Prompt resolution of hypoglycemia by hepatic transarterial embolization for malignant insulinoma with multiple liver metastases.

A 45-year-old female who presented with loss of consciousness and a cold sweat was found to have a pancreatic tumor and multiple liver metastases. Laboratory studies showed marked hypoglycemia and inappropriately elevated serum insulin, C-peptide, and serum tumor markers. Fine needle aspiration revealed Grade 3 small-cell type primary pancreatic neuroendocrine carcinoma. Consequently, the diagnosis of malignant insulinoma was made. Transarterial embolization (TAE) for hepatic metastases resulted in the reduction of tumor volume and prompt resolution of hypoglycemic attacks, whereas diazoxide and systemic chemotherapy had been ineffective for controlling blood glucose levels, and octreotide was unavailable due to the allergic effect. This case report highlights the potential usefulness of TAE for malignant insulinomas in the management of hypoglycemia.

A case of an inverted tooth in the nasal cavity.

We report a case of an inverted tooth in the nasal cavity. The patient was a 27-year-old man who attended our hospital in May 1998, complaining of left cheek-pain. There was nothing remarkable in his medical or family history. Fiberscopic (intranasal) and radiological examinations revealed a white foreign body in the left nasal cavity, within 2 cm of the left nostril. This foreign body was diagnosed as an inverted tooth. It was removed under general anesthesia and found to be 17 mm in length. Although the tooth showed a single root, it possessed two cusps and we deduced it to be a molar.

A case of carcinoid tumor of the middle ear.

We report here a case of a carcinoid tumor observed in the middle ear (ME), which was initially diagnosed as ME adenoma. The patient was a 64-year-old woman who was first seen in our hospital in March 2001 for a 7-month hearing loss. On otoscopic examination, a whitish mass could be observed through the intact tympanic membrane. High-resolution computed tomography demonstrated a tumor-like lesion in the ME with no evidence of bone destruction. A myringotomy and biopsy were performed and an initial diagnosis of ME adenoma was made. Light microscopy showed fragments of cellular tissue in which both glandular (adenomatous) and trabecular (carcinoid) growth patterns could be identified, but neuroendocrine differentiation was not detected by immunohistochemistry (negative staining for chromogranin A and synaptophysin). On the basis of this diagnosis, the patient underwent a tympanomastoidectomy in June 2001, in which the presumed ME adenoma was completely excised and the diagnosis was modified to ME carcinoid tumor. Immunohistochemical examinations at that time showed positive staining of the tumor cells for chromogranin A and synaptophysin. This case suggests the difficulties in distinguishing ME carcinoid tumors from ME adenomas. The patient is without recurrence of her disease to date.

The management of possible fishbone ingestion.

OBJECTIVE: We assessed the usefulness of computed tomography (CT) in cases of suspected impaction of fish bones in the esophagus. The findings of this study were also compared with those of studies in which surgery was used to remove or confirm the presence of fish bones. We accordingly propose a management protocol to ensure optimum outcome for patients with a history of fish bone ingestion. METHODS: X-ray and CT imaging were performed in 76 patients in whom esophageal impaction of fish bones was suspected. RESULTS: Plain X-ray revealed impacted fish bones in 17 patients (22%), soft-tissue swelling but no evidence of foreign body in 5 (7%), and no abnormal findings in 54 (71%). These findings were apparent on CT scans in 31 (41%), 8 (10%), and 37 (49%), respectively. Of the 31 patients in whom CT revealed a fishbone, 17 (55%) also exhibited X-ray evidence of foreign body. Of the remainder, X-ray revealed only soft-tissue swelling in 3 (10%), and was unremarkable in 11 (35%). Among the 5 patients in whom X-ray demonstrated only soft-tissue swelling, CT was positive for foreign body in 3 (60%). Of the 54 patients in whom X-ray appearances were normal, CT revealed foreign bodies in 11 (20%) and other abnormalities in 6 (11%). CONCLUSION: In the present study, sensitivity and specificity of plain X-ray was 54.8% (17 of 31) and 100% (45 of 45), respectively. However, for CT, both sensitivity and specificity were 100%. CT was determined to be very useful in the diagnosis of impacted fish bones in the esophagus.

End-to-end anastomosis in chronic tracheal stenosis.

OBJECTIVE: This study assessed the efficacy and safety of end-to-end anastomosis of the trachea following segmental resection in chronic tracheal stenosis. METHODS: End-to-end anastomoses of the trachea were performed in 35 patients with chronic tracheal stenosis; 18 patients with tracheal invasion of thyroid cancer and 17 patients with long-term intubation and blunt injuries of the trachea. RESULTS: All operations were successful, except one whose unilateral recurrent nerve had not been identified in the recurrent thyroid cancer invasion with trachea. CONCLUSION: This operation provides a one-step cure for the stenosed trachea and can be applied to the resection of less than six tracheal segments.

Sensitization of head and neck squamous cell carcinoma cells to Fas-mediated apoptosis by the inhibition of Bcl-X(L) expression.

BACKGROUND: Various types of malignant tumor cells are known to acquire resistance to Fas receptor (Fas)-mediated apoptosis. In Fas-sensitive cells, Fas-mediated apoptosis is observed when anti-Fas antibody is bound to Fas. Bcl-2 and Bcl-X(L) are representative anti-apoptosis proteins reported to be capable of suppressing Fas-mediated apoptosis. OBJECTIVE: To investigate the mechanism of resistance acquisition to Fas-mediated apoptosis in cultured human head and neck squamous cell carcinoma cells (HNSCCs). METHODS AND RESULTS: We applied an anti-Fas antibody (CH11) to Fas-expressing HNSCCs (HSC-2) and the CH11 did not induce cell death in HSC-2. Treatment with actinomycin D (ActD) converted the phenotypes of HSC-2 from CH11-resistant to CH11-sensitive. Western blot analysis showed no differences between ActD-treated and ActD-untreated HSC-2 in the expression of Bcl-2. On the other hand, the expression of Bcl-X(L) was greatly reduced in ActD-treated HSC-2. Moreover, the reduction of Bcl-X(L) by specific antisense oligonucleotide treatment enhanced the CH11-induced cell death of HSC-2. CONCLUSION: Our data suggest that Fas-signaling might be regulated by a Bcl-X(L)-inhibitable step in CH11-resistant HSC-2.

Inhibition of caspase-9 activity and Apaf-1 expression in cisplatin-resistant head and neck squamous cell carcinoma cells.

We have previously reported that cisplatin induces caspase-9 (Casp9) activation in head and neck squamous cell carcinoma cells in vitro (HNSCCs). Our purpose here was to examine whether HNSCCs selected for resistance to cisplatin fail to exhibit Casp9 activation in response to cisplatin. The cisplatin-resistant HNSCCs (HSC-2CR) were selected from cisplatin-sensitive HNSCCs (HSC-2) for growth in the presence of cisplatin. Following cisplatin treatment, protelyzed Casp9 subunits were detected in HSC-2, but not detected in HSC-2CR. Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), Casp9 activity in cisplatin-treated HSC-2CR was less than that in cisplatin-treated HSC-2. Apoptotic protease-activating factor 1 (Apaf-1) has been shown to participate as an adaptor molecule in Casp9 activation. In the presence of cytochrome c (Cyt c) released from mitochondria, Apaf-1 binds to Casp9 and causes its activation. HSC-2 expressed 2-fold higher levels of Apaf-1 compared with HSC-2CR. On the other hand, following cisplatin treatment, the same degree of increase in cytoplasmic Cyt c was detected in both HSC-2 and HSC-2CR. These results suggest that in a certain type of HNSCCs, the inhibition of Casp9 activity and Apaf-1 expression may represent a mechanism of acquired cisplatin resistance.

[Inhibition of caspase-9 activity in cisplatin-resistant head and neck squamous cell carcinoma].

We have previously reported that cisplatin induces caspase-9 activation in head and neck squamous cell carcinoma cells (HNSCCs) in vitro, and the use of a specific inhibitor of caspase-9 blocks cisplatin-induced apoptosis in HNSCCs. Our purpose here was to determine whether HNSCCs selected for resistance to cisplatin fail to exhibit caspase-9 activation in response to cisplatin. Cisplatin-resistant HNSCCs (CRHNSCCs) were selected for growth in the presence of cisplatin. Following cisplatin treatment, no protelyzed caspase-9 subunits were detected in the CRHNSCCs, whereas proteolytic degradation of procaspase-9 was observed in parental cisplatin-sensitive HNSCCs (CSHNSCCs). Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), caspase-9 activity in cisplatin-treated CRHNSCCs was less than that in cisplatin-treated CSHNSCCs. Because caspase-9 activation requires the release of mitochondorial cytochrome c (Cyt c) into the cytoplasm, we determined the level of cytoplasmic Cyt c in response to cisplatin treatment. Interestingly, following cisplatin treatment, the same extent of increase in cytoplasmic Cyt c was evident and the expression of Bcl-2 family proteins (Bcl-2 and Bcl-XL) remained unchanged in both CRHNSCCs and CSHNSCCs. These results suggest that in certain HNSCC cell types, inhibition of caspase-9 activity represents another mechanism of acquired cisplatin resistance. This inhibition mechanism may be independent of the release of Cyt c into the cytoplasm.

Crosslinking of the CD69 molecule enhances S100A9 production in activated neutrophils.

Expression of CD69 on neutrophils and generation of anti-CD69 autoantibodies in patients with rheumatoid arthritis (RA) have been reported. Thus natural ligands for CD69 not yet identified and/or the anti-CD69 autoantibodies possibly affect neutrophils by evoking CD69 signaling, which may further affect joint-composing cells in RA. However, the effect of the CD69 signaling in neutrophils remains largely unclear. To elucidate the issue, we tried to identify proteins affected by the crosslinking of CD69 on neutrophils using a proteomic approach. Specifically, CD69 on granulocyte-macrophage colony stimulating factor (GM-CSF)-activated neutrophils was crosslinked by anti-CD69 monoclonal antibodies, and then intracellular proteins were detected using 2-dimensional electrophoresis and further identified by mass spectrometry and subsequent protein database searching. As a result, we successfully identified multiple proteins that increased their production by the CD69 signaling. Among the proteins, we focused on one of the up-regulated proteins, S100A9 calcium binding protein (S100A9), and investigated proteome changes brought by a recombinant S100A9 in a human synovial sarcoma cell line (SW982), a human chondrosarcoma cell line (OUMS-27), and a human T leukemia cell line (Jurkat). This revealed that the recombinant S100A9 altered proteomes of SW982 and OUMS-27, and to a lesser extent, that of the Jurkat cells. Further, S100A9 induced IL-1beta production from neutrophils and the SW982 cells. These data suggest that unidentified natural ligands for CD69 and/or the anti-CD69 autoantibodies possibly affect joint-composing cell types through the increased production of S100A9 in neutrophils, providing a new insight into functions of CD69 on neutrophils in RA.

Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia.

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.

Identification of beta-tubulin isoform V as an autoantigen in allergic rhinitis by a proteomic approach.

Autoantibodies to IgE and beta2-adrenergic receptor have been reported in patients with allergic rhinitis. To investigate whether autoimmunity in allergic rhinitis is directed to such limited molecules or directed to a wide range of self proteins, we here attempted to survey autoantigens/autoantibodies comprehensively, using proteomics. Specifically, we separated proteins extracted from peripheral blood mononuclear cells by 2-dimensional electrophoresis and then detected autoantigens by subsequent western blotting with sera from patients with allergic rhinitis. As a result, we detected multiple autoantigens, some of which were further identified by mass fingerprinting. Next, we confirmed antigenicity of one of the identified autoantigens, beta-tubulin isoform V (beta-tubV), using a recombinant protein and then measured prevalence of the anti-beta-tubV autoantibodies. As a result, 52% of the tested patients with allergic rhinitis were found to possess anti-beta-tubV autoantibodies. Our study indicates that autoimmunity is a common phenomena and beta-tubV is one of the major autoantigens in allergic rhinitis.