AIM To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODS Jap...AIM To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODS Japanese patients with predominant GERD symptoms recruited according to the Montreal definition were treated for 4 wk using a standard dose of proton pump inhibitor(PPI). The GERD-TEST and the Medical Outcome Study Short Form-8 Health Survey(SF-8) were administered at baseline and after 4 wk of treatment. The GERD-TEST contains three domains: the severity of GERD and functional dyspepsia(FD) symptoms(5 items),the level of dissatisfaction with daily life(DS)(4 items),and the therapeutic efficacy as assessed by the patients and medication compliance(4 items).RESULTS A total of 290 patients were eligible at baseline; 198 of these patients completed 4 wk of PPI therapy. The internal consistency reliability as evaluated using the Cronbach's α values for the GERD,FD and DS subscales ranged from 0.75 to 0.82. The scores for the GERD,FD and DS items/subscales were significantly correlated with the physical and mental component summary scores of the SF-8. After 4 wk of PPI treatment,the scores for the GERD items/subscales were greatly reduced,ranging in value from 1.51 to 1.87 and with a large effect size(P < 0.0001,Cohen's d; 1.29-1.63). Statistically significant differences in the changes in the scores for the GERD items/subscales were observed between treatment responders and non-responders(P < 0.0001).CONCLUSION The GERD-TEST has a good reliability,a good convergent and concurrent validity,and is responsive to the effects of treatment. The GERD-TEST is a simple,easy to understand,and multifaceted PRO instrument applicable to both clinical trials and the primary care of GERD patients.展开更多
AIM: To analyze the diagnostic utility of a small-caliber endoscope(SC-E) and clinicopathological features of false-negative gastric cancers(FN-GCs). METHODS: A total of 21638 esophagogastroduodenoscopy(EGD) gastric c...AIM: To analyze the diagnostic utility of a small-caliber endoscope(SC-E) and clinicopathological features of false-negative gastric cancers(FN-GCs). METHODS: A total of 21638 esophagogastroduodenoscopy(EGD) gastric cancer(GC) screening examinations were analyzed. Secondary endoscopic examinations(n = 3352) were excluded because most secondary examinations tended to be included in the conventional endoscopy(C-E) group. Detection rates of GCs and FN-GCs were compared between SC-E and C-E groups. FN-GC was defined as GC performed with EGD within the past 3 years without GC detection. Macroscopic types, histopathological characteristics and locations of FN-GCs were compared with firstly foundgastric cancers(FF-GCs) in detail. RESULTS: SC-E cases(n = 6657) and C-E cases(n = 11644), a total of 18301 cases, were analyzed. GCs were detected in 16(0.24%) SC-E cases and 40 C-E(0.34%) cases(P = 0.23) and there were 4 FN-GCs(0.06%) in SC-E and 13(0.11%) in C-E(P = 0.27), with no significant difference. FN-GCs/GCs ratio between SC-E and C-E groups was not significantly different(P = 0.75). The comparison of endoscopic macroscopic types of FN-GCs tended to be a less advanced type(P = 0.02). Histopathologically, 70.6% of FN-GCs were differentiated and 29.4% undifferentiated type. On the other hand, 43.0% of FF-GCs were differentiated and 53.8% undifferentiated type, so FN-GCs tended to be more differentiated type(P = 0.048). CONCLUSION: The diagnostic utility of SC-E for the detection of GCs and FN-GCs was not inferior to that of C-E. Careful observation for superficially depressed type lesions in the upper lesser curvature region is needed to decrease FN-GCs.展开更多
A 78-year-old male was admitted to our hospital because of choledocholithiasis.ERC demonstrated choledocholithiases with a maximum diameter of 13 mm, and we performed endoscopic papillary large balloon dilation(EPLBD)...A 78-year-old male was admitted to our hospital because of choledocholithiasis.ERC demonstrated choledocholithiases with a maximum diameter of 13 mm, and we performed endoscopic papillary large balloon dilation(EPLBD) with a size of 15 mm.Immediately following the balloon deflation, spurting hemorrhage occurred from the orifice of the duodenal papilla.Although we performed endoscopic hemostasis by compressing the bleeding point with the large balloon catheter, we could not achieve hemostasis.Therefore, we placed a 10 mm fully covered selfexpandable metallic stent(SEMS) across the duodenal papilla, and the hemorrhage stopped immediately.After 1 wk of SEMS placement, duodenal endoscopy revealed ulcerative lesions in both the orifice of the duodenal papilla and the lower bile duct.A direct peroral cholangioscopy using an ultra-slim upper endoscope revealed a visible vessel with a longitudinal mucosal tear in the ulceration of the lower bile duct.We believe that the mucosal tear and subsequent ruptured vessel were caused by the EPLBD procedure.展开更多
AIM:To examine the frequency and prevention of musculoskeletal pain in Japanese gastrointestinal endoscopists and non-endoscopist physicians.METHODS:Questionnaires were sent to 275 endoscopists and 173 non-endoscopist...AIM:To examine the frequency and prevention of musculoskeletal pain in Japanese gastrointestinal endoscopists and non-endoscopist physicians.METHODS:Questionnaires were sent to 275 endoscopists and 173 non-endoscopists working in Hiroshima University Hospital and its affiliated hospitals.RESULTS:The completed questionnaires were returned by 190(69%)endoscopists and 120(69%)non-endoscopists.The frequency of pain in the hand and wrist,and especially the left thumb,was significantly higher in endoscopists than in non-endoscopists(17%vs 6%,P=0.004).Using multivariate analysis,the only significant factor associated with this pain was the age of the endoscopist(odds ratio 2.77,95%confidence interval,1.23-6.71,P=0.018).Interestingly,endoscopists had made significantly fewer modifications to their endoscopic practices than non-endoscopists(12%vs 33%,P <0.0001)to prevent pain.CONCLUSION:Pain in the hand and wrist may be endoscopy-related.However,endoscopists made little modifications in practice to prevent such pain.More attention to prevention appears necessary.展开更多
A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels ...A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.展开更多
IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cho...IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.展开更多
BACKGROUND: Early recurrence (ER) after hepatic resection (HR) is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). This study aimed to identify the clinico- pathological features, outc...BACKGROUND: Early recurrence (ER) after hepatic resection (HR) is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS: We retrospectively examined 130 patients who underwent HR for small HCC (___30 mm). Recurrence was clas- sifted into ER (〈2 years) and late recurrence (LR) (_〉2 years). The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS: ER was observed in 39 patients (30.0%). The sur- vival rate of the ER group was significantly lower than that of the LR group (P〈0.005), and ER was an independent prognos- tic factor for poor survival (P=0.0001). The ER group had a significantly higher frequency (P=0.0039) and shorter interval (P=0.027) of development to carcinoma beyond the Milan criteria (DBMC) compared with the LR group, and ER was an independent risk factor for DBMC (P〈0.0001). Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER (P=0.012, 0.010, and 0.019, respectively).CONCLUSIONS: ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.展开更多
This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inf...This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD.IBDassociated with PSC(PSC-IBD)shows an increased incidence of pancolitis,mild symptoms,and colorectal malignancy.Although an increased incidence of pancolitis is a characteristic finding,some cases are endoscopically diagnosed as right-sided ulcerative colitis.Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon.The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition.The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)are similar to those of PSC.The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.展开更多
AIM: To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis. METHODS: Acute hemorrhagic pancreatitis(AP) was induced in male rats by intr...AIM: To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis. METHODS: Acute hemorrhagic pancreatitis(AP) was induced in male rats by intraductal infusion of 40 μl/100 g body weight of 3% sodium taurocholate. All rats took food ad libitum. At 24 h after induction of AP, rats were divided into four groups: control(AP-C), pancreas rest(AP-R), stimulation(AP-S), and rest/stimulation(AP-R/S). Rats in the AP-C, AP-R and AP-S groups received oral administration of 2 ml/kg body weight saline, cholecystokinin(CCK)-1 receptor antagonist, and endogenous CCK release stimulant, respectively, twice daily for 10 d, while those in the AP-R/S group received twice daily CCK-1 receptor antagonist for the first 5 d followed by twice daily CCK release stimulant for 5 d. Rats without any treatment were used as control group(Control). Biochemical andhistological changes in the pancreas, and secretory function were evaluated on day 12 at 24 h after the last treatment. RESULTS: Feeding ad libitum(AP-C) delayed biochemical, histological and functional recovery from AP. In AP-C rats, bombesin-stimulated pancreatic secretory function and HOMA-β-cell score were significantly lower than those in other groups of rats. In AP-R rats, protein per DNA ratio and pancreatic exocrine secretory function were significantly low compared with those in Control rats. In AP-S and AP-R/S rats, the above parameters recovered to the Control levels. Bombesinstimulated pancreatic exocrine response in AP-R/S rats was higher than in AP-S rats and almost returned to control levels. In the pancreas of AP-C rats, destruction of pancreatic acini, marked infiltration of inflammatory cells, and strong expression of α-smooth muscle actin, tumor necrosis factor-α and interleukin-1β were seen. Pancreatic rest reversed these histological alterations, but not atrophy of pancreatic acini and mild infiltration of inflammatory cells. In AP-S and AP-R/S rats, the pancreas showed almost normal architecture. CONCLUSION: The favorable treatment strategy for AP is to keep the pancreas at rest during an early stage followed by pancreatic stimulation by promoting endogenous CCK release.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirr...Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.展开更多
AIM: To investigate risk factors for development of hepatocellular carcinoma(HCC) in patients with hepatitis C virus-related liver cirrhosis(LC-C).METHODS: To evaluate the relationship between clinical factors includi...AIM: To investigate risk factors for development of hepatocellular carcinoma(HCC) in patients with hepatitis C virus-related liver cirrhosis(LC-C).METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon(IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.RESULTS: HCC was diagnosis in 50(21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older(P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein(AFP)(P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio(OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/m L(P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin(DCP) levels of ≥ 40 m AU/mL at 24 wk after the completion of IFN and ribavirin therapy(P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.展开更多
Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic sc...Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic scraper Trefle~? has been reported and demonstrated high cancer detectability in malignant biliary strictures. This device is used to scrape the stricture over the guidewire, and, in the original method, the tissue and/or cell samples obtained are subjected to histological and/or cytological analysis separately. However, discrimination of chunks of tissue is hampered by the opacity of the surrounding fluid. We have developed a cell block technique for the Trefle~? device without dividing obtained specimens into tissue and cellular components, which is the simplest method and enables immunohistochemical analysis. We present a case of obstructive jaundice diagnosed immunohistochemically as pancreatic metastasis from colon cancer using cell block sections obtained with the Trefle~? device, which procedure is as easy as conventional brush cytology.展开更多
In inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD), the duration and severity of inflammation are responsible for the development of colorectal cancer. Inflammatory cytokine...In inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD), the duration and severity of inflammation are responsible for the development of colorectal cancer. Inflammatory cytokines such as interleukin (IL)-8 and tumor necrotic factor (TNF)-a, which are released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Current treatments for advanced colorectal cancers focus primarily on targeting epidermal growth factor receptor (EGFR) signaling. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of theproheparin-binding epidermal growth factor—like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM), so that the resulting soluble HB-EGF activates EGFR. In parallel, the carboxy-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, where HB-EGF-CTF binds the nuclear promyelocytic leukemia zinc finger (PLZF) protein, resulting in the nuclear export of the PLZF transcriptional repressor and thereby affecting cell proliferation. Screening for potent chemical inhibitors of the interactions between HB-EGF-CTF and PLZF identified telmisartan (and related compounds in corporating a biphenyl tetrazole moiety) as inhibitors of cell proliferation. Here we focus on the inhibitory effects of these compounds on cell proliferation, demonstrating the potential for targeting the nuclear translocation of HB-EGF-CTF in the treatment of colitis-associated cancer.展开更多
BACKGROUND Hybrid endoscopic submucosal dissection(ESD)that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner,has been developed for endoscopic resection of gastroint...BACKGROUND Hybrid endoscopic submucosal dissection(ESD)that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner,has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD.Although the superiority of hybrid ESD with SOUTEN,a single multifunctional device,over conventional ESD has been indicated,the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group,but not to the conventional ESD group,due to ethical issue in clinical practice.AIM To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study.METHODS Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University,performing 32 procedures each for hybrid ESD and conventional ESD.Mock lesions(10-15 mm,diameter)were created in the porcine stomach.The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection,perforation,procedure time/speed for both,mucosal incision,and submucosal dissection.Factors associated with difficulty in ESD including longer procedure time,incomplete resection,and perforation,were also investigated.Categorical and continuous data were analyzed using the chi-square test or Fisher’s exact test and the Mann-Whitney U test,respectively.RESULTS The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD(median:8.3 min vs 16.2 min,P<0.001).Time,speed,and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD(time,5.2 min vs 10.4 min,P<0.001;speed,43.7 mm^(2)/min vs 23.8 mm^(2)/min,P<0.00;injection volume,1.5 mL vs 3.0 mL,P<0.001),although no significant differences in those factors were observed between both groups during mucosal incision.There was also no significant difference between both groups in the en bloc/complete resection rate and perforation rate(complete resection,93.8%vs 87.5%,P=0.67;perforation,0% vs 3.1%,P=1).Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD(odds ratio=10.2;highest among factors).CONCLUSION Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions.It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.展开更多
Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis(UC). Proposed mediators of inflammation in UC inc...Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis(UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α) and interleukin-2, and the cellsurface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues(azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody(vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin(ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease(IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.展开更多
Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of I...Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of Ig G4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated Ig G4-SC displayed hilar biliary strictures, whereas isolated Ig G4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic Ig G4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum Ig G4 levels were within the normal limits. The mean serum Ig G4 level measured before surgery was 202.1 mg/d L(4 cases). Isolated intrapancreatic Ig G4-SC is difficult to diagnose, especially if the Ig G4 level remains normal. Thus, this type of Ig G4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.展开更多
AIM To assess the clinical characteristics of patients with complicated erosive esophagitis(EE) and their associated factors.METHODS This prospective, cross-sectional study included patients diagnosed with EE by upper...AIM To assess the clinical characteristics of patients with complicated erosive esophagitis(EE) and their associated factors.METHODS This prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios(aO R) and 95%CI for the association with complicated EE.RESULTS During the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors(PPIs) were included. Of them, 143(8.2%) had EE complications. Esophageal bleeding occurred in 84(4.8%) patients, esophageal strictures in 45(2.6%) patients, and 14(0.8%) patients experienced both. Multivariate analysis showed that increased age(a OR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents(a OR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B(a OR: 2.69; 95%CI: 1.48-4.96), C(aO R: 15.38; 95%CI: 8.62-28.37), and D(aO R: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated(a OR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age(a OR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B(aO R: 3.60; 95%CI: 1.52-8.50), C(a OR: 27.61; 95%CI: 12.34-61.80), and D(a OR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age(a OR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom(aO R: 2.51; 95%CI: 1.39-4.51), concomitantuse of psychotropic agents(a OR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C(aO R: 7.35; 95%CI: 3.32-16.25), and D(a OR: 20.34; 95%CI: 8.36-49.53) and long-segment Barrett's esophagus(a OR: 4.63; 95%CI: 1.64-13.05).CONCLUSION Aging and severe EE were common associated factors, although there were more associated factors in esophageal strictures than esophageal ulcer bleeding. Despite the availability and widespread use of PPIs, EE complications are likely to remain a problem in Japan owing to the aging population and high-stress society.展开更多
BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is controversial.AIM To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endosc...BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is controversial.AIM To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)for SNADETs.METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs,which included eight hospitals in Fukuoka,Japan,between April 2001 and October 2017.A total of 142 patients with SNADETs treated with EMR or ESD were analyzed.Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups.We analyzed the treatment outcomes,including the rates of en bloc/complete resection,procedure time,adverse event rate,hospital stay,and local or metastatic recurrence.RESULTS Twenty-eight pairs of patients were created.The characteristics of patients between the two groups were similar after matching.The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group[median procedure time(interquartile range):6(3-10.75)min vs 87.5(68.5-136.5)min,P<0.001,hospital stay:8(6-10.75)d vs 11(8.25-14.75)d,P=0.006].Other outcomes were not significantly different between the two groups(en bloc resection rate:82.1%vs 92.9%,P=0.42;complete resection rate:71.4%vs 89.3%,P=0.18;and adverse event rate:3.6%vs 17.9%,P=0.19,local recurrence rate:3.6%vs 0%,P=1;metastatic recurrence rate:0%in both).Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation.CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD,and provides acceptable curability and safety compared to ESD.Accordingly,EMR for SNADETs is associated with lower medical costs.展开更多
BACKGROUND A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection(ESD)for gastrointestinal tract tumors.The assistant during the ESD using a clutch cutter(ESD-C)needs to rotate the device and...BACKGROUND A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection(ESD)for gastrointestinal tract tumors.The assistant during the ESD using a clutch cutter(ESD-C)needs to rotate the device and grasp the target tissue appropriately;therefore,the assistant’s skill may affect the technical outcomes of ESD-C.AIM To determine how assistant skill level affected the technical outcomes of gastric ESD-C using an ex vivo porcine training model.METHODS In this pilot study,mock lesions of 15-30 mm in diameter were created in the middle or lower third of the porcine stomach.A total of 32 ESD-C procedures were performed by 16 trainees.Each trainee operator performed two ESD-C procedures;one ESD-C was assisted by an expert(ESD-C-E),and the other was assisted by a non-expert(ESD-C-NE).The total procedure time of the ESD was set as the primary outcome,and en bloc resection rate,complete procedure rate,perforation rate,and each procedure time/speed for mucosal incision or submucosal dissection were set as the secondary outcomes.In addition,we investigated factors associated with the difficulty of ESD including incompletion of ESD procedure,a long procedure time(≥20 min)or intraoperative perforation.RESULTS The median total procedure time of the ESD-C-E was significantly shorter than that of the ESD-C-NE(12.9 min vs 21.9 min,P=0.001).The en bloc resection rate was 100%in both groups.Complete resection rates of the ESD-C-E and ESD-C-NE groups were 100%and 93.8%,respectively.No intraoperative perforation was observed in both groups.In the multivariate analysis,assistant skill was significantly associated with the difficulty of ESD,with the highest odds ratio of 16.5.CONCLUSION Assistance by an expert is an important factor when trainees perform ESD-C procedures.展开更多
基金Supported by Financial support for this clinical study was provided by GERD Society(Osaka,Japan)
文摘AIM To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODS Japanese patients with predominant GERD symptoms recruited according to the Montreal definition were treated for 4 wk using a standard dose of proton pump inhibitor(PPI). The GERD-TEST and the Medical Outcome Study Short Form-8 Health Survey(SF-8) were administered at baseline and after 4 wk of treatment. The GERD-TEST contains three domains: the severity of GERD and functional dyspepsia(FD) symptoms(5 items),the level of dissatisfaction with daily life(DS)(4 items),and the therapeutic efficacy as assessed by the patients and medication compliance(4 items).RESULTS A total of 290 patients were eligible at baseline; 198 of these patients completed 4 wk of PPI therapy. The internal consistency reliability as evaluated using the Cronbach's α values for the GERD,FD and DS subscales ranged from 0.75 to 0.82. The scores for the GERD,FD and DS items/subscales were significantly correlated with the physical and mental component summary scores of the SF-8. After 4 wk of PPI treatment,the scores for the GERD items/subscales were greatly reduced,ranging in value from 1.51 to 1.87 and with a large effect size(P < 0.0001,Cohen's d; 1.29-1.63). Statistically significant differences in the changes in the scores for the GERD items/subscales were observed between treatment responders and non-responders(P < 0.0001).CONCLUSION The GERD-TEST has a good reliability,a good convergent and concurrent validity,and is responsive to the effects of treatment. The GERD-TEST is a simple,easy to understand,and multifaceted PRO instrument applicable to both clinical trials and the primary care of GERD patients.
文摘AIM: To analyze the diagnostic utility of a small-caliber endoscope(SC-E) and clinicopathological features of false-negative gastric cancers(FN-GCs). METHODS: A total of 21638 esophagogastroduodenoscopy(EGD) gastric cancer(GC) screening examinations were analyzed. Secondary endoscopic examinations(n = 3352) were excluded because most secondary examinations tended to be included in the conventional endoscopy(C-E) group. Detection rates of GCs and FN-GCs were compared between SC-E and C-E groups. FN-GC was defined as GC performed with EGD within the past 3 years without GC detection. Macroscopic types, histopathological characteristics and locations of FN-GCs were compared with firstly foundgastric cancers(FF-GCs) in detail. RESULTS: SC-E cases(n = 6657) and C-E cases(n = 11644), a total of 18301 cases, were analyzed. GCs were detected in 16(0.24%) SC-E cases and 40 C-E(0.34%) cases(P = 0.23) and there were 4 FN-GCs(0.06%) in SC-E and 13(0.11%) in C-E(P = 0.27), with no significant difference. FN-GCs/GCs ratio between SC-E and C-E groups was not significantly different(P = 0.75). The comparison of endoscopic macroscopic types of FN-GCs tended to be a less advanced type(P = 0.02). Histopathologically, 70.6% of FN-GCs were differentiated and 29.4% undifferentiated type. On the other hand, 43.0% of FF-GCs were differentiated and 53.8% undifferentiated type, so FN-GCs tended to be more differentiated type(P = 0.048). CONCLUSION: The diagnostic utility of SC-E for the detection of GCs and FN-GCs was not inferior to that of C-E. Careful observation for superficially depressed type lesions in the upper lesser curvature region is needed to decrease FN-GCs.
文摘A 78-year-old male was admitted to our hospital because of choledocholithiasis.ERC demonstrated choledocholithiases with a maximum diameter of 13 mm, and we performed endoscopic papillary large balloon dilation(EPLBD) with a size of 15 mm.Immediately following the balloon deflation, spurting hemorrhage occurred from the orifice of the duodenal papilla.Although we performed endoscopic hemostasis by compressing the bleeding point with the large balloon catheter, we could not achieve hemostasis.Therefore, we placed a 10 mm fully covered selfexpandable metallic stent(SEMS) across the duodenal papilla, and the hemorrhage stopped immediately.After 1 wk of SEMS placement, duodenal endoscopy revealed ulcerative lesions in both the orifice of the duodenal papilla and the lower bile duct.A direct peroral cholangioscopy using an ultra-slim upper endoscope revealed a visible vessel with a longitudinal mucosal tear in the ulceration of the lower bile duct.We believe that the mucosal tear and subsequent ruptured vessel were caused by the EPLBD procedure.
文摘AIM:To examine the frequency and prevention of musculoskeletal pain in Japanese gastrointestinal endoscopists and non-endoscopist physicians.METHODS:Questionnaires were sent to 275 endoscopists and 173 non-endoscopists working in Hiroshima University Hospital and its affiliated hospitals.RESULTS:The completed questionnaires were returned by 190(69%)endoscopists and 120(69%)non-endoscopists.The frequency of pain in the hand and wrist,and especially the left thumb,was significantly higher in endoscopists than in non-endoscopists(17%vs 6%,P=0.004).Using multivariate analysis,the only significant factor associated with this pain was the age of the endoscopist(odds ratio 2.77,95%confidence interval,1.23-6.71,P=0.018).Interestingly,endoscopists had made significantly fewer modifications to their endoscopic practices than non-endoscopists(12%vs 33%,P <0.0001)to prevent pain.CONCLUSION:Pain in the hand and wrist may be endoscopy-related.However,endoscopists made little modifications in practice to prevent such pain.More attention to prevention appears necessary.
文摘A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.
文摘IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.
文摘BACKGROUND: Early recurrence (ER) after hepatic resection (HR) is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS: We retrospectively examined 130 patients who underwent HR for small HCC (___30 mm). Recurrence was clas- sifted into ER (〈2 years) and late recurrence (LR) (_〉2 years). The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS: ER was observed in 39 patients (30.0%). The sur- vival rate of the ER group was significantly lower than that of the LR group (P〈0.005), and ER was an independent prognos- tic factor for poor survival (P=0.0001). The ER group had a significantly higher frequency (P=0.0039) and shorter interval (P=0.027) of development to carcinoma beyond the Milan criteria (DBMC) compared with the LR group, and ER was an independent risk factor for DBMC (P〈0.0001). Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER (P=0.012, 0.010, and 0.019, respectively).CONCLUSIONS: ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.
文摘This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD.IBDassociated with PSC(PSC-IBD)shows an increased incidence of pancolitis,mild symptoms,and colorectal malignancy.Although an increased incidence of pancolitis is a characteristic finding,some cases are endoscopically diagnosed as right-sided ulcerative colitis.Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon.The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition.The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)are similar to those of PSC.The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.
基金Supported by Scientific Research from the Ministry of Education,Science,Sports and Culture,Japan,No.10470144the Japanese Ministry of Health,Labour and Welfare(Intractable Diseases of the Pancreas)
文摘AIM: To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis. METHODS: Acute hemorrhagic pancreatitis(AP) was induced in male rats by intraductal infusion of 40 μl/100 g body weight of 3% sodium taurocholate. All rats took food ad libitum. At 24 h after induction of AP, rats were divided into four groups: control(AP-C), pancreas rest(AP-R), stimulation(AP-S), and rest/stimulation(AP-R/S). Rats in the AP-C, AP-R and AP-S groups received oral administration of 2 ml/kg body weight saline, cholecystokinin(CCK)-1 receptor antagonist, and endogenous CCK release stimulant, respectively, twice daily for 10 d, while those in the AP-R/S group received twice daily CCK-1 receptor antagonist for the first 5 d followed by twice daily CCK release stimulant for 5 d. Rats without any treatment were used as control group(Control). Biochemical andhistological changes in the pancreas, and secretory function were evaluated on day 12 at 24 h after the last treatment. RESULTS: Feeding ad libitum(AP-C) delayed biochemical, histological and functional recovery from AP. In AP-C rats, bombesin-stimulated pancreatic secretory function and HOMA-β-cell score were significantly lower than those in other groups of rats. In AP-R rats, protein per DNA ratio and pancreatic exocrine secretory function were significantly low compared with those in Control rats. In AP-S and AP-R/S rats, the above parameters recovered to the Control levels. Bombesinstimulated pancreatic exocrine response in AP-R/S rats was higher than in AP-S rats and almost returned to control levels. In the pancreas of AP-C rats, destruction of pancreatic acini, marked infiltration of inflammatory cells, and strong expression of α-smooth muscle actin, tumor necrosis factor-α and interleukin-1β were seen. Pancreatic rest reversed these histological alterations, but not atrophy of pancreatic acini and mild infiltration of inflammatory cells. In AP-S and AP-R/S rats, the pancreas showed almost normal architecture. CONCLUSION: The favorable treatment strategy for AP is to keep the pancreas at rest during an early stage followed by pancreatic stimulation by promoting endogenous CCK release.
基金Supported by The Japan Society for the Promotion of Science(JSPS)KAKENHI Grant,No.19300254,22300264 and 25282029(Takeuchi M)Kanazawa Medical University,No.SR2012-04(Tsutsumi M)the Ministry of Education,Culture,Sports,Science,and Technology(MEXT),Regional Innovation Strategy Support Program(Takeuchi M)
文摘Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.
基金Supported by the Research Committee of Intractable Diseases of the Pancreas (Chairman M. Otsuki) provided by the Ministry of Health, Labour, and Welfare, Japan
基金Supported by A Grant--in--Aid from the Japanese Ministry of Health,Welfare and Labour
文摘AIM: To investigate risk factors for development of hepatocellular carcinoma(HCC) in patients with hepatitis C virus-related liver cirrhosis(LC-C).METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon(IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.RESULTS: HCC was diagnosis in 50(21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older(P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein(AFP)(P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio(OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/m L(P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin(DCP) levels of ≥ 40 m AU/mL at 24 wk after the completion of IFN and ribavirin therapy(P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.
文摘Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic scraper Trefle~? has been reported and demonstrated high cancer detectability in malignant biliary strictures. This device is used to scrape the stricture over the guidewire, and, in the original method, the tissue and/or cell samples obtained are subjected to histological and/or cytological analysis separately. However, discrimination of chunks of tissue is hampered by the opacity of the surrounding fluid. We have developed a cell block technique for the Trefle~? device without dividing obtained specimens into tissue and cellular components, which is the simplest method and enables immunohistochemical analysis. We present a case of obstructive jaundice diagnosed immunohistochemically as pancreatic metastasis from colon cancer using cell block sections obtained with the Trefle~? device, which procedure is as easy as conventional brush cytology.
文摘In inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD), the duration and severity of inflammation are responsible for the development of colorectal cancer. Inflammatory cytokines such as interleukin (IL)-8 and tumor necrotic factor (TNF)-a, which are released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Current treatments for advanced colorectal cancers focus primarily on targeting epidermal growth factor receptor (EGFR) signaling. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of theproheparin-binding epidermal growth factor—like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM), so that the resulting soluble HB-EGF activates EGFR. In parallel, the carboxy-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, where HB-EGF-CTF binds the nuclear promyelocytic leukemia zinc finger (PLZF) protein, resulting in the nuclear export of the PLZF transcriptional repressor and thereby affecting cell proliferation. Screening for potent chemical inhibitors of the interactions between HB-EGF-CTF and PLZF identified telmisartan (and related compounds in corporating a biphenyl tetrazole moiety) as inhibitors of cell proliferation. Here we focus on the inhibitory effects of these compounds on cell proliferation, demonstrating the potential for targeting the nuclear translocation of HB-EGF-CTF in the treatment of colitis-associated cancer.
文摘BACKGROUND Hybrid endoscopic submucosal dissection(ESD)that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner,has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD.Although the superiority of hybrid ESD with SOUTEN,a single multifunctional device,over conventional ESD has been indicated,the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group,but not to the conventional ESD group,due to ethical issue in clinical practice.AIM To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study.METHODS Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University,performing 32 procedures each for hybrid ESD and conventional ESD.Mock lesions(10-15 mm,diameter)were created in the porcine stomach.The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection,perforation,procedure time/speed for both,mucosal incision,and submucosal dissection.Factors associated with difficulty in ESD including longer procedure time,incomplete resection,and perforation,were also investigated.Categorical and continuous data were analyzed using the chi-square test or Fisher’s exact test and the Mann-Whitney U test,respectively.RESULTS The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD(median:8.3 min vs 16.2 min,P<0.001).Time,speed,and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD(time,5.2 min vs 10.4 min,P<0.001;speed,43.7 mm^(2)/min vs 23.8 mm^(2)/min,P<0.00;injection volume,1.5 mL vs 3.0 mL,P<0.001),although no significant differences in those factors were observed between both groups during mucosal incision.There was also no significant difference between both groups in the en bloc/complete resection rate and perforation rate(complete resection,93.8%vs 87.5%,P=0.67;perforation,0% vs 3.1%,P=1).Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD(odds ratio=10.2;highest among factors).CONCLUSION Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions.It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.
基金Supported by Grant-in-Aid for Scientific Research(C)from Japan Society for the Promotion of Science,No.25460957
文摘Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis(UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α) and interleukin-2, and the cellsurface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues(azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody(vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin(ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease(IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.
基金Supported by Health Labor Science Research Grants from Research on Measures for Intractable Diseases,the IntractableHepato-Biliary Diseases Study Group in Japan
文摘Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of Ig G4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated Ig G4-SC displayed hilar biliary strictures, whereas isolated Ig G4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic Ig G4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum Ig G4 levels were within the normal limits. The mean serum Ig G4 level measured before surgery was 202.1 mg/d L(4 cases). Isolated intrapancreatic Ig G4-SC is difficult to diagnose, especially if the Ig G4 level remains normal. Thus, this type of Ig G4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.
基金Supported by An Investigator Sponsored Study Programme of Astra Zeneca
文摘AIM To assess the clinical characteristics of patients with complicated erosive esophagitis(EE) and their associated factors.METHODS This prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios(aO R) and 95%CI for the association with complicated EE.RESULTS During the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors(PPIs) were included. Of them, 143(8.2%) had EE complications. Esophageal bleeding occurred in 84(4.8%) patients, esophageal strictures in 45(2.6%) patients, and 14(0.8%) patients experienced both. Multivariate analysis showed that increased age(a OR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents(a OR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B(a OR: 2.69; 95%CI: 1.48-4.96), C(aO R: 15.38; 95%CI: 8.62-28.37), and D(aO R: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated(a OR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age(a OR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B(aO R: 3.60; 95%CI: 1.52-8.50), C(a OR: 27.61; 95%CI: 12.34-61.80), and D(a OR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age(a OR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom(aO R: 2.51; 95%CI: 1.39-4.51), concomitantuse of psychotropic agents(a OR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C(aO R: 7.35; 95%CI: 3.32-16.25), and D(a OR: 20.34; 95%CI: 8.36-49.53) and long-segment Barrett's esophagus(a OR: 4.63; 95%CI: 1.64-13.05).CONCLUSION Aging and severe EE were common associated factors, although there were more associated factors in esophageal strictures than esophageal ulcer bleeding. Despite the availability and widespread use of PPIs, EE complications are likely to remain a problem in Japan owing to the aging population and high-stress society.
基金We thank all members at the Department of Medicine and Bioregulatory Science,Graduate School of Medical Sciences,Kyushu University for cooperating with us in the data collection.
文摘BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is controversial.AIM To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)for SNADETs.METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs,which included eight hospitals in Fukuoka,Japan,between April 2001 and October 2017.A total of 142 patients with SNADETs treated with EMR or ESD were analyzed.Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups.We analyzed the treatment outcomes,including the rates of en bloc/complete resection,procedure time,adverse event rate,hospital stay,and local or metastatic recurrence.RESULTS Twenty-eight pairs of patients were created.The characteristics of patients between the two groups were similar after matching.The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group[median procedure time(interquartile range):6(3-10.75)min vs 87.5(68.5-136.5)min,P<0.001,hospital stay:8(6-10.75)d vs 11(8.25-14.75)d,P=0.006].Other outcomes were not significantly different between the two groups(en bloc resection rate:82.1%vs 92.9%,P=0.42;complete resection rate:71.4%vs 89.3%,P=0.18;and adverse event rate:3.6%vs 17.9%,P=0.19,local recurrence rate:3.6%vs 0%,P=1;metastatic recurrence rate:0%in both).Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation.CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD,and provides acceptable curability and safety compared to ESD.Accordingly,EMR for SNADETs is associated with lower medical costs.
文摘BACKGROUND A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection(ESD)for gastrointestinal tract tumors.The assistant during the ESD using a clutch cutter(ESD-C)needs to rotate the device and grasp the target tissue appropriately;therefore,the assistant’s skill may affect the technical outcomes of ESD-C.AIM To determine how assistant skill level affected the technical outcomes of gastric ESD-C using an ex vivo porcine training model.METHODS In this pilot study,mock lesions of 15-30 mm in diameter were created in the middle or lower third of the porcine stomach.A total of 32 ESD-C procedures were performed by 16 trainees.Each trainee operator performed two ESD-C procedures;one ESD-C was assisted by an expert(ESD-C-E),and the other was assisted by a non-expert(ESD-C-NE).The total procedure time of the ESD was set as the primary outcome,and en bloc resection rate,complete procedure rate,perforation rate,and each procedure time/speed for mucosal incision or submucosal dissection were set as the secondary outcomes.In addition,we investigated factors associated with the difficulty of ESD including incompletion of ESD procedure,a long procedure time(≥20 min)or intraoperative perforation.RESULTS The median total procedure time of the ESD-C-E was significantly shorter than that of the ESD-C-NE(12.9 min vs 21.9 min,P=0.001).The en bloc resection rate was 100%in both groups.Complete resection rates of the ESD-C-E and ESD-C-NE groups were 100%and 93.8%,respectively.No intraoperative perforation was observed in both groups.In the multivariate analysis,assistant skill was significantly associated with the difficulty of ESD,with the highest odds ratio of 16.5.CONCLUSION Assistance by an expert is an important factor when trainees perform ESD-C procedures.