Nobutaka Fujisawa

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

BackgroundColorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients.Methods/DesignThis study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation.DiscussionThis is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps.Trial registrationThis trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000006254

Characterization of Portal Vein Thrombus With the Use of Contrast-Enhanced Sonography

Objectives. To select an appropriate treatment regimen, it is essential to accurately characterize the nature of a thrombus. This study prospectively assessed the ability of contrast‐enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high‐risk patients. Methods. Fifty‐five patients (43 men and 12 women; mean age, 66 years; range, 55–83 years) with thrombi of the portal venous system were examined by power Doppler sonography and contrast‐enhanced sonography with the intravenous contrast agent SH U 508A (Levovist; Schering AG, Berlin, Germany). Of the thrombi, 40 were characterized as malignant and 15 as benign. Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast‐enhanced sonography were judged as indications of a malignant thrombus. The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated. Results. The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5% and specificity of 100%, whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100% for each. Conclusions. Contrast‐enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi.

Comparison of the effect on intragastric pH of a single dose of omeprazole or rabeprazole: Which is suitable for on-demand therapy?

Background and Aims:  An ideal medication for heartburn should have the rapid onset of action needed for on‐demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole.

Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study.

Background/Aims Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan. Methods Right-sided diverticulitis and left-sided diverticulitis patients (total of 215) were compared with respect to background, particularly obesity-related factors to identify risk factors for diverticulitis. Results There were 166 (77.2%) right-sided diverticulitis patients and 49 (22.8%) left-sided diverticulitis patients. The proportions of obese patients (body mass index ≥25 kg/m2, p=0.0349), viscerally obese patients (visceral fat area ≥100 cm2, p=0.0019), patients of mean age (p=0.0003), and elderly patients (age ≥65 years, p=0.0177) were significantly higher in the left-sided-diverticulitis group than in the right-sided-diverticulitis group. The proportion of viscerally obese patients was significantly higher in the left-sided-diverticulitis group than in the left-sided-diverticulosis group (p=0.0390). Conclusions This study showed that obesity, particularly visceral obesity, was a risk factor for left-sided diverticulitis in Japan.

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

BACKGROUND/PURPOSE Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs. METHODS Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic ducts largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations. RESULTS Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2-8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2-5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323). CONCLUSIONS The incidence of K-ras mutation may be associated with the hypersecretion of mucin.

Autoimmune pancreatitis associated with pancreatic cyst: how can we manage it?

Autoimmune pancreatitis (AIP) with cyst formation (ACF) is often refractory to corticosteroid treatment (CST).

Protein-losing gastroenteropathy and gastric polyps: successful treatment by Helicobacter pylori eradication.

day, and he was diagnosed as having protein-losing gastroenteropathy. We tried H. pylori eradication therapy for reduction of the polyps. After 1 month, an urea breath test revealed that H. pylori had been eradicated from his stomach. Two months after H. pylori eradication therapy, endoscopic examination showed that the gastric polyps were smaller in size. His body weight increased, and the serum total protein level also increased to 5.8 g/dl and the albumin concentration to 3.8 g/dl. We succeeded in treating protein-losing gastroenteropathy associated with gastric hyperplastic polyps by H. pylori eradication. Dear Sir, Protein-losing gastroenteropathy is a disease associated with excessive loss of plasma protein into the gastrointestinal tract and is caused by a wide variety of disorders. A 71-year-old man was admitted to our hospital for edema and body weight loss. His serum total protein level was 4.2 g/dl, and the albumin concentration was 2.6 g/dl. Endoscopy of the upper gastrointestinal tract showed a lot of reddish pedunculated polyps, measuring 5–20 mm in diameter, in gastric body and antrum ( fig. 1 ). Histological investigation of biopsy specimens revealed hyperplastic changes, and Helicobacter pylori was confirmed. His 1 -antitrypsin clearance was 120 ml/ Published online: May 18, 2007

Gastrointestinal: Colonic spirochetosis

Spirochetes are a heterogeneous group of motile, gram-negative bacilli. There are at least two families that have been called Spirochaetaceae and Treponemataceae. The latter family includes established human pathogens of the genera treponema, borrelia and leptospira. In relation to the former family, several members have been identified in the human colon and infestation has been called intestinal spirochetosis. These organisms are up to 10 mm in length, 0.2–0.5 mm in diameter and usually adopt a spiral or coiled form. They can be detected in rectal biopsies in 2–8% of heterosexual adults and in up to 35% of homosexual males. Whether infestation is responsible for gastrointestinal symptoms has not been clarified but, in case reports, infestation has been associated with symptoms such as diarrhea, perianal discomfort, tenesmus and rectal bleeding. The organism has also been associated with acute appendicitis. Mucosal changes at colonoscopy appear to be rare. The diagnosis is usually made by histological evaluation of colorectal biopsies. With hematoxylin and eosin stains, the luminal surface has a blue “fringe” while more striking changes can sometimes be observed with periodic acid Schiff and Warthin-Starry stains. Antibiotics that are effective in eliminating spirochetes include metronidazole and clarithromycin. Although no controlled trials of antibiotic therapy have been performed, antibiotics appear to have been helpful in at least some symptomatic patients, particularly those with human immunodeficiency virus (HIV). The patient illustrated below was a heterosexual male, aged 23 years, who was investigated because of persistent diarrhea for 3 months. Various investigations were negative including stool microscopy and culture and serological tests for syphilis, HIV and Entamoeba dysenteriae. Colonoscopy revealed patchy edema throughout the colon with areas of erythema and several small erosions (Fig. 1). Histological evaluation of colonic biopsies revealed patchy mucosal inflammation and numerous basophilic spirochetes, 5–10 mm in length, adhering to the surface epithelium (hematoxylin & eosin x400, Fig. 2). The diarrhea resolved after treatment with clarithromycin, 800 mg per day, for 10 days. At follow-up colonoscopy, the colon had a normal appearance and spirochetes were not identified in colonic biopsies.

Gastrointestinal : Gastrointestinal metastases from malignant melanoma

The incidence of malignant melanoma has been increasing in most of the world for several decades. In the USA, melanoma now accounts for approximately 4% of all diagnosed cancers. Important risk factors include the degree of exposure to ultraviolet light and a history of blistering sunburn. In addition, there are higher risks for melanoma in individuals with fair skin, red or blond hair and those with higher numbers of nevi or freckles. Most patients are cured by surgical excision of the lesion, particularly if the diagnosis is made at a relatively early stage. A minority of patients develop metastases in lymph nodes (sometimes without an identifiable cutaneous primary site) or in distant organs. The patient whose images are shown below was a 62-year-old man who, 3 months previously, had surgery for a melanoma in his left lacrimal duct. Investigations revealed metastases in his liver and lungs and he was treated with chemotherapy. Endoscopy was performed because of the development of abdominal pain. There were numerous small lesions in the body and antrum of the stomach that were either dark brown or black in color (Fig. 1). One of the larger lesions had the appearance of a small submucosal neoplasm with minor central necrosis (Fig. 2). Although many cancers have preferred sites for metastases, malignant melanoma has the unusual ability to spread to almost any organ in the body including the gastrointestinal tract. Metastases can be small and multiple as in this case but other patients have a small number of larger metastases that may result in occult blood loss, intussusception and/or bowel obstruction. Although most patients with metastatic melanoma have a poor prognosis, those with a limited number of gastrointestinal metastases should be considered for bowel resection as a minority have prolonged survival.

Magnetic resonance elastography increases usefulness and safety of non-invasive screening for esophageal varices: Non-invasive screening for esophageal varices

The Baveno VI criteria enable non‐invasive screening for esophageal varices. However, these criteria were established based on studies examining a large proportion of patients with viral hepatitis and relatively few patients with non‐alcoholic fatty liver disease (NAFLD). Furthermore, because vibration‐controlled transient elastography (VCTE) has a high incidence of measurement error, improved criteria are needed. We aimed to develop criteria based on magnetic resonance elastography (MRE) even among patients with NAFLD.