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Biomedical subjects

Toshiyuki Matsuoka

Publications and source records attributed to Toshiyuki Matsuoka.

At least 19 recordsLinked to original sources

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Carcinoma, Hepatocellular↗

Fluorine-18-fluorodeoxyglucose positron emission tomography for assessment of patients with unresectable recurrent or metastatic lung cancers after CT-guided radiofrequency ablation: preliminary results.

OBJECTIVES: We compared the diagnostic value of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with that of computed tomography (CT) following radiofrequency ablation (RFA) of inoperable recurrent or metastatic cancers in the lung. METHODS: Twelve patients (9 males and 3 females; 5 had recurrent lung cancer and the other 7 had metastatic nodules from a variety of primary cancers) were treated by RFA for 17 pulmonary nodules. FDG-PET was performed before and 2 months after RFA, and the mean standardized uptake value (SUV) was calculated. The response evaluation was based on the percent reduction relative to the baseline and the absolute values of SUV on FDG-PET performed at 2 months after RFA. We compared the response evaluations made based on findings of FDG-PET and CT at 2 and > or =6 months (mean 10.2) after RFA. RESULTS: The percent reduction in uptake at 2 months was significantly lower in nodules considered progressive (69.6 +/- 18.6%) than nonprogressive disease (38.7 +/- 12.5%; p < 0.01) based on CT findings at > or =6 months after RFA. The absolute SUV at 2 months was significantly higher in nodules considered progressive (2.61 +/- 0.75) than nonprogressive disease (1.05 +/- 0.67; p < 0.01) based on CT findings at > or =6 months post-RFA. CONCLUSION: Although our pilot study comprised few cases of various histopathological types of cancers in the lung, the results suggest that FDG-PET could predict regrowth on subsequent follow-up CT. Regrowth could be diagnosed earlier by FDG-PET than by CT, and nodules with residual uptake and with <60% reduction of uptake relative to baseline on FDG-PET at 2 months after ablation might require additional therapy.

Adult↗

18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided radiofrequency ablation on implanted VX2 lung tumors in rabbits.

UNLABELLED: The primary goals of this study were to investigate the behavior of normal lung tissues after radiofrequency ablation (RFA) and to determine the suitability of 18F-FDG PET, using a dedicated small-animal scanner, for monitoring the early therapeutic effects of RFA on VX2 lung tumors (VX2s) in rabbits. METHODS: Fourteen Japanese white rabbits with normal lungs underwent RFA, followed by 18F-FDG PET at 1 d and at 1, 2, 4, and 8 wk. In addition, 7 rabbits with untreated VX2s underwent 18F-FDG PET, and 13 rabbits with RFA-treated VX2s underwent 18F-FDG PET at 1 d (n = 7) or 1 wk (n = 6) after the treatment. RESULTS: After RFA of normal lungs, ring-shaped accumulations of 18F-FDG, which coincided with inflammation caused by ablation, were observed. The mean early- (40-60 min after injection) and delayed (100-120 min)-phase ablated lesion-to-muscle ratios were, respectively, 2.9 +/- 1.0 and 3.3 +/- 0.8 (1 d), 4.1 +/- 0.6 and 5.2 +/- 0.9 (1 wk), 4.1 +/- 1.0 and 5.3 +/- 1.5 (2 wk), 3.1 +/- 0.5 and 3.6 +/- 1.1 (4 wk), and 1.8 +/- 0.1 and 2.3 +/- 0.1 (8 wk). At 4 and 8 wk, the uptake was less than that at 1 and 2 wk (P < 0.05). VX2s showed mean tumor-to-muscle ratios of 6.6 +/- 2.1 and 8.6 +/- 3.3 at the early and delayed phases, respectively. For ablated tumors, the respective ratios were 0.8 +/- 0.4 and 1.1 +/- 0.7 (1 d) and 1.2 +/- 0.5 and 1.5 +/- 0.7 (1 wk). These values were significantly lower than those for nonablated tumors (P < 0.001). Histopathologic examination confirmed the absence of viable tumors. 18F-FDG accumulation around ablated tumors reflected thermally damaged normal tissues and was significantly lower than that of control VX2s (P < 0.01). CONCLUSION: Our data suggest that 18F-FDG PET is promising for evaluating the therapeutic response of lung malignancies to RFA: Accumulation of 18F-FDG in surrounding normal tissues appears to be time dependent, and the data suggest that, clinically, 18F-FDG PET should be performed 4 wk or more after RFA. Delayed-phase images seem to better distinguish tumor from inflammation than do early-phase images.

Animals↗

Neural crest origins of the neck and shoulder.

The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel-Feil syndrome, Sprengel's deformity and Arnold-Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.

Amphibians↗

Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3.

Prostaglandins, including PGD(2) and PGE(2), are produced during allergic reactions. Although PGD(2) is an important mediator of allergic responses, aspirin-like drugs that inhibit prostaglandin synthesis are generally ineffective in allergic disorders, suggesting that another prostaglandin-mediated pathway prevents the development of allergic reactions. Here we show that such a pathway may be mediated by PGE(2) acting at the prostaglandin E receptor EP3. Mice lacking EP3 developed allergic inflammation that was much more pronounced than that in wild-type mice or mice deficient in other prostaglandin E receptor subtypes. Conversely, an EP3-selective agonist suppressed the inflammation. This suppression was effective when the agonist was administered 3 h after antigen challenge and was associated with inhibition of allergy-related gene expression. Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions.

Allergens↗

Multiple hypervascular liver nodules in a heavy drinker of alcohol.

A case of hypervascular nodules in the liver, but without hepatitis B or C virus infection in a 38-year-old woman with a history of alcohol abuse is presented. An ultrasound disclosed 1-2-cm hypoechoic tumors in the right and left lobes. Magnetic resonance imaging showed high-intensity tumors at both the T1-weighted and T2-weighted sequences. Incremental dynamic computed tomography and hepatic angiography revealed hypervascular tumors. Ultrasound-guided needle biopsy revealed no evidence of hepatocellular carcinoma, metastatic liver cancer, hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but demonstrated stellate-scar fibrosis septa, which contained small unpaired arteries without hyperplasia dividing the nodule. Moreover, marked pericellular fibrosis, neutrophilic infiltration and Mallory bodies were observed in the cytoplasm. There was no evidence of bile duct proliferation. From these findings, the diagnosis of alcohol-induced fibrosis, distinctly different from focal nodular hyperplasia, was tenable. Further studies may provide insights into the pathogenesis of nodule formation and hypervascularity in heavy drinkers of alcohol.

Adult↗

Primary sclerosing cholangitis and hepatitis C virus infection.

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.

Bile Ducts↗

Radiofrequency ablation in a porcine lung model: correlation between CT and histopathologic findings.

OBJECTIVE: The objective of our study was to investigate the time course changes of the ablated lesion after radiofrequency ablation in the porcine lung and the correlation between CT and histopathologic findings. CONCLUSION: Ground-glass attenuation on CT led to overestimation of the size of necrotic lesions. The layered structural findings on CT were consistent with the histopathologic findings. Although CT findings reflect the histopathologic findings, attention should be paid to the dissociation of ablated lesions and high-density areas in clinical interpretation of CT images.

Animals↗

Assessment of cerebral microembolism during percutaneous radiofrequency ablation of lung tumors using diffusion-weighted imaging.

OBJECTIVE: It is well known that radiofrequency ablation generates microbubbles in the liver. We hypothesized that microbubbles generated during percutaneous radiofrequency ablation of lung tumors flow into the pulmonary veins and are distributed to the systemic arteries, as with radiofrequency ablation of liver tumors. To assess the risk of cerebral infarction during radiofrequency ablation of lung tumors, we performed diffusion-weighted imaging and, if possible, monitored microemboli in the carotid artery during radiofrequency ablation. SUBJECTS AND METHODS: We prospectively studied 20 patients (19 men and one woman) who underwent radiofrequency ablation of lung tumors. Pre- and postoperative MRI examinations were performed in all 20 patients, and during 17 radiofrequency ablation sessions, sonography was used to monitor whether microemboli were generated. RESULTS: Radiofrequency ablation was technically feasible for the treatment of selected pulmonary tumors. Microemboli, which were believed to represent microbubbles, were seen on sonography during three of the 17 radiofrequency ablation sessions. They were rarely observed when a lung tumor was small, the treatment session was brief, and the radiofrequency emission power was low. No new area of abnormal intensity was seen on postoperative MRI in all 20 patients. Although the microemboli were observed, MRI could not confirm infarction. CONCLUSION: We concluded that cerebral infarction as a result of microbubbles generated during radiofrequency ablation of lung tumors has a low possibility of becoming a clinical problem.

Aged↗

Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity.

Physical interaction of T cells and dendritic cells (DCs) is essential for T cell proliferation and differentiation, but it has been unclear how this interaction is regulated physiologically. Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP). In vitro, a TP agonist enhances random cell movement (chemokinesis) of naive but not memory T cells, impairs DC-T cell adhesion, and inhibits DC-dependent proliferation of T cells. In vivo, immune responses to foreign antigens are enhanced in TP-deficient mice, which also develop marked lymphadenopathy with age. Similar immune responses were seen in wild-type mice treated with a TP antagonist during the sensitization period. Thus, TXA2-TP signaling modulates acquired immunity by negatively regulating DC-T cell interactions.

Animals↗

Clinical evaluation of digital radiography based on a large-area cesium iodide-amorphous silicon flat-panel detector compared with screen-film radiography for skeletal system and abdomen.

The aim of this clinical study was to compare the image quality of digital radiography using the new digital Bucky system based on a flat-panel detector with that of a conventional screen-film system for the skeletal structure and the abdomen. Fifty patients were examined using digital radiography with a flat-panel detector and screen-film systems, 25 for the skeletal structures and 25 for the abdomen. Six radiologists judged each paired image acquired under the same exposure parameters concerning three observation items for the bone and six items for the abdomen. Digital radiographic images for the bone were evaluated to be similar to screen-film images at the mean of 42.2%, to be superior at 50.2%, and to be inferior at 7.6%. Digital radiographic images for the abdomen were judged to be similar to screen-film images at the mean of 43.4%, superior at 52.4%, and inferior at 4.2%; thus, digital radiographic images were estimated to be either similar as or superior to screen-film images at over 92% for the bone and abdomen. On the statistical analysis, digital radiographic images were also judged to be preferred significantly in the most items for the bone and abdomen. In conclusion, the image quality of digital radiography with a flat-panel detector was superior to that of a screen-film system under the same exposure parameters, suggesting that dose reduction is possible with digital radiography.

Adult↗

Development of multicentric hepatocellular carcinoma after completion of interferon therapy.

We report a case of multicentric hepatocellular carcinoma that developed in a 74-year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis C, despite sustained virologic, biochemical, and histological improvement. Initially, serum hepatitis C virus RNA was positive and the patients' serum level of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV) in the serum was negative for surface antigen, surface antibody, core antibody, and DNA. The patient was started on 10 x 10(6) international units (IU) of IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

Aged↗

Inhibition of neointimal hyperplasia by heat stress in an experimental model.

PURPOSE: To evaluate the potential effect of heat stress in inhibiting neointimal hyperplasia after angioplasty in an experimental model. MATERIALS AND METHODS: In vitro, proliferation and migration of heat-stress-induced and noninduced cells were compared with use of an endothelial cell/smooth muscle cell coculture model (five culture dishes in each experiment). Mild heat stress was induced via exposure of cultures to a temperature of 42 degrees C for 2 hours. In vivo, the neointimal thickness of ear arteries of Japanese white rabbits 7 days after denudation of endothelium was histologically evaluated in the control and heat-stress-induced groups (three rabbits in each group). RESULTS: Proliferation of heat-stress-induced smooth muscle cells declined significantly compared with that of noninduced cells in single-culture and coculture models. The migration rates of neither endothelial cells nor smooth muscle cells were significantly affected by heat stress. In vivo, the mean neointimal thickness was 13.8 micro m +/- 8.0 in the control group and 3.9 micro m +/- 2.1 in the induced group (P <.05). CONCLUSION: Induction of mild heat stress has great potential to reduce neointimal hyperplasia after angioplasty because it inhibits smooth muscle cell proliferation without inhibiting endothelial migration in vitro and suppresses neointimal growth in vivo.

Angioplasty↗

CEA producing primary hepatic carcinoid.

Imaging studies of a hepatic tumor in a 53-year-old woman with elevated serum levels of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and 5-hydroxyindole acetic acid (5HIAA) revealed a hypervascular tumor in the right lobe. Grossly, the brownish tumor was measured 13.5x12 cm with four daughter nodules. Microscopically, the majority of these columnar and round tumor cells had ribbon-or rosette-like patterns with the expression of neuroendocrine marker proteins, such as Grimelius, NSE, chromogranin A, and synaptophysin, and moderate expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6; the minority had glandular patterns with a strong expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6. Ultrastructurally, most tumor cells contained populations of electron-dense core granules ranging between 100 and 200 nm in diameter. After hepatectomy, serum CEA, NSE, and 5HIAA reverted to normal ranges and persisted for 19 months. These findings suggested that the diagnosis of primary hepatic carcinoid was tenable and that the tumor might derive from hepatic stem cells which acquired the additional nature of producing CEA without cytokeratins characteristic of hepatocytes or bile duct cells. Some molecular based approaches have attributed unique biological behavior and histogenesis to this carcinoid tumor.

Journal Article↗

Eosionophilic pseudotumor of the liver due to Ascaris suum infection.

A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is described in a 34-year-old-man with a high serum level of immunoglobulin E and hypereosinophilia ascribed to a history of atopic dermatitis since childhood. Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low-density nodules on computed tomography (CT), and as low and high signal intensity lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT during arteriography (CTA) and arterial portography revealed multiple nodules with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver tissue specimens did not contain tumor cells or atypical cells; instead, they showed marked infiltration of eosinophils with necrosis and Charcot-Leyden crystals in the portal tracts and hepatic sinusoides, suggesting parasitic infection, although neither larvae nor eggs were detected. The diagnosis of visceral larva migrans (VLM) due to A. suum was based on immunoserological tests. The patient was a habitual consumer of raw bovine liver, which may explain the A. suum infection. After drug therapy with albendazole, the hypoechoic nodules disappeared. Differential diagnoses and the possible transfection route of A. suum are discussed.

Journal Article↗

The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut.

We used mice deficient in each of the eight types and subtypes of prostanoid receptors and examined the roles of prostanoids in dextran sodium sulfate-induced (DSS-induced) colitis. Among the prostanoid receptor-deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. This phenotype was mimicked in wild-type mice by administration of an EP4-selective antagonist (AE3-208). The EP4 deficiency impaired mucosal barrier function and induced epithelial loss, crypt damage, and aggregation of neutrophils and lymphocytes in the colon. Conversely, administration of an EP4-selective agonist (AE1-734) to wild-type mice ameliorated severe colitis normally induced with 7% DSS, while that of AE3-208 suppressed recovery from colitis and induced significant proliferation of CD4+ T cells. In vitro AE3-208 enhanced and AE1-734 suppressed the proliferation and Th1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP4-deficient mice. We conclude that EP4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response.

Animals↗