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Biomedical subjects

Takahiro Uenishi

Publications and source records attributed to Takahiro Uenishi.

At least 19 recordsLinked to original sources
PubMed2006

Influence of interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma.

Influence of interferon (IFN) therapy on postoperative outcomes in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is still inconclusive. Of 518 patients who underwent hepatic resection for HCV-related HCC, 312 patients with Japan integrated staging score 0-2 were included in this study. Of 50 patients underwent IFN therapy, 29 patients who obtained a normalized alanine aminotransferase (ALT) activity irrespective of disappearance of serum HCV RNA were classified as the response group, while 21 patients were classified as the non-response group because their ALT activities were not normalized and serum HCV RNA persisted. The non-IFN group included 262 patients who had not received IFN therapy. The tumor-free and the overall survival rates for patients in the response group were significantly higher than those in other groups. Only one patient in the response group died of HCC recurrence, and the proportion of deaths associated with liver disease (HCC recurrence or cirrhosis) was significantly lower in the response group than other two groups. IFN therapy can improve postoperative outcomes in patients with HCV-related HCC because of suppression of recurrence and preventing progress of cirrhosis, especially when IFN therapy has controlled their active hepatitis.

Journal Article↗
PubMed2006

High serum concentrations of Sialyl Lewisx predict multilevel N2 disease in non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to analyze the clinical significance of serum Sialyl Lewisx (SLX) concentrations as a predictor of N2 disease in patients with non-small-cell lung cancer. METHODS: The study included 272 patients with non-small-cell lung cancer who underwent pulmonary resection in our institution between January 1998 and December 2003. Of 272 patients, the serum concentrations of SLX were measured by using a commercially available radioimmunoassay kit. RESULTS: The 5-year survival rates of patients with concentrations of SLX > 38 U/mL and those with lower concentrations were 32% and 69%, respectively (P < .0001). The median serum concentration of SLX in patients with multilevel N2 or N3, single-level N2, and N0/1 disease were 44, 30, and 27 U/mL, respectively. The concentrations of serum SLX in patients with multilevel N2 disease were significantly higher than those in patients with single-level N2 or those with N0/1 disease (Mann-Whitney U-test; P < .0001). Although the sensitivity of SLX for identifying patients with non-small-cell lung cancer was only 24% in all patients, the sensitivity of SLX increased as the N-factor increased; the sensitivity of N0/1 disease was 15%, that of single-level N2 disease was 22%, and that of multilevel N2 or N3 disease was 71%. CONCLUSIONS: High serum concentrations of SLX predicted multilevel N2 disease and the associated poor outcome. Although the sensitivity of serum SLX is not acceptable for use as a screening tumor marker, we suggest that the serum concentration of SLX is useful as a staging marker to determine the strategy of treatment.

Adenocarcinoma↗
PubMed2006

Clinicopathologic characteristics of hepatitis C virus-associated intrahepatic cholangiocarcinoma.

BACKGROUND: Although hepatitis C virus (HCV) infection is a possible pathogenetic factor for intrahepatic cholangiocarcinoma (ICC), clinicopathologic features of ICC patients with HCV infection remain unclear. PATIENTS AND METHODS: Of 50 patients with ICC treated, 19 were infected with HCV (HCV-positive group) and 38 underwent surgical treatment. Clinicopathologic features and postoperative outcome were compared between patients with and without HCV infection. RESULTS: In 15 patients in the HCV-positive group, ICC was detected during follow-up for chronic hepatitis C. The proportion of patients who underwent curative resection was significantly higher in the HCV-positive than in the HCV-negative group, and tumors were significantly smaller in the HCV-positive than in the HCV-negative group. In the HCV-positive group, tumors were significantly smaller in patients who were followed up for chronic hepatitis C than in patients who were not followed up. Although cumulative survival rates did not differ significantly between groups, prognoses of patients with small ICC were significantly better than those with large ICC. CONCLUSION: Follow-up for patients with chronic hepatitis C by imaging series at regular intervals is important and provides the possibility to detect a small ICC as well as a hepatocellular carcinoma. Resection should be guided by liver function and the tumor stage in patients with HCV-associated ICC.

Adult↗
PubMed2006

Clinical significance of serum cytokeratin-19 fragment (CYFRA 21-1) in hepatocellular carcinoma.

BACKGROUND/PURPOSE: CYFRA 21-1, a soluble fragment of cytokeratin 19, is increased in serum in some patients with hepatocellular carcinoma, but the clinical significance of this increase is still unknown. METHODS: Serum concentrations of CYFRA 21-1 were measured in 240 patients with hepatocellular carcinoma prior to hepatic resection. The relationships between serum CYFRA 21-1 concentrations and clinicopathologic features were analyzed. RESULTS: The sensitivity of CYFRA 21-1 as a test for hepatocellular carcinoma was 18.8%. Serum CYFRA 21-1 was significantly higher in patients with portal vein tumor thrombus, and serum CYFRA 21-1 increased with the progression of portal vein tumor thrombus. Tumor size was related to serum CYFRA 21-1, but there were no significant correlations between serum CYFRA 21-1 concentrations and tumor differentiation or number of tumors. Although patients with stage IV tumor had significantly higher CYFRA 21-1 concentrations than those with stages I, II, and III, CYFRA 21-1 was not associated with postoperative prognosis. CONCLUSIONS: Although high concentrations of CYFRA 21-1 were often detected in patients with a tumor diameter greater than 5 cm or tumor thrombus in the major portal vein, CYFRA 21-1 is not a useful diagnostic tool for hepatocellular carcinoma because of its low sensitivity.

Adult↗
PubMed2006

Clinicopathological implications of immunohistochemically demonstrated mucin core protein expression in hepatocellular carcinoma.

METHODS: We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group). RESULTS: MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358). CONCLUSIONS: In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC.

Adult↗
PubMed2006

Immunohistochemical demonstration of c-Kit protooncogene product in gallbladder cancer.

BACKGROUND/PURPOSE: Although some gallbladder carcinomas are immunoreactive for c-Kit, the reasons for the c-Kit expression and its clinicopathologic implications are unknown. METHODS: We investigated the prevalence of c-Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c-Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM-based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c-Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma. RESULTS: Cytoplasmic immunostaining for c-Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c-Kit positivity; however, there were no significant differences in the incidence of c-Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c-Kit-positive gallbladder carcinoma compared with c-Kit-negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19. CONCLUSIONS: Gallbladder carcinomas positive for c-Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.

Adult↗
PubMed2005

Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma.

AIM: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. METHODS: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. RESULTS: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. CONCLUSION: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

Analysis of Variance↗
PubMed2005

Serosal invasion in TNM staging of mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND/PURPOSE: The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer. METHODS: Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors. RESULTS: By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV. CONCLUSIONS: Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.

Adult↗
PubMed2005

Prognostic effects of causative virus in hepatocellular carcinoma according to the Japan integrated staging (JIS) score.

BACKGROUND: The Japan integrated staging (JIS) score is recognized to be useful in managing hepatocellular carcinoma (HCC). We evaluated the effects of the causative virus in patients stratified by this system. METHODS: We compared clinicopathologic features, cumulative and tumor-free survival rates, and causes of death between 301 hepatitis C virus-positive patients (HCV group) and 60 hepatitis B virus-positive patients (HBV group). RESULTS: Among patients with low JIS scores (0 or 1), the proportions of patients with high aspartate and alanine aminotranferase activities, moderate-to-severe active hepatitis, and with cirrhosis were significantly higher in the HCV than in the HBV group. Among patients with high JIS scores (2 to 4), the proportion with moderate-to-severe active hepatitis was also significantly higher in the HCV group. In patients with low JIS scores, those in the HCV group had significantly lower tumor-free and cumulative survival rates than those in the HBV group. Although no patient in the HBV group died of causes other than liver disease (HCC or hepatic failure), some patients in the HCV group died of causes other than liver disease. The proportion of patients who died because of HCC recurrence tended to be higher among patients with high JIS scores than among patients with a low JIS score. CONCLUSIONS: The effects of viral status on survival outcomes are greatest in patients with JIS scores of 0 or 1.

Carcinoma, Hepatocellular↗
PubMed2005

Clinicopathologic features and outcome after liver resection for hepatocellular carcinoma in patients with concurrent versus previous chronic hepatitis B.

PURPOSE: We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B. METHODS: Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome. RESULTS: The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors. CONCLUSION: Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.

Age Distribution↗
PubMed2005

Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: Immunohistochemical evidence.

Hypothesizing that combined hepatocellular and intrahepatic cholangiocellular carcinoma originates from hepatic stem cells, we conducted a series of immunohistochemical studies using hepatic stem cell markers to better understand the origin of the tumor. Specially, we investigated 15 combined tumors confirmed to be immunoreactive to anti-hepatocyte paraffin 1, and anti-cytokeratin 7 and 19 antibodies. Macroscopic investigation revealed cancer cells morphologically intermediate between neoplastic hepatocytes and cholangiocytes (combined tumor with intermediate morphology) in 11 of 15 tumors. The remaining four tumors lacking these cells were considered ordinary combined tumors. We used 20 hepatocellular carcinomas and 10 cholangiocarcinomas as controls. Immunohistochemical analysis was performed using stem cell markers (c-kit and CD34). Of the 15 combined tumors, 8 stained for c-kit (2 of the 4 ordinary tumors and 6 of the 11 intermediate morphologic tumors). Both of the tumor cell types in both of the ordinary combined tumors stained for c-kit. The c-kit staining was present in cells of all three morphologic types, including the intermediate cells, in all six of the intermediate combined tumors. None of the cells in the combined tumors showed immunoreactivity for CD34. None of the 30 control tumors expressed CD 34 or c-kit. The present study suggests that combined hepatocellular and intrahepatic cholangiocellular carcinomas originate not from a hepatic stem cell, but from a hepatic precursor cell, such as the canal of Hering cell. Alternatively, these tumors might show up-regulation of c-kit in relation to angiogenesis.

Journal Article↗
PubMed2005

Surgical management of bilateral adrenal metastases from hepatocellular carcinoma after transcatheter arterial embolization.

Despite progress in therapy for hepatocellular carcinoma, management of extrahepatic metastatic lesions remains problematic. A 73-year-old man who underwent transcatheter arterial embolization for hepatocellular carcinoma presented bilateral adrenal metastases. Ten months after transcatheter arterial embolization, computed tomography detected huge tumors in both adrenal glands. Simultaneous resection of both adrenal lesions was performed under hydrocortisone replacement therapy. These tumors were confirmed histopathologically to represent adrenal metastatic lesions of hepatocellular carcinoma. The patient died of respiratory failure due to lung metastasis 9 months after adrenalectomy, although intrahepatic tumor was controlled by transcatheter arterial embolization. It is necessary to clarify the therapeutic effectiveness and the indication of adrenalectomy for patients with adrenal metastasis.

Adrenal Gland Neoplasms↗
PubMed2004

Clinicopathologic characteristics of small intrahepatic cholangiocarcinomas of mass-forming type.

We investigated the clinicopathologic characteristics of and outcome after treatment for small intrahepatic cholangiocarcinomas of mass-forming type (3cm or smaller) in nine patients to study appropriate treatment. In seven of the nine patients, the cancer was detected during follow-up for hepatitis C virus-related disease. One patient was seropositive for anti-hepatitis B core antibody alone. One patient had alcoholic cirrhosis. Three patients also had hepatocellular carcinoma. Seven patients underwent liver resection and two other patients underwent microwave coagulation therapy. In the resection specimens, no vascular or lymphatic invasion, or invasion of perineural spaces, was evident pathologically. No patient had intrahepatic metastasis or lymph node metastasis; all had hepatic fibrosis. Lung metastases developed after surgery in one patient whose surgical margin was positive for cancer. In one patient with both type of carcinoma, the hepatocellular carcinoma recurred. Screening for not only hepatocellular carcinoma but also intrahepatic cholangiocarcinoma is necessary in patients with hepatic fibrosis, especially those infected with hepatitis C virus. For small intrahepatic cholangiocarcinomas of mass-forming type located peripherally in the liver, partial resection or ablation therapy with care to obtain a negative surgical margin may be appropriate.

Journal Article↗
PubMed2004

Clinicopathologic analysis of risk factors for distant metastasis of hepatocellular carcinoma.

Background: Numbers of patients with extrahepatic metastasis of hepatocellular carcinoma (HCC) are increasing. As characteristics of HCC patients who develop distant metastasis remain uncertain, we analyzed potential risk factors. Methods: Among patients followed up after hepatic resection for HCC, we identified 31 patients with extrahepatic metastasis (extrahepatic metastasis group, EM). In 46 other patients we found intrahepatic metastasis synchronously with the primary HCC. In these patients no extrahepatic metastasis occurred during 5 years of follow-up (intrahepatic metastasis group, IM). During the 5-year follow-up period, 14 patients have remained alive with no metastasis (no metastasis group, NM). We compared age, gender, hepatitis virus infection status, grade of liver dysfunction, serum alpha-fetoprotein (AFP) concentration, tumor size, tumor differentiation, presence of portal or hepatic venous infiltration, and surgical strategy among these three groups. Results: No significant difference in clinicopathologic factors was noted among the three groups except for immunohistochemical staining for CD44. A significantly higher proportion of tumors was immunoreactive for CD44v3 in the EM group than in the other groups ( [Formula: see text] ). By multivariate analysis, CD44v3 expression (risk ratio, 9.28; [Formula: see text] ) was a significant independent risk factor for extrahepatic metastasis. Conclusion: CD44v3 expression in HCC may be a useful predictor of likelihood of distant metastasis.

Journal Article↗