Non-alcoholic fatty liver disease(NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver(NAFL) or ...Non-alcoholic fatty liver disease(NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver(NAFL) or non-alcoholic steatohepatitis(NASH) based on the existence of ballooned hepatocytes,although the states have been known to transform into each other. Moreover,since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus,identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.展开更多
AIM： To clarify whether mucosal crypt patterns observed with magnifying colonoscopy are feasible to distinguish non-neoplastic polyps from neoplastic polyps. METHODS： From June 1999 through March 2000, 180 consecuti...AIM： To clarify whether mucosal crypt patterns observed with magnifying colonoscopy are feasible to distinguish non-neoplastic polyps from neoplastic polyps. METHODS： From June 1999 through March 2000, 180 consecutive patients with 210 lesions diagnosed with a magnifying colonoscope （CF-200Z, Olympus Optical Co., Ltd., Tokyo, Japan） were enrolled. Magnification and chromoendoscopy with 0.2% indigo-carmine dye was applied to each lesion for mucosal crypt observation. Lesions showing types Ⅰ and Ⅱ crypt patterns were considered non-neoplastic and examined histologically by biopsy, whereas lesions showing types Ⅲ to Ⅴ crypt patterns were removed endoscopically or surgically. The correlation of endoscopic diagnosis and histologic diagnosis was then investigated. RESULTS： At endoscopy, 24 lesions showed a type Ⅰ or Ⅱ pit pattern, and 186 lesions showed type Ⅲ to Ⅴ pit patterns. With histologic examination, 26 lesions were diagnosed as non-neoplastic polyps, and 184 lesions were diagnosed as neoplastic polyps. The overall diagnostic accuracy was 99.1% （208/210）. The sensitivity and specificity were 92.3% （24/26） and 99.8% （184/186）, respectively. CONCLUSION： Magnifying colonoscopy could be used as a non-biopsy technique for differentiating neoplastic and non-neoplastic polyps.展开更多
AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studi...AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studies published from January 1, 1994 through January 31, 2015. The search terms included "laparoscopic," "total gastrectomy," and "gastric cancer." First, we selected 16 non-randomized controlled trials(RCTs) comparing LTG with open total gastrectomy(OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system(NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0%(30 of 984 patients) among LTG procedures and 2.1%(31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG(odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I2 = 0%). Anastomotic stenosis related to EJS was reported in 72(2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG(OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I2 = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar(1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the Or VilTM device was used(8.8%) compared with other procedures(1.0% to 3.6%).CONCLUSION:The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the Or VilTM device was used.展开更多
Retroperitoneal fibrosis is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.Retroperitoneal fibrosis can be of 2 types...Retroperitoneal fibrosis is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.Retroperitoneal fibrosis can be of 2 types:idiopathic and secondary.The recently advocated concept and diagnostic criteria of immunoglobulin G4(IgG4)-related disease,derived from research on autoimmune pancreatitis(AIP),has led to widespread recognition of retroperitoneal fibrosis as a condition caused by IgG4-related disease.We now know that previously diagnosed idiopathic retroperitoneal fibrosis includes IgG4-related disease;however,the actual prevalence is unclear.Conversely,some reports on AIP suggest that retroperitoneal fibrosis is concurrently found in about 10% of IgG4-related disease.Because retroperitoneal fibrosis has no specific symptoms,diagnosis is primarily based on diagnostic imaging(computed tomography and magnetic resonance imaging),which is also useful in evaluating the effect of therapy.Idiopathic retroperitoneal fibrosis can occur at different times with other lesions of IgG4-related disease including AIP.Thus,the IgG4 assay is recommended to diagnose idiopathic retroperitoneal fibrosis.High serum IgG4 levels should be treated and monitored as a symptom of IgG4-related disease.The first line of treatment for retroperitoneal fibrosis is steroid therapy regardless of its cause.For patients with concurrent AIP,i.e.,IgG4-related retroperitoneal fibrosis,the starting dose of steroid is usually 30-40 mg/d.The response to steroid therapy is generally favorable.In most cases,the pancreatic lesion and retroperitoneal fibrosis improve after the initial treatment.However,the epidemiology,treatment for recurring retroperitoneal fibrosis,and long-term prognosis are still largely unknown.Further analysis of such cases and research are necessary.展开更多
Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due ...Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due to a decrease in gastric acid caused by atrophic gastritis.In addition,the cellular components of H.pylori travel through the intestinal tract,so the bacterial infection affects the immune system.Therefore,the effects of H.pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines.In particular,meta-analyses reported that H.pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer.Moreover,a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H.pylori vacuolating cytotoxin A antibody.In addition,it has been reported that H.pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers.On the other hand,some studies have reported that the frequency of ulcerative colitis,Crohn’s disease,and celiac disease is low in H.pylori-infected individuals.Thus,H.pylori infection is considered to have various effects on the small and large intestines.However,few studies have reported on these issues,and the details of their effects have not been well elucidated.Therefore,additional studies are needed.展开更多
We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved a...We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.展开更多
AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on live...AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD. METHODS A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with nonalcoholic steatohepatitis, 26% with advanced fibrosis(F3-4)] were divided into the mild drinking group withe thanol consumption of less than 20 g/d(mild drinking group, n = 93) and the non-drinking group(n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma(HCC) occurrence were compared between the groups.RESULTS We observed significant differences in male prevalence(P = 0.01), platelet count(P = 0.04), and gammaglutamyl transpeptidase(P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group(6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox's regression model revealed that hepatic advanced fibrosis(F3-4)(P < 0.01, risk ratio: 11.60), diabetes mellitus(P < 0.01, risk ratio: 89.50), and serum triglyceride(P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal(P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis(F3-4), however, a drinking habit(P = 0.04, risk ratio: 4.83), alpha-fetoprotein(P = 0.01, risk ratio: 1.23), and diabetes mellitus(P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence. CONCLUSION A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.展开更多
This study analyzed the difference between using a downward breaststroke kick and a horizontal breaststroke kick in a sample of world class elite swimmers.We compared average muscle activity of the gluteus maximus,qua...This study analyzed the difference between using a downward breaststroke kick and a horizontal breaststroke kick in a sample of world class elite swimmers.We compared average muscle activity of the gluteus maximus,quadriceps femoris(vastus medialis and rectus femoris),hamstring/long head of the biceps femoris,gastrocnemius medialis,rectus abdominal,and erector spinae when using the downward breaststroke kick technique.We find that when this sample of swimmers utilized the downward breaststroke kick,max speed and velocity per stroke increased,measured by 12,788 EMG samples,where the results are highly correlated to duration of the aerodynamic buoyant force in breaststroke kick technique.The increases in performance observed from measuring the world class elite swimmers is highly correlated to the duration of the kick aerodynamic buoyant force.Among this sample of elite swimmers,the longer a swimmer demonstrates a buoyant force breaststroke kick,the lower the time in a 100 breaststroke.展开更多
Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestin...Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.展开更多
A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed a...A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.展开更多
AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) ...AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012.We retrospectively evaluated the clinical profiles of the patients,the endoscopic interventions,short-term outcomes,and complications.RESULTS:Of 44 ERCPs,26 were diagnostic ERCP,and 18 were therapeutic ERCP.The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct.The overall success rate of minor papilla cannulation was 80%(35/44),which was significantly improved by wire-guided cannulation(P = 0.04).Endoscopic minor papillotomy(EMP) was performed in 17 of 34 patients(50%) using a needle-knife(13/17) or a pull-type papillotome(4/17).EMP with pancreatic stent placement,which was the main therapeutic option for patients with chronic pancreatitis,recurrent acute pancreatitis,and pancreatic pseudocyst,resulted in short-term clinical improvement in 83% of patients.Mild post-ERCP pancreatitis occurred as an early complication in 2 cases(4.5%).CONCLUSION:The endoscopic minor papilla approach is technically feasible,safe,and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.展开更多
AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had u...AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.展开更多
BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens b...BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 5展开更多
It is often difficult to explain why ulcerative lesions are found in the small intestine because there are no obvious aggressors such as gastric acid.In particular,the treatment of small intestinal ulcerative lesions ...It is often difficult to explain why ulcerative lesions are found in the small intestine because there are no obvious aggressors such as gastric acid.In particular,the treatment of small intestinal ulcerative lesions in asymptomatic patients with no symptoms,normal physical examinations,and normal blood test findings is not well documented.According to a summary of capsule endoscopy studies in healthy subjects,approximately 10%of subjects have small intestinal mucosal breaks.The number of mucosal breaks in these instances is approximately 1-3.We examined small intestinal mucosal breaks in healthy subjects recruited from our past two studies.Mucosal breaks were observed in approximately 10%of subjects,and the average number was 0.24±1.21.The number of mucosal breaks in the small intestine was correlated with body mass index and was significantly higher in Helicobacter pylori-infected subjects and higher in males.These results indicate that 1-2 small ulcerative lesions,such as erosions in the small intestine,can be considered to be in the normal range,and close examination is not required.It is assumed that a follow-up medical examination is required for such asymptomatic persons.The presence of many small ulcerative lesions or an unequivocal ulcer indicates an abnormality for which close examination is desired.However,in many cases,it is sufficient to scrutinize after detecting anemia,but it is difficult to make a judgment due to insufficient reports,and future studies are required.展开更多
AIM To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and nonneoplastic colorectal diminutive polyps.METHODS Patients who underwent endocytoscopy between October and Decembe...AIM To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and nonneoplastic colorectal diminutive polyps.METHODS Patients who underwent endocytoscopy between October and December 2016 at Sano Hospital were prospectively recruited. When diminutive polyps(≤5 mm) were detected, the lesions were evaluated by endocytoscopy after being stained with 0.05% crystal violet and 1% methylene blue. The diminutivepolyps were classified into five categories(EC 1 a, 1 b, 2, 3 a, and 3 b). Endoscopists were asked to take a biopsy from any lesion diagnosed as EC1 b(indicator of hyperplastic polyp) or EC2(indicator of adenoma). We have assessed the diagnostic performance of endocytoscopy for EC2 and EC1 b lesions by comparison with the histopathology of the biopsy specimen. RESULTS A total of 39 patients with 63 diminutive polyps were analyzed. All polyps were evaluated by endocytoscopy. The mean polyp size was 3.3 ± 0.9 mm. Among the 63 diminutive polyps, 60 were flat and 3 were pedunculated. The mean time required for EC observation, including the time for staining with crystal violet and methylene blue, was 3.0 ± 1.9 min. Histopathologic evaluation showed that 13 polyps were hyperplastic and 50 were adenomas. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of EC2 for adenoma compared with EC1 b for hyperplastic polyp were 98.0%, 92.3%, 96.8%, 98.0% and 92.3%, respectively. There were only two cases of disagreement between the endoscopic diagnosis made by endocytoscopy and the corresponding histopathological diagnosis.CONCLUSION Endocytoscopy showed a high diagnostic performance for differentiating between neoplastic and non-neoplastic colorectal diminutive polyps, and therefore has the potential to be used for "real-time histopathology".展开更多
AIMTo assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred twenty-six NAFLD patients who had undergone percut...AIMTo assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores.RESULTSSerum LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P < 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological findings.CONCLUSIONLBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.展开更多
Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer(GC),although outcomes remain unfavorable.Many molecular-targeted therapies inhibiting signaling pathway...Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer(GC),although outcomes remain unfavorable.Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed,and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC.Hepatocyte growth factor and its receptor,c-MET(MET),play key roles in tumor growth through activated signaling pathways from receptor in GC cells.Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC.This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC.Preclinical studies in animal models have shown that MET antibodies or smallmolecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells.These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.展开更多
AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retr...AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancersand their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive(1-5 mm) lesions in 402 patients and 197 cases of small(6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal(SM) scanty invasive carcinomas, 1 and 1 were SM deeply invasive carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically.CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.展开更多
Introduction Autoimmune pancreatitis(AIP)is one of the recently established immunoglobulin G4-related diseases(IgG4-RD)[1].The detailed pathogenic mechanisms have been an intensive research area for prophylactic and t...Introduction Autoimmune pancreatitis(AIP)is one of the recently established immunoglobulin G4-related diseases(IgG4-RD)[1].The detailed pathogenic mechanisms have been an intensive research area for prophylactic and therapeutic purposes because aberrant immune activation and tissue fibrosis in AIP are the major factors that worsen the disease outcomes in these patients.展开更多
AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolis...AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SV展开更多
文摘Non-alcoholic fatty liver disease(NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver(NAFL) or non-alcoholic steatohepatitis(NASH) based on the existence of ballooned hepatocytes,although the states have been known to transform into each other. Moreover,since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus,identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.
文摘AIM： To clarify whether mucosal crypt patterns observed with magnifying colonoscopy are feasible to distinguish non-neoplastic polyps from neoplastic polyps. METHODS： From June 1999 through March 2000, 180 consecutive patients with 210 lesions diagnosed with a magnifying colonoscope （CF-200Z, Olympus Optical Co., Ltd., Tokyo, Japan） were enrolled. Magnification and chromoendoscopy with 0.2% indigo-carmine dye was applied to each lesion for mucosal crypt observation. Lesions showing types Ⅰ and Ⅱ crypt patterns were considered non-neoplastic and examined histologically by biopsy, whereas lesions showing types Ⅲ to Ⅴ crypt patterns were removed endoscopically or surgically. The correlation of endoscopic diagnosis and histologic diagnosis was then investigated. RESULTS： At endoscopy, 24 lesions showed a type Ⅰ or Ⅱ pit pattern, and 186 lesions showed type Ⅲ to Ⅴ pit patterns. With histologic examination, 26 lesions were diagnosed as non-neoplastic polyps, and 184 lesions were diagnosed as neoplastic polyps. The overall diagnostic accuracy was 99.1% （208/210）. The sensitivity and specificity were 92.3% （24/26） and 99.8% （184/186）, respectively. CONCLUSION： Magnifying colonoscopy could be used as a non-biopsy technique for differentiating neoplastic and non-neoplastic polyps.
文摘AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studies published from January 1, 1994 through January 31, 2015. The search terms included "laparoscopic," "total gastrectomy," and "gastric cancer." First, we selected 16 non-randomized controlled trials(RCTs) comparing LTG with open total gastrectomy(OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system(NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0%(30 of 984 patients) among LTG procedures and 2.1%(31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG(odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I2 = 0%). Anastomotic stenosis related to EJS was reported in 72(2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG(OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I2 = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar(1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the Or VilTM device was used(8.8%) compared with other procedures(1.0% to 3.6%).CONCLUSION:The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the Or VilTM device was used.
基金Supported by The Research Program of Intractable Disease and the Research Committee of Intractable Pancreatic Diseases of the Ministry of Health,Labor and Welfare of Japan
文摘Retroperitoneal fibrosis is a rare disease characterized by the development of inflammation and fibrosis in the soft tissues of the retroperitoneum and other abdominal organs.Retroperitoneal fibrosis can be of 2 types:idiopathic and secondary.The recently advocated concept and diagnostic criteria of immunoglobulin G4(IgG4)-related disease,derived from research on autoimmune pancreatitis(AIP),has led to widespread recognition of retroperitoneal fibrosis as a condition caused by IgG4-related disease.We now know that previously diagnosed idiopathic retroperitoneal fibrosis includes IgG4-related disease;however,the actual prevalence is unclear.Conversely,some reports on AIP suggest that retroperitoneal fibrosis is concurrently found in about 10% of IgG4-related disease.Because retroperitoneal fibrosis has no specific symptoms,diagnosis is primarily based on diagnostic imaging(computed tomography and magnetic resonance imaging),which is also useful in evaluating the effect of therapy.Idiopathic retroperitoneal fibrosis can occur at different times with other lesions of IgG4-related disease including AIP.Thus,the IgG4 assay is recommended to diagnose idiopathic retroperitoneal fibrosis.High serum IgG4 levels should be treated and monitored as a symptom of IgG4-related disease.The first line of treatment for retroperitoneal fibrosis is steroid therapy regardless of its cause.For patients with concurrent AIP,i.e.,IgG4-related retroperitoneal fibrosis,the starting dose of steroid is usually 30-40 mg/d.The response to steroid therapy is generally favorable.In most cases,the pancreatic lesion and retroperitoneal fibrosis improve after the initial treatment.However,the epidemiology,treatment for recurring retroperitoneal fibrosis,and long-term prognosis are still largely unknown.Further analysis of such cases and research are necessary.
文摘Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due to a decrease in gastric acid caused by atrophic gastritis.In addition,the cellular components of H.pylori travel through the intestinal tract,so the bacterial infection affects the immune system.Therefore,the effects of H.pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines.In particular,meta-analyses reported that H.pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer.Moreover,a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H.pylori vacuolating cytotoxin A antibody.In addition,it has been reported that H.pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers.On the other hand,some studies have reported that the frequency of ulcerative colitis,Crohn’s disease,and celiac disease is low in H.pylori-infected individuals.Thus,H.pylori infection is considered to have various effects on the small and large intestines.However,few studies have reported on these issues,and the details of their effects have not been well elucidated.Therefore,additional studies are needed.
文摘We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.
文摘AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD. METHODS A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with nonalcoholic steatohepatitis, 26% with advanced fibrosis(F3-4)] were divided into the mild drinking group withe thanol consumption of less than 20 g/d(mild drinking group, n = 93) and the non-drinking group(n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma(HCC) occurrence were compared between the groups.RESULTS We observed significant differences in male prevalence(P = 0.01), platelet count(P = 0.04), and gammaglutamyl transpeptidase(P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group(6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox's regression model revealed that hepatic advanced fibrosis(F3-4)(P < 0.01, risk ratio: 11.60), diabetes mellitus(P < 0.01, risk ratio: 89.50), and serum triglyceride(P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal(P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis(F3-4), however, a drinking habit(P = 0.04, risk ratio: 4.83), alpha-fetoprotein(P = 0.01, risk ratio: 1.23), and diabetes mellitus(P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence. CONCLUSION A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.
文摘This study analyzed the difference between using a downward breaststroke kick and a horizontal breaststroke kick in a sample of world class elite swimmers.We compared average muscle activity of the gluteus maximus,quadriceps femoris(vastus medialis and rectus femoris),hamstring/long head of the biceps femoris,gastrocnemius medialis,rectus abdominal,and erector spinae when using the downward breaststroke kick technique.We find that when this sample of swimmers utilized the downward breaststroke kick,max speed and velocity per stroke increased,measured by 12,788 EMG samples,where the results are highly correlated to duration of the aerodynamic buoyant force in breaststroke kick technique.The increases in performance observed from measuring the world class elite swimmers is highly correlated to the duration of the kick aerodynamic buoyant force.Among this sample of elite swimmers,the longer a swimmer demonstrates a buoyant force breaststroke kick,the lower the time in a 100 breaststroke.
文摘Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.
文摘A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.
基金Supported by (In part) the Research Committee of Intractable Diseases of the Pancreas (principal investigator:Tooru Shimosegawa) provided by the Ministry of Health,Labour and Welfare Japan
文摘AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012.We retrospectively evaluated the clinical profiles of the patients,the endoscopic interventions,short-term outcomes,and complications.RESULTS:Of 44 ERCPs,26 were diagnostic ERCP,and 18 were therapeutic ERCP.The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct.The overall success rate of minor papilla cannulation was 80%(35/44),which was significantly improved by wire-guided cannulation(P = 0.04).Endoscopic minor papillotomy(EMP) was performed in 17 of 34 patients(50%) using a needle-knife(13/17) or a pull-type papillotome(4/17).EMP with pancreatic stent placement,which was the main therapeutic option for patients with chronic pancreatitis,recurrent acute pancreatitis,and pancreatic pseudocyst,resulted in short-term clinical improvement in 83% of patients.Mild post-ERCP pancreatitis occurred as an early complication in 2 cases(4.5%).CONCLUSION:The endoscopic minor papilla approach is technically feasible,safe,and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.
文摘AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.
基金The study was reviewed and approved by the Nippon Medical School Institutional Review Board(Approval No.B-2020-164).
文摘BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 5
文摘It is often difficult to explain why ulcerative lesions are found in the small intestine because there are no obvious aggressors such as gastric acid.In particular,the treatment of small intestinal ulcerative lesions in asymptomatic patients with no symptoms,normal physical examinations,and normal blood test findings is not well documented.According to a summary of capsule endoscopy studies in healthy subjects,approximately 10%of subjects have small intestinal mucosal breaks.The number of mucosal breaks in these instances is approximately 1-3.We examined small intestinal mucosal breaks in healthy subjects recruited from our past two studies.Mucosal breaks were observed in approximately 10%of subjects,and the average number was 0.24±1.21.The number of mucosal breaks in the small intestine was correlated with body mass index and was significantly higher in Helicobacter pylori-infected subjects and higher in males.These results indicate that 1-2 small ulcerative lesions,such as erosions in the small intestine,can be considered to be in the normal range,and close examination is not required.It is assumed that a follow-up medical examination is required for such asymptomatic persons.The presence of many small ulcerative lesions or an unequivocal ulcer indicates an abnormality for which close examination is desired.However,in many cases,it is sufficient to scrutinize after detecting anemia,but it is difficult to make a judgment due to insufficient reports,and future studies are required.
文摘AIM To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and nonneoplastic colorectal diminutive polyps.METHODS Patients who underwent endocytoscopy between October and December 2016 at Sano Hospital were prospectively recruited. When diminutive polyps(≤5 mm) were detected, the lesions were evaluated by endocytoscopy after being stained with 0.05% crystal violet and 1% methylene blue. The diminutivepolyps were classified into five categories(EC 1 a, 1 b, 2, 3 a, and 3 b). Endoscopists were asked to take a biopsy from any lesion diagnosed as EC1 b(indicator of hyperplastic polyp) or EC2(indicator of adenoma). We have assessed the diagnostic performance of endocytoscopy for EC2 and EC1 b lesions by comparison with the histopathology of the biopsy specimen. RESULTS A total of 39 patients with 63 diminutive polyps were analyzed. All polyps were evaluated by endocytoscopy. The mean polyp size was 3.3 ± 0.9 mm. Among the 63 diminutive polyps, 60 were flat and 3 were pedunculated. The mean time required for EC observation, including the time for staining with crystal violet and methylene blue, was 3.0 ± 1.9 min. Histopathologic evaluation showed that 13 polyps were hyperplastic and 50 were adenomas. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of EC2 for adenoma compared with EC1 b for hyperplastic polyp were 98.0%, 92.3%, 96.8%, 98.0% and 92.3%, respectively. There were only two cases of disagreement between the endoscopic diagnosis made by endocytoscopy and the corresponding histopathological diagnosis.CONCLUSION Endocytoscopy showed a high diagnostic performance for differentiating between neoplastic and non-neoplastic colorectal diminutive polyps, and therefore has the potential to be used for "real-time histopathology".
文摘AIMTo assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores.RESULTSSerum LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P < 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological findings.CONCLUSIONLBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.
文摘Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer(GC),although outcomes remain unfavorable.Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed,and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC.Hepatocyte growth factor and its receptor,c-MET(MET),play key roles in tumor growth through activated signaling pathways from receptor in GC cells.Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC.This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC.Preclinical studies in animal models have shown that MET antibodies or smallmolecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells.These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.
基金Supported by Institute of Minimally Invasive Endoscopic Care(iM EC),Sano Hospital,No.2014-02
文摘AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancersand their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive(1-5 mm) lesions in 402 patients and 197 cases of small(6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal(SM) scanty invasive carcinomas, 1 and 1 were SM deeply invasive carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically.CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.
基金supported by the Japan Agency for Medical Research and Development[JP21gm0910010,JP21ak0101070 to S.Y.]the Japan Society for the Promotion of Science KAKENHI[JP23H00403,JP22H05183 to S.Y.and JP16K08740,JP20K07539,JP23H04784 to K.S.]and the Kurozumi Medical Foundation to K.S.
文摘Introduction Autoimmune pancreatitis(AIP)is one of the recently established immunoglobulin G4-related diseases(IgG4-RD)[1].The detailed pathogenic mechanisms have been an intensive research area for prophylactic and therapeutic purposes because aberrant immune activation and tissue fibrosis in AIP are the major factors that worsen the disease outcomes in these patients.
基金Supported by grants from Research Program of Intractable Disease provided by the Ministry of Health,Labor and Welfare of Japan,and a Grant-in-Aid for Clinical Research from the National Hospital Organization of Japan
文摘AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SV
