H, Kuriyama K, Kusumoto M, Johkoh T, Nakamura H.

Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

PURPOSE: To compare the diagnostic accuracy for anterior mediastinal tumors among CT, MRI, and both CT and MRI, and to determine the optimal CT and MRI procedures for the diagnosis of anterior mediastinal tumors. MATERIALS AND METHODS: Both CT and MRI were performed in 127 patients with pathologically diagnosed anterior mediastinal tumors. The patients included 48 cases of thymoma, 12 cases of thymic carcinoma, 12 cases of thymic cyst, 20 cases of mature teratoma, 13 cases of malignant germ cell tumor, and 22 cases of malignant lymphoma. The CT and MRI scans were assessed by two chest radiologists without knowledge of their clinical and pathologic data. The observers recorded various CT and MRI findings and their first choice of diagnosis. RESULTS: The two observers made a correct first-choice diagnosis in an average of 78 (61%) of 127 cases on CT, 71 (56%) of 127 cases on MRI, and 85.5 (67%) of 127 cases on both CT and MRI. These included 83% cases of thymoma on CT, 84% on MRI, and 85% on both CT and MRI; 38% cases of thymic carcinoma on CT and 13% on MRI, and 33% on both CT and MRI; 46% cases of thymic cyst on CT and 71% on MRI, and 63% on both CT and MRI; 58% cases of mature teratoma and 38% on MRI, and 78% on both CT and MRI; 35% cases of malignant germ cell tumor on CT and 27% on MRI, and 31% on both CT and MRI; and 55% cases of malignant lymphoma on CT and 43% on MRI, and 61% on both CT and MRI. There were significant differences between the diagnostic accuracy by CT and MRI in the cases with both thymic cysts and thymic carcinoma (p<0.05). CONCLUSION: CT is equal or superior to MRI in the diagnosis of anterior mediastinal tumors except for thymic cyst. CT should be considered the modality of choice following chest radiography, however, in certain circumstances, such as thymic cyst with hemorrhage or inflammation which mimic solid tumor despite low enhancement, MRI may be better in distinguishing anterior mediastinal tumors. For more helpful information in the diagnosis of mature teratoma after CT, MRI may follow.

PMID: 18023547 [PubMed - as supplied by publisher]

29: J Clin Immunol. 2007 Nov 14 [Epub ahead of print]
Related Articles, Links: Thymopoiesis, Regulatory T Cells, and TCRVbeta Expression in Thymoma With and Without Myasthenia Gravis, and Modulatory Effects of Steroid Therapy.

Fattorossi A, Battaglia A, Buzzonetti A, Minicuci G, Riso R, Peri L, Scambia G, Evoli A.

Laboratory of Immunology, Oncology Department, Catholic University, Campobasso, Italy, cytogyn@rm.unicatt.it.

We analyzed thymocyte and thymic regulatory T cell (CD4SPCD25(+)Foxp3(+)cells, Treg) development in thymoma with and without myasthenia gravis (MG, MG-thymoma, non-MG-thymoma) and in MG-associated non-neoplastic thymus (MG-NNT). An increased number of immature CD4(+)CD8(-)CD3(-) thymocytes through the CD4(+)CD8(+) to CD4(+)CD8(-) transition and an abnormal T cell receptor Vbeta (TCRVbeta) development through the CD4(+)CD8(+) to CD4(-)CD8(+) transition were seen both in MG-and non-MG-thymomas. Terminal thymopoiesis, i.e., CD45RA(+) cells within the CD4(+)CD8(-)CD3(+) and CD8(+)CD4(-)CD3(+) subsets, was skewed towards the CD4(+) compartment in MG-thymoma and CD8(+) compartment in non-MG-thymoma, but thymic export was increased only in the latter in keeping with the hypothesis that CD8(+) lymphocytes may play a role in the initial stages of autosensitization and in disagreement with the relevance of an increased output of CD4(+) T lymphocytes in paraneoplastic MG. Treg level in normal thymus and MG-NNT and both MG- and non-MG-thymoma was similar, and TCRVbeta development in Treg cells was slightly altered in thymoma but irrespective of MG presence. Thus, the relevance of a defective Treg development in MG context remains to be established. Most alterations in thymopoiesis were corrected by therapeutic corticosteroid administration, and the effects of steroid administration may be mediated by thymic microenvironment.

PMID: 18000743 [PubMed - as supplied by publisher]

30: Vaccine. 2007 Nov 7;25(45):7763-72. Epub 2007 Sep 20.
Related Articles, Links

Enhanced antigen delivery via cell death induced by the vaccine adjuvants.

Yang YW, Shen SS.

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

The objective of this study was to examine the effect of cell death induced by the emulsion adjuvants on the in vitro delivery of antigens into the antigen-presenting cells (APCs). J774A.1 murine macrophage-like cells, serving as the APCs, were pulsed with various vaccine adjuvants, and incubated with fluorescein isothiocyanate-conjugated bovine serum albumin (BSA-FITC), with or without adjuvants-pretreated EL4 murine thymoma cells, followed by analysis by flow cytometry and fluorescence microscopy. To assess the potential oxidative burst in the macrophages after adjuvant treatment, cells were probed with 2',7'-dichlorofluorescein diacetate (DCFH-DA) and hydroethidine (HE), and analyzed by flow cytometry. Treatment of macrophages with the emulsion adjuvants, followed by co-incubation with the adjuvant-induced dead EL4 cells, resulted in a substantial uptake of soluble antigens into the APCs and generation of a considerable amount of reactive oxygen species (ROS), including hydrogen peroxide and superoxide. Pre-treatment of J774A.1 cells with several endocytosis inhibitors, including amiloride, brefeldin A or cytochalasin B, on the other hand, reduced internalization of soluble antigens. It was concluded that co-treatment of macrophages with the emulsion adjuvants and the adjuvant-induced dead cells facilitated delivery of soluble antigens, via both phagocytosis and macropinocytosis, into the antigen-presenting cells.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17928111 [PubMed - in process]

31: Biol Reprod. 2007 Nov;77(5):813-21. Epub 2007 Jul 18.
Related Articles, Links

Direct evidence for the action of phosphatidylinositol (3,4,5)-trisphosphate-mediated signal transduction in the 2-cell mouse embryo.

Li Y, Chandrakanthan V, Day ML, O'Neill C.

Disciplines of Medicine and Physiology, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.

Paf (1-o-alkyl-2-acetyl-sn-gylcero-3-phosphocholine) is a putative autocrine survival factor for the preimplantation embryo. It acts to induce receptor-mediated calcium transients in the early embryo. Inhibitors of 1-o-phosphatidylinositol-3-kinase (PI3kinase), such as wortmannin and LY 294002, blocked these calcium transients, implicating the generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in autocrine signal transduction in the early embryo. Perfusion of the embryo cytoplasm with a blocking antibody to PIP3 inhibited paf-induced calcium transients and hyperpolarization of the membrane potential. Furthermore, direct infusion of PIP3 into the embryo induced a nifedipine (10 micromol/L)- and diltiazem (10 micromol/L)-sensitive calcium current in the 2-cell embryo. PIP3 acts as a docking site on membranes for proteins that contain pleckstrin homology domains, such as the thymoma viral proto-oncogene protein (AKT) and phospholipase C gamma. The 2-cell embryo expressed three genes for AKT (Akt 1-3) and two genes for phospholipase C gamma (Plcg1 and Plcg2), and we confirmed the expression of both AKT and phospholipase C gamma 1 by immunolocalization. Paf induced increased accumulation of serine 473-phosphorylated AKT in the region of the plasma membrane, consistent with its recruitment to membrane PIP3. Inhibitors of PI3kinase, such as LY294002, and of AKT, e.g., deguelin and AKT-inhibitor, reduced zygote development in a dose-dependent manner, and this inhibition was partially reversed by the addition of paf to the culture medium. These results provide the first direct evidence that PIP3 and its responsive signaling pathways act in the 2-cell embryo. Since signal transduction via PI3kinase has important roles in governing the cell survival pathways, these results support the hypothesis that autocrine embryotropins, such as paf, act as survival factors.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17634444 [PubMed - in process]

32: Biol Reprod. 2007 Nov;77(5):872-9. Epub 2007 Jul 11.
Related Articles, Links

Insulin signaling in mouse oocytes.

Acevedo N, Ding J, Smith GD.

Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan 48109, USA.

Continuous exposure of follicles/oocytes to elevated levels of insulin compromises embryonic developmental competence, although the underlying cellular mechanisms are unknown. The objectives of the present study were to determine whether mouse oocytes have insulin receptors and a functional insulin signaling cascade, and whether insulin exposure during oocyte growth or maturation influences meiotic progression and chromatin remodeling. Immunoblot and immunocytochemical analyses of germinal vesicle-intact (GVI) oocytes demonstrated the presence of insulin receptor-beta. Insulin receptor expression in oocytes was increased by gonadotropin stimulation, and remained elevated throughout meiotic maturation. Fully grown GVI oocytes contained 3-phosphoinositide-dependent protein kinase-1 (PDPK1), thymoma viral proto-oncogene 1 (AKT1), and glycogen synthase kinase 3 (GSK3). In vitro maturation of GVI oocytes in 5 microg/ml insulin had no influence on meiotic progression or the incidence of normal metaphase II (MII) chromosome condensation. Treatment of oocytes during maturation had no effect on GSK3A/B protein expression or phosphorylation of S21/9. However, the culturing of preantral follicles for 10 days with 5 microg/ml insulin increased the phosphorylation of oocyte GSK3B, indicating GSK3 inactivation. The rates of development to metaphase I (MI) were similar for oocytes obtained from insulin-treated follicles and controls, whereas the incidence of abnormal MI chromatin condensation was significantly higher in oocytes obtained from follicles cultured with insulin compared to those cultured without insulin. These results demonstrate that oocytes contain a functional insulin signaling pathway, and that insulin exposure during oocyte growth results in chromatin remodeling aberrations. These findings begin to elucidate the mechanisms by which chronic elevated insulin influences oocyte meiosis, chromatin remodeling, and embryonic developmental competence.

Publication Types:

Research Support, N.I.H., Extramural

PMID: 17625112 [PubMed - in process]

33: Clin Rheumatol. 2007 Nov;26(11):1981-3. Epub 2007 Apr 6.
Related Articles, Links: Microscopic polyangiitis and myasthenia gravis: the battle of Occam and Hickam.

Holmes MV, Sen D.

Centre for Rheumatology, University College Hospital, 3rd Floor Central, 250 Euston Road, London, NW1 2PQ, UK.

Microscopic polyangiitis (MPA) is a pauci-immune, necrotising, small-vessel vasculitis with an incidence of 3.6 per million population that typically presents in adulthood. Myasthenia gravis (MG), the most common disorder of the neuromuscular junction is rare, with an incidence of four per million population. We present the case of an adolescent girl previously diagnosed with MPA at age 7 years who presented with breathlessness and respiratory failure aged 15 years. The respiratory symptoms were due to thymoma-MG, which was successfully treated with cholinesterase inhibitors and thymectomy. This case report illustrates that the well-established doctrines of Occam's razor and of 'common conditions occurring commonly' are not universally applicable, and that in the adolescent age group, one should still consider Hickam's dictum.

PMID: 17415507 [PubMed - in process]

34: Diagn Cytopathol. 2007 Nov;35(11):705-9.
Related Articles, Links: Diagnostic accuracy of image-guided percutaneous fine needle aspiration biopsy of the mediastinum.

Assaad MW, Pantanowitz L, Otis CN.

Baystate Medical Center, Tufts University School of Medicine, Springfield, A 01199, USA.

Interpreting a fine needle aspiration biopsy (FNAB) from the mediastinum is challenging as this location may harbor many lesions, including primary and metastatic tumors. Image-guided transthoracic (percutaneous) FNAB is less invasive than mediastinoscopy or endoscopic-guided FNAB. The aim of this study was to determine the diagnostic accuracy of FNAB performed percutaneously for evaluating mediastinal lesions.A retrospective study of 157 consecutive CT-guided transthoracic FNAB of the mediastinum was performed (1988-2004). Direct smears (N = 145; average 13 slides/case), ThinPrep slides (N = 25), and adequate cell blocks (N = 131) were prepared from procured cytologic material. When needed, ancillary studies included immunocytochemistry (N = 53) and flow cytometry (N = 8). Subsequent histologic tissue diagnoses available for 68 cases were also reviewed.Patients were of average age 57 yr (range 1-88 yr), including 75 males and 82 females. A definitive diagnosis was rendered in 128 (82%) cases. Primary neoplasms (N = 38) included 24 lymphomas (6 Hodgkin and 18 non-Hodgkin), 7 thymomas, 1 thymic carcinoma, and 6 peripheral nerve sheath tumors. Metastases (N = 72) were mainly carcinomas (N = 71) and 1 melanoma. There were 4 non-neoplastic lesions (1 granulomatous process; 2 bronchogenic and 1 pericardial cyst), 1 case of undifferentiated malignant large cell neoplasm, 13 cases negative for malignancy, and 29 (18%) that were indeterminate, due largely to insufficient cellularity. Subsequent histologic diagnoses were concordant with FNAB diagnoses in 53/68 cases (78%). Nine FNAB were inadequate/nondiagnostic. There were 6 discordant cases, including 5 FNAB that were of adequate cellularity but interpreted as negative for malignant cells (on subsequent histology 2 turned out to be Hodgkin lymphoma, 2 carcinomas, and 1 diffuse large cell lymphoma), and 1 diagnosed as thymoma that on histologic evaluation was a thymic large cell lymphoma.Adequate diagnostic cytologic material was obtained by image-guided percutaneous FNAB of mediastinal lesions in 82% of our cases. Sufficient material was available to make cell blocks and perform ancillary studies when necessary. These data also show a high proportion of agreement (78%) between FNAB and subsequent histologic diagnoses for a wide variety of mediastinal lesions. The majority of discordant cases were primarily interpretive, with a final cytologic diagnosis negative for malignancy. Only one problematic case misdiagnosed on FNAB as thymoma was found on subsequent surgical excision to be a thymic large B cell lymphoma. Cases with nondefinitive FNAB diagnoses were largely due to sampling error and/or insufficient cellularity. Therefore, percutaneous FNAB of the mediastinum is a diagnostically helpful, minimally invasive procedure that can be performed in patients of all ages as part of the evaluation of a mediastinal mass lesion. (c) 2007 Wiley-Liss, Inc.

PMID: 17924408 [PubMed - in process]

35: Int J Neurosci. 2007 Nov;117(11):1603-10.
Related Articles, Links: Myasthenia gravis accompanied by thymomas not related to foamy virus genome in Belarusian's patients.

Kuzmenok OI, Dvoryanchikov GA, Ponomareva EN, Goncharov AA, Fomin IK, Lee ST, Sanberg PR, Potapnev MP.

Belarusian Research & Production Center for Hematology & Transfusiology, Minsk, Republic of Belarus. okuzmeno@hsc.usf.edu

The spectrum and features of neurological disorders have been changed due to the Chernobyl catastrophe in the Republic of Belarus. More recently neurologists in Belarus have noted a significant increase in the frequency of myasthenia gravis (MG) with concomitant rise in the thymomas. There is some evidence suggesting that retroviruses play a key role in the development and pathogenesis of autoimmune diseases. This study analyzed thymomas from 45 MG patients from the Republic of Belarus by using PCR and primers for two regions of FV--gag and bel-2 genes. The results showed that none of the varied thymuses from the 45 MG patients contained FV genome. No relationship can be confirmed between FV and this disease and the results suggest that no pathological link between FV and MG exists.

PMID: 17917929 [PubMed - indexed for MEDLINE]

36: J Clin Neurosci. 2007 Nov;14(11):1116-20. Epub 2007 Feb 2.
Related Articles, Links: Multiple brain metastases from malignant thymoma.

Ersahin M, Kilic K, Gögüsgeren MA, Bakirci A, Vardar Aker F, Berkman Z.

Department of Neurosurgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.

A rare case of thymic carcinoma with multiple brain metastasis is reported. In our extensive review of the literature only six of 30 reports of intracranial thymoma metastasis describe multiple metastases. A 38-year-old man presented with signs of raised intracranial pressure that had began 15 days previously. Cranial MRI revealed over 70 cystic lesions in the supra and infratentorial regions. Stereotactic biopsy was planned. On the second day of his admission he deteriorated and died the following day. The autopsy revealed a mass in the mediastinum. In the brain parenchyma were multiple cystic lesions between 0.5 and 3 cm in diameter. Histopathologically they were diagnosed as metastases from the thymic carcinoma. The mean survival with a single brain metastasis is approximately 256 days, whereas with multiple brain metastases it is only 64 days, thus treatment of this tumor demands prompt surgery whenever possible and optimal adjuvant therapy.

PMID: 17276689 [PubMed - in process]

37: J Coll Physicians Surg Pak. 2007 Nov;17(11):658-61.
Related Articles, Links: Thymoma : a clinicopathologic association of world health organization histologic subtype and invasive behaviour.

Azad NS, Ahmad Z, Ahsan A, Fatimi S, Ahmed R, Kayani N, Pervez S, Hasan SH.

Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi.

Objective: To re-classify thymic epithelial neoplasms reported at Aga Khan University Hospital during the past seven years according to the revised WHO classification, to assess the ease of application and determine association between WHO histological subtype and invasive behaviour. Design: Descriptive study. Place and Duration of Study: The study was carried out in the section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, from January 2000 to October 2006. Material and Methods: All cases of thymic epithelial neoplasms reported in the past seven years were retrieved using SNOMED coding system. Small biopsies where the tissue was insufficient for definite classification were not included. All cases were reviewed and reclassified according to WHO classification into types A, AB, B1, B2 and B3. Capsular invasion as well as extension into neighboring structures such as perithymic fat, pleura, pericardium, lung etc. was noted on morphology. Results: A total of 62 cases were diagnosed as Thymic Epithelial Tumors (TET). Out of these, there were 5 type A (6 %), 17 type AB (21%), 7 type B1 (8.6%), 26 type B2 (32%) and 7 type B3 (8.6%) thymomas. Age range was from 22-78 years with a median age of 46 years. Male to female ratio was 6:1. History of associated myasthenia gravis was present in 21% of cases. A significant association was observed between WHO histologic subtype and invasive behaviour where types A, AB and B1 have lesser number of invasive cases as compared to non-invasive, whereas in types B2 and B3, more cases have shown invasion as compared to non-invasive cases (c2 = 14.093, df =1, p-value < 0.001 ). Conclusion: The WHO classification is simple and easy to apply and has significant association with aggressive behavior. To some extent, it reflects the clinical behaviour of thymomas along with stage and status of resection. However, morphologically benign looking thymomas can behave aggressively. Hence, tumour stage, extent of resection and histology should be combined to predict the clinical behaviour of thymomas.

PMID: 18070571 [PubMed - in process]

38: J Neurol. 2007 Nov;254(11):1601-3. Epub 2007 Aug 3.
Related Articles, Links: Myasthenia gravis, paraneoplastic pemphigus and thymoma, a rare triade.

Winkler DT, Strnad P, Meier ML, Roten S, Went P, Lyrer P, Steck AJ.

Dept. of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

PMID: 17668261 [PubMed - in process]

39: J Pediatr Hematol Oncol. 2007 Nov;29(11):797-8.
Related Articles, Links: Thymoma in the offspring of a patient with Isaacs syndrome.

Coulter D, Gold S.

Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7220, USA. dcoulter@unch.unc.edu

Thymoma is a diagnosis most often made in adults, and is exceedingly rare in children. The diagnosis of a thymoma is often times linked to an autoimmune process, and the association of thymoma and myasthenia gravis in children has been previously reported. We present the first description of a child of a parent with Isaacs syndrome (congenital or acquired neuromyotonia) presenting with a thymoma. In our patient, an evaluation of underlying disease led to a presumptive diagnosis of congenital Isaacs syndrome. This case demonstrates that for the rare child diagnosed with thymoma, evaluation for an underlying neurologic disorder should be considered.

PMID: 17984702 [PubMed - in process]

40: J Pediatr Hematol Oncol. 2007 Nov;29(11):774-5.
Related Articles, Links

Advanced pediatric inoperable thymus carcinoma (type C thymoma): case report on a novel therapeutic approach.

Kertesz GP, Hauser P, Varga P, Dabasi G, Schuler D, Garami M.

2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. gkertesz@yahoo.com

Although there has been considerable advancement in treatment techniques but still there are some illnesses that continue to exhibit a rather poor curability, such as thymoma. This report highlights the benefit of octreotide and prednisolone therapy in a 15-year-old girl, who was diagnosed with inoperable thymus carcinoma, with chemotherapy and radiotherapy being the last resort. The detection of type 2 somatostatin receptors on the surface of the tumor justified the introduction of treatment with somatostatin analog and prednisolone. Fortunately, after 6 months of this treatment, the tumor showed partial regression. However, 2 months later, somatostatin receptor negative metastases appeared; therefore, a switch over to imatinib became essential, because the tumor was CD-117 positive. Despite the therapy change, the patient's condition deteriorated owing to tumor progression.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17984697 [PubMed - in process]

41: J Thorac Cardiovasc Surg. 2007 Nov;134(5):1376-8.
Related Articles, Links

Four thymus-related syndromes in a case of invasive thymoma.

Lucchi M, Viti A, Ricciardi R, Murri L, Mussi A.

Division of Thoracic Surgery, Department of Cardiac and Thoracic Surgery, University of Pisa, Pisa, Italy. m.lucchi@med.unipi.it

Publication Types:

Case Reports

PMID: 17976491 [PubMed - indexed for MEDLINE]

42: Nihon Kokyuki Gakkai Zasshi. 2007 Nov;45(11):879-83.
Related Articles, Links

[Successful corticosteroid therapy of a recurrent thymoma with pure red cell aplasia]

[Article in Japanese]

Koshio J, Tsukada H, Nagasawa Y, Maeda T, Yokoyama A.

Department of Internal Medicine, Niigata Cancer Center Hospital.

A 71-year-old man underwent extended thymomectomy with partial resection of the upper lobe of the left lung and pericardium for stage III invasive thymoma in March, 2000. Postoperative chemotherapy and radiation therapy were carried out. The patient did well until June 2005, when a mediastinal mass and pleural dissemination were detected. The recurrence of the thymoma was strongly suspected radiographically. Combination chemotherapy of carboplatin and paclitaxel achieved partial remission. About three months after the last chemotherapy, the patient had a severe anemia in February 2006. Based on the blood data and the bone marrow examination, pure red cell aplasia was diagnosed. Prednisolone treatment (50 mg daily) resulted in dramatic regression of recurrent mediastinal and pleural tumors, as well as improvement of pure red cell aplasia.

Publication Types:

English Abstract

PMID: 18051792 [PubMed - in process]

43: Respirology. 2007 Nov;12(6):934-6.
Related Articles, Links: Middle mediastinal thymoma.

Huang TW, Cheng YL, Tzao C, Chang H, Tsai WC, Lee SC.

Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Thymoma is a common primary neoplasm of the anterior mediastinum. However, it can also arise in other locations, including the neck, the posterior mediastinum, the lung, base of the skull and the pleural cavity. There are only three previous case reports of thymoma located in the middle mediastinum. This report describes a patient together with a review of the literature on middle mediastinal thymoma.

PMID: 17986129 [PubMed - in process]

44: Int J Radiat Biol. 2007 Oct 19;:1-11 [Epub ahead of print]
Related Articles, Links: An essential role of integrin-linked kinase in the cellular radiosensitivity of normal fibroblasts during the process of cell adhesion and spreading.

Hehlgans S, Eke I, Cordes N.

OncoRay - Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Germany.

Purpose: In addition to focal adhesion kinase (FAK), Paxillin and p130 Crk-associated substrate (p130Cas), integrin-linked kinase (ILK) mediates signals from beta integrins for controlling, e.g., survival, adhesion and spreading. To evaluate the role of ILK in the cellular radiosensitivity at different stages of cell adhesion and spreading, ILK(floxed/floxed (fl/fl)) and ILK(-/-) mouse fibroblasts were examined. Materials and methods: Cells were irradiated (0 - 4 Gy, X-rays) in suspension, after varying time periods on fibronectin (FN) or after 24 h on different matrix proteins. Irradiation was combined with phosphatidylinositol-3 kinase (PI3K) inhibition using Ly294002. Clonogenic radiation survival, cell adhesion, and kinetics of protein expression and phosphorylation during FN adhesion (ILK, v-akt murine thymoma viral oncogene homolog 1 (AKT), FAK, Paxillin, p130Cas) were examined. Results: In suspension and during the first hour on FN, irradiated ILK(fl/fl) cells survived significantly better than ILK(-/-) cells in a PI3K- and serum-dependent manner. 24-h cell cultures on different matrix proteins showed no difference in radiosensitivity. During FN adhesion, which was slightly impaired in ILK(-/-) cells, protein kinetics uncovered differences in AKT, FAK, Paxillin and p130Cas phosphorylation in the two cell lines. Phosphorylation of FAK, Paxillin and p130Cas was downregulated upon exposure to ionizing radiation in an ILK-independent manner. Conclusions: These findings indicate a critical function of ILK in the cellular radiosensitivity during the early stages of adhesion to and spreading on FN. On the basis of the presented data, a precise correlation of adhesion-, serum- and PI3K-mediated changes in PI3K/AKT and FAK/Paxillin/p130Cas signaling cascades was not found. However, identifying the underlying mechanisms of adhesion- and spreading-related changes in the cellular radiosensitivity might be relevant for an optimization of radiotherapeutic strategies specifically targeting cells located at the invasive edge of a malignant tumor.

PMID: 17952767 [PubMed - as supplied by publisher]

45: Int J Cardiol. 2007 Oct 18;121(3):312-4. Epub 2006 Dec 22.
Related Articles, Links

Is transesophageal echocardiography useful in planning surgery of mediastinal thymomas? Transesophageal investigation of a mediastinal thymoma.

Oneglia C, Di Fabio D, Bonora-Ottoni D, Rusconi C.

Thymomas are the commonest tumors arising in the anterior mediastinum, sometimes representing an incidental finding at radiological examination. Surgery of these neoplasms must be planned after accurately assessing the invasive or non-invasive nature of the mass. In the present case this could be achieved also by submitting the patient to transesophageal echocardiography which could accurately exclude infiltration of heart walls. We therefore think that this technique can be considered a useful complement to radiological ones in defining the surgical strategy of mediastinal thymomas.

Publication Types:

PMID: 17188379 [PubMed - indexed for MEDLINE]

46: Surg Endosc. 2007 Oct 18 [Epub ahead of print]
Related Articles, Links: Alternative choices of total and partial thymectomy in video-assisted resection of noninvasive thymomas.

Sakamaki Y, Kido T, Yasukawa M.

Department of Chest Surgery, Osaka Police Hospital, 10-31 Kitayama-cho, Tennouji-ku, Osaka, 543-0035, Japan, sak@serenade.plala.or.jp.

BACKGROUND: The purpose of this report is to discuss the appropriate choice of procedures for video-assisted resection of thymoma according to factors such as the presence of myasthenia gravis or location of the tumor. METHODS: We evaluated the short-term results of thoracoscopic surgery for 30 consecutive cases of noninvasive thymoma. Unilateral thoracoscopic partial (or subtotal) thymectomy (UTPT) was employed in patients with nonmyasthenic thymoma localized to the unilateral mediastinum, and extended (or total) thymectomy by an infrasternal mediastinal approach (ETIS) in myasthenic cases or those in which total thymectomy was considered inevitable. RESULTS: UTPT was performed on 11 nonmyasthenic patients, and ETIS on 19 (13 myasthenics and six nonmyasthenics). Three patients in the ETIS group underwent conversion to sternotomy because of pericardial dissemination, pleural adhesion, and vascular injury, respectively. The mean surgical duration was 163 min and 224 min and mean blood loss was 123 g versus 149 g for UTPT and ETIS, respectively. Post-thymomectomy myasthenia occurred in a patient after UTPT who made an excellent recovery to remission after the re-UTPT. There has not been any recurrence detected for 48 months of mean postoperative follow-up. CONCLUSIONS: Our trial regarding the choice of total or partial thymectomy in thoracoscopic surgery for thymomas yielded acceptable results that warrant further investigations into long-term survival and recurrence after longer-term observation of patients undergoing these procedures.

PMID: 17943356 [PubMed - as supplied by publisher]

47: Clin Neurol Neurosurg. 2007 Oct 5 [Epub ahead of print]
Related Articles, Links: Amyotrophic lateral sclerosis patients and ocular ptosis.

Pinto S, de Carvalho M.

Neuromuscular Unit, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal.

Ptosis is not a feature observed in amyotrophic lateral sclerosis (ALS). We describe two old women with bulbar-onset ALS and rapid progression, in whom ptosis and diplopia were noted. They did not improve on pyridostigmine or steroids. Antibodies against acetylcholine receptor were negative, thymoma was excluded, but neurophysiological showed marked neuromuscular transmission failure in orbicularis oculi. We discuss the association between ALS and ocular myasthenia gravis in these cases.

PMID: 17920189 [PubMed - as supplied by publisher]

48: Acta Cardiol. 2007 Oct;62(5):517-8.
Related Articles, Links: Mediastinal thymoma invading the superior vena cava and the right atrium.

Aladdin M, Bozlar U, Turba UC, Kron IL, Ahmed H, Hagspiel KD.

Department of Radiology, University of Virginia Health System, VA 22908, USA.

An 86-year-old male patient presented with a large mediastinal tumor. A needle biopsy was performed and revealed a diagnosis of invasive thymoma. Multidetector computed tomography (MDCT) angiography was performed in order to assess operability of the tumor. This showed a heterogeneously enhancing anterior mediastinal mass. The tumor had invaded the left brachiocephalic vein, presumably via the inferior thymic veins, which is a known feature of these tumors. The thymoma grew then endovenously through the superior vena cava into the right atrium. A pacemaker lead was completely encased by tumor tissue. The patient was deemed inoperable and underwent radiation therapy.

PMID: 17982975 [PubMed - in process]

49: Bone Marrow Transplant. 2007 Oct;40(7):705-6. Epub 2007 Aug 6.
Related Articles, Links

Lymphocyte reconstitution after allogeneic bone marrow transplantation in a previously thymectomized patient--no evidence of extrathymic T-cell maturation.

Giebel S, Dziaczkowska J, Wysoczanska B, Wojnar J, Krawczyk-Kulis M, Lange A, Holowiecki J.

Publication Types:

PMID: 17680024 [PubMed - indexed for MEDLINE]

50: Dtsch Med Wochenschr. 2007 Oct;132(40):2090-5.
Related Articles, Links

[Thymoma--incidence, classification and therapy]

[Article in German]

Stremmel C, Dango S, Thiemann U, Kayser G, Passlick B.

Abteilung Thoraxchirurgie der Ludwig-Albert Universität Freiburg, Freiburg. christian.stremmel@uniklinik-freiburg.de

Thymomas are a rare tumor entity. However, they represent 50 % of all tumors of the anterior mediastinum. There are no specific early symptoms. Overall in 10 - 15 % of patients with myasthenia gravis a thymoma is evident. Two major classifications are relevant in clinical practise: the Masaoka-classification and the WHO-classification. For their clinical and prognostic significance both classifications should be used for patients with thymomas. Additional, only resection status (RO) is known as a significant prognostic factor. Thymomas are compulsory malignant tumors. Distant metastasis is found as well as local recurrence in all stages of the disease. The 5-year-mortality rate constitutes about 80 %, not meaning any healing because local recurrences occur as late as five years after surgery. 60 % of all patients die from tumor-independent reasons making a clear prognostic statement difficult. Surgical treatment remains the gold standard and must be performed whenever possible. The most common approach is a median sternotomy. When dealing with a thymuscarcinoma, radical lymph node dissection is advisable. With respect of treatment only adjuvant radiation can possibly improve long term survival and reduces local recurrence rates for incomplete resected patients. There is no evidence for a benefit in patients with thymoma receiving adjuvant chemotherapy. A neo-adjuvant chemotherapy in combination with an adjuvant radiotherapy improves outcome after surgical resection in stage III and IV and goes along with better survival rates. Larger studies have not been performed so far. A multimodal therapy strategy is advised when dealing with thymomas in stage III and IV.

Publication Types:

PMID: 17899505 [PubMed - indexed for MEDLINE]

51: J Am Acad Dermatol. 2007 Oct;57(4):683-9. Epub 2007 Apr 16.
Related Articles, Links

Thymoma-associated multiorgan autoimmunity: a graft-versus-host-like disease.

Wadhera A, Maverakis E, Mitsiades N, Lara PN, Fung MA, Lynch PJ.

Permanente Medical Group, Fremont, California, USA.

Graft-versus-host disease (GVHD) is a T cell-mediated disease seen most commonly after hematopoietic stem cell transplantation. Rarely, a GVHD-like disease can be seen in patients with malignant thymoma. We describe a 50-year-old man with malignant thymoma who developed skin, liver, and intestinal manifestations similar to that seen in GVHD. We also review other reported cases of GVHD-like manifestations in the setting of thymoma and propose "thymoma-associated multiorgan autoimmunity" as a name for this novel disease. Specifically, thymoma-associated multiorgan autoimmunity is defined as a disease of the liver, intestine, or skin, which on histopathology resembles GVHD but is seen in the setting of malignant thymoma and not after hematopoietic stem cell transplantation.

Publication Types:

Case Reports

PMID: 17433850 [PubMed - indexed for MEDLINE]

52: J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1109-12. Epub 2007 Mar 12.
Related Articles, Links: Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology.

Tsinzerling N, Lefvert AK, Matell G, Pirskanen-Matell R.

Department of Medicine, Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology. SETTING: The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and at the Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. PATIENTS AND METHODS: Information was collected retrospectively from 1956 and prospectively from 1975 on clinical data, concomitant diseases, concentration of serum acetylcholine receptor antibodies (AChR-abs), immunosuppressive treatment (IS) and response to it, in 537 patients of whom 326 were thymectomised. Follow-up time was 1.5-50 years. RESULTS: Age at onset of MG increased from a median age of 24 years before 1975 to a median age of 61 years after 2000. Thymoma was found in 65, hyperplasia (HPL) in 185 and a normal thymus in 76 patients. The trans-sternal surgical approach for thymectomy was used in 255 patients (78%). In five patients with thymoma, MG appeared after thymectomy. Of 537 patients, 466 (87%) had circulating AChR-abs. IS was given to 300 (56%) patients, mostly those with thymoma (85%). In total, 441 patients (82%) showed an improvement. One-third of patients with HPL, a quarter of those with thymoma, one-fifth of those with a normal thymus and one-seventh of those not operated on went into remission. CONCLUSION: The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy.

PMID: 17353257 [PubMed - indexed for MEDLINE]

53: Masui. 2007 Oct;56(10):1200-2.
Related Articles, Links

[Anesthetic management for thymectomy in a patient with stiff-person syndrome]

[Article in Japanese]

Nakamura T, Oda Y, Matsushita M, Mori T, Ikeshita K, Asada A.

Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka City University, Osaka 545-8586.

Stiff-person syndrome is an autoimmune disease characterized by muscle rigidity accompanied by decreased respiratory function. We report a patient with this syndrome who underwent thymectomy under general anesthesia. A 79-year-old woman complaining of increasing muscle rigidity over the past four months was transferred to this hospital. Marked speech disturbance and dysphagia were observed on admission. The diagnosis of stiff-person syndrome was made based on an increase in serum anti-glutamic acid decarboxylase antibody level and thymoma in the anterior mediastinum. Following alleviation of muscle rigidity by high-dose gamma-globulin, thymectomy was scheduled. General anesthesia was given with propofol, fentanyl and epidural ropivacaine. Propofol was continuously infused to maintain BIS below 60 and vecuronium was intermittently administered when muscle contraction was observed in response to electrical stimulation of the ulnar nerve. Despite full recovery of muscle contractility following surgery, tidal volume was too low to remove the tracheal tube, and mechanical ventilation was continued in ICU. One hour after admission to ICU, the tracheal tube was removed, with no marked changes in respiratory condition thereafter. Since many anesthetics are respiratory suppressants that can delay the recovery of respiratory function, careful monitoring of respiratory condition is required postoperatively.

Publication Types:

PMID: 17966628 [PubMed - indexed for MEDLINE]

54: Pediatr Surg Int. 2007 Oct;23(10):1015-7.
Related Articles, Links: Cystic thymoma in a child: a rare case and review of the literature.

Honda S, Morikawa T, Sasaki F, Okada T, Naito S, Itoh T, Kubota K, Todo S.

Department of Pediatric Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Kita 15, Nishi 7, Sapporo, 060-8638, Japan. shohei@sam.hi-ho.ne.jp

Thymomas are rare mediastinal tumors in pediatrics and cystic thymoma, is characterized by a predominantly cystic formation, is extremely rare. This report describes a 13-year-old girl with cystic thymoma, who was treated by video-assisted thoracoscopic surgery. The microscopic findings were characteristic of cystic thymoma. The literature on cystic thymoma is reviewed here and the clinical characteristics of cystic thymoma are discussed.

PMID: 17674012 [PubMed - in process]

55: Saudi Med J. 2007 Oct;28(10):1603-4.
Related Articles, Links: An invasive thymoma complicated with airway stenosis causing sudden hypoxia during surgery.

Chen CY, Lee SC, Chang H.

Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.

PMID: 17914529 [PubMed - in process]

56: Neurology. 2007 Sep 18;69(12):1302-3.
Related Articles, Links

Thymoma, myasthenia gravis, encephalitis, and a novel anticytoplasmic neuronal antibody.

Khella SL, Souyah N, Dalmau J.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. katiek@mail.med.upenn.edu

Publication Types:

PMID: 17875920 [PubMed - indexed for MEDLINE]

57: J Biol Chem. 2007 Sep 7;282(36):26369-80. Epub 2007 Jul 10.
Related Articles, Links

Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation.

Hayakawa H, Hayakawa M, Kume A, Tominaga S.

Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.

The ST2 gene produces a soluble secreted form and a transmembrane form, referred to as soluble ST2 and ST2L, respectively. A recent study has reported that interleukin (IL)-33 is a specific ligand of ST2L and induces production of T helper type 2 (Th2) cytokines. Although soluble ST2 is highly produced in sera of asthmatic patients and plays a critical role for production of Th2 cytokines, the function of soluble ST2 in relation to IL-33 signaling remains unclear. Here we show antagonistic effects of soluble ST2 on IL-33 signaling using a murine thymoma EL-4 cells stably expressing ST2L and a murine model of asthma. Soluble ST2 directly bound to IL-33 and suppressed activation of NF-kappaB in EL-4 cells stably expressing ST2L, suggesting that the complex of soluble ST2 and IL-33 fails to bind to ST2L. In a murine model of asthma, pretreatment with soluble ST2 reduced production of IL-4, IL-5, and IL-13 from IL-33-stimulated splenocytes. These results indicate that soluble ST2 acts as a negative regulator of Th2 cytokine production by the IL-33 signaling. Our study provides a molecular mechanism wherein soluble ST2 modulates the biological activity of IL-33 in allergic airway inflammation.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17623648 [PubMed - indexed for MEDLINE]

58: Chirurg. 2007 Sep 6 [Epub ahead of print]
Related Articles, Links: [Plastic surgical reconstruction of extensive thoracic wall defects after oncologic resection.]

[Article in German]

Riedel K, Kremer T, Hoffmann H, Pfannschmidt J, Reimer P, Dienemann H, Germann G, Sauerbier M.

Klinik für Hand-, Plastische und Rekonstruktive Chirurgie- Schwerbrandverletztenzentrum-, BG-Unfallklinik Ludwigshafen, Klinik für Plastische und Handchirurgie an der Universität Heidelberg, Ludwigshafen, Deutschland.

In defect reconstruction following radical oncologic resection of malignant chest wall tumors, adequate soft-tissue reconstruction must be achieved along with function, stability, integrity, and aesthetics of the chest wall. The purpose of this retrospective analysis was to evaluate the oncoplastic concept following radical resection of malignant chest wall infiltration with an interdisciplinary approach. Between 1999 and 2005, 36 consecutive patients (nine males, 27 females, mean age 55 years, range 20-78) were treated with resection for malignant tumors of the chest wall. Indications were locally recurrent breast carcinoma (patient n=22), thymoma (n=1), and desmoid tumor (n=1). Primary lesions of the chest wall were spinalioma (n=1), sarcoma (n=7), and non-small-cell lung cancer (n=2). There were distant metastases of colon and cervical cancer in one patient each. Soft-tissue reconstruction was carried out using primary closure (n=1), external oblique flap (n=1), pectoralis major myocutaneous flap (n=3), latissimus dorsi myocutaneous flap (n=18), vertical or transversal rectus abdominis myocutaneous flap (n=9), free tensor fascia lata- flap (n=6), trapezius flap (n=1), serratus flap (n=1), and one filet flap. In 15 reconstructive procedures microvascular techniques were used. An average of 3.4 ribs were resected. Stability of the chest wall was obtained with synthetic meshes. The latissimus dorsi flap is considered the flap of choice in chest wall reconstruction. However, alternatives such as pectoralis major flap, VRAM/TRAM flap, free TFL flap, and serratus flap must also be considered. Low mortality and morbidity rates allow tumor resection and chest wall reconstruction even in a palliative setting.

PMID: 17786394 [PubMed - as supplied by publisher]

59: BMC Genomics. 2007 Sep 3;8:305.
Related Articles, Links

Genome-wide genetic aberrations of thymoma using cDNA microarray based comparative genomic hybridization.

Lee GY, Yang WI, Jeung HC, Kim SC, Seo MY, Park CH, Chung HC, Rha SY.

Cancer Metastasis Research Center, National Biochip Research Center, Yonsei University College of Medicine, Seoul, Korea. leegy@yuhs.ac

BACKGROUND: Thymoma is a heterogeneous group of tumors in biology and clinical behavior. Even though thymoma is divided into five subgroups following the World Health Organization classification, the nature of the disease is mixed within the subgroups. RESULTS: We investigated the molecular characteristics of genetic changes variation of thymoma using cDNA microarray based-comparative genomic hybridization (CGH) with a 17 K cDNA microarray in an indirect, sex-matched design. Genomic DNA from the paraffin embedded 39 thymoma tissues (A 6, AB 11, B1 7, B2 7, B3 8) labeled with Cy-3 was co-hybridized with the reference placenta gDNA labeled with Cy-5. Using the CAMVS software, we investigated the deletions on chromosomes 1, 2, 3, 4, 5, 6, 8, 12, 13 and 18 throughout the thymoma. Then, we evaluated the genetic variations of thymoma based on the subgroups and the clinical behavior. First, the 36 significant genes differentiating five subgroups were selected by Significance Analysis of Microarray. Based on these genes, type AB was suggested to be heterogeneous at the molecular level as well as histologically. Next, we observed that the thymoma was divided into A, B (1, 2) and B3 subgroups with 33 significant genes. In addition, we selected 70 genes differentiating types A and B3, which differ largely in clinical behaviors. Finally, the 11 heterogeneous AB subtypes were able to correctly assign into A and B (1, 2) types based on their genetic characteristics. CONCLUSION: In our study, we observed the genome-wide chromosomal aberrations of thymoma and identified significant gene sets with genetic variations related to thymoma subgroups, which might provide useful information for thymoma pathobiology.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17764580 [PubMed - in process]

60: Ann Thorac Surg. 2007 Sep;84(3):1029-31.
Related Articles, Links

Satisfactory results of diaphragmatic plication for bilateral phrenic nerve paralysis.

Ohta M, Ikeda N, Tanaka H, Matsumura A, Ohsumi H, Iuchi K.

Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino City, Osaka, Japan. ootami@opho.jp

Bilateral diaphragmatic plication was performed in a 44-year-old man who underwent complete resection of a thymoma infiltrating the right lung, bilateral brachiocephalic vein, pericardium, and bilateral phrenic nerves. The plication procedure allowed him to be weaned from the ventilator on postoperative day 4. He demonstrated no restrictive or obstructive pattern of lung function, and after respiratory rehabilitation he returned to work full time 5 weeks after the operation. The present results indicate that ventilatory movement of the thoracic cage can compensate for loss of bilateral diaphragmatic ventilation for at least 18 months.

Publication Types:

Case Reports

PMID: 17720431 [PubMed - indexed for MEDLINE]

61: Arch Pharm Res. 2007 Sep;30(9):1102-10.
Related Articles, Links

Establishment of an in vitro test system to evaluate the down-regulatory activities of natural products on IL-4.

Choi JJ, Park BK, Song GY, Kim JS, Kim JH, Kim DH, Jin M.

Lab of Pathology, College of Oriental Medicine, Daejeon University, Daejeon, 300-716, Korea.

Interleukin-4 (IL-4), a representative TH2 cytokine, plays a pathologic role in the onset of various allergic diseases including atopic dermatitis, atopic rhinitis, and asthma. Several drug candidates that down-regulate IL-4 expression have been studied for their possible use as antiallergic agents in clinical settings. Therefore, an in vitro test to evaluate IL-4 promoter activities might be useful for selecting candidates of novel natural therapeutics. The promoter region (-741 to +56) of IL-4 was cloned upstream of a luciferase gene in the plasmid pGL4.14 with a hygromycin resistance gene as a selection marker to generate pGL4.14-IL-4. Treatment with PMA and A23187 highly increased luciferase activity by approximately 10-fold compared with the control in both EL-4 thymoma and RBL-2H3 cells transiently transfected with pGL4.14-IL-4, as well as in stable cell lines constantly expressing pGL4.14-IL-4. Cyclosporin A and dexamethasone, well-known anti-allergic agents, significantly down-regulated the activity in a dose-dependent manner. The feasibility of this system was evaluated by measuring the down-regulatory activities of various extracts from the TBRC plant library on PMA- and A23187-induced luciferase activities of IL-4 promoter, and by measuring IL-4 production in cultured cells using ELISA assays. The results of this study suggest that this primary screening system is simple and time-saving, and might be suitable for the selection of natural therapeutic candidates for allergic disease by measuring the down-regulatory effects of natural products on the IL-4 promoter.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17958327 [PubMed - indexed for MEDLINE]

62: Clin Exp Immunol. 2007 Sep;149(3):504-12. Epub 2007 Jun 22.
Related Articles, Links

Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas.

Scarpino S, Di Napoli A, Stoppacciaro A, Antonelli M, Pilozzi E, Chiarle R, Palestro G, Marino M, Facciolo F, Rendina EA, Webster KE, Kinkel SA, Scott HS, Ruco L.

Dip. di Istopatologia ed Anatomia Patologica, Ospedale Sant'Andrea, II Facoltà di Medicina e Chirurgia, Università 'La Sapienza', Rome, Italy. stefania.scarpino@uniroma1.it

Expression of the autoimmune regulator gene (AIRE) and the presence of CD25(+)/forkhead box p3 (FoxP3)(+) T regulatory (T(reg)) cells were investigated in histologically normal adult thymi and in thymomas using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). In the normal thymus staining for AIRE was detected in the nucleus of some epithelial-like cells located in the medulla; in thymomas AIRE-positive cells were extremely rare and could be detected only in the areas of medullary differentiation of two B1 type, organoid thymomas. RNA was extracted from 36 cases of thymoma and 21 non-neoplastic thymi obtained from 11 myasthenic (MG(+)) and 10 non-myasthenic (MG(-)) patients. It was found that AIRE is 8.5-fold more expressed in non-neoplastic thymi than in thymomas (P = 0.01), and that the amount of AIRE transcripts present in the thymoma tissue are not influenced by the association with MG, nor by the histological type. A possible involvement of AIRE in the development of MG was suggested by the observation that medullary thymic epithelial cells isolated from AIRE-deficient mice contain low levels of RNA transcripts for CHRNA 1, a gene coding for acetylcholine receptor. Expression of human CHRNA 1 RNA was investigated in 34 human thymomas obtained from 20 MG(-) patients and 14 MG(+) patients. No significant difference was found in the two groups (thymoma MG(+), CHRNA1 = 0.013 +/- 0.03; thymoma MG-, CHRNA1 = 0.01 +/- 0.03). In normal and hyperplastic thymi CD25(+)/Foxp3(+) cells were located mainly in the medulla, and their number was not influenced by the presence of MG. Foxp3(+) and CD25(+) cells were significantly less numerous in thymomas. A quantitative estimate of T(reg) cells revealed that the levels of Foxp3 RNA detected in non-neoplastic thymi were significantly higher (P = 0.02) than those observed in 31 cases of thymomas. Our findings indicate that the tissue microenvironment of thymomas is defective in the expression of relevant functions that exert a crucial role in the negative selection of autoreactive lymphocytes.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17590173 [PubMed - indexed for MEDLINE]

63: Eukaryot Cell. 2007 Sep;6(9):1552-61. Epub 2007 Jul 13.
Related Articles, Links

Role of laeA in the Regulation of alb1, gliP, Conidial Morphology, and Virulence in Aspergillus fumigatus.

Sugui JA, Pardo J, Chang YC, Müllbacher A, Zarember KA, Galvez EM, Brinster L, Zerfas P, Gallin JI, Simon MM, Kwon-Chung KJ.

Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

The alb1 (pksP) gene has been reported as a virulence factor controlling the pigmentation and morphology of conidia in Aspergillus fumigatus. A recent report suggested that laeA regulates alb1 expression and conidial morphology but not pigmentation in the A. fumigatus strain AF293. laeA has also been reported to regulate the synthesis of secondary metabolites, such as gliotoxin. We compared the role of laeA in the regulation of conidial morphology and the expression of alb1 and gliP in strains B-5233 and AF293, which differ in colony morphology and nutritional requirements. Deletion of laeA did not affect conidial morphology or pigmentation in these strains, suggesting that laeA is not involved in alb1 regulation during conidial morphogenesis. Deletion of laeA, however, caused down-regulation of alb1 during mycelial growth in a liquid medium. Transcription of gliP, involved in the synthesis of gliotoxin, was drastically reduced in B-5233laeADelta, and the gliotoxin level found in the culture filtrates was 20% of wild-type concentrations. While up-regulation of gliP in AF293 was comparable to that in B-5233, the relative mRNA level in AF293laeADelta was about fourfold lower than that in B-5233laeADelta. Strain B-5233laeADelta caused slower onset of fatal infection in mice relative to that with B-5233. Histopathology of sections from lungs of infected mice corroborated the survival data. Culture filtrates from B-5233laeADelta caused reduced death in thymoma cells and were less inhibitory to a respiratory burst of neutrophils than culture filtrates from B-5233. Our results suggest that while laeA is not involved in the regulation of alb1 function in conidial morphology, it regulates the synthesis of gliotoxin and the virulence of A. fumigatus.

Publication Types:

PMID: 17630330 [PubMed - indexed for MEDLINE]

64: Eukaryot Cell. 2007 Sep;6(9):1562-9. Epub 2007 Jun 29.
Related Articles, Links

Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone.

Sugui JA, Pardo J, Chang YC, Zarember KA, Nardone G, Galvez EM, Müllbacher A, Gallin JI, Simon MM, Kwon-Chung KJ.

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the mycotoxin is not important for pathogenesis of A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on the pathobiological role of gliotoxin in two different mouse strains, 129/Sv and BALB/c, that were immunosuppressed by hydrocortisone alone to avoid neutropenia. These strains of mice were infected using the isogenic set of a wild type strain (B-5233) and its mutant strain (gliPDelta) and the the glip reconstituted strain (gliP(R)). The gliP gene encodes a nonribosomal peptide synthase that catalyzes the first step in gliotoxin biosynthesis. The gliPDelta strain was significantly less virulent than strain B-5233 or gliP(R) in both mouse models. In vitro assays with culture filtrates (CFs) of B-5233, gliPDelta, and gliP(R) strains showed the following: (i) deletion of gliP abrogated gliotoxin production, as determined by high-performance liquid chromatography analysis; (ii) unlike the CFs from strains B-5233 and gliP(R), gliPDelta CFs failed to induce proapoptotic processes in EL4 thymoma cells, as tested by Bak conformational change, mitochondrial-membrane potential disruption, superoxide production, caspase 3 activation, and phosphatidylserine translocation. Furthermore, superoxide production in human neutrophils was strongly inhibited by CFs from strain B-5233 and the gliP(R) strain, but not the gliPDelta strain. Our study confirms that gliotoxin is an important virulence determinant of A. fumigatus and that the type of immunosuppression regimen used is important to reveal the pathogenic potential of gliotoxin.

Publication Types:

PMID: 17601876 [PubMed - indexed for MEDLINE]

65: Eur J Neurol. 2007 Sep;14(9):1029-34.
Related Articles, Links

Clinical and experimental features of MuSK antibody positive MG in Japan.

Ohta K, Shigemoto K, Fujinami A, Maruyama N, Konishi T, Ohta M.

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

We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1-2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity (P = 0.01 by Kruskal-Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17718696 [PubMed - indexed for MEDLINE]

66: Infez Med. 2007 Sep;15(3):195-8.
Related Articles

[EBV reactivation in a patient undergoing chemotherapy for invasive thymoma]

[Article in Italian]

Giordano S, Pampinella D, Alù M, Agostara B, Romano A.

U.O. Malattie Infettive-ARNAS Civico Palermo, Italy.

Over the last few years evidence has emerged to indicate the involvement of herpes viruses in several infectious complications observed in patients undergoing antiblastic chemotherapy. We present a case of bilateral parotiditis due to EBV reactivation in a patient who had received chemotherapy because of an invasive thymoma. In October 2006, a 53-year-old man with pulmonary and pleural metastases owing to an invasive thymoma, was started on chemotherapy with cisplatin, adriamycin and cyclophosphamide. In January 2007, after consultation with an infectious disease specialist, the patient was admitted to the oncology department because of bilateral swelling of the parotid glands which was most likely of infectious or mycotic origin and attributed to immunosuppression by chemotherapy (the last cycle was completed on 28th December 2006). During his hospital stay, the patient underwent routine blood tests, serological tests (EBV-VCA IgM/IgG: positive/positive, EBV-EBNA IgG: positive), cultural and instrumental tests. Due to the serological results, we decided to search for EBV in blood by using PCR (23,000 copies/100,000 cells). We hypothesize that EBV infection could have caused both thymoma and bilateral parotiditis. Accordingly, a multidisciplinary approach, including consultation with an oncologist, infectious disease and microbiology specialists, is the best way to manage infectious complications in patients with a deficit of cells-mediated immunity.

Publication Types:

English Abstract

PMID: 17940405 [PubMed - in process]

67: J Craniofac Surg. 2007 Sep;18(5):1055-8.
Related Articles, Links

Parotid gland mucoepidermoid carcinoma associated with myasthenia gravis.

Ozcan C, Talas D, Görür K.

From the Department of Otorhinolaryngology, School of Medicine, Mersin University, Mersin, Turkey. cozcan@mersin.edu.tr

Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Although most MG cases do not have accompanying malignant disease, patients with thymoma may have an increased risk for secondary malignancy. The reason MG patients are prone to developing cancer is not very well known. Salivary gland tumors account for approximately 3% of head and neck tumors, and approximately 80% of these occur in the parotid gland. Mucoepidermoid carcinoma is the most common malignant tumor of the parotid gland. MG may be associated with squamous cell carcinoma of the head and neck. We present a patient with MG who developed parotid gland mucoepidermoid carcinoma. MG patients with parotid gland cancer have not been previously reported. We also discuss the possible mechanisms of tumor development in an MG patient.

Publication Types:

Case Reports

PMID: 17912081 [PubMed - indexed for MEDLINE]

68: J Thorac Cardiovasc Surg. 2007 Sep;134(3):812-3.
Related Articles, Links

Suppurative Salmonella thyroiditis coexistence with invasive thymoma.

Chen KC, Chang YL, Pan CT, Lee YC.

Division of Thoracic Surgery, and Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Publication Types:

Case Reports

PMID: 17723846 [PubMed - indexed for MEDLINE]

69: J Thorac Cardiovasc Surg. 2007 Sep;134(3):799-801.
Related Articles, Links

Primary intrapulmonary thymoma associated with congenital hyperhomocysteinemia.

Stefani A, Boulenger E, Mehaut S, Ciupea A, Alifano M.

Department of Thoracic Surgery, Hôtel-Dieu University Hospital, Paris, France. stefani.alessandro@unimore.it

Publication Types:

Case Reports

PMID: 17723840 [PubMed - indexed for MEDLINE]

70: J Thorac Cardiovasc Surg. 2007 Sep;134(3):601-7.
Related Articles, Links

Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma.

Kim HK, Park MS, Choi YS, Kim K, Shim YM, Han J, Kim BJ, Kim J.

Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

OBJECTIVES: The objectives of this study were to compare the clinical features and the outcomes after thymectomy between patients with and without thymoma and to evaluate the influence of thymectomy on the subsequent clinical course of myasthenia gravis. METHODS: Between 1995 and 2003, 64 consecutive patients underwent thymectomy, and of these, 60 patients were followed up for at least 12 months postoperatively. The study population was divided into 2 groups based on the presence of thymoma. We performed a retrospective analysis to compare the neurologic outcomes of thymectomy between patients with thymomatous myasthenia gravis and those with nonthymomatous myasthenia gravis. RESULTS: Twenty-four patients had a thymoma. No significant differences were observed between the 2 groups regarding the preoperative severity of myasthenia gravis. There was no significant difference in the follow-up duration between the 2 groups. There was no significant difference in the overall remission rate between the 2 groups (P = .064). The mean time required to reach a remission was 10.6 months and 23.5 months in the thymoma and nonthymoma groups, respectively. The mean duration of remission was 43.1 months and 30.8 months in the thymoma and nonthymoma groups, respectively. In the early phase of follow-up, more patients reached remission in the thymoma group than those in the nonthymoma group (P = .040). CONCLUSIONS: Neurologic outcomes of the thymoma group were no worse than those of the nonthymoma group. It is expected that earlier thymectomy is likely to result in a better prognosis by shortening the disease period, even for patients with nonthymomatous myasthenia gravis.

Publication Types:

PMID: 17723805 [PubMed - indexed for MEDLINE]

71: J Thorac Oncol. 2007 Sep;2(9):879-80.
Related Articles, Links

Paraneoplastic limbic encephalitis attributable to thymoma.

Chaudhry MS, Waters M, Gilligan D.

Department of Oncology, Addenbrookes Hospital, Cambridge, United Kingdom.

Publication Types:

Case Reports

PMID: 17805070 [PubMed - indexed for MEDLINE]

72: Neurologist. 2007 Sep;13(5):261-71.
Related Articles, Links

Limbic encephalitis and variants: classification, diagnosis and treatment.

Tüzün E, Dalmau J.

Division of Neuro-Oncology, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

BACKGROUND AND OBJECTIVE: Recent studies suggest that a substantial number of patients with autoimmune limbic encephalitis may improve if properly diagnosed and treated. This is due, in part, to the increasing recognition of disorders that associate with antibodies to neuronal cell membrane antigens. This review focuses in these disorders, framed in a clinically useful immunologic classification of limbic encephalitis. REVIEW SUMMARY: Patients with limbic encephalitis usually present with rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. After excluding viral and systemic autoimmune disorders, many patients with limbic encephalitis (paraneoplastic or not) have cerebrospinal fluid inflammatory findings, EEG or MRI abnormalities in the temporal lobes, and antineuronal antibodies. These antibodies are directed against 2 broad categories of antigens: (1) intracellular or classic paraneoplastic antigens, including Hu, Ma2, CV2/CRMP5, and amphiphysin among others, and (2) cell membrane antigens, including voltage-gated potassium channels, N-methyl-D-aspartate receptor, and others expressed in the neuropil of hippocampus and cerebellum (pending characterization). Whereas the disorders related to the first category of antibodies associate with cancer (lung, testis and other), prominent brain infiltrates of cytotoxic T-cells, and limited response to treatment, the disorders related to the second category of antibodies associate less frequently with cancer (thymoma, teratoma), seem to be antibody-mediated, and respond significantly better to immunotherapy. CONCLUSIONS: Once considered an extremely rare disorder, almost always related to cancer, and refractory to treatment, limbic encephalitis is now regarded as a relatively frequent disorder, often unrelated to cancer, and with clinical-immunologic variants that respond to treatment.

Publication Types:

PMID: 17848866 [PubMed - indexed for MEDLINE]

73: Rev Med Interne. 2007 Sep;28(9):627-30. Epub 2007 Jun 8.
Related Articles, Links

[Stiff person syndrome associated with thymoma. Efficacy of thymectomy]

[Article in French]

Essalmi L, Meaux-Ruault N, Hafsaoui C, Gil H, Curlier E, Dupond JL.

Service de médecine interne et immunologie clinique, hôpital Jean-Minjoz, CHU de Besançon, 2, boulevard Fleming, 25030 Besançon cedex, France.

INTRODUCTION: Stiff person syndrome is a rare autoimmune neurologic disorder characterized by axial muscular rigidity and intermittent painful spasms. Three distinct forms are described: auto-immune, paraneoplastic and idiopathic. EXEGESIS: We report the case of a 51-year-old man with an history of Stiff Person Syndrome with typical clinical, electrophysiological and immunological findings. Anti-glutamic acid decarboxylase antibodies were present, as well as anti-amphiphysin antibodies, commonly reported in the paraneoplastic syndrome. CT scan revealed a thymoma. Surgical resection was followed by reduction of the neurologic symptoms, without lowering the auto antibodies titer. CONCLUSIONS: The association between Stiff Person Syndrome and thymoma is exceptional. Thymectomy is an effective treatment and may act without change of the autoantibodies titer. Patients with Stiff Person Syndrome should be systematically tested for thymoma.

Publication Types:

PMID: 17624641 [PubMed - indexed for MEDLINE]

74: Tumori. 2007 Sep-Oct;93(5):508-10.
Related Articles, Links

Solitary fibrous tumor of the anterior mediastinum: a rare extrapleural neoplasm.

Gannon BR, O'Hara CD, Reid K, Isotalo PA.

Department of Pathology, Queen's University, Kingston, Ontario, Canada.

Solitary fibrous tumors are uncommon spindle cell neoplasms originally thought to be restricted to the pleura. We describe a 62-year-old woman who presented with stridor and an anterior mediastinal mass. At thoracotomy, a 10.5 x 6.5 x 5.5 cm, circumscribed, firm mediastinal mass demonstrated no direct cardiac or pulmonary involvement. The tumor consisted of spindle cells organized in a patternless pattern with collagenous stroma and hemangiopericytoma-like vessels. Spindle cells were immunoreactive for CD34, CD99, desmin, vimentin and bcl-2 protein and a diagnosis of mediastinal solitary fibrous tumor was confirmed. The differential diagnosis of mediastinal solitary fibrous tumors is extensive and includes spindle cell thymoma, sarcomatoid carcinoma, malignant mesothelioma, inflammatory myofibroblastic tumor, peripheral nerve sheath tumors and various sarcomas. Despite their rarity in the mediastinum, solitary fibrous tumors can be recognized by their classic patternless morphology and immunophenotypic pattern. Their accurate classification is important, as solitary fibrous tumors are intermediate (rarely metastasizing) neoplasms that require complete surgical excision and long-term clinical follow-up for optimum therapy.

Publication Types:

Case Reports

PMID: 18038888 [PubMed - indexed for MEDLINE]

75: Cardiovasc Intervent Radiol. 2007 Aug 21 [Epub ahead of print]
Related Articles, Links: Cardiac Metastasis from Invasive Thymoma Via the Superior Vena Cava: Cardiac MRI Findings.

Dursun M, Sarvar S, Cekrezi B, Kaba E, Bakir B, Toker A.

Department of Radiology, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul, Turkey, memduhdursun@yahoo.com.

Cardiac tumors are rare, and metastatic deposits are more common than primary cardiac tumors. We present cardiac magnetic resonance imaging (MRI) findings of a 50-year-old woman with invasive thymoma. Cardiac MRI revealed a heterogeneous, lobulated anterior mediastinal mass invading the superior vena cava and extending to the right atrium. In cine images there was no invasion to the right atrial wall.

PMID: 17710475 [PubMed - as supplied by publisher]

76: Blood. 2007 Aug 15;110(4):1184-90. Epub 2007 May 2.
Related Articles, Links

Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function.

Voskoboinik I, Sutton VR, Ciccone A, House CM, Chia J, Darcy PK, Yagita H, Trapani JA.

Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Australia. ilia.voskoboinik@petermac.org

Perforin (PRF), a pore-forming protein expressed in cytotoxic lymphocytes, plays a key role in immune surveillance and immune homeostasis. The A91V substitution has a prevalence of 8% to 9% in population studies. While this variant has been suspected of predisposing to various disorders of immune homeostasis, its effect on perforin's function has not been elucidated. Here we complemented, for the first time, the cytotoxic function of perforin-deficient primary cytotoxic T lymphocytes (CTLs) with wild-type (hPRF-WT) and A91V mutant (hPRF-A91V) perforin. The cytotoxicity of hPRF-A91V-expressing cells was about half that of hPRF-WT-expressing counterparts and coincided with a moderate reduction in hPRF-A91V expression. By contrast, the reduction in cytotoxic function was far more pronounced (more than 10-fold) when purified proteins were tested directly on target cells. The A91V substitution can therefore be manifested by abnormalities at both the lymphocyte (presynaptic) and target cell (postsynaptic) levels. However, the severe intrinsic defect in activity can be partly rescued by expression in the physiological setting of an intact CTL. These findings provide the first direct evidence that hPRF-A91V is functionally abnormal and provides a rationale for why it may be responsible for disordered immune homeostasis if inherited with another dysfunctional perforin allele.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17475905 [PubMed - indexed for MEDLINE]

77: Am J Clin Oncol. 2007 Aug;30(4):389-94.
Related Articles, Links: Adjuvant radiotherapy for thymic epithelial tumor: treatment results and prognostic factors.

Kundel Y, Yellin A, Popovtzer A, Pfeffer R, Symon Z, Simansky DA, Oberman B, Sadezki S, Brenner B, Catane R, Levitt ML.

Department of Oncology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel. yuliak@clalit.org.il

OBJECTIVE: To determine whether the use of adjuvant radiation in the treatment of invasive thymic tumors affects survival and to identify prognostic factors. METHODS: The files of 47 patients with thymic tumors treated by adjuvant radiation in our institute from 1984 to 2003 were reviewed for data on prognosis and survival. All patients underwent thoracotomy followed by either total macroscopic resection (n = 42) or biopsy (n = 5). The radiation dose ranged from 26 to 60 Gy. RESULTS: Median duration of follow-up was 10.6 years. Overall 5-year survival was 73% (60%-88%): 77% for thymoma (n = 35/45) versus 33% for thymic carcinoma (n = 2/6) (P = 0.14). Better survival was associated with lower disease stage (II vs. III/IVA, P = 0.01), resection (P = 0.0004), myasthenia gravis at presentation (P = 0.04), and higher radiation dose (<or=45 vs. >45 Gy, P = 0.02); sex, smoking, tumor size, pathology, and margin status had no effect. Locoregional relapse occurred in 11 patients and distant metastasis in 4. The 5-year disease-free survival was 67% (52%-86%), with a median time to recurrence of 8.3 years. The better overall survival and disease-free survival associated with higher doses of radiation were also true for stage II patients. On multivariate analyses after adjusting for age, higher disease stage and lower radiation dose were found to adversely affect overall survival and disease-free survival. Thymic carcinoma had an impact only on disease-free survival. CONCLUSION: Postoperative radiation therapy to doses above 45 Gy may improve the disease-free and overall survival of patients with invasive thymoma, especially stage II. Thymic carcinoma has a worse prognosis.

PMID: 17762439 [PubMed - indexed for MEDLINE]

78: Arch Neurol. 2007 Aug;64(8):1121-4.
Related Articles, Links

Classification of myasthenia gravis based on autoantibody status.

Suzuki S, Utsugisawa K, Nagane Y, Satoh T, Terayama Y, Suzuki N, Kuwana M.

Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan. shigeaki@sc.itc.keio.ac.jp

OBJECTIVES: To investigate the autoantibody status of patients with myasthenia gravis (MG) and to evaluate its usefulness for disease classification. DESIGN: Retrospective cohort study of patients with MG, who have autoantibodies to receptors and ion channels expressed at neuromuscular junctions and in muscles that impair neuromuscular transmission. One of the autoantibodies studied was a recently identified, novel, MG-specific autoantibody to a voltage-gated potassium (Kv) channel, Kv1.4. SETTING: Keio University Hospital, Tokyo, and Iwate Medical University Hospital, Morioka. PATIENTS: Two hundred nine patients with MG. MAIN OUTCOME MEASURES: Anti-Kv1.4 antibody was measured by an immunoprecipitation assay with sulfur 35-labeled extract from rhabdomyosarcoma cells. Antititin antibody was detected with a commercially available enzyme-linked immunosorbent assay. RESULTS: Anti-acetylcholine receptor, anti-Kv1.4, and antititin antibodies were detected in 150 (72%), 26 (12%), and 50 (24%) of the 209 patients with MG, respectively. All of the patients who were positive for anti-Kv1.4 or antititin antibody were seropositive for the anti-acetylcholine receptor antibody. They were classified into 4 groups based on their status in regard to 3 MG-related autoantibodies: anti-Kv1.4, antititin, and anti-acetylcholine receptor. Clinical associations were found between anti-Kv1.4 and bulbar involvement, myasthenic crisis, thymoma, and concomitant myocarditis and/or myositis; between antititin and older-onset MG; between anti-acetylcholine receptor alone and younger-onset MG; and between seronegativity and ocular MG. In addition, patients with MG in the anti-Kv1.4 group had more severe manifestations of disease than those in the other 3 groups. CONCLUSION: Classification of patients with MG based on autoantibody status may be useful in defining clinical subsets.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17698702 [PubMed - indexed for MEDLINE]

79: Cancer Immunol Immunother. 2007 Aug;56(8):1251-64. Epub 2007 Jan 23.
Related Articles, Links: Encapsulation in liposomal nanoparticles enhances the immunostimulatory, adjuvant and anti-tumor activity of subcutaneously administered CpG ODN.

de Jong S, Chikh G, Sekirov L, Raney S, Semple S, Klimuk S, Yuan N, Hope M, Cullis P, Tam Y.

Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.

Immunostimulatory oligodeoxynucleotides (ODN) containing cytosine-guanine (CpG) motifs are powerful stimulators of innate as well as adaptive immune responses, exerting their activity through triggering of the Toll-like receptor 9. We have previously shown that encapsulation in liposomal nanoparticles (LN) enhances the immunostimulatory activity of CpG ODN (LN-CpG ODN) (Mui et al. in J Pharmacol Exp Ther 298:1185, 2001). In this work we investigate the effect of encapsulation on the immunopotency of subcutaneously (s.c.) administered CpG ODN with regard to activation of innate immune cells as well as its ability to act as a vaccine adjuvant with tumor-associated antigens (TAAs) to induce antigen (Ag)-specific, adaptive responses and anti-tumor activity in murine models. It is shown that encapsulation specifically targets CpG ODN for uptake by immune cells. This may provide the basis, at least in part, for the significantly enhanced immunostimulatory activity of LN-CpG ODN, inducing potent innate (as judged by immune cell activation and plasma cytokine/chemokine levels) and adaptive, Ag-specific (as judged by MHC tetramer positive T lymphocytes, IFN-gamma secretion and cytotoxicity) immune responses. Finally, in efficacy studies, it is shown that liposomal encapsulation enhances the ability of CpG ODN to adjuvanate adaptive immune responses against co-administered TAAs after s.c. immunization, inducing effective anti-tumor activity against both model and syngeneic tumor Ags in murine tumor models of thymoma and melanoma.

PMID: 17242927 [PubMed - indexed for MEDLINE]

80: Int J Clin Oncol. 2007 Aug;12(4):300-2. Epub 2007 Aug 20.
Related Articles, Links

Hepatic lesion of invasive thymoma: possibility of direct invasion.

Okamoto T, Teruya T, Nishiyama K, Maruyama R, Shoji F, Wataya H, Ichinose Y.

Department of Thoracic Oncology, National Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan.

Thymomas grow slowly but tend to invade the surrounding tissue. We herein report four patients with hepatic lesions of thymomas, which were thought to have directly invaded the liver. These patients had received combined modality treatments throughout the clinical course, and the hepatic lesions appeared a long time after the initial treatment - 11.8 years on average. In these patients, the prognoses after the appearance of hepatic invasion were poor. Appropriate local control in the early stages of the clinical course may therefore be essential for preventing the extrathoracic spread of invasive thymoma.

Publication Types:

Case Reports

PMID: 17701011 [PubMed - indexed for MEDLINE]

81: J Clin Oncol. 2007 Aug 1;25(22):3374-5.
Related Articles, Links

Thymoma-associated severe aplastic anemia treated with surgical resection followed by allogeneic stem-cell transplantation.

Trisal V, Nademanee A, Lau SK, Grannis FW Jr.

Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA.

Publication Types:

Case Reports

PMID: 17664486 [PubMed - indexed for MEDLINE]

82: J Dermatol. 2007 Aug;34(8):503-11.
Related Articles, Links

Paraneoplastic pemphigus.

Zhu X, Zhang B.

Department of Dermatology, Peking University First Hospital, Beijing, China. zhuxj@public.bta.net.cn

Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune blistering skin disease. Clinically, it is characterized by severe mucosal erosions and various cutaneous lesions associated with lymphoproliferative neoplasmas. Suprabasal acantholysis and clefts with scattered necrotic keratinocytes are the unique histopathological features. PNP patient sera recognize multiple antigens, which have been identified as the plakin protein family that includes desmoplakin, bullous pemphigoid antigen I (BPAG1), envoplakin and periplakin, and desmogleins 1 and 3. Castleman's tumor, non-Hodgkin's lymphoma, thymoma, follicular dendritic cell sarcoma and chronic lymphocytic leukemia are the commonly associated neoplasmas in PNP. We have also demonstrated that the autoantibodies reacting to epidermal proteins are directly produced by the cells in the associated tumors. Bronchiolitis obliterans is frequently found in PNP and may cause respiratory failure and death. In our experience, the early detection and removal of the tumor and i.v. administration of immunoglobulin are critical for the treatment of PNP.

Publication Types:

Review

PMID: 17683379 [PubMed - indexed for MEDLINE]

83: J Immunol. 2007 Aug 1;179(3):1803-13.
Related Articles, Links: Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an endosomal pathway.

Kurotaki T, Tamura Y, Ueda G, Oura J, Kutomi G, Hirohashi Y, Sahara H, Torigoe T, Hiratsuka H, Sunakawa H, Hirata K, Sato N.

Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.

It is well-established that heat shock proteins (HSPs)-peptides complexes elicit antitumor responses in prophylactic and therapeutic immunization protocols. HSPs such as gp96 and Hsp70 have been demonstrated to undergo receptor-mediated uptake by APCs with subsequent representation of the HSP-associated peptides to MHC class I molecules on APCs, facilitating efficient cross-presentation. On the contrary, despite its abundant expression among HSPs in the cytosol, the role of Hsp90 for the cross-presentation remains unknown. We show here that exogenous Hsp90-peptide complexes can gain access to the MHC class I presentation pathway and cause cross-presentation by bone marrow-derived dendritic cells. Interestingly, this presentation is TAP independent, and followed chloroquine, leupeptin-sensitive, as well as cathepsin S-dependent endosomal pathways. In addition, we show that Hsp90-chaperoned precursor peptides are processed and transferred onto MHC class I molecules in the endosomal compartment. Furthermore, we demonstrate that immunization with Hsp90-peptide complexes induce Ag-specific CD8(+) T cell responses and strong antitumor immunity in vivo. These findings have significant implications for the design of T cell-based cancer immunotherapy.

PMID: 17641047 [PubMed - indexed for MEDLINE]

84: Neurol Sci. 2007 Aug;28(4):175-80. Epub 2007 Aug 10.
Related Articles, Links

Somatostatin receptor scintigraphy in the follow-up of myasthenia gravis.

Gao ZR, Kornblum C, Flacke S, Logvinski T, Yüksel M, An R, Klockgether T, Biersack HJ, Ezziddin S.

Department of Nuclear Medicine Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

To evaluate the potential value of somatostatin receptor scintigraphy (SRS) using 111In-DTPA (diethylenetriaminepenta acetic acid)-D-Phe1-octreotide (111In-pentetreotide) in patients with recurring or persisting symptoms of myasthenia gravis (MG), 14 consecutive cases with such supplemental receptor imaging during neurological routine follow-up were retrospectively evaluated in this study. All 14 patients underwent SRS in addition to chest computed tomography (CT). Mean follow-up after imaging was 34 months. Eight patients had previous thymectomy, and three patients were referred to surgery after scintigraphy and chest CT. SRS was positive in one of the 14 patients with local recurrence of thymoma and pleural invasion, and negative in the remaining 13 patients. CT was positive for thymoma in three patients, inconclusive in four patients and negative in seven patients. In conclusion, while SRS may be able to detect thymoma lesions including metastases, it seems of limited value in patients with inconspicuous CT findings. Our initial experience fails to point out a benefit of SRS in the management of persisting or recurring MG (with regard to detection of thymic disorders) compared to CT. Whether SRS is useful for differentiating thymoma from non-neoplastic thymic disease may be investigated by larger series. A predominant proportion of patients with unsatisfactory treatment response, however, continue to suffer an unfavourable clinical course despite absent evidence for thymic pathology.

Publication Types:

Evaluation Studies

PMID: 17690847 [PubMed - indexed for MEDLINE]

85: Thorac Cardiovasc Surg. 2007 Aug;55(5):336-8.
Related Articles, Links

Resection of giant right-sided thymoma using a lateral thoracotomy approach followed by median sternotomy for completion thymectomy.

Gotte JM, Bilfinger TV.

Division of Cardiothoracic Surgery, Stony Brook University Hospital, Stony Brook, NY 11794, USA. jgotte@notes.cc.sunysb.edu

A 48-year-old woman was diagnosed with a giant, 20 x 18 x 9 cm, right-sided thymoma. A right posterolateral thoracotomy was performed to resect this lesion. The pathological diagnosis revealed a stage I thymoma according to Masaoka et al. [1]. Although, in general, a sternotomy approach is preferred for thymectomies, because of its sheer size, this tumor was approached through a right thoracotomy. Recurrent thymomas originating from remnants of the thymus gland have been described in several individual case reports. Apart from these experiences, recent studies indicate a significant increase in the risk of recurrence for thymomas larger than 8 cm. In our patient, the remaining thymus gland portions were removed through a midline sternotomy. There is no information in the literature how often a thoracotomy has had to be chosen over a preferred sternotomy as the initial surgical procedure in order to resect a giant thymoma.

Publication Types:

Case Reports

PMID: 17629872 [PubMed - indexed for MEDLINE]

86: Thorax. 2007 Aug;62(8):666, 695.
Related Articles, Links

A pleural mass with pulmonary infiltrates.

Ryerson CJ, Malhotra S, Lam S, English JC, Ionescu DN.

Department of Respiratory Medicine, Gordon & Leslie Diamond Health Care Centre, Vancouver General Hospital, Vancouver, Canada V5Z 1M9. cryerson@interchange.ubc.ca

Publication Types:

Case Reports

PMID: 17687096 [PubMed - indexed for MEDLINE]

87: Zhonghua Wai Ke Za Zhi. 2007 Aug 1;45(15):1044-7.
Related Articles, Links

[Surgical treatment of tumor invading important vessel]

[Article in Chinese]

Zhang XM, Shen CY, Li W, Zhang XM.

Department of Vascular Surgery, Peking University, People's Hospital, Beijing 100044, China. rmxywk@yahoo.com.cn

OBJECTIVE: To sum up preliminary experience of successful resection of tumor involving important vessel in 77 cases. METHODS: Seventy-seven cases were treated in this series including 47 cases in male and 30 cases in female. The ages ranged from 18 to 75 years with the average of 57. The tumor involving thoraco-abdominal cavity was in one case with malignant neuroblastoma. The tumor from retro-peritoneum invaded into the whole inferior vena cava (IVC), and into two-thirds of the right atrium. Tumor located in thoracic cavity were in 13 cases including IVC leiomyosarcoma in 2 cases, thymic carcinoma in 3 cases, malignant thymoma in 4 cases, malignant seminoma of superior mediatinum in 1 case, malignant lymphoma in 1 case, lung cancer in 2 cases. The tumor located in abdominal cavity were in 24 cases including renal carcinoma with tumor thrombi in 11 cases, inflammatory pseudotumor of retro-peritoneum in 4 cases, malignant fibrous histiocytoma of retro-peritoneum in 1 case, non-Hodgkin's disease of retro-peritoneum in 1 case, lymph metastasis of retro-peritoneum in 2 cases, paraganglion tumor of the right adrenal gland in 1 case, ampullary carcinoma in 1 case, leiomyosarcoma of abdominal IVC in 1 case, leiomyosarcoma of pelvic cavity and IVC in 1 cases, fibrosarcoma of pelvic cavity in 1 case. Tumor located in four extremities in 6 cases including osteogenic sarcoma in 3 cases, vascular endotheliosarcoma of the left iliac fossa in 1 case, fibroneuroma of the left upper extremity in 1 case, lymphoma of double groin in 1 case. Tumor located in neck in 33 cases including carotid body tumor in 32 cases and fibroneuroma of the left upper extremity in 1 case. RESULTS: Complete resection of tumor was in 72 cases, with a rate of 93.5%, palliative resection of tumor was in 5 cases with a rate of 6.5%. No operative death occurred. Four cases died during peri-operative period. Reconstruction of involving vessel with vascular graft was in 13 cases, and shaping or patch closure of vessel was applied in 22 cases. Temporary shunt of carotid artery for neck tumor was used in 18 cases. No death occurred for benign tumor. The survival rate more than half year was 90.4%, and more than one year was 84.9%. CONCLUSION: The radical resection rate for tumor involving important vessel may be improved with the help of vascular technique.

Publication Types:

English Abstract

PMID: 18005586 [PubMed - in process]

88: Nature. 2007 Jul 26;448(7152):439-44. Epub 2007 Jul 4.
Related Articles, Links

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.

Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE.

Division of Integrated Cancer Genomics, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, Arizona 85004, USA.

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17611497 [PubMed - indexed for MEDLINE]

89: Cancer Res. 2007 Jul 15;67(14):7028-36.
Related Articles, Links

A polyepitope DNA vaccine targeted to Her-2/ErbB-2 elicits a broad range of human and murine CTL effectors to protect against tumor challenge.

Scardino A, Alimandi M, Correale P, Smith SG, Bei R, Firat H, Cusi MG, Faure O, Graf-Dubois S, Cencioni G, Marrocco J, Chouaib S, Lemonnier FA, Jackson AM, Kosmatopoulos K.

Institut National de la Santé et de la Recherche Médicale U753, Institut Gustave Roussy, Villejuif, France. antoscardo@yahoo.it

A cDNA vaccine (pVax1/pet-neu) was designed to encode 12 different Her-2/ErbB-2-derived, HLA-A*0201-restricted dominant and high-affinity heteroclitic cryptic epitopes. Vaccination with pVax1/pet-neu triggered multiple and ErbB-2-specific CTL responses in HLA-A*0201 transgenic HHD mice and in HLA-A*0201 healthy donors in vitro. Human and murine CTL specific for each one of the 12 ErbB-2 peptides recognized in vitro both human and murine tumor cells overexpressing endogenous ErbB-2. Furthermore, vaccination of HHD mice with pVax1/pet-neu significantly delayed the in vivo growth of challenged ErbB-2-expressing tumor (EL4/HHD/neu murine thymoma) more actively when compared with vaccination with the empty vector (pVax1) or vehicle alone. These data indicate that the pVax1/pet-neu cDNA vaccine coding for a poly-ErbB-2 epitope is able to generate simultaneous ErbB-2-specific antitumor responses against dominant and cryptic multiple epitopes.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17638916 [PubMed - indexed for MEDLINE]

90: Cancer Res. 2007 Jul 15;67(14):7011-9.
Related Articles, Links

The vascular disrupting agent, DMXAA, directly activates dendritic cells through a MyD88-independent mechanism and generates antitumor cytotoxic T lymphocytes.

Wallace A, LaRosa DF, Kapoor V, Sun J, Cheng G, Jassar A, Blouin A, Ching LM, Albelda SM.

Thoracic Oncology Research Laboratory, Department of Medicine, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

5,6-Di-methylxanthenone-4-acetic acid (DMXAA) is a small molecule in the flavanoid class that has antitumor activity. Although classified as a "vascular disrupting agent," we have recently conducted studies showing that DMXAA has remarkable efficacy in a range of tumors, working primarily as an immune modulator that activates tumor-associated macrophages and induces a subsequent CD8(+) T-cell-mediated response. To more completely analyze the effect of DMXAA on CD8(+) T-cell generation, we treated mice bearing tumors derived from EG7 thymoma cells that express the well-characterized chicken ovalbumin neotumor antigen. Treatment with DMXAA led to cytokine release, tumor cell necrosis, and ultimately reduction in tumor size that was lymphocyte dependent. Within 24 h of administration, we observed dendritic cell activation in tumor-draining lymph nodes (TDLN). This was followed by a rapid and marked increase in the number of tetramer-specific CD8(+) T cells in the spleens of treated animals. In contrast, the vascular disrupting agent combretastatin A4-phosphate, which caused a similar amount of immediate tumor necrosis, did not activate dendritic cells, nor induce an effective antitumor response. Using in vitro systems, we made the observation that DMXAA has the ability to directly activate mouse dendritic cells, as measured by increased expression of costimulatory molecules and proinflammatory cytokine release via a pathway that does not require the Toll-like receptor adaptor molecule MyD88. DMXAA thus has the ability to activate tumor-specific CD8(+) T cells through multiple pathways that include induction of tumor cell death, release of stimulatory cytokines, and direct activation of dendritic cells.

Publication Types:

Research Support, N.I.H., Extramural

PMID: 17638914 [PubMed - indexed for MEDLINE]

91: Lung Cancer. 2007 Jul 3 [Epub ahead of print]
Related Articles, Links: Multimodal treatment of thymic carcinoma: Report of nine cases.

Magois E, Guigay J, Blancard PS, Margery J, Milleron B, Lher P, Jounieaux V.

University Hospital, Amiens, France.

Thymic carcinoma (TC) is thymic epithelial tumor which differs from thymoma because of its rarity, agressiveness and poor prognosis. We studied nine patients with TC according to the WHO (World Health Organization) criteria. Three of these nine patients had stage III disease and six patients had stage IV disease with the classification of Masaoka. Epidermoid TC was the most common subtype. Six patients received VIP chemotherapy comprising cisplatin, ifosfamide, uromitexan and etoposide. Five patients underwent surgical resection, preceded by neoadjuvant chemotherapy for four patients. After surgery, one patient received adjuvant radiotherapy and two patients received adjuvant radiochemotherapy. Six deaths were related to TC progression. The survival time ranged from 1 to 54 months with a median survival of 20 months for the group as a whole. Our descriptive study, based on nine stages III and IV TC, shows a documented efficacy of multimodal treatment (neoadjuvant chemotherapy, surgery and adjuvant treatment). VIP protocol was used for neoadjuvant chemotherapy. High-dose cisplatin (120mg/m(2)cycle), ifosfamide (6g/m(2)cycle) and etoposide (450mg/m(2)cycle) achieved better results than VIP (cisplatin 80mg/m(2)cycle), ifosfamide (4.8g/m(2)cycle) and etoposide (300mg/m(2)cycle). Surgical resection remains the main step in the treatment of TC and the modalities of adjuvant treatment must be defined in further studies.

PMID: 17614156 [PubMed - as supplied by publisher]

92: Acta Cytol. 2007 Jul-Aug;51(4):672-5.
Related Articles, Links

Fine needle aspiration cytology of ectopic hamartomatous thymoma.

Choi JH, Shim YR, Song SY.

Publication Types:

Letter

PMID: 17718153 [PubMed - indexed for MEDLINE]

93: Am J Med. 2007 Jul;120(7):594-7.
Related Articles, Links

A deferred dilemma.

Srinivas R, Agarwal R, Aggarwal AN.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. visitsrinivasan@gmail.com

Publication Types:

Case Reports

PMID: 17602932 [PubMed - indexed for MEDLINE]

94: Am J Surg Pathol. 2007 Jul;31(7):1038-44.
Related Articles, Links: Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms.

Nonaka D, Henley JD, Chiriboga L, Yee H.

Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. daisuke.nonaka@med.nyu.edu

Foxn1 and CD205 (DEC205) are novel thymic epithelial markers that are important for thymic organogenesis and the positive selection process for thymocytes, respectively. These markers were immunohistochemically applied to a total of 77 cases of thymic epithelial neoplasms comprised of 58 cases of thymomas, 17 cases of thymic carcinomas, and 2 cases of thymic neuroendocrine carcinomas. Foxn1 was diffusely expressed in nuclear staining in all cases of type B thymoma and all but 1 case of type A thymoma, whereas the expression was generally focal in thymic carcinoma (76%). The expression was identified in all cases of mixed AB thymoma, with the expression in type A component being more variable than the one in type B component. CD205 cytoplasmic expression in the form of coarse granular staining with membranous accentuation was strong and diffuse in all cases of type B thymoma (100%), and a majority of type A thymoma (89%), and focal with variable intensity in thymic carcinoma (59%). Mixed AB thymoma demonstrated diffuse expression in type B component (100%), and variable expression in type A component (94%). Neither Foxn1 nor CD205 was expressed in 2 cases of thymic neuroendocrine carcinoma. Foxn1 was focally expressed in 13% of cutaneous squamous cell carcinoma and completely negative in cutaneous basal cell carcinoma, whereas it was completely negative in squamous cell carcinoma from head and neck, esophagus and uterine cervix, and normal tissue and malignant neoplasms from all other organs other than thymus. CD205 was expressed in 4% of nonsmall cell carcinomas of lung, 27% of squamous cell carcinoma of head and neck, and 10% of squamous cell carcinoma of esophagus, but the staining pattern was different from that of thymic epithelial neoplasm and was characterized by rather homogeneous and amorphous quality without granularity or membranous reaction. CD205 was expressed in myeloid dendritic cells of various organs and tissues as well. Foxn1 is a sensitive and specific marker for thymoma and thymic carcinoma, and it appears to be superior to CD5 and CD117 for the diagnosis of thymic carcinoma. CD205 is a sensitive and specific marker for thymoma but its sensitivity to thymic carcinoma is lower than CD5 and CD117.

PMID: 17592270 [PubMed - indexed for MEDLINE]

95: Anticancer Res. 2007 Jul-Aug;27(4C):3025-8.
Related Articles, Links

Successful treatment with cyclosporine of thymoma-related aplastic anemia.

Gaglia A, Bobota A, Pectasides E, Kosmas C, Papaxoinis G, Pectasides D.

Second Department of Internal Medicine-Propaedeutic, Oncology Section, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece. gagliam2000@hotmail.com

Aplastic anemia is a rare immune-mediated complication of thymoma. Thymomas, especially of the cortical type, have the capacity to generate mature T-cells from their immature precursors. Furthermore, mature intratumorous T-cells have an increased autoantigen-specific potential. We present the case of a 75-year-old patient with an inoperable cortical thymoma who developed aplastic anemia 7 years after the initial diagnosis. The infiltration of the bone marrow by these cells was accompanied by the production of cytokines such as tumor necrosis factor alpha (TNF-alpha) in the microenvironment of bone marrow and in the serum sample. The patient was successfully treated with oral cyclosporine A for 14 months and when she died due to progression of the thymoma, 9 months after the discontinuation of cyclosporine, the aplastic anemia had not recurred.

Publication Types:

Case Reports

PMID: 17695491 [PubMed - indexed for MEDLINE]

96: Cancer Gene Ther. 2007 Jul;14(7):661-75. Epub 2007 May 4.
Related Articles, Links

Engineered CD8+ cytotoxic T cells with fiber-modified adenovirus-mediated TNF-alpha gene transfection counteract immunosuppressive interleukin-10-secreting lung metastasis and solid tumors.

Ye Z, Shi M, Chan T, Sas S, Xu S, Xiang J.

Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, Canada.

T-cell suppression derived from tumor-secreted immunosuppressive interleukin (IL)-10 becomes a major barrier to CD8+ T-cell immunotherapy of tumors. Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine capable of activating T and dendritic cells (DCs) and counteracting IL-10-mediated DC inhibition and regulatory T-cell-mediated immune suppression. In this study, we constructed a recombinant adenovirus (MF)AdVTNF with fiber-gene modified by RGD insertion into the viral knob's H1 loop and a melanoma cell line B16(OVA/IL-10) engineered to express ovalbumin (OVA) and to secrete IL-10 (2.2 ng/ml/10(6) cells/24 h). We transfected OVA-specific CD8+ T cells with (MF)AdVTNF, and found a fivefold increase in transgene human TNF-alpha secretion (4.3 ng/ml/10(6) cells/24 h) by the engineered CD8+ T(TNF) cells transfected with (MF)AdVTNF, compared to that (0.8 ng/ml/10(6) cells/24 h) by CD8+ T cells transfected with the original AdVTNF without viral fiber modification. The engineered CD8+ T(TNF) cells exhibited enhanced cytotoxicity and elongated survival in vivo after adoptive transfer. TNF-alpha derived from both the donor CD8+ T cells and the host cells plays an important role in donor CD8+ T-cell survival in vivo after adoptive transfer. We also demonstrated that the transfected B16(OVA/IL-10) tumor cells secreting IL-10 are more resistant to in vivo CD8+ T-cell therapy than the original B16(OVA) tumor cells without IL-10 expression. Interestingly, the engineered CD8+ T(TNF) cells secreting transgene-coded TNF-alpha, but not the control CD8+ T(control) cells without any transgene expression eradicated IL-10-secreting 12-day lung micrometastasis in all 10/10 mice and IL-10-secreting solid tumors ( approximately 5 mm in diameter) in 6/10 mice. Transfer of the engineered CD8+ T(TNF) cells further induced both donor- and host-derived memory CD8+ T cells, leading to a stronger long-term antitumor immunity against the IL-10-secreting B16(OVA/IL-10) tumor cell challenges. Therefore, CD8+ T cells engineered to secrete TNF-alpha may be useful when designing strategies for adoptive T-cell therapy of solid tumors.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17479109 [PubMed - indexed for MEDLINE]

97: Clin Exp Immunol. 2007 Jul;149(1):16-22. Epub 2007 Apr 2.
Related Articles, Links

Antibodies to CRMP3-4 associated with limbic encephalitis and thymoma.

Knudsen A, Bredholt G, Storstein A, Oltedal L, Davanger S, Krossnes B, Honnorat J, Vedeler CA.

Department of Neurology, Haukeland University Hospital, Bergen, Norway. anette.knudsen.nevro@helse-bergen.no

We present a case with subacute limbic encephalitis (LE) and thymoma. Neither classical onconeural antibodies nor antibodies to voltage gated potassium channels (VGKC) were detected, but the serum was positive for anti-glutamic acid decarboxylase (GAD). The patient serum also stained synaptic boutons of pyramidal cells and nuclei of granule cells of rat hippocampus. The objective of the study was to identify new antibodies associated with LE. Screening a cDNA expression library identified collapsin response mediator protein 3 (CRMP3), a protein involved in neurite outgrowth. The serum also reacted with both CRMP3 and CRMP4 by Western blot. Similar binding pattern of hippocampal granule cells was obtained with the patient serum and rabbit anti-serum against CRMP1-4. The CRMP1-4 antibodies stained neuronal nuclei of a biopsy from the patient's temporal lobe, but CRMP1-4 expression in thymoma could only be detected by immunoblotting. Absorption studies with recombinant GAD failed to abolish the staining of the hippocampal granule cells. Our findings illustrate that CRMP3-4 antibodies can be associated with LE and thymoma. This has previously been associated with CRMP5.

Publication Types:

PMID: 17403058 [PubMed - indexed for MEDLINE]

98: Gen Thorac Cardiovasc Surg. 2007 Jul;55(7):281-3.
Related Articles, Links

Thymoma with intracystic dissemination arising in a unilocular thymic cyst.

Kitami A, Kamio Y, Uematsu S, Sato Y, Kadokura M.

Respiratory Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki-ku, Yokohama, Kanagawa 224-8503, Japan. akitami@med.showa-u.ac.jp

A 33-year-old asymptomatic woman was referred to our hospital for evaluation of an abnormal shadow on a chest radiograph. A chest-computed tomogram revealed a cystic, partially solid tumor in the right inferior mediastinum. Following an initial diagnosis of cystic teratoma, surgery was performed. The tumor, a well-encapsulated, thin-walled cyst located within the right inferior lobe of the thymus, was extirpated by partial resection of the thymus. The cut surface revealed a unilocular cyst containing multiple grayish-white tumors on the inner cyst walls. Some tumors detached from the wall owing to loose connections. Microscopic findings revealed that the cyst was lined with squamous epithelium. The tumor on the cyst wall was diagnosed to be a type B1 thymoma. Based on these findings, we diagnosed this case as a thymoma originating from the wall of a thymic cyst, accompanied by intracystic dissemination from the tumor.

Publication Types:

Case Reports

PMID: 17679255 [PubMed - indexed for MEDLINE]

99: Hum Pathol. 2007 Jul;38(7):1092-5.
Related Articles, Links

Ectopic hamartomatous thymoma: a case demonstrating skin adnexal differentiation with positivity for epithelial membrane antigen, androgen receptors, and BRST-2 by immunohistochemistry.

Weinreb I, O'Malley F, Ghazarian D.

Department of Pathology, University Health Network, Toronto, Ontario, Canada. weinrebi@yahoo.ca

Ectopic hamartomatous thymoma is a rare tumor of the lower neck occurring in adult men, which follows a benign course. They are triphasic with epithelial, adipocytic, and spindled elements in variable amounts. The origin of this tumor has been debated, but it is now believed to arise from remnants of the cervical sinus of His from early development. We describe a case of ectopic hamartomatous thymoma with typical features, as well as multifocal areas of skin adnexal differentiation. These included sebaceous, eccrine, and apocrine elements. We highlighted these by using immunohistochemistry to epithelial membrane antigen, BRST-2, and androgen receptors (AR). Epithelial membrane antigen stained sebaceous cells and the luminal borders of eccrine and apocrine ducts. BRST-2 and AR stained apocrine elements in a cytoplasmic and a nuclear pattern, respectively. The spindled component also expressed nuclear AR. AR positivity has not been described previously and may explain the occurrence primarily in men in postpubertal life.

Publication Types:

Case Reports

PMID: 17574947 [PubMed - indexed for MEDLINE]

100: Indian J Pathol Microbiol. 2007 Jul;50(3):553-5.
Related Articles, Links

Ectopic cervical thymoma--the great mimic: a case report.

Ramdas A, Jacob SE, Varghese RG, Dasiah S, Rai R.

Department of Pathology, Pondicherry Institute of Medical Sciences, Kalapet, Pondicherry. anitaramdas2002@yahoo.co.in

Ectopic cervical thymoma is a rare tumour that probably arises from thymic tissue trapped during the migration of the thymus into the anterior mediastinum from the third and fourth pharyngeal pouches. As it occurs in the region of the thyroid gland it mimics thyroid lesions and can cause confusion to the clinician, sonologist and cytologist. Misinterpretation of frozen sections can also occur if knowledge of this entity is not present. We are reporting a case of this rare entity in an elderly lady who presented with a neck mass that mimicked a thyroid lesion. Ectopic cervical thymoma should be considered in the list of differential diagnosis of neck masses in the elderly.

Publication Types:

Case Reports

PMID: 17883132 [PubMed - indexed for MEDLINE]

101: J Card Surg. 2007 Jul-Aug;22(4):330-2.
Related Articles, Links

Radical operation for invasive thymoma with intracaval, intracardiac, and lung invasion.

Shudo Y, Takahashi T, Ohta M, Ikeda N, Matsue H, Taniguchi K.

Department of Cardiovascular Surgery, Japan Labour Health and Welfare Organization, Osaka Rosai Hospital, Osaka, Japan. shudo@s5.dion.ne.jp

We report a rare case of invasive type AB thymoma (WHO classification system) with intracaval and intracardiac extension into the right atrium. A cardiopulmonary bypass facilitated an en bloc excision of the tumor with a lobectomy, along with a combined resection of the right atrium and reconstruction of the bilateral brachiocephalic veins and right atrium. Aggressive surgical intervention should be considered in such cases, as long-term prognosis is primarily dependent on a complete resection of the extended thymoma.

Publication Types:

Case Reports

PMID: 17661777 [PubMed - indexed for MEDLINE]

102: J Pediatr Hematol Oncol. 2007 Jul;29(7):492-5.
Related Articles, Links

Primary pericardial synovial sarcoma confirmed by molecular genetic studies: a case report.

Hing SN, Marshall L, Al-Saadi R, Hargrave D.

Section of Paediatric Oncology, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.

Primary pericardial synovial sarcoma is an extremely rare tumor. The awkward tumor site and clinical features associated with quite advanced disease at presentation make obtaining adequate biopsy material challenging. Ambiguous histologic features may also make diagnosis difficult. We present a case of a 15-year-old patient with an original diagnosis of a spindle cell thymoma. After definitive surgery the diagnosis was amended to a primary pericardial synovial sarcoma. Molecular confirmation of the SYT-SSX fusion gene was critical in reaching an accurate diagnosis. This highlights the necessity for routine molecular genetic studies, so that patient therapy can be directed accordingly.

Publication Types:

Case Reports

PMID: 17609629 [PubMed - indexed for MEDLINE]

103: Lung Cancer. 2007 Jul;57(1):115-7. Epub 2007 Mar 26.
Related Articles, Links

Myasthenia gravis in ectopic thymoma presenting as pleural masses.

Kim HS, Lee HJ, Cho SY, Koh JS, Ryoo BY, Kim CH, Lee JC.

Department of Internal Medicine, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea.

Multiple pleural masses were found in a 52-year-old female suggesting malignant mesothelioma or pleural metastasis from other malignancy. Unexpectedly, ectopic thymoma was diagnosed by percutaneous needle biopsy and subsequent myasthenia gravis developed during admission. Although ectopic thymoma in pleura is unusual, it should be considered as one of the possible etiologies causing diffuse pleural masses.

Publication Types:

Case Reports

PMID: 17368624 [PubMed - indexed for MEDLINE]

104: Mol Ther. 2007 Jul;15(7):1273-9. Epub 2007 Apr 24.
Related Articles, Links: Correction of DNA Protein Kinase Deficiency by Spliceosome-mediated RNA Trans-splicing and Sleeping Beauty Transposon Delivery.

Zayed H, Xia L, Yerich A, Yant SR, Kay MA, Puttaraju M, McGarrity GJ, Wiest DL, McIvor RS, Tolar J, Blazar BR.

1University of Minnesota Cancer Center, Department of Pediatrics, Division of Hematology-Oncology, Blood and Marrow Transplantation, University of Minnesota, Minneapolis, USA.

Spliceosome-mediated RNA trans-splicing (SMaRT) is an emerging technology for the repair of defective pre-messenger RNA (pre-mRNA) molecules. It is especially useful in the treatment of genetic disorders involving large genes. Although viral vectors have been used for achieving long-lasting expression of trans-splicing molecules, the immunogenicity and suboptimal safety profiles associated with viral-based components could limit the widespread application of SMaRT in the repair of genetic defects. Here, we tested whether the non-viral Sleeping Beauty (SB) transposon system could mediate stable delivery of trans-splicing molecules designed to correct the genetic defect responsible for severe combined immune deficiency (SCID). This immunological disorder is caused by a point mutation within the 12.4 kilobase (kb) gene encoding the DNA protein kinase catalytic subunit (DNA-PKcs) and is associated with aberrant DNA repair, defective T- and B-cell production, and hypersensitivity to radiation-induced injury. Using a novel SB-based trans-splicing vector, we demonstrate stable mRNA correction, proper DNA-PKcs protein production, and conference of a radiation-resistant phenotype in a T-cell thymoma cell line and SCID multipotent adult progenitor cells (MAPCs). These results suggest that SB-based trans-splicing vectors should prove useful in facilitating the correction of endogenous mutated mRNA transcripts, including the DNA-PKcs defect present in SCID cells.Molecular Therapy (2007) 15 7, 1273-1279. doi:10.1038/sj.mt.6300178.

PMID: 17457319 [PubMed - in process]

105: Nat Clin Pract Neurol. 2007 Jul;3(7):405-10.
Related Articles, Links

Antibodies to AChR, MuSK and VGKC in a patient with myasthenia gravis and Morvan's syndrome.

Díaz-Manera J, Rojas-García R, Gallardo E, Juárez C, Martínez-Domeño A, Martínez-Ramírez S, Dalmau J, Blesa R, Illa I.

Neuromuscular Diseases Section, Department of Neurology, at Hospital de la Santa Creu i Sant Pau in Barcelona, Spain.

BACKGROUND: A 46-year-old woman presented to a local hospital with acute respiratory failure and a 2-year progressive history of fatigue, personality changes, increased sweating, dysphagia with substantial weight loss, dysarthria, and intermittent ptosis and diplopia. Neurological examination showed facial weakness, lingual atrophy and bulbar palsy, which necessitated the use of a feeding tube and ventilatory support. Mild limb weakness with severe muscle atrophy and diffuse muscle twitches were observed. The patient had also developed visual hallucinations and persecutory delusions. Her personal and family medical histories were unremarkable. INVESTIGATIONS: Sensory and motor nerve conduction studies, repetitive nerve stimulation, electromyogram, blood-cell counts, general chemistry and metabolic function tests, a CT scan, an [(18)F]fluorodeoxyglucose-PET scan, and tests for serum antibodies to acetylcholine receptors, muscle-specific tyrosine kinase, voltage-gated potassium channels, P/Q-type voltage-gated calcium channels, and paraneoplastic antigens, were carried out. DIAGNOSIS: Myasthenia gravis associated with antibodies to acetylcholine receptor and muscle-specific tyrosine kinase, and Morvan's syndrome associated with antibodies to voltage-gated potassium channels in the absence of thymoma. MANAGEMENT: Combined treatment with prednisone, intravenous immunoglobulin, ciclosporin, and rituximab.

Publication Types:

Case Reports

PMID: 17611489 [PubMed - indexed for MEDLINE]

106: Rev Port Pneumol. 2007 Jul-Aug;13(4):553-85.
Related Articles, Links

Malignant thymomas--the experience of the Portuguese Oncological Institute, Porto, and literature review.

[Article in English, Portuguese]

Sousa B, Araújo A, Amaro T, Azevedo I, Soares M, Sousa O.

Medical Oncology, Instituto Português de Oncologia do Porto Francisco Gentil-EPE, Rua Dr António Bernardino de Almeida, 4200-072 Porto.

INTRODUCTION: Epithelial thymic tumours (ETT), which comprise the majority of thymomas, are neoplasias developed from the epithelial cells of the thymus and constitute around 30% of anterior mediastinal masses in adults. Thymomas consist of cells with no cytological characteristics of malignity; malignant behaviour is determined by invasion of the capsule and adjacent structures. These tumours present a broad spectrum of clinical and morphological characteristics and the small series of known patients makes establishing a standard treatment difficult. MATERIAL AND METHODS: A retrospective study was made into thymoma diagnosed patients admitted to the Portuguese Oncology Institute in Porto (IPO-Porto) from 1983 to 2004. Clinical characteristics were analysed and a histological classification made in accordance with World Health Organization criteria, Masaoka staging, and their relation to treatment methods. A review of the clinical records of these patients was then made, as well as a review of histological material for classification in line with 1999 WHO criteria. RESULTS: Twenty-eight ETT patients were treated at the IPO-Porto between 1983 and 2004. Of these, 21 had invasive thymomas and these are the subject of this study. Eleven subjects were male and 10 female, with a median age of 55 years (24-79 years). The WHO histological classification was as follows: 2 patients (9.5%) type A, 6 (28.6%) type AB, 4 (19%) type B1, 2 (9.5%) type B2, 7 (33.4%) type B3. Masaoka staging was 9 patients (42.8%) with stage II, 6 (28.6%) with stage III and 6 (28.6%) with stage IVa. The majority of patients had local symptoms, with only one subject diagnosed with erythrocyte aplasia and five with Myasthenia Gravis (MG). The 6 patients who were given complete surgical resection only showed no evidence of disease recurrence (2 type A-II, 2 type AB-II, 1 type B1-II, 1 type B2- IVa), with follow-up from 8-144 months. Ten patients with complete resection received adjuvant treatment; 6 radiotherapy (4 B3-II patients, 2 B3-III patients), 2 chemotherapy (AB-IVa) and 2 chemo and radiotherapy (B1-IVa, B2-III). Only the 2 patients who underwent adjuvant chemotherapy relapsed, at 168 and 46 months, dying at 168 and 49 months, respectively. The remaining patients who were given adjuvant treatment did not present signs of disease. Of the 5 subjects having incomplete resection followed by complementary treatment (2 AB-III patients, 2 B1-IVa patients, 1 B3-III patient), 3 died, at 11 months (B3-III), 12 months (B1-IVa) and 241 months (AB-III), the latter with MG. CONCLUSIONS: Predictive factors of bad prognosis here were incomplete resection, advanced staging and B3 histological subtype, the smallness of this series notwithstanding. It is necessary to investigate the role of adjuvant and neoadjuvant treatment in a group of subjects with advanced disease of the B3 histological subtype.

Publication Types:

Review

PMID: 17898913 [PubMed - indexed for MEDLINE]

107: Rinsho Shinkeigaku. 2007 Jul;47(7):423-8.
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[Concurrence of myasthenia gravis, polymyositis, thyroiditis and eosinophilia in a patient with type B1 thymoma]

[Article in Japanese]

Inoue M, Kojima Y, Shinde A, Satoi H, Makino F, Kanda M, Shibasaki H.

Department of Neurology, Ijinkai Takeda General Hospital.

We presented a 43-year-old Japanese woman who acutely developed weakness of all extremities and difficulty in swallowing and drooping of eyelids, characterized by easy fatigability at the end of December, 2005. On general physical examination, she had moderate goiter. No cervical lymphadenopathy, cardiac murmur, or skin rash was noted. Neurologically, she had blepharoptosis, more on the right, only in the upright position with easy fatigability and marked weakness in the neck flexor, trunk, and all limb muscles much more proximally than distally. She had neither muscular atrophy nor upper motor neuron sign. Laboratory data showed slight leukocytosis with eosinophilia (up to 31%), and serum creatine kinase was markedly increased to over 2,000 IU/l. TSH receptor antibody (11.9%) and anti-acetylcholine receptor antibody (46.6 nmol/L) were also increased. Edrophonium test was positive. Electrophysiologically, muscle evoked potentials by repetitive motor nerve stimulation showed 13% and 50% waning in abductor pollicis brevis and deltoid muscle, respectively, at low frequency and no waxing at high frequency. Needle EMG showed fibrillation potentials and positive sharp waves in proximal muscles. Polymyositis was diagnosed by muscle biopsy which showed infiltration of lymphocytes in the endomysium and around non-necrotic muscle fibers. Upper arm muscle MRI showed multifocal high signal intensity lesions on T2-weighted images which were likely related to myositis. This finding is atypical for polymyositis. X-ray and CT of chest showed a mass lesion in the left pulmonary hilum, which was histologically diagnosed as type B1 thymoma. Thus, the present case had myasthenia gravis, polymyositis, thyroidititis and eosinophilia associated with type B1 thymoma. After the thymectomy, corticosteroid administration and immunoadsorption therapy, clinical symptoms and all laboratory abnormalities markedly improved.

Publication Types:

PMID: 17710886 [PubMed - indexed for MEDLINE]

108: Oncogene. 2007 Jun 28;26(30):4415-27. Epub 2007 Feb 5.
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Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice.

Luo F, Brooks DG, Ye H, Hamoudi R, Poulogiannis G, Patek CE, Winton DJ, Arends MJ.

Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

K-ras mutation occurs in 40-50% of human colorectal adenomas and carcinomas, but its contribution to intestinal tumorigenesis in vivo is unclear. We developed K-ras(V12) transgenic mice that were crossed with Ah-Cre mice to generate K-ras(V12)/Cre mice, which showed beta-naphthoflavone-induction of Cre-mediated LoxP recombination that activated intestinal expression of K-ras(V12) 4A and 4B transcripts and proteins. Only very occasional intestinal adenomas were observed in beta-naphthoflavone-treated K-ras(V12)/Cre mice aged up to 2 years, suggesting that mutated K-ras expression alone does not significantly initiate intestinal tumourigenesis. To investigate the effects of mutated K-ras on DNA mismatch repair (MMR)-deficient intestinal tumour formation, these mice were crossed with Msh2(-/-) mice to generate K-ras(V12)/Cre/Msh2(-/-) offspring. After beta-naphthoflavone treatment, K-ras(V12)/Cre/Msh2(-/-) mice showed reduced average lifespan of 17.3+/-5.0 weeks from 26.9+/-6.8 (control Msh2(-/-) mice) (P<0.01). They demonstrated increased adenomas in the small intestine from 1.41 (Msh2(-/-) controls) to 7.75 per mouse (increased fivefold, P<0.01). In the large intestine, very few adenomas were found in Msh2(-/-) mice (0.13 per mouse) whereas K-ras(V12)/Cre/Msh2(-/-) mice produced 2.70 adenomas per mouse (increased 20-fold, P<0.01). Over 80% adenomas from K-ras(V12)/Cre/Msh2(-/-) mice showed transgene recombination with expression of K-ras(V12) 4A and 4B transcripts and proteins. Sequencing of endogenous murine K-ras showed mutations in two out of 10 tumours examined from Msh2(-/-) mice, but no mutations in 17 tumours from K-ras(V12)/Cre/Msh2(-/-) mice. Expression of K-ras(V12) in tumours caused activation of the mitogen-activated protein kinase and Akt/protein kinase B signaling pathways, demonstrated by phosphorylation of p44MAPK, Akt and GSK3beta, as well as transcriptional upregulation of Pem, Tcl-1 and Trap1a genes (known targets of K-ras(V12) expression in stem cells). Thus, mutated K-ras cooperates synergistically with MMR deficiency to accelerate intestinal tumorigenesis, particularly in the large intestine.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 17297472 [PubMed - indexed for MEDLINE]

109: Crit Rev Oncol Hematol. 2007 Jun 12 [Epub ahead of print]
Related Articles, Links: Management of thymomas.

Wright CD.

Division of Thoracic Surgery, Massachusetts General Hospital, Harvard Medical School, Blake 1570, Boston, MA 02114, USA.

Thymoma is a rare neoplasm usually with an indolent growth pattern, however, local invasion and/or metastases may occur. The association with several paraneoplastic syndromes, especially myasthenia gravis, is noteworthy. Surgery has been the standard of care for early stage disease with high cure rates anticipated. The most important prognostic factors after resection are Masaoka stage, World Health Organization (WHO) histology, complete resection status and size. Multimodality therapy can result in long-term disease-free survival for patients presenting with locally advanced disease. Thymomas are sensitive to both chemotherapy and radiation therapy and are utilized with good effects in unresectable patients.

PMID: 17570676 [PubMed - as supplied by publisher]

110: Ai Zheng. 2007 Jun;26(6):657-60.
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[Application of mediastinoscopy to diagnosis of mediastinal diseases and staging of lung cancer]

[Article in Chinese]

Chen C, Lin PQ, Lin RB, Kang MQ, Zheng W, Chen DZ.

Department of Thoracic Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, P. R. China.

BACKGROUND & OBJECTIVE: It is still very difficult to make a definite diagnosis for some mediastinal diseases through some examinations, such as CT scan and fibrobronchoscopy. To judge the metastasis of mediastinal lymph nodes exactly for lung cancer patients and make proper staging of lung cancer are important for defining therapeutic schedule and estimating prognosis. This study was to explore the application value and summarize the experience of mediastinoscopy in the diagnosis of mediastinal diseases and the staging of lung cancer with enlarged mediastinal lymph nodes. METHODS: Mediastinoscopy and biopsy were performed in 16 patients with different mediastinal diseases detected by imaging examinations and 14 lung cancer patients with enlarged mediastinal lymph nodes diagnosed by CT scan, PET, or fibrobronchoscopy. The staging of lung cancer was identified according to pathologic diagnosis. RESULTS: Of the 16 patients with different mediastinal diseases clarified by mediastinoscopy, 5 had nodule diseases, 3 had mediastinal lymph node tuberculosis, 2 had mediastinal lymphnoditis, 2 had lymphoma, 1 had extra-gastrointestinal type gastrointestinal malignant interstitialoma,1 had thymoma, 1 had metastatic small cell carcinoma, and 1 had metastatic adenocarcinoma. Of the 14 lung cancer patients with enlarged mediastinal lymph nodes, 6 had metastatic lymph nodes, and 8 had not; all of the 14 cases were accurately staged and received successful operations without severe postoperative complications. CONCLUSION: Mediastinoscopy is a safe, accurate and effective procedure for the diagnosis of mediastinal diseases and the staging of lung cancer.

Publication Types:

English Abstract

PMID: 17562276 [PubMed - in process]

111: Ann Thorac Cardiovasc Surg. 2007 Jun;13(3):198-202.
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Solitary fibrous tumor of the thymus with local invasiveness and pleural dissemination: report of a case.

Iwata T, Nishiyama N, Izumi N, Tsukioka T, Suehiro S.

Department of Thoracic Surgery, Osaka City University Hospital, Osaka, Japan.

A 74-year-old asymptomatic female presented with an anterior mediastinal mass incidentally discovered on a routine chest X-ray. Systemic evaluation demonstrated no metastatic lesions. The patient underwent an extended thymectomy via median sternotomy on suspicion of a thymoma. The tumor had arisen from the left half of the thymus without a pedicle and had directly invaded into the left lung and pericardium. The tumor was resected with the entire thymic tissue, and the invaded lung and pericardium were resected en-bloc. The size of the tumor was 5.3x4.0 cm. A disseminated lesion on the mediastinal pleura was also resected. Histopathologically, the lesion mainly consisted of non-atypical spindle-shaped tumor cells in a so-called "patternless pattern" with various densities of collagenous background. Pleomorphism and mitoses were not significant. Immunohistochemical analysis revealed mesenchymal positive markers such as vimentin and CD34. Epithelial markers such as CAM 5.2 and AE1/AE3 were negative. S-100 protein and desmin were not stained. Solitary fibrous tumor of the thymus was diagnosed histologically. Postoperative adjuvant chemotherapy or radiotherapy was not undertaken because the benefits were uncertain. She is well without recurrence 3 months after the operation.

Publication Types:

Case Reports

PMID: 17592430 [PubMed - indexed for MEDLINE]

112: Biol Reprod. 2007 Jun;76(6):1016-24. Epub 2007 Feb 28.
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