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Biomedical subjects

Ichiro Yasuda

Publications and source records attributed to Ichiro Yasuda.

18 recordsLinked to original sources

Volvulus of the gall bladder diagnosed by ultrasonography, computed tomography, coronal magnetic resonance imaging and magnetic resonance cholangio-pancreatography.

A 54-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Upon physical examination the vital signs of the patient were within normal ranges. Ultrasonography and computed tomography (CT) examination of the abdomen was obtained, which demonstrated a large dilatated cystic structure, measuring approximately 68.6 mm multiply 48.6 mm, with marked distension and inflammation. Additionally, the enhanced CT was characterized by the non-enhanced wall of the gallbladder. As the third examination in this study, magnetic resonance imaging (MRI), namely coronal MRI and magnetic resonance cholangio-pancreatogra (MRCP), were performed. The MRCP demonstrated a dilatation of the gallbladder but detected no neck of the gallbladder. Simple cholecystectomy was performed. Macroscopic findings included a distended and gangrenous gallbladder, and closer examination revealed a counterclockwise torsion of 360 degrees on the gallbladder mesentery. Coronal MRI and MRCP showing characteristic radiography may be useful in making a definitive diagnosis.

Cholangiopancreatography, Magnetic Resonance↗

Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. Updated analysis of the long-term follow-up data.

Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid's effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive alpha-fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration.

Antineoplastic Agents↗

[The best choice of biliary stents in hilar distal strictures due to inoperable malignacies].

Recently, the treatment using biliary stents play an important role to improve the quality of life (QOL) in patients with inoperable malignant biliary obstruction. Long-term patency is preferable, but the convenience of treatment for stent obstruction should also be considered. In this study, we investigated which stent is currently the most appropriate in hilar and extrahepatic bile duct obstruction. In hilar obstruction, metallic stents (MS) had significantly longer patency than plastic tube stents (TS). As for extrahepatic bile duct obstruction, covered MS (CMS) and MS had significantly longer patency than TS. On the other hand, many difficulties occurred when the MS was obstructed. In some of these patients, it was difficult to place the internal drainage again and their QOL was severely impaired. CMS was more convenient because it could be removed when it was obstructed. These results may suggest that MS should be used carefully in the hilar obstruction and that CMS is the best for the treatment of extrahepatic bile duct obstruction.

Biliary Tract Neoplasms↗

Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate.

BACKGROUND: The treatment of pancreatic fistula can be difficult. A novel endoscopic approach to sealing pancreatic fistulas by using N-butyl-2-cyanoacrylate is described. METHODS: Twelve patients with pancreatic fistulas underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, in addition to endoscopic drainage. RESULTS: Fistulas were closed successfully in 8 of 12 patients. A single treatment session was successful in 7 patients; a second session was required in one patient. In two patients, closure was temporary, and, in one patient, the treatment failed. One patient died 24 hours after treatment. He developed a pulmonary thromboembolism from a left popliteal vein thrombosis and died from complications of surgical thromboembolectomy. At autopsy, a pulmonary embolus was found, but there was no evidence of N-butyl-2-cyanoacrylate in the lungs. No procedure-related complication occurred over a median follow-up of 20.7 months (range 9-51 months). CONCLUSIONS: In this preliminary study, occlusion of pancreatic fistulas by using N-butyl-2-cyanoacrylate glue was safe and effective, and obviated the need for surgery in a substantial proportion of patients. Further studies of the use of N-butyl-2-cyanoacrylate for closure of pancreatic fistula are warranted.

Adult↗

EUS-guided FNA of the left adrenal gland in patients with thoracic or GI malignancies.

BACKGROUND: The diagnostic yield and safety of trans-gastric EUS-guided FNA of the left adrenal gland are not well defined. METHODS: All patients with an enlarged left adrenal gland on abdominal imaging and known or suspected malignancy referred to two EUS centers over a 3-year period were included in this study. EUS-guided FNA was performed on an outpatient basis by one of 4 experienced endosonographers. RESULTS: Thirty-one consecutive patients (21 men, 10 women; mean age 64.8 years) were evaluated. Tissue adequate for interpretation was obtained in all patients; no attempt to obtain tissue was unsuccessful. The median number of needle passes was 4.5 (range 1-8). No immediate complications were encountered. EUS-guided FNA confirmed malignant left adrenal involvement in 42% (13/31) of the patients. Patients with malignant left adrenal masses were more likely to have known cancer at another site (OR 12.0: 95% CI[1.6, 87.9]). Patients with benign masses were more likely to have preservation of the normal sonographic appearance of the adrenal gland ("seagull" configuration) compared with those with malignant masses (OR 9.8: 95% CI[1.9, 51.0]). The accuracy of EUS imaging based on size (> or =3 cm) alone was 81%: 95% CI[63, 93]). Of the patients with malignant adrenal masses, 85% (11/13) died or their clinical condition deteriorated during follow-up, while 15% (2/13) were being treated and were stable clinically. CONCLUSIONS: EUS-guided FNA of the left adrenal gland is a minimally invasive, safe, and highly accurate method that confirms or excludes malignant adrenal involvement in patients with thoracic or GI malignancies.

Adrenal Gland Neoplasms↗

[Enantiomeric determination of ephedrine derivatives in unregulated drugs using capillary electrophoresis].

Capillary electrophoresis (CE) was applied to enantiomeric separation of chiral ephedrine derivatives (d/l-ephedrine, d/l-methylephedrine, d/l-pseudoephedrine, and d/l-norephedrine) in unregulated drug products. Unregulated drugs, referred to as dietary supplements in U.S.A., have been used legally as tonic agents, but illegal substances such as ephedrine were often detected. Baseline separation of all enantiomers of ephedrine derivatives was achieved using an electrophoretic solution containing heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DM-CD) as a chiral selector. The optimal conditions were established to be: capillary column of fused silica (50 microm i.d. x 56 cm); running buffer of 20 mM DM-CD with 50 mM potassium dihydrogenphosphate background electrolyte, pH 2.6; capillary temperature of 20 degrees C; applied voltage of 30 kV; on-column detection at 195 nm; and injection pressure of 50 mbar x 3 s. Under these conditions, all four pairs of enantiomers were sufficiently resolved, and eight peaks were observed with resolution factors of greater than 1.5. The calibration curves of all enantiomers showed good linearity over the concentration range of 2.5-10 microg/ml (r =0.999). The present method was used in a survey of marketed products. The resultant chiral contents were reported and the analytical data were also compared with those from HPLC. This method is useful in the simple and rapid analysis of ephedrine derivatives in marketed products.

Chromatography, High Pressure Liquid↗

Endoscopic sphincterotomy and endoscopic papillary balloon dilatation for bile duct stones: A prospective randomized controlled multicenter trial.

BACKGROUND: Endoscopic papillary balloon dilatation may be an alternative to endoscopic sphincterotomy in the treatment of bile duct stones. However, there is a controversy as to the effectiveness and safety of endoscopic papillary balloon dilatation. METHODS: Two hundred eighty-two patients with bile duct stones were enrolled and randomized to an endoscopic sphincterotomy or endoscopic papillary balloon dilatation group. The success rate for duct clearance as well as the frequency and types of complications were evaluated prospectively. Endoscopic sphincterotomy was performed in a standard manner. Endoscopic papillary balloon dilatation was carried out with gradual inflation of a 4-, 6-, or 8-mm diameter balloon. RESULTS: Complete duct clearance was achieved in 100% in the endoscopic sphincterotomy group and 99.3% in the endoscopic papillary balloon dilatation group (not significant). Complications occurred in 11.8% of patients in the endoscopic sphincterotomy group and 14.5% of those in the endoscopic papillary balloon dilatation group (not significant). No complication was severe; there was no mortality. The frequency of acute pancreatitis was higher in the endoscopic papillary balloon dilatation group than the endoscopic sphincterotomy group (respectively, 10.9% vs. 2.8%; p < 0.045). Hemorrhage occurred only in the endoscopic sphincterotomy group. CONCLUSIONS: Endoscopic sphincterotomy and endoscopic papillary balloon dilatation were approximately equal in terms of successful clearance of bile duct stones. They were also similar with respect to overall complications. Endoscopic papillary balloon dilatation is an alternative to endoscopic sphincterotomy as a treatment of bile duct stones.

Adult↗

Retinoids in liver fibrosis and cancer.

Pathobiological functions and metabolism of retinoids (vitamin A and its derivatives) in liver fibrosis and hepatocellular carcinoma (HCC) are discussed in the present review. Retinoic acid (RA, active metabolite) exacerbates liver fibrosis that is not accompanied by hepatic necroinflammation, in which RA acts directly on hepatic stellate cells (HSCs); RA enhances plasminogen activator/plasmin levels and thereby induces proteolytic activation of latent transforming growth factor-beta (TGF-beta), a strong fibrogenic cytokine, resulting in enhanced collagen production. We have developed a protease inhibitor, camostat mesilate, that suppresses TGF-beta activation and thereby inhibits the transformation of HSCs, leading to reduced matrix production by the cells. The compound is effective not only in preventing but also in reducing hepatic fibrosis in rats when administered orally. HCC is refractory to RA due to its local depletion in the tumors and also due to malfunction of its nuclear receptor, retinoid X receptor-alpha (RXRalpha) Oral supplementation of a synthetic retinoid named acyclic retinoid led to the disappearance of serum lectin-reactive alpha-fetoprotein (AFP-L3) and subsequently suppressed posttherapeutic recurrence of HCC in cirrhotic patients. These results suggest eradication of AFP-L3-producing latent malignant clones from the liver by the retinoid. We propose the concept of "clonal deletion" therapy for cancer chemoprevention, a new category of cancer chemotherapy.

Animals↗

Acyclic retinoid induces partial differentiation, down-regulates telomerase reverse transcriptase mRNA expression and telomerase activity, and induces apoptosis in human hepatoma-derived cell lines.

BACKGROUND/AIMS: Acyclic retinoid (AR; all trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid) prevented hepatocarcinogenesis in animal models and in a randomized clinical trial by eradicating premalignant and latent malignant clones of transformed cells from the liver. We investigated the possible mechanism of this clonal deletion at the cellular level. METHODS: Human hepatoma-derived cell lines, PLC/PRF/5, HuH-7, and JHH-7, were treated in vitro with AR. Secretion of albumin and that of lectin-reactive isoform of alpha-fetoprotein (AFP-L3) were measured as markers of differentiation and dedifferentiation of the cells, respectively. Telomerase reverse transcriptase (TERT) mRNA expression and telomerase activity were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and stretch PCR assay, respectively. Caspase activities were measured by colorimetric protease assay. Mitochondrial membrane permeability transition was examined by Rhodamine staining. RESULTS: Production of albumin was recovered while that of AFP-L3 was reduced after exposure of the cells to 10 microM AR for 2 days. This differentiation was maintained for another 2 days without retinoid. In parallel, both TERT mRNA expression and telomerase activity were down-regulated. The cells subsequently died due to apoptosis after 4-6 experimental days. Serial increases in mitochondrial membrane permeability and caspase-9 and -3 activities induced apoptosis. CONCLUSIONS: AR first induces differentiation and reduces telomerase activity. Subsequent apoptosis may contribute to the eradication of the clone.

Alitretinoin↗

Synergistic induction of apoptosis by acyclic retinoid and interferon-beta in human hepatocellular carcinoma cells.

Acyclic retinoid, a synthetic retinoid analog, as well as interferon alfa (IFN-alpha) and IFN-beta induce apoptosis in hepatocellular carcinoma (HCC) cells and are used clinically in the prevention of HCC. Here, we show that acyclic retinoid acts synergistically with IFNs in suppressing the growth and inducing apoptosis (as characterized by DNA fragmentation and chromatin condensation) in 5 human HCC cell lines (JHH7, HuH7, PLC/PRF/5, HLE, and HLF). This synergism was only observed when cells were pretreated with the acyclic retinoid, whereas natural retinoic acids (all-trans and 9-cis retinoic acid) were ineffective. This promotion may be due to up-regulation of type 1 IFN receptor (IFNR) expression by the retinoid. Accordingly, incubation with antitype 1 IFNR antibody abolished the synergy. Enhanced IFNR expression was accompanied by increased expression and DNA-binding activity of STAT1, an intracellular signal transducing molecule of IFNR, and increased induction of 2', 5'-oligoadenyl-5'-triphosphate synthetase, which is a target gene of STAT1. Acyclic retinoid did not have any effects on the growth of normal human hepatocytes (Hc) probably because of a lack of IFNR and STAT1 up-regulation. In conclusion, these results provide a rationale for combined biochemoprevention of HCC using acyclic retinoid and IFN-beta.

Antineoplastic Agents↗

Free radical scavenging activity of propolis.

We investigated the radical scavenging activity of propolis by ESR spectroscopy using spin trapping method. In addition, we examined the influence of a diet of 2% propolis on mice under oxidative stress. At low concentrations, the methanolic extract of propolis exhibited strong scavenging activity in vitro towards both the superoxide anion radical, generated by the hypoxanthine-xanthine oxidase reaction, and the NO radical, generated from the mixture of NOC-7 (NO generator) and carboxy-PTIO (spin trapping agent). An inhibitory effect of propolis on lipid peroxidation in vivo was observed, as determined by measurement of thiobarbituric acid-reactive substances in mouse liver homogenate. The level of vitamin C in the brain of mice under oxidative stress significantly increased compared with control mice under atmosphere, which was not observed in the mice given 2% propolis. The level of alpha-tocopherol in the brain of mice given 2% propolis significantly increased compared with control mice under atmosphere, which was not observed in mice under oxidative stress. SOD activity in the brain and plasma of mice given 2% propolis significantly decreased under atmosphere and oxidative stress compared with control mice. These results suggest that propolis possesses potent antioxidant activity in vitro and in vivo.

Animals↗

Thick-section half-Fourier rapid acquisition with relaxation enhancement MR cholangiopancreatography: effects of i.v. administration of gadolinium chelate.

OBJECTIVE: Our purpose was to investigate the effects of i.v. administration of gadolinium chelate on thick-section MR cholangiopancreatography performed with half-Fourier rapid acquisition with relaxation enhancement sequence. SUBJECTS AND METHODS: Unenhanced and enhanced MR cholangiopancreatograms obtained in 50 consecutive patients were quantitatively analyzed with region-of-interest measurements and were qualitatively evaluated by three independent radiologists unaware the patient information. A phantom study was performed to verify the effects. RESULTS: The mean contrast-to-noise ratios of the gallbladder, common bile duct, and main pancreatic duct significantly increased after gadolinium chelate administration (p < 0.005). The mean depiction score of the main pancreatic duct increased significantly with one radiologist (p < 0.05) and marginally with another (p < 0.06), and the mean depiction scores of the background structures and renal pelvis significantly decreased with all three radiologists (p < 0.001). The phantom study showed the results, indicating that T2- and T2(*)-shortening effects of gadolinium chelate caused the effects in vivo. CONCLUSION: i.v. administration of gadolinium chelate improves the depiction of pancreaticobiliary ducts in some selected patients, while decreasing the depiction in others with less frequency. There may be a value of enhanced MR cholangiopancreatography when unenhanced MR cholangiopancreatography is not sufficient.

Adult↗

[A new combination therapy with low-dose FP and daily oral administration of low-dose etoposide--a report of 2 cases].

We report 2 patients with advanced gastric cancer treated with a new combination chemotherapy of low-dose FP and daily oral administration of low-dose etoposide. Patient 1 was an 84-year-old man. He was diagnosed with cancer of the remnant stomach with multiple liver metastases. For eight months, he was treated as an outpatient and his performance status (PS) stayed at stage 1. Patient 2 was a 67-year-old man with lymph node metastasis of the lung. For the first 6 weeks, he was treated under hospitalization and for the following 10 months he was treated as an outpatient. His PS remained in stage 1 and blood CEA value fell from 2,420 ng/ml to 46.9 ng/ml. Upper gastrointestinal series showed a recovery of the extension of his lower gastric body. Both cases were so-called prolonged NC. From the viewpoint of patient QOL, this new combination is a possible candidate for a more effective chemotherapy.

Adenocarcinoma↗