Seigo Sakaguchi

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

BackgroundIt 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.MethodsSixty-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.ResultsThe 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.ConclusionsThere 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.

Effects of the Japanese herbal medicine 'Inchinko-to' (TJ-135) on concanavalin A-induced hepatitis in mice.

Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-gamma was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.

Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis.

Interleukin-12 (IL-12) is an important cytokine for maintainence of normal systemic defense and bioregulation. The Japanese herbal medicine Sho-saiko-to (TJ-9) has been administered to 1.5 million Japanese patients with chronic liver diseases. TJ-9 is known to significantly suppress cancer development in the liver and has macrobiotic effects. In the present study, we examined the in vitro production of IL-12 by circulating mononuclear cells from liver cirrhosis patients and the effects of TJ-9 on IL-12 production. The monocyte/macrophage fraction and the lymphocyte fraction of peripheral blood were obtained from 11 HCV-positive liver cirrhosis patients and 12 healthy subjects. Interleukin-12 levels in the supernatants were measured using ELISA kits. The levels of IL-12 produced by the patients fractions were significantly lower than those produced by healthy subjects (p < 0.01, p < 0.05). However, when TJ-9 was added to the cultures, the IL-12 production levels in both cell fractions increased approximately three fold, and the levels from the monocyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ-9 was attributable to two of its seven herb components, that is, scutellaria root and glycyrrhiza root. One possible mechanism for the macrobiotic effects of TJ-9 on liver cirrhosis patients may be the improvement in IL-12 production.

A novel biomarker TERTmRNA is applicable for early detection of hepatoma

BackgroundsWe previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and des-γ-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.MethodsIn 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.ResultshTERTmRNA 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.ConclusionshTERTmRNA 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 α-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-γ-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.

Influence of hepatitis b virus infection and age on mode of growth of hepatocellular carcinoma

According to the extent of hepatic involvement of the tumor and that of portal vein invasion at the time of initial diagnosis, patients with hepatocellular carcinoma (HCC) were grouped into three or four groups. Correlations among the extent of hepatic involvement, extent of portal vein invasion, and prevalence of hepatitis B surface antigen (HBsAg) and age distribution were examined. The extent of hepatic involvement of the tumor and that of portal vein invasion were significantly greater in patients with positive HBsAg compared with findings in the negative patients (P < 0.001). For cases of both positive and negative HBsAg, patients with a more extensive HCC were significantly younger. Results of the multivariate logistic regression analysis showed that hepatitis B antigenemia and younger age were statistically significant and independent positive predictors of extensive HCC. These results strongly suggest that hepatitis B surface antigenemia and age play an important role in the growth mode and the kinetics of HCC in Japanese patients.

Reversibility of pulmonary telangiectasia in liver cirrhosis evidenced by serial dynamic pulmonary perfusion imaging

Pulmonary perfusion Imaging with Tc-99m MAA revealed significant uptake in the lungs, brain, spleen, and both kidneys of a 48-year-old woman with liver cirrhosis and pulmonary telangiectasia associated with marked hypoxemia and cyanosis. Dynamic pulmonary perfusion imaging revealed a gradual reduction after peak uptake in both lungs. Several weeks after albumin replacement, the hypoxia and dyspnea disappeared with no change in hepatocellular function. At that time, dynamic pulmonary perfusion imaging revealed a plateau-like time-activity curve of uptake in the lungs, as compared with the findings obtained during the state of severe hypoxemia. These observations suggest that pulmonary teleangiectasia in a patient with liver cirrhosis may be due to functional vasodilatation. Serial dynamic pulmonary perfusion imaging indicates the passage of the MAA particles through the widened lumen of the pulmonary alveolar capillaries.

Detection of pulmonary teleangiectasia using dynamic pulmonary perfusion imaging in patients with liver cirrhosis

Two cases of liver cirrhosis associated with marked hypoxemia are presented. Chest radiographs and cardiopulmonary function showed no abnormalities, except for the low diffusion capacity of carbon monoxide and slight elevation of the shunt ratio (20 and 6.2%, respectively), as estimated under conditions of 100% oxygen inhalation. Pulmonary perfusion imaging with Tc-99m macroaggregated albumin (MAA) revealed a significant radioisotope uptake in the lungs, brain, spleen, and both kidneys. Shunt ratios, estimated by the quantitative radionuclide method, were 60 and 68%, respectively. Dynamic pulmonary perfusion imaging revealed a gradual reduction in uptake in all areas of both lungs. The discrepancy of the shunt ratio between the two methods results from an abnormal dilatation of alveolar capillaries. The gradual reduction of radioactivity In areas of the lungs is caused by the passage of MAA particles through widened pulmonary capillaries.

Effects of the Japanese herbal medicine ‘Sho-saiko-to’ as a cytokine inducer

The herbal medicine, Sho-saiko-to (TJ-9), has been widely prescribed to chronic viral liver disease patients in Japan. This study examined the inductions of such sytokines as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and granulocyte-colony stimulating factor (G-CSF), on some fractions of peripheral blood mononuclear cells (PBMC) by TJ-9 and each of its seven components. IL-1β, TNF-α, and G-CSF were highly induced by scutellaria root and glycyrrhiza root on monocytes/macrophages. By repeating the same experiments using taxol (an LPS antagonist)-treated substances, authors confirmed that these inductions were not attributable to the presence of quite low LPS in TJ-9 solution, and the cytokine inductions are the specific effect of TJ-9. Because TJ-9s macrobiotic effect in liver cirrhosis patients has been proven statistically in an etiological study, TJ-9 could be a new important therapy in chronic liver diseases.

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.