A novel biomarker TERTmRNA is applicable for early detection of hepatoma.

BACKGROUNDS: We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course. METHODS: In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies. RESULTS: hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers. CONCLUSIONS: hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.

Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma.

Currently available tumor markers for hepatocellular carcinoma (HCC) are alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-gamma-carboxy prothrombin (DCP). However, their positive rate can not surpass abdominal ultrasonography (US) as modalities to detect small HCC at early stage, resulting in a possible delay of its diagnosis. There is a need to develop an additional sensitive marker to improve the early detection of HCC. We here introduced a newly developed quantitative detection method for serum hTERT mRNA, which has a clinical significance in HCC diagnosis. Briefly, we examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical parameters. Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression independently correlated with clinical parameters such as differentiation degree (p < 0.001). The sensitivity/specificity of hTERT mRNA in HCC diagnosis showed 88.2/70.0%. hTERT mRNA proved to be expectedly superior to AFP mRNA , AFP and DCP in HCC diagnosis. Importantly, hTERT mRNA in serum correlated with that in HCC tissue. Thus, we report that serum hTERT mRNA is a novel and available marker for HCC diagnosis.

Comparison between ulinastatin and gabexate mesylate for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a prospective, randomized trial.

BACKGROUND: It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis. METHODS: Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150,000 units) or gabexate mesylate (600 mg), beginning 60-90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain. RESULTS: The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis. There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups. CONCLUSIONS: There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence of post-ERCP pancreatitis.

Factors regulating tumor pressure in cases of small hepatocellular carcinoma.

BACKGROUND/AIMS: There is scare information regarding tumor pressure in hepatocellular carcinoma. As the tumor diameter increases, histological manifestations become more diverse. Therefore, studies based on relatively small tumors are needed in order to search for those underlying factors that are directly related to tumor pressure in hepatocellular carcinoma. The purpose of this study was to determine which factors regulate tumor pressure in cases of hepatocellular carcinoma where the diameter of the tumor is 3cm or less. METHODOLOGY: The study included 54 patients with small hepatocellular carcinoma in whom tumor pressure had been determined and in whom the tumor had been confirmed histologically. Tumor pressure was determined percutaneously under ultrasonographic guidance. RESULTS: Hepatic tissue pressure (p = 0.01), tumor size (p < 0.01), number of tumors (p = 0.01), degree of tumor differentiation (p < 0.01), ultrasonographic halo (p < 0.01), angiographic tumor staining (p < 0.01) and angiographic tumor vessel (p = 0.03) all showed significant correlation with tumor pressure. Multivariate analysis revealed that angiographic tumor staining (p = 0.001), hepatic tissue pressure (p = 0.013), and tumor size (p = 0.044) were significant factors associated with tumor pressure. CONCLUSIONS: It was suggested that tumor pressure in small hepatocellular carcinoma was mainly regulated through development of the neovasculature.

Abnormal pancreatic imaging in Crohn's disease: prevalence and clinical features.

BACKGROUND: This study aimed to delineate the incidence and the clinical features of abnormal pancreatic imaging in patients suffering from Crohn's disease. METHODS: The subjects of this retrospective study were 255 patients with Crohn's disease who were treated at our unit and who were followed-up for more than 3 years. RESULTS: Sixteen of the 255 Crohn's disease patients (6.3%) had morphological abnormalities of the pancreas. The cumulative incidence of abnormal pancreatic imaging as a complication of Crohn's disease was 5.2% at 5 years and 6.3% at 10 years after the initial diagnosis of Crohn's disease. Four of the patients with Crohn's disease already showed abnormal pancreatic imaging at the initial examination. Morphological examinations of the pancreas showed that none of the sixteen suffered from severe conditions. The abnormal pancreatic imaging was unrelated to the therapeutic regimens employed for Crohn's disease or to its activity. When patients with Crohn's disease with and without abnormal pancreatic imaging were compared, there were no significant differences in any of the background clinical features of Crohn's disease. When we compared pancreatic imaging according to the type of Crohn's disease, in the solely aphthous ulcerations type, the occurrence of abnormal pancreatic imaging was significantly higher (P = 0.02) than that in the other types. In 7 patients who had suffered from Crohn's disease for more than 10 years, the clinical course of abnormal pancreatic imaging was not progressive, regardless of the progression of Crohn's disease. CONCLUSIONS: It is suggested that abnormal pancreatic imaging is not serious a complication of Crohn's disease, and is unrelated to the course of Crohn's disease.

Three-dimensional computed tomography pancreatography of an annular pancreas with special reference to embryogenesis.

OBJECTIVES: Several hypotheses have been proposed to explain the embryogenesis of an annular pancreas. Three-dimensional (3D) imaging of the annular pancreas may be useful to elucidate the embryogenesis. The aim of this case report is to clarify the pancreatic ducts in the annular pancreas by 3D computed tomography pancreatography (3D-CTP), stereographically. METHODS: Three-dimensional CTP under endoscopic retrograde pancreatography using a balloon catheter was performed with a helical CT scanner. Three-dimensional images of the pancreatic duct were obtained with simple threshold, shaped surface display. RESULTS: Wirsung duct that surrounds the ventral side of the descending portion of the duodenum and Santorini duct that surrounds the dorsal side of the descending portion of the duodenum were reconstructed by 3D-CTP, stereographically, and the presence of an annular pancreas was confirmed. These findings suggest that the formation of the annular pancreas in the current case may be attributable not only to abnormal development of the right lobe of the ventral pancreatic bud, but also to overgrowth of the dorsal pancreatic bud toward the ventral aspect of the duodenum or excessive rotation of the duodenum following fusion of the ventral bud to the dorsal bud. CONCLUSION: Three-dimensional CTP is expected to contribute usefully toward clarifying the embryogenesis of an annular pancreas.

Usefulness of tumor pressure as a prognostic factor in cases of hepatocellular carcinoma where the diameter of the tumor is 3 cm or less.

BACKGROUND: The current study was designed to determine the usefulness of pretreatment tumor pressure as a new prognostic factor in patients with small hepatocellular carcinoma (HCC; 3 cm or smaller in diameter). METHODS: The study included 39 patients with small HCC in whom tumor pressure was determined. They underwent percutaneous ethanol (with Lipiodol) injection therapy (Lp-PEI) or transcatheter arterial embolization (TAE) of the hepatic artery. Tumor pressure was determined percutaneously under ultrasonographic guidance. The factors analyzed were age, gender, mean blood pressure, the presence/absence of antibody to hepatitis C virus (anti-HCV), alcohol abuse, Child's classification, the presence/absence of esophagogastric varices, serum alpha-fetoprotein (AFP) level, tumor size, number of tumors, degree of tumor differentiation, the presence/absence of tumor capsule, tumor pressure, and the method of treatment. Multivariate analysis using Cox proportional hazards model was conducted on the factors that may have affected prognosis (P < 0.25) according to the univariate analysis using a proportional hazards model. RESULTS: The rates of local and distant recurrence were higher (P < 0.01, P < 0.01, respectively) and the survival rate was lower (P = 0.03) in patients with high tumor pressure than in those with low tumor pressure. Multivariate analysis revealed that tumor pressure (P < 0.01), AFP level (P = 0.01), and age (P = 0.01) were significant predictive factors associated with local recurrence. Tumor pressure (P < 0.01) and AFP level (P < 0.01) were both significantly associated with distant recurrence. The only significant predictive factor associated with survival rate was tumor pressure (P < 0.04). CONCLUSIONS: The current study revealed that tumor pressure was associated significantly with survival rates after Lp-PEI or TAE in patients with small HCC. There were also significant predictive factors associated with local recurrence, these being tumor pressure, AFP level, and age, and with distant recurrence, namely, tumor pressure and AFP level. Tumor pressure measured before the initial treatment of patients with small HCC may be a useful new prognostic factor.

M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan.

Mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) tumor suppressor- gene mutation is an early event in human hepatocellular carcinoma (HCC) formation in the United States, but its role in hepatocarcinogenesis in Japan is unclear. We therefore determined M6P/IGF2R mutation frequency in HCCs from patients who resided in the southern, central, and northern regions of Japan. Ten single nucleotide polymorphisms were used to identify HCCs and dysplastic liver nodules with M6P/IGF2R loss of heterozygosity. The retained allele in these tumors was also assessed for point mutations and deletions in the M6P/IGF2R ligand binding domains by direct sequencing of polymerase chain reaction (PCR) amplified DNA products. Fifty-eight percent (54 of 93) of the patients were heterozygous at the M6P/IGF2R locus, and 67% (43 of 64) of the HCCs and 75% (3 of 4) of the dysplastic nodules had loss of heterozygosity. The remaining allele in 21% of the HCCs contained either M6P/IGF2R missense mutations or deletions, whereas such mutations were not found in the dysplastic lesions. In conclusion, M6P/IGF2R is mutated in HCCs from throughout Japan with a frequency similar to that in the United States. Loss of heterozygosity in dysplastic liver nodules provides additional evidence that M6P/IGF2R haploid insufficiency is an early event in human hepatocarcinogenesis.