Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal,healthy stomach

AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high risk of gastric cancer or peptic ulcer diseases.METHODS:Among 162 Japanese outpatients,pepsinogen-(Pg-)and(Pg)were measured using a conventional Japanese technique,and the European GastroPanel examination(Pg and Pg,gastrin-17 and H pylori antibodies).Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa,H pylori non-atrophic gastritis or atrophic gastritis.RESULTS:Pg-and Pg assays with the GastroPanel and the Japanese method showed a highly significant correlation.For methodological reasons,however,serum Pg-,but not Pg,was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5%of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies.GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy,95% sensitivity and 93% specifi city.CONCLUSION:Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhage,perforation,infection(cholangitis or cholecystitis) or other complicationss were 0%(0/60),0%(0/60),0%(0/60),0%(0/60),0%(0/60),respectively,in the stent group.Univariate analysis revealed no significant differences in high risk factors between the two groups.The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.CONCLUSION:Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis.Therefore authors recommend pancreatic stent placement after ERCP in high risk patients.

Novel role of toll-like receptors in Helicobacter pylori-induced gastric malignancy

Helicobacter pylori(H.pylori)infects the human stomach during infancy and develops into chronic activeinflammation.The majority of H.pylori tend to colonize within the mucous gel layer of the stomach.Thestomach lacks its own immune function,thus innateimmunity as the first line of defense is vital for specificimmunity against H.pylori.We review recent discoveries in the pathophysiologic roles of toll-like receptors(TLRs),mainly TLR2 and TLR4,in H.pylori-induced inflammation.In addition,the TLR pathways activated byH.pylori-induced inflammation have been shown to beclosely associated not only with gastric carcinogenesis,but also with formation of the tumor microenvironmentthrough the production of pro-inflammatory cytokines,chemokines,and reactive oxygen species.Althoughthe correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear,a recent study demonstrated that STAT3-driven upregulation of TLR2 might promote gastric tumorigenesis independent of inflammation.Further research onthe regulation of TLRs in H.pylori-associated gastriccarcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.

Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases?

In immunoglobulin G4(IgG4)-related disease(RD),organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs.Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis,it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD,because none of the following is observed in these lesions:a mass-like formation;dense fibrosis;or obliterative phlebitis.Based on our review of the literature,there appear to be two types of IgG4-related gastrointestinal disease.One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach,consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells,which usually show submucosal spreading.The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach,colon,and major duodenal papilla,showing polypoid or mass-like lesions.Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose.It is of utmost importance to rule out malignancy.However,these lesions may respond to steroid therapy.To avoid unnecessary resection,IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells

AIM: To clarify the role of Janus kinase-signal transducersand activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs).METHODS: PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2,STAT1, STAT3, and ERK was determined by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2′deoxyuridine.RESULTS: PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGFinduced activation of STAT1 and STAT3 was inhibited bya Src inhibitor PP1 and a JAK2 inhibitor AG490, whereasPDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense oligonucleotide.CONCLUSION: PDGF-BB activated JAK2-STAT pathwayvia Src-dependent mechanism. Activation of JAK2-STAT3pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.

Management of acute pancreatitis in Japan: analysis of nationwide epidemiological survey

Acute pancreatitis(AP) is an acute inflammatory disease of the exocrine pancreas. In Japan, nationwide epidemiological surveys have been conducted every 4 to 5 years by the Research Committee of Intractable Pancreatic Diseases, under the support of the Ministry of Health, Labour, and Welfare of Japan. We reviewed the results of the nationwide surveys focusing on the severity assessment and changes in the therapeutic strategy for walled-off necrosis. The severity assessment system currently used in Japan consists of 9 prognostic factors and the imaging grade on contrastenhanced computed tomography. By univariate analysis, all of the 9 prognostic factors were associated with AP-related death. A multivariate analysis identified 4 out of the 9 prognostic factors(base excess or shock, renal failure, systemic inflammatory response syndrome criteria, and age) that were associated with AP-related death. Receiver-operating characteristics curve analysis showed that the area under the curve was 0.82 for these 4 prognostic factors and 0.84 for the 9 prognostic factors, suggesting the comparable utility of these 4 factors in the severity assessment. We also examined the temporal changes in treatment strategy for walled-off necrosis in Japan according to the 2003, 2007, and 2011 surveys. Step-up approaches and lessinvasive endoscopic therapies were uncommon in 2003 and 2007, but became popular in 2011. Mortality has been decreasing in patients who require intervention for walled-off necrosis. In conclusion, the nationwide survey revealed the comparable utility of 4 prognostic factors in the severity assessment and the increased use of less-invasive, step-up approaches with improved clinical outcomes in the management of walled-off necrosis.

Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B

瞄准：由严峻的 TH1 和 TH2 承诺和规章的 T 房间学习 HBV 特定的 CD4+ T 房间的 hyporesponsiveness 的机制。方法：有长期的肝炎 B 的九个病人被注册。外部血单音的原子房间与 HBcAg 或 HBsAg 被刺激评估他们的潜力承诺 TH1 和 TH2 区别。规章的 T 房间的 HBcAg 特定的活动被与抗体染色到 CD4， CD25， CTLA-4 和 interleukin-10 评估。规章的 T 房间的角色被治疗进一步与 anti-interleukin-10 抗体和 CD4+CD25+ 房间的弄空估计。结果：为 T 赌注， IL-12R beta2 和 IL-4 的 mRNAs 的水平比在有 HBcAg 刺激的健康题目在病人是显著地更低的。尽管 CD4+CD25highCTLA-4+ T 房间的人口不在病人和健康题目之间是不同的， IL-10 secreting 房间响应 HBcAg 在病人在 CD4+ 房间和 CD4+CD25+ 房间被发现，并且他们没在与 HBsAg 被刺激的房间被发现。anti-IL-10 抗体的增加与控制抗体相比恢复了 HBcAg 特定的 TH1 抗体的数量(P 【 0.01， 0.34%+/-0.12% 对 0.15%+/-0.04%) 。当时， CD4+CD25+ T 房间的删除增加了 HBcAg 特定的 TH1 抗体的数量与淋巴细胞相比使用规章的 T 房间重新组成(P 【 0.01， 0.03%+/-0.02% 对 0.18%+/-0.05%) 。结论：结果显示到 HBcAg 的 T 房间 hyporesponsiveness 的机制响应 HBsAg 与承诺 TH2 的房间的增加相对照包括导致 HBcAg 的规章的 T 房间的激活。

Radiation therapy has been shown to be adaptable for various stages of hepatocellular carcinoma

In addition to surgical procedures, radiofrequency ablation is commonly used for the treatment of hepatocellular carcinomas(HCCs) of limited size and number. Transcatheter arterial chemoembolization(TACE), using iodized poppy seed oil, Lipiodol and anticancer drugs, has been actively performed for the treatment of unresectable HCC, particularly in Asian countries. Recently, Sorafenib become available for advanced HCCs when the liver is still sufficiently functional. Sorafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects. However, the effect of sorafenib seems to be inadequate to control the progression of HCC. Radiation therapy(RT)for HCC has a potential role across all stages of HCC. However, RT is generally not considered an option in HCC consensus documents or national guidelines, primarily because of insufficient supporting evidence. However, the method of RT has much improved because of advances in technology. Moreover, combined treatment of RT plus other treatments(TACE, sorafenib and chemotherapy etc.) has become one of the alternative therapies for HCC. Therefore, we should understand the various kinds of RT available for HCC. In this review, we focus on various kinds of external beam radiation therapy.

Micro RNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

AIM: To investigate the microR NA(miR NA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miR NA expression profiles were compared in colonic lesions from matched samples; histologically, nonneoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miR NA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miR NA mimics. mR NA and protein levels of the target gene in colon cancer cell lines with a mimic control or miR NA mimics were measured using qR TPCR and Western blotting. The expression levels of miR NA and target gene in colorectal tissue samples were also measured.RESULTS: Microarray analysis identified that the miR-320 family, including miR-320 a, miR-320 b, miR-320 c, miR-320 d and miR-320 e, were differentially expressed in adenomaand submucosal invasive carcinoma. The mi R-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mR NA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression.CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Establishment and characterization of a rat pancreatic stellate cell line by spontaneous immortalization

AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous immortalization.METHODS: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift assay.Activation of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme immunoassay.RESULTS: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution,and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely immortalized.SIPS cells retained morphological characteristics of primary,culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type Ⅰ collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP kinases.Interleukin-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP kinases.CONCLUSION: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.

Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells

AIM: To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BBinduced proliferation and migration of pancreatic stellate cells (PSCs).METHODS: PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Cell migration was assessed using modified Boyden chambers. CyclinD1, p21waf1, and p27kip1 expression and phosphorylation of PDGF β-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phosphatidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide. RESULTS: EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyondthe G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF β-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/ Akt pathways.CONCLUSION: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibrdon of PDGF-mediated signaling pathways.

Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells

AIM: To examine the ability of ET-1 to affect the cell functions of PSCs and the underlying molecular mechanisms.METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and ET receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain (MLC), extracellular-signal regulated kinase (ERK), and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine.RESULTS: Culture-activated PSCs expressed ETA and ETB receptors, and ET-1. ET-1 induced phosphorylation of MLC and ERK, but not Akt. ET-1 induced contraction and migration,but did not alter proliferation of PSCs. ET-1-induced contraction was inhibited by an ETA receptor antagonist BQ-123 and an ETB receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and migration.CONCLUSION: ET-1 induced contraction and migration of PSCs through ET receptors and activation of Rho-Rho kinase. ETA and ETB receptors play different roles in the regulation of these cellular functions in response to ET-1.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review

Since Isaacson and Wright first reported on the extranodal marginal zone B-cell lymphoma of the stomach in 1983,following studies have clarified many aspects of this disease.We now know that the stomach is the most affected organ by this disease,and approximately90% of gastric mucosa-associated lymphoid tissue(MALT) lymphomas are related to Helicobacter pylori(H.pylori) infection.This implies that approximately 10% of gastric MALT lymphomas occur independent of H.pylori infection.The pathogenesis of these H.pylori-negative gastric MALT lymphomas remains unclear.To date,there have been several speculations.One possibility is that genetic alterations result in nuclear factor-kappa B(NF-κB) activation.Among these alterations,t(11;18)(q21;q21) is more frequently observed in H.pylori-negative gastric MALT lymphomas,and such translocation results in the synthesis of fusion protein API2-MALT1,which causes canonical and noncanonical NF-κB activation.Another possibility is infection with bacteria other than H.pylori.This could explain why H.pylori eradication therapy can cure some proportions of H.pylori-negative gastric MALT lymphoma patients,although the bacteria responsible for MALT lymphomagenesis are yet to be defined.Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment.A certain proportion of H.pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence,H.pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H.pylori infection status.

Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis:A multicenter study in Japan

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis.AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan.METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography(CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria.RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis(sensitivity,73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis(specificity, 62.5%). The area under the curve(AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade.CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

Transition of early-phase treatment for acute pancreatitis: An analysis of nationwide epidemiological survey

Treatment of acute pancreatitis(AP) is one of the critical challenges to the field of gastroenterology because of its high mortality rate and high medical costs associated with the treatment of severe cases. Early-phase treatments for AP have been optimized in Japan, and clinical guidelines have been provided. However, changes in early-phase treatments and the relationship between treatment strategy and clinical outcome remain unclear. Retrospective analysis of nationwide epidemiological data shows that time for AP diagnosis has shortened, and the amount of initial fluid resuscitation has increased over time, indicating the compliance with guidelines. In contrast, prophylactic use of broad-spectrum antibiotics has emerged. Despite the potential benefits of early enteral nutrition, its use is still limited. The roles of continuous regional arterial infusion in the improvement of prognosis and the prevention of late complications are uncertain. Furthermore, early-phase treatments have had little impact on late-phase complications, such as walledoff necrosis, surgery requirements and late(> 4 w) AP-related death. Based on these observations, earlyphase treatments for AP in Japan have approached the optimal level, but late-phase complications have become concerning issues. Early-phase treatments and the therapeutic strategy for late-phase complications both need to be optimized based on firm clinical evidence and cost-effectiveness.

Helicobacter pylori-negative,non-steroidal anti-inflammatory drug:Negative idiopathic ulcers in Asia

Since the discovery of Helicobacter pylori(H.pylori)infection in the stomach,the bacteria infection and non-steroidal anti-inflammatory drugs(NSAIDs)use had been considered to be the 2 main causes of peptic ulcers.However,there have been recent reports of an increase in the proportion of peptic ulcers without these known risk factors;these are termed idiopathic peptic ulcers.Such trend was firstly indicated in 1990s from some reports in North America.In Asia,numerous studies reported that idiopathic ulcers accounted for a small percentage of all ulcers in the 1990s,but in the2000s,multiple studies reported that the proportion of idiopathic ulcers had reached 10%-30%,indicating that the incidence of idiopathic ulcers in Asia has also been rising in recent years.While a decline in H.pylori infection rates of general population in Asia is seen as the main reason for the increased incidence of idiopathic ulcers,it is also possible that the absolute number of idiopathic ulcer cases has increased.Advanced age,serious systemic complication,and psychological stress are considered to be the potential risk factors for idiopathic ulcers.Management of idiopathic ulcers is challenging,at present,because there is no effective preventative measure against recurrence in contrast with cases of H.pylori-positive ulcers and NSAIDs-induced ulcers.As it is expected that H.pylori infection rates in Asia will decline further in the future,measures to treat idiopathic ulcers will also likely become more important.

Consensus of primary care in acute pancreatitis in Japan

在日本的尖锐胰腺炎的发生正在增加并且每百万张人口从 187 ～ 347 个盒子。盒子命运是 0.2% 为对温和中等，并且 9.0% 为在在 2003 的日本的严重尖锐胰腺炎。在日本的胰腺炎的专家做了与尖锐胰腺炎在病人的早管理集中于实际方面的这个文件。尖锐胰腺炎和严厉层化的正确诊断应该为尖锐胰腺炎的诊断用标准在所有病人被做并且多，因素得分系统尽早由胰的难处理的疾病的研究委员会求婚了。与尖锐胰腺炎诊断的所有病人应该在医院里被管理。血压监视，脉搏和呼吸率，体温，时时尿的体积，和血氧饱和水平在如此的病人的管理是必要的。早精力旺盛的静脉内的水和具有最前的重要性稳定循环动力学。有鸦片剂的足够的疼痛地势也是重要的。在严重尖锐胰腺炎，在一个早阶段的抗菌素的预防静脉内的管理被推荐。一旦尖锐胰腺炎的诊断被证实，朊酶禁止者的管理应该被开始。如果没有肠塞痛并且胃肠的流血的清楚的症状，从早舞台用非肠道的营养喂的肠内的联合被推荐。有严重尖锐胰腺炎的病人应该尽早被转移到 ICU 执行象朊酶的连续地区性的动脉的注入那样的特殊措施禁止者和抗菌素，和连续牙齿过敏过滤。日本政府为难处理的疾病作为关于措施的研究的工程之一为严重尖锐胰腺炎盖住医疗保健开销。

Useful strategies to prevent severe stricture after endoscopic submucosal dissection for superficial esophageal neoplasm

The minimal invasiveness of endoscopic submucosal dissection(ESD) prompted us to apply this technique to large-size early esophageal squamous cell carcinoma and Barrett's adenocarcinoma, despite the limitationsin the study population and surveillance duration. A post-ESD ulceration of greater than three-fourths of esophageal circumference was advocated as an important risk factor for refractory strictures that require several sessions of dilation therapy. Most of the preoperative conditions are asymptomatic, but dilatation treatment for dysphagia associated with the stricture has potential risks of severe complications and a worsening of quality of life. Possible mechanisms of dysphasia were demonstrated based on dysmotility and pathological abnormalities at the site:(1) delayed mucosal healing;(2) severe inflammation and disorganized fibrosis with abundant extracellular matrices in the submucosa; and(3) atrophy in the muscularis proper. However, reports on the administration of anti-scarring agents, preventive dilation therapies, and regenerative medicine demonstrated limited success in stricture prevention, and there were discrepancies in the study designs and protocols of these reports. The development and consequent long-term assessments of new prophylactic technologies on the promotion of wound healing and control of the inflammatory/tumor microenvironment will require collaboration among various research fields because of the limited accuracy of preoperative staging and high-risk of local recurrence.

Impaired glucose tolerance in acute pancreatitis

Acute pancreatitis(AP) is an acute inflammatory disease of the exocrine pancreas. In spite of the pivotal role of the endocrine pancreas in glucose metabolism, the impact of impaired glucose tolerance on AP has not been fully elucidated. A meta-analysis of seven observational studies showed that type 2 diabetes mellitus(DM) was associated with an increased risk of AP. The increased risk of AP shown in the meta-analysis was independent of hyperlipidemia, alcohol use and gallstones. Antidiabetic drugs including incretins might increase the risk of AP, but no intervention trials have confirmed this. Although a controversial finding, DM seems to be associated with severe attacks and organ failure in AP. We analyzed the results of a nationwide epidemiological survey of AP in Japan. We studied the impact of pre-existing DM on the clinical course of AP in 1954 cases for which information on DM status was available at the onset of AP. The prevalence of DM in AP patients(12.8%) was higher than that in the general population in Japan(10.5%). AP patients with DM had higher morbidity of cardiovascular and renal failure than those without DM. About 35% of the idiopathic AP patients with DM had renal failure. The mortality of AP patients with DM(4.0%) was higher than that of AP patients without DM(1.7%). If stratified by etiology, idiopathic, but not alcoholic or biliary, AP patients with DM were predisposed to increased mortality(9.7%). In conclusion, impaired glucose tolerance might have an impact on the development and clinical outcome of AP. However, the impact might depend on the cause of hyperglycemia, the condition of DM including severity, duration and treatment, and the characteristics of the AP patients including age, etiology and comorbidity.