Syntactic and Semantic Processing in Japanese Sentence Reading: A Research Using Functional Near-Infrared Spectroscopy (fNIRS).

In order to examine whether syntactic processing is a necessary prerequisite for semantic integration in Japanese, cortical activation was monitored while participants engaged in silent reading task. Congruous sentences (CON), semantic violation sentences (V-SEM), and syntactic violation sentences (V-SYN) were presented in the experiment. The participants' oxygenated hemoglobin concentration changes during the reading task were measured using functional near-infrared spectroscopy. The results suggest that the CON sentences did not require additional cognitive load on syntactic processing or semantic processing. The V-SEM sentences demanded great cognitive load on semantic processing. Besides, it also elicited great cognitive load on syntactic processing. The V-SYN sentences induced great cognitive load on syntactic processing, but it did not induce additional load on semantic processing. These evidence demonstrates that, in Japanese language processing, the difficultness of semantic processing could influence the difficultness of syntactic processing, while the difficultness of syntactic processing would not influence the difficultness of semantic processing. Our findings are suggestive of the possibility that in Japanese language reading, semantic processing precedes syntactic processing, or semantic processing and syntactic processing are in parallel.

A case of "ETV6-FISH-negative" secretory carcinoma of the parotid gland: immunohistochemical study.

Secretory carcinoma of the salivary glands is a relatively new disease concept, and is characterized by "morphological resemblance to mammary secretory carcinoma and ETV6-NTRK3 gene fusion." Herein we describe a confusing case and briefly discuss practical diagnostic problems. The patient was a 71-year-old Japanese man who had a tumor consistent with secretory carcinoma at the microscopic and immunohistochemical levels. Immunohistochemically, EMA and S100 protein were noted to be positive along with various cytokeratins as well as mammaglobin and pSTAT5. Moreover, vimentin was focally positive. Smooth muscle actin, p63, p40, and androgen receptor were negative. However, a search using fluorescence in situ hybridization did not reveal a definite split signal for the ETV6 gene. It is presumed that confirming the diagnosis of secretory carcinoma without genetic retrieval will be accepted as a diagnostic method, and we hope that worldwide general recognition may earlier reach "gradual acceptance."

The pathological challenge of establishing a precise diagnosis for pulmonary tumour thrombotic microangiopathy: identification of new diagnostic criteria.

AIMS: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease of patients with cancer that causes progressive pulmonary hypertension (PH). Its pathology is characterised by fibrocellular intimal proliferation and thrombosis caused by tumour emboli in microscopic pulmonary arteries. However, such PTTM-like lesions often appear incidentally. We sought to identify features that distinguished PTTM from incidental pulmonary tumour emboli, and to gain an overall picture of PTTM morphology in terms of its pathogenesis. METHODS AND RESULTS: Twenty-five PTTM cases were classified into two groups: (i) a definite group (n = 14), clinically diagnosed with PH; and (ii) a suspicious group (n = 11) with respiratory symptoms but without a clinical evidence of PH. As a control group, autopsy cases with PTTM-like lesions lacking progressive respiratory symptoms were selected (n = 7). PTTM-like lesions in these groups were studied and a diagnostic guide for PTTM formulated as follows: PTTM-like lesions with >17 affected vessels observed in a 1-cm2 area of lung specimen, and the absence of pulmonary metastatic nodules. PTTM due to gastric cancers was shown to have a significantly shorter course and larger arterial involvement than cases with non-gastric cancers. Serial sections revealed a PTTM lesion to be a longitudinal obstruction that accumulated in microscopic pulmonary arteries and that showed a proximal extension via supernumerary arteries. CONCLUSION: We suggest novel pathological diagnostic characteristics for PTTM deduced from a study of 25 autopsy cases. This includes PTTM-like lesions with >17 affected vessels in a 1-cm2 area of lung specimen and the absence of pulmonary metastatic nodules.

A case of 37 year long Behçet disease resembling Takayasu arteritis: An autopsy report.

A 19-year-old woman with a history of recurrent aphthous stomatitis and genital ulceration was diagnosed with Behçet disease. She was treated with steroids and immunosuppressive agents for more than 30 years, but multiple complications manifested including ileocecal ulcer, aortic valve regurgitation, renal failure, ischemic enterocolitis, and arteriosclerotic obliterans until her death at the age of 56 from pneumonia. An autopsy examination demonstrated an entirely calcified aorta and major aortic branches. The ascending aorta was dilatated 55 mm in diameter and branches were all stenosed. Microscopically, the aortic arch and its branches showed collagenous fibrosis of the outer media and adventitia, whereas coronary and abdominal aortic branches showed conventional atherosclerosis. Although the ante-mortem diagnosis was angio-Behçet disease, its pathophysiology along with her clinical history, morphology of the lead pipe-like aorta, predominant destruction of the outer arteries, and a human leukocyte antigen (HLA) haplotype of B39 were all suggestive of Takayasu arteritis. Thus, this case implies that HLA-B39 may be associated with the pathogenesis of arteritis like Takayasu arteritis, even if the primary disease is Behçet disease.

A case of multiple pulmonary cavernous hemangioma.

A 61-year-old male who originally visited a different hospital, underwent a health checkup in which multiple lung nodules were detected. Multiple well-defined small nodules were observed in both lungs, with lesions reaching the arteries. Metastatic lung cancer, with unknown origin, was suspected. A computed tomography-guided percutaneous lung biopsy was performed; however, a pathological diagnosis could not be established. Then the patient was referred to our hospital for surgical lung biopsy. Macroscopically, the nodule was dark-red in color and solid without a capsule. Microscopically, the nodule was composed of dilated vascular spaces lined by flattened bland cells. They were positive for CD34, but were negative for TTF-1, consistent with lesions of endothelial origin. Microscopic and immunohistochemical findings supported the diagnosis of multiple pulmonary cavernous hemangiomas. After diagnosis, the lesions were left untreated and thereafter showed no signs of deterioration.

[Primary left atrial myxofibrosarcoma; report of a case].

We herein report a very rare case of a primary left atrial myxofibrosarcoma. A 61-year-old female presented with dyspnea and a wet cough. Chest X-ray film showed cardiomegaly and pulmonary congestion. Echocardiography and computed tomography revealed a left atrial tumor obstructing blood flow to the left ventricle. She was diagnosed with acute congestive heart failure due to functional mitralstenosis secondary to a left atrial tumor, and an emergency operation was performed. The tumor, which occupied left atrium, attached to the posterior wall of the left atrium and to the mitral valve, but had not invaded the left atrial wall. The tumor was removed from the left atrial wall, preserving the mitral valve and valve leaflets. The patient's post operative course was uneventful. The pathological diagnosis was myxofibrosarcoma, which rarely develops in the heart.

Assessment of FDG retention differences between the FDG-avid benign pulmonary lesion and primary lung cancer using dual-time-point FDG-PET imaging.

PURPOSE: The aim of this study was to clarify FDG retention differences between FDG-avid benign pulmonary lesions (BPLs) and primary lung cancers (PLCs), and between tuberculous and non-tuberculous BPLs using dual-time-point FDG-PET imaging. METHODS: Thirty-four BPLs and 47 PLCs with a maximal standardized uptake value (SUVmax) >2.5 and a maximal axial diameter >10 mm were enrolled. We compared the retention index (RI) among different types of lesions, and evaluated the relationship between RI and SUVmax at 1 h (SUV1). Glucose transporter-1 (Glut-1) and hexokinase (HK)-2 expression was assessed in eight non-tuberculous BPLs. RESULTS: BPLs and PLCs showed similar high RIs (mean ± SD 33.6 ± 22.6 and 32.5 ± 23.7, respectively; p = 0.95). In BPLs, both tuberculous and non-tuberculous lesions showed high RIs (39.1 ± 25.8 and 30.3 ± 20.3, respectively; p = 0.43). However, BPLs and PLCs exhibited a different relationship between RI and SUV1. BPLs tended to show lower RIs with higher SUV1s, and a mild negative correlation, whereas PLCs showed persistent high RIs and no significant correlation. Glut-1 and HK-2 expression was found in 75 and 12.5 % of non-tuberculous BPLs, respectively. CONCLUSIONS: FDG-avid BPLs could show high RIs regardless of their being tuberculous and non-tuberculous lesions, and no significant difference with PLC RIs was found. FDG-avid BPLs and PLCs showed different relationships between RI and SUV1, and it seemed to be related with different mechanisms of high FDG retention. However, the mechanisms of high FDG retention in FDG-avid BPLs remain unclear, and this matter requires further investigation.

Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases.

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and ß-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of ß-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Gallbladder carcinoma with a large monolocular cystic cancerous component.

The monolocular cystic formation associated with gallbladder carcinoma is an extremely rare condition. A 79-year-old female suffering from upper abdominal pain and distention was admitted to our hospital. Ultrasonography and computed tomography revealed a monolocular cyst with an irregular wall thickness of 15 cm in diameter concomitant with a solid mass of 8 cm in diameter around the gallbladder bed. During celiotomy, the tumor was found to have a large pale gray cystic component at the fundus of the gallbladder, and disseminated nodules were observed in the peritoneum. We diagnosed the patient with gallbladder carcinoma and performed a simple cholecystectomy that included the tumor without systematic lymphadenectomy. On the cut face of the gallbladder, the lumen was occupied by a solid neoplasm. The cyst included a large amount of serous fluid and protruded continuously from the body of the gallbladder, but it did not communicate with the gallbladder lumen. Although the mechanism responsible for the development of cyst-forming papillary carcinoma of the gallbladder remains unknown, the present case is crucial for understanding the mechanism of cystogenesis in gallbladder carcinoma.

Pleomorphic xanthoastrocytoma as a component of a temporal lobe cystic ganglioglioma: a case report.

We report a case of pleomorphic xanthoastrocytoma (PXA) as a component of a ganglioglioma in a 13-year-old Japanese boy. Magnetic resonance imaging showed a large cystic lesion with an enhanced mural nodule of the left temporal lobe. Microscopic examination of the tumor showed that it was composed of two distinct neoplastic components: dysplastic ganglion cells and a PXA. There were gradual transitions between the two neoplastic components, and the PXA constituted the gliomatous component of the ganglioglioma. The PXA component showed spindle-shaped and pleomorphic large cells with lipidized cytoplasm. The tumor cells were surrounded by numerous reticulin fibers. Immunohistochemically, the ganglion cells were negative for glial fibrillary acidic protein (GFAP), but showed positive staining for a 70-kDa neurofilament protein, synaptophysin, and NeuN. In contrast, PXA cells were positive for GFAP but negative for neuronal markers. Our case is therefore histologically classified as ganglioglioma with PXA as the glial component. These results suggested that PXA and ganglioglioma share a common origin and that the combination of PXA-ganglioglioma would be positioned along the spectrum between PXA and ganglioglioma. Alternatively, these results may support the hypothesis that PXA originates from glioneuronal progenitor cells capable of generating astrocytic and neuronal cell types.

Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas.

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a key role in responses to hypoxia and expression of HIF-1alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1alpha expression in gastric carcinoma. METHODS: We examined HIF-1alpha, vascular endothelial growth factor (VEGF), and insulin-like growth factor-2 (IGF-2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF-1alpha expression, clinicopathological features, and survival were examined. RESULTS: HIF-1alpha expression correlated with tumor size (P<0.005), depth of invasion (P=0.018), VEGF expression (P=0.03), and intra-tumor MVD (P<0.005). IGF-2 expression was more prevalent in HIF-1alpha positive than in HIF-1alpha negative tumors and the 5-year survival rate was 58.4% for HIF-1alpha positive patients and 81.5% for HIF-1alpha negative patients (P=0.009). HIF-1alpha expression is an independent prognostic factor in gastric carcinoma (P=0.032). CONCLUSIONS: Overexpression of HIF-1alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.

Successful therapy with whole-lung lavage and autologous peripheral blood stem cell transplantation for pulmonary alveolar proteinosis complicating acute myelogenous leukemia.

A 43-year-old man with acute myelogenous leukemia (AML) was found to be complicated with pulmonary alveolar proteinosis (PAP), which was confirmed by biochemical and histological findings. After achievement of complete remission of AML, he underwent whole-lung lavages twice between intensive chemotherapies. Subsequently, he received high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT), which was performed safely without any infections. He has been in remission for 25 months after transplant with no recurrence of PAP. Autologous PBSCT in combination with whole-lung lavage may be a promising strategy in the treatment of PAP associated with hematological malignancies.

Hsp90 inhibitors cause G2/M arrest associated with the reduction of Cdc25C and Cdc2 in lung cancer cell lines.

PURPOSE: Hsp90, a molecular chaperone, is involved in folding, assembly, maturation, and stabilization of the client proteins which regulate survival of cancer cells, and thus Hsp90 inhibitors may be potential molecular targeting agents for cancer treatment. We investigated whether Hsp90 inhibitors have therapeutic value in lung cancer. METHODS: First, expression levels of Hsp90 in lung cancer cells were examined by western blotting and immunohistochemical analyses. Next, the effect of Hsp90 inhibitors, geldanamycin and 17-allylaminogeldanamycin (17-AAG), on lung cancer cell growth was examined. RESULTS: Remarkable high expression of Hsp90 protein in lung cancer cell lines and a more intense signal for Hsp90 by immunohistochemistry in males, patients with smoking index over 600, and squamous cell carcinoma were observed. Both Hsp90 inhibitors dose dependently inhibited the growth of lung cancer cell lines and induced G2/M arrest concomitant with decreased protein levels of Cdc25C and Cdc2. Moreover, combination of an Hsp90 inhibitor and irradiation had an additive effect on cell growth inhibition and reduction of Cdc25C and Cdc2 protein levels. CONCLUSION: Hsp90 inhibitor is thus a therapeutic tool for lung cancer based on its target proteins, which are involved in tumor progression and antiproliferative activity in lung cancer cells.

Optimal treatment strategy for elderly patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: The age distribution of patients with hepatocellular carcinoma (HCC) now peaks at nearly 70 years in Japan and this is continually increasing. Whether such elderly patients with HCC aged 80 years or older should be treated, and if so, how they should be selected for treatment remains uncertain. The present study was undertaken to determine any differences in the clinical characteristics and prognostic features between patients with HCC aged 80 years or older and those younger than 80 years of age. We also aimed to identify any significant variables in the prognosis of elderly patients with HCC aged 80 years or older. METHODS: Seven hundred and four patients with HCC, diagnosed during a 12-year period from January 1989 to December 2000, were categorized into two groups as follows: (i) 36 patients aged 80 years or older at the detection of HCC were defined as the elderly group and; (ii) 668 patients younger than 80 years of age were placed in the non-elderly group. Clinical variables were analyzed and compared between the two groups, and any significant variables in the prognosis were simultaneously determined. RESULTS: Regarding sex, viral markers, concentration of serum alpha-fetoprotein, diameter and number of tumors, Child's grade, presence of portal thrombosis, histology grade of HCC and any types of treatment, no significant difference was found between the two groups. The 1-year and 3-year survival rates in the elderly group (54.1 and 28.1%, respectively) were not significantly different from those in the non-elderly group (69.9 and 43.2%, respectively; P = 0.1053). The only significant factor in the prognosis in the elderly group was the presence of portal thrombosis, although a Child's grade of B or C was almost a significant factor with a P-value of 0.063. Tumor size measuring more than 3 cm in the greatest dimension, non-solitary tumor, Child's grade of B or C, and the presence of portal thrombosis were all found to be prognostic factors in the non-elderly group using a multivariate analysis. CONCLUSIONS: An advanced stage of HCC, not advanced age, influenced the survival rate in these elderly patients. Therefore, an optimal treatment strategy should be applied for elderly patients with HCC who demonstrate less prognostic factors in the same manner as that for non-elderly patients.

Impact of hepatologists to extend survival of hepatocellular carcinoma patients with cirrhosis: a comparison with non-hepatologists.

BACKGROUND/AIMS: Whether or not generalists and specialist physicians can make an appropriate adaptation of their practice patterns when caring for their patients currently remains a matter of debate. The present study was undertaken to explore whether the clinical characteristics of hepatocellular carcinoma at its time of detection, the initial treatment options and the survival vary between patients with hepatocellular carcinoma associated with cirrhosis who were treated by hepatologists and those who were treated by non-hepatologists. METHODOLOGY: A retrospective study with 626 patients with hepatocellular carcinoma associated with cirrhosis was performed. The patients were stratified into three groups as follows; 1) a hepatologist group: 280 patients followed up and treated consistently by hepatologists, 2) a non-hepatologist group: 126 patients followed up and treated consistently by non-hepatologists, and 3) the other group: 220 patients either followed up by hepatologists and treated by non-hepatologists, or vice versa, or those identified to have tumors incidentally without any follow-up. To confirm the clear difference between generalists and specialists, the gender ratio, age, hepatitis B and C virus markers, serum alpha-fetoprotein level, tumor size, the number of tumors, Child's grade, portal thrombosis at the initial detection, the types of follow-up until the initial detection of hepatocellular carcinoma, the initial treatments chosen, and survival were compared between the hepatologist group and the non-hepatologist group. RESULTS: There were no statistically significant differences between the two groups with respect to gender ratio, age, hepatitis virus markers and the alpha-fetoprotein level. However, the tumor size, the number of tumors, Child's grade and portal thrombosis at the initial detection were more advanced in the non-hepatologist group, which was most likely due to the poorer follow-up until the detection of hepatocellular carcinoma compared with that in the hepatologist group (p value: 0.0237). Regarding therapy for hepatocellular carcinoma, intensive therapies were more often performed in the hepatologist group and, in addition, non-treated cases were less frequently found in the hepatologist group. Consequently, the 1-, 3- and 5-year survivals of the patients in the hepatologist group were 84.7, 61.1 and 35.1%, respectively, which were significantly longer than those in the non-hepatologist group, which were 80.7, 45.8 and 31.8%, respectively (p value: 0.0434). CONCLUSIONS: Hepatocellular carcinoma patients with cirrhosis who were treated by hepatologists can expect to obtain a longer survival because hepatocellular carcinoma tends to be detected at a smaller size, while such patients also usually receive more appropriate treatment modalities.

MRI of clear cell hidradenoma.

Clear cell hidradenoma is a rare benign skin appendageal tumor whose imaging findings have been even more rarely reported. We experienced a large clear cell hidradenoma of the left elbow in a 22-year-old man. MRI revealed a complex solid and cystic appearance with enhancing solid component.

Trends in clinical characteristics, treatment and prognosis of hepatocellular carcinoma.

BACKGROUND/AIMS: This study was undertaken to evaluate the serial changes of various factors in patients with hepatocellular carcinoma, including hepatitis viruses, age distribution, female-to-male ratio, size and the number of hepatocellular carcinoma tumors at initial detection, the types of treatment and survival during a 12-year period. METHODOLOGY: Seven hundred and four consecutive patients with hepatocellular carcinoma lesions observed from Jan 1989 to Dec 2000 (12 years) at the Internal Medicine Department, Saga Prefectural Hospital Koseikan were retrospectively enrolled in the study. The follow-up period was divided into four terms as follows: 1989-91, 1992-94, 1995-97 and 1998-2000. The serial changes of causal hepatitis viruses, age distribution, gender ratio, tumor size, the number of hepatocellular carcinoma tumors at initial detection, the types of treatment and survival were analyzed and compared among the four different terms. RESULTS: Regarding viral markers, the association of an HCV infection has become more predominant in hepatocellular carcinoma cases, while the ratio of hepatocellular carcinoma patients infected with HBV has decreased during this 12-year period. In addition, the rate of hepatocellular carcinoma measuring 3 cm or less in diameter or solitary hepatocellular carcinoma at initial detection has increased during the 12-year period. The female-to-male ratio has increased from 33.6% in 1989-1991, 34.8% in 1992-1994, 48.7% in 1995-1997 to 60.6% in 1998-2000, respectively. Due to increased early detection, the types of treatment for hepatocellular carcinoma have shifted from arterial interventional therapy to local ablation therapy combined with or without interventional therapy. Therefore, although the age distribution of all 704 hepatocellular carcinoma patients has shifted to slightly older ages as shown by the ages of 64.1 years old, 63.4 years old, 66.6 years old and 67.3 years old in the four terms, respectively, the survival of the patients with hepatocellular carcinoma proved to had become significantly longer than before during the 12-year period. CONCLUSIONS: Hepatocellular carcinoma patients tended to show an increased prevalence of HCV, a higher age distribution, an increasing female prevalence, an earlier detection, advanced multidisciplinary therapies and prolonged survival in the last 12 years.