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Biomedical subjects

K Wakasa

Publications and source records attributed to K Wakasa.

At least 19 recordsLinked to original sources
PubMed2005

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression.

We previously reported the beneficial effects of combination therapy of interferon (IFN)-alpha/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumour thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than double the number of patients relative to the original report, and evaluates the role of IFN-alpha/type 2 interferon receptor (IFNAR2) expression on the response to the combination therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least two courses of IFN-alpha/5-FU without major complication. In the 55 patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27 (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was detected in nine out of 13 (69.2%) patients. There was significant difference in the time-to-progression survival (P = 0.0002) and the overall survival (P < 0.0001) between IFNAR2-positive and -negative cases. There was a significant correlation between IFNAR2 expression and response to IFN-alpha/5-FU combination therapy in univariate analysis (P = 0.0070). IFN-alpha/5-FU combination therapy is a promising modality for advanced HCC with tumour thrombi in the major portal branches and could significantly depend on IFNAR2 expression.

Adult↗
PubMed2005

Efficacy of Helicobacter pylori eradication on the chronic mucosal inflammation of the remnant stomach after distal gastrectomy for early gastric cancer.

Although eradication of Helicobacter pylori (Hp) after early gastric carcinoma has been recommended, very limited studies have been reported and the method differs from standard therapy. Here, we attempted the eradication of Hp in the remnant stomach after surgery for primary gastric cancer with the standardized method. We examined efficacy and the safeness of the treatment. Thirty-three H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based triple therapies. After eradication, endoscopic and histological changes were classified on the basis of the Updated Sydney System. The eradication rate in the remnant stomach was 90.9% (30 out of 33 cases) after triple therapy. Temporal minor side effects were notified in 3 cases. After eradication, the remnant stomach showed significant decreases in inflammation- and activity-scores. Moreover, significant improvement in glandular atrophy to normal mucosa was found. In conclusion, PPI-based standard therapy is just as effective for Hp eradication in the remnant stomach than it is in the non-operative stomach. Eradication therapy could be performed safely and resulted in a significant improvement in inflammation and atrophy of the mucosal layer in the remnant stomach after early gastric cancer surgery.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Development of malignant glioma 15 months after anterior temporal lobectomy in a patient with temporal lobe epilepsy.

We report a 36-year-old woman, who had previously undergone anterior temporal lobectomy for intractable temporal lobe seizures; fifteen months later, magnetic resonance (MR) images showed a space-occupying lesion in the temporal lobectomy cavity. After a second operation, a histopathological examination showed a grade III astrocytoma. The fortuitous co-occurrence of temporal lobe epilepsy and a tumour was suspected, but histopathological and immunohistochemical examination of original resected temporal lobe parenchyma did not show evidence of neoplasm. The patient had not undergone postoperative radiotherapy and had not experienced viral infections. We propose that two factors possibly associated with the development of glioma were chemical exposure from anticonvulsant agents and trauma from resection of the anterior temporal lobe during initial surgery.

Adult↗
PubMed2003

Pathological significance of oxidative cellular damage in human alcoholic liver disease.

AIMS: To investigate the pathological significance of oxidative stress-induced lipid peroxidation and oxidative DNA damage in alcoholic liver disease. METHODS AND RESULTS: Hepatic expression of 4-hydroxy-2'-nonenal (HNE) adducts and 8-hydroxydeoxyguanosine (8-OHdG) as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was analysed immunohistochemically and compared with histological findings in alcoholic liver disease. While no HNE adducts were observed in control livers, HNE adducts were frequently (37 of 40 cases, 92.5%) detected in alcoholic liver disease. The localization of HNE adducts was the cytoplasm of hepatocytes and sinusoidal cells in zone 3. As for 8-OHdG, 29 of 40 cases (72.5%) with alcoholic liver disease exhibited positive immunolabelling for 8-OHdG, while 8-OHdG expression was not evident in control livers. The nuclear expression of 8-OHdG was mainly detected in the hepatocytes within the areas of active inflammation. Among histological parameters, the grade of necro-inflammation activity as well as the presence of Mallory bodies were significantly associated with the expression of HNE adducts and 8-OHdG. In addition, the severity of steatosis also correlated with HNE adduct expression. CONCLUSIONS: Lipid peroxidation and oxidative DNA damage occur widely and may be associated with certain pathological features in human alcoholic liver disease.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Clinicopathological significance of hypoxia-inducible factor-1alpha expression in human pancreatic carcinoma.

AIMS: The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) plays a key role in the cellular adaptation to hypoxia and the activation of several genes that have been implicated in tumour growth. The aim of this study was to investigate the clinicopathological significance of HIF-1alpha expression in pancreatic carcinoma. METHODS AND RESULTS: We investigated HIF-1alpha expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF-1alpha expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over-expression of HIF-1alpha was frequently (29 of 49 cases, 59.2%) detected in pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%), whereas HIF-1alpha expression was almost absent in non-cancerous pancreatic tissues. HIF-1alpha expression was significantly associated with tumour size (P = 0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II versus stage IV, P = 0.027). Moreover, HIF-1alpha expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo-angiogenesis (P = 0.038), but not with apoptosis. CONCLUSIONS: HIF-1alpha may play a critical role in the progression of pancreatic carcinoma.

Adenocarcinoma, Papillary↗
PubMed2002

Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma.

Malignant transformation of a mature cystic teratoma of the ovary is rare, that of an adenocarcinoma is extremely rare. A 32-year-old woman was suspected as having a malignant transformation of her mature cystic teratoma of the ovary because the preoperative level of carcinoembryonic antigen (CEA) was extremely high. Resections of her ovarian cysts were performed, and this particular tumor was histopathologically diagnosed as an adenocarcinoma arising from a mature cystic teratoma of the left ovary. Because adenocarcinomas arising from mature cystic teratomas of the ovary are extremely rare, we report this case with a review of some of the literature.

Adenocarcinoma↗
PubMed2002

Endoscopic resection of a cavernous haemangioma of the stomach.

A lesion, suspected, from the endoscopic appearance, to be an isolated gastric haemangioma was incidentally detected in a 66-year-old male. At follow-up endoscopy, 5 years later, tumour size had increased and its appearance had changed with respect to previous examinations. On endoscopic ultrasonography, the tumour was solid and confined mainly to the submucosal layer of the gastric wall. Examination of biopsy specimens failed to provide any useful information. After biopsy, tumour size and the area of reddish discoloration decreased and endoscopic ultrasonography revealed multiple small cystic lesions in the tumour. Endoscopic resection was then performed with complete excision of the tumour without complications or recurrence. Pathological examination of resected tissue demonstrated cavernous haemangioma of the stomach.

Aged↗
PubMed2001

Clonal analysis of hepatocellular carcinoma and dysplastic nodule by methylation pattern of X-chromosome-linked human androgen receptor gene.

To investigate the monoclonality of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) and the origin of multiple lesions, patterns of inactivation of X-linked human androgen receptor gene were studied. Fourteen of 15 patients (93%) were heterozygous in the size of the target, and were informative for clonal analysis. Monoclonal composition was demonstrated in all 17 HCCs and two DNs, whereas all non-cancerous hepatic tissues were polyclonal. Of four patients with more than two lesions of HCC or DN, two patients had two lesions with different patterns of X-chromosome inactivation, indicating that the two lesions were multicentric in origin.

Adult↗
PubMed2001

Elevated expression of UDP-N-acetylglucosamine: alphamannoside beta1,6 N-acetylglucosaminyltransferase is an early event in hepatocarcinogenesis.

Previous reports have suggested that changes in oligosaccharide structures, especially beta1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:alpha mannoside beta1,6 N-acetylglucosaminyltransferase (GnT-V), are linked to tumor metastasis and invasion. In the present study, we investigated GnT-V expression in human hepatocellular carcinoma (HCC) tissues. High expression of GnT-V mRNA was observed in both HCC and the surrounding tissues but not in normal liver. Immunohistochemical study using a newly established monoclonal antibody against GnT-V revealed that positive staining of GnT-V was observed in 75% of HCC tissues and 60% of surrounding tissues and that liver cirrhosis showed much stronger staining of GnT-V than chronic hepatitis without liver cirrhosis (p = 0.0035). In contrast, all of 12 cases of atypical adenomatous hyperplasia diffusely expressed GnT-V. beta1-6 branching in N-glycans, products of GnT-V, was increased in HCC tissues with high expression of GnT-V, as judged by lectin blotting. Levels of GnT-V expression in HCC tissues were positively correlated with a low Ki-67 labeling index (p = 0.0009), small size (p < 0.0001), poor differentiation (p < 0.0001) and absence of portal invasion (p = 0.018). Furthermore, HCC cases with low or no expression of GnT-V were more likely to show recurrence than cases with high expression (p = 0.0373). These findings strongly suggest that GnT-V expression is concerned mainly with an early phase of hepatocarcinogenesis.

Aged↗
PubMed2001

A case of leiomyoma of the breast.

Leiomyomas are common in the genitourinary and gastrointestinal tracts and less frequent in skin and soft tissue. It is quite uncommon for them to develop in the breast, especially in the breast parenchyma. Only 12 cases of leiomyoma in the breast parenchyma proper apart from the areola have been reported. We present a thirteenth case, the first to be reported in Japan. Its clinical features, mammographic and ultrasonographic findings, histological and immunohistochemical characteristics are quite consistent with previous reports.

Breast Neoplasms↗
PubMed2001

Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer.

BACKGROUND: The development of a second primary cancer in the gastric remnant after gastrectomy for early gastric carcinoma is a problem, and eradication of Helicobacter pylori after the operation has been recommended. However, to date, practical indications for H. pylori eradication after gastric cancer surgery have not yet been reported. METHODS: We examined H. pylori infection in the gastric remnant after distal gastrectomy for primary gastric cancer. One hundred and nine patients who had had a gastrectomy were studied. Endoscopic findings and results from the urease test, bacteriologic assessment, serological test, and histopathological examination were analyzed. RESULTS: Seventy-one patients (65.1%) were judged to be positive for H. pylori infection. The prevalence of H. pylori infection was found to be significantly decreased in older patients, patients in whom the operation had been performed a long time before examination, patients with symptoms, and patients with severe reflux gastritis. On the other hand, histologically, chronic and acute gastritis correlated significantly with H. pylori infection. H. pylori prevalence was highest in mildly atrophic mucosa and decreased with more extensive atrophic changes of the mucosa. CONCLUSIONS: The persistence of H. pylori-related active gastritis in the gastric remnant after gastric cancer surgery was suggested in younger patients with mild atrophic gastritis and without reflux gastritis. These patients may be the best candidates for H. pylori eradication therapy.

Adult↗
PubMed2001

The value of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls.

This study was conducted to assess the diagnostic potential and pitfalls of performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We retrospectively analyzed 1,012 aspirated samples obtained from 806 thyroid nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had been surgically treated, 152 (67%) of which were histologically diagnosed as malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a diameter of less than 5mm (73%, P = 0.10); either calcified (77%, P = 0.043) or benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate diagnosis was 16%, the false negative rate was 13%, and the positive malignancy rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008, and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy was improved to 81% by repeating the procedure. These findings indicated that repeated aspiration may be a simple and effective method of improving the diagnostic potential of FNAC.

Adenocarcinoma, Follicular↗
PubMed2001

Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype.

BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.

Carcinoma, Hepatocellular↗
PubMed2001

In situ detection of oxidative DNA damage, 8-hydroxydeoxyguanosine, in chronic human liver disease.

BACKGROUND/AIMS: 8-Hydroxydeoxyguanosine (8-OHdG) is a promutagenic DNA lesion produced by oxygen radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. METHODS: Hepatic expression of 8-OHdG was immunohistochemically investigated in control and diseased human livers. RESULTS: While no positive immunolabeling for 8-OHdG was observed in control livers, 8-OHdG was widely evident in diseased livers. Nuclear expression of 8-OHdG in the hepatocytes and bile duct cells were found in various forms of chronic hepatitis. 8-OHdG-positive hepatocytes were especially abundant in the periportal area with piecemeal necrosis and prominent cell infiltration. The number of positive hepatocytes significantly increased with the progression of severity of chronic hepatitis activity (r(s)=0.68, P<0.05). In alcoholic liver disease, nuclear expression of 8-OHdG was detected in the hepatocytes in the area of alcoholic hepatitis. Regarding primary biliary cirrhosis, 8-OHdG was preferentially detected in the nuclei of injured bile ducts (11 of 12 cases, 91.7%) and occasionally (2 of 12 cases, 16.7%) in the nuclei of hepatocytes around the bile duct lesions. CONCLUSIONS: These results indicate that oxidative DNA damage is common in various forms of chronic liver disease suggesting a possible link between chronic inflammation and hepatocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Heterogeneity of hepatic parenchymal enhancement on computed tomography during arterial portography: quantitative analysis of correlation with severity of hepatic fibrosis.

Background/Aims: In patients with chronic liver disease, heterogeneous enhancement of liver parenchyma is often noted on computed tomography during arterial portography (CTAP). We investigated the factors contributing to the heterogeneous enhancement and its relationship with postoperative histopathological findings. Methodology: Eighty-seven patients who had undergone a right lobectomy for liver tumor after CTAP were evaluated. The heterogeneity of hepatic parenchymal enhancement on CTAP was assessed quantitatively using standard deviation of mean CT numbers for five ROIs (S.D.) set in the right hepatic lobe, and comparatively evaluated among three histological groups (liver cirrhosis (LC, n=41), chronic hepatitis (CH, n=33), and normal liver (Normal, n=13)). Severity of fibrosis and degree of splenomegaly (Sp) were taken up as factors contributory to the heterogeneity, and were assessed for correlation with the S.D. Results: The range (mean) of S.D. was LC, 3.07-17.64 (9.10); CH, 1.83-11.12 (6.77); and Normal, 2.06-8.89 (5.64) (Scheffe's F-test: LC vs CH, P<0.0005; LC vs Normal, P<0.0002). The higher fibrosis group exhibited significantly greater S.D. values as compared with the lower fibrosis group (Scheffe's F-test: P<0.00003). Coefficient of correlation between the S.D. and the Sp was 0.295 (P<0.005). Conclusion: There was a fair possibility of LC in patients with heterogeneous enhancement of liver parenchyma on CTAP. The severity of liver fibrosis and the degree of splenomegaly were considered to be factors contributing to the heterogeneous enhancement.

Journal Article↗
PubMed2001

Previous or occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma without hepatic fibrosis.

We investigated the role of hepatitis B virus infection in development of hepatocellular carcinoma in hepatitis C virus-infected patients without hepatic fibrosis. Of 253 patients, 8 lacked hepatic fibrosis (group 1); group 2 included the remaining 245 patients. Clinicopathologic findings were compared between the groups. Hepatitis B x gene was sought in cancers and adjoining noncancerous liver. Group 1 showed better liver function parameters and milder active hepatitis than group 2. The proportion of patients with anti-hepatitis B virus antibody tended to be higher in group 1 than in group 2. The proportion of patients with hepatitis B x RNA in cancers was significantly higher in group 1 than in group 2. All group 1 patients had previous or occult hepatitis B virus infection. Previous or occult hepatitis B virus infection may be critical in development of hepatocellular carcinomas in hepatitis C virus-infected patients without hepatic fibrosis.

Aged↗
PubMed2001

Frequent loss of heterozygosity at 1p36.3 and p73 abnormality in parathyroid adenomas.

Although 1p is one of the most common loci showing loss of heterozygosity (LOH) in primary parathyroid adenoma, fine mapping has not been previously examined. In this study, we analyzed LOH in 32 primary parathyroid adenomas using five microsatellite markers at 1p36 (proximal-D1S507-D1S450-D1S2893-D1S468-D1S243-distal). All cases were heterozygous for at least one marker. The frequency of LOH varied from 41.2% (D1S468) to 7.1% (D1S507) among the different markers. LOH was detected consistently in a group of nine adenomas (28.1%, 9/32). A single region (7 cM) showing a consistent LOH at 1p36.3 was obtained that was flanked distally by D1S468 and proximally by D1S2893. Because the p73 gene is localized within this region and acts as a tumor suppressor gene, we examined the possible involvement of p73 in the development of parathyroid tumor. Allelic loss of p73 was identified in four adenomas (25%, 4/16 informative cases) that were all from the group of the nine adenomas with LOH, but somatic mutation was not detected in the remaining allele. At the StyI polymorphism of Exon 2, four of the six adenomas with LOH at 1p36 were heterozygous and expressed the GC allele. Of the six heterozygous adenomas without LOH, 4 showed biallelic and 2 monoallelic expressions (GC allele). All adenomas mainly expressed the p73alpha isoform. p73 protein was observed in five of the six adenomas with LOH and in two of the six adenomas without LOH. There were no differences in p73 protein levels between the samples with and without LOH. In conclusion, a candidate gene for parathyroid tumorigenesis is present within a 7-cM region at 1p36.3, however p73 is unlikely to be the target of the LOH at 1p36.3.

Adenoma↗