Abstract: Apelin-APJ signalling is known to play important roles in heart physiology and pathology; however, its functions in liver physiology and pathology remain unclear. On the other hand, Fas is an important molecule in hepatitis and other liver disease that belongs to the death receptor family. The aim of this study was to assess the relationship between apelin-APJ signaling and Fas-mediated liver injury in mice.
Abstract: OBJECTIVES:Chronic intestinal pseudo-obstruction (CIPO) is a rare, serious motility disorder, with life-threatening complications over time. However, lack of an established, non-invasive diagnostic method has caused delays in the diagnosis of this intractable disease. Cine-magnetic resonance imaging (MRI) is an emerging technique, with a potential to evaluate the motility of the entire bowel. We compared small bowel motility in healthy volunteers, patients with irritable bowel syndrome (IBS), and those with CIPO, using cine-MRI, and evaluated the usefulness of cine-MRI as a novel diagnostic method for CIPO.METHODS:Twelve healthy volunteers, IBS patients, and CIPO patients prospectively underwent cine-MRI at 1.5 T. Luminal diameter, contraction ratio, and contraction cycle were measured and compared between the groups.RESULTS:Cine-MRI provided sufficient dynamic images to assess the motility of the entire small bowel. Luminal diameter (mean±s.d.) in CIPO patients was significantly higher than that in healthy volunteers and IBS patients (43.4±14.1, 11.1±1.5, and 10.9±1.9 mm, respectively), and contraction ratio was significantly lower in CIPO patients than that in healthy volunteers and IBS patients (17.1±11.0%, 73.0±9.3%, and 74.6±9.4%, respectively). No significant differences were observed in the contraction cycle.CONCLUSIONS:This study is the first to assess the clinical utility of cine-MRI in CIPO patients. Cine-MRI clearly detected contractility impairments in CIPO patients. Cine-MRI is noninvasive, radiation-free, and can directly evaluate the entire small bowel peristalsis, and can detect the affected loops at a glance; therefore, it might be extremely useful for the diagnosis and follow-up of CIPO patients in clinical practice.Am J Gastroenterol advance online publication, 19 March 2013; doi:10.1038/ajg.2013.57.
Abstract: A 75-year-old man was admitted to the hospital with a loss of consciousness. His blood glucose level was 24 mg/dL. Abdominal computed tomography revealed multiple metastatic lesions in the liver, while upper endoscopy disclosed advanced gastric cancer. The hypoglycemia was refractory despite the administration of glucose and steroid therapy. The patient died within one month of admission. An autopsy revealed neuroendocrine-type gastric cancer, which, on examination with immunohistochemistry, was found to be negative for insulin and insulin-like growth factor I and positive for insulin-like growth factor II (IGF-II). The patient was diagnosed as having gastric cancer with non-islet cell tumor hypoglycemia (NICTH) caused by IGF-II.
Abstract: Background: We estimated the prevalence and incidence of chronic intestinal pseudo-obstruction (CIPO) in Japan, investigated the patterns of hospital visits among those with CIPO, and examined present knowledge of CIPO among medical professionals.Methods: A self-administered questionnaire survey was distributed to targeted hospitals throughout Japan, which were selected using stratified random sampling. The questionnaire asked about the number of patients receiving treatment for CIPO, the frequency of their hospital visits, and overall clinical knowledge of CIPO among medical professionals.Results: CIPO prevalence was estimated to be 1.00 and 0.80 cases per 100 000 males and females, respectively. Incidence was 0.21 and 0.24 cases per 100 000 males and females, respectively. Prevalence and incidence did not significantly differ males and females. Mean age of patients was 63.1 years for males and 59.2 for females. Accurate diagnosis of CIPO sometimes required more than 3 months after initial presentation. Most medical professionals were unaware of or poorly understood CIPO.Conclusions: We estimated the prevalence and incidence of CIPO in Japan, using data from a nationwide survey. The findings suggest that knowledge of CIPO should be further disseminated so that the disease is not overlooked and is diagnosed without delay.
Abstract: The aim of this study was to verify the effectiveness of PET (positron emission tomography) or PET/CT (fusion images of PET with computed tomography) in detecting synchronous cancer in patients with head and neck carcinoma. We reviewed 682 patients with carcinoma of the head and neck between January 2001 and December 2010. In 98 patients, 111 synchronous cancers were diagnosed. Of these 98 patients, the index cancer was predominantly located in the hypopharynx (47 cases), followed by the larynx (23 cases), oropharynx (12 cases) and the oral cavity (6 cases). Esophageal cancer was diagnosed as the most synchronous cancer (57 lesions), followed by gastric cancer (20 lesions), lung cancer (9 lesions) and head and neck cancer (8 lesions). Among these 98 patients, PET or PET/CT was performed in 82 patients. Of these 82 patients, PET or PET/CT detected 34 out of 94 (36.2 %) synchronous cancers. No significant difference was observed between PET and PET/CT in terms of lesion detectability (p = 0.21). Regarding synchronous T1 and Tis upper gastrointestinal (UGI) cancer, PET or PET/CT detected 4 out of 43 (9.3 %) of the cancers. No statistical difference in detectability was observed in patients who underwent PET or PET/CT scanning before or after histological examination of synchronous UGI cancer. In conclusion, synchronous cancer was most frequently observed in the UGI, especially in the esophagus in patients with head and neck carcinoma. PET and PET/CT have limitations in the detection of these lesions.
Abstract: The aim of this study was to examine the convenience of the quality of life and utility evaluation survey technology (QUEST) questionnaire and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire as self-assessment diagnostic instrument.
Abstract: BACKGROUNDAIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the (13)C-acetic acid breath test.
Abstract: AIM: To identify the predictive factors for the presence of small bowel lesions in patients with obscure gastrointestinal bleeding (OGIB). METHODS: A total of 242 patients with OGIB (overt 149: occult 93) were retrospectively included in the present study. Capsule endoscopy (CE) was carried out to investigate the small bowel, and detected lesions were classified according to the P0-P2 system. Only P2 lesions were defined as significant lesions. Univariate and multivariate logistic regression analyses were carried out to define the predictive factors for the presence of small bowel lesions. RESULTS: In patients with overt OGIB, chronic kidney disease (CKD) ≥stage 4 (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.45-11.1, P = 0.007) was identified as an independent predictor of the presence of vascular lesions, and a history of non-steroidalanti-inflammatory drug (NSAID) use as that of erosive/ulcerated lesions (OR 4.73; 95% CI 1.47-15.2, P = 0.009). However, in patients with occult OGIB, no significant predictors of the presence of vascular lesions were identified, whereas a history of low-dose aspirin (LDA) (OR 3.57; 95% CI 1.21-10.5, P = 0.02) and proton pump inhibitor (PPI) use (OR 3.18; 95% CI 1.02-9.92, P = 0.05) were identified as independent predictors of the presence of erosive/ulcerated lesions. CONCLUSIONS: Our results indicated that bleeding pattern and clinical characteristics could contribute to predicting the origin of OGIB.
Abstract: Although many terminally ill cancer patients desire to receive medical treatment in palliative care units(PCUs or hospices), very few patients are actually able to receive such treatment. Our aim is to provide palliative care to as many people as possible. We have practiced palliative care in general wards and prioritized care according to the patient's prognosis on admission to our hospice. From April 2007 to March 2011, 87% patients were admitted to our hospital in accordance with their wishes. By adequate management of hospital wards, including PCUs, and unitizing the health resources of the area, terminally ill cancer patients may be able to spend more time at home prior to hospitalization.
Abstract: Before the introduction of capsule endoscopy and double-balloon endoscopy, there were no effective modalities for reliable evaluation of the small bowel. Recently, the SmartPill, a wireless pH/ pressure recording capsule, has been utilized to measure the whole gut transit time. However, there are few studies on the small bowel pH. The aim of this study was to investigate the relationship between small bowel disease and the small bowel pH, we designed a new modality, the 'pH capsule', to non-invasively record sequential images and the pH.
Abstract: The ideal medication for acid-related diseases should have a rapid onset of action to promote hemostasis and cause efficient resolution of symptoms. The aim of our study was to comparatively investigate the inhibitory effect on gastric acid secretion of a single oral administration of omeprazole plus mosapride with that of omeprazole alone.
Abstract: Background/Aims: Effectiveness of gastric emptying after pylorus-preserving gastrectomy (PPG) remains unclear and a method for continuous assessment is needed. We assessed post-PPG gastric emptying with a continuous real-time 13C breath test (BreathID system, Oridion, Israel). Methodology: Gastric emptying function was assessed by 13C breath test in 12 post-PPG patients and 9 post-distal gastrectomy (DG) patients. Continuous 13C-acetic acid breath test was performed using the BreathID system. Endoscopic study was also completed. Results: Diarrhea was significantly less common in PPG than DG patients (p=0.021). No other questionnaire items and endoscopic findings showed a significant difference. In the 13C-acetic acid breath test, the gastric emptying coefficient (GEC) was significantly greater in PPG than DG patients (p=0.025). No other test parameters showed a significant difference. Conclusions: Emptying function in the remnant stomach was assessed successfully by the continuous 13C-acetic acid breath test. A greater GEC suggested better gastric emptying in PPG patients.
Abstract: Recently, high serum DPP-4 activity was found in patients with NAFLD. Therefore, the possibility of NAFLD adversely influencing the therapeutic effect afforded by DPP-4 inhibitors in type 2 diabetic patients was suggested.
Abstract: Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC.
Abstract: The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress-related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H(2)-receptor antagonist, roxatidine 75 mg.
Abstract: The aim of this study was to characterize the pancreatic cystic lesions in von Hippel-Lindau (VHL) disease and to document the changes that occur in the pancreas.
Abstract: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are being used increasingly to treat superficial oropharyngeal and hypopharyngeal carcinomas. The aim of this study was to clarify whether ESD provided better results than EMR for en bloc and complete resection of superficial pharyngeal carcinomas.
Abstract: The differences in the small intestinal toxicity of low-dose aspirin based on the type of aspirin used remains unclear. The purpose of this study was to evaluate the differences in the small bowel mucosal injury between buffered and enteric-coated aspirin users by capsule endoscopy.
Abstract: Chronic intestinal pseudo-obstruction (CIPO) is an intractable disease in which clinical symptoms of intestinal obstruction appear without mechanical cause. No clear diagnostic criteria have been established; therefore, we proposed diagnostic criteria to facilitate the diagnosis of this rare disease and aim to evaluate their usefulness and validity.
Abstract: The Prague C and M Criteria have been developed for the objective endoscopic diagnosis of Barrett's esophagus (BE). BE arises between the squamocolumnar junction and the gastroesophageal junction at the proximal margin of the gastric folds. In this study, we reported that 43.0% of the subjects examined were diagnosed with BE based on the Prague C and M Criteria. Previous criticism by John Dent proposed that our data should be considered invalid because the prevalence of BE reported in our study was extraordinarily high and discordant with previous studies. Dent predicted that the position of the gastroesophageal junction in our study was judged to be lower than the actual position due to the effacement of the proximal ends of the gastric folds because of the routine use of a high degree of air distension during typical Japanese endoscopic examinations. The endoscopic evaluation of the superior gastric folds is certainly influenced by the degree of air distension of the esophagus. However, in our study, the proximal limit of the gastric mucosal folds was prospectively imaged while the oesophagus was minimally insufflated. Then, under a high level of air distension, the distal ends of the palisade-shaped longitudinal vessels were imaged because they are more easily observed when distended. In the majority of patients, the distal ends of the palisade-shaped longitudinal vessels correspond to the proximal limit of the gastric mucosal folds. Our endoscopic evaluation was appropriately performed according to the Prague C and M Criteria. We suspect that the high prevalence of BE in our study may be due to the inclusion of ultrashort-segment BE, which defines BE with an affected mucosal length under 5 mm, in our positive results.
Abstract: Oral sumatriptan administration has been reported to delay gastric emptying after liquid meals. The aim of this study was to determine whether delayed gastric emptying is caused by enhanced gastric accommodation, impaired antral contractions, or both using ultrasonography.
Abstract: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas.
Abstract: The main aim of this study was to determine whether questionnaire evaluations of clinical symptoms in gastroesophageal reflux disease were useful to assess proton pump inhibitor therapy.
Abstract: Endoscopic screening and removal of colorectal adenomas can reduce the incidence of colorectal cancer. However, given the possibility of adenoma recurrence, surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal adenomas. Aberrant crypt foci (ACF) have been shown to serve as a reliable surrogate marker of colorectal carcinogenesis. In this study, the relationship between the number of ACF at the initial endoscopic polypectomy and the likelihood of colorectal adenoma recurrence after polypectomy were investigated.
Abstract: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage.
Abstract: A case-controlled study was performed to investigate the association of colonic angiectasia with other conditions and to identify risk factors for bleeding.
Abstract: The aim of this study was to determine whether oral Itopride hydrochloride (itopride) intake might have any effect on the rate of gastric emptying, using a novel non-invasive technique for measuring the rate of gastric emptying, namely, the continuous real time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel).
Abstract: Low-dose aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases. However, administration of low-dose aspirin is associated with an increased risk of upper gastrointestinal complications, such as upper gastrointestinal erosions, ulcers and bleeding. The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal complications associated with low-dose aspirin treatment.
Abstract: Capsule endoscopy is limited by the poor image quality of the distal bowel and incomplete small bowel transit. The aim of this study was to establish an optimal medication protocol for capsule endoscopy performed using a real-time viewer.
Abstract: This study examines the effect of systemic chemotherapy with gemcitabine (GEM) on survival in elderly patients (aged > or =70 years) with unresectable biliary tract cancer and compares it with best supportive care (BSC).
Abstract: The incidence of Clostridium difficile infection (CDI) has increased throughout the world and patients with ulcerative colitis (UC) are at a high risk for CDI. Potentially, CDI can exacerbate UC. Therefore, knowledge on the prevalence of CDI should contribute to better management of UC patients.
Abstract: Ideally, medications for the treatment of acid-related diseases should have a rapid onset of action to promote hemostasis and the resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of lafutidine alone or combined with peppermint oil.
Abstract:   The diagnostic use of magnification endoscopy with narrow-band imaging (ME-NBI) to assess histopathologically undifferentiated-type early gastric cancers (UD-type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME-NBI images and histopathological findings in UD-type EGCs.
Abstract: The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low-dose aspirin (LDA) using a CE scoring index.
Abstract: A 19-year-old Japanese male with a BMI of 55.4 kg/m(2) who also had liver dysfunction, dyslipidemia and hyperuricemia underwent repeated intragastric balloon therapy. The percent excess weight loss was 22.5% at the first balloon removal and 28.6% at the second balloon removal. The hepatic dysfunction resolved after the second balloon therapy, however, the dyslipidemia and hyperuricemia did not improve. The Japanese population is regarded as a high-risk race for obesity-related diseases at lower BMI values, and morbidly obese Japanese patients may need more serious weight reduction protocols to improve the comorbidities than similarly obese Americans or Europeans.
Abstract: Liver abscess is recognized as a life-threatening disease. However, even in recent years, approximately 50% of liver abscess cases are considered to be cryptogenic. Here, we report a case of liver abscess associated with periodontal bacterial infection by Fusobacterium necrophorum, which is commonly found in the oropharyngeal flora. A 36-year-old man presented with fever and contrast-enhanced abdominal computed tomography revealed multiple liver abscesses. F.necrophorum was isolated from oral smears, liver aspirates and blood samples. Liver abscesses caused by periodontal bacterial infection are rare, however, the incidence is expected to increase in the future, as periodontitis is extremely common and is on the rise as one of the most common chronic infections in the world. A systemic survey including periodontitis may be required for the exact diagnosis of the source of infection.
Abstract: Pretreatment with a proton pump inhibitor (PPI) reportedly decreases the efficacy of Helicobacter pylori (H. pylori) eradication, however, the effect of pretreatment with an H2 receptor antagonist (H2RA) on H. pylori eradication has not yet been studied. We compared the efficacy of eradication regimen (lansoprazole/amoxicillin/clarithromycin) in patients with H. pylori infection with or without H2RA pretreatment.
Abstract: It still remains controversial whether simple obesity, as measured by the body mass index (BMI), is an independent risk factor for Barrett's esophagus (BE). Recent studies have shown abdominal obesity, as defined by the waist circumference (WC) and the waist-to-hip ratio (WHR), to be a risk factor for BE, independent of the BMI, with the association between BMI and BE being no longer observed after adjustment for the WC and WHR. Moreover, visceral obesity, as directly measured by the surface area of the visceral adipose tissue (VAT) on abdominal CT images, has also been reported to have an association with the risk of BE. In addition to the mechanical effects of abdominal obesity, that is, increase of the intra- abdominal pressure by the large amount of adipose tissue, circulating factors secreted from the VAT, such as tumor necrosis factor-α, interleukin-6, leptin, and adiponectin, have also been proposed to be pathogenetically linked to BE and esophageal adenocarcinoma. Obesity is associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal obesity, especially visceral obesity. This raises several questions regarding the pathogenesis of obesity-related BE. Larger studies with prospective enrollment of patients are required for further examination of this issue.
Abstract: Differentiation of sclerosing cholangitis-associated autoimmune pancreatitis (SC-AIP), primary sclerosing cholangitis (PSC) and cancer of the hilar part of the bile duct (CHB) has been challenging. The aim of the present study was to evaluate characteristic intraductal ultrasonography (IDUS) features that could be used to discriminate SC-AIP from PSC and CHB.
Abstract: Expression of the forkhead/winged helix family of transcription factor P3+ regulatory T cells (FOXP3(+) Treg), a master gene of regulatory T cells (Treg) is observed in patients with autoimmune pancreatitis (AIP). We investigated the usefulness of detection of FOXP3(+) Treg in the main duodenal papilla for differential diagnosis between AIP and pancreatic cancer (Pca).
Abstract: Although sporadic nonampullary duodenal adenoma (SNDA) is regarded as a precancerous lesion, its natural course is uncertain. The aim of this study was to evaluate the risk of development of adenocarcinoma in SNDA lesions initially diagnosed as showing low-grade dysplasia (LGD; category 3) or high-grade dysplasia (HGD; category 4.1).
Abstract: The possible role of leptin in colorectal tumors has been investigated in previous studies; however, to date, the conclusions remain under debate. Therefore, we investigated the serum leptin levels in colorectal adenoma patients. In addition, expression of the leptin receptor, and the leptin receptor-mediated signaling pathways were investigated in biopsy specimens collected from human patients with colorectal adenoma. No significant difference in the mean serum leptin level was observed between the colorectal adenoma patients and the control subjects; however, increased expression and activation of the leptin receptor, as indicated by findings such as the phosphorylation of Tyr 1141, was observed in the colorectal adenoma tissues. In addition, activation of the JAK/STAT signaling pathway mediated by the leptin receptor and increased transcriptional regulation of downstream target molecules were observed in colorectal adenomas compared with the non-adenoma tissues. These results indicate STAT3-mediated leptin receptor signaling pathways may be activated in human colorectal adenomas.
Abstract: The factors involved in the progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH) are not fully understood and thus it is urgently needed to elucidate these factors. Steatosis is not causal in the development of NASH, but rather it sensitizes the liver to the damaging effects of second hits such that stressors innocuous to a healthy liver lead to the development of NASH in the steatotic liver. In the previous study, most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, very-low-density lipoprotein (VLDL) synthesis, especially hepatic microsomal triglyceride transfer protein (MTP) mRNA expression, was impaired in the NASH group. Moreover, NASH showed significantly higher incidence of minor alley appearance compared with NAFL, indicating the possibility of association between NASH pathogenesis and decreased congenital MTP activity. MTP is one of the enzymes that transfer triglycerides to nascent apolipoprotein B, producing VLDL and removing lipid from the hepatocyte. A growing body of literature suggests that the measurement of hepatic MTP expression may be helpful for diagnosis; and moreover, hepatic MTP activator may be a possible therapeutic agent for the treatment of NASH.
Abstract: A visceral fat area of more than 100 cm2 as measured by computed tomography (CT) at the umbilical level has been included as a criterion for obesity in all the proposed criteria for metabolic syndrome. However, CT cannot be used frequently because of radiation exposure. We evaluated the usefulness of measurement of the serum levels of nitric oxide (NO), instead of CT and the waist circumference, as a marker of abdominal visceral fat accumulation.
Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury, and is considered as the hepatic manifestation of metabolic syndrome. However, no effective drug therapy for NAFLD has been established yet. In the present study, we evaluated the efficacy of 4 months of treatment with sitagliptin in NAFLD patients with type 2 diabetes mellitus (DM).
Abstract: This study examined the effect of systemic chemotherapy with gemcitabine (GEM) on survival in elderly patients (aged > or = 70 years) with unresectable biliary tract cancer as compared with best supportive care (BSC).
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, for which the development of new biomarkers and therapeutic targets has become critical. The main cause of poor prognosis in PDAC patients is the high invasive and metastatic potential of the cancer. In the present study, we report a new signaling pathway that was found to mediate the enhanced tumor cell motility in pancreatic cancer. Semaphorin 4D (Sema4D) is a ligand known to be expressed on different cell types, and has been reported to be involved in the regulation of immune functions, epithelial morphogenesis, and tumor growth and metastasis. In this study, we revealed for the first time that the cancer tissue cells expressing Sema4D in PDAC are tumor-infiltrating lymphocytes. The overexpression of Sema4D and of its receptor, plexinB1, was found to be significantly correlated with clinical factors, such as lymph node metastasis, distant metastasis, and poor prognosis in patients with PDAC. Through in vitro analysis, we demonstrated that Sema4D can potentiate the invasiveness of pancreatic cancer cells and we identified the downstream molecules. The binding of Sema4D to plexinB1 induced small GTPase Ras homolog gene family, member A activation and resulted in the phosphorylation of MAPK and Akt. In addition, in terms of potential therapeutic application, we clearly demonstrated that the enhanced-cell invasiveness induced by Sema4D could be inhibited by knockdown of plexinB1, suggesting that blockade of plexinB1 might diminish the invasive potential of pancreatic cancer cells. Our findings provide new insight into possible prognostic biomarkers and therapeutic targets in PDAC patients.
Abstract: Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, characterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross appearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated with two independent rectal cancers extending into the submucosal layer. We speculate that long-standing MPS may increase the risk of malignant transformation.
Abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse mucosal inflammation, traditionally regarded as being limited to the colorectum. Although several gastroduodenal lesions have also been reported recently in cases of UC, in general, small-bowel lesions in UC are believed to be extremely rare. The aim of this study was to examine the small bowel by capsule endoscopy in patients with UC.
Abstract: The role of percutaneous endoscopic gastrostomy(PEG)in palliative care has not been well discussed. With the evolution of endoscopic techniques and PEG devices, we can perform PEG more safely, even in difficult cases. Actually, PEG is very useful in home care of cancer patients. We should discuss the indications of PEG in the field of palliative medicine. We suggest the following indications for PEG: 1.Difficulty in ingestion of sufficient quantities of food and water because of pain on swallowing, or an obstruction caused by cancer. 2.Normal gastrointestinal function. 3.Expected survival time of more than four weeks in addition to absence of cachexia. 4.Patient's consent for PEG.
Abstract: Duodenal variceal rupture is rare, and there is little agreement on the best therapeutic option. A 72-year old man treated for liver cirrhosis with HCV visited the emergency room complaining of dizziness and tarry stool. Fiberscope images showed varices (F2CbRC+) with white plaques at the horizontal region of the duodenum. The patient was treated using endoscopic variceal ligation (EVL), and no more bleeding has been detected.
Abstract: The administration of liquid nutrients to patients is often accompanied by complications such as gastroesophageal reflux. To prevent gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it still remains controversial whether high-viscosity liquid meals have any effect on the rate of gastric emptying. The present study was conducted with the aim of determining whether high-viscosity liquid meals had any effect on the rate of gastric emptying and mosapride might accelerate the rate of gastric emptying of high-viscosity liquid meals.
Abstract: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous (13)C breath test (BreathID system, Exalenz Bioscience Ltd, Israel).
Abstract: Although the majority of patients with Mallory-Weiss syndrome (MWS) have a benign course, in some patients MWS results in a fatal outcome. Therefore, this study was carried out to analyze the risk factors for mortality in patients with MWS.
Abstract: Few studies have investigated measures to prevent small bowel injuries induced by aspirin. Our aim was to evaluate the effect of probiotic treatment on the small bowel injuries induced by chronic low-dose aspirin use.
Abstract: To determine the correlation between domperidone and gastric emptying using the continuous real time 13C breath-test (BreathID system), a novel non-invasive technique for measuring gastric emptying.
Abstract: The immunochemical faecal occult blood test (IFOBT) is widely performed for colorectal cancer screening, but the usefulness of IFOBT in the detection of disorders of the small intestine is unknown. The objective of this study was to investigate what proportion of IFOBT-positive subjects with negative colonoscopy and oesophagogastroduodenoscopy has pathologies of the small intestine detected by capsule endoscopy (CE).
Abstract: ABSTRACT: Introduction A hamartomatous polyp without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome is diagnosed as a solitary Peutz-Jeghers type hamartomatous polyp. As compared with Peutz-Jeghers Syndrome, Peutz-Jeghers type hamartomatous polyps are diagnosed with a lower risk of cancer and are regarded as a different disorder. Case presentation In case one, we describe an 84-year-old Japanese man with a 14mm duodenal polyp. Endoscopic mucosal resection was performed and histological examination showed findings suggestive of a hamartomatous polyp with a focus of well-differentiated adenocarcinoma. In case two, we describe a 76-year-old Japanese man who had been treated for prostate, rectal and lung cancer. Upper gastrointestinal endoscopy revealed a duodenal polyp measuring 15mm in diameter. Endoscopic mucosal resection was performed, and histological examination showed findings suggestive of a hamartomatous polyp. Liver and thyroid cancers were found after the endoscopic treatment. Conclusion Although duodenal solitary hamartomatous polyps are associated with a lower risk of cancer, four patients, including our cases, have been diagnosed with cancerous polyps. Patients with duodenal solitary hamartomatous polyps should be treated by endoscopic or surgical resection and need whole-body screening.
Abstract: There are few reports on the correlation between chewing gum and the gastrointestinal functions. But previous report showed use of chewing gum to be an effective method for controlling gastrointestinal symptoms. The aim of this study was to determine the correlation between chewing gum and gastric emptying using the continuous real time (13)C breath test (BreathID system).
Abstract: Patients with autoimmune pancreatitis (AIP) sometimes present with Mikulicz disease (MD); however, the clinical features regarding these AIP patients with MD have not yet been fully elucidated. Our aim is to study the clinical differences between AIP with and without MD.
Abstract: Aim: Although non-alcoholic fatty liver disease (NAFLD) is now a common cause of chronic liver disease, discriminating between simple steatosis and non-alcoholic steatohepatitis (NASH), especially early-stage NASH, remains difficult. We investigated the clinical usefulness of measuring the spleen volume as a marker of early-stage NASH. Methods: We evaluated computed tomography (CT) images obtained in 84 patients with histologically diagnosed NAFLD (22 with simple steatosis, 62 with NASH with mild fibrosis [stages 1-2]). We defined the data obtained by the following formula as a spleen-body index (SBI): SBI = maximal CT axial section area of the spleen (cm(2))/body surface area (BSA) (cm(2)) x 10(4). We compared the SBI between patients with simple steatosis and those with NASH with mild fibrosis. Results: The mean SBI of the simple steatosis group was 15.8 +/- 3.9, while that of the NASH with mild fibrosis group was 18.7 +/- 5.7. This difference between the two groups was significant (P = 0.0314). A multiple logistic regression analysis showed that the SBI was significantly correlated with the discrimination of simple steatosis and NASH with mild fibrosis. The area under the receiver-operator curve was 0.661 for distinguishing between simple steatosis and NASH with mild fibrosis (P = 0.026, 95% confidence interval = 0.532-0.789). Conclusion: Spleen enlargement may be a distinct feature of NASH, especially early-stage NASH. SBI might be a non-invasive and simple method of differentiating NASH and simple steatosis.
Abstract: Paraganglioma, a sporadically occurring rare tumor should be included in the differential diagnosis of retroperitoneal tumors, such as malignant lymphomas, gastrointestinal stromal tumors, sarcoma and carcinoma of unknown primary site. A 58-year-old Japanese woman presented with a large retroperitoneal tumor detected by ultrasonography (US). She had no medical history of hypertension. Computed tomography showed a mass, 7 cm in diameter, located between the pancreas and the inferior vena cava. It was unclear whether the mass originated from the duodenum or the mesentery. Endoscopic ultrasonography (EUS) demonstrated a large solid paraduodenal mass. Doppler US revealed sparse vascularity in the tumor. With the differential diagnosis of retroperitoneal tumor, we carried out EUS-FNA. At the time of the third needle puncture, transient severe hypertension was noted, with a blood pressure measurement of 269/130 mmHg. Data obtained from urine and blood examinations after EUS-fine-needle aspiration indicated a diagnosis of paraganglioma.
Abstract: Metformin is widely used for the treatment of diabetes mellitus. Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin and to inhibit the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the protein translational machinery and cell proliferation. We examined the effect of metformin on the suppression of colorectal carcinogenesis in chemical carcinogen-induced models. Seven-wk-old BALB/c mice were intraperitoneally (i.p.) injected with azoxymethane (AOM, 10 mg/kg) and then treated with or without metformin (250 mg/kg/d) for 6 wk (for the investigation of aberrant crypt foci [ACF] formation) or 32 wk (for polyp formation). We next investigated colonic epithelial proliferation using bromodeoxyuridine (BrdU) and the proliferating cell nuclear antigen (PCNA) labeling indices. Furthermore, to examine the indirect effect of metformin, the insulin resistance status and the serum lipid levels were assessed. Treatment with metformin significantly reduced ACF formation. The effect of metformin on colon polyp inhibition was relatively modest. No significant difference in body weight or glucose concentration was observed. The BrdU and PCNA indices decreased in mice treated with metformin. A Western blot analysis revealed that the phosphorylated mTOR, S6 kinase, and S6 protein levels in the colonic mucosa decreased significantly in mice treated with metformin. In conclusion, metformin suppresses colonic epithelial proliferation via the inhibition of the mTOR pathway through the activation of AMPK. As metformin is already used daily as an antidiabetic drug, it might be a safe and promising candidate for the chemoprevention of colorectal cancer.
Abstract: Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC), but treatment failure can be difficult to predict. We and others have reported a relation between lipid values and sustained viral responses in patients with CHC. However, the relationship between lipid values and treatment failure has not been previously reported. The present study investigated the association between the profiles of phospholipids and free cholesterol (FC), the main constitutive ingredients of the surface of lipoprotein, classified according to particle size and hepatitis C treatment, and determined the usefulness of these parameters for predicting the outcome of treatment. Fifty-five patients with CHC (33 men and 22 women) were included in the study. The serum total cholesterol, triglyceride, phospholipids, and FC levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, enabling the lipoproteins to be classified into 13 subclasses according to particle size. According to a univariate analysis, the treatment failure group had a significantly higher serum phospholipid level overall in the high-density lipoprotein (HDL) and medium HDL fractions as well as a higher serum FC level in the HDL fraction and all HDL subclass fractions compared with the corresponding values in the non-nonvirological response group. Higher serum phospholipid and FC concentrations in the HDL subclasses were predictive of a failure to respond in patients with genotype 1b.
Abstract: A 45-year-old man under treatment for liver cirrhosis (LC) due to chronic hepatitis C and hemophilia A was seen in our emergency room because of a 10-kg weight gain in the previous week due to ascites. Portal vein thrombosis (PVT) was detected with computer tomography (CT) and ultrasonographic (US). Danaparoid sodium (DS) and antithrombin III (AT III) were administrated and doppler US images showed improvement of portal venous blood flow. DS or AT III may be safe and alternative therapies for PVT.
Abstract: A 71-year-old man was diagnosed with ulcerative colitis (UC) complicated by bacterial infections, and his active disease proved difficult to treat with steroid therapy or antibiotics. Although the patient's UC failed to respond to several types of induction therapy, his condition finally improved when treated using Bifidobacterium. Probiotics could be one of the treatment agents for induction of remission in UC.
Abstract: Aim: Non-alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations. Methods: We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50-60%, fat 20-30%, protein 15-20%) and exercise counseling from 3 months before the ezetimibe treatment. Results: The serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow-up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage. Conclusion: Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future.
Abstract: The role of gastric acid reflux is difficult to separate from that of pancreatic-biliary reflux in the pathogenesis of erosive esophagitis (EE) and Barrett's esophagus (BE). Gastric surgery patients provide a good model for both significant pancreatic-biliary reflux and marked gastric acid inhibition. We assessed the risk of EE and BE after distal gastrectomy in a case-controlled study.
Abstract: Pretreatment with a proton pump inhibitor (PPI) has been reported to decrease the efficacy of Helicobacter pylori (H. pylori) eradication. We compared the efficacy of an eradication regimen (lansoprazole/amoxicillin/clarithromycin) first or following pretreatment with a PPI.
Abstract: To clarify the gender differences about the clinical features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients.
Abstract: Percutaneous endoscopic gastrostomy is the standard method for enteral feeding in patients predicted to require long-term enteral nutrition because of dysphagia. A direct techinique with gastropexy is available, in which oropharyngeal passage of the internal bumper can be avoided. The aim of this study was to assess the early complications of percutaneous endoscopic gastrostomy performed using the new direct technique.
Abstract: Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC). Some groups have reported a relation between lipid values and response while others have reported that microsomal triglyceride transfer protein, a key enzyme in the assembly and secretion of lipoproteins, was related to hepatitis C virus (HCV). The aim of this study was to investigate the association between the lipoprotein profiles, classified according to size, and hepatitis C treatment and the usefulness for predicting the outcome of treatment. Forty-four patients with CHC (27 men and 17 women) were included in the study. The serum cholesterol and triglyceride (TG) levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, which classified lipoproteins into 20 subfractions based on particle size. According to a univariate analysis, those who achieved an sustained viral response (SVR) had a significantly higher serum total cholesterol level, higher cholesterol levels in the low-density lipoprotein subfraction (25.5 nm in diameter) and the very low-density lipoprotein (VLDL) subfraction (44.5 and 36.8 nm), and a higher serum TG level in the VLDL subfraction (44.5 nm), compared with the corresponding values in the non-SVR group. Higher serum cholesterol and TG concentrations in the lipoprotein subfractions were predictive of an SVR to therapy for HCV infection with genotype 1b prior to the start of interferon treatment.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.
Abstract: The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear. Recently, the 2-hit hypothesis was proposed, in which nitric oxide production, representing oxidative stress, was proposed as a very important candidate for the second hit.
Abstract: This study aims to investigate whether histamine H2-receptor antagonists are sufficient to treat nonerosive reflux disease in Japanese patients. The efficacy of lafutidine in Japanese nonerosive reflux disease patients was studied.
Abstract: The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 +/- 6.45 before treatment versus 5.11 +/- 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 +/- 6.65 versus 7.56 +/- 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer.
Abstract: There are few epidemiological studies of asymptomatic chlamydial infection among students in non-medical settings with minimal bias and improved accuracy; thus, useful data from screening among students are limited. We aimed to obtain accurate epidemiological information about asymptomatic chlamydial infection among students in non-medical settings. A population-based cross-sectional survey of 10,440 >or=18-year-old asymptomatic students who volunteered for a urine screening test for chlamydia was conducted. The prevalences of asymptomatic infection were 9.5% for women and 6.7% for men. Multivariate analysis revealed the risk factors to be a lifetime history of >or=4 sexual partners for women (odds ratio [OR] 3.17) and inconsistent condom use for men (OR 4.18). For both sexes, younger age at first intercourse was associated with a higher rate of inconsistent condom use. This study produced accurate epidemiological information on asymptomatic chlamydial infection. These results may contribute to the establishment of preventive countermeasures against such infection.
Abstract: A 68-year-old female with liver cirrhosis presented at the Emergency Room of our hospital with copious tarry stools. Upper gastrointestinal endoscopy showed an isolated gastric variceal rupture, and we performed endoscopic injection sclerotherapy using cyanoacrylate, on four occasions, resulting in successful hemostasis. Injection of CA is a useful emergency treatment option for gastric variceal bleeding without gastro-renal shunt.
Abstract: The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal bleeding (UGIB) associated with low-dose aspirin (LDA) treatment.
Abstract: In human subjects, aberrant crypt foci (ACF) can be classified as dysplastic or non-dysplastic using magnifying colonoscopy. Dysplastic ACF are thought to be a biomarker for the risk of colorectal cancer (CRC). Hyperinsulinemia and insulin-like growth factor-1 (IGF-1) have also been reported to be associated with an increased risk of CRC. To clarify this association, we investigated the relationship between diabetes risk, IGF-1 and the number of dysplastic ACF. Assessment of the number of dysplastic ACF in the entire colorectum is technically difficult, and we imaged the lower rectum only. Blood collections were taken in the morning on the day of colonoscopy. A total of 512 ACF were counted in 84 male participants, and a correlation was demonstrated to exist between age, body mass index (BMI), fasting blood sugar (FBS), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), plasma leptin levels, plasma IGF-1 levels and the number of dysplastic ACF. A significant association between plasma IGF-1 levels and the number of dysplastic ACF was still demonstrable after adjustment for age, BMI, FBS, insulin, HOMA-IR and plasma leptin levels. Our findings suggest that increased plasma leptin and IGF-1 levels, hyper-insulinemia and insulin resistance may promote the growth of dysplastic ACF. The results of multiple regression analysis revealed that increased plasma IGF-1 levels are associated with the number of dysplastic ACF present, and may be an independent risk factor for CRC. In conclusion, elevated plasma IGF-1 may promote the growth of dysplastic ACF and play a key role in colon carcinogenesis in male individuals.
Abstract: ABSTRACT : INTRODUCTION : Penetration of the colon to the posterior uterine wall secondary to diverticulitis is unusual, with diagnostic methods not yet established. Non-invasive imaging, such as computed tomography and magnetic resonance imaging may help to establish a proper diagnosis, but confirmation may be reached only after surgical exploration. CASE PRESENTATION : We report the case of a 78-year-old Japanese woman who presented with a low grade fever and mild diarrhea which occurred two or three times a week. Computed tomography and magnetic resonance imaging demonstrated a capsular lesion including an air structure with a diameter of 5 cm, between the posterior aspect of the uterine body and the sigmoid colon. A gastrograffin enema and colonoscopy demonstrated a giant diverticulum of the sigmoid colon with no evidence of malignancy. These data confirmed the diagnosis of diverticulitis complicated by a giant diverticulum. Because of a relapsing fever after therapy with antibiotics, the patient had en bloc surgical treatment of the uterus, fallopian tubes, ovaries and sigmoid colon, the organs involved in the diverticulitis, followed by an uneventful recovery. CONCLUSION : This is a rare case report of penetration of the sigmoid colon to the posterior uterine wall secondary to diverticulitis.
Abstract: The management of acute intestinal bleeding is not standardized. The aim of this study was to determine the most suitable method of bowel preparation for urgent colonoscopy.
Abstract: Hepatic mitochondrial beta-oxidation is considered to play a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to determine whether there were differences between patients with NASH and healthy controls in a breath test with 13C-octanoate, a medium-chain fatty acid. Methodology: The subjects were 8 patients (5 men, 3 women, median age 46.5 years) with histologically proven NASH and 6 healthy controls (5 men, 1 women, and median age 27.8 years). The 13C breath test was performed for 4 hours using the BreathID system with a 100 mL of water containing 100 mg 13C-octanoate.
Abstract: The antithrombotic effects of low-dose aspirin (LDA) are well established, and it is used for primary and secondary prevention of cardiovascular events. However, the small intestinal toxicity of LDA remains unclear. The aim of this study was to review the characteristics of small bowel injury in long-term LDA users with capsule endoscopy (CE).
Abstract: The aim of the study was to evaluate bowel dysmotility in patients with a history of abdominal surgery by measuring both gastric transit time and small bowel transit time during capsule endoscopy and assessing the completeness of the examination. The study included 26 patients who had undergone abdominal surgery (postoperative group) and 52 patients who had not (control group). The capsule reached the cecum in 50.0% of the postoperative group and 80.8% of the control group (P=0.005). While there was no significant difference in gastric transit time between the two groups (P=0.882), small bowel transit time was significantly longer in the postoperative group (338.3+/-119.2 min) than in the control group (266.4+/-110.8 min, P=0.010). This is the first study to report that the small bowel transit time during capsule endoscopy is prolonged in patients who had a history of abdominal surgery, resulting in a lower frequency of complete examination.
Abstract: Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE).
Abstract: In contrast to Western countries where erosive esophagitis (EE) is more prevalent in males, there is a high incidence of EE in elderly females in Japan. We aimed to examine the gender differences in the age-stratified prevalence of EE and Barrett's epithelium.
Abstract: We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection.
Abstract: Small intestinal toxicity of low-dose aspirin remains unclear. The purpose of this capsule endoscopy study was to assess the incidence of small bowel injury in healthy volunteers treated with short-term low-dose aspirin.
Abstract: The association between obesity and the risk of colorectal cancer (CRC) cannot be easily evaluated because CRC itself is associated with a gradual loss of bodyweight. Aberrant crypt foci (ACF) can be classified as dysplastic ACF or non-dysplastic ACF by magnifying colonoscopy, and dysplastic ACF are thought to be a biomarker of CRC. Ninety-four participants who underwent colonoscopy at Yokohama City University Hospital, Japan, were enrolled in the current study. We detected 557 ACF, including 67 dysplastic ACF (12.0%). Univariate regression analysis was conducted to determine correlations between the number of dysplastic ACF and various potential risk factors, including patient age, waist circumference, body mass index, visceral fat area (VFA), and plasma adiponectin level. The results of multiple regression analysis revealed that the number of dysplastic ACF correlated with age (correlation coefficient r=0.212, P=0.0383) and plasma adiponectin level (r=-0.201, P=0.0371), even after adjustments for sex, waist circumference, body mass index, and VFA. Our univariate correlation analysis data showed a significant correlation with the number of dysplastic ACF with VFA (r=0.238, P=0.0209), no correlation with subcutaneous fat area, and an inverse correlation with the plasma level of adiponectin (r=-0.258, P=0.0118). Thus, our results suggest that aging and visceral fat accumulation could correlate moderately with colorectal carcinogenesis. The novelty of our study lies in the finding that visceral fat accumulation and a low plasma adiponectin level may promote colorectal carcinogenesis; therefore, these obesity-related parameters may serve as novel targets for CRC prevention.
Abstract: The aim of this study was to determine whether there is a correlation between aperitif and gastric emptying. Ten healthy male volunteers participated in this randomized, two-way crossover study. Under two conditions (after drinking an aperitif versus not), the (13)C breath test was performed for 4 h with a liquid meal (200 kcal/200 ml) containing 100 mg (13)C acetate. We used 50 ml of umeshu as the aperitif. This is a traditional Japanese plum liqueur, and contains 7 ml alcohol (14%). In the aperitif group, T(1/2), T(lag), and T(peak) were significantly delayed [T(1/2) (132: 113-174) versus (112: 92-134) (P = 0.0069); T(lag) (80: 63-94) versus (55: 47-85) (P = 0.0069); and T(peak) (81: 62-96) versus (54: 34-84) (P = 0.0069), (median: range, aperitif versus control, min)]. Gastric emptying was significantly delayed in the aperitif group as compared with the control group. This study revealed that even a small amount of alcohol such as an aperitif may contribute to delayed gastric emptying.
Abstract: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis.
Abstract: The goal of this study was to investigate Cystatin SN, a cysteine protease inhibitor, as a novel tumor marker for colorectal cancer (CRC). Gene expression profiles of mRNA from normal tissues and cancer cell lines were performed. Twenty-eight monoclonal antibodies for Cystatin SN were generated and serum Cystatin SN was quantified using ELISA in sera from 159 patients with CRC and 40 healthy controls. Cystatin SN was highly expressed in colon cancer cells. Employing a receiver-operating characteristic curve, we obtained an area under the curve of 0.708 for Cystatin SN, 0.819 for carcinoembryonic antigen (CEA) and 0.703 for carbohydrate antigen 19-9 (CA19-9). The combination assay of Cystatin SN, CEA and CA19-9 showed 62.9% sensitivity and 90.0% specificity. Especially, the sensitivity of the combination assay in stages I and II detection, in which stages curative operation would be possible, was improved over that of the assay testing only for CEA and CA19-9 (from 37.5 to 42.5% in stage I, from 49.0 to 60.8% in stage II). Furthermore, Western blot analysis revealed that Cystatin SN was increased in the urine from patients with CRC. Our results suggest the possibility of utilizing this novel tumor marker that can be tested in urine samples. These observations suggest that Cystatin SN in combination with CEA and CA19-9 is a useful tumor marker for detecting early stage CRC and that it is a unique urinary excretory protein, suggesting that Cystatin SN might be a novel candidate for use in mass screening for CRC.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver.
Abstract: Aim: Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD. Methods: A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study. Results: We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P-value in the allele frequency model (P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32-0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822. Conclusion: This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.
Abstract: The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH.
Abstract: Coffee is one of the most popular beverages worldwide, however, few studies have examined the effects of coffee on the gastrointestinal system. The aim of this study was to determine whether there was a correlation between coffee intake and gastric emptying using a novel non-invasive technique for measuring gastric emptying with a continuous real time 13C breath test (BreathID system: Oridion, Israel).
Abstract: The association between obesity and the risk of Barrett's esophagus (BE) is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown.
Abstract: The molecular mechanisms underlying the promotion of colorectal carcinogenesis by a high-fat diet (HFD) remain unclear. We investigated the role of the insulin-signal pathway and the c-Jun N-terminal kinase (JNK) pathway, which reportedly play crucial roles in insulin resistance, during colorectal carcinogenesis in the presence of hyperinsulinaemia induced by a HFD.
Abstract: Aim: Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment. Methods: The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses. Results: The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group. Conclusions: The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.
Abstract: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor.
Abstract: The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of lansoprazole 30 mg and famotidine 20 mg.
Abstract: The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis and resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after a single oral administrations of lafutidine, is a newly synthesized H2-receptor antagonist, with mosapride 5 mg or lafutidine alone.
Abstract: The effect of adiponectin on colorectal carcinogenesis has been proposed but not fully investigated. We investigated the effect of adiponectin deficiency on the development of colorectal cancer.
Abstract: Adiponectin is secreted by adipocytes and is a key hormone responsible for insulin sensitization. Recent studies have shown that plasma adiponectin is decreased in patients with breast, endometrial and gastric cancer. However, the effect of adiponectin on colorectal carcinogenesis is controversial. It is now well known that the adiponectin receptor exists in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). We examined the expression of the adiponectin receptors on normal colon mucosa and colon cancer tissues in a human study using real-time RT-PCR, Western blotting and immunohistochemical staining. Adiponectin receptors, AdipoR1/AdipoR2, were expressed in normal colon epithelial and colon cancer cells. Furthermore, laser microdissection was performed to confirm our results. These results suggest that adiponectin may exert some effects on normal colon epithelium or colon cancer cells directly through adiponectin receptors. Further studies are required to elucidate the function of the AdipoRs activated by adiponectin and the downstream mechanisms of AdipoRs in colon cancer cells.
Abstract: The endoscopic examination of a 64-year-old male patient revealed a gastric submucosal tumor in the anterior wall of the gastric antrum. The lesion increased in diameter to 25 mm and was resected completely with endoscopic submucosal dissection (ESD). Histological examination of the submucosal tumor gave a diagnosis of an inflammatory fibroid polyp (IFP). It is suggested that ESD may be an effective and safe therapy for gastric submucosal tumors.
Abstract: Valproic acid (VPA) is a commonly prescribed and approved treatment for epilepsy, including Angelman syndrome, throughout the world. However, the long-term administration of drugs like VPA is associated with the possible development of gastric varices and splenic obstruction as a result of chronic pancreatitis. Such cases can be difficult to treat using endoscopy or interventional radiology because of hemodynamic abnormalities; therefore, surgical treatment is often necessary.
Abstract: Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor gamma coactivator 1alpha polymorphism (PPARGC1A) and NAFLD.
Abstract: Aim: Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD) and sometimes progresses to cirrhosis and liver failure. In this study we analyzed the expression profile of genes and biological pathways involved in NASH in comparison with non-NASH by gene set enrichment analysis (GSEA) employing a DNA microarray technique. Methods: mRNA from liver biopsy specimens was collected from a group of NASH patients and a group of non-NASH patients. We analyzed the relative abundance of mRNA using high-density oligonucleotide microarrays containing probes for 54 675 known genes, and investigated the pathogenetic mechanisms of NASH by means of a powerful technique for analyzing molecular profiling data, GSEA. Results: The results showed that the level of expression of 27 gene sets was significantly higher and the level of expression of 25 gene sets was significantly lower in the NASH samples than in the non-NASH samples. Based on these results we created an online, publicly available, searchable database containing the data for the gene expression profiles of the NASH patients (http://www2.genome.rcast.u-tokyo.ac.jp/___/NASH/NASH_GSEA2/). Conclusion: Our data revealed differences in expression of many gene sets that are involved in the pathogenesis of NASH.
Abstract: No effective drugs have been developed to date to prevent or treat non-alcoholic fatty liver disease (NAFLD), although diet modification and exercise to improve obesity have been attempted. Therefore, development of a novel drug/strategy to treat NAFLD is urgently needed. In the present study, a novel concept is proposed for the treatment of NAFLD.
Abstract: A 65-year-old man was admitted with penile tenderness and dysuria due to priapism. Enhanced computed tomography revealed metastatic tumors in the liver, lung, sacrum and lymph nodes. Advanced rectal cancer, detected by colonoscopy as a primary tumor, was treated with chemotherapy (FOLFOX4). Although the rectal cancer showed no change, five months of chemotherapy improveid the priapism, suggesting that chemotherapy can improve rare symptoms of rectal cancer.
Abstract: Barrett's epithelium is currently believed to be related to acid gastroesophageal reflux. The aim was to determine the role of pancreatic-biliary reflux in the genesis of Barrett's epithelium.
Abstract: Hepatocellular carcinoma with portal venous invasion has a poor prognosis. We report a case treated successfully by intra-arterial 5-fluorouracil with systemic pegylated-interferon-alpha-2b instead of conventional interferon-alpha. A 66-year-old man was admitted to our hospital, and diagnosed with hepatocellular carcinoma with portal venous invasion. Following informed consent, he was treated with eight week cycles of combination chemotherapy using intra-arterial 5-fluorouracil (500 mg/body/day i.a., days 1-5, 8-12 continuously) and pegylated-interferon-alpha-2b (100 microg body s.c., days 1, 8). No significant side effects were observed during his therapy. After 4 cycles, computed tomography scan revealed a partial response of tumor reduction. This is the first report of advanced hepatocellular carcinoma effectively treated using subcutaneous pegylated-interferon-alpha-2b with intra-arterial 5-fluorouracil. While the conventional therapy of interferon-alpha with 5-fluorouracil has significant side effects, no significant side effects were observed in our case. The use of subcutaneous pegylated-interferon-alpha-2b combined with intraarterial 5-fluorouracil, may improve patients' quality of life.
Abstract: The aim of this study was to determine whether there was a correlation between body positions and gastric emptying, using a novel non-invasive technique for measuring gastric emptying with a continuous real time 13C breath test (BreathID system).
Abstract: The benefits of bowel preparation prior to capsule endoscopy (CE) are controversial. The aim of this study was to examine whether ingesting a small amount of polyethylene glycol (PEG) during, not before, the CE procedure improves the image quality and the cecal completion rate. A prospective single-blind controlled study was conducted including 59 patients. The initial 32 patients (group A) received no preparation, and the subsequent 27 patients (group B) ingested 500 ml of PEG starting 30 min after swallowing the capsule. The capsule reached the cecum in 65.6% of the patients in group A and 88.9% of the patients in group B (P = 0.038). The use of PEG during CE examination significantly improved the image quality, and this effect was more pronounced in the distal ileum. Ingesting a small amount of PEG during CE examination significantly improves both the CE image quality and the cecal completion rate.
Abstract: The granulocyte-colony stimulating factor-producing tumor was first reported in 1977, however, anaplastic pleomorphic type carcinoma of the pancreas producing granulocyte-colony stimulating factor is still rare.
Abstract: Evidence regarding the association between alcohol consumption and the gastro-esophageal reflux disease (GERD) spectrum has been conflicting. We examined the association between alcohol consumption and erosive esophagitis and Barrett's epithelium in Japanese men.
Abstract: The changes in the liver in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However it has remained difficult to differentiate between NASH and non-progressive NAFLD on the basis of the clinical findings alone.
Abstract: We report a rare case of adenosquamous carcinoma of the pancreas associated with humoral hypercalcemia of malignancy (HHM) in which parathyroid hormone-related protein (PTH-rP) was identified as the causative factor of hypercalcemia. A 72-year-old Japanese man was admitted to our institution complaining of fever and abdominal pain. Abdominal computed tomography demonstrated a large tumor in the body of the pancreas, with multiple liver metastases. Both serum calcium and PTH-rP levels were elevated. No accumulation was observed on bone scan with technetium-99. The patient died of pneumonia 3 months after admission. Autopsy demonstrated that the neoplasm in the pancreas showed an abrupt histological transition from adenocarcinoma to squamous cell carcinoma. PTH-rP was identified in the primary pancreatic tumor cells by immunohistochemical examination and a reverse-transcription polymerase chain reaction (RTPCR) method. We concluded that PTH-rP was the causative factor of the HHM, based on the laboratory data, immunohistochemical examination, and messenger RNA (mRNA) expression. This is a very rare report of adenosquamous cell carcinoma of the pancreas associated with HHM.
Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that has been implicated in the carcinogenesis and progression of various solid tumors, including pancreatic carcinomas. We aimed to clarify the role of this receptor in pancreatic cell motility in vitro and in metastasis in vivo. Cell motility was examined by assaying transwell migration and wound filling in Capan-1 and Panc-1 pancreatic cancer cells, with or without the PPARgamma-specific inhibitor T0070907. A severe combined immunodeficiency xenograft metastasis model was used to examine the in vivo effect of PPARgamma inhibition on pancreatic cancer metastasis. In both transwell-migration and wound-filling assays, inhibition of PPARgamma activity suppressed pancreatic cell motility without affecting in vitro cell proliferation. Inhibition of PPARgamma also suppressed liver metastasis in vivo in metastatic mice. In PPARgamma-inhibited cells, p120 catenin accumulation was induced predominantly in cell membranes, and the Ras-homologous GTPases Rac1 and Cdc42 were inactive. Inhibition of PPARgamma in pancreatic cancer cells decreased cell motility by altering p120ctn localization and by suppressing the activity of the Ras-homologous GTPases Rac1 and Cdc42. Based on these findings, PPARgamma could function as a novel target for the therapeutic control of cancer cell invasion or metastasis.
Abstract: Differentiating primary sclerosing cholangitis (PSC) and sclerosing cholangitis caused by autoimmune pancreatitis (SC-AIP) is often challenging. Recently, endoscopic findings of the duodenal papilla in cases with AIP or PSC were reported by Unno and Parlak, although the endoscopic differentiation of these 2 conditions has not yet been fully clarified.
Abstract: Although peroxisome proliferator-activated receptor gamma (PPARgamma) is strongly expressed in the intestinal epithelium, the role of PPARgamma in intestinal tumorigenesis has not yet been elucidated. To address this issue, we investigated the effect of PPARgamma inhibition and its mechanism on intestinal tumorigenesis using a selective antagonist, T0070907. We treated Apc(Min/+) mice and carcinogen-induced colon cancer model C57BL/6 mice with T0070907 and counted the number of spontaneous polyps and aberrant crypt foci and observed cell proliferation and beta-catenin protein in the colon epithelium. To investigate its mechanism, the changes of beta-catenin/TCF (T cell factor) transcriptional activity and location of beta-catenin induced by T0070907 were investigated in the colon cancer cell lines. T0070907 promoted polyp formation in the small intestine of Apc(Min/+) mice and aberrant crypt foci in the colon of C57BL/6 mice. PPARgamma inhibition promoted cell proliferation and increased expressions of the c-myc and cyclin D1 genes and the beta-catenin protein in the colon epithelium. In vitro, cell proliferation was promoted, but it was inhibited by the transfection of dominant-negative Tcf4. T0070907 increased beta-catenin/TCF transcriptional activity and beta-catenin protein in the cytsol and nucleus, but relatively decreased it on the cell membrane. PPARgamma antagonist promotes tumorigenesis in the small intestine and colon through stimulation of epithelial cell proliferation. beta-Catenin contributes to the promotion of tumorigenesis by PPARgamma antagonist due to activation of TCF/LEF (lymphoid enhancer factor) transcriptional factor.
Abstract: There have been few reports of primary carcinoma of the cystic duct (CCD) included in advanced cases. The aim of this study was to elucidate the clinical features of resected CCD.
Abstract: The differential diagnosis between intracystic hemorrhage and cystadenocarcinoma of the liver is often difficult even with the use of various imaging modalities. A 73-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Ultrasonography (US) demonstrated a heterogeneous echogenic cyst measuring 11 cm multiply 8 cm in size in S2 of the liver, indicated intracystic hemorrhage of simple liver cyst or cystadenocarcinoma, but the differential diagnosis was considerably difficult. Levovist (Schering, Berlin, Germany) US revealed no enhancement of the intracystic structures, suggesting a clot in the case of intracystic hemorrhage. An operation was performed and the resected lesion showed a solitary benign liver cyst, measuring 5.5 cm multiply 4.7 cm multiply 8.5 cm containing a large blood clot. The patient had an uneventful recovery after the surgery. Levovist US may play an important role in discrimination between intracystic hemorrhage of simple hepatic cysts and cystadenocarcinoma of the liver.
Abstract: Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis.
Abstract: 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.
Abstract: The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine(GEM)alone and to predict survival time by carbohydrate antigen(CA)19-9, enhanced computed tomography(CT), and 18F-fluoro-2-deoxy-D-glucose positron emission tomography(FDG-PET) in monitoring the response to chemotherapy. Twenty-one patients with unresectable pancreatic cancer were enrolled in this study. All patients were evaluated by serum CA19-9 level, tumor size of CT, maximum standardized uptake value (SUVmax)with FDG-PET and other factors before chemotherapy(GEM alone at a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest), and they received chemotherapy until obviously progressive disease. Serum CA19-9, tumor size of CT and SUVmax with PET were measured after three courses of chemotherapy in ten patients. We compared these three modalities in terms of two points: Which is the best modality to predict survival time ? Which is the best monitoring modality to evaluate the efficacy of chemotherapy on unresectable pancreatic cancer ? A significant difference in survival time was not found between high level group and low level group of serum CA19-9 level and SUVmax with FDG-PET and also longest length of tumor by enhanced CT. In ten patients we evaluated the response rate of each parameter CA19-9(IU/mL), CT(longest length of tumor), and SUVmax with FDG-PET. We defined the response rate(pretreatment level of CA19-9 or longest length of tumor or SUVmax-after 3 courses chemotherapy level of CA19-9 or longest length of tumor or SUVmax/pretreatment level of CA19-9 or longest length of tumor or SUVmax). Response rate of CA19-9 was significantly correlated with survival time(r=0.633, p=0.0481). However, the response rate of SUVmax with FDG-PET had no significant correlation with survival time(r=0.019, p=0.9630). In the present study, the response rate of CA19-9 is the best monitoring modality to evaluate the efficacy of chemotherapy.
Abstract: The precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding.
Abstract: The changes in nonalcoholic fatty liver disease range over a wide spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients.
Abstract: The changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH.
Abstract: The aim of this study was to determine whether there was a correlation between peppermint oil and gastric emptying by using a novel noninvasive technique for measuring gastric emptying with a continuous real-time (13)C breath test (BreathID system, Oridion, Israel).
Abstract: There have been few reports of separate orifices (SPO) for the bile and pancreatic ducts. The aim of this study was to elucidate the clinical significance of SPO.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Insulin resistance has been found to increase the risk of NASH, and obesity, and decreased levels of adiponectin are important factors in determining the severity of insulin resistance. Recent evidence has indicated that hypoadiponectinemia is involved in hepatic steatosis and NASH.
Abstract: The term nonalcoholic steatohepatitis (NASH) has recently been proposed to identify a fatty liver disease accompanied by diffuse fatty infiltration and inflammation. However, no drug therapy has been established for NASH as yet. In the present study, we demonstrate the effect of the angiotensin II type 1 receptor antagonist telmisartan on the development of NASH in a rat model. Telmisartan, but not the angiotensin receptor antagonist valsartan, markedly attenuated hepatic steatosis, inflammation, and fibrosis in these rats. The quantitative parameters of steatosis, inflammation, and fibrosis were also ameliorated by treatment with telmisartan. Compared with telmisartan, the peroxisome proliferator-activated receptor-gamma agonist pioglitazone attenuated hepatic steatosis and fibrosis of the liver to a similar degree. However, telmisartan, but not pioglitazone, dramatically decreased both subcutaneous and visceral fat. In conclusion, these results indicated that telmisartan should be the drug of first choice for the treatment of patients with NASH.
Abstract: The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.
Abstract: To evaluate the clinical significance of a swollen main duodenal papilla and the associated immunohistopathologic findings in patients with autoimmune pancreatitis (AIP).
Abstract: Life style-related diseases are associated with an increased risk of colorectal cancer (CRC). Recently, an association has been demonstrated between obesity and CRC. CRC has been associated with markers of insulin or glucose control, and insulin resistance might be the unifying mechanism by which several risk factors affect colorectal carcinogenesis. We evaluated the association between the number of aberrant crypt foci (ACF) and obesity, insulin resistance, hyperlipidemia, and other factors of life style-related disease. As a result, age, body mass index (BMI), waist circumference, and visceral fat obesity were significantly associated with the number of ACF. These results suggest that visceral fat obesity is an important target for CRC prevention. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and is highly expressed in CRC. PPARgamma ligand administration for 1 to 8 months significantly reduced the number of ACF in human subjects. PPARgamma ligand is a promising candidate as a chemopreventive agent. Further investigation is needed to elucidate these mechanisms.
Abstract: Insulin resistance (IR) is known to be associated with the visceral adipose tissue area. Elucidation of the relationship between hepatitis C virus (HCV) and IR is of great clinical relevance, because IR promotes liver fibrosis. In this study, we tested the hypothesis that HCV infection by itself may promote IR. We prospectively evaluated 47 patients with chronic HCV infection who underwent liver biopsy. Patients with obesity, type 2 diabetes mellitus (DM), or a history of alcohol consumption were excluded. IR was estimated by calculation of the modified homeostasis model of insulin resistance (HOMA-IR) index. Abdominal fat distribution was determined by computed tomography. Fasting blood glucose levels were within normal range in all the patients. The results of univariate analysis revealed a significant correlation between the quantity of HCV-RNA and the HOMA-IR (r = 0.368, P = 0.0291). While a significant correlation between the visceral adipose tissue area and the HOMA-IR was also observed in the 97 control, nondiabetic, non-HCV-infected patients (r = 0.398, P < 0.0001), no such significant correlation between the visceral adipose tissue area and the HOMA-IR (r = 0.124, P = 0.496) was observed in the patients with HCV infection. Multiple regression analysis with adjustment for age, gender and visceral adipose tissue area revealed a significant correlation between the HCV-RNA and the HOMA-IR (P = 0.0446). HCV is directly associated with IR in a dose-dependent manner, independent of the visceral adipose tissue area. This is the first report to demonstrate the direct involvement of HCV and IR in patients with chronic HCV infection.
Abstract: Endoscopic injection sclerotherapy is in widespread use for patients with esophageal varices. It is well known that pleural effusions are among complications following endoscopic sclerotherapy. However, there are few studies regarding the proportion of patients developing pleural effusions after sclerotherapy.
Abstract: Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis.
Abstract: The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine (GEM) alone and to predict survival time after the first course of treatment. Eighteen consecutive patients (median age 65.3 years, range 49-77 years; 12 males, 6 females) with unresectable pancreatic cancer and a baseline Karnofsky's performance state = or >60 were treated with GEM in a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest until progression. The overall response rate was 0% (CR 0, PR 0, SD 11 cases, and PD 5 cases), and the median survival time (MST) was 268 days. We observed a statistically significant difference in the patients with or without liver metastasis at the start of treatment (131.6 vs 324.9 days; p=0.0045). We also evaluated the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with unresectable pancreatic cancer receiving GEM alone. We classified two subgroups into responders (patients with a decrease of = or >10% of the baseline CA 19-9 level after 4 weeks of chemotherapy) and non-responder (patients with a increase of the baseline CA 19-9 level or with a decrease of <10% of the baseline CA 19-9 level after 4 weeks of chemotherapy). Responder had a significantly better median survival than non-responders (416.6 vs 138.3 days; p=0.009). In conclusion, CA 19-9 serum concentration serves as an early indicator of response to chemotherapy with GEM alone in unresectable pancreatic cancer.
Abstract: A case of undifferentiated spindle-cell carcinoma of the gallbladder is described. A 72-year-old man presented with right hypochondralgia and fever. Imaging studies revealed a well-demarcated solid tumor (with a necrotic center) in the gallbladder that invaded the liver and transverse colon. On gross examination of the surgical specimen, the cut surface of the polypoid tumor showed nodular invasive growth. Microscopically, the tumor was composed of atypical spindle-shaped tumor cells that proliferated in a whirling or interlacing pattern. The tumor also showed foci with a malignant epithelial component that simulated a carcinosarcoma. Immunohistochemically, the biphasic differentiation of the tumor was highlighted by the different immunoreactivity to antibodies against cytokeratins, epithelial membrane antigen (EMA), and vimentin shown by the malignant epithelial components and the spindle-cell components. However the latter showed faint positivity for cytokeratin antibody. These results suggested that the spindle-cell carcinoma of the gallbladder originated from cholecystic mucosa and showed sarcomatous reaction or dedifferentiation, as indicated by the presence of vimentin-positive cells. The proliferation index, as detected by ki-67, in the spindle-cell component was higher than that in the epithelial component, which may account for the more aggressive biological behavior of the spindle-cell component.
Abstract: Triple therapy consisting of lansoprazole, amoxicillin, and clarithromycin (LAC regimen) is widely used to eradicate Helicobacter pylori in Japan. However, the need for appropriate treatment after failure of initial therapy to eradicate H. pylori has been increasing. We therefore assessed the efficacy of a combination of rabeprazole, amoxicillin, and faropenem for second-line eradication therapy.
Abstract: A cDNA library derived from the anterior neuroectoderm (ANE) of Xenopus late-gastrula embryos was systematically screened to isolate novel developmental regulatory genes involved in early brain development. We isolated 1,706 5 expressed sequence tags (ESTs), which were subdivided into 1,383 clusters and categorized into 19 classes based on predicted functions according to their similarities to other known genes. Of these, 757 clusters that were considered possible novel regulatory genes or unknown genes were subjected to expression pattern analysis using whole-mount in situ hybridization. Genes from 69 clusters (9%) were expressed in the ANE region. Based on their expression patterns and predicted amino acid sequences, 25 genes were selected for further analysis as novel Xenopus genes expressed broadly or region-specifically in the ANE. Eighteen genes were expressed in postulated patterning centers in the neuroectoderm, including the anterior (four genes) and lateral (nine genes) neural ridges, the midbrain-hindbrain boundary region (one gene) and the midline region of the neural plate (two genes), whereas 13 genes were expressed in the eye anlagen. Therefore, early regionalization of the neuroectoderm appears to occur mainly in those neural patterning centers and the eye anlagen. We determined the entire coding regions of p54nrb, Semaphorin 6D and a novel gene designated scribble-related protein 1 (SCRP1). Interestingly, Semaphorin 6D is expressed in the mesoderm with a dorsoventral gradient, as well as in the ectoderm at the gastrula stage, implying a new role for this protein in development other than in axon guidance.
Abstract: Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.
Abstract: Endoscopic gallbladder stenting is useful palliative therapy for acute cholecystitis in high-risk patients. Although the success rate of endoscopic gallbladder stenting is 79%-100%, an alternative method has not been reported. We succeeded in employing a method for percutaneous gallbladder stenting (PTGS) and herein describe this new method. A patient with acute acalculous cholecystitis related to ischemic atherosclerotic vascular disease, cholangitis due to Lemmel syndrome, and severe congestive heart failure underwent PTGS through the cystic duct from the gallbladder to the duodenal papilla, because an endoscopic method failed in the treatment of Lemmel syndrome. Because we were unable to place endoscopic transpapillary gallbladder drainage, percutaneous transhepatic gallbladder drainage (PTGBD) was performed and both the cholecystitis and cholangitis ceased. PTGS was performed as an alternative to endoscopic gallbladder stenting. Access to the cystic duct and gallbladder was obtained by the PTGBD route, using a guidewire (0.035-inch diameter) and seeking catheter (6.5 Fr) under fluoroscopic control. A 7-Fr 12-cm double-pigtail biliary polyethylene stent was placed. The patient remained asymptomatic for 3 months after the PTGS until he died, of an acute recurrent myocardial infarction. This new PTGS placement is an alternative treatment for symptomatic gallbladder disease in patients with increased operative risk when the endoscopic method is unsuccessful.
Abstract: The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20mg and famotidine 20 mg.
Abstract: Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined.
Abstract: 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.
Abstract: Natural immunomodulator lactoferrin is known to exert an anti-inflammatory effect. However, there have been no studies that examine the mode of action of lactoferrin in reducing intestinal damage. We investigated the effect of lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats. Bovine lactoferrin was given once daily through gavage, starting 3 days before (preventive mode) or just after TNBS administration (treatment mode) until death. The distal colon was removed to be examined. Colitis was attenuated by lactoferrin via both modes in a dose-dependent manner, as reflected by improvement in macroscopic and histological scores and myeloperoxidase activity. Lactoferrin caused significant induction of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, significant reductions in the proinflammatory cytokines tumor necrosis factor-alpha and IL-1beta, and downregulation of the nuclear factor-kappaB pathway. We concluded that lactoferrin exerts a protective effect against colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.
Abstract: The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis.
Abstract: A 42-year-old woman with diabetes mellitus lost consciousness and was transferred to the Yokohama City University Hospital. Blood chemistry findings indicated low blood sugar levels and chest X-ray examination revealed cardiomegaly and bilateral pleural effusions. These clinical abnormalities were corrected by treatment with glucose, diuretics, angiotensin converting enzyme inhibitor and digitalis. Cardiological laboratory examinations were performed after admission. Electrocardiography revealed first degree atrioventricular block and incomplete right bundle branch block. Ultrasonography showed lower grade of ejection fraction and diffuse hypokinesis of the cardiac wall. After admission, sinus arrest suddenly occurred. The diagnosis was sick sinus syndrome. Scintigraphy using iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid showed abnormal mottled defects. Coronary angiography found no significant stenosis of the coronary artery. Electron microscopy showed abnormally shaped mitochondrial accumulations in an endomyocardial biopsy specimen. Mitochondrial DNA amplification by polymerase chain reaction followed by restriction enzyme Apa I digestion revealed adenine-to-guanine transition at 3243 of the mitochondrial tRNA(LEU)(UUR) gene.
