Kazuhiko Tokita

L-menthol improves adenoma detection rate during colonoscopy: a randomized trial.

BACKGROUND AND STUDY AIMS Colonoscopy is one of the most reliable methods for the detection of colorectal neoplasms. However, colonic peristalsis during colonoscopy results in some neoplastic lesions being hidden from view and commonly requires an intravenous or intramuscular injection of antispasmodic agents, which may sometimes causes unexpected adverse reactions. The aim of this study was to evaluate the efficacy of L-menthol spray as an antiperistaltic agent and its effect on adenoma detection. PATIENTS AND METHODS This was a prospective, randomized, single-blind placebo-controlled trial. A total of 226 patients who were scheduled to undergo colonoscopy were randomly assigned to receive either 20 mL of 1.6 % L-menthol (n = 118) or placebo (n = 108). Both treatments were sprayed locally onto the colonic mucosa via an endoscope. The adenoma detection rate (ADR) and the proportion of patients with no peristalsis were the primary and secondary outcomes, respectively. RESULTS The ADR was significantly higher in the L-menthol group than in the placebo group (60.2 % vs. 42.6 %; P = 0.0083). The proportion of patients with no peristalsis after treatment with L-menthol was significantly higher than in the placebo group (71.2 % vs. 30.9 %; P < 0.0001). There were no adverse effects in either group. CONCLUSIONS The results suggest that the suppression of colonic peristalsis by L-menthol sprayed directly onto the colonic mucosa improves the ADR. CLINICAL TRIAL REGISTRATION ID: UMIN 000007972.

A Synthetic Prostaglandin E1 Analog, Alprostadil Alfadex, Relaxes Sphincter of Oddi in Humans

It is well established that prostaglandins (PGs) exert potent pharmacological actions on vascular and nonvascular smooth muscle, although their effects on the sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to investigate the effect of PGE1 on motility of the human SO. Twenty patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) examination were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), or alprostadil alfadex, a synthetic PGE1 analog, at a dose of either 0.05 or 0.1 μg/kg/min (seven patients for each condition). Endoscopic biliary manometry was done with a recording of basal SO pressure, amplitude of SO phasic contractions, and phasic contractile frequency before and 5 min after intravenous infusions, using a 4-French microtransducer catheter. There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure at a dose of 0.05 μg/kg/min, and significantly decreased all parameters at a dose of 0.1 μg/kg/min. A synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the human SO. This drug may be of clinical application as a SO-relaxing agent.

The critical role of the PE21 element in oncostatin M-mediated transcriptional repression of the p53 tumor suppressor gene in breast cancer cells

Cytokine oncostatin M (OM) exerts growth-inhibitory and differentiative effects on breast cancer cells. Previously we showed that the transcription from the p53 gene in breast cancer cells was down regulated by OM. To elucidate the molecular mechanisms underlying the OM effect on p53 transcription, in this study, we dissected the p53 promoter region and analysed the p53 promoter activity in breast tumor cells. We showed that treatment of MCF-7 cells with OM induced a dose- and time-dependent suppression of p53 promoter activity. The p53 promoter activity was decreased to 35% of control at 24 h and further decreased to 20% at 48 h by OM at concentrations of 5 ng/ml and higher. Deletion of the 5′-flanking region of the p53 promoter from −426 to −97 did not affect the OM effect. However, further deletion to −40 completely abolished the repressive effect of OM. The p53 promoter region −96 to −41 contains NF-κB and c-myc binding sites, and a newly identified UV-inducible element PE21. Mutations to disrupt NF-κB binding or c-myc binding to the p53 promoter decreased the basal promoter activity without affecting the OM-mediated suppression, whereas mutation at the PE21 motif totally abolished the OM effect. We further demonstrated that insertion of PE21 element upstream of the thymidine kinase minimal promoter generated an OM response analogous to that of the p53 promoter. Finally, we detected the specific binding of a nuclear protein with a molecular mass of 87 kDa to the PE21 motif. Taken together, we demonstrate that OM inhibits the transcription of the p53 gene through the PE21 element. Thus, the PE21 element is functionally involved in p53 transcription regulated by UV-induction and OM suppression.

Endoscopic transgastric drainage of a gastric wall abscess after endoscopic submucosal dissection

A 63-year-old woman was referred to our hospital for further examination because of an incidental finding of early gastric cancer. Endoscopic submucosal dissection (ESD) was successfully performed for complete resection of the tumor. On the first post-ESD day, the patient suddenly complained of abdominal pain after an episode of vomiting. Abdominal computed tomography (CT) showed delayed perforation after ESD. The patient was conservatively treated with an intravenous proton pump inhibitor and antibiotics. On the fifth post-ESD day, CT revealed a gastric wall abscess in the gastric body. Gastroscopy revealed a gastric fistula at the edge of the post-ESD ulcer, and pus was found flowing into the stomach. An intradrainage stent and an extradrainage nasocystic catheter were successfully inserted into the abscess for endoscopic transgastric drainage. After the procedure, the clinical symptoms and laboratory test results improved quickly. Two months later, a follow-up CT scan showed no collection of pus. Consequently, the intradrainage stent was removed. Although the gastric wall abscess recurred 2 wk after stent removal, it recovered soon after endoscopic transgastric drainage. Finally, after stent removal and oral antibiotic treatment for 1 mo, no recurrence of the gastric wall abscess was found.

HEPATOBILIARY SARCOIDOSIS: TYPICAL APPEARANCE IN LAPAROSCOPY

We present a case of systemic sarcoidosis. A 72‐year‐old Japanese woman, who was diagnosed with asymptomatic enlarged abdominal para‐aortic lymph nodes in April 2000, was admitted to our hospital in December 2003 because of multiple mass lesions of the liver and spleen. She had hepatosplenomegaly and asymptomatic pulmonary fibrosis. Blood examination revealed cholestasis and progressing liver synthetic dysfunction. In laparoscopic photographs, various sizes of whitish flat lesions were scattered on the surface of the liver. Liver biopsy showed non‐caseating epithelioid cell granulomas. These lesions of the spleen disappeared on contrast‐enhanced computed tomography imaging, and serum liver dysfunction was improved rapidly after steroid therapy. Laparoscopy may be useful for the diagnosis of granulomatous liver disease, such as hepatobiliary sarcoidosis.

Ischemic hepatitis induced by mesenteric volvulus in a patient with chronic obstructive lung disease

Abstract: A 66-year-old man with chronic obstructive lung disease was admitted to our hospital, presenting with mesenteric volvulus and mild liver injury. A superior mesenteric angiogram revealed that the arteries supplying the small intestine were twisted in the arterial phase, while the portal vein was not visualized in the late phase. A celiac angiogram demonstrated that portal blood flow from the splenic venous return was maintained. The patients symptoms had almost resolved the day after admission, and his serum transaminases level had gradually decreased to normal with conservative therapy. A superior mesenteric angiogram on the 13th hospital day showed a normal arteriogram and the portal vein demonstrated blood flow from the superior mesenteric vein. Liver biopsy revealed hemorrhagic necrosis around the central veins, which was compatible with ischemic hepatitis. Since the patients O2 saturation level on admission was not low enough to have caused ischemic hepatitis by itself, we suspect that a sudden decrease in portal blood flow was the additional factor that allowed the threshold for the initiation of ischemic liver damage to be reached.

6998 Effects of synthetic prostaglandins e1 and f2a on motility of the sphincter of oddi in humans.

Background/Aim: Prostaglandins (PGs), widely distributed in the human and animal gastrointestinal tract, play important roles in cytoprotection, secretion and absorbtion, and motility of the digestive tract. However, their effects on the biliary tract are not well studied. The aim of the present study is to investigate effects of PGs E1 and F2a on motility of the human sphincter of Oddi (SO). Methods: Twenty-seven patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), alprostadil alfadex, a synthetic PGE1 analogue, at a dose of either 0.05 or 0.1 μg/kg/min (seven patients for each condition), or dinoprost, a synthetic PGF2α analogue, at a dose of 1.0 μg/kg/min (seven patients). Endoscopic biliary manometry was done with a recording of basal SO pressure (mmHg), SO phasic wave amplitude (mmHg) and frequency (/min) before and 5 min after intravenous infusions, using a 4 Fr microtransducer catheter (Galtec Ltd). Values are reported as the mean±SEM. Paired Students t tests were used to compare variables before and after injection. Differences with p values of less than 0.05 were considered significant. Results: There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure and SO phasic wave frequency at a dose of 0.05 μg/kg/min and significantly decreased all parameters at a dose of 0.1 μg/kg/min, while dinoprost significantly increased only SO phasic wave frequency. Conclusion: A synthetic PGE1 analogue, alprostadil alfadex, has an inhibitory effect on motility of the human SO.This drug may be applicable to clinical use as a SO relaxing agent.

Endoscopically Treated Angiodysplasia of the Ileum

Abstract: Angiodysplasia has been recognized as one of the main causes of gastrointestinal bleeding, but few such lesions have been found, or treated by an endoscopic procedure, in the ileum. We endoscopically identified angiodysplasia in the ileum of an 85‐year‐old female who had tarry stools. Because she had severe aortic stenosis, we treated the lesion endoscopically by combining polidocanol injection and electrocoagulation with hot biopsy forceps. This method was considered to be safe and efficient, especially for lesions in the thin walled intestine.