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1.
Intest Res ; 22(1): 82-91, 2024 Jan.
Article En | MEDLINE | ID: mdl-38326999

BACKGROUND/AIMS: Transabdominal ultrasonography (US) helps evaluate Crohn's disease (CD) activity. We investigated whether the US could predict subsequent adverse outcomes for patients with CD in clinical remission. METHODS: This single-center retrospective study included patients with CD in clinical remission who underwent US between April 2011 and April 2021, focusing on the predictability of subsequent adverse outcomes within 5 years. We used the US-CD, which was calculated using multiple US findings. Predictive variables were assessed using Cox proportional hazards regression analysis, and the predictive value was evaluated using receiver operating characteristic curves. RESULTS: Seventy-three patients were included. During a median follow-up of 1,441 days (range, 41-1,825 days), 16.4% (12/73) experienced clinical relapse, 9.6% (7/73) required endoscopic balloon dilation (EBD), 58.9% (43/73) required enhanced treatment, and 20.5% (15/73) underwent surgery. In the multivariate analysis, US-CD was significantly associated with clinical relapse (P= 0.038) and the need for enhanced treatment (P= 0.005). The area under the receiver operating characteristic curve for predicting clinical relapse and the need for EBD was 0.77 and 0.81, respectively, with US-CD (cutoff value = 11), and that for requiring enhanced treatment was 0.74 with US-CD (cutoff value = 6). Patients with US-CD ≥ 11 demonstrated a significantly higher occurrence of clinical relapse (P= 0.001) and EBD (P= 0.002) within 5 years. Patients with US-CD ≥ 6 experienced a significantly higher likelihood of requiring enhanced treatment (P< 0.001) within 5 years. CONCLUSIONS: High US-CD is associated with subsequent adverse outcomes in patients with CD.

2.
J Clin Biochem Nutr ; 73(1): 77-83, 2023 Jul.
Article En | MEDLINE | ID: mdl-37534095

Compositional changes in the microbiota are associated with various inflammatory diseases, including ulcerative colitis (UC). Aim: This study aimed to investigate the mucosa-associated microbiota (MAM) in patients with UC and its difference related with disease activity and classification. Brush samples were collected from the terminal ileum and sigmoid colon during endoscopic procedures. The microbiota of samples was profiled using the Illumina MiSeq platform. The V3-V4 regions of the gene encoding 16S rRNA (460 bp) were amplified using PCR. Fifty UC patients and twenty healthy controls were enrolled. UC patients displayed significantly reduced α-diversity in both the ileum and sigmoid colon compared to controls. A difference in ß-diversity in the unweighted analysis was observed between the two groups. The abundance of Lactobacillus and Veillonella was significantly higher and that of Butyricicoccus, Ruminococcus and Lachnospiraceae was significantly lower in the ileum of UC patients than in controls. The abundance of Odoribacter in the ileum was significantly lower in left-sided colitis and pancolitis patients than in proctitis patients and lower in patients with highly severe disease activity than with mild disease activity. The reduction in abundance of butyric acid-producing bacteria, especially Odoribacter, in ileal MAM may play an important role in the pathophysiology of UC.

4.
Intest Res ; 21(1): 126-136, 2023 Jan.
Article En | MEDLINE | ID: mdl-35860848

BACKGROUND/AIMS: The usefulness of ultrasonography (US) in diseases of the gastrointestinal tract has been reported recently. This prospective study aimed to determine the features of US findings in immune-mediated colitis (IMC), an adverse event induced by immune checkpoint inhibitor, and examine the correlation between US findings, colonoscopy (CS) findings, and severity of colitis. METHODS: We studied patients examined using CS and US upon suspicion of IMC in Hokkaido University Hospital between April 2018 and February 2021. Endoscopic findings of IMC were assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). The severity of US findings in IMC was evaluated using US grade, which is the ultrasonographic grading scale in ulcerative colitis. Bowel wall thickness and the intensity of the color Doppler signal were also analyzed. Severity of colitis was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) grade version 5. RESULTS: Fourteen patients with IMC were enrolled. The US findings were bowel wall thickening, loss of stratification, ulceration and increased blood flow signal. The US grade was moderately correlated with the UCEIS (r=0.687, p=0.009) and CTCAE grade (r=0.628, p=0.035). Bowel wall thickness and UCEIS (r=0.628, p=0.020), as well as color Doppler signal grade and CTCAE grade (r=0.724, p=0.008), were significantly correlated. CONCLUSIONS: US findings in IMC were mainly similar to those of ulcerative colitis, but there were some findings that were characteristic only of IMC. Significant correlation was found between US findings, CS findings, and severity of colitis. Hence, US could be useful for the evaluation of IMC.

5.
J Clin Biochem Nutr ; 70(2): 182-188, 2022 Mar.
Article En | MEDLINE | ID: mdl-35400819

Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.

6.
Intern Med ; 60(22): 3517-3523, 2021.
Article En | MEDLINE | ID: mdl-34776464

Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.


Capsule Endoscopy , Intestinal Diseases , Aged , Aged, 80 and over , Aspirin/adverse effects , Female , Humans , Intestine, Small , Male , Platelet Aggregation Inhibitors/adverse effects
7.
Eur J Gastroenterol Hepatol ; 33(10): 1260-1265, 2021 10 01.
Article En | MEDLINE | ID: mdl-34581688

BACKGROUND AND AIM: The usefulness of a radio-tag-free PillCam patency capsule (PatCap) has been reported to evaluate the patency of the small intestine. If the PatCap is not excreted within 33 h, the location of the failed PatCap must be confirmed. Although several methods for locating the failed PatCap have been reported, a universal method has not been established. In this study, we aimed to confirm the clinical feasibility of abdominal ultrasonography combined with abdominal X-ray in the determination of the location of a failed PatCap. PATIENTS AND METHODS: Consecutive patients who were scheduled to undergo the capsule endoscopy and had received PatCap examination between July 2012 and September 2019 were retrospectively analyzed. Failed PatCap was assessed using ultrasonography combined with abdominal X-ray. RESULTS: Among the eligible 250 patients, 129 retrieved the PatCap in their stool within 33 h after ingestion. Among the remaining 121 patients, abdominal X-ray was performed and the PatCaps were suspected to be in the small bowel in 57 patients. Among these 57 patients, abdominal ultrasonography identified 17 PatCaps in the small bowel. Among the selected 250 patients, 233 patients (93.2%) were eligible for capsule endoscopy examination, while 17 patients (6.8%) were not eligible. Capsule endoscopy passed through the small intestine without any incident. CONCLUSION: We confirmed that the abdominal ultrasonography with a radiographic targeting of the PatCap location is a reliable indicator to avoid the risk of capsule endoscopy retention or impaction and can be performed in most hospitals and clinics.


Capsule Endoscopy , Intestinal Obstruction , Humans , Intestinal Obstruction/diagnostic imaging , Intestine, Small/diagnostic imaging , Retrospective Studies , Ultrasonography
8.
Scand J Gastroenterol ; 56(10): 1140-1145, 2021 10.
Article En | MEDLINE | ID: mdl-34423734

OBJECTIVES: Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone. MATERIALS AND METHODS: Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record. RESULTS: Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42-7.27) and BMI (OR, 1.14; 95% CI, 1.02-1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea. CONCLUSIONS: Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.


Constipation , Lubiprostone , Aged , Chronic Disease , Constipation/drug therapy , Female , Humans , Lubiprostone/adverse effects , Male , Retrospective Studies
9.
Dig Liver Dis ; 53(7): 841-845, 2021 07.
Article En | MEDLINE | ID: mdl-34059446

OBJECTIVE: We have previously revealed the clinical factors and genetic polymorphisms associated with gastrointestinal mucosal injury and bleeding, induced by low-dose aspirin (LDA). After performing genome-wide analysis of single nucleotide polymorphisms (SNPs) using the Drug Metabolizing Enzymes and Transporters (DMET) system among drug metabolism and transporter genes, certain SNPs were found to increase the risk for LDA-induced small bowel bleeding. The aim of this study was to identify the SNPs involved in LDA-induced small bowel bleeding. SUBJECTS AND METHODS: Subjects were patients taking LDA, with small bowel bleeding diagnosed using capsule endoscopy. We investigated the clinical characteristics and the previously identified SNPs, that were examined by the DNA direct sequence method. RESULTS: 56 patients with bleeding and 410 controls taking LDA were enrolled. The risk factors associated with small bowel bleeding included smoking, cerebrovascular diseases, chronic renal failure, non-steroidal anti-inflammatory drug (NSAID) or anticoagulants combination, and two SNPs (CYP4F11 20043G>A (D446N) rs1060463, GSTP1 313A>G rs1695). After propensity score matching, GSTP1 rs1695 was significantly associated with small bowel bleeding. CONCLUSION: The GSTP1 SNP may be a predictive marker for small bowel bleeding among patients taking LDA.


Aspirin/adverse effects , Cytochrome P450 Family 4/genetics , Gastrointestinal Hemorrhage/genetics , Glutathione S-Transferase pi/genetics , Intestinal Diseases/genetics , Pharmacogenomic Variants/genetics , Aged , Aspirin/administration & dosage , Capsule Endoscopy , Female , Gastrointestinal Hemorrhage/chemically induced , Genome-Wide Association Study , Humans , Intestinal Diseases/chemically induced , Intestine, Small/pathology , Male , Polymorphism, Single Nucleotide/genetics , Propensity Score , Risk Factors
10.
Esophagus ; 18(3): 655-662, 2021 07.
Article En | MEDLINE | ID: mdl-33586076

BACKGROUND: Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett's esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear. AIMS: Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells. METHODS: Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting. RESULTS: There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells. CONCLUSION: Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.


Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Membrane Proteins , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Apoptosis/physiology , Barrett Esophagus/pathology , Cell Proliferation , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Humans , Membrane Proteins/metabolism
11.
Esophagus ; 18(2): 306-314, 2021 04.
Article En | MEDLINE | ID: mdl-32728973

BACKGROUND: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. METHODS: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. RESULTS: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). CONCLUSIONS: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) (000004004).


Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Adenocarcinoma/pathology , Barrett Esophagus/diagnosis , Biomarkers , Endoscopy, Gastrointestinal , Esophageal Neoplasms/pathology , Humans , United States
12.
Digestion ; 102(1): 49-56, 2021.
Article En | MEDLINE | ID: mdl-33271532

BACKGROUND: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM). AIMS: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). METHODS: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. RESULTS: There were no differences in MAM composition between terminal ileum and sigmoid colon according to ß-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group. CONCLUSION: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.


Irritable Bowel Syndrome , Microbiota , Diarrhea , Feces , Humans , Mucous Membrane , RNA, Ribosomal, 16S/genetics
13.
Scand J Gastroenterol ; 56(1): 86-93, 2021 Jan.
Article En | MEDLINE | ID: mdl-33202164

BACKGROUND AND AIM: With recent technological advances in the field of endoscopic hemostasis, the prognosis of patients with gastrointestinal (GI) bleeding has improved. However, few studies have reported on the clinical course of patients with GI bleeding. This study aimed to evaluate the differences in clinical outcomes of patients with lower GI bleeding (LGIB) compared with upper GI bleeding (UGIB) and the factors related to their prognosis. METHODS: Patients who had undergone emergency endoscopy for GI bleeding were retrospectively reviewed. The severity of GI bleeding was evaluated using the Glasgow-Blatchford (GB), AIMS65, and NOBLADS scores. Patients in whom obvious GI bleeding relapsed and/or iron deficiency anemia persisted after emergency endoscopy were considered to exhibit rebleeding. RESULTS: We reviewed 1697 consecutive patients and divided them into UGIB (1054 patients) and LGIB (643 patients) groups. The proportion of patients with rebleeding was significantly greater in the UGIB group than in the LGIB group; the mortality rate was significantly higher in the UGIB group than in the LGIB group. Multivariate analysis showed that a GB score ≥12 and an AIMS65 score ≥2 were significantly associated with rebleeding in the UGIB group, whereas a NOBLADS score ≥4 was significantly associated with rebleeding in the LGIB group. Notably, the influence of emergency endoscopy differed according to GI bleeding location. CONCLUSIONS: The clinical course was significantly worse in patients with UGIB than in patients with LGIB. The influence of emergency endoscopy differed according to GI bleeding location.


Gastrointestinal Hemorrhage , Hemostasis, Endoscopic , Endoscopy , Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Humans , Retrospective Studies , Risk Assessment , Severity of Illness Index
14.
J Clin Biochem Nutr ; 65(2): 132-137, 2019 Sep.
Article En | MEDLINE | ID: mdl-31592051

The mucosa-associated microbiota is an important component in human microbiota. The aim was to investigate mucosa-associated microbiota using brush samples during endoscopic procedures and compare with fecal microbiota. Seven patients who were planning to undergo a routine colonoscopy were recruited. Mucosal brushing samples were taken from 3 sites (terminal ileum, ascending and sigmoid colon), and a fecal sample was taken on the morning of colonoscopy. The samples were immediately placed in microcentrifuge tubes containing DNA stabilization reagent and analyzed using the next generation sequencer. The individual differences in microbiota were more evident than the differences of the sampling sites. Actinobacteria was more abundant and Bacteroidetes was less in the brush samples than those in the fecal samples. Taxonomic composition at the genus level and the proportion of genes responsible for some functions in the brushing samples tended to be different from those in the fecal samples. Bulleidia and Oribacteriumi were significantly more abundant and the proportions of genes responsible for transcription factors and phosphotransferase system were higher in ileal mucous than those in fecal samples. Brushing during colonoscopic procedure instead of using feces samples might be useful to analyze mucosa-associated microbiota.

15.
Nihon Shokakibyo Gakkai Zasshi ; 116(6): 515-522, 2019.
Article Ja | MEDLINE | ID: mdl-31178581

A man in his 60s visited a local clinic because of repeated bouts of intermittent epigastric and back pain since July 2017. He was referred to our department because of suspected acute abdomen. Contrast-enhanced computed tomography revealed an aneurysm in the anterior inferior pancreaticoduodenal artery, and a retroperitoneal hematoma was observed. Although no extravascular leakage of contrast medium was observed, rupture of the aneurysm was suspected based on his vital signs, which indicated a state of shock. Emergency arteriography and coil embolization were performed. After coil embolization, the hematoma started to decrease, and no recurrent bleeding was observed. However, on hospitalization day 10, mucosal edema of the descending limb of the duodenum, thought to be an ischemic change, was observed along with gastrointestinal obstruction. A stomach tube was placed, and the patient was treated with central venous hyperalimentation for approximately 3 weeks. Because the gastrointestinal contrast radiography performed on hospitalization day 30 indicated improvement in the obstruction, liquid diet was started. Subsequently, the patient's gastrointestinal obstruction gradually improved. He was discharged on hospitalization day 47. The cause of the aneurysm in the anterior inferior pancreaticoduodenal artery was segmental arterial mediolysis (SAM). SAM is a degenerative arterial disease of unknown etiology that mainly develops in the bifurcations of the abdominal aorta. It requires immediate attention because the formation of aneurysms due to SAM can cause rupture and sudden intraperitoneal cavity bleeding. The prognosis for visceral artery aneurysms is poor, with a mortality rate of approximately 50% for cases involving pancreaticoduodenal artery aneurysm rupture. However, we believe that our experience is remarkable, as we saved our patient's life with conservative treatment involving coil embolization. Duodenal mucosal edema due to ischemic changes after coil embolization was observed, but this condition improved with conservative treatment.


Aneurysm, Ruptured , Duodenal Obstruction/diagnosis , Embolization, Therapeutic , Duodenum , Humans , Male , Middle Aged , Pancreas
16.
Gan To Kagaku Ryoho ; 46(2): 199-204, 2019 Feb.
Article Ja | MEDLINE | ID: mdl-30914517

Recent developments in techniques of metabologenomics have given a better understanding the association of gut microbiota with various diseases. Gut microbiota has a strong impact on host immunostasis and homeostasis of gut function for maintaining the health condition. Dysbiosis leads to an increase in bacterial populations that stimulate tumorigenesis, and contributes to epithelial carcinogenesis and tumor progression by altering metabolic properties(such as bile acid and butyric acid)and inflammatory process. Inflammation aid the bacterial translocation into the neoplastic tissue, which in turn promotes production of inflammatory cytokines subsequently leading to tumor growth. The colonic microbiota such as enterotoxigenic Bacteroides fragilis(ETBF)may also promote colorectal cancer by stimulating exaggerated immune responses via Th17 cells. Dysbiosis caused by a deficiency of the NLRP6 inflammasome promotes cancer development via interleukin-6(IL- 6)-induced epithelial proliferation. Emerging data suggest that certain groups of bacteria might promote whereas others might protect against colon cancer. Indeed, Fusobacteriumnucleatum (F. nucleatum)seems to play a central role in the tumor microenvironment as its abundance correlates with cancer progression as well as the dysbiotic tumor microbiota composition including Bacteroides and Prevotella species. Moreover, gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of cancer immunotherapy, especially immune checkpoint inhibitors by targeting the programmed death receptor 1(PD-1)and the cytotoxic T lymphocyte antigen 4(CTLA-4).


Carcinogenesis , Colorectal Neoplasms , Gastrointestinal Microbiome , Cell Transformation, Neoplastic , Dysbiosis , Humans
17.
J Dig Dis ; 19(5): 288-294, 2018 May.
Article En | MEDLINE | ID: mdl-29687957

OBJECTIVE: Heparin bridging therapy (HBT) reportedly increases the risk of post-procedural bleeding, and its safety during endoscopic interventions remains unclear. We aimed to evaluate the effects of peri-procedural HBT in patients taking anticoagulants who underwent colonic endoscopic mucosal resection (EMR) for polyps. METHODS: Patients who underwent colonic EMR while taking a single anticoagulant agent were enrolled in this study. Anticoagulants were temporarily ceased in all patients either without (the non-HBT group, prospectively enrolled) or with HBT (the HBT group, retrospectively enrolled). The incidences of post-procedural bleeding and anemia exacerbation and their length of hospitalization were evaluated and compared. RESULTS: There were altogether 43 consecutive adult patients (30 men; mean age 72.2 ± 7.4 years) in the non-HBT group and 41 sex- and age-matched adults (32 men; mean age 72.9 ± 8.3 years) in the HBT group. There were no significant differences in the location, number or size of resected polyps between the two groups. The percentage of patients with post-procedural bleeding within 2 weeks after colonic EMR in the non-HBT group was lower than that in the HBT group (2.3% vs 9.8%, P = 0.15), although the frequency of anemia exacerbation was not significantly different between the two groups. The total hospitalization length was shorter in the non-HBT compared with the HBT group (4.5 days vs 6.0 days, P < 0.001). CONCLUSIONS: No patient in either group developed embolism during hospitalization. Colonic EMR with the temporary cessation of anticoagulants without HBT may be acceptable and beneficial for patients taking anticoagulants.


Anticoagulants/adverse effects , Colonic Polyps/surgery , Endoscopic Mucosal Resection/methods , Heparin/adverse effects , Aged , Female , Humans , Length of Stay , Male , Middle Aged , Postoperative Hemorrhage/epidemiology
18.
Digestion ; 97(2): 154-162, 2018.
Article En | MEDLINE | ID: mdl-29310112

BACKGROUND/AIM: The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs. METHODS: Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood. RESULTS: A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32-8.47), women (OR 2.22; 95% CI 1.33-3.72) and corpus atrophy (OR 1.82; 95% CI 1.14-2.90). CONCLUSION: PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.


Gastric Mucosa/pathology , Gastrins/blood , Gastritis, Atrophic/drug therapy , Helicobacter Infections/drug therapy , Proton Pump Inhibitors/adverse effects , Aged , Antibodies, Bacterial/blood , Atrophy , Cross-Sectional Studies , Cytochrome P-450 CYP2C19/genetics , Female , Gastric Mucosa/diagnostic imaging , Gastritis, Atrophic/blood , Gastritis, Atrophic/diagnostic imaging , Gastritis, Atrophic/microbiology , Gastroscopy , Helicobacter Infections/blood , Helicobacter Infections/diagnostic imaging , Helicobacter Infections/microbiology , Helicobacter pylori/immunology , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Pepsinogen A/blood , Polymorphism, Genetic , Sex Factors , Time Factors
19.
Scand J Gastroenterol ; 52(12): 1365-1370, 2017 Dec.
Article En | MEDLINE | ID: mdl-28925290

BACKGROUND AND AIMS: Patients suspected of having upper gastrointestinal bleeding (UGIB) admitted during the weekend tend to have a poor outcome in western countries. However, no Japanese studies have been reported on this matter. We aimed to evaluate differences in the clinical course of patients with UGIB between weekday and weekend admissions in Japan. METHODS: Medical records of patients who had undergone emergency endoscopy for UGIB were retrospectively reviewed. The severity of UGIB was evaluated using the Glasgow-Blatchford (GB) and AIMS65 score. Patients in whom UGIB was stopped and showed improved iron deficiency anemia after admission were considered as having a good clinical course. RESULTS: We reviewed 516 consecutive patients and divided them into two groups: Group A (daytime admission on a weekday: 234 patients) and Group B (nighttime or weekend admission: 282 patients). There was no significant difference in GB and AIM65 scores between the Groups. The proportions of patients with good clinical course were not significantly different between groups (A, 67.5% and B, 67.0%; p = .90). However, patients in Group B underwent hemostatic treatments more frequently compared with those in Group A (58.5% vs 47.4%, p = .012). Multivariate analysis showed that taking acid suppressants, no need for blood transfusions, use of hemostatic treatments, and GB score <12 were associated with a good clinical course. CONCLUSIONS: There were no significant differences in the clinical outcomes of patients with UGIB admitted during daytime on weekdays and those admitted at nighttime or weekends partly owing to the sufficient performance of endoscopic hemostatic treatments.


Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/physiopathology , Gastrointestinal Hemorrhage/therapy , Hospital Mortality , Patient Admission/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Blood Transfusion , Child , Child, Preschool , Comorbidity , Cross-Sectional Studies , Endoscopy , Female , Humans , Infant , Infant, Newborn , Japan/epidemiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Assessment , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
20.
Clin J Gastroenterol ; 10(2): 154-156, 2017 Apr.
Article En | MEDLINE | ID: mdl-28110444

The Kirschner wire (K-wire) is used in the treatment of hip fractures, and migration of a K-wire into the pelvis with resultant colon injury is a very rare complication. We report a case in which a forgotten K-wire passing across the sigmoid colon was accidentally found by screening colonoscopy in a patient with no abdominal symptoms. Surgery was performed to remove the K-wire. Although the migration of a K-wire is extremely rare, it is important for it to be considered in patients with a history of orthopedic surgery.


Bone Wires/adverse effects , Colon, Sigmoid/injuries , Foreign-Body Migration/complications , Intestinal Perforation/etiology , Adult , Colon, Sigmoid/diagnostic imaging , Colon, Sigmoid/surgery , Colonoscopy , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/surgery , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/instrumentation , Fractures, Bone/surgery , Humans , Intestinal Perforation/diagnostic imaging , Intestinal Perforation/surgery , Male , Pelvic Bones/injuries , Tomography, X-Ray Computed
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