Thymoma Database VIII Publication Date from 2008/01/01 to 2008/12/31 updated:2008.7.22 134 new entries

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1: Ann Diagn Pathol. 2008 Aug;12(4):293-5. Epub 2007 Sep 14.

Angiomyolipoma of the anterior mediastinum.

Knight CS, Cerfolio RJ, Winokur TS.

Department of Pathology, University of Alabama School of Medicine, Birmingham,
AL, USA.

Angiomyolipoma is a benign tumor composed of varying proportions of smooth muscle
cells, blood vessels, and adipose tissue that most commonly occurs in the kidney.
Sporadic lesions and lesions arising in the setting of the tuberous sclerosis
complex have been reported in extrarenal sites. We present the case of an
incidentally discovered angiomyolipoma in the anterior mediastinum. Thymoma was
suspected clinically, and the lesion was composed mainly of
spindled-to-epithelioid cells arranged in a histologic pattern reminiscent of
hemangiopericytoma, a pattern that has been described in thymoma.
Immunohistochemical stains revealed positivity for smooth muscle actin and
HMB-45, revealing the expression of smooth muscle and melanocytic markers
characteristic of angiomyolipoma and other lesions in the PEComa family.

PMID: 18620999 [PubMed - in process]

2: Ann Thorac Surg. 2008 Aug;86(2):673-84.

The role of surgery in the management of thymoma: a systematic review.

Davenport E, Malthaner RA.

Division of Thoracic Surgery, Department of Surgery, The University of Western
Ontario, London, Ontario, Canada.

The literature describing multimodal treatment of thymomas consists almost
exclusively of retrospective case series. We have used a systematic review to
investigate the role of surgery in the management of thymomas. The use of surgery
as the sole therapeutic maneuver in thymoma depends on the stage considered.
Subtotal resection followed by adjuvant treatment may prolong survival, but
studies are equivocal. Some data supports re-resection of recurrent thymoma in
the belief that survival will be prolonged. Approaches to thymectomy other than
sternotomy in early stage thymoma are technically sound, but long-term outcome
data are lacking.

PMID: 18640366 [PubMed - in process]

3: Autoimmunity. 2008 Aug;41(5):377-82.

Infrequent and low AIRE expression in thymoma: difference in AIRE expression
among WHO subtypes does not correlate with association of MG.

Suzuki E, Kobayashi Y, Yano M, Fujii Y.

Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.

Thymoma is frequently associated with autoimmune diseases, including myasthenia
gravis (MG). The failure of thymoma microenvironment to induce T cell tolerance
may be responsible for its association of MG. Autoimmune regulator (AIRE)
expression in the medullary thymic epithelial cells has been reported to play a
role in presenting autoantigen and induction of tolerance. We studied AIRE mRNA
in 45 thymomas and three normal thymi using quantitative reverse transcription
polymerase chain reaction (RT-PCR). Only 23/45 (51.1%) of thymomas expressed AIRE
mRNA at low levels while all normal thymi expressed AIRE mRNA. There was no
correlation between AIRE mRNA and association of MG or presence of
anti-acetylcholine receptor antibody. The infrequent and low expression of AIRE
mRNA may play a role the induction of autoimmune diseases but other factors also
seem to be involved.

PMID: 18568643 [PubMed - indexed for MEDLINE]

4: Biol Psychiatry. 2008 Jul 17. [Epub ahead of print]

AKT Signaling within the Ventral Tegmental Area Regulates Cellular and Behavioral
Responses to Stressful Stimuli.

Krishnan V, Han MH, Mazei-Robison M, Iñiguez SD, Ables JL, Vialou V, Berton O,
Ghose S, Covington HE 3rd, Wiley MD, Henderson RP, Neve RL, Eisch AJ, Tamminga
CA, Russo SJ, Bolaños CA, Nestler EJ.

Department of Psychiatry and Neuroscience, University of Texas Southwestern
Medical Center, Dallas, Texas.

BACKGROUND: The neurobiological mechanisms by which only a minority of
stress-exposed individuals develop psychiatric diseases remain largely unknown.
Recent evidence suggests that dopaminergic neurons of the ventral tegmental area
(VTA) play a key role in the manifestation of stress vulnerability. METHODS:
Using a social defeat paradigm, we segregated susceptible mice (socially
avoidant) from unsusceptible mice (socially interactive) and examined VTA punches
for changes in neurotrophic signaling. Employing a series of viral vectors, we
sought to causally implicate these neurotrophic changes in the development of
avoidance behavior. RESULTS: Susceptibility to social defeat was associated with
a significant reduction in levels of active/phosphorylated AKT (thymoma viral
proto-oncogene) within the VTA, whereas chronic antidepressant treatment (in mice
and humans) increased active AKT levels. This defeat-induced reduction in AKT
activation in susceptible mice was both necessary and sufficient to recapitulate
depressive behaviors associated with susceptibility. Pharmacologic reductions in
AKT activity also significantly raised the firing frequency of VTA dopamine
neurons, an important electrophysiologic hallmark of the susceptible phenotype.
CONCLUSIONS: These studies highlight a crucial role for decreases in VTA AKT
signaling as a key mediator of the maladaptive cellular and behavioral response
to chronic stress.

PMID: 18639865 [PubMed - as supplied by publisher]

5: J Psychopharmacol. 2008 Jul 17. [Epub ahead of print]

Lack of association between AKT1 variances versus clinical manifestations and
social function in patients with schizophrenia.

Liu YC, Huang CL, Wu PL, Chang YC, Huang CH, Lane HY.

Department of Psychiatry, Shinyin Hospital, Department of Health, Executive Yuan,
Tainan, Taiwan.

Abstract The elucidation of genotype-phenotype relationships in psychiatric
research is at an early stage. V-akt murine thymoma viral oncogene homolog 1
(AKT1) is a serine/threonine kinase known as protein kinase B. Emerging studies
have implicated the role of AKT1 in pathogenesis of schizophrenia; however, the
findings have not been consistent. This study aims to examine the association of
AKT1 polymorphisms with drug-free and post-treatment symptomatology and social
function in patients with schizophrenia. One hundred and twenty newly
hospitalised patients with acutely exacerbated schizophrenia who had never been
treated by atypical antipsychotics were recruited. They received optimal
treatment of risperidone for up to 42 days in the inpatient research unit.
Clinical manifestations were monitored by Positive and Negative Syndrome Scale
(PANSS) and social function by Nurses' Observation Scale for Inpatients
Evaluation (NOSIE). Patients were genotyped for eight AKT1 Single Nucleotide
Polymorphism (SNPs), which have been previously investigated for association with
schizophrenia. At drug-free status and after best possible treatment of
risperidone, genotypes of each SNP did not influence performances in NOSIE,
PANSS-total, -positive, -negative and -general psychopathology profiles. These
results suggest that AKT1 does not play a significant role in clinical and
functional manifestations in patients with schizophrenia who receive risperidone
treatment. Future research should also focus on the relationships between
genotypes of other susceptibility genes and phenotypes or functional outcomes of
schizophrenia.

PMID: 18635704 [PubMed - as supplied by publisher]

6: Int J Surg Pathol. 2008 Jul 8. [Epub ahead of print]

Papillary Adenocarcinoma of the Thymus: Case Report and Review of the Literature.

Furtado A, Nogueira R, Ferreira D, Tente D, Eisele R, Parente B.

A 44-year-old male with a mediastinal mass measuring 3.5 x 3.5 x 3 cm was
diagnosed with papillary adenocarcinoma of the thymus. Other origins of papillary
adenocarcinoma were excluded by clinical, imaging, and immunocytochemical methods
before assuming this diagnosis. Residual thymus was seen under the microscope.
Focal CD5 immunoreactivity was present. There was no associated thymoma. The
patient underwent surgery, radiotherapy, and chemotherapy. He disclosed systemic
recurrence at 18 months (subcutaneous nodule). He is alive after 24 months of
follow-up with active disease. There had been only 7 cases of this rare entity
published before.

PMID: 18611939 [PubMed - as supplied by publisher]

7: Cancer Gene Ther. 2008 Jul 4. [Epub ahead of print]

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not
therapeutic antitumor effects.

Jin HT, Youn JI, Choi SY, Seo SH, Park SH, Song MY, Yang SH, Sung YC.

1Research Institute, Genexine Co. Ltd, Seoul, Republic of Korea.

A novel cytokine interleukin (IL)-23 bears a structural and functional
resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant
replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23
was constructed and compared with rAd/IL-12N220L in terms of immunological and
antitumor effects. In a prophylactic setting, vaccination with rAd/ovalbumin
(OVA) and rAd/IL-23N220L enhanced OVA-specific CD8(+) T-cell responses that were
closely associated with complete protection against the subsequent challenge of
OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral
injection of rAd/IL-23N220L showed only marginal antitumor activity against
several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas
IL-23 still induced tumor-specific CD8(+) T-cell responses, it could not activate
natural killer (NK) cells in vitro and in vivo. In addition, the adoptive
transfer of activated NK cells partially restored the therapeutic antitumor
effect of IL-23, indicating that NK cells are one of the crucial factors
responsible for the regression of established tumors. Taken together, we
demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent
prophylactic, but not a therapeutic, antitumor effect.Cancer Gene Therapy advance
online publication, 4 July 2008; doi:10.1038/cgt.2008.41.

PMID: 18600259 [PubMed - as supplied by publisher]

8: J Neuroimmunol. 2008 Jul 4. [Epub ahead of print]

Autoantibodies against TRPC3 and ryanodine receptor in myasthenia gravis.

Takamori M.

Neurological Center, Kanazawa-Nishi Hospital, 6-15-41, Ekinishi-Honmachi,
Kanazawa, Ishikawa-ken, 920-0025, Japan.

The transient receptor potential canonical type-3 (TRPC3, receptor- and
store-operated Ca(2+) influx channel) participates in skeletal muscle
contraction; its functional interactions with ryanodine receptor-1 (RyR1) are
independent of sarcoplasmic Ca(2+) content and dihydropyridine receptor. In 25
generalized myasthenia gravis (MG), we detected antibodies against human TRPC3
peptide in 9 patients (8 with thymoma and one with hyperplastic thymus) and those
against human RyR1 peptides in 16 patients (15 with thymoma and one with
hyperplastic thymus). Both antibodies were found in patients with more severe
myasthenia and could contribute to the contractile abnormalities in MG.

PMID: 18602703 [PubMed - as supplied by publisher]

9: J Neurol Sci. 2008 Jul 2. [Epub ahead of print]

Prognosis of ocular myasthenia in Korea: A retrospective multicenter analysis of
202 patients.

Hong YH, Kwon SB, Kim BJ, Kim BJ, Kim SH, Kim JK, Park KS, Park KJ, Sung JJ, Sohn
EH, Lee YB, Jeong D, Joo IS, Choi BO, Choi YC; for the Korean Research Group for
Neuromuscular Diseases.

Seoul National University Boramae Hospital, South Korea.

OBJECTIVES: The aims of this study were to obtain data on the frequency with
which Korean patients with autoimmune myasthenia gravis (MG) present solely with
ocular disturbances and progress to develop generalized disease and to identify
the prognostic factors associated with secondary generalization. METHODS: We
conducted a retrospective multicenter survey in which a total of 376 adult
patients who were newly diagnosed with MG from 2000 through 2005 were reviewed
for analysis. Patients with ocular MG at the time of symptom presentation (n=202,
53.7%) were divided into two subgroups according to their prognosis: the patients
whose disease remained ocular throughout the follow-ups were placed in the OMG-R
group, and the patients who progressed to develop generalized disease were placed
in the OMG-G group. Clinical characteristics and laboratory findings were
compared between the two subgroups. RESULTS: Secondary generalization developed
in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after
symptom presentation, while the disease remained ocular throughout the follow-up
duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR
antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were
more frequently observed in the patients in the OMG-G group than in those in the
OMG-R group (p<0.01 in all). In seropositive cases, the titers of AChR antibody
were also significantly higher in the OMG-G group than in the OMG-R group
(median, 3.8 nM vs. 6.4 nM; p<0.05). Cox proportional hazards regression analyses
showed that early oral prednisolone treatment significantly reduced the risk of
secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR
antibody (HR, 5.34; 95% CI, 1.60-17.8) and thymoma (HR, 2.32; 95% CI, 1.21-4.45)
were predictive of the development of secondary generalization. CONCLUSIONS: Our
findings suggest that several factors, including the AChR antibody, thymoma,
early corticosteroid treatment, and possibly latent neuromuscular abnormality
revealed by RNST, may have an impact on the risk of developing generalized
disease in Korean patients presenting with ocular myasthenia.

PMID: 18602121 [PubMed - as supplied by publisher]

10: Ann Oncol. 2008 Jul;19(7):1361-2. Epub 2008 Jun 4.

Response of malignant thymoma to erlotinib.

Christodoulou C, Murray S, Dahabreh J, Petraki K, Nikolakopoulou A, Mavri A,
Skarlos D.

Publication Types:
Letter

PMID: 18534960 [PubMed - in process]

11: Ann Thorac Surg. 2008 Jul;86(1):299-301.

Recurrent myasthenia gravis due to a pleural implant 3 years after radical
thymectomy.

Heyman SR, De Raeve H, Mercelis R, De Pooter C, Van Schil P.

Department of Thoracic and Vascular Surgery, Antwerp University Hospital,
Antwerp, Belgium. stijn_heyman@hotmail.com

Although recurrence of a thymoma is rare, pleural dissemination or local relapses
have been described. We present a patient who underwent complete thymectomy for a
thymoma, type AB according to the World Health Organization classification and
stage II according to Masaoka, followed by adjuvant radiotherapy. Three years
later, a relapse of the myasthenic symptoms occurred. An isolated pleural implant
above the left diaphragm was removed by video-assisted thoracoscopy. Pathology
confirmed the recurrence of the thymoma. As this is a rare occurrence, no precise
therapeutic guidelines exist. In our case, surgical resection of the recurrence
with adjuvant immunomodulating therapy for myasthenia provided good results.

Publication Types:
Case Reports

PMID: 18573446 [PubMed - indexed for MEDLINE]

12: Clin Gastroenterol Hepatol. 2008 Jul 1. [Epub ahead of print]

Serologic Profiles Aiding the Diagnosis of Autoimmune Gastrointestinal
Dysmotility.

Dhamija R, Tan KM, Pittock SJ, Foxx-Orenstein A, Benarroch E, Lennon VA.

Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota.

BACKGROUND & AIMS: Autoimmune gastrointestinal dysmotility is a limited
autoimmune dysautonomia occurring idiopathically or in the context of an
anatomically remote neoplasm, previously documented or unsuspected. Here we
report 24 Mayo Clinic patients in whom the profile of serum autoantibodies aided
this diagnosis. METHODS: All patients were ascertained serologically in the
course of service evaluation for autoantibodies consistent with neurologic
autoimmunity. Review of their histories, motility studies, and laboratory
findings revealed that all had presented with subacute gastrointestinal
dysmotility. RESULTS: Recorded motility abnormalities included esophageal
dysmotility 8 (6 had achalasia), delayed gastric emptying 12, slow small
intestinal transit 7, slow colonic transit 4, and pelvic floor dyssynergia 4.
Four patients underwent abdominal surgery; 2 commenced total parenteral
nutrition. Plasma membrane cation channel autoantibodies were detected in 23
patients: neuronal voltage-gated calcium channel (5 N-type and 1 P/Q-type),
acetylcholine receptor (11 ganglionic-type and 4 muscle-type), and neuronal
voltage-gated potassium channel autoantibodies (4). Two patients had antineuronal
nuclear autoantibodies, type 1. Approximately half of the patients had neural
autoantibodies (including skeletal muscle striational and glutamic acid
decarboxylase, 65kd isoform) or other antibody markers of organ-specific
autoimmunity (thyroid or gastric parietal cell specificities). Neoplasia was
diagnosed in 11 patients (9 recent, 2 remote): lung, breast and endometrial,
gastrointestinal and thymoma. Moderate to dramatic improvement in
gastrointestinal symptoms was reported after immunotherapy in 4 of 4 patients
treated and after pyridostigmine treatment in 2 of 2 patients treated.
CONCLUSIONS: Autoimmune serology aids the diagnosis of autoimmune
gastrointestinal dysmotility, both paraneoplastic and idiopathic, and might guide
management.

PMID: 18599359 [PubMed - as supplied by publisher]

13: J Am Anim Hosp Assoc. 2008 Jul-Aug;44(4):210-7.

Granulocytopenia associated with thymoma in a domestic shorthaired cat.

Fidel JL, Pargass IS, Dark MJ, Holmes SP.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine,
Washington State University, Pullman, Washington 99164-6610, USA.

A 5-year-old, spayed female cat was referred because of a mass in the cranial
mediastinum noted on thoracic radiographs. A thymoma was diagnosed following
ultrasound and biopsy of the mass. Treatment was initiated with coarse-fraction
radiation therapy using external-beam therapy (four fractions of 5 Gy). The mass
responded, but granulocytopenia developed. Bone marrow examination showed a
myeloid to erythroid ratio of approximately 1:1, with a left shift within the
myeloid line. These findings, as well as the lack of toxic changes within the
peripheral blood neutrophils, suggested immune-mediated destruction of peripheral
granulocytes. Immune suppression with prednisone and cyclosporine was instituted.
After 7 weeks, the neutrophil count returned to normal. The tumor was removed,
and cyclosporine was reduced and eventually discontinued 3 weeks postsurgery.

PMID: 18593858 [PubMed - in process]

14: J Cancer Res Clin Oncol. 2008 Jul;134(7):789-92. Epub 2008 Jan 22.

Establishment of thymoma-prone congenic rat strain, ACI.BUF/Mna-Tsr1/Tsr1.

Matsuyama M, Kato K, Higo-Moriguchi K, Yamada T, Kuramoto T, Kuroda M.

Department of Surgical Pathology, School of Medicine, Fujita Health University,
1-98 Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi-ken, 470-1192, Japan,
mmatsuya@fujita-hu.ac.jp.

PURPOSE: To confirm the presence of the susceptible gene for the thymoma
development in the region that was assumed by the previous linkage study by Oyabu
et al. (J Natl Cancer Inst 91:279-282, 1999), we tried to establish a congenic
strain of rats. METHODS: Backcrossings between the BUF/Mna strain as a donor
strain and the ACI/NMna strain as an inbred partner were repeated for 12
generations, examining whether rats had the thymoma development region, and then
homozygous rats were yielded by mating among the heterozygotes. To detect the
phenotypic expression, heterozygous ACI.BUF/Mna-Tsr1/+ (ACI-Tsr1/+) rats were
generated by crossing female ACI.BUF/Mna-Tsr1/Tsr1 (ACI-Tsr1/Tsr1) rats with male
ACI/NMna rats and were maintained for 24 months. RESULTS: These ACI-Tsr1/+ rats
produced thymoma in 71%, showing a dominant trait. The thymomas were of the
lymphocyte predominant type, as those developed in rats of the original BUF/Mna
strain. CONCLUSIONS: Thus, a new rat congenic strain, ACI-Tsr1/Tsr1, was
established, revealing that thymoma develops in the dominant trait in ACI-Tsr1/+
rats.

PMID: 18210152 [PubMed - in process]

15: Kyobu Geka. 2008 Jul;61(7):599-601.

[True thymic hyperplasia which was difficult to distinguish from malignancy in
adult; report of a case]

[Article in Japanese]

Takashima S, Nakano H, Misao T.

Department of Surgery, National Hospital Organization Shikoku Cancer Center,
Matsuyama, Japan.

We report a case of 45-year-old man with true thymic hyperplasia. Three years
earlier he had undergone operation for carcinoma of the floor of mouth. He had no
symptoms but had been pointed out an anterior mediastinal mass on chest computed
tomography (CT). Chest CT revealed a well defined solid mass in front of the
ascending aorta. The mass showed sail sign. The size of this mass did not
increase on a follow-up chest CT. The signal intensity of this mass was slightly
inhomogeneous on chest magnetic resonance imaging (MRI). No invasion of the
surround tissues was observed. Since the possibility of thymoma or other
malignancy, extended thymectomy under median sternotomy was performed. His
postoperative course was uneventful. Histopathological examination revealed true
thymic hyperplasia.

Publication Types:
English Abstract

PMID: 18616111 [PubMed - in process]

16: Muscle Nerve. 2008 Jul;38(1):916-20.

Myotonic dystrophy type 1 coexisting with myasthenia gravis and thymoma.

Feyma T, Carter GT, Weiss MD.

Department of Neurology, University of Washington Medical Center, Box 356115,
1959 NE Pacific Street, Seattle, Washington 98195, USA.

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multisystemic disorder
that may rarely be associated with benign and malignant neoplasms. Cases of both
thymoma and myasthenia gravis in association with DM1 are extremely rare. A
literature review revealed only three prior reports. We present a 51-year-old man
with a family history of DM1 and fluctuating diplopia and ptosis, who was found
to have acetylcholine receptor-binding antibodies, thymoma, and a clinical
presentation compatible with ocular myasthenia gravis as well as positive genetic
testing for DM1. Needle electromyographic (EMG) study demonstrated diffuse runs
of myotonic discharges in multiple muscles, consistent with the diagnosis of DM1.
Single-fiber EMG showed both increased jitter and blocking. Due to somatic
instability, which has been shown previously in DM1, the myotonin protein kinase
(DMPK) gene appears to act as a tumor suppressor. Therefore, abnormal CTG repeat
expansions in the gene could lead to the development of thymoma and myasthenia
gravis. Muscle Nerve 38: 916-920, 2008.

PMID: 18563724 [PubMed - in process]

17: Placenta. 2008 Jun 19. [Epub ahead of print]

Differential Activation of Multiple Signalling Pathways Dictates eNOS
Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells.

Mata-Greenwood E, Liao WX, Zheng J, Chen DB.

Division of Maternal-Fetal Medicine (MC0802), Department of Reproductive
Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA
92093-0802, USA;

Fibroblast growth factor (FGF2), but not vascular endothelial growth factor
(VEGF), upregulates endothelial nitric oxide synthase (eNOS) protein expression,
at least partially, via activation of extracellular signal-regulated kinase 2/1
(ERK2/1) in ovine fetoplacental artery endothelial (oFPAE) cells. Herein we
further investigated the temporal effects of FGF2 and VEGF on other signalling
pathways including members (Jun N-terminal kinase JNK1/2 and p38MAPK) of
mitogen-activated protein kinases (MAPK), phosphatidylinositol-3 kinase/v-akt
murine thymoma viral oncogene homologue 1 (PI3K/AKT1), and the tyrosine kinase
c-SRC, and examined if either one or more of these pathways play a role in the
differential regulation of eNOS by FGF2 and VEGF. We first confirmed that in
oFPAE cells, FGF2, but not VEGF, increased eNOS protein. FGF2 stimulated eNOS
protein in a time- and concentration-dependent manner, which also depended on
cell density. FGF2 provoked sustained (5min to 12h) whereas VEGF only stimulated
transient (5min) ERK2/1 phosphorylation. FGF2 was 1.7-fold more potent in
stimulating ERK2/1 phosphorylation than VEGF. FGF2 and VEGF only transiently
activated JNK1/2 and AKT1 within 5min; however, FGF2 was a stronger stimulus than
VEGF. FGF2 and VEGF did not significantly activate p38MAPK at 5min; however, VEGF
stimulated p38MAPK phosphorylation at 60min. VEGF but not FGF2 significantly
stimulated c-SRC phosphorylation. Inhibitors of MEK-ERK2/1 (PD98059), JNK1/2
(SP600125) and PI3K (wortmannin), but not p38MAPK (SB203580) and SRC (PP2),
decreased the FGF2-increased eNOS protein expression. Thus, the FGF2-induced eNOS
protein expression requires activation of multiple signalling pathways including
ERK2/1, JNK1/2 and PI3K/AKT1. Differences in intensity and temporal patterns of
activation of these pathways by FGF2 and VEGF may account for their differential
effects on eNOS expression in OFPAE cells.

PMID: 18571718 [PubMed - as supplied by publisher]

18: Mol Ther. 2008 Jun 17. [Epub ahead of print]

Stable and Functional Lymphoid Reconstitution in Artemis-deficient Mice Following
Lentiviral Artemis Gene Transfer Into Hematopoietic Stem Cells.

Benjelloun F, Garrigue A, Demerens-de Chappedelaine C, Soulas-Sprauel P,
Malassis-Séris M, Stockholm D, Hauer J, Blondeau J, Rivière J, Lim A, Le Lorc'h
M, Romana S, Brousse N, Pâques F, Galy A, Charneau P, Fischer A, de Villartay JP,
Cavazzana-Calvo M.

1Institut National de la Santé et de la Recherche (INSERM), U768, Université
Paris Descartes, Hôpital Necker-Enfants Malades, Paris,France.

Patients with mutations in the Artemis gene display a complete absence of T- and
B lymphocytes, together with increased cellular radiosensitivity; this leads to a
radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic
hematopoietic stem-cell (HSC) transplantation is only partially successful in the
absence of an human leukocyte antigen-genoidentical donor, and this has prompted
a search for alternative therapeutic approaches such as gene therapy. In this
study, a self-inactivated lentiviral vector expressing Artemis was used to
complement the Artemis knockout mouse (Art(-/-)). Transplantation of
Artemis-transduced HSCs into irradiated Art(-/-) mice restored a stable (over a
15-month period of follow-up) and functional T- and cell repertoire that was
comparable to that of control mice. The success of secondary transplantations
demonstrated that the HSCs had been transduced. One of thirteen mice developed a
thymoma 6 months after gene therapy. Although thymic cells were seen to be
carrying two lentiviral integration sites, there was no evidence of
lentivirus-driven oncogene activation. The Art(-/-) mice were found to be prone
to develop T-cell lymphomas, either spontaneously or after irradiation. These
data indicate that the observed lymphoproliferation was probably the consequence
of the chromosomal instability associated with the Artemis-deficient background.
As a whole, our work provides a basis for supporting the gene therapy approach in
Artemis-deficient SCID.Molecular Therapy (2008); doi:10.1038/mt.2008.118.

PMID: 18560421 [PubMed - as supplied by publisher]

19: Cancer. 2008 Jun 15;112(12):2780-8.

Evidence-based pathology and the pathologic evaluation of thymomas: the World
Health Organization classification can be simplified into only 3 categories other
than thymic carcinoma.

Marchevsky AM, Gupta R, McKenna RJ, Wick M, Moran C, Zakowski MF, Suster S.

Department of Pathology Laboratory Medicine, Cedars-Sinai Medical Center, Los
Angeles, California 90048, USA. marchevsky@cshs.org

BACKGROUND: The clinical validity and applicability of the World Health
Organization (WHO) histopathologic classification of thymomas ('classification')
has been questioned. Evidence-based pathology promotes the use of systematic
reviews and analysis of data with meta-analysis rather than subjective reviews of
the literature. METHODS: The authors performed a review of the English literature
from 1999 to the present to identify 'best evidence' regarding the use of the
'classification.' The data were analyzed with meta-analysis software. RESULTS: To
the authors' knowledge, only Level-3 or -4 evidence published in retrospective
cases series is currently available regarding the use of the 'classification.'
Meta-analysis demonstrated that only 3 WHO categories of thymomas are associated
with significant survival differences: A/AB/B1, B2, and B3. It also indicated
significant heterogeneity with regard to the results published in different
studies. To the authors' knowledge there is no current evidence to determine
whether thymoma types are significant prognostic features for patients previously
stratified by stage. CONCLUSIONS: There is a lack of randomized clinical trials
evaluating the prognosis of patients with thymomas and the effects of various
treatment modalities. The WHO classification of thymomas needs revision and could
most likely be simplified into fewer classes with significant prognostic value.
Future studies are needed to evaluate the prognostic and/or predictive value for
thymoma patients previously stratified by stage. The latter information is
important to help select those patients who may benefit from neoadjuvant
chemotherapy or postoperative radiotherapy and other modalities. Copyright (c)
2008 American Cancer Society.

Publication Types:
Meta-Analysis
Review

PMID: 18442102 [PubMed - indexed for MEDLINE]

20: Clin Cancer Res. 2008 Jun 15;14(12):3966-74.

Transforming growth factor-beta receptor blockade augments the effectiveness of
adoptive T-cell therapy of established solid cancers.

Wallace A, Kapoor V, Sun J, Mrass P, Weninger W, Heitjan DF, June C, Kaiser LR,
Ling LE, Albelda SM.

Thoracic Oncology Research Laboratory, University of Pennsylvania, Pennsylvania,
USA.

PURPOSE: Adoptive cellular immunotherapy is a promising approach to eradicate
established tumors. However, a significant hurdle in the success of cellular
immunotherapy involves recently identified mechanisms of immune suppression on
cytotoxic T cells at the effector phase. Transforming growth factor-beta
(TGF-beta) is one of the most important of these immunosuppressive factors
because it affects both T-cell and macrophage functions. We thus hypothesized
that systemic blockade of TGF-beta signaling combined with adoptive T-cell
transfer would enhance the effectiveness of the therapy. EXPERIMENTAL DESIGN:
Flank tumors were generated in mice using the chicken ovalbumin-expressing
thymoma cell line, EG7. Splenocytes from transgenic OT-1 mice (whose CD8 T cells
recognize an immunodominant peptide in chicken ovalbumin) were activated in vitro
and adoptively transferred into mice bearing large tumors in the presence or
absence of an orally available TGF-beta receptor-I kinase blocker (SM16).
RESULTS: We observed markedly smaller tumors in the group receiving the
combination of SM16 chow and adoptive transfer. Additional investigation revealed
that TGF-beta receptor blockade increased the persistence of adoptively
transferred T cells in the spleen and lymph nodes, increased numbers of
adoptively transferred T cells within tumors, increased activation of these
infiltrating T cells, and altered the tumor microenvironment with a significant
increase in tumor necrosis factor-alpha and decrease in arginase mRNA expression.
CONCLUSIONS: We found that systemic blockade of TGF-beta receptor activity
augmented the antitumor activity of adoptively transferred T cells and may thus
be a useful adjunct in future clinical trials.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 18559619 [PubMed - in process]

21: Int J Cancer. 2008 Jun 15;122(12):2719-25.

Establishment, characterization and drug sensitivity testing in primary cultures
of human thymoma and thymic carcinoma.

Ehemann V, Kern MA, Breinig M, Schnabel PA, Gunawan B, Schulten HJ, Schlaeger C,
Radlwimmer B, Steger CM, Dienemann H, Lichter P, Schirmacher P, Rieker RJ.

Institute of Pathology, University Hospital, Heidelberg, Germany.

Thymomas and thymic carcinomas are peculiar epithelial tumors of the anterior
mediastinum. They may show aggressive clinical behavior and are a paradigm for
the interaction between the tumor and the immune system. So far, adequate
functional studies enabling a better understanding of this malignancy have not
been performed, since human thymoma/thymic carcinoma cell lines have not been
available. Here, the authors describe the establishment, characterization and
functional analyses of epithelial cell lines from a Type B1-thymoma and a poorly
differentiated thymic carcinoma. By Fluorescence-activated cell sorting (FACS)
analyses, both cell lines were aneuploid. The aneuploid cell fraction of the
thymic carcinoma cell line was characterized by a high proliferation index of
55.9%, in contrast to a lower proliferation rate of the aneuploid cell fraction
of the thymoma (19.7%). Array-based comparative genomic hybridization (aCGH) and
conventional cytogenetic analysis of the thymoma revealed only minor imbalances
whereas the thymic carcinoma was characterized by a complex karyotype in the
hyperdiploid range that was readily defined with multicolor FISH (mFISH).
Application of a selective COX-2 inhibitor reduced cell viability in both cell
lines in a dose-dependent manner. In conclusion, these first cell lines of a
thymoma and a CD5-positive thymic carcinoma are useful tools for further in vitro
studies of cellular, molecular and genetic aspects of the disease and for
functional tests to evaluate new therapeutic targets. (c) 2008 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18360827 [PubMed - in process]

22: J Neurol Sci. 2008 Jun 15;269(1-2):176-9. Epub 2008 Apr 1.

Potassium channel antibody-associated encephalitis with hypothalamic lesions and
intestinal pseudo-obstruction.

Sekiguchi Y, Takahashi H, Mori M, Ito S, Shimada H, Hattori T, Kuwabara S.

Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1
Inohana, Chuo-ku, Chiba-city, Chiba 260-8677, Japan. syukari36@nifty.co.jp

A subgroup of limbic encephalitis is associated with antibodies against
voltage-gated potassium channels (VGKC), and responds well to immuno-modulating
therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's
syndrome, both of which are sometimes complicated by thymoma. We describe a
52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who
presented with autonomic dysfunctions such as severe intestinal
pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid
therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed
hypothalamic lesions, in addition to the bilateral involvement of the medial
temporal lobes. This patient had severe autonomic dysfunctions resembling those
of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody
associated syndromes with a wide spectrum of symptoms, including Isaacs'
syndrome, Morvan's syndrome, and limbic encephalitis.

PMID: 18378260 [PubMed - in process]

23: PLoS ONE. 2008 Jun 11;3(6):e2392.

Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.

Soreq L, Gilboa-Geffen A, Berrih-Aknin S, Lacoste P, Darvasi A, Soreq E, Bergman
H, Soreq H.

Department of Physiology, The Hebrew University, Hadassah Medical School,
Jerusalem, Israel. soreq@cc.huji.ac.il

BACKGROUND: The vast majority of human genes (>70%) are alternatively spliced.
Although alternative pre-mRNA processing is modified in multiple tumors,
alternative hyper-splicing signatures specific to particular tumor types are
still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot
hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic
tumors which develop in patients with MG and discriminate them from colon cancer
changes. METHODOLOGY/PRINCIPAL FINDINGS: We combined GO term to parent
threshold-based and threshold-independent ad-hoc functional statistics with
in-depth analysis of key modified transcripts to highlight various exon-specific
changes. These denote alternative splicing in MG-thymoma tumors compared to
healthy human thymus and to in-house and Affymetrix datasets from colon cancer
and healthy tissues. By using both global and specific, term-to-parent Gene
Ontology (GO) statistical comparisons, our functional integrative ad-hoc method
allowed the detection of disease-relevant splicing events.
CONCLUSIONS/SIGNIFICANCE: Hyper-spliced transcripts spanned several categories,
including the tumorogenic ERBB4 tyrosine kinase receptor and the connective
tissue growth factor CTGF, as well as the immune function-related
histocompatibility gene HLA-DRB1 and interleukin (IL)19, two muscle-specific
collagens and one myosin heavy chain gene; intriguingly, a putative new exon was
discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding
changes in spliceosome composition were indicated by co-decreases in the splicing
factors ASF/SF(2) and SC35. Parallel tumor-associated changes occurred in colon
cancer as well, but the majority of the apparent hyper-splicing events were
particular to MG-thymoma and could be validated by Fluorescent In-Situ
Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
and mass spectrometry (MS) followed by peptide sequencing. Our findings
demonstrate a particular alternative hyper-splicing signature for transcripts
over-expressed in MG-thymoma, supporting the hypothesis that alternative
hyper-splicing contributes to shaping the biological functions of these and other
specialized tumors and opening new venues for the development of diagnosis and
treatment approaches.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18545673 [PubMed - in process]

24: Ann N Y Acad Sci. 2008 Jun;1132:329-335.

Thoracoscopic Thymectomy with the da Vinci Robotic System for Myasthenia Gravis.

Rückert JC, Ismail M, Swierzy M, Sobel H, Rogalla P, Meisel A, Wernecke KD,
Rückert RI, Müller JM.

Klinik für Allgemein-, Viszeral-, Gefäß- und Thoraxchirurgie,
Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin,
Germany. jens-c.rueckert@charite.de.

Complete thymectomy (Thx) is a crucial part of treatment for myasthenia gravis
(MG) and thymoma. The discussion about the necessity of radical, complete Thx and
reduced invasiveness has led to no less than 14 different surgical approaches for
Thx. The latest development is robotic-assisted surgery. Though its impact on
minimally invasive surgery is not yet clear, it seems to be most promising for
surgery in remote, narrow anatomical regions like the mediastinum. One hundred
six consecutive robotic-assisted thymectomies (rThx) with the da Vinci robotic
surgical system were performed between January 2003 and April 2007 in a
prospective single-center study. Postoperative morbidity was recorded according
to the Myasthenia Gravis Foundation of America (MGFA) classification. With zero
mortality, the overall postoperative morbidity rate was 2%. The cumulative
complete stable remission rate of MG was > 40% for all patients, and there was no
statistical difference as compared to non-thymomatous MG patients. The cumulative
rate of minimal manifestations (MM0-MM3) according to the MGFA classification
showed a postoperative improvement in quality of life for most of the patients.
The da Vinci robotic system allowed for technical refinements of the well-defined
operation technique of thoracoscopic Thx (tThx). From the technical point of
view, rThx has advantages for mediastinal dissection. rThx had a shorter learning
curve. There might be better outcome results for rThx in MG patients, as compared
with nonrobotic tThx. Therefore, rThx is a promising technique for minimally
invasive Thx.

PMID: 18567884 [PubMed - as supplied by publisher]

25: Ann N Y Acad Sci. 2008 Jun;1132:238-43.

Myasthenia gravis in the elderly: is it different?

Aarli JA.

Grønnestølvegen 52, N-5073 Bergen, Norway. Johan.Aarli@nevro.uib.no.

We have defined myasthenia gravis (MG) in the elderly as onset after the age of
50 years. MG is diagnosed more often today than previously. The increase is
mainly found in patients over the age of 50 years. Neurologists therefore see
more old patients with MG now than before. Prevalence of the early-onset form of
MG seems to be unchanged. Recent data indicate that MG may still be substantially
underdiagnosed in very old people. Ptosis, diplopia, weakness of the facial
muscles, and problems of articulation are important clinical signs in MG and are
easier to detect in a youthful appearance. Since ageing causes a decrease in the
total eyelid area with sagging of the lower eyelids, a ptosis may be more
difficult to diagnose in the elderly. In addition, diplopia may not be detected
because of reduced vision due to macular degeneration or cataract formation.
Ocular symptoms of MG are therefore more easily missed in the elderly.
Thymomatous MG is more common among older patients than it is in younger onset.
The mean age at onset of MG for thymoma cases is 50-60 years. Approximately
10-15% of all MG patients have a thymoma, and around 40% of all thymoma cases are
associated with MG. During normal aging, the thymus tissue becomes atrophic and
replaced with fat. Recent data on MG thymus pathology suggest that lymphocyte
accumulation indicating residual thymus may also be found in the elderly, and
that there is little qualitative difference between the young and the old thymus
from MG patients. The mean concentration of antibodies to acetylcholine receptor
(AChR) is lower in MG in the elderly than in early-onset or thymoma-associated
MG. Seronegative MG is less common among older patients. Approximately 30% of
patients with late-onset, nonthymoma MG have antibodies to titin, while such
antibodies are extremely scarce in early-onset MG. Titin antibodies in MG
patients seem to be associated with a higher frequency of DR7 antigen and a
decrease of DR3 antigen. The antibody response in MG may therefore be influenced
by the genetic background.

PMID: 18567874 [PubMed - in process]

26: Ann N Y Acad Sci. 2008 Jun;1132:163-73.

Autoimmunizing mechanisms in thymoma and thymus.

Willcox N, Leite MI, Kadota Y, Jones M, Meager A, Subrahmanyam P, Dasgupta B,
Morgan BP, Vincent A.

Neuroscience Group, Weatherall Institute for Molecular Medicine, University of
Oxford, OX3 9DS, UK. nick.willcox@imm.ox.ac.uk.

Autoimmunizing mechanisms are very hard to study in humans, so we have focused on
vital clues in thymomas and hyperplastic thymuses in myasthenia gravis (MG).
According to our multi-step hypothesis: thymic epithelial cells (TEC) present
epitopes from the isolated acetylcholine receptor (AChR) subunits they express,
and autoimmunize helper T cells; subsequently, these evoke "early antibodies"
that then attack rare thymic myoid cells expressing intact AChR; in the resulting
germinal centers, autoantibodies diversify to recognize native AChR. We have
studied: 1) thymomas, to identify autoimmunizing cell types, focusing on
IFN-alpha, against which many patients have high titer autoantibodies, as in
another highly informative autoimmune syndrome. Although IFN-alpha is much easier
to label than the sparse and delicate AChR subunits, we have not yet located
obviously autoimmunizing micro-environments; 2) hyperplastic MG thymuses, where
we find (a) upregulation of complement receptors and regulators on hyperplastic
TEC and deposition of activated C3b complement component on them, (b) absence of
complement regulators from almost all myoid cells, indicating vulnerability to
attack, and (c) deposition of C3b, and even of the terminal membrane attack
complex, especially on the myoid cells close to the infiltrating germinal
centers. The changes are very similar in over 50% of the so-called seronegative
patients with generalized MG (SNMG) but without detectable autoantibodies against
AChR or MuSK, consistently with other evidence that they belong to the spectrum
of AChR-seropositive MG. Together, moreover, our findings implicate both myoid
cells and TEC in autoimmunization, and thus strongly support our hypothesis.

PMID: 18567866 [PubMed - in process]

27: Ann N Y Acad Sci. 2008 Jun;1132:143-56.

Common Cellular and Diverse Genetic Basis of Thymoma-associated Myasthenia
Gravis: Role of MHC Class II and AIRE Genes and Genetic Polymorphisms.

Ströbel P, Chuang WY, Chuvpilo S, Zettl A, Katzenberger T, Kalbacher H, Rieckmann
P, Nix W, Schalke B, Gold R, Müller-Hermelink HK, Peterson P, Marx A.

Institute of Pathology, University Medical Center Mannheim, University of
Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany.
philipp.stroebel@path.ma.uni-heidelberg.de.

Generation of autoreactive CD4(+) effector T cells and defective production of
regulatory CD4(+) T cells inside thymomas contribute to the development of
myasthenia gravis (MG) in >90% of MG(+) thymomas. The molecular basis of these
abnormalities is unknown. We report here that a) expression levels of class II
major histocompatibility complex (MHCII) genes are variably decreased in
thymomas, most prominently in histological WHO types A and AB; b) epithelial
cells of type A and AB thymomas exhibit signal transducer and activator of
transcription (STAT-1)-related defects of interferon-gamma (IFN-gamma) signaling
and human leukocyte antigen (HLA)-DR expression in vitro; c) the promoter III
(pIII)- and pIV-driven splice variants of the MHCII transactivator (CIITA) play a
key role in MHCII gene expression in thymus and thymomas; and d) the pIV CIITA
promoter is heavily methylated in thymomas. Recently, we also found that
expression of the autoimmune regulator (AIRE) gene is absent from approximately
95% of thymomas. Among all theses abnormalities, only better preserved expression
levels of MHCII (P < 0.001) in thymomas were significantly associated with the
presence of MG. Taking the association of a gain-of-function polymorphism of the
CTLA-4 and PTPN22 gene with MG in thymomas into account, we conclude that these
acquired cellular abnormalities of the thymoma microenvironment in concert with
inherited genetic high-risk polymorphisms of immunoregulatory genes have an
impact on intratumorous thymopoiesis and appear to tip the balance toward central
tolerance failure and development of MG. The findings imply that IFN-gamma and
STAT-1 signaling play a role in MHCII expression in the human thymus and in the
pathogenesis of paraneoplastic MG.

PMID: 18567864 [PubMed - in process]

28: Ann N Y Acad Sci. 2008 Jun;1132:254-63. Epub 2007 Dec 20.

Tacrolimus for myasthenia gravis: a clinical study of 212 patients.

Ponseti JM, Gamez J, Azem J, López-Cano M, Vilallonga R, Armengol M.

Unit of Myasthenia Gravis, Department of Surgery, Hospital General Universitari
Vall d'Hebron, Passeig Vall d'Hebron 119-129, E-08035 Barcelona, Spain.
jmponseti@vhebron.net.

Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia
gravis (MG) patients to affect muscle contraction (ryanodine receptor by
modulating intracellular calcium-release channels and increasing muscular
strength), glucocorticoid receptors (increasing intracellular concentration of
steroids and blocking the steroid export mechanism), and an increase in T cell
apoptosis. In this study, we report the results of low-dose tacrolimus (0.1
mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized,
cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who
started tacrolimus early postoperatively (24 h after operation); and 34 patients
over 60 years old with nonthymomatous generalized MG or in whom thymectomy was
contraindicated. The mean follow-up time 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. The acetylcholine receptor antibodies decreased significantly from
a mean of 33.5 nmol/L at base line 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
because of major adverse effects. Our results suggest that a 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 - in process]

29: Ann Nucl Med. 2008 Jun;22(5):379-85. Epub 2008 Jul 4.

Evaluation of whole-body cancer screening using 18F-2-deoxy-2-fluoro-D-glucose
positron emission tomography: a preliminary report.

Terauchi T, Murano T, Daisaki H, Kanou D, Shoda H, Kakinuma R, Hamashima C,
Moriyama N, Kakizoe T.

Screening Technology and Development Division, Research Center for Cancer
Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo
104-0045, Japan. tterauch@ncc.go.jp

OBJECTIVE: (18)F-2-deoxy-2-fluoro-D-glucose positron emission tomography
(FDG-PET) is a promising screening modality targeting whole body. However, the
validity of PET cancer screening remains to be assessed. Even the screening
accuracy for whole-body screening using FDG-PET has not been evaluated. In this
study, we investigated the screening accuracy of PET cancer screening. METHODS: A
total of 2911 asymptomatic participants (1629 men and 1282 women, mean age 59.79
years) underwent both FDG-PET and other thorough examinations for multiple organs
(gastrofiberscopy, total colonofiberscopy or barium enema, low-dose thin section
computed tomography and sputum cytology, abdominal ultrasonography, an assay of
prostate-specific antigen, mammography, mammary ultrasonography, Pap smear for
the uterine cervix, and magnetic resonance imaging for the endometrium and
ovaries) between February 2004 and January 2005, and followed sufficiently. The
detection rate, sensitivity, specificity, and positive predictive value of
FDG-PET were calculated using cancer data obtained from all examinations along
with a 1 year follow-up. RESULTS: From among 2911 participants FDG-PET found 28
cancers, 129 cancers were PET negative. PET-positive cancers comprised seven
colorectal cancers, four lung cancers, four thyroid cancers, three breast
cancers, two gastric cancers, two prostate cancers, two small intestinal sarcomas
(gastrointestinal stromal tumors), one malignant lymphoma, one head and neck
malignancy (nasopharyngeal carcinoid tumor), one thymoma, and one hepatocellular
carcinoma. PET-negative cancers included 22 gastric cancers and 20 prostate
cancers that were essentially difficult to detect using FDG-PET. The overall
detection rate, sensitivity, specificity, and positive predictive value were
estimated to be 0.96%, 17.83%, 95.15%, and 11.20%, respectively. CONCLUSIONS:
FDG-PET can detect a variety of cancers at an early stage as part of a whole-body
screening modality. The detection rate of PET cancer screening was higher than
that of other screening modalities, which had already shown evidence of efficacy.
However, the sensitivity of PET cancer screening was lower than that of other
thorough examinations performed at our institute. FDG-PET has some limitations,
and cancer screening using only FDG-PET is likely to miss some cancers.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18600415 [PubMed - in process]

30: Ann Thorac Cardiovasc Surg. 2008 Jun;14(3):181-3.

Resection of mediastinal granulocytic sarcoma triggered the rapid progression of
acute myeloid leukemia.

Suemitsu R, Fukuyama S, Ondo K, Ueda H.

Department of Thoracic Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Mediastinal granulocytic sarcoma (GS) is a relatively rare disease. We
experienced a case of acute myeloid leukemia (AML) that took a rapid turn for the
worse after the resection of a mediastinal GS. A healthy 60-year-old man had been
in good general health all his life, but was diagnosed with a mediastinal tumor
by his family physician and was referred to our department. The patient underwent
resection of the mediastinal tumor because thymoma was highly suspected. On
postoperative day (POD) 3, the patient suffered a fever as well as an elevated
white blood cell (WBC) count and a high C-reactive protein level. His WBC count
was 77,240 at its peak on POD 9, at which point the patient was diagnosed with
AML by bone marrow aspiration. The immunohistological findings showed the
features of leukemia, and GS was diagnosed. Despite chemotherapy, the patient
died on POD 28 as a result of rapid disease progression.

PMID: 18577899 [PubMed - in process]

31: Ann Thorac Surg. 2008 Jun;85(6):1874-8.

Comment in:
Ann Thorac Surg. 2008 Jun;85(6):1879.

Endobronchial ultrasound-guided miniforceps biopsy in the biopsy of subcarinal
masses in patients with low likelihood of non-small cell lung cancer.

Herth FJ, Morgan RK, Eberhardt R, Ernst A.

Department of Pneumology and Critical Care Medicine, Thoraxklinik at University
Heidelberg, Germany.

BACKGROUND: Transbronchial needle aspiration (TBNA) is used to sample mediastinal
masses, but the value may be limited by the small specimen size obtained. In
benign diseases and hematologic malignancies, the sample size from TBNA is often
considered insufficient for diagnosis. We evaluated the safety and efficacy of
obtaining histologic specimens from subcarinal masses using a 1.15-mm miniforceps
under endobronchial ultrasound (EBUS) guidance and compared the diagnostic yield
with TBNA alone. METHODS: Patients being evaluated for subcarinal lesions
exceeding 2.5 cm (short axis) and without known or suspected non-small cell lung
cancer were included. Bronchoscopy was performed, and EBUS-guided BNA of the
lesion was performed first with a 22-gauge needle, followed by the 19-gauge
needle. The miniforceps was then passed through the airway into the lesion (three
to five passes) under real-time EBUS guidance. Three biopsy specimens were
obtained. RESULTS: The study enrolled 75 patients (41 men; mean age, 51.5 years).
Specimens were acquired from each patient using the three techniques and
processed separately. A specific diagnosis was made in 36% of patients with the
22-gauge needle, 49% with the 19-gauge needle, and in 88% with the miniforceps.
The increase in diagnostic yield with miniforceps was most significant in
patients with sarcoidosis (88% vs 36% for TBNA, p = 0.001) or lymphoma (81% vs
35%, p = 0.038). No complications occurred. CONCLUSIONS: Miniforceps biopsy,
performed under real-time EBUS guidance, can be used to obtain tissue specimens
from subcarinal masses adjacent to the airway. The diagnostic yield for lymphoma
and sarcoidosis is superior to TBNA alone, and the procedure appears safe.

PMID: 18498786 [PubMed - indexed for MEDLINE]

32: Arch Pathol Lab Med. 2008 Jun;132(6):926-30.

Evidence-based pathology and the pathologic evaluation of thymomas: transcapsular
invasion is not a significant prognostic feature.

Gupta R, Marchevsky AM, McKenna RJ, Wick M, Moran C, Zakowski MF, Suster S.

Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

CONTEXT: Evaluation of transcapsular invasion is currently considered very
important in the pathologic examination of thymomas. However, recent studies have
questioned the prognostic value of stratifying thymoma patients into stage I and
II disease. Evidence-based pathology promotes the use of systematic reviews of
literature and meta-analysis of data to synthesize the results of multiple
publications. OBJECTIVE: To analyze the data in the literature regarding the
prognostic importance of transcapsular invasion in thymoma stage I and II.
DESIGN: A systematic review of the English literature was carried out for
"thymoma," "stage," and "prognoses." Case reports, case series with fewer than 10
cases, and studies with follow-up periods shorter than 5 years were excluded.
Twenty-one retrospective publications reporting the experience with 2451 thymomas
were selected for review, including 1419 stage I and 1032 stage II patients.
Meta-analysis was performed, and possible publication bias was studied with
funnel plots of precision and various statistics. RESULTS: Meta-analysis yielded
no significant differences in disease-free or overall survival rates in stage I
and II thymoma patients. Funnel plots of precision and statistical tests such as
the Egger regression intercept test showed no significant publication bias.
CONCLUSIONS: The lack of significant differences in the prognosis of patients
with stages I and II thymoma suggests that evaluation of transcapsular invasion
is of no clinical value in tumors that lack invasion of neighboring organs or the
pleura. The data regarding the prognosis of stage II thymoma patients is somewhat
heterogenous, with only some individuals having been treated with radiation
therapy, suggesting the need for future randomized controlled trials.

Publication Types:
Meta-Analysis

PMID: 18517274 [PubMed - indexed for MEDLINE]

33: Cancer Sci. 2008 Jun;99(6):1265-73.

The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia
vera cells carrying the JAK2V617F mutation.

Manshouri T, Quintás-Cardama A, Nussenzveig RH, Gaikwad A, Estrov Z, Prchal J,
Cortes JE, Kantarjian HM, Verstovsek S.

Department of Leukemia, The University of Texas, M D Anderson Cancer Center,
Houston, TX 77030, USA.

The somatic activating janus kinase 2 mutation (JAK2)(V617F) is detectable in
most patients with polycythemia vera (PV). Here we report that CP-690,550 exerts
greater antiproliferative and pro-apoptotic activity against cells harboring
JAK2(V617F) compared with JAK2(WT). CP-690,550 treatment of murine
factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells
harboring human wild-type or V617F JAK2 resulted in inhibition of cell
proliferation with a 50% inhibitory concentration (IC(50)) of 2.1 microM and 0.25
microM, respectively. Moreover, CP-690,550 induced a significant pro-apoptotic
effect on murine FDCP-EpoR cells carrying JAK2(V617F), whereas a lesser effect
was observed for cells carrying wild-type JAK2. This activity was coupled with
inhibition of phosphorylation of the key JAK2(V617F)-dependent downstream
signaling effectors signal transducer and activator of transcription (STAT)3,
STAT5, and v-akt murine thymoma viral oncogene homolog (AKT). Furthermore,
CP-690,550 treatment of ex-vivo-expanded erythroid progenitors from
JAK2(V617F)-positive PV patients resulted in specific, antiproliferative (IC(50)
= 0.2 microM) and pro-apoptotic activity. In contrast, expanded progenitors from
healthy controls were less sensitive to CP-690,550 in proliferation (IC(50) > 1.0
microM), and apoptosis assays. The antiproliferative effect on expanded patient
progenitors was paralleled by a decrease in JAK2(V617F) mutant allele frequency,
particularly in a patient homozygous for JAK2(V617F). Flow cytometric analysis of
expanded PV progenitor cells treated with CP-690,550 suggests a possible
transition towards a pattern of erythroid differentiation resembling expanded
cells from normal healthy controls.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 18482053 [PubMed - indexed for MEDLINE]

34: Eur J Cardiothorac Surg. 2008 Jun;33(6):1155-6. Epub 2008 Apr 3.

Thymoma appearing 10 years after an extended thymectomy for myasthenia gravis.

Toker A, Tanju S, Ozluk Y, Serdaroglu P.

Istanbul University, Istanbul Medical Faculty, Department of Thoracic Surgery,
Istanbul, Turkey. aetoker@superonline.com

Occurrence of thymoma after an extended thymectomy through a full median
sternotomy for nonthymomatous thymectomy has been very rarely reported. A
60-year-old male patient who had myasthenia gravis (MG) for 11 years had an
extended thymectomy operation with a pathology of thymic hyperplasia and
developed a mass in the aortopulmonary window. We resected the mass via anterior
left thoracotomy by dividing the ductus arteriosus and mobilizing the aorta. Cord
vocal augmentation procedure was done due to the resection of the left recurrent
laryngeal nerve.

PMID: 18394913 [PubMed - in process]

35: Hematol Oncol Clin North Am. 2008 Jun;22(3):543-62.

Thymic epithelial neoplasms: a review of current concepts using an evidence-based
pathology approach.

Marchevsky AM, McKenna RJ Jr, Gupta R.

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center,
8700 Beverly Boulevard, Los Angeles, CA 90048, USA. marchevsky@cshs.org

Evidence-based pathology promotes the critical evaluation of current clinical
information and the development of evidence-based diagnostic and prognostic
guidelines. No randomized clinical trials of patients who have thymomas or thymic
carcinomas are available to evaluate the validity of the current World Health
Organization (WHO) histologic classification or the widely used Masaoka staging
system. A meta-analysis of over 2000 thymoma patients estimated that only three
WHO histologic types of thymomas are associated with significant survival
differences. Prospective randomized clinical trials and an international registry
of patients who have Thymic epithelial neoplasms are needed to stratify patients
who may benefit from neoadjuvant chemotherapy, postoperative radiation therapy,
and other nonsurgical modalities.

PMID: 18514132 [PubMed - in process]

36: Hematol Oncol Clin North Am. 2008 Jun;22(3):527-42.

Prognostic factors for thymic epithelial neoplasms, with emphasis on tumor
staging.

Wick MR.

Division of Surgical Pathology and Cytopathology, University of Virginia Medical
Center, University of Virginia Health System, Charlottesville, VA 22908-0214,
USA. mrw9c@virginia.edu

The prognosis of thymic epithelial tumors depends on their separation into
thymoma and thymic carcinoma, as well as the extent to which they involve
adjacent tissues and organs. To formalize evaluations of the latter attribute,
several staging systems have been developed over the past 30 years. These include
the Masaoka, Bergh, Wilkins-Castleman, Groupe d'Etudes des Tumeurs Thymiques, and
tumor-nodal-metastasis schemes. The first of those formulations is most commonly
employed in clinical practice, at least in the United States. The author believes
that surgical-pathologic staging is the most powerful and reliable prognosticator
for thymoma, as compared with histologic subtype-related prediction of behavior
for that tumor type. Those topics, as well as affiliated issues concerning tissue
sampling and staging techniques, are discussed in this article.

PMID: 18514131 [PubMed - in process]

37: Hematol Oncol Clin North Am. 2008 Jun;22(3):509-26.

Thymoma, myasthenia gravis, and other paraneoplastic syndromes.

Tormoehlen LM, Pascuzzi RM.

Department of Neurology, Indiana University School of Medicine, Emerson Hall Room
125, 545 Barnhill Drive, Indianapolis, IN 46202, USA. laumjone@iupui.edu

The relationship between myasthenia gravis and thymic pathology, including
thymoma, is well known. Approximately 10% to 15% of patients who have myasthenia
gravis are observed to have a thymoma. Myasthenia gravis may be considered as the
most common of the paraneoplastic syndromes in patients who have thymoma. This
article summarizes the clinical aspects of myasthenia gravis, followed by a
review of the less often recognized paraneoplastic disorders noted to occur in
patients who have thymoma.

PMID: 18514130 [PubMed - in process]

38: Hematol Oncol Clin North Am. 2008 Jun;22(3):489-507.

Radiotherapy for thymoma and thymic carcinoma.

Fuller CD, Housman DM, Thomas CR.

Department of Radiation Oncology, Graduate Division of Radiological Sciences, The
University of Texas Health Science Center at San Antonio, 7979 Wurzbach Road, San
Antonio, TX 78229-3900, USA.

The role of radiotherapy for patients who have thymic neoplasms remains unclear.
The low incidence of thymic malignancies, excellent outcome with complete
resection, and limited body of evidence obfuscate the role of radiation therapy
within the current multidisciplinary management of disease. Nonetheless, existing
literature reports and novel radiotherapy techniques show increasing potential
for integration of radiotherapy into the standard therapeutic milieu for
carefully selected patient subpopulations.

PMID: 18514129 [PubMed - in process]

39: Hematol Oncol Clin North Am. 2008 Jun;22(3):457-73.

Clinical management of thymoma patients.

Casey EM, Kiel PJ, Loehrer PJ Sr.

Indiana University School of Medicine, 535 Barnhill Dr. RT 473, Indianapolis, IN
46202, USA. caseye@iupui.edu

Thymoma and thymic carcinomas are rare epithelial tumors that arise from the
thymus gland. Current management depends on staging, with surgery being the
mainstay of therapy for stages I and II disease. Combined modality therapy,
including radiation and chemotherapy, is recommended for patients who have
invasive and metastatic disease. Relapse has been documented decades after
initial therapy with options for treating recurrent advanced stage disease.
Prospective studies have been limited, and current studies aim to evaluate novel
treatment options.

PMID: 18514127 [PubMed - in process]

40: Hematol Oncol Clin North Am. 2008 Jun;22(3):433-42.

Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.

Wakely PE Jr.

Department of Pathology, Ohio State University College of Medicine, 414 Doan
Hall, 410 West 10th Avenue, Columbus, OH 43210, USA. paul.wakely@osumc.edu

Fine-needle aspiration (FNA) biopsy of thymoma is a demanding diagnostic exercise
by the cytopathologist because of an overwhelming, often obscuring population of
benign lymphocytes in many cases. Diagnosis requires the presence of a dual
population of unequivocal epithelial cells and lymphocytes in the correct
clinical-radiologic context. Cytologic examination alone is not insufficient to
discriminate among the various subtypes of thymoma, nor can capsular invasion or
invasion of adjacent structures be determined using FNA. The cytopathology of
various thymic carcinomas (including neuroendocrine carcinoma) imitate their
appearance in extra-thymic sites, and are generally recognizable using FNA.
Separation of moderately differentiated neuroendocrine carcinoma from poorly
differentiated small cell neuroendocrine carcinomas is generally not possible.

PMID: 18514125 [PubMed - in process]

41: Hematol Oncol Clin North Am. 2008 Jun;22(3):381-92.

Histologic classification of thymoma: the World Health Organization and beyond.

Suster S, Moran CA.

Department of Pathology and Laboratory Medicine, Medical College of Wisconsin,
9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. ssuster@mcw.edu

Thymoma classification has remained for many years a troubled and contentious
field. In recent years, the World Health Organization (WHO) presented a proposal
for the histopathologic classification of thymic epithelial neoplasms that has
been adopted as the standard by many pathologists throughout the world. Yet,
controversy still exists regarding its validity, accuracy, usefulness, and
reproducibility in routine clinical practice. This article reviews the basic
criteria of the current WHO classification of thymoma, along with its weaknesses
and limitations, and presents alternate proposals for the histopathologic
approach to the classification of thymic epithelial neoplasms.

PMID: 18514122 [PubMed - in process]

42: Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):420-7. Epub 2007 Dec 31.

Novel prognostic groups in thymic epithelial tumors: assessment of risk and
therapeutic strategy selection.

D'Angelillo RM, Trodella L, Ramella S, Cellini N, Balducci M, Mantini G, Cellini
F, Ciresa M, Fiore M, Evoli A, Sterzi S, Russo P, Grozio A, Cesario A, Granone P.

Campus Bio-Medico University, Rome, Italy. r.dangelillo@unicampus.it

PURPOSE: To assess the role of multimodality treatment on patients with thymic
epithelial tumors (TETs) (i.e., thymomas and thymic squamous cell carcinoma) and
to define the prognostic classes according to the Masaoka and World Health
Organization histologic classification systems. METHODS AND MATERIALS: Primary
surgery was the mainstay of therapy. Extended thymectomy was performed in all
cases. The cases were primarily staged according to the Masaoka system. Adjuvant
radiotherapy was given to patients diagnosed with Masaoka Stage II, III, and IVA
TET. Adjuvant chemotherapy was administered in selected cases. RESULTS: We
reviewed the records of 120 patients with TETs, with a mean follow-up of 13.8
years. Of the 120 patients, 98 (81.6%) received adjuvant radiotherapy. Of these
98 patients, Grade 1-2 pulmonary or esophageal toxicity was acute in 12 (12.2%)
and late in 8 (8.2%). The median overall survival was 21.6 years. Of the 120
patients, 106 were rediagnosed and reclassified according to the World Health
Organization system, and the survival rate was correlated with it. Three
different prognostic classes were defined: favorable, Masaoka Stage I and
histologic grade A, AB, B1, B2 or Masaoka Stage II and histologic grade A, AB,
B1; unfavorable, Stage IV disease or histologic grade C or Stage III and
histologic grade B3; intermediate, all other combinations. The 10- and 20-year
survival rate was 95% and 81% for the favorable group, 90% and 65% for the
intermediate group, and 50% and 0% for the unfavorable group, respectively. Local
recurrence, distant recurrence, and tumor-related deaths were also evaluated.
CONCLUSION: The analysis of our experience singled out three novel prognostic
classes and the assessment of risk identified treatment selection criteria.

Publication Types:
Evaluation Studies

PMID: 18164843 [PubMed - indexed for MEDLINE]

43: Nihon Kokyuki Gakkai Zasshi. 2008 Jun;46(6):497-500.

[Pulmonary alveolar proteinosis noted in a patient with thymoma]

[Article in Japanese]

Matsunaga K, Nagata N, Iwata Y, Kumazoe H, Komori M, Shigyo M, Wakamatsu K,
Kajiki A, Kitahara Y.

Department of Respiratory Internal Medicine, National Hospital Organization
Ohmuta Hospital.

A 74-year-old woman had general fatigue and mild fever in August 2004. Her chest
X-ray showed slight ground glass opacities in the upper and middle lung fields of
both lungs. Though she was prescribed antibacterial drugs, the abnormal shadows
on chest X-ray did not improve. The chest CT showed ground glass opacities and
reticular shadows with thickened alveolar septa (crazy-paving appearance) in both
lungs, and a clearly defined mass in the anterior mediastinum. She underwent
thymo-thymectomy with wedge resection of the upper lobe of the left lung.
Anterior mediastinum tumor was pathologically diagnosed as thymoma. Lung biopsy
demonstrated alveoli filled with SP-A positive granular materials, and we
diagnosed pulmonary alveolar proteinosis. About 1 month after operation, the
shadows on chest CT showed improvement. We think there might be some relationship
between thymoma and pulmonary alveolar proteinosis.

Publication Types:
English Abstract

PMID: 18592998 [PubMed - in process]

44: Nippon Rinsho. 2008 Jun;66(6):1140-8.

[Overview: MuSK/Dok-7]

[Article in Japanese]

Motomura M, Fukuda T, Yoshimura T, Tsujihata M.

The First Department of Internal Medicine, Graduate School of Biomedical
Sciences, Nagasaki University.

MuSK/Dok-7 mediate the clustering of acetylcholine receptor (AChR) during synapse
formation and are expressed at the mature neuromuscular junction. These proteins
are deeply associated with myasthenia gravis (MG) and congenital myasthenic
syndrome (CMS). Compared with MG patients with AChR antibodies, those with
muscle-specific tyrosine kinase (MuSK) antibodies are more likely to present
oculobulbar than limb weakness, myasthenic crisis and muscle wasting. None have
thymoma, so the indication for thymectomy should be investigated. MuSK antibodies
do not appear to cause complement-mediated morphological motor endplate damage,
but how they cause myasthenic symptoms is unclear. As the results, the three
types of MG presently characterized by known antibody targets are classified into
1) AChR antibody-positive, 2) MuSK antibody -positive, and 3) double seronegative
type which the above-mentioned antibodies are negative. In 2006, MuSK-interacting
cytoplasmic protein termed Dok-7 has been found. Subsequently, mutations in Dok-7
as a cause of CMS were identified, providing evidence for a crucial role of Dok-7
in maintaining synaptic structure. Their effect on MuSK/Dok -7 function needs to
be explored.

Publication Types:
English Abstract

PMID: 18540360 [PubMed - in process]

45: Thorac Cardiovasc Surg. 2008 Jun;56(4):241.

Surgical approach to giant thymoma: is the hemi-clamshell incision the best
option?

Incarbone M, Voulaz E, Alloisio M.

Department of Thoracic Surgery, Istituto Clinico Humanitas, Rozzano, Italy.
matteo.incarbone@humanitas.it

PMID: 18481249 [PubMed - in process]

46: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Jun;25(3):311-4.

[Expression of Toll-like receptors in thymus of myasthenia gravis patients.]

[Article in Chinese]

Gao K, Wang Y, Ma X, Li T, Wu Z, Liu L, Che G, Kou Y, Huang Y, Wang Y.

Department of Thoracic and Cardiovascular Surgery, West China Hospital, Sichuan
University, Chengdu, Sichuan, 610041 P. R. China. cdwangyun@yahoo.com.cn.

OBJECTIVE: To investigate the expression of Toll-like receptors (TLRs) in thymus
of myasthenia gravis (MG) patients and the relationship with clinical features.
METHODS: Thymic specimens of 36 patients received extended thymectomy for MG were
divided into three groups by pathological type: 13 thymoma tissues (thymoma
group) and 13 thymic tissues adjacent to thymomas (parathymoma group) from 13
cases of MG patients with thymomas, and 23 thymic tissues from MG patients
without thymomas (MG nonthymoma group). Twenty-one normal thymic specimens from
cardiac surgery were used as controls. The levels of TLR2-4 mRNA were examined by
RT-PCR, then the levels of TLR4 mRNA were assayed by real time RT-PCR and their
relationship with clinical features were analyzed. RESULTS: The levels of TLR4
mRNA among the different groups had significant differences, while there was no
difference in TLR2 and TLR3 levels. The real time RT-PCR showed that the level of
TLR4 mRNA in nonthymoma group was significantly higher than that in control
group(0.8544+/- 0.1200 vs 0.6851+/- 0.1524, P=0.018). And so is parathymoma group
compared with the thymoma group (0.8214+/- 0.1019 vs 0.7101+/- 0.0916, P=0.005).
No significant difference of TLR4 mRNA level was found between the parathymoma
and nonthymoma groups. Nevertheless, the expression of TLR4 in both groups was
increased compared with control group. The levels of TLR4 mRNA had positive
correlation with Osserman type(R=0.609; P=0.004) . CONCLUSION: TLR4 may play a
key role in the pathogenesis of MG. It was the thymic tissues adjacent to
thymomas but not thymomas themselves participated in the onset of MG.

Publication Types:
English Abstract

PMID: 18543224 [PubMed - in process]

47: Ann Surg Oncol. 2008 May 30. [Epub ahead of print]

Videothoracoscopic Resection of Encapsulated Thymic Carcinoma: Retrospective
Comparison of the Results Between Thoracoscopy and Open Methods.

Cheng YJ.

Division of Thoracic Surgery, Department of Surgery, E-Da Hospital/I-Shou
University, 1 E-Da Road, Jiau-shu Tsuen, Yan-chau Shiang, Kaohsiung County, 824,
Taiwan, yujen.cheng@msa.hinet.net.

BACKGROUND: Although videothoracoscopic (VTS) resection of thymoma has been
reported to be a less invasive technique than open sternotomy, the usefulness of
this method in the treatment of encapsulated thymic carcinoma has not yet been
evaluated. We retrospectively compared the VTS and open methods (median
sternotomy) to investigate whether VTS resection could be performed as
successfully as open surgery to treat resectable thymic carcinoma. METHODS:
Between November 2002 and March 2007 a retrospective review was made of eight
patients (four women and four men) with Masaoka stage I and II encapsulated
thymic tumor. Four patients (the VTS group) underwent tumor resection by means of
a three-port endoscopic technique. The other four patients (the open group)
underwent tumor excision via a standard sternotomy approach. The resected thymic
carcinoma tissues were all confirmed by histopathological examination. RESULTS:
No patient died nor did any major morbidity or recurrence occur during the mean
follow-up period of 3.76 +/- 1.43 years. The open group sustained more blood loss
(246.3 ml more) and pleural drainage time (5.7 days more), and were hospitalized
for a longer period (12.5 days more). However in the open group the tumor size
was larger (38.6 cm(3 )more ) and the mean follow-up time was longer (1.4 years
more). CONCLUSION: These results have encouraged us to treat more patients with
encapsulated thymic carcinoma by means of VTS resection.

PMID: 18512103 [PubMed - as supplied by publisher]

48: Biol Reprod. 2008 May 28. [Epub ahead of print]

Protein Phosphatase 3 Differentially Modulates Vascular Endothelial Growth
Factor- and Fibroblast Growth Factor 2-Stimulated Cell Proliferation and
Signaling in Ovine Fetoplacental Artery Endothelial Cells.

Wang K, Song Y, Chen DB, Zheng J.

A critical process for vascular endothelial growth factor (VEGF)- and fibroblast
growth factor 2 (FGF2)-regulated cellular function is reversible protein
phosphorylation, which is tightly controlled by a balance of protein kinases and
phosphatases. We have reported that in ovine fetoplacental artery endothelial
(OFPAE) cells, VEGF and FGF2 stimulate cell proliferation partially via
activation of mitogen-activated protein kinase kinase 1/2
(MAP2K1/2)/mitogen-activated protein kinase 3/1 (MAPK3/1) and phosphoinositide
3-kinase (PI3K)/v-akt murine thymoma viral oncogen homolog 1 (AKT1) pathways. In
this study, we examined if protein phosphatase 3 (PPP3) mediated VEGF- and
FGF2-stimulated OFPAE cell proliferation via modulating activation of MAPK3/1 and
AKT1. Small interfering RNA (siRNA) targeting human PPP3 catalytic subunit alpha
(PPP3CA) was used to suppress PPP3CA protein expression in OFPAE cells. As
compared with the scrambled siRNA, PPP3CA siRNA decreased PPP3CA protein levels
by ~ 97% without altering protein levels of protein phosphatase 2 (PPP2)
catalytic subunit alpha (PPP2CA), total MAPK3/1, total AKT1, or
glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Knockdown of PPP3CA protein
expression enhanced VEGF-, but not FGF2-stimulated cell proliferation. Knockdown
of PPP3CA protein expression did not significantly affect VEGF-induced MAPK3/1
and AKT1 phosphorylation, while attenuated FGF2-induced MAPK3/1 and AKT1
phosphorylation. Thus, this is the first report demonstrating successful
knockdown of PPP3CA protein expression in any cell model using a single pair of
double-strained siRNA. Moreover, specific knockdown of PPP3CA protein expression
enhances VEGF-, but not FGF2-stimulated OFPAE cell proliferation and attenuates
FGF2-, but not VEGF-induced MAPK3/1 and AKT1 activation. Thus, PPP3CA
differentially modulates the VEGF- and FGF2-stimulated cell proliferation and
signaling cascades in OFPAE cells. These data also suggest that signaling
molecules other than MAPK3/1 and AKT1 play an important role in VEGF- and
FGF2-stimulated cell proliferation after knockdown of PPP3CA in OFPAE cells.

PMID: 18509162 [PubMed - as supplied by publisher]

49: Leuk Res. 2008 May 20. [Epub ahead of print]

Pure red cell aplasia associated with thymoma: Is thymectomy the cure?

Bhargava R, Dolai TK, Singhal D, Mahapatra M, Mishra P, Rathod N, Rathi S.

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

Publication Types:
LETTER

PMID: 18499248 [PubMed - as supplied by publisher]

50: Cancer Res. 2008 May 15;68(10):3854-62.

Cancer immunotherapy using in vitro genetically modified targeted dendritic
cells.

Wei H, Wang H, Lu B, Li B, Hou S, Qian W, Fan K, Dai J, Zhao J, Guo Y.

International Joint Cancer Institute, The Second Military Medical University, and
Shanghai Center for Cell Engineering and Antibody, Shanghai, People's Republic of
China.

Modest clinical outcomes of dendritic cell (DC) vaccine trials call for novel
strategies. In this study, we have created a chimeric CD40 molecule that
incorporates a single chain Fv (scFv) molecule specific for human ErbB2 antigen
and fusing to the membrane spanning and cytosolic domains of murine CD40. After
adenoviral transfer to bone marrow-derived DC, this chimeric receptor (CR)
induced nuclear factor-kappaB (NF-kappaB)-dependent DC activation and effector
function when cultured with immobilized ErbB2 protein or ErbB2-positive tumor
cells in vitro. In vivo migration assays showed that approximately 40% injected
CR-modified DC (scFv-CD40-DC) effectively migrated to ErbB2-positive tumors,
where they were activated after ErbB2 antigen stimulation, and sequentially homed
into the draining lymph nodes. In murine ErbB2-positive D2F2/E2 breast tumor
(BALB/c) and EL4/E2 thymoma (C57BL/6) models, i.v. injection of 1 x 10(6)
scFv-CD40-DC significantly inhibited tumor growth and cured established tumors.
Importantly, the cured mice treated by injection of scFv-CD40-DC were effective
in preventing both ErbB2-positive and parental ErbB2-negative tumor rechallenge.
Analysis of the underlying mechanism revealed that i.v. infusion of scFv-CD40-DC
elicited tumor-specific CTL responses, and the transfer of CTLs from
scFv-CD40-DC-treated mice protected naive mice against a subsequent tumor
challenge. These results support the concept that genetic modification of DC with
tumor-associated antigen-specific CD40 chimeric receptor might be a useful
strategy for treatment of human cancers.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18483270 [PubMed - indexed for MEDLINE]

51: Int J Surg Pathol. 2008 May 14. [Epub ahead of print]

Thymoma and Thymic Carcinoma Arising in a Thymolipoma: Report of a Unique Case.

Haddad H, Joudeh A, El-Taani H, Mansour A, Morcos B, Fayoumi S, Sughayer M.

Thymic carcinoma arising within a thymolipoma has not been reported previously.
The authors present a unique case of thymoma and undifferentiated thymic
carcinoma arising within a thymolipoma in a 36-year-old woman. The bulk of the
resected mass was composed of benign fatty tissue admixed with foci of
unremarkable thymic tissue; however, it also harbored a central solid mass
showing undifferentiated thymic carcinoma associated with a type B2 thymoma. The
carcinoma cells were positive for cytokeratin AE1/AE3, cytokeratin 19, and
cytokeratin 8/18. They were negative for vimentin, cytokeratin 7, cytokeratin 20,
CD5, epithelial membrane antigen, CD30, placental alkaline phosphatase,
carcinoembryonic antigen, CD99, leukocyte common antigen, Epstein-Barr virus,
inhibin alpha, and protein gene product 9.5. Rare tumor cells showed positive
staining for chromogranin and synaptophysin.

PMID: 18480395 [PubMed - as supplied by publisher]

52: Neurology. 2008 May 13;70(20):1883-90.

Clinical spectrum of voltage-gated potassium channel autoimmunity.

Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ.

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

OBJECTIVE: To document neurologic, oncologic, and serologic associations of
patients in whom voltage-gated potassium channel (VGKC) autoantibodies were
detected in the course of serologic evaluation for neuronal, glial, and muscle
autoantibodies. METHODS: Indirect immunofluorescence screening of sera from
130,000 patients performed on a service basis for markers of paraneoplastic
neurologic autoimmunity identified 80 patients whose IgG bound to the
synapse-rich molecular layer of mouse cerebellar cortex in a pattern consistent
with VGKC immunoreactivity. Antibody specificity was confirmed in all cases by
immunoprecipitation of detergent-solubilized brain synaptic proteins complexed
with (125)I-alpha-dendrotoxin. RESULTS: Clinical information was available for 72
patients: 51% women, median age at symptom onset 65 years, and median follow-up
period 14 months. Neurologic manifestations were acute to subacute in onset in
71% and multifocal in 46%; 71% had cognitive impairment, 58% seizures, 33%
dysautonomia, 29% myoclonus, 26% dyssomnia, 25% peripheral nerve dysfunction, 21%
extrapyramidal dysfunction, and 19% brainstem/cranial nerve dysfunction.
Creutzfeldt-Jakob disease was a common misdiagnosis (14%). Neoplasms encountered
(confirmed histologically in 33%) included 18 carcinomas, 5 adenomas, 1 thymoma,
and 3 hematologic malignancies. Hyponatremia was documented in 36%, other
organ-specific autoantibodies in 49%, and a co-existing autoimmune disorder in
33% (including thyroiditis 21%, type 1 diabetes mellitus 11%). Benefit was
reported for 34 of 38 patients (89%) receiving immunotherapy and was marked in
50%. CONCLUSIONS: The spectrum of neurologic manifestations and neoplasms
associated with voltage-gated potassium channel (VGKC) autoimmunity is broader
than previously recognized. Evaluation for VGKC antibodies is recommended in the
comprehensive autoimmune serologic testing of subacute idiopathic neurologic
disorders.

PMID: 18474843 [PubMed - indexed for MEDLINE]

53: Can J Neurol Sci. 2008 May;35(2):265-6.

Malignant thymoma presenting as sensorineural deafness.

Hunter G, Ringrose J, Kirk A.

Publication Types:
Letter

PMID: 18574948 [PubMed - in process]

54: Carcinogenesis. 2008 May;29(5):1077-82. Epub 2008 Mar 20.

The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular
endothelial growth factor (VEGF) production in TRAMP prostates.

Fritz WA, Lin TM, Peterson RE.

School of Pharmacy,University of Wisconsin, 777 Highland Avenue, Madison, WI
53705, USA.

Hypoxia-inducible factor-1 alpha (HIF-1alpha) and aryl hydrocarbon receptor
nuclear translocator (ARNT) are basic helix-loop-helix/per-arnt-sim (PAS) family
transcription factors. During angiogenesis and tumor growth, HIF-1alpha dimerizes
with ARNT, inducing expression of many genes, including vascular endothelial
growth factor (VEGF). ARNT also dimerizes with the aryl hydrocarbon receptor
(AhR). AhR-null (Ahr(-/-)) transgenic adenocarcinoma of the mouse prostate
(TRAMP) mice develop prostate tumors with greater frequency than AhR wild-type
(Ahr(+/+)) TRAMP mice, even though prevalence of prostate epithelial hyperplasia
is not inhibited. This suggests that Ahr inhibits prostate carcinogenesis. In
TRAMP mice, prostatic epithelial hyperplasia results in stabilized HIF-1alpha,
inducing expression of VEGF, a prerequisite for tumor growth and angiogenesis.
Since ARNT is a common dimerization partner of AhR and HIF-1alpha, we
hypothesized that the AhR inhibits prostate tumor formation by competing with
HIF-1alpha for ARNT, thereby limiting VEGF production. Prostates from Ahr(+/+),
Ahr(+/-) and Ahr(-/-) C57BL/6J TRAMP mice were cultured in the presence of graded
concentrations of vanadate, an inducer of VEGF through the HIF-1alpha-ARNT
pathway. Vanadate induced VEGF protein in a dose-dependent fashion in Ahr(+/-)
and Ahr(-/-) TRAMP cultures, but not in Ahr(+/+) cultures. However, vanadate
induced upstream proteins in the phosphatidylinositol 3-kinase-signaling cascade
to a similar extent in TRAMPs of each Ahr genotype, evidenced by v-akt murine
thymoma viral oncogene homolog (Akt) phosphorylation. These findings suggest that
AhR sequesters ARNT, decreasing interaction with HIF-1alpha reducing VEGF
production. Since VEGF is required for tumor vascularization and growth, these
studies further suggest that reduction in VEGF correlates with inhibited prostate
carcinogenesis in Ahr(+/+) TRAMP mice.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 18359762 [PubMed - in process]

55: Clin Exp Dermatol. 2008 May;33(3):229-33. Epub 2008 Mar 18.

Subcorneal pustular dermatosis: 50 years on.

Cheng S, Edmonds E, Ben-Gashir M, Yu RC.

Departments of Dermatology and Histopathology, University College London
Hospital, London, UK. suzanne.cheng@gmail.com

We review the key developments in our understanding of subcorneal pustular
dermatosis (SCPD, also known as Sneddon-Wilkinson disease) over the past 50
years. SCPD is a rare, chronic, sterile pustular eruption that was first
described by Sneddon and Wilkinson in 1956. The primary lesions are pea-sized
pustules classically described as half-pustular, half-clear flaccid fluid
blisters. Histologically the salient feature is a subcorneal accumulation of
neutrophils, suggesting the presence of chemoattractants such as tumour necrosis
factor (TNF)alpha in the uppermost epidermis. However, to date its exact
pathophysiology is unknown. Cases in association with pyoderma gangrenosum,
benign monoclonal IgA gammopathy and multiple myeloma are well documented. There
are anecdotal reports of SCPD associated with other internal malignancies such as
chronic lymphocytic leukaemia, thymoma, apudoma and epidermoid carcinoma of the
lung. The treatment of choice is dapsone. Therapeutic alternatives include
retinoids, phototreatment with psoralen ultraviolet (UV) A, broadband or narrow
band UVB and corticosteroids. Anecdotal uses of tacalcitol, ketoconazole,
azithromycin, tetracycline, minocycline, vitamin E, ciclosporin, colchicine,
mizoribine, mebhydrolin, infliximab and adalimumab with mycophenolate mofetil
have all been reported.

PMID: 18355359 [PubMed - in process]

56: Histopathology. 2008 May;52(6):759-66. Epub 2008 Apr 5.

Classifying thymomas.

Addis BJ, den Bakker MA.

Department of Cellular Pathology, Southampton University Hospitals Trust,
Southampton, UK. bruce.addis@suth.swest.nhs.uk

PMID: 18397282 [PubMed - indexed for MEDLINE]

57: Int Immunopharmacol. 2008 May;8(5):732-40. Epub 2008 Feb 14.

A comparative study on cannabidiol-induced apoptosis in murine thymocytes and
EL-4 thymoma cells.

Lee CY, Wey SP, Liao MH, Hsu WL, Wu HY, Jan TR.

Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.

It has been shown that leukemia and glioma cells are sensitive to cannabidiol
(CBD)-induced apoptosis, whereas primary monocytes and glia cells are relatively
insensitive. In the current study, the cellular events and sensitivity to
CBD-induced apoptosis between murine thymocytes and EL-4 thymoma cells were
compared. Cannabidiol markedly induced apoptosis in a time- and
concentration-related manner in both cells. The efficacy of CBD to induce
apoptosis was comparable between the 2 types of T cells, whereas CBD induced
apoptosis in thymocytes with a slightly greater potency than in EL4 cells.
Time-course analyses revealed CBD-mediated apoptosis occurred earlier in EL-4
cells than that in thymocytes. An increased level of cellular reactive oxygen
species (ROS) was detected in both cells with the peak response at 2 h post CBD
treatment. Concordantly, CBD triggered a gradual diminishment in the cellular
thiols. The presence of N-acetyl-L-cysteine (NAC), a precursor of glutathione,
markedly attenuated the induction of apoptosis, and restored the diminished
levels of cellular thiols. The results demonstrated that both thymocytes and EL-4
thymoma cells were susceptible to CBD-induced apoptosis and that ROS played a
critical role in the apoptosis induction.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18387516 [PubMed - in process]

58: Lung Cancer. 2008 Apr 28. [Epub ahead of print]

Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

Yoh K, Nishiwaki Y, Ishii G, Goto K, Kubota K, Ohmatsu H, Niho S, Nagai K, Saijo
N.

Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1
Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

This study was conducted to evaluate the prevalence of EGFR and KIT mutations in
thymomas and thymic carcinomas as a means of exploring the potential for
molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was
isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17
thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17,
were analyzed for mutations by PCR and direct sequencing. Protein expression of
EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in
2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR
mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR
protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas.
The mutational analysis of KIT revealed only a missense mutation (L576P) in exon
11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic
carcinomas and 0% of the thymomas. The results of this study indicate that EGFR
and KIT mutations in thymomas and thymic carcinomas are rare, but that many of
the tumors express EGFR or KIT protein.

PMID: 18448188 [PubMed - as supplied by publisher]

59: Neurology. 2008 Apr 23. [Epub ahead of print]

A trial of mycophenolate mofetil with prednisone as initial immunotherapy in
myasthenia gravis.

The Muscle Study Group.

OBJECTIVE: To test the hypothesis that mycophenolate mofetil (MMF) with
prednisone provides better control of myasthenic weakness than prednisone alone
in the initial management of generalized myasthenia gravis (MG). METHODS: Eighty
immunosuppression naïve subjects with mild to moderate generalized, acetylcholine
receptor positive MG at 13 centers were randomized to 2.5 g/day MMF plus 20
mg/day prednisone (n = 41) or placebo plus 20 mg/day prednisone (n = 39) and
followed in a double-blind fashion for 12 weeks. Subjects over 18 years of age
were included if judged to be candidates for immunosuppression; excluded were
those with thymoma or severe oropharyngeal or respiratory muscle weakness. The
primary measure of efficacy was change in the quantitative MG (QMG) score from
baseline to week 12. Study completers could take open-label MMF for an additional
24 weeks, while prednisone was reduced to the minimally effective dosage.
RESULTS: The mean change in QMG score was similar in the treated (-4.4+/-5.1) and
placebo (-3.6 +/- 5.0) groups (p = 0.71). The dosage of prednisone was reduced by
a similar amount in both groups during the open-label phase. Subjects tolerated
the study drug well, without unexpected adverse events. CONCLUSIONS: This study
demonstrated no benefit of mycophenolate mofetil (MMF) with 20 mg/ day prednisone
compared to 20 mg/day of prednisone alone after 12 weeks. This may be due to
greater than predicted benefit from the prednisone dosage used, the short
duration of the study, or the absence of any benefit of MMF in this population of
patients with myasthenia gravis.

PMID: 18434639 [PubMed - as supplied by publisher]

60: J Am Vet Med Assoc. 2008 Apr 15;232(8):1186-92.

Results of excision of thymoma in cats and dogs: 20 cases (1984-2005).

Zitz JC, Birchard SJ, Couto GC, Samii VF, Weisbrode SE, Young GS.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The
Ohio State University, Columbus, OH 43210, USA.

OBJECTIVE: To provide long-term follow-up information for a series of dogs and
cats with invasive and noninvasive thymomas treated by excision alone. DESIGN:
Retrospective case series. ANIMALS: 9 cats and 11 dogs with thymoma. PROCEDURES:
Medical records were reviewed. The following factors were analyzed for their
effect on prognosis: age of dog or cat, invasiveness of the tumor, percentage of
lymphocytes in the mass (percentage lymphocyte composition) on histologic
evaluation, and mitotic index of the mass. RESULTS: All patients were treated
with excision of the tumor alone. Median overall survival time for the cats was
1,825 days, with a 1-year survival rate of 89% and a 3-year survival rate of 74%.
Median overall survival time for the dogs was 790 days, with a 1-year survival
rate of 64% and a 3-year survival rate of 42%. Recurrence of thymoma was observed
in 2 cats and 1 dog, and a second surgery was performed in each, with subsequent
survival times of 5, 3, and 4 years following the first surgery. Percentage
lymphocyte composition of the mass was the only factor that was significantly
correlated with survival time; animals with a high percentage of lymphocytes
lived longer. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated
that most cats and dogs with thymomas did well after excision. Even cats and dogs
with invasive masses that survived the surgery and the few cats and dogs with
recurrent thymomas or paraneoplastic syndromes had a good long-term outcome.
Excision should be considered an effective treatment option for dogs and cats
with thymomas.

PMID: 18412532 [PubMed - indexed for MEDLINE]

61: Int J Surg Pathol. 2008 Apr 7. [Epub ahead of print]

Metaplastic Thymoma: Report of an Unusual Thymic Epithelial Neoplasm Arising in a
Thymic Cyst Wall.

Poorabdollah M, Mehdizadeh E, Mohammadi F, Sabeti S.

In this report, a case of metaplastic thymoma arising in a thymic cyst wall is
discussed. The patient was a 61-year-old male whose chief complaint was sweating
and chest pain. Imaging study revealed a mediastinal mass with right hemithoracic
extension. He underwent surgical resection of the mass and remnants of the
thymus. Histologic studies showed a primary thymic neoplasm with a biphasic
histologic pattern composed of 2 distinct epithelial and stromal components
arising in a thymic cyst wall. Immunohistochemically, the epithelial component
was cytokeratin positive and focally reactive for EMA. Marked expression of EMA
and vimentin was seen in spindle cells. Metaplastic thymoma is an extremely rare
variant of primary thymic epithelial neoplasms with only a few cases reported in
the literature.

PMID: 18397900 [PubMed - as supplied by publisher]

62: Ann Thorac Cardiovasc Surg. 2008 Apr;14(2):119-22.

Long-term clinical outcome after extended thymectomy combined postoperative
high-dose steroid therapy for juvenile myasthenia gravis.

Kanzaki M, Obara T, Sasano S, Hikawa Y, Onuki T.

Department of Thoracic Surgery, Tokyo Metropolitan Fuchu Hospital, Fuchu, Japan.

Myasthenia gravis (MG) is considered to be an autoimmune disorder of
neuromuscular transmission and is rare in childhood. We report 3 juvenile MG
(JMG) cases of extended thymectomy (ETMX) combined postoperative high-dose
steroid therapy. All patients developed MG symptoms under the age of 14 years and
were given cholinergic drugs and had generalized MG: the Myasthenia Gravis
Foundation of America classification II was present in 1 case and classification
III was in 2. All patients were taking pyridostigmine before surgery; none was
treated with prednisone preoperatively. All patients performed the ETMX combined
postoperative high-dose steroid therapy. Muscle weakness of extremities and
bulbar symptoms improved in all patients, but not all exhibited an unstable phase
in their clinical course as a result of combined therapy. There was no
postoperative morbidity or mortality. All patients had follicular lymphoid
hyperplasia without thymoma. Follow-up for more than 5 years has shown one to be
in complete remission and the others to have improved symptoms. Although our
results are inconclusive because we used only a few JMG patients, the ETMX
combined postoperative high-dose steroid therapy appeared to provide a better
chance of remission or control of symptoms.

PMID: 18414352 [PubMed - in process]

63: Br J Radiol. 2008 Apr;81(964):e127-9.

Multilocular thymic tuberculosis: case report.

Ganesan S, Ganesan K.

Department of Radiology and Imaging, GKNM Hospital and Research Centre, PN
Palayam, Coimbatore, India.

Tuberculosis is a widely prevalent disease in India. However, primary thymic
involvement is an extremely uncommon presentation of this entity; a review of the
literature revealed only seven documented cases of primary thymic tuberculosis.
With the increasing prevalence of human immunodeficiency virus (HIV) in India,
however, the occurrence of tuberculosis in previously uncommon anatomical
locations may become more frequent. We report the unusual clinical, radiological
and pathological findings in a HIV seronegative 30-year-old Indian man with
primary multilocular thymic tuberculosis.

Publication Types:
Case Reports
Review

PMID: 18344272 [PubMed - indexed for MEDLINE]

64: Eur J Cardiothorac Surg. 2008 Apr;33(4):707-11. Epub 2008 Feb 20.

Surgical treatment of pleural recurrence from thymoma.

Lucchi M, Basolo F, Mussi A.

Division of Thoracic Surgery, Cardiac and Thoracic Department, University of
Pisa, Via Paradisa 2, Pisa 56124, Italy. m.lucchi@med.unipi.it

A complete surgical resection represents the cornerstone of the therapy of the
thymic tumours. Pleural disease may already be present at the diagnosis
representing an advanced stage thymoma (Masaoka IVA) or it may appear during the
follow-up, representing a pleural recurrence. The treatment of Stage IVA thymoma
is quite examined in the medical literature; however just a few reports analysed
the surgical treatment of thymoma recurrences, whose exclusive pleural
recurrences represent more than 90%. Our aim was to review the literature laying
the stress on the incidence, diagnosis, treatment options and prognosis of this
highly selected group of patients with pleural recurrence from thymoma.

PMID: 18282761 [PubMed - in process]

65: Gen Thorac Cardiovasc Surg. 2008 Apr;56(4):143-50. Epub 2008 Apr 10.

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia
gravis.

Okumura M, Fujii Y, Shiono H, Inoue M, Minami M, Utsumi T, Kadota Y, Sawa Y.

Department of General Thoracic Surgery (L5), Osaka University Graduate School of
Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
meinosin@surg1.med.osaka-u.ac.jp

Thymoma and thymic carcinoma are the representative tumors arising from the
thymic epithelium. Thymoma is well known for association with autoimmune diseases
including myasthenia gravis, suggesting its biological activity. Herein, recent
progress in research of thymoma is reviewed with reference to its immunological
function. Myasthenia gravis is frequently associated with WHO type B1 and B2
thymomas. These types of thymomas hold a significant number of CD4(+)CD8(+)
double-positive T cells, and at the same time, the neoplastic epithelial cells
express HLA-DR molecules at a slightly reduced level compared with the normal
thymus. The impaired expression of HLA-DR molecules in neoplastic epithelial
cells of thymomas possibly affects positive selection of CD4(+)CD8(-)
single-positive T cells and may result in alteration of its repertoire. The
function of thymoma neoplastic cells as the cortical epithelium of the thymus and
the morphological resemblance of thymomas to the cortex suggest that thymoma is
of cortical epithelial origin; this might imply that thymoma lacks the functional
medulla where professional antigen-presenting cells are engaged in negative
selection. These findings suggest that thymoma generates autoreactive T cells
causing autoimmunity. Further investigation on immunological function of thymoma
is supposed to elucidate the pathogenesis of thymoma-related autoimmunity and the
high affinity of thymoma with myasthenia gravis. In addition, studying the
biology of thymoma is also expected to contribute to further understanding of
T-cell development and immunological tolerance in the human, because thymoma can
be considered an acquired thymus.

PMID: 18401674 [PubMed - in process]

66: Hematology. 2008 Apr;13(2):88-91.

Spectrum of pure red cell aplasia in adult population of north-west India.

Malhotra P, Muralikrishna GK, Varma N, Kumari S, Das R, Ahluwalia J, Jain S,
Varma S.

Deparment of Internal Medicine, Post Graduate Institute of Medical Education and
Research, Chandigarh 160012, India.

Pure red cell aplasia (PRCA) is a rare haematological disorder characterised by
selective inhibition of red cell precursors in the bone marrow. We conducted a
retrospective analysis of nine cases of PRCA seen in our adult haematology clinic
from January 2000 to December 2003. All patients had baseline hemogram, bone
marrow examination, CT scan of chest, autoimmune and infectious disease markers.
The diagnosis of PRCA was made on bone marrow examination showing normal
granulocytic and megakaryocytic series with erythroblastopenia. The age range was
14-68 years (median: 40 years) and a male to female ratio of 3 : 1. In five
patients, the aetiology of PRCA could not be identified with available
investigations and were labelled as primary PRCA. The secondary causes of PRCA
included three cases of thymoma and one case of non-Hodgkin lymphoma. Out of nine
patients, three patients had died and two lost to follow-up. At the last
available follow-up till December 2006, three patients (one secondary and two
primary PRCA) are maintaining normal haemoglobin and one patient still has active
disease. The retrospective review shows that causes and outcome of PRCA in the
developing world are different to those seen in the West.

PMID: 18616874 [PubMed - in process]

67: Hong Kong Med J. 2008 Apr;14(2):142-4.

Good's syndrome in a patient with cytomegalovirus retinitis.

Yong DS, Tsang MK, Chan EY, Tse DM.

Department of Medicine and Geriatrics, Caritas Medical Centre, Shamshuipo,
Kowloon, Hong Kong.

Thymoma-related adult-onset immunodeficiency or Good's syndrome is an uncommon
condition. This case, of a 50-year-old woman who was human immunodeficiency
virus-negative and developed herpes zoster and severe cytomegalovirus retinitis 6
months after removal of a thymoma, is the first to be reported in Hong Kong.
Immunological investigations revealed no B cells, hypogammaglobulinaemia, a low
CD4 count, and a low CD4/CD8 ratio. We recommend that immunological
investigations, including T-cell subsets, B cells, and quantitative
immunoglobulins, should be part of the routine diagnostic evaluation of patients
with thymoma and infections.

Publication Types:
Case Reports

PMID: 18382022 [PubMed - indexed for MEDLINE]

68: Interact Cardiovasc Thorac Surg. 2008 Apr;7(2):347-8. Epub 2007 Dec 6.

Thymoma accompanied by lichen planus.

Hayashi A, Shiono H, Okumura M.

Department of General Thoracic Surgery, Osaka University Graduate School of
Medicine, 2-2(L5), Yamadaoka, Suita, Osaka, 565-0871, Japan.
19720522@surg1.med.osaka-u.ac.jp

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.

Publication Types:
Case Reports

PMID: 18063606 [PubMed - indexed for MEDLINE]

69: J Am Acad Dermatol. 2008 Apr;58(4):713.

Comment on:
J Am Acad Dermatol. 2007 Oct;57(4):683-9.

Neoplasia-induced autoimmunity encompasses a spectrum of changes.

Helm TN, Grover R, Beutner E.

Publication Types:
Comment
Letter

PMID: 18342723 [PubMed - indexed for MEDLINE]

70: J Clin Oncol. 2008 Apr 1;26(10):1752-5.

Widespread metastases after resection of noninvasive thymoma.

Gamboa EO, Sawhney V, Lanoy RS, Haller NA, Powell AT, Hazra SV.

Department of Medicine, Akron General Medical Center, Akron, OH, USA.

Publication Types:
Case Reports

PMID: 18375905 [PubMed - indexed for MEDLINE]

71: J Eur Acad Dermatol Venereol. 2008 Apr;22(4):506-7.

Oral erosive lichen planus and Good's syndrome: just a coincidence or a direct
link between the two diseases?

Seneschal J, Orlandini V, Duffau P, Viallard JF, Pellegrin JL, Doutre MS,
Beylot-Barry M.

Publication Types:
Case Reports
Letter

PMID: 18363920 [PubMed - indexed for MEDLINE]

72: Lung Cancer. 2008 Apr;60(1):4-13. Epub 2008 Mar 17.

A review of thymic tumours.

Srirajaskanthan R, Toubanakis C, Dusmet M, Caplin ME.

Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free Hospital,
Pond Street, London NW3 2QG, UK.

Tumours of the thymus are uncommon and are generally regarded as being indolent.
Whilst this is often true of thymomas; thymic adenocarcinoma and thymic
neuroendocrine cancer can be aggressive and have a poor prognosis. Understanding
the biology of these tumours is important for prognosis and management. The
pathological features of these tumours are examined in detail. Imaging modalities
for aiding in diagnosis and staging of these tumours are described; this includes
CT and MRI, plus more recent advances including the use of FDG-PET and Indium-111
Octreotide scintigraphy. The treatment options available including curative
surgery, debulking surgery, chemotherapy, somatostatin analogues and peptide
receptor radionuclide therapy are discussed. The optimal chemotherapy regimens
are still unclear, although promising results have been obtained with
platinum-based chemotherapy. The role for adjuvant therapy in both thymic
carcinoma and thymoma is unclear except, in patients with stage I thymomas. There
is a high expression of somatostatin receptors in thymic tumours and anti-tumour
benefit has been reported in patients treated with somatostatin analogues. A new
development is the role of peptide receptor radionuclide therapy. This has become
an established therapy in management of gastroenteropancreatic neuroendocrine
tumours and its use has been recently described in case reports in both thymoma
and thymic carcinoma.

PMID: 18343528 [PubMed - in process]

73: Nervenarzt. 2008 Apr;79(4):470-4.

[Diagnosis and differential diagnosis of granulomatous myositis]

[Article in German]

Gdynia HJ, Mogel H, Kühnlein P, Dorst J, Osterfeld N, von Arnim CA, Sperfeld AD.

Muskellabor der Neurologischen Klinik der Universität Ulm, Oberer Eselsberg 45,
89081, Ulm, Deutschland. hans-juergen.gdynia@uni-ulm.de

Granulomatous myositis is a rare neuromuscular disorder histologically
characterized by the development of endomyseal and/or perimyseal granulomas.
Clinical hallmarks are generalized muscle weakness, myalgias, and bulbar
symptoms. The association of granulomatous myositis with sarcoidosis is well
known; less recognized is the association with several infectious diseases,
inflammatory bowel diseases, malignancy, thymoma, graft-vs-host disease, and
myasthenia gravis. In absence of sarcoidosis or other underlying disorders, the
diagnosis of isolated or primary granulomatous myositis must be considered.
Therapeutic strategies focus on immunosuppression, whereas the therapy response
is unpredictable. Here we discuss the clinical features, diagnosis, and
differential diagnosis and therapeutic strategies of primary and secondary
granulomatous myositis.

Publication Types:
Case Reports
English Abstract

PMID: 18210045 [PubMed - indexed for MEDLINE]

74: Nihon Kokyuki Gakkai Zasshi. 2008 Apr;46(4):297-301.

[A case of Pneumocystis jiroveci pneumonia that presented with cavity and cystic
changes in a malignant thymoma patient]

[Article in Japanese]

Kono M, Fujii M, Akamatsu T, Suda T, Chida K.

Department of Internal Medicine, Yaizu General Hospital.

A 53-year-old man had received various chemotherapy and steroid treatments for
malignant thymoma. He had demonstrated persistent fever since the beginning of
January 2006, and chest radiograph showed consolidation in the left middle lung
fields. Bacterial pneumonia was suspected, but antibiotics were not effective. He
was referred and admitted to our hospital on January 16. Chest radiograph and CT
scan on admission showed diffuse ground-glass opacities, consolidation with
cavity, and cystic changes. Pneumocystis jiroveci Pneumonia was diagnosed by
examination of alveolar lavage. This patient was regarded as immunodeficient
because of steroid treatment, low counts of CD4-positive lymphocytes, and the
complication of hypogammagloblinemia. We reported this case of a non-HIV patient
with atypical images demonstrating Pneumocystis jiroveci pneumonia.

Publication Types:
English Abstract

PMID: 18516993 [PubMed - in process]

75: Surg Endosc. 2008 Apr;22(4):1135-6. Epub 2008 Feb 21.

Comment on:
Surg Endosc. 2008 Jan;22(1):265.

Inclusion of the transcervical approach in video-assisted thoracoscopic extended
thymectomy (VATET) for myasthenia gravis: a prospective trial.

Shiono H, Shigemura N, Okumura M.

Publication Types:
Comment
Letter

PMID: 18288532 [PubMed - indexed for MEDLINE]

76: J Med Case Reports. 2008 Mar 19;2:89.

Managing a locally advanced malignant thymoma complicated by nephrotic syndrome:
a case report.

Teoh DC, El-Modir A.

Cancer Centre, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
dcy_teoh@hotmail.com.

ABSTRACT: INTRODUCTION: The management of locally advanced inoperable malignant
thymoma is difficult as there are no large randomized clinical trial data to
guide treatment. However various case series have shown that malignant thymoma is
often a chemosensitive disease. Cisplatin-based chemotherapy has been the
gold-standard in the management of these patients. However when thymic cancers
are complicated by paraneoplastic syndromes that damage kidney and neurological
function, cisplatin use is often contraindicated. CASE PRESENTATION: We report a
case of a 37 year old man with locally advanced malignant thymoma complicated by
significant nephrotic syndrome and renal impairment. He responded to a novel
combination of carboplatin, epirubicin and cyclophosphamide chemotherapy used as
first line therapy. CONCLUSION: The treatment with chemotherapy of locally
advanced malignant thymoma complicated by nephrotic syndrome and renal impairment
is difficult due to the increase of toxicity. In this case, a novel chemotherapy
combination with lesser toxicity was used successfully. In addition this
chemotherapy combination did not impede the later use of conventional
cisplatin-based chemotherapy. Therefore we suggest a course of carboplatin-based
chemotherapy for locally advanced malignant thymoma in patients who are
unsuitable for cisplatin.

PMID: 18353189 [PubMed - in process]

77: Ann Acad Med Singapore. 2008 Mar;37(3):253-4.

Pericardial thymoma: an unusual cause of sudden death.

Turkmen N, Eren B, Comunoglu N, Fedakar R, Senel B.

Publication Types:
Letter

PMID: 18392312 [PubMed - in process]

78: Biomaterials. 2008 Mar;29(7):917-24. Epub 2007 Nov 26.

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.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18035411 [PubMed - indexed for MEDLINE]

79: Ceylon Med J. 2008 Mar;53(1):25-6.

A case of generalised myasthenia gravis with membranous nephropathy.

Prasad KP, Alahakoon DG, Vidanagama U.

Teaching Hospital, Kandy, Sri Lanka. ruwan@med.ruh.ac.lk

We report a 40-year old woman with bilateral partial ptosis, complete external
ophthalmoplegia, and weakness and fatiguability of upper limbs. She was on
treatment for hypertension for 5 months at the time of admission. She was found
to have generalised myasthenia gravis and membranous nephropathy with end-stage
renal disease. Her symptoms and signs improved within 2 months on treatment with
neostigmine and prednisolone. It is postulated that either thymic hyperplasia or
the subclinical stage of a thymoma may be the underlying aetiological factor in
this patient.

PMID: 18590268 [PubMed - in process]

80: Clin Nucl Med. 2008 Mar;33(3):234-5.

F-18 FDG PET/CT demonstration of thymoma followed by development of lung cancer.

Choi JJ, Ahn MI, Park MY, Jeon JS, Park YH.

Department of Radiology and Nuclear Medicine, St. Vincent's Hospital, The
Catholic University of Korea, 93 Ji-dong, Paidal-gu, Suwon, Korea.

It is well-known that thymoma can be associated with diverse extrathymic
malignancies. The authors present a case of a 72-year-old man with myasthenia
gravis in which F-18 FDG PET/CT demonstrated high FDG uptake in both an anterior
mediastinal mass and a lung nodule. The FDG uptake in the lung nodule was
significantly higher than that of the thymic lesion, which might suggest the
possibility of a second development of lung cancer in this thymoma patient.
Surgical resection was done for the 2 tumors, and histologic examination revealed
anterior mediastinal thymoma and primary adenocarcinoma of the lung. This case
demonstrates the potential usefulness of PET/CT in detecting and assessing the
second extrathymic malignancy in a patient with thymoma.

Publication Types:
Case Reports

PMID: 18287859 [PubMed - indexed for MEDLINE]

81: Clin Ter. 2008 Mar;159(2):91-95.

[Medical treatment for thymoma: an update.]

[Article in Italian]

Lalle M, Bellini V, Antimi M.

Unità Operativa complessa di Oncologia Medica, Ospedale S. Eugenio, Roma, Italia.

Stage of disease at diagnosis and histologic type according to WHO classifi
cation are the most important prognostic factors for thymoma and complete
surgical resection represents a crucial point for disease free survival. When
surgery is not feasible, neoadjuvant or palliative chemotherapy, is the most
appropriate treatment because of the high chemosensitivity of the thymoma. The
role of predictive factors to response of treatment seems relevant: the presence
of modifi cations of tumor related genes and expression of different thymoma cell
recep-tors could allow to identify subsets of patients who can benefi t from
target therapies, with the aim of optimizing treatments and improving survival.

PMID: 18463767 [PubMed - as supplied by publisher]

82: J Clin Immunol. 2008 Mar;28(2):194-206. Epub 2007 Nov 14.

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.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18000743 [PubMed - indexed for MEDLINE]

83: J Thorac Oncol. 2008 Mar;3(3):270-6.

Pathologic radioresponse of preoperatively irradiated invasive thymomas.

Onuki T, Ishikawa S, Yamamoto T, Ito H, Sakai M, Onizuka M, Sakakibara Y, Iijima
T, Noguchi M, Ohara K.

Department of Chest Surgery and Radiation Oncology, Graduate School of
Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki, Japan.

BACKGROUND: We have been applying preoperative radiotherapy (RT) to Masaoka stage
III thymomas intending to make surgical resection more complete by reducing mass
volume, to prevent possible dissemination caused by surgical manipulation and to
get better survival as a result. However, the radioresponses vary from tumor to
tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending
on pretreatment histology. MATERIALS AND METHODS: Twenty-one of stage III
thymomas underwent preoperative RT plus surgery followed by postoperative RT
between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO
histologic criteria, resectability, long-term survival, and disease control, by
preoperative RT were analyzed. RESULTS: Pretreatment WHO subtypes were type AB (n
= 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%)
decreased in size after preoperative RT with a mean (median) reduction ratio of
30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group
(mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01).
Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both
lymphocyte and epithelial cells diminished in type B2, whereas none of the B3
tumors showed any histologic change. The values of all the cases is 90.5% in
complete resection, 19.0% in no combined resection of the adjacent organs, and
77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and
these value do not differ according to the WHO histologic criteria. CONCLUSIONS:
This modality at modest doses was macroscopically and histopathologically
effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma.
The therapeutic benefit of preoperative RT followed by surgery and postoperative
RT for stage III thymomas should be defined thoroughly.

Publication Types:
Comparative Study

PMID: 18317070 [PubMed - indexed for MEDLINE]

84: J Thorac Oncol. 2008 Mar;3(3):265-9.

Thymic carcinoma: 30 cases at a single institution.

Yano M, Sasaki H, Yokoyama T, Yukiue H, Kawano O, Suzuki S, Fujii Y.

Department of Oncology, Immunology, and Surgery, Nagoya City University Graduate
School of Medical Sciences, Nagoya, Japan. motoki@med.nagoya-cu.ac.jp

INTRODUCTION: Thymic carcinoma is a rare and invasive mediastinal neoplasm that
often metastasizes. It constitutes a heterogeneous group of tumors that displays
different biologic behavior and prognosis. The clinical prognostic factors and
treatment of thymic carcinoma are not yet standardized. METHODS: Thirty patients
with thymic carcinoma have been treated at Nagoya City University Hospital since
1983. The clinical and pathologic data of these patients were retrospectively
reviewed. Thirteen cases were considered to be unresectable or inoperable and
received chemotherapy or chemoradiotherapy. Seventeen cases underwent resection;
total in 7 cases and subtotal in 10 cases. Postoperative irradiation was added as
adjuvant therapy in the tolerable cases. The most recent five cases received
induction chemotherapy. RESULTS: In 17 of the 30 cases, the patients died. The
survival periods in the death cases were from 2.4 to 78.1 months (mean, 32.4
months; median, 21.0 months). The observation periods in the 13 live cases were
6.3 to 232 months (average follow-up, 64.6 months). The 5-year survival rate was
47.5%, and median survival time (MST) was 49.0 months. Cases that underwent total
resection showed significantly better prognosis than cases with subtotal
resection (p = 0.011) and inoperable cases (p = 0.002). The cases that underwent
subtotal resection showed significantly better prognosis than the inoperable
cases (p = 0.050). The cases with hematogenous metastasis demonstrated
significantly poorer prognosis (p = 0.021), but lymphogenous metastasis was not a
significant predictor of poor prognosis. Only resectability was a significant
prognostic factor in multivariate Cox regression analysis, and the hazard ratio
was 5.123. CONCLUSIONS: Resectability was the only prognostic factor in thymic
carcinoma. We suggest the importance of preoperative precise evaluation to
exclude unresectable Masaoka stage IVb disease and expect preoperative
chemotherapy or chemoradiotherapy to improve the respectability.

Publication Types:
Comparative Study

PMID: 18317069 [PubMed - indexed for MEDLINE]

85: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Mar;105(3):e57-60.

A case of vulvovaginal gingival lichen planus in association with Good's
syndrome.

Moutasim KA, Poate TW, Setterfield JF, Challacombe SJ.

King's College London Dental Institute at Guy's, King's and St. Thomas'
Hospitals, London, UK. karwan.moutasim@kcl.ac.uk

Vulvovaginal gingival lichen planus (VVG LP) is a distinct variant of LP
frequently associated with mucocutaneous scarring and vaginal stricture
formation. Good's Syndrome (thymoma with hypogammaglobulinemia) is a rare cause
of immunodeficiency in adults. The clinical features, investigation findings, and
challenges in the management of a patient presenting with VVG LP and Good's
Syndrome are discussed.

PMID: 18280948 [PubMed - indexed for MEDLINE]

86: Singapore Med J. 2008 Mar;49(3):e64-7.

Pleural and transdiaphragmatic retroperitoneal metastasis developing two and half
years after resection of invasive thymoma.

Debnath J, Chawla N, Talwar R, Vohra LS, George RA, Singh HP, Vaidya A, Satija L.

Department of Radiodiagnosis & Imaging, Command Hospital (SC), Wanowrie, Pune,
Maharashtra 411040, India. jyotindu_debnath@rediffmail.com

We report transdiaphragmatic pleural and retroperitoneal metastasis developing
two and half years after resection of invasive thymoma (Masaoka stage III; WHO
type B1, lymphocyte-rich) in a 34-year-old man. Post-surgery, he received
radiotherapy and chemotherapy. Follow-up computed tomography (CT) one year
post-surgery did not reveal any local recurrence or metastasis. He remained
asymptomatic throughout. A follow-up CT done two and half years later revealed an
enhancing retrocrural-retroperitoneal (posterior pararenal space) soft tissue
mass measuring 12 cm x 10 cm x 6 cm. Another enhancing deposit was found in the
left pleural space. This lesion was found infiltrating into the subjacent lung.
Both these deposits were resected along with wedge resection of the affected
subsegment of the lung. Histopathology confirmed these lesions to be metastases
from the lymphocyte-rich thymoma.

Publication Types:
Case Reports

PMID: 18362988 [PubMed - indexed for MEDLINE]

87: Virchows Arch. 2008 Mar;452(3):319-24.

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 - in process]

88: Lung Cancer. 2008 Feb 25. [Epub ahead of print]

Utility of (18)FDG-PET for differentiating the grade of malignancy in thymic
epithelial tumors.

Endo M, Nakagawa K, Ohde Y, Okumura T, Kondo H, Igawa S, Nakamura Y, Tsuya A,
Murakami H, Takahashi T, Yamamoto N, Ito I, Kameya T.

Division of Endoscopy and Diagnostic Radiology, Shizuoka Cancer Center,
Nagaizumi, Shizuoka 411-8777, Japan.

PURPOSE: The objective of this study was to assess the value of (18)F-FDG PET in
thymic epithelial tumors according to the WHO histologic classification and to
evaluate its potential for differentiating the grade of malignancy in thymic
epithelial tumors. MATERIALS AND METHODS: Thirty-six patients with a thymic
epithelial tumor who underwent (18)F-FDG PET examination before treatment were
enrolled in the present study. The T/M ratio, which is the ratio of the peak
standardized uptake value (SUV) of the tumor to the mean SUV of mediastinum, was
compared in subgroups of a simplified WHO histological classification; low-risk
thymoma (Types A, AB and B1), high-risk thymoma (Types B2 and B3), and thymic
carcinoma. RESULTS: Tumors included 15 low-risk thymomas, 10 high-risk thymomas
and 11 thymic carcinomas. Upon visual inspection, all tumors showed (18)F-FDG
accumulation and the mean T/M ratio in these three subgroups was 2.64, 4.29 and
8.90, respectively. The differences between the three subgroups were
statistically significant (low-risk vs. high-risk: p=0.01, high-risk vs. thymic
carcinoma: p=0.01). CONCLUSION: A significant relationship was seen between
(18)F-FDG PET accumulation and histologic subtype in thymic epithelial tumors
when they were classified into three groups. PET may be useful for predicting the
grade of malignancy in thymic epithelial tumors.

PMID: 18304691 [PubMed - as supplied by publisher]

89: Surg Endosc. 2008 Feb 23. [Epub ahead of print]

Long-term outcome and quality of life after open and thoracoscopic thymectomy for
myasthenia gravis: analysis of 131 patients.

Bachmann K, Burkhardt D, Schreiter I, Kaifi J, Busch C, Thayssen G, Izbicki JR,
Strate T.

Department of General, Visceral, and Thoracic Surgery, University Medical Center
Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

BACKGROUND: Myasthenia gravis is an autoimmune disease with a great impact on
quality of life. Besides conservative treatment with mestinon and
immunosuppressive medication, thymectomy is an established intervention that
offers substantial improvements of the disease. Since the past decade, minimally
invasive procedures have been performed. This study aimed to report on the
long-term results for all the patients who underwent thymectomy for myasthenia
gravis, paying special attention to postoperative disease-related outcome,
quality of life, and differences regarding the operative approach. METHODS: This
report describes a series of 131 patients with generalized myasthenia gravis who
underwent thymectomy between 1980 and 2005. The clinical course data during the
hospitalization and consultation in our outpatient clinic were reviewed, and
survival data were generated. The patients were seen in the outpatient clinic,
where a modified Osserman and quality-of-life score was evaluated at the end of
the follow-up period for all surviving patients. RESULTS: A total of 106 patients
with myasthenia gravis were followed up after thymectomy for a median time of 8
years (range, 1-27 years). Eight patients died during this period. The
perioperative mortality rate was 0%, and the morbidity rate was 19.8%. The
patients with thymoma and a high preoperative Osserman score had a significantly
shorter survival. With minimally invasive procedures, the hospital stay was
significantly shorter, and the rate for improvement of myasthenia
gravis-associated symptoms was significantly higher. The rate of perioperative
complications and myasthenia-related complications during the follow-up period
showed no significant differences. CONCLUSIONS: Transsternal and minimally
invasive thymectomy contribute to an improvement in myasthenia gravis symptoms
for all subgroups. Surgery can be performed with low individual risks. In our
trial, minimally invasive surgery was found to be superior in terms of
improvement in myasthenia gravis-associated symptoms. Additionally, the hospital
stay was shorter, and the patients felt less disturbed by direct effects of the
operation. Therefore, minimally invasive thymectomy can be regarded as the
treatment of choice for patients undergoing surgery for myasthenia gravis.

PMID: 18297352 [PubMed - as supplied by publisher]

90: Cancer Lett. 2008 Feb 18;260(1-2):137-45.

Effective induction of anti-tumor immune responses with oligomannose-coated
liposome targeting to intraperitoneal phagocytic cells.

Ikehara Y, Shiuchi N, Kabata-Ikehara S, Nakanishi H, Yokoyama N, Takagi H, Nagata
T, Koide Y, Kuzushima K, Takahashi T, Tsujimura K, Kojima N.

Molecular Medicine Team of Research Center for Medical Glycoscience, National
Institute of Advanced Industrial Science and Technology, Centeral 2-12, Room 211,
1-1-1 Umezono, Tsukuba, Japan. yuzuru-ikehara@aist.go.jp

We recently established a novel drug delivery system (DDS) using
oligomannose-coated liposomes (OMLs) which are probably taken up by macrophages
(Mvarphi) to carry anti-cancer drugs to milky spots known as preferential
metastatic sites of gastric cancers [Y. Ikehara, T. Niwa, L. Biao, S.K. Ikehara,
N. Ohashi, T. Kobayashi, Y. Shimizu, N. Kojima, H. Nakanishi, A carbohydrate
recognition-based drug delivery and controlled release system using
intraperitoneal macrophages as a cellular vehicle, Cancer Res. 66 (2006)
8740-8748]. In the present study, we applied this intraperitoneal DDS for
systemic cancer immunotherapy employing ovalbumin (OVA) as a model antigen. The
cells taking up the OMLs containing FITC-OVA injected into the peritoneal cavity
were predominantly Mvarphi, as they showed adhesive characteristics and expressed
F4/80 and CD11b almost exclusively. The phagocytic cells also took up bare OVA
directly to the same extent as OML-enclosed OVA (OML-OVA), as it is a highly
mannosilated protein. The phagocytic cells taking up OML-OVA, however, could
activate OVA-specific CD8+ (from OT-I: H-2Kb/OVA257-264-specific) and CD4+ (from
OT-II: H-2Ab/OVA323-339-specific) T cells much more effectively in vitro than
those taking up bare OVA. Furthermore, only the mice pre-immunized with OML-OVA
rejected E.G7-OVA (OVA-transfected EL4) but not EL4. These results indicate that
the OMLs can also be used as an effective antigen delivery system for cancer
immunotherapy activating both CTL and Th subsets.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18077084 [PubMed - indexed for MEDLINE]

91: Ann Thorac Surg. 2008 Feb;85(2):385-9.

Comment in:
Ann Thorac Surg. 2008 Feb;85(2):365-7.

Induction chemoradiotherapy followed by resection for locally advanced Masaoka
stage III and IVA thymic tumors.

Wright CD, Choi NC, Wain JC, Mathisen DJ, Lynch TJ, Fidias P.

Division of Thoracic Surgery, Massachusetts General Hospital, Boston,
Massachusetts 02114, USA. wright.cameron@mgh.harvard.edu

BACKGROUND: The treatment of locally advanced thymic tumors is not uniform.
Recently, several centers have reported the results of induction chemotherapy
followed by resection and then radiation. Our center adopted an alternative
strategy and treated locally advanced thymic tumors with induction
chemoradiotherapy in an effort to maximize the intensity of the induction
therapy. METHODS: A retrospective review was performed of 10 patients with
locally advanced thymic tumors treated from 1997 to 2006. Seven patients were
clinically staged as Masaoka stage III and 3 as stage IVA. The treatment plan
included two cycles of cisplatin and etoposide with concurrent radiation.
Patients then had resection followed by postoperative chemotherapy if they were
judged to be at high risk for relapse. RESULTS: Four patients had a partial
radiographic response to induction therapy and 6 had no response. Eight patients
had a R0 resection and 2 had a R1 resection. Four patients had substantial (>90%)
necrosis in the resected specimen. There was no postoperative mortality. Seven
patients had two more cycles of chemotherapy. The median follow-up was 41 months.
Three patients had recurrences. The 5-year estimated survival was 69% (95%
confidence interval: 32% to 100%). CONCLUSIONS: Induction therapy for locally
advanced thymic tumors with cisplatin, etoposide, and radiation is well
tolerated, with many patients having a partial radiographic response. The
majority of patients can undergo a complete resection with this treatment. The
survival of these patients compares favorably with those undergoing other
induction regimens. Further efforts to maximize the intensity of induction
therapy for locally advanced thymic tumors is warranted. We have initiated a
multicenter phase 2 clinical trial (NCT00387868) to prospectively test this
concept.

PMID: 18222230 [PubMed - indexed for MEDLINE]

92: Ann Thorac Surg. 2008 Feb;85(2):365-7.

Comment on:
Ann Thorac Surg. 2008 Feb;85(2):385-9.

Multimodality therapy for locally advanced thymomas: state of the art or
investigational therapy?

Huang J, Riely GJ, Rosenzweig KE, Rusch VW.

Publication Types:
Comment
Editorial

PMID: 18222226 [PubMed - indexed for MEDLINE]

93: Ann Thorac Surg. 2008 Feb;85(2):S768-71.

Video-assisted thoracoscopic surgery versus robotic-assisted thoracoscopic
surgery thymectomy.

Augustin F, Schmid T, Sieb M, Lucciarini P, Bodner J.

Clinical Department of General and Transplant Surgery, Innsbruck Medical
University, Innsbruck, Austria.

Publication Types:
Comparative Study
Review

PMID: 18222214 [PubMed - indexed for MEDLINE]

94: Cancer Immunol Immunother. 2008 Feb;57(2):227-32. Epub 2007 Jul 27.

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.
sissel.monstad@helse-bergen.no

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.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17657489 [PubMed - indexed for MEDLINE]

95: Cancer Invest. 2008 Feb;26(1):53-9.

Biologic markers of angiogenesis: circulating endothelial cells in patients with
advanced malignancies treated on phase I protocol with metronomic chemotherapy
and celecoxib.

Twardowski PW, Smith-Powell L, Carroll M, VanBalgooy J, Ruel C, Frankel P, Synold
TW.

Department of Medical Oncology and Therapeutics Research, City of Hope
Comprehensive Cancer Center, Duarte, California 91010, USA. ptwardowski@coh.org

Preclinical studies demonstrate anti-angiogenic activity of low doses of
chemotherapy; selective cox-2 inhibitors are also inhibitors of angiogenesis.
Animal data indicates the presence of circulating endothelial cells (CEC),
tumor-derived activated endothelial cells (AEC) and endothelial cell progenitors
(ECP). Bone marrow-derived ECP have been shown to be incorporated into tumor
vasculature. We conducted two combination Phase I studies of celecoxib with
either cyclophosphamide or etoposide. Exploratory correlative studies were
performed to evaluate the detectability of CEC, AEC and ECP in patients treated
with these anti-angiogenic combinations. Patients were treated with oral
cyclophosphamide at 50 mg daily or etoposide at 50 mg daily. Celecoxib was given
at 400 mg twice daily. Blood samples were collected on days 0, 7, 28 and monthly
until disease progression. Blood from healthy volunteers was collected on days 0
and 28. Peripheral mononuclear cells (PMNC) were isolated and stained with
fluorescent antibodies and analyzed utilizing 5-color flow cytometry. Forty-four
heavily pretreated patients (20 F; 24 M) with various solid tumors were enrolled.
Median age was 65 (23-72). Therapy was well tolerated. No responses were seen.
Six patients had stable disease for at least 16 weeks. The longest duration on
therapy is 420 days in a patient with metastatic thymoma. Pre-therapy CEC were
detected in cancer patients and normal controls with mean concentrations of 0.47
cells/uL and 0.14 cells/uL, respectively. Mean ECP in patients and controls were
0.09 cells/uL and 0.03 cells/uL, respectively. No AEC were detected. No
consistent changes were seen in CEC or ECP during therapy. The combinations of
oral cyclophosphamide or etoposide at 50 mg daily with celecoxib at 400 mg twice
daily are well tolerated with occasional prolonged disease stabilizations
observed. CEC and ECP are detectable in cancer patients but their levels did not
change significantly during therapy with our regimen. Further evaluation of CEC
and ECP in patients treated with clinically more active anti-angiogenic therapies
would be of interest.

Publication Types:
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

PMID: 18181046 [PubMed - indexed for MEDLINE]

96: Chirurg. 2008 Feb;79(2):164-74.

[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.

Publication Types:
English Abstract

PMID: 17786394 [PubMed - in process]

97: Clin Neurol Neurosurg. 2008 Feb;110(2):168-70. Epub 2007 Oct 24.

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.

Publication Types:
Case Reports

PMID: 17920189 [PubMed - indexed for MEDLINE]

98: Crit Rev Oncol Hematol. 2008 Feb;65(2):109-20. Epub 2007 Jun 14.

Management of thymomas.

Wright CD.

Division of Thoracic Surgery, Massachusetts General Hospital, Harvard Medical
School, Blake 1570, Boston, MA 02114, USA. wright.cameron@mgh.harvard.edu

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 - in process]

99: Histopathology. 2008 Feb;52(3):409-11.

Sarcomatoid carcinoma of the thymus arising in metaplastic thymoma.

Moritani S, Ichihara S, Mukai K, Seki Y, Inoue S, Yasuda A, Hakiri S, Yatabe Y,
Eimoto T.

Publication Types:
Case Reports
Letter

PMID: 18269593 [PubMed - indexed for MEDLINE]

100: J Med Invest. 2008 Feb;55(1-2):17-28.

Optimal therapy for thymoma.

Kondo K.

Department of Adult and Gerontological Nursing, School of Health Sciences, The
University of Tokushima, Tokushima, Japan.

Thymoma is the most common tumor of the anterior mediastinum. This tumor is
associated with unique paraneoplastic syndromes (myasthenia gravis, pure red cell
aplasia, hypogammaglobulinemia, and other autoimmune diseases). The rarity of
this tumor has somewhat obscured the optimal treatment. Although the histologic
classification of thymoma has remained a subject of controversy for many years,
the WHO classification system, published in 1999, appeared to be an advance in
our understanding of thymoma. The optimal treatment for thymoma depends on its
clinical stage. Surgery remains the mainstay of treatment for thymic epithelial
tumors. Thymomas also have a high response rate to chemotherapy or radiotherapy.
Only surgical resection is performed for patients with stage I (non-invasive)
thymoma. The value of postoperative radiotherapy in completely resected stage II
or III tumors is questionable. Multimodality therapy involving surgery,
chemotherapy and radiotherapy appears to increase the rate of complete resection
and survival in advanced (stage III and IV) thymomas.

Publication Types:
Review

PMID: 18319541 [PubMed - indexed for MEDLINE]

101: J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):202-4.

Hypothermia in VGKC antibody-associated limbic encephalitis.

Jacob S, Irani SR, Rajabally YA, Grubneac A, Walters RJ, Yazaki M, Clover L,
Vincent A.

Department of Clinical Neurology, Weatherall Institute of Molecular Medicine,
John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis
(LE) is a recently described syndrome that broadens the spectrum of
immunotherapy-responsive central nervous system disorders. Limbic encephalitis is
typically characterised by a sub-acute onset of disorientation, amnesia and
seizures, but the clinical spectrum is not yet fully defined and the syndrome
could be under-diagnosed. We here describe the clinical profile of four patients
with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the
patients also described a prodrome of severe neuropathic pain preceding the
development of limbic symptoms. Both of these novel symptoms responded well to
immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.

Publication Types:
Case Reports
Research Support, Non-U.S. Gov't

PMID: 18202210 [PubMed - indexed for MEDLINE]

102: J Neurotrauma. 2008 Feb;25(2):130-9.

Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K/Akt
pathway, and increase of neurogenesis are associated with therapeutic improvement
after traumatic brain injury.

Wu H, Lu D, Jiang H, Xiong Y, Qu C, Li B, Mahmood A, Zhou D, Chopp M.

Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA.

This study was undertaken to evaluate the effect of simvastatin, a
cholesterol-lowering agent, on the Akt-mediated signaling pathway and
neurogenesis in the dentate gyrus (DG) of the hippocampus in rats after traumatic
brain injury (TBI). Adult male Wistar rats were divided into three groups: (1)
sham group (n = 8); (2) saline control group (n = 40); and (3)
simvastatin-treated group (n = 40). Controlled cortical impact (CCI) injury was
performed over the left parietal lobe. Simvastatin was administered orally at a
dose of 1 mg/kg starting at day 1 after TBI and then daily for 14 days.
Bromodeoxyuridine (BrdU) was injected intraperitoneally into rats. A modified
Morris Water Maze (WM) task was performed between 31 and 35 days after treatment
to test spatial memory (n = 8/group). Animals were sacrificed at 1, 3, 7, 14, and
35 days after treatment (n = 8/group/time point). Western blot was utilized to
investigate the changes in the Akt-mediated signaling pathway. Enzyme-linked
immunosorbent assay (ELISA) analyses were employed to measure vascular
endothelial growth factor (VEGF) and brain-derived neurotrophin factor (BDNF)
expression. Immunohistochemical and fluorescent staining were performed to detect
the BrdU- and neuronal nuclei (NeuN)/BrdU-positive cells. Our data show that
simvastatin treatment increases phosphorylation of v-akt murine thymoma viral
oncogene homolog (Akt), glycogen synthase kinase-3beta (GSK-3beta), and cAMP
response element-binding proteins (CREB); elevates the expression of BDNF and
VEGF in the DG; increases cell proliferation and differentiation in the DG; and
enhances the recovery of spatial learning. These data suggest that the
neurorestorative effect of simvastatin may be mediated through activation of the
Akt-mediated signaling pathway, subsequently upregulating expression of growth
factors and inducing neurogenesis in the DG of the hippocampus, thereby leading
to restoration of cognitive function after TBI in rats.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 18260796 [PubMed - indexed for MEDLINE]

103: Mol Cell Biol. 2008 Feb;28(3):907-12. Epub 2007 Nov 26.

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 at San Francisco, San Francisco,
California 94143, USA.

Runx1 binds the silencer and represses CD4 transcription in immature thymocytes.
In this study, using looping chromatin immunoprecipitation and chromatin
conformation capture assays, we demonstrated that interactions between Runx1 and
positive elongation factor b (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 the 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 of P-TEFb away
from the promoter mediate active repression of the CD4 gene during thymocyte
development.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 18039856 [PubMed - indexed for MEDLINE]

104: Nihon Kokyuki Gakkai Zasshi. 2008 Feb;46(2):101-5.

[Case of agranulocytosis associated with thymoma]

[Article in Japanese]

Sato K, Nojiri S, Numata T, Kinoshita A, Sakaguchi S, Homma S.

Department of Respiratory Medicine, Ikegami Hospital.

A 75-year-old-woman had undergone extended thymectomy, right upper and middle
lobe resection, and radiation therapy (40 Gy) for thymoma at the age of 63. She
visited our hospital complaining of low grade fever, cough, anorexia and a sore
throat. Peripheral blood count revealed agranulocytosis. Agranulocytosis
associated with thymoma was diagnosed, because there were no other possible
causes of agranulocytosis such as drugs, infection, recent radiation therapy, or
bone marrow invasion. In spite of giving G-CSF, steroid therapy and
immunosuppressants, she died of pneumonia caused by agranulocytosis. We consider
that agranulocytosis is a very rare complication of thymoma.

Publication Types:
Case Reports
English Abstract
Review

PMID: 18318251 [PubMed - indexed for MEDLINE]

105: Radiol Med (Torino). 2008 Feb;113(1):3-15. Epub 2008 Feb 25.

CT-guided percutaneous transthoracic biopsy in the diagnosis of mediastinal
masses: evaluation of 73 procedures.

[Article in English, Italian]

Priola AM, Priola SM, Cataldi A, Ferrero B, Garofalo G, Errico L, Marci V, Fava
C.

Radiologia Diagnostica, Università degli Studi di Torino, A.S.O. San Luigi
Gonzaga, Regione Gonzole 10, 10043 Orbassano (TO), Italy.
adriano.priola@inwind.it

PURPOSE: This study was performed to evaluate the factors affecting the
diagnostic accuracy and rate of complications of CT-guided percutaneous
transthoracic needle biopsy of mediastinal masses. MATERIALS AND METHODS: We
reviewed 73 consecutive mediastinal biopsies in 70 patients. Final diagnoses were
based on a retrospective analysis of surgical outcomes, results of repeat
biopsies or findings of imaging and clinical follow-up lasting at least 4 months.
Benign and malignant biopsy findings were compared with the final outcomes to
determine the diagnostic accuracy of the method. Finally, we analysed the
complications. RESULTS: CT-guided percutaneous transthoracic needle biopsy
provided adequate samples in 61/73 cases, with a total sample rate of 83.6%. Of
these 61 biopsies, 51 yielded a correct diagnosis with specific histological
typing, mainly in the case of thymoma and metastasis. Lymphomas were less
reliably diagnosed. The overall sensitivity, specificity, positive predictive
value, negative predictive value and diagnostic accuracy values were 83.6%, 100%,
100%, 35.3% and 83.6%, respectively. Pneumothorax was the most common
complication (5.5%). CONCLUSIONS: CT-guided percutaneous transthoracic needle
biopsy is an easy, reliable and safe procedure that obviates the need for
exploratory surgery in medically treatable or unresectable cases. It should be
the first invasive procedure in the diagnostic workup of mediastinal masses.

Publication Types:
Evaluation Studies

PMID: 18338123 [PubMed - indexed for MEDLINE]

106: Semin Ultrasound CT MR. 2008 Feb;29(1):47-59.

Uncommon epiloptogenic lesions affecting the temporal lobe.

Ramos A, Ballenilla F, Martin P.

Neuroradiology Section, Radiology Department, Hospital Doce de Octubre, Madrid,
Spain. ramosana3@yahoo.es

There are several processes implicated as uncommon causes of temporal lobe
epilepsy. Trauma is the leading cause of epilepsy in young adults, intracerebral
blood collection being the most consistent risk factor of seizures, especially
subdural hematomas and brain contusions. Infarction is the entity most commonly
related to epilepsy in the elderly population. Seizures usually present as
complex seizures with high recurrence between 6 months and 2 years after stroke.
There are some radiological characteristics of the affectation associated with
high risk of early and late seizures. Noninfectious limbic encephalitis is a
syndrome characterized by seizures, memory loss, and confusion. It includes
paraneoplasic and non-paraneoplasic limbic encephalitis, both presenting as
hyperintense lesion affecting temporobasal regions more evident with
fluid-attenuated inversion recovery sequences. Paraneoplasic limbic encephalitis
is associated with several types of tumor-induced autoimmunity against the
nervous system. The tumors most frequently implicated are the lungs, testis, and
breast, including Hodgkin's lymphoma, teratoma, and thymoma in young patients.
Once a tumor is excluded, non-paraneoplasic limbic encephalitis has to be
considered by investigating the presence of antibodies against voltage-gated
potassium channels. It is associated with hyponatremia and responds to regimens
of steroids, plasma exchange, and intravenous immunoglobulins. Finally, herpetic
limbic encephalitis is also associated with seizures, accompanied by fever and
neurologic symptoms. It presents characteristic findings and distribution on
magnetic resonance imaging, which shows abnormalities in more than 90% of
patients with proven Herpes simplex virus type 1.

Publication Types:
Review

PMID: 18383907 [PubMed - indexed for MEDLINE]

107: J Immunol. 2008 Jan 15;180(2):988-97.

Erratum in:
J Immunol. 2008 Mar 1;180(5):3613.

Protein interactions between CD2 and Lck are required for the lipid raft
distribution of CD2.

Nunes RJ, Castro MA, Gonçalves CM, Bamberger M, Pereira CF, Bismuth G, Carmo AM.

Group of Cell Activation and Gene Expression, Instituto de Biologia Molecular e
Celular, Universidade do Porto, Portugal.

In T lymphocytes, lipid rafts are preferred sites for signal transduction
initiation and amplification. Many cell membrane receptors, such as the TCR,
coreceptors, and accessory molecules associate within these microdomains upon
cell activation. However, it is still unclear in most cases whether these
receptors interact with rafts through lipid-based amino acid modifications or
whether raft insertion is driven by protein-protein interactions. In murine T
cells, a significant fraction of CD2 associates with membrane lipid rafts. We
have addressed the mechanisms that control the localization of rat CD2 at the
plasma membrane, and its redistribution within lipid rafts induced upon
activation. Following incubation of rat CD2-expressing cells with
radioactive-labeled palmitic acid, or using CD2 mutants with Cys226 and Cys228
replaced by alanine residues, we found no evidence that rat CD2 was subjected to
lipid modifications that could favor the translocation to lipid rafts, discarding
palmitoylation as the principal mechanism for raft addressing. In contrast, using
Jurkat cells expressing different CD2 and Lck mutants, we show that the
association of CD2 with the rafts fully correlates with CD2 capacity to bind to
Lck. As CD2 physically interacts with both Lck and Fyn, preferentially inside
lipid rafts, and reflecting the increase of CD2 in lipid rafts following
activation, CD2 can mediate the interaction between the two kinases and the
consequent boost in kinase activity in lipid rafts.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18178839 [PubMed - indexed for MEDLINE]

108: Nippon Naika Gakkai Zasshi. 2008 Jan 10;97(1):141-3.

[Thymoma extending into the right atrium]

[Article in Japanese]

Saito M, Shikama N, Kuriyama N, Takiguchi Y, Yamamoto K, Terano T, Takahashi O,
Shimura H, Uchiyama R, Komuro I.

Internal Medicine, Chiba Aoba Municipal Hospital.

Publication Types:
Case Reports

PMID: 18283900 [PubMed - indexed for MEDLINE]

109: N Engl J Med. 2008 Jan 3;358(1):70-4.

Clinical problem-solving. Failure to respond--a 52-year-old man presented to his
primary care physician with dyspnea and cough.

Ezzie ME, Janssen WJ, O'Brien JM, Fox CC, Schwarz MI.

Department of Medicine, Division of Pulmonary, Critical Care, Allergy, and Sleep
Medicine, Ohio State University, Columbus, OH 43210, USA. michael.ezzie@osumc.edu

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18172177 [PubMed - indexed for MEDLINE]

110: Acta Chir Belg. 2008 Jan-Feb;108(1):102-6.

Extended transsternal thymectomy for myasthenia gravis: a report of 19
consecutive cases.

Durieux R, Radermecker MA, Dekoster G, Limet R.

Department of Cardiothoracic and Vascular Surgery, University of Liège, Liège,
Belgium. rodolphedurieux@hotmail.com

BACKGROUND: Thymectomy is considered as an effective therapeutic option for
patients with myasthenia gravis (MG). This study reports the experience of our
centre's investigation into the efficacy and the safety of the procedure and the
influence of different pre-operative factors on the surgical outcome. METHODS: A
retrospective chart review/interview was made of 19 consecutive patients who
underwent extended transsternal thymectomy for MG from 1992 to 2003. The severity
of the disease was determined according to the Osserman Classification. Efficacy
was measured by determining the change in clinical status, the rate of remission
during follow-up, and the reduction in medication requirements after thymectomy.
Complete remission (CR) was defined as asymptomatic off medication for 6 months.
The CR rate was calculated using the Kaplan-Meyer method. RESULTS: The mean age
of the patients at surgery was 34 years (range, 9-63) and 78.9% were female. Mean
length of follow up was 86 months (range, 24-163). The overall complication rate
was 10.6% (1 episode of atrial fibrillation and a left recurrent laryngeal nerve
palsy that resolved after the first postoperative month). There was no operative
mortality. The mean hospital stay was 9.4 days (range, 5-23). The crude CR rate
was 32% (n = 6). The Kaplan-Meier estimate of CR was 42% at 6 years. Age, gender,
duration of symptoms, thymic histology, Osserman stage and the presence of
thymoma were not identified as prognostic variables. The average daily dose of
Medrol and Mestinon decreased significantly between the pre-operative period and
the last follow-up (Medrol, p = 0.0081; Mestinon, p = 0.0013). CONCLUSIONS:
Transsternal thymectomy for MG is safe and effective. It benefits patients with
MG at all stages. Patients with thymoma are not associated with poorer remission
rates. Complete responses are durable, as the CR rate remains stable over time.

PMID: 18411583 [PubMed - indexed for MEDLINE]

111: Ann Anat. 2008;190(3):238-45. Epub 2008 Feb 1.

Immunohistochemical expression of vascular endothelial growth factor A (VEGF),
and its receptors (VEGFR1, 2) in normal and pathologic conditions of the human
thymus.

Cimpean AM, Raica M, Encica S, Cornea R, Bocan V.

Department of Histology, "Victor Babeş" University of Medicine and Pharmacy,
Timişoara, Eftimie Murgu Square nr. 2, Timişoara 300041, Romania.

Vascular endothelial growth factor A (VEGF-A) is an angiogenic growth factor that
is a primary stimulant of the vascularization of solid tumors. In the tumor
microenvironment, an upregulation of both VEGF and its receptors occurs, leading
to a high concentration of occupied receptors on tumor vascular endothelium.
Also, VEGF is involved in the development of the normal vascular network of the
thymus. Little is known about VEGF expression in normal and malignant thymic
tissue. Our purpose was to study the pattern and localization of VEGF expression
in benign conditions of the thymus and thymoma to determine a possible
correlation with VEGF receptors VEGFR1, VEGFR2 and microvascular density. All
cases were positive for VEGF and VEGFR1, 2 in the epithelial cells, in a
cytoplasmic, granular pattern. In the normal thymus, there were positive
epithelial cells with subcapsular distribution and Hassall's corpuscle epithelial
cells. In acute thymic involution, the positive fields were correlated with
dilation and stasis of blood vessels and lymphocyte depletion. Rare positive
cells were found in other types of involution; the myasthenic thymus showed an
intense and diffuse reaction in lymphoid follicles of the medulla. A strong
reaction for VEGF was observed in type B3 thymomas in neoplastic epithelial
cells, normal endothelial cells, plasma within the blood vessels and focally in
the stroma adjacent to the tumor. Receptors for VEGF were positive in neoplastic
epithelial cells and endothelium. We hypothesized that VEGF acts as an
immunoregulatory factor in the normal thymus and as proangiogenic and autocrine
factor in thymomas.

PMID: 18356031 [PubMed - in process]

112: Ann Clin Lab Sci. 2008 Winter;38(1):83-7.

IgG anti-cardiomyocyte antibodies in giant cell myocarditis.

HooKim K, deRoux S, Igbokwe A, Stanek A, Koo J, Hsu J, Pincus MR, Bluth MH.

Department of Pathology, SUNY Downstate Medical Center, Box 40, 450 Clarkson
Avenue, Brooklyn, NY 11203, USA.

Giant cell myocarditis, a rare, fatal, and poorly understood cause of
myocarditis, requires pathological examination for diagnosis. It is considered to
be an autoimmune disease and is frequently associated with other conditions, in
particular thymoma and myasthenia gravis. The typical patient with giant cell
myocarditis is young and has severe, progressive congestive cardiac failure that
is unresponsive to standard medical therapy and ultimately requires cardiac
transplantation. Hence giant cell myocarditis is the most dangerous form of
myocarditis. Here we report an unusual presentation of giant cell myocarditis,
which mimicked acute myocardial infarction in an elderly woman with myasthenia
gravis and a previous diagnosis of thymoma. This patient had evidence of
anti-myocyte antibodies, consistent with an autoimmune mechanism.

Publication Types:
Case Reports

PMID: 18316787 [PubMed - indexed for MEDLINE]

113: Biol Reprod. 2008 Jan;78(1):143-50. Epub 2007 Sep 26.

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 Obstetrics and Gynecology, University of Wisconsin-Madison,
Perinatal Research Laboratories, PAB1 Meriter Hospital, Madison, WI 53715, USA.
jzheng@wisc.edu

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.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 17901071 [PubMed - indexed for MEDLINE]

114: Chirurg. 2008 Jan;79(1):18-25.

[Minimally invasive thymus surgery.]

[Article in German]

Rückert JC, Ismail M, Swierzy M, Braumann C, Badakhshi H, Rogalla P, Meisel A,
Rückert RI, Müller JM.

Klinik für Allgemein-, Viszeral-, Gefäß- und Thoraxchirurgie, Charité –
Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin,
Deutschland, jens-c.rueckert@charite.de.

There are absolute and relative indications for complete removal of the thymus
gland. In the complex therapy of autoimmune-related myasthenia gravis, thymectomy
plays a central role and is performed with relative indication. In case of
thymoma with or without myasthenia, thymectomy is absolutely indicated. Thymus
resection is further necessary for cases of hyperparathyroidism with ectopic
intrathymic parathyroids or with certain forms of multiple endocrine neoplasia.
The transcervical operation technique traditionally reflected the well-founded
desire for minimal invasiveness for thymectomy. Due to the requirement of
radicality however, most of these operations were performed using sternotomy.
With the evolution of therapeutic thoracoscopy in thoracic surgery, several pure
or extended minimally invasive operation techniques for thymectomy have been
developed. At present uni- or bilateral, subxiphoid, and modified transcervical
single or combination thoracoscopic techniques are in use. Recently a very
precise new level of thoracoscopic operation technique was developed using
robotic-assisted surgery. There are special advantages of this technique for
thymectomy. An overview of the development and experiences with minimally
invasive thymectomy is presented, including data from the largest series
published so far.

PMID: 18209982 [PubMed - as supplied by publisher]

115: Chirurg. 2008 Jan;79(1):9-17.

[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]

116: Clin Imaging. 2008 Jan-Feb;32(1):54-7.

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. lmloltlolol@gmail.com

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.

Publication Types:
Case Reports

PMID: 18164397 [PubMed - indexed for MEDLINE]

117: Eur J Cancer. 2008 Jan;44(1):123-30.

Thymic epithelial tumours: a population-based study of the incidence, diagnostic
procedures and therapy.

de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ.

Department of Pulmonology, University Medical Center Groningen, University of
Groningen, NL-9700 RB, Groningen, The Netherlands. w.k.de.jong@int.umcg.nl

The population-based incidence, diagnostic procedures, therapy and survival of
thymic epithelial tumours were determined using the Netherlands National
Pathological Archives and the Netherlands Cancer Registry. Excess mortality
compared to the Netherlands standard population was estimated by relative
survival analysis. Between 1994 and 2003, 537 thymic epithelial tumours were
diagnosed. The incidence of all thymic epithelial tumours was 3.2/1,000,000.
Diagnosis was obtained by primary resection in 56% of cases. Survival data were
available for 232 cases. Not only thymic carcinomas (type C) but also thymomas
(types B1-B3) were associated with excess mortality. Cases that underwent
resection (78%) had a better survival than non-operated cases (median survival
>10 years versus 1.1 years, p<0.001). Amongst the surgically treated cases
(n=180), the completeness of resection did not predict survival (p=0.53). Thymic
epithelial tumours are rare. Excess mortality was observed in the majority of
tumours. Surgery offers the best perspectives, even if the resection is
incomplete.

Publication Types:
Multicenter Study
Research Support, Non-U.S. Gov't

PMID: 18068351 [PubMed - indexed for MEDLINE]

118: Eur J Haematol. 2008 Jan;80(1):10-9.

Intracellular HMGB1 transactivates the human IL1B gene promoter through
association with an Ets transcription factor PU.1.

Mouri F, Tsukada J, Mizobe T, Higashi T, Yoshida Y, Minami Y, Izumi H, Kominato
Y, Kohno K, Tanaka Y.

The first Department of Internal Medicine, School of Medicine, University of
Occupational and Environmental Health, Kitakyushu, Japan.

High mobility group box 1 protein (HMGB1), originally described as a non-histone,
DNA binding protein, was recently identified as a late mediator of inflammation
via its extracellular release from activated macrophages/monocytes. In the
present study, we report that intracellular HMGB1 synergizes with a
macrophage/monocyte-specific E26 transformation-specific sequence (Ets)
transcription factor PU.1 to transactivate the promoter of the IL1B gene coding a
31-kDa proIL-1beta protein. The -131 to +12 IL1B promoter, which possesses a PU.1
binding motif essential for its transactivation, was induced when HMGB1
expression vector was transfected into murine RAW264.7 macrophage cells. Our
glutathione S-transferase-pulldown and coimmunoprecipitation assays demonstrated
direct physical interaction of HMGB1 with PU.1. Deletion of the PU.1 winged
helix-turn-helix DNA-binding domain inhibited the association of the two
proteins. In electrophoretic mobility shift assay using recombinant PU.1 protein,
a ternary complex of PU.1, HMGB1 and PU.1-binding element within the IL1B
promoter was generated. The importance of PU.1 was further supported by our
observation that induction of the IL1B promoter was obtained only after PU.1
expression in PU.1-deficient murine EL4 thymoma cells. Thus, our data raise the
possibility of a novel mechanism which sustains and amplifies inflammatory
reactions through physical interaction of PU.1 with intracellular HMGB1 in
macrophages/monocytes.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18173740 [PubMed - indexed for MEDLINE]

119: Gen Thorac Cardiovasc Surg. 2008 Jan;56(1):10-6. Epub 2008 Jan 22.

Clinical and pathological aspects of thymic epithelial tumors.

Okumura M, Shiono H, Minami M, Inoue M, Utsumi T, Kadota Y, Sawa Y.

Department of General Thoracic Surgery (L5), Osaka University Graduate School of
Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
meinosin@surgl.med.osaka-u.ac.jp

A histological classification of thymic epithelial tumors was presented by the
World Health Organization (WHO) in 1999 and again in 2004 following slight
modifications, in which thymic epithelial tumors were categorized as thymomas and
thymic carcinomas. Whereas thymoma is defined as an organotypic (thymus-like)
tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology
similar to that of malignant neoplasms arising from other organs. Herein, the
recent progress in research of thymic epithelial tumors is reviewed with
reference to the WHO histological classification system, with the focus on
thymomas. Thymomas are classified into five types--A, AB, B1, B2, B3--according
to the shape and atypia of their epithelial cells as well as the abundance of
lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have
been shown to be related to this classification system. Myasthenia gravis is
frequently associated with types B1 and B2. The WHO histological classification
of thymomas is not only useful for treatment but reflects their biological
characteristics, including genetic alterations. Advances are expected in future
studies of thymomas from the standpoint of their clinical, pathological, and
biological aspects.

Publication Types:
Review

PMID: 18213465 [PubMed - indexed for MEDLINE]

120: Haematologica. 2008 Jan;93(1):27-33.

Long-term response and outcome following immunosuppressive therapy in
thymoma-associated pure red cell aplasia: a nationwide cohort study in Japan by
the PRCA collaborative study group.

Hirokawa M, Sawada K, Fujishima N, Nakao S, Urabe A, Dan K, Fujisawa S, Yonemura
Y, Kawano F, Omine M, Ozawa K; PRCA Collaborative Study Group.

Division of Hematology and Oncology, Department of Medicine, Akita University
School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
mhirokawa@hos.akita-u.ac.jp

BACKGROUND: Thymoma-associated pure red cell aplasia (PRCA) accounts for a
significant proportion of cases of secondary PRCA and immunosuppressive therapy
has been reported to be useful in this condition. However, because of its rarity,
the long-term response and relapse rates after immunosuppressive therapy are
largely unknown, and optimal management of this disorder remains unclear. The aim
of this study was to collect more information on the outcome of patients with
thymoma-associated PRCA. DESIGN AND METHODS: We conducted a nationwide survey in
Japan. From a total of 185 patients, comprising 73 with idiopathic and 112 with
secondary PRCA, 41 patients with thymoma were evaluated for this report.
End-points of this study were the response rate, duration of the response after
immunosuppressive therapy and overall survival. RESULTS: Surgical removal of
thymoma was reported in 36 patients, 16 of whom developed PRCA at a median of 80
months post-thymectomy. First remission induction therapy was effective in 19 of
20 patients treated with cyclosporine, 6 of 13 patients treated with
corticosteroids and 1 of 1 treated with cyclophosphamide. No
cyclosporine-responders relapsed within a median observation period of 18 months
(range; 1 to 118 months). Relapse of anemia was observed in three
corticosteroid-responders who did not receive additional cyclosporine. Only two
patients were in remission after stopping therapy for 19 and 67 months. The
estimated median overall survival time of all patients was 142 months.
CONCLUSIONS: Thymoma-associated PRCA showed an excellent response to cyclosporine
and cyclosporine-containing regimens were effective in preventing relapse of
anemia. It does, however, remain uncertain whether cyclosporine can induce a
maintenance-free hematologic response.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 18166782 [PubMed - indexed for MEDLINE]

121: Hell J Nucl Med. 2008 Jan-Apr;11(1):43-5.

Incidental pathologic extracardiac uptake of 99mTc-tetrofosmin in myocardial
perfusion imaging.

Kotsalou I, Georgoulias P, Fourlis S, Zoumboulidis A, Giaslakiotis K, Androulaki
A, Chronopoulos P, Dimakopoulos N.

Department of Nuclear Medicine, NIMTS Hospital, Athens, Hellas.

Technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion studies have
incidentally detected various extracardiac abnormalities. The interpretation of
these findings may be essential for early diagnosis and treatment of important
diseases. We present a rare case of a mediastinal thymoma incidently detected
during myocardial perfusion imaging. A 60 year-old woman, with precardiac
symptoms of possible myocardial ischemia, underwent a (99m)Tc-TF stress-rest
single photon emission tomography test. Intense uptake of the radiotracer in the
left paracardiac area, was observed. The computerized tomography and the magnetic
resonance imaging tests revealed a mass in the left lower anterior mediastinal
area. Biopsy and subsequent histology showed that this mass was a thymoma.

PMID: 18392227 [PubMed - in process]

122: Int J Hematol. 2008 Jan;87(1):56-9. Epub 2007 Dec 6.

Dramatic remission of anemia after thymectomy in a patient of idiopathic
myelofibrosis with thymoma.

Shih YY, Hsiao LT, Yang CF, Wu YC, Chiou TJ.

Division of Hematology and Oncology, Department of Medicine, Taipei Veterans
General Hospital, National Yang-Ming University School of Medicine, No. 201, Sec.
2, Shih-Pai Road, Taipei, 112, Taiwan, tjchiou@vghtpe.gov.tw.

Anemia is one of the characteristics of idiopathic myelofibrosis (IMF), and
malignant thymoma is usually associated with various hematologic disorders,
including anemia, pancytopenia, and hypogammaglobulinemia. However, the
relationship between IMF and malignant thymoma has not been published before.
Here, we report a 48-year-old woman who was initially diagnosed of IMF with
severe anemia and transfusion dependent. Five years later, malignant thymoma was
found when she was examined for chronic cough. After performing extended
thymectomy, her anemia dramatically recovered to normal and sustained for 2 years
till last follow-up. Her splenomegaly and myelofibrosis were also improved. We
hypothesized that her malignant thymoma induced the progression of IMF,
especially in anemia.

PMID: 18224414 [PubMed - in process]

123: Intern Med. 2008;47(11):1009-12. Epub 2008 Jun 2.

Malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH.

Lee BW, Ihm SH, Shin HS, Yoo HJ.

Division of Endocrinology and Metabolism, Department of Internal Medicine,
College of Medicine, Hallym University, Seoul, Korea.

Patients with thymoma are likely to present with associated autoimmunologic
disorders. The occurrence of syndrome of inappropriate antidiuretic hormone
(SIADH) attributable to thymoma is extremely rare. We herein present an extremely
rare case of a 59-year-old man patient who was discovered to have malignant
thymoma associated with myasthenia gravis, Graves' disease, and SIADH. He was
admitted for evaluation and treatment of hyponatremia (Na 125 mEq/l). SIADH was
diagnosed, and thymoma was identified as its cause. The patient was also found to
have both Graves' disease and myasthenia gravis. The hyponatremia was normalized
with water restriction and 3% saline therapy before thymectomy. The thymic tumor
was a Masaoka stage III thymoma that resulted in direct invasion to the wall of
the innominate vein, but there was no finding of invasion to other mediastinal
organs. Complete thymectomy with innominate vein graft was performed. Microscopic
histopathology findings corresponded to those of a mixed-type thymoma and type
B2. However, immunohistochemical stain for antidiuretic hormone was negative in
the tumor cells. Adjuvant radiation therapy was employed postoperatively, and the
patient's postoperative recovery was uneventful. He subsequently reached a
euthyroid state. And the reversal to normal sodium and osmolality levels was
continued after the tumor removal without any further management for
hyponatremia. The observation of this interesting case and a literature review
provided us with the opportunity to explore the pathogenesis and clinical aspects
of thymoma-related autoimmune and/or endocrine disorders which must be suspected
in patients with thymoma.

PMID: 18520111 [PubMed - in process]

124: Intern Med. 2008;47(9):877-8. Epub 2008 May 1.

Dysgeusia limited to sweet taste in myasthenia gravis.

Nakazato Y, Ito Y, Naito S, Tamura N, Shimazu K.

Department of Neurology, Saitama Medical University, Saitama.
nakachan@saitama-med.ac.jp

Total dysgeusia, an inability to interpret all of the basic tastes, often occurs
with zinc deficiency. Partial dysgeusia (dissociation dysgeusia) is a rare
inability to interpret a limited number of these basic tastes. We present the
case of a patient with myasthenia gravis who became unable to discern sweet
taste, but other basic tastes were unaffected. Such dysgeusia can be explained by
obstruction of selective taste receptors in taste cells. We considered that this
symptom was induced by an autoimmune mechanism related to myasthenia gravis.

Publication Types:
Case Reports

PMID: 18451583 [PubMed - indexed for MEDLINE]

125: J Thorac Oncol. 2008 Jan;3(1):98-100.

Successful multimodal treatment in a patient with thymoma accompanied by hepatic
metastasis.

Hoshino S, Furukawa M, Aragane K, Horimoto M, Suzuki K, Shiono H, Minami M,
Okumura M, Kijima T, Kawase I.

Department of Internal Medicine, Osaka Saiseikai Senri Hospital, Osaka, Japan.
shoshino@senri.saiseikai.or.jp

Despite a benign histologic appearance, thymomas have metastatic potential. Here
we report a case of a patient with a Masaoka stage IVb thymoma who was
successfully treated using a multimodal strategy including systemic chemotherapy,
radiofrequency ablation, and thoracic surgery. Despite complete remission after
treatment, the patient developed myasthenia gravis with ptosis and neck drop
symptoms. Hepatic metastasis of thymoma is a relatively rare occurrence and, to
the best of our knowledge, this is the first report about the application of
radiofrequency ablation to thymoma.

Publication Types:
Case Reports

PMID: 18166848 [PubMed - indexed for MEDLINE]

126: J Thorac Oncol. 2008 Jan;3(1):75-81.

Comment in:
J Thorac Oncol. 2008 Jan;3(1):1-2.

Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire
hemithorax irradiation in patients with pleural dissemination.

Sugie C, Shibamoto Y, Ikeya-Hashizume C, Ogino H, Ayakawa S, Tomita N, Baba F,
Iwata H, Ito M, Oda K.

Department of Radiology, Nagoya City University Graduate School of Medical
Sciences, Mizuho-ku, Nagoya, Japan. chikao@bg8.so-net.ne.jp

INTRODUCTION: We evaluated the results of postoperative mediastinal radiotherapy
(MRT) for invasive thymoma and low-dose entire hemithorax radiotherapy (EHRT) for
pleural dissemination. METHODS: Sixty patients were treated with a nearly uniform
policy. Generally, we administered 30 to 40 Gy MRT after surgery at 2 Gy daily
fractions for Masaoka stage II tumors or suspected residual diseases, and 50 to
55 Gy MRT for stage III tumors and for highly-suspected or macroscopic residual
diseases. Since 1992, we have administered EHRT in patients with pleural
dissemination, with 11.2 Gy in 7 fractions or 15 to 16 Gy in 10 fractions after
removal of disseminated lesions in addition to MRT. We treated 52 patients with
MRT alone and 8 with EHRT and MRT. In addition, we gave EHRT to four patients who
developed pleural dissemination later. RESULTS: For all 60 patients, the overall
and cause-specific survival and local and pleural-dissemination control rates at
5 years were 79, 87, 86, and 69%, respectively. Both Masaoka stage and tumor
resectability were associated with prognosis. In stage IVa patients, pleural
dissemination control rate was 71% at 3 years after EHRT, whereas it was 49% in
patients receiving MRT alone (p = 0.38). Grade 2 or higher radiation pneumonitis
was observed in only 3 of 52 patients (5.8%) undergoing MRT initially. In 12
patients who underwent EHRT, 3 patients (25%) experienced grade 2 or 4
pneumonitis. CONCLUSIONS: Postoperative MRT appeared to prevent local recurrence
with acceptable toxicity. EHRT is generally safe and may contribute to control of
pleural dissemination.

Publication Types:
Comparative Study

PMID: 18166844 [PubMed - indexed for MEDLINE]

127: J Thorac Oncol. 2008 Jan;3(1):53-8.

"Salvage" surgery for primary mediastinal malignancies: is it worthwhile?

Petrella F, Leo F, Veronesi G, Solli P, Borri A, Galetta D, Gasparri R, Lembo R,
Radice D, Scanagatta P, Spaggiari L.

Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy.
francesco.petrella@ieo.it

INTRODUCTION: Indications and results of salvage surgery in mediastinal tumors
are still unclear. This study analyzes a single-center experience to assess its
mortality, morbidity, and long-term results. METHODS: Mediastinal salvage surgery
(MSS) was defined as surgical resection of persistent or recurrent primary
mediastinal tumors after previous local treatments with curative intent or
exclusive chemotherapy in case of bulky tumors. Clinical data of patients
undergoing MSS between 1998 and 2005 were analyzed. Overall and disease-specific
long-term survival was calculated. RESULTS: Twenty-one patients (15 men and 6
women, mean age 41 years) underwent MSS. Eleven patients suffered from thymic
tumors (eight thymomas, three thymic carcinoma) whereas 10 patients suffered from
nonthymic tumors (one lung adenocarcinoma + thymoma, two mediastinal monophasic
sinovial sarcoma, one mediastinal neuroendocrine tumor, one mediastinal
teratoblastoma, one mediastinal disgerminoma, one Hodgkin's lymphoma, one
mediastinal atypic carcinoid, two medullary thyroid carcinoma). MSS required
extended vascular resection in 10 cases and cardiopulmonary bypass in one case.
Median operation time was 215 minutes (range 140-720). One postoperative death
and four major complications were recorded (overall mortality 4.7%, morbidity
19.0%). With a median follow-up of 30.6 months, overall 1-, 3-, and 5-year
Kaplan-Meier survival was 89.7, 71.2, and 56.6%, respectively. Thymic neoplasms
had a better prognosis (1-, 3-, and 5-year survival was 100, 87.5, 87.5%,
respectively) when compared with others (1-, 3-, and 5-year survival was 77.8,
53.3, 26.7%, respectively--logrank p = 0.0128). CONCLUSIONS: MSS can offer a
chance of curative treatment in selected patients with an acceptable morbidity
and mortality. Thymic tumors obtain the best results in term of long-term
survival.

Publication Types:
Comparative Study

PMID: 18166841 [PubMed - indexed for MEDLINE]

128: J Thorac Oncol. 2008 Jan;3(1):1-2.

Comment on:
J Thorac Oncol. 2008 Jan;3(1):75-81.

Defining the role of hemithorax irradiation for thymomas is difficult.

Schild SE.

Publication Types:
Comment
Editorial

PMID: 18166832 [PubMed - indexed for MEDLINE]

129: Korean J Radiol. 2008 Jan-Feb;9(1):80-3.

Metastatic thymoma of the breast.

Kim SM, Ko EY, Han BK, Shin JH, Kang SS, Nam SJ, Cho EY.

Department of Radiology and the Center for Imaging Science, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Kangnam-Gu, Seoul, Korea.

Breast metastasis from nonmammary malignant neoplasms is uncommon, and it
accounts for approximately 2% of all breast tumors. Distant metastasis of thymoma
is very rare, and especially to extrathorcic areas. We report a female who had a
metastatic thymoma in her breast 20 years after undergoing resection for a
non-invasive thymoma. She presented with a palpable mass in her left breast.
Mammography and ultrasonogram showed a lobular mass at the anterior glandular
portion. Histological examination after surgical excision revealed a metastatic
thymoma.

Publication Types:
Case Reports

PMID: 18253080 [PubMed - indexed for MEDLINE]

130: Lung Cancer. 2008 Jan;59(1):126-32. Epub 2007 Jul 5.

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. eline.mag@voila.fr

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.

Publication Types:
Case Reports

PMID: 17614156 [PubMed - indexed for MEDLINE]

131: Medicina (B Aires). 2008;68(1):43-7.

[Flow cytometry for the study of mediastinal tumors with abundant lymphoid
elements]

[Article in Spanish]

Vides Almonacid G, García A, Denninghoff V, Avagnina A, Castiglioni T, Elsner B.

Servicio de Patología, Centro de Educación Médica e Investigaciones Clínicas
(CEMIC), Buenos Aires, Argentina.

The anterior mediastinum is a common site of tumors with abundant lymphoid
elements. Flow cytometry is a useful complementary technique to analyze this type
of tumors, which provides qualitative and quantitative information. A
differential diagnosis can be sometimes made between thymoma and precursor
T-lymphoblastic lymphoma (T-LBL). Correct identification is of utmost importance
for patient treatment. A total of 38 mediastinal tumors were analyzed, and
samples were separated for flow cytometry. Flow cytometry data from thymomas and
normal thymic tissue were compared with 42 cases of T-LBL from other anatomical
locations. Among 38 mediastinal tumors, we found 6 benign lesions, 9 diffuse
large B-cell lymphomas (DLBCL), 10 Hodgkin lymphomas (HL), 11 thymomas and 2
T-LL. Flow cytometry provided positive information in 24 cases, and defined
lymphoid neoplastic cells immunophenotype or the typical lymphocytes accompanying
thymomas. Flow cytometry helped differentiate 10 cases of HL and 4 benign lesions
from other lymphomas (DLBCL, T-LBL, etc.). CD3, CD4 and CD8 expressions were most
useful for the differential diagnosis of thymomas and T-LL. To conclude, flow
cytometry is a valid complementary technique, which promptly provides information
on mediastinal lesions, requiring small quantities of tissue for both early
diagnosis and follow up of these diseases.

Publication Types:
English Abstract

PMID: 18416319 [PubMed - in process]

132: Surg Endosc. 2008 Jan;22(1):265. Epub 2007 Oct 18.

Comment in:
Surg Endosc. 2008 Apr;22(4):1135-6.

Comment on:
Surg Endosc. 2006 Oct;20(10):1614-8.

Inclusion of the transcervical approach in the video-assisted thoracoscopic
extended thymectomy (BATET) for myasthenia gravis: a prospective trial.

Maat AP, Van Doorn PA, Bogers AJ.

Publication Types:
Clinical Trial
Comment
Letter

PMID: 17943375 [PubMed - indexed for MEDLINE]

133: Surg Today. 2008;38(4):300-4. Epub 2008 Mar 27.

Limited upper sternotomy in general thoracic surgery.

Alifano M, Parri SN, Arab WA, Bonfanti B, Lacava N, Porrello C, Boaron M.

Thoracic Surgery Department, Maggiore-Bellaria Hospital, Bologna, Italy.

PURPOSE: To evaluate the status of limited upper sternal split in general
thoracic surgery. METHODS: We reviewed the clinical files of 100 consecutive
patients operated on through limited upper sternotomy at a hospital in Italy
during the 10 years between January 1995 and December 2004. RESULTS: Thymus
surgery represented the main indication for this approach (n = 51): for
myasthenia without thymoma in 28 patients, for thymus neoplasms with or without
myasthenia in 22, and for intrathymic parathyroid adenoma in 1. Thyroid surgery
constituted the second main indication for upper sternal split (n = 32) for
benign retrosternal goiter in 18 patients, for mediastinal nodal metastasis of
thyroid cancer in 11, and for malignant retrosternal goiter in 3. The remaining
indications were as follows: to assess residual disease following chemotherapy
for Hodgkin's disease in 7 patients and for non-Hodgkin lymphoma in 1; for
tracheal surgery in 7; and for excision of nodal mediastinal metastasis of
non-thyroid cancer in 2. All operations were completed through the upper sternal
split. There was no surgical mortality but complications developed in eight
patients. CONCLUSION: The upper sternal split provides a satisfactory access to
perform a surgical procedure in the superior mediastinum in most diseases. The
procedure is safe and involves minimal surgical trauma.

PMID: 18368317 [PubMed - in process]

134: Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(3):4-10.

[Clinical and electrophysiological peculiarities of seronegative myasthenia]

[Article in Russian]

[No authors listed]

Thirty-seven patients with myasthenia gravis (MG) underwent AChR-Ab analysis,
clinical study and neurophysiological examination - repetitive nerve stimulation
(RNS). About 16,2% of MG patients who were anti-AChR-negative constituted a
so-called seronegative MG group (SNMG). Compared to the AChR-Ab positive patients
(SPMG), the SNMG was characterized by the higher female/male ratio (6:1), higher
frequency of infantile onset of MG (33,3%), absence of association with thymoma
and highest frequency of myasthenic crisis (83,3%). The clinical pattern of SNMG
differed from SPMG and was characterized by predominant affect of mimic bulbar
and respiratory muscles that determined severity of the course and high frequency
of myasthenic crises. The identical clinical pattern was found in 19,3% of SPMG
patients. However the character of neuromuscular transmission in orbicularis
oculi muscle was different in SNMG and this SPMG-group. The pathological
decrement was observed in 83,3% muscles of the SPMG-group (from -20% to -74%) and
only in one case in the SNMG-group (-48%). Besides, the absence of clinical and
neurophysiological responses to anticholinesterase was noted in the SNMG-group.
Cholinergic neuromuscular hyperactivity in SNMG patients manifested itself in
clinical fasciculations and myokymic contractions of muscles which prevailed in
facial muscles in 66,7% of SNMG patients. Neurophysiologic examination displayed
extra repetitive discharges after the compound motor action potential (R-CMAP) at
low-frequency stimulation after acetylcholine esterase inhibitors in 100% cases.

Publication Types:
English Abstract

PMID: 18427534 [PubMed - in process]