Showing papers in "Journal of Gastroenterology in 2012"
TL;DR: The prevalence of nonalcoholic fatty liver disease has increased in the general population, especially in males, and there is a linear relationship between the prevalence of NAFLD and various metabolic parameters, even in nonobese subjects.
Abstract: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. This study aimed to assess the recent prevalence of NAFLD and to predict the prevalence of nonalcoholic steatohepatitis (NASH) with liver fibrosis using established scoring systems in the general population. A cross-sectional study was conducted among 8352 subjects who received health checkups from 2009 to 2010 in three health centers in Japan. Subjects with an intake over 20 g of alcohol/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. The probability of NASH with advanced fibrosis was calculated according to the body mass index, age, ALT, and triglyceride (BAAT) and FIB-4 (based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet counts) indices. A total of 5075 subjects were enrolled. The overall prevalence of NAFLD was 29.7%. There was a significant threefold difference in the mean prevalence between males (41.0%) and females (17.7%). This prevalence showed a linear increase with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even without obesity. The estimated prevalence of NASH according to the BAAT index ≥3 was 2.7%, and according to the FIB-4 index it was 1.9%. The prevalence of NAFLD has increased in the general population, especially in males. There is a linear relationship between the prevalence of NAFLD and various metabolic parameters, even in nonobese subjects. The prevalence of NASH with advanced fibrosis is estimated to be considerably high in subjects with NAFLD.
413 citations
TL;DR: Dysbiosis in CD patients was shown by a multi-IBD center study and a logistic model to predict disease activity based on the fecal microbiota composition was developed, which proposed the feasibility of using the feces profile as a predictive marker for disease activity.
Abstract: We analyzed the fecal microbiota profiles of patients with Crohn’s disease (CD) at 4 inflammatory bowel disease (IBD) centers located in different districts in Japan. Terminal restriction fragment length polymorphism (T-RFLP) analysis was performed in 161 fecal samples from CD patients and 121 samples from healthy individuals. The bacterial diversity was evaluated by the Shannon diversity index (SDI). There were no regional differences in the fecal microbiota profiles of the healthy individuals in Japan. A setting of similarity generated three major clusters of T-RFs: one included almost all the healthy individuals (118/121), and the other two clusters were mainly formed by CD patients at different stages of disease activity. The changes in simulated bacterial composition indicated that the class Clostridia, including the genus Faecalibacterium, was significantly decreased in CD patients with active disease and those in remission as compared with findings in the healthy individuals. In contrast, the genus Bacteroides was significantly increased in CD patients during the active phase as compared with findings in the healthy individuals. The genus Bifidobacterium was significantly decreased during the active phase of CD and increased to healthy levels during the remission phase. The bacterial diversity measured by the SDI was significantly reduced in CD patients during the active and remission phases as compared with findings in the healthy individuals. From the clinical data and T-RFLP analysis, we developed a logistic model to predict disease activity based on the fecal microbiota composition. Dysbiosis in CD patients was shown by a multi-IBD center study. The feasibility of using the fecal microbiota profile as a predictive marker for disease activity is proposed.
145 citations
TL;DR: These guidelines are created to provide assistance in the clinical practice of PBM management; their contents focus on clinical utility, and they include general information on PBM to make this disease more widely recognized.
Abstract: There have been no clinical guidelines for the management of pancreaticobiliary maljunction (PBM) The Japanese Study Group on Pancreaticobiliary Maljunction (JSPBM) has proposed to establish clinical practice guidelines on how to deal with PBM, with the support of the Japan Biliary Association (JBA) Because the body of evidence-based literature is relatively small, we decided to create guidelines based on the consensus of experts, using the medical literature for reference A total of 46 clinical questions (CQs) were considered by the members of the editorial committee responsible for the guidelines The CQs covered distinct aspects of PBM: (1) Concepts and Pathophysiology (10 CQs); (2) Diagnosis (10 CQs); (3) Pancreatobiliary complications (9 CQs); and (4) Treatments and prognosis (17 CQs) Statements and comments for each CQ were prepared by the guidelines committee members and collaborating partners The CQs were completed after review by members of the editorial committee, meetings of this committee, public comments on the homepages of the JSPBM and the JBA, public hearings, and assessment and approval by the guidelines evaluation board PBM includes cases where the bile duct is dilated (PBM with biliary dilatation) and those in which it is not (PBM without biliary dilatation) In these guidelines, PBM with biliary dilatation is defined as being identical to congenital biliary dilatation of Todani type I (except for type Ib) and type IV-A, both of which are accompanied by PBM in almost all cases These guidelines are created to provide assistance in the clinical practice of PBM management; their contents focus on clinical utility, and they include general information on PBM to make this disease more widely recognized
140 citations
TL;DR: Although the fibrotic mechanisms underlying NASH are largely similar to those observed in other chronic liver diseases, the altered patterns of circulating adipokines, the generation of oxidative stress, and the hormonal profile associated with the metabolic syndrome might play unique roles in the fibrogenesis associated in the disease.
Abstract: Nonalcoholic fatty liver disease consists of a range of disorders characterized by excess accumulation of triglyceride within the liver. Whereas simple steatosis is clinically benign, nonalcoholic steatohepatitis (NASH) often progresses to cirrhosis. Inflammation and fibrogenesis are closely inter-related and are major targets of NASH research. Experimental data have shown that inflammation in NASH is caused by insulin resistance, systemic lipotoxicity due to overnutrition, lipid metabolites, the production of proinflammatory cytokines and adipokines by visceral adipose tissue, gut-derived bacteria, and oxidative stress. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is recognized as the hepatic stellate cell. Although the fibrotic mechanisms underlying NASH are largely similar to those observed in other chronic liver diseases, the altered patterns of circulating adipokines, the generation of oxidative stress, and the hormonal profile associated with the metabolic syndrome might play unique roles in the fibrogenesis associated with the disease. Information on the basic pathogenesis of NASH with a focus on the generation of inflammation and fibrosis will be discussed.
134 citations
TL;DR: The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996, however, recently, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients.
Abstract: Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for “acute liver failure” for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.
123 citations
TL;DR: In 10 years after H. pylori eradication, atrophy at all sites and IM in the lesser curvature of the corpus gradually and significantly decreased, suggesting that the improvement of gastric atrophy and IM might have association with the reduction of Gastric cancer occurrence.
Abstract: Background
Atrophic gastritis and intestinal metaplasia (IM) are well known as precancerous lesions of gastric cancer. The present study evaluated the gastric mucosa for 10 years after H. pylori eradication at five points of the stomach as recommended by the updated Sydney system to clarify the relationship between H. pylori eradication and gastric cancer prevention.
113 citations
TL;DR: Clinical evidence suggest that in complex and multifactorial diseases such as irritable bowel syndrome, psychological disorders represent significant factors in the pathogenesis and course of the syndrome.
Abstract: The interaction between the brain and the gut as a pathological mechanism of functional gastrointestinal disorders has been recently recognized in the pathophysiology of the irritable bowel syndrome. Communication between central nervous system and enteric nervous system is two-directional: the brain can influence the function of the enteric nervous system and the gut can influence the brain via vagal and sympathetic afferents. In patients with irritable bowel syndrome, symptoms may be caused by alterations either primarily in the central nervous system (top-down model), or in the gut (bottom-up model), or in a combination of both. The brain–gut axis may be stimulated by various stressors either directed to the central nervous system (exteroreceptive stress) or to the gut (interoceptive stress). Particularly, clinical evidence suggest that in complex and multifactorial diseases such as irritable bowel syndrome, psychological disorders represent significant factors in the pathogenesis and course of the syndrome. Neuroimaging techniques have shown functional differences between central process in healthy subjects and patients with irritable bowel syndrome. Moreover, a high prevalence of psychological/psychiatric disorders have been reported in IBS patients compared to controls. Several data also suggest an alteration of neuro-endocrine and autonomic output to the periphery in these patients. This review will examine and discuss the complex interplay of neuro-endocrine–immune pathways, closely associated with neuropsychiatric disorders.
112 citations
TL;DR: Diagnostic criteria for IgG4-SC based on cholangiographic classification are useful for distinguishing it from PCa, PSC, and CC.
Abstract: Background
IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria for IgG4-SC based on cholangiographic classification by comparison with several diagnostic modalities.
111 citations
TL;DR: It is found that in oxazolone colitis IL-25 production derives from intestinal epithelial cells and that IL-17BR+ IL-13-producing natural killer T (NKT) cells and nuocytes drive the intestinal inflammation.
Abstract: Background
Interleukin-25 (IL-25) is a potent activator of type-2 immune responses. Mucosal inflammation in ulcerative colitis is driven by type-2 cytokines. We have previously shown that a neutralizing anti-IL-25 antibody abrogated airways hyperreactivity in an experimental model of lung allergy. Therefore, we asked whether blocking IL-25 via neutralizing antibodies against the ligand or its receptor IL-17BR could protect against inflammation in an oxazolone-induced mouse model of colitis.
110 citations
TL;DR: Low-dose rectal diclofenac can prevent post-ERCP pancreatitis, and the incidence of hyperamylasemia after ERCP was not significantly different between the two groups.
Abstract: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.
108 citations
TL;DR: EPLBD should be considered as an alternative to EST for patients in whom EST could not be routinely performed and also recommended for removal of large or difficult common bile duct stones in patients with an underlying coagulopathy or need for anticoagulation following ERCP.
Abstract: Background
Endoscopic sphincterotomy (EST) is the most frequently used technique for removal of stones from the bile duct. In recent years, endoscopic papillary large balloon dilation (EPLBD) has been shown to be a safe and effective technique for the removal of large or difficult common bile duct stones. However, comparison of EPLBD and EST for effectiveness in bile duct stone removal has given inconsistent results. The present meta-analysis was carried out to compare the effect of EPLBD and EST in retrieval of choledocholithiasis.
TL;DR: Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HV PG > 12 mmHg.
Abstract: Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated. One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6 weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG ≤ 12 mmHg. Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4 ± 16.5 vs. 70.3 ± 7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21 ± 5 vs. 26 ± 5 vs. 26 ± 4 mmHg). The correlation of LS and HVPG was stronger in controls with HVPG ≤ 12 mmHg (R = 0.951; P 12 mmHg (R = 0.538; P = 0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS (R = 0.930; P 12 mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.
TL;DR: Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease. Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn’s disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS). Serum NGAL levels were elevated in IBD patients (88.19 ± 40.75 ng/mL) compared with either HC (60.06 ± 24.18 ng/mL) or IBS patients (60.80 ± 20.30 ng/mL), P < 0.0001. No significant difference was shown between UC (86.62 ± 35.40 ng/mL) and CD (89.92 ± 46.05 ng/mL). Significantly higher levels of serum NGAL were observed in patients with active (120.1 ± 38.46) versus inactive IBD (61.58 ± 15.98), P < 0.0001. Serum NGAL displayed a strong ability to distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively, performing better than erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in both UC and CD. Urinary NGAL levels showed neither significant difference among patients and controls nor correlation with disease activity. Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.
TL;DR: Mortalities and morbidities associated with therapeutic procedures for liver tumors were acceptably low in Japan, but were affected by patient and institutional characteristics.
Abstract: Background
Reported mortalities and morbidities of therapeutic procedures for liver tumors vary between studies, because of different designs and small sample sizes. We investigated the mortalities and complication rates for hepatectomy, radiofrequency ablation (RFA), and trans-catheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) in a large sample, using a nationwide Japanese database (the Diagnosis Procedure Combination database).
TL;DR: In this article, the role of COX-2/PGE2 pathway in the development and maintenance of an inflammatory microenvironment in colorectal cancer has been investigated.
Abstract: Accumulating evidence has indicated that inflammatory responses are important for cancer development. Epidemiological studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of colon cancer development. Subsequently, mouse genetic studies have shown that cyclooxygenase (COX)-2, one of the target molecules of NSAIDs, and its downstream product, prostaglandin E2 (PGE2), play an important role in gastrointestinal tumorigenesis. Bacterial infection stimulates the Toll-like receptor (TLR)/MyD88 pathway in tumor tissues, which leads to the induction of COX-2 in stromal cells, including macrophages. Induction of the COX-2/PGE2 pathway in tumor stroma is important for the development and maintenance of an inflammatory microenvironment in gastrointestinal tumors. In such a microenvironment, tumor-associated macrophages express proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, and these cytokines, respectively, activate the nuclear factor (NF)-κB and Stat3 transcription factors in epithelial cells, as well as in stromal cells. Recent mouse studies have uncovered the role of such an inflammatory network in the promotion of gastrointestinal tumor development. Genetically engineered and chemically induced mouse tumor models which mimic sporadic or inflammation-associated tumorigenesis were used in these studies. In this review article, we focus on mouse genetic studies using these tumor models, which have contributed to the elucidation of the molecular mechanisms associated with the inflammatory network in gastrointestinal tumors, and we also discuss the role of each pathway in cancer development. The involvement of immune cells such as macrophages, mast cells, and regulatory T cells in tumor promotion is also discussed.
TL;DR: Increased number of weakly acidic reflux and higher rate of proximal reflux are the main discriminant features in patients with normal AET and SAP+, and can be of help in diagnosing patients withnormal oesophageal acid exposure who fail to have symptoms during MII-pH testing.
Abstract: Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed. To evaluate whether impedance-pH reflux patterns are useful to differentiate NERD from FH. Endoscopy-negative reflux patients underwent impedance-pH off-therapy. Oesophageal AET, characteristics of reflux episodes and symptom association probability (SAP) were measured. Twenty patients asymptomatic during the first test repeated a second examination. Of 329 patients, 130 (40%) were pH-POS, 120 (36%) pH-NEG/SAP+ (hypersensitive oesophagus = HO) and 79 (24%) pH-NEG/SAP− (FH). Total and acid reflux episodes were significantly higher (p < 0.01) in pH-POS compared to pH-NEG/SAP+, pH-NEG/SAP− and healthy volunteers (HVs). Patients pH-NEG/SAP+ had a significantly increased number of weakly acidic reflux episodes compared to pH-POS, pH-NEG/SAP− and HVs (p < 0.01). The rate of proximal reflux episodes in pH-POS (50%) and pH-NEG/SAP+ (47%) was higher (p < 0.01) than in pH-NEG/SAP− (33%) and HVs (33%). Measuring AET, number of reflux episodes and percentage of proximal reflux events permits to identify FH in 70% of cases and HO in 80% of cases who repeated the examination. In patients with normal AET and SAP+, increased number of weakly acidic reflux and higher rate of proximal reflux are the main discriminant features. There is large overlap between FH and HVs. These differences can be of help in diagnosing patients with normal oesophageal acid exposure who fail to have symptoms during MII-pH testing.
TL;DR: TE may perform better than RTE and ARFI in predicting fibrosis and significant fibrosis, but larger studies are needed to determine their diagnostic accuracy in the prediction of liver fibrosis.
Abstract: Background
Real-time tissue elastography (RTE), acoustic radiation force impulse (ARFI) imaging, and transient elastography (TE) are new technologies that are used for liver stiffness evaluation. The aim of this study was to compare these methods in the same population and to determine their diagnostic accuracy in the prediction of liver fibrosis.
TL;DR: It is suggested that older age at IBD onset could be an additional factor to start surveillance in IBD patients, as a high proportion of IBD-associated CRCs developing before the recommended start of surveillance is emphasized.
Abstract: Background
Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development.
TL;DR: The advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years are reviewed.
Abstract: Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years.
TL;DR: An important insight is provided into the mechanism of 5-FU resistance in colorectal cancers and potential targets of miR-19b mediating the cell cycle under treatment with5-FU are revealed.
Abstract: Background
Drug resistance in colorectal cancers is assumed to be mediated by changes in the expression of microRNAs, but the specific identities and roles of microRNAs are largely unclear. We examined the effect of 5-fluorouracil (5-FU) resistance on microRNA expression.
TL;DR: ARFI elastography of the pancreas showed high elasticity in chronic pancreatitis compared to findings in the normal pancreatitis, and this modality is feasible to use for the diagnosis of chronic Pancreas disease.
Abstract: Endoscopic ultrasonography or real-time elastography has been applied for the diagnosis of chronic pancreatitis. Acoustic radiation force impulse (ARFI) imaging is another tissue strain imaging technology, and recent technological advances have enabled quantification of the stiffness of some tissues by measuring the shear wave velocity (SWV) during routine B-mode ultrasonography. ARFI elastography was performed in 52 healthy volunteers and 46 patients with chronic pancreatitis. SWV was measured in the head, body, and tail of the pancreas. The diagnostic performance was assessed using receiver-operating characteristic (ROC) curves. SWV in patients with chronic pancreatitis was significantly higher than that in healthy volunteers in each part of the pancreas, although the measurement was difficult in the tail of the pancreas. The area under the ROC curve was 0.78 in the body of the pancreas, with an optimal cut-off value of 1.40 m/s, and the sensitivity, specificity, positive predictive value, and negative predictive value were 75, 72, 69, and 78%, respectively. In the patients with chronic pancreatitis, alcoholic etiology and decreased body mass index (BMI) were associated with high SWV. ARFI elastography of the pancreas showed high elasticity in chronic pancreatitis compared to findings in the normal pancreas. This modality is feasible to use for the diagnosis of chronic pancreatitis.
TL;DR: Clinical evidence strongly suggests that GERD is associated with sleep disturbances such as shorter sleep duration, difficulty falling asleep, arousals during sleep, poor sleep quality, and awakening early in the morning.
Abstract: Nighttime reflux during sleep plays a crucial role in several conditions associated with gastroesophageal reflux disease (GERD). Reflux patterns during arousal and sleep are different because of delayed gastric emptying, reduced esophageal peristalsis, decreases in swallowing and salivary secretion, and prolonged esophageal clearance during sleep. Clinical evidence strongly suggests that GERD is associated with sleep disturbances such as shorter sleep duration, difficulty falling asleep, arousals during sleep, poor sleep quality, and awakening early in the morning. New mechanisms on how GERD affects sleep have been recently identified by using actigraphy, and sleep deprivation was found to induce esophageal hyperalgesia to acid perfusion. Thus, the relationship between GERD and sleep disturbances is bidirectional. Among lifestyle modifications, avoidance of a late night meal plays a role in prevention of nighttime reflux. Treatment with a proton pump inhibitor (PPI) improves both nighttime symptoms and subjective sleep parameters, but its effects on objective sleep parameters remain unclear. Better control of nighttime acid secretion by administering a PPI at different times or by providing a double-dose PPI, adding H2 receptor antagonists, or other new agents is proposed. The effects of such treatments on sleep disturbances remain to be elucidated. GERD patients with sleep disturbances report more severe symptoms and poorer quality of life as compared to those without sleep disturbances. Consequently, GERD should also be classified as GERD with sleep disturbance and GERD without sleep disturbance.
TL;DR: The molecular basis and recent progress of this novel pathogen-dependent mechanism of H,K-ATPase inhibition, which contributes significantly to the current understanding of H. pylori pathophysiology, are reviewed.
Abstract: Infection of the human stomach mucosa by Helicobacter pylori induces strong inflammatory responses and a transitory hypochlorhydria which can progress in ~2 % of patients to atrophic gastritis, dysplasia, or gastric adenocarcinoma. H. pylori infection of gastric biopsies or cultured gastric epithelial cells in vitro represses the activity of endogenous or transfected promoter of the alpha-subunit (HKα) of gastric H,K-adenosine triphosphatase (H,K-ATPase), the parietal cell enzyme mediating acid secretion. Some mechanistic details of H. pylori-mediated repression of HKα and ensuing hypochlorhydria have been recently elucidated. H. pylori strains expressing a type IV secretion system (T4SS) encoded by the cag pathogenicity island are known to upregulate the transcription factor nuclear factor (NF)-κB. The NF-κB-binding regions in the HKα promoter were identified and shown to repress its transcriptional activity. Interaction studies have indicated that although active phosphorylated NF-κB p65 is present in infected cells, an NF-κB p50/p65 heterodimeric complex fails to bind to the HKα promoter. Point mutations at −159 and −161 bp in the HKα promoter NF-κB binding sequence prevent the binding of NF-κB p50 and prevent H. pylori repression of point-mutated HKα promoter activity. The T4SS factors CagL, CagE, CagM, and possibly CagA and the lytic transglycosylase Slt, are mechanistically involved in NF-κB activation and repression of HKα transcription. CagL, a T4SS pilus component, binds to the integrin α5β1 to mediate translocation of virulence factors into the host cell and initiate signaling. During acute H. pylori infection, CagL dissociates ADAM 17 (a disintegrin and a metalloprotease 17) from the integrin α5β1 complex and stimulates ADAM17-dependent release of heparin-binding epidermal growth factor (HB-EGF), EGF receptor (EGFR) stimulation, ERK1/2 kinase activation, and NF-κB-mediated repression of HKα. These studies suggest that H. pylori inhibits HKα gene expression by an integrin α5β1 → ADAM17 → HB-EGF → EGFR → ERK1/2 → NF-κB pathway mediating NF-κB p50 homodimer binding to the HKα promoter. Here we review the molecular basis and recent progress of this novel pathogen-dependent mechanism of H,K-ATPase inhibition, which contributes significantly to our current understanding of H. pylori pathophysiology.
TL;DR: The spatial correlation among increased colonic innervation density, TRPV1 receptor expression, stimulated SP release, and colitis severity suggested that TRPv1/SP-expressing sensory neurons should be considered as a therapeutic target in human ulcerative colitis.
Abstract: Transient receptor potential vanilloid type-1 (TRPV1)-expressing sensory neurons release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), which play a crucial role in the pathomechanism of experimental colitis. We investigated whether innervation density and neuropeptide release were responsible for the proximodistal aggravation of murine dextran-sulfate-sodium-salt (DSS) colitis. Whole mount TRPV1/CGRP immunostained mouse colon preparations were semiquantitatively analyzed. TRPV1 activation by capsaicin and acidic solution (pH 5.1) induced colonic CGRP/SP release, measured by EIA. Single cell quantitative PCR was employed to measure TRPV1 expression levels in DiI-labeled colonic dorsal root ganglion (DRG) neurons. The proximodistal gradient of DSS colitis severity was investigated in WT, CGRP−/−, SP−/−, and resiniferatoxin (RTX)-desensitized mice, employing mouse endoscopy, histology, and body weight measurement. TRPV1/CGRP-positive nerve fiber density was increased in the distal colon wall. CGRP/SP release induced by TRPV1 activation from the distal colon was greater than that from the proximal colon. This gradient further increased in colitis. TRPV1 gene expression increased in colonic DRGs projecting to the distal, compared to that in colonic DRGs projecting to the proximal colon, and was further enhanced during colitis. In contrast to WT and CGRP−/− mice, SP−/− and RTX-desensitized mice showed amelioration of DSS colitis accompanied by a loss of the proximodistal gradient of inflammation. The spatial correlation among increased colonic innervation density, TRPV1 receptor expression, stimulated SP release, and colitis severity suggested that TRPV1/SP-expressing sensory neurons should be considered as a therapeutic target in human ulcerative colitis.
TL;DR: Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients with gastroesophageal reflux disease.
Abstract: Background
To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients.
TL;DR: Non-gastrinomas with a tumor size of ≥15 mm and all gastrinomas would be an indication for pancreatectomy with lymph node dissection in patients with PNETs based on the tumor size and hormonal production.
Abstract: Background
Because of the rarity and variety of pancreatic neuroendocrine tumors (PNETs), there have been few reports regarding the indication for lymph node dissection in patients with these tumors. This study aimed to evaluate the risk of lymph node metastasis of PNETs based on the tumor size and hormonal production.
TL;DR: The development of metabolome analysis using mass spectrometry will aid the discovery of novel biomarkers, hopefully leading to the early detection of various diseases.
Abstract: Recently, metabolome analysis has been increasingly applied to biomarker detection and disease diagnosis in medical studies. Metabolome analysis is a strategy for studying the characteristics and interactions of low molecular weight metabolites under a specific set of conditions and is performed using mass spectrometry and nuclear magnetic resonance spectroscopy. There is a strong possibility that changes in metabolite levels reflect the functional status of a cell because alterations in their levels occur downstream of DNA, RNA, and protein. Therefore, the metabolite profile of a cell is more likely to represent the current status of a cell than DNA, RNA, or protein. Thus, owing to the rapid development of mass spectrometry analytical techniques metabolome analysis is becoming an important experimental method in life sciences including the medical field. Here, we describe metabolome analysis using liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry (GC–MS), capillary electrophoresis–mass spectrometry, and matrix assisted laser desorption ionization–mass spectrometry. Then, the findings of studies about GC–MS-based metabolome analysis of gastroenterological diseases are summarized, and our research results are also introduced. Finally, we discuss the realization of disease diagnosis by metabolome analysis. The development of metabolome analysis using mass spectrometry will aid the discovery of novel biomarkers, hopefully leading to the early detection of various diseases.
TL;DR: In this paper, the authors evaluated gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs.
Abstract: Background
We aimed to evaluate gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs.
TL;DR: There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN, and KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreaticcancer in IPMN patients.
Abstract: Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes. Surgically resected IPMNs (n = 25) were classified into four subtypes by hematoxylin and eosin (HE p < 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (p < 0.01). All cases with KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p < 0.05%). There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.
TL;DR: NBI does not improve theAdenoma detection rate during primary colonoscopy; however, it has a lower miss rate for adenoma lesions in the proximal colon than WLI.
Abstract: Previous studies have yielded conflicting results on the adenoma detection rate with narrow band imaging (NBI) compared with white light imaging (WLI). To overcome the confounding factors of these studies, we aimed to evaluate the colonic adenoma detection rate with primary NBI versus that with primary WLI by using consistent NBI system, endoscope, and imaging settings, and experienced colonoscopists. In this multicenter prospective trial, 813 patients were randomized to undergo high-definition, tandem colonoscopy in the right colon with either NBI followed by WLI (NBI–WLI group) or WLI followed by NBI (WLI–NBI group). The NBI settings were fixed at surface structure enhancement level A-5 and adaptive index of hemoglobin color enhancement level 3. All detected polyps were resected or biopsied for histopathological analysis. The primary and secondary outcome measures were the adenoma detection rates and miss rates, respectively, with primary imaging. The NBI–WLI and WLI–NBI groups comprised 389 and 393 patients, respectively, who met the inclusion criteria. The groups did not differ significantly in age, gender, institution, indication for colonoscopy, bowel preparation, or observation time. The adenoma detection rates of primary NBI and WLI were 42.3 and 42.5 %, respectively [difference not significant (NS)]. The adenoma miss rate was significantly less with primary NBI than with primary WLI (21.3 vs. 27.8 %; p = 0.03). NBI does not improve the adenoma detection rate during primary colonoscopy; however, it has a lower miss rate for adenoma lesions in the proximal colon than WLI.