Characteristics of factors contributing to follow-up for suspect delayed bleeding after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Delayed bleeding (DB) is a major adverse event associated with colorectal endoscopic submucosal dissection (ESD) that sometimes causes difficulties in making decisions regarding endoscopic hemostasis. This study identified the factors that contribute to follow-up without endoscopic hemostasis when DB is suspected after colorectal ESD. METHODS: In total, 583 patients (603 tumors) who underwent ESD or hybrid ESD for colorectal tumors at Chiba University Hospital between June 2009 and January 2022 were retrospectively registered. Of these, 141 cases (141 tumors) with DB; with hematochezia or hemoglobin decrease ≥2 g/dL after colorectal ESD were analyzed. The DB group was divided into the Hemostasis group (H group; endoscopic hemostasis performed) and no-Hemostasis group (no-H group; no endoscopy performed, or endoscopy performed but no hemostasis performed after hematochezia or hemoglobin decrease). Univariate and multivariate logistic regression analyses were performed to assess the factors contributing to follow-up. RESULTS: Thirty-one patients with 31 tumors were categorized into the H group, while 110 patients with 110 tumors were in the no-H group. Multivariate regression analysis revealed that date from ESD to first hematochezia ≤Day 3 (odds ratio [OR] 4.55, 95% confidence interval [CI] 1.44-14.33; p = 0.010) and bleeding duration ≤1 day (OR 3.35, 95% CI 1.35-8.34; p = 0.009) contributed to follow-up. CONCLUSIONS: In cases of DB after colorectal ESD, a bleeding duration ≤1 day or date from ESD to first hematochezia ≤Day 3 may contribute to follow-up observation without endoscopic hemostasis.

Utility of prophylactic clipping after colorectal cold snare polypectomy in patients on oral antithrombotic agents.

BACKGROUND AND AIMS: There is no consensus on the effectiveness of prophylactic clipping after colonic cold snare polypectomy (CSP). This study aimed to evaluate the utility of prophylactic clipping in preventing delayed bleeding (DB) after colorectal CSP in patients on antithrombotic agents. METHODS: We retrospectively recruited consecutive patients on antithrombotic agents who underwent colorectal CSP in Chiba University Hospital. The DB rate was compared between patients with and without prophylactic clipping. RESULTS: The study included 133 patients (422 polyps) requiring prophylactic clipping and 85 patients (282 polyps) not requiring prophylactic clipping. There were no significant differences in DB and hematochezia rates between the groups. By weighted logistic regression analysis, the odds ratio of hematochezia was 0.557 (95% confidence interval, 0.225-1.378; P = .205) in patients without clipping compared to those with clipping. CONCLUSIONS: Prophylactic clipping may not be necessary to prevent DB after colorectal CSP in patients on antithrombotic agents.

Intensive triamcinolone acetonide injection regimen can highly prevent stricture after extensive esophageal endoscopic submucosal dissection.

BACKGROUND: This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD). METHODS: This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections. RESULTS: Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p < 0.001). CONCLUSIONS: Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.

A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Differences Between Patients with Heartburn Refractory to Vonoprazan and Those Refractory to Proton Pump Inhibitors.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn. METHODS: This study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance-pH (MII-pH) testing with vonoprazan/PPI discontinuation. Patients' backgrounds, symptom scores from four questionnaires, MII-pH results and high-resolution manometry results were compared between the two groups. RESULTS: The vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII-pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII-pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0-0.3]). CONCLUSION: Patients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn.

Two onset types of achalasia and the long-term course to diagnosis.

BACKGROUND: Recently, the incidence of achalasia has been increasing, but its cause remains unknown. This study aimed to examine the initial symptoms and the course of symptoms and to find new insights into the cause and course of the disease. METHODS: Altogether, 136 patients diagnosed with achalasia by high-resolution manometry (HRM) were enrolled. Questionnaires and chart reviews were conducted to investigate the initial symptoms, time from onset to diagnosis, and comorbidities, as well as the relationship between HRM results, time to diagnosis, and symptom severity. RESULTS: In total, 67 of 136 patients responded to the questionnaire. The median ages of onset and diagnosis were 42 and 58 years, respectively. The median time from onset to diagnosis was 78.6 months, with 25 cases (37.3%) taking > 10 years to be diagnosed. The symptom onset was gradual and sudden in 52 (77.6%) and 11 (16.4%) patients, respectively. Of the 11 patients with acute onset, three (27.3%) developed anhidrosis at the same time. There was no correlation between the time from onset to diagnosis and esophageal dilatation, resting LES pressure, or mean integrated relaxation pressure (IRP). No correlation was also found between the degree of symptoms and resting LES pressure or IRP. CONCLUSION: Esophageal achalasia can have acute or insidious onsets. This finding may help to elucidate the cause of achalasia.

Long-term course of gastric submucosal tumors: growth speed and size-increasing factors.

BACKGROUND AND AIMS: Gastric submucosal tumors (SMTs) are treated or monitored according to GI stromal tumor guidelines, but the adequacy of the guidelines has not been thoroughly examined. We investigated the long-term course of gastric SMTs to determine the validity of guideline-based follow-up methods and the factors contributing to their size increase. METHODS: This study included gastric SMTs diagnosed as GI mesenchymal tumors (GIMTs) by using EUS and followed up with EUS. The percentage and speed of GIMT enlargement and factors associated with the enlargement were investigated by using the Cox proportional hazards model. RESULTS: From January 1994 to May 2022, a total of 925 gastric SMTs were evaluated with EGD, and 231 SMTs were diagnosed as GIMTs. Of the 231 GIMTs, 145 were examined by EUS more than twice and were followed up for >6 months. The mean ± standard deviation follow-up period was 5.20 ± 4.04 years (range, 0.5-17.3 years), with 39 (26.9%) of 145 GIMTs increasing in size with a mean doubling time of 3.60 ± 3.37 years. A multivariate analysis of factors influencing tumor growth revealed that irregular extraluminal borders were an increasing factor (hazard ratio, 3.65; 95% confidence interval, 1.26-10.52), initial tumor size ≤9.5 mm (hazard ratio, .23; 95% confidence interval, 0.07-0.77) was a nonincreasing factor, and GIMTs with calcification (n = 13) did not increase in size. CONCLUSIONS: Tumor growth in gastric GIMTs <9.5 mm in diameter and/or with calcification is rare. Follow-up intervals for these lesions could be extended.

Clinical Features Focusing on Extraintestinal Manifestations in Japanese Patients with Inflammatory Bowel Diseases: Far East 1000.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) can develop extraintestinal manifestations (EIMs) during the disease course, which sometimes impact their quality of life. OBJECTIVES: This study aimed to clarify the prevalence and types of EIMs using a hospital-based IBD cohort in Japan. METHODS: A patient cohort with IBD was established in 2019, as participated by 15 hospitals in Chiba Prefecture of Japan. Using this cohort, the prevalence and types of EIMs, which are defined based on previous reports and the Japanese guidelines, were investigated. RESULTS: This cohort enrolled 728 patients, including 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). Of these patients with IBD, 10.0% were identified with one or more EIMs (57 (10.5%) with UC and 16 (8.6%) with CD). Arthropathy and arthritis were the most common EIM in 23 (4.2%) patients with UC, followed by primary sclerosing cholangitis (PSC) (2.6%). Arthropathy and arthritis were also the most common in patients with CD, but no cases of PSC were observed. EIMs were more frequently observed in patients with IBD treated by specialists than in those treated by non-specialists (12.7% vs. 5.5%, p = 0.011). The incidence of EIMs in patients with IBD was not significantly different over time. CONCLUSIONS: The prevalence and types of EIMs in our hospital-based cohort in Japan did not significantly differ from those reported in previous or Western studies. However, the incidence might be underestimated due to the limited ability of non-IBD specialists to discover and describe EIMs in patients with IBD.

[A case of irreversible metronidazole encephalopathy during liver abscess treatment].

Metronidazole (MNZ) is a widely used drug for protozoan and anaerobic infections. The continuous use of MNZ causes various neurological symptoms, such as cerebellar ataxia, visual disturbance, vestibulocochlear symptoms, gait disturbance, dysarthria, and epileptic seizures of unknown cause, named MNZ-induced encephalopathy (MIE), in rare cases. MIE is a reversible disease that often improves within a few days of MNZ discontinuation, but irreversible neurological symptoms rarely remain. Herein, we report a case of MIE that developed during MNZ administration for a liver abscess, causing prolonged unconsciousness and death even after drug discontinuation. An 85-year-old female patient complained of fever, elevated liver enzymes, and a multifocal abscess in the right hepatic lobe, as seen on computed tomography. Percutaneous transhepatic abscess drainage and antibiotic therapy were initiated. The causative agent of the liver abscess could not be identified, thus meropenem was started, which demonstrated no inflammation improvement, thus oral MNZ was added. The inflammation recurred when MNZ was discontinued, and the patient continued taking MNZ. Vomiting, upper limb tremors, consciousness disturbance, and convulsions appeared on day 46 (total dose of MNZ 73.5mg), and the patient was hospitalized. T2-weighted, diffusion-weighted, and FLAIR head magnetic resonance imaging (MRI) revealed symmetrical abnormal high-signal areas in the cerebellar dentate nucleus, corpus callosum, cerebral white matter, and periventricular areas. MIE was diagnosed based on the patient's course and MRI images, and MNZ was discontinued. The patient continued to suffer from impaired consciousness and convulsions after MNZ discontinuation and died due to aspiration pneumonia. Suggestively, MIE development is related to long-term MNZ administration, poor nutrition, liver disease, underlying diseases (such as advanced cancer), and serious complications. A systematic review of MIE cases revealed that 4.8-5.9% of the patients demonstrated little improvement of symptoms after MNZ discontinuation, and some deaths were reported. Patients with poor prognosis were often suffering from impaired consciousness and convulsions. Furthermore, impaired consciousness was the most common residual symptom. Abnormal signals in characteristic areas, such as the dentate nucleus cerebri and corpus callosum, on head MRI are useful for MIE diagnosis, especially in patients with abnormal findings in the cerebral white matter, which is associated with a poor prognosis. We should pay close attention to the onset of MIE when MNZ is administered.

Anti-TNFα antibody versus non-anti-TNFα molecular agents for ulcerative colitis patients who failed initial anti-TNFα therapy.

BACKGROUND AND AIM: Anti-tumor necrosis factor (TNF)α antibody (ATA) and biologics/molecular targeted agents with other mechanisms (non-ATA) are currently available for refractory ulcerative colitis (UC). However, the knowledge about optimal drug selection after the initial treatment with ATA failure is lacking. This study assessed whether the response to the initial ATA could be a basis for selecting subsequent agents in UC patients. METHODS: Ulcerative colitis patients treated with ATA or non-ATA as the subsequent biologic after the failure of initial ATA were retrospectively analyzed. The efficacy at 14 weeks was examined according to the response to initial ATA. RESULTS: Of 163 patients treated with the first ATA, the efficacy of subsequent ATA and non-ATA was evaluated in 63 and 36, respectively. Remission and response to subsequent-line therapy, regardless of ATA or non-ATA, were lower in patients with primary nonresponse (PNR) to initial ATA than in patients with efficacy to initial ATA (33.3% vs 69.2%, P < 0.01). In patients with PNR to initial ATA, the remission rate with subsequent ATA was significantly lower than with subsequent non-ATA (4.3% vs 26.3%, P = 0.04). In patients who showed efficacy to initial ATA, the remission rate with subsequent ATA was also lower than that with subsequent non-ATA (30.6% vs 56.3%, P = 0.08). PNR with initial ATA was the predictor of PNR to subsequent ATA (odds ratio: 5.62, 95% confidence interval: 1.50-21.7). CONCLUSION: Non-ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA.

Evaluation of Usability and Learning Motivation of e-Learning Courses for People With Chronic Kidney Disease.

Nurses need to increase patient education opportunities so that more people with chronic kidney disease can understand the disease accurately from its early stages. We developed an e-learning course based on the Dick and Carey system approach model and the attention, relevance, confidence, satisfaction model for people with chronic kidney disease. People with chronic kidney disease, on average, are aged around 50 to 60 years, and this population tends to lack perceived susceptibility toward and concern for the disease owing to the asymptomatic nature of early chronic kidney disease. Therefore, e-learning should be easy to use and motivate learning. This study aimed to evaluate the usability and learning motivation of this course. The participants included 10 outpatients (mean age, 51.2 years) with chronic kidney disease whose mastery percentage of learning objectives was compared by the knowledge tests immediately before and after the course. We also observed the participants' operation status and measured their motivation for using instructional materials with a questionnaire. The results demonstrated that this course facilitates independent operation, improves postcourse performance, and motivates participants in all areas of learning motivation. Thus, this e-learning course can be recommended as easy to use and motivating for people with chronic kidney disease.

Impact of ineffective esophageal motility on chemical clearance in patients with gastroesophageal reflux symptoms.

Ineffective esophageal motility (IEM) is the most common manometric abnormality in gastroesophageal reflux disease (GERD). However, the impact of IEM on esophageal chemical clearance has not been fully investigated. This study aimed to determine the impact of IEM on esophageal chemical clearance in patients with GERD. A total of 369 patients with GERD symptoms who underwent upper endoscopy and high-resolution manometry (HRM) test were retrospectively analyzed. The relationship between IEM and erosive esophagitis was examined. In addition, the impact of IEM on chemical clearance was examined in patients who underwent an additional combined multichannel intraluminal impedance-pH (MII-pH) test. Esophageal chemical clearance capability was evaluated via postreflux swallow-induced peristaltic wave (PSPW) index and acid clearance time (ACT). Of 369 patients, 181 (49.1%) had esophageal motility disorders, of which 78 (21.1%) had IEM. The proportion of IEM patients in those with erosive esophagitis and those without were 16.2% and 21.7%, respectively, and no significant difference was observed (P = 0.53). After excluding patients other than those with IEM and normal esophageal motility, 64 subsequently underwent MII-pH test. The median values of the PSPW index in the IEM and normal esophageal motility group were 11.1% (4.2%-20.0%) and 17.1% (9.8%-30.6%), respectively. The PSPW index was significantly lower in the IEM group than in the normal esophageal motility group (P < 0.05). The median ACT values in the IEM group and normal esophageal motility group were 125.5 (54.0-183.5) seconds and 60.0 (27.2-105.7) seconds, respectively. The ACT was significantly longer in the IEM group than in the normal esophageal motility group (P < 0.05). In conclusion, IEM was found to be associated with chemical clearance dysfunction as measured against the PSPW index and ACT. As this condition could be a risk factor for GERD, future treatments should be developed with a focus on chemical clearance.

Chiral intertwined spirals and magnetic transition dipole moments dictated by cylinder helicity.

The presence of anomalous chirality in a roll of graphitic carbon sheets has been recognized since the discovery of carbon nanotubes, which are becoming available in higher quantities through the isolation of chiral single-wall congeners with high purity. Exploration of the properties arising from cylinder chirality is expected to expand the scope of tubular entities in the future. By studying molecular fragments of helical carbon nanotubes, we herein reveal interesting properties that arise from this chirality. The chirality of nanoscale cylinders resulted in chirality of larger dimensions in the form of a double-helix assembly. Cylinder chirality in solution gave rise to a large dissymmetry factor of metal-free entities in circular polarized luminescence. Theoretical investigations revealed the pivotal role of cylindrical shapes in enhancing magnetic dipole transition moments to yield extreme rotatory strength. Unique effects of cylinder chirality in this study may prompt the development of tubular entities, for instance, toward chiroptical applications.

[Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine].

A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse. The patient received the GDP regimen as salvage therapy with the addition of vorinostat for skin involvement; however, he failed to respond, and the disease systemically progressed. Furthermore, he also exhibited progression in the skin after stopping vorinostat due to hematologic toxicity. A lymph node biopsy at progression revealed CD20 re-expression by immunohistochemistry. At progression, the patient received mogamulizumab but failed to respond, and he died owing to disease progression 8 months after relapse. In this case, we demonstrated CD20-negative conversion following rituximab and CD20-positive reversion after using vorinostat and gemcitabine.

Negative feedback by IRE1ß optimizes mucin production in goblet cells.

In mammals, the prototypical endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1 (IRE1) has diverged into two paralogs. IRE1α is broadly expressed and mediates the unconventional splicing of X-box binding protein 1 (XBP1) mRNA during ER stress. By contrast, IRE1ß is expressed selectively in the digestive tract, and its function remains unclear. Here, we report that IRE1ß plays a distinctive role in mucin-secreting goblet cells. In IRE1ß(-/-) mice, aberrant mucin 2 (MUC2) accumulated in the ER of goblet cells, accompanied by ER distension and elevated ER stress signaling such as increased XBP1 mRNA splicing. In contrast, conditional IRE1α(-/-) mice showed no such ER distension but a marked decrease in spliced XBP1 mRNA. mRNA stability assay revealed that MUC2 mRNA was greatly stabilized in IRE1ß(-/-) mice. These findings suggest that in goblet cells, IRE1ß, but not IRE1α, promotes efficient protein folding and secretion in the ER by optimizing the level of mRNA encoding their major secretory product, MUC2.

Non-Hodgkin lymphoma diagnosed by a percutaneous trans-hepatic needle biopsy of portal vein tumor emboli.

A 58-year-old woman was admitted to our hospital for evaluation of left flank pain. Abdominal computed tomography showed a greatly enlarged splenic tumor with a massive portal vein tumor thrombosis (PVTT). We suspected non-Hodgkin lymphoma (NHL) based on the high values of serum soluble interleukin-2 receptor and lactate dehydrogenase. Because there was no superficial lymph node enlargement, ultrasound-guided percutaneous trans-hepatic needle biopsy was performed to obtain a pathological diagnosis of PVTT, instead of a splenectomy, after the patient had provided informed consent. This procedure was thought to be less invasive than splenectomy. Histologic examination revealed CD20-positive NHL. A complete response was achieved after six courses of R-CHOP and it was confirmed by splenectomy. A PVTT due to NHL is extremely rare as compared with that due to hepatocellular carcinoma, gastric cancer, and colon cancer. However, NHL should be considered in the differential diagnosis for a patient with a PVTT, because B cell-NHL tends to have a good prognosis when rituximab combined chemotherapy is administered. We suggest that a percutaneous trans-hepatic needle biopsy may be useful for diagnosing PVTT due to NHL.

Versatile chiral chromatography with mixed stationary phases of water-impregnated silica gel and reversed-phase packing.

A novel chiral chromatographic scheme is proposed, which requires no organic syntheses in stationary phase preparation. A normal phase chiral chromatography stationary phase is prepared by simple passage of an aqueous solution of an appropriate chiral selector through e.g. a silica gel column. For this scheme, a mixed-bed of bare silica gel and octadecylsilanized silica gel (ODS) provides much better separation performance than a silica gel column. Isolation of silica gel particles in the column is important for successful chiral separation based on the present scheme.

Clinical outcomes and reintervention after endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis in absence of cholangitis.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis. METHODS: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome. RESULTS: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28). CONCLUSION: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis.

Differences in Mucosal Permeability Among Patients With Ulcerative Colitis Classified Based on the Colonic Location and Disease Activity.

INTRODUCTION: Factors affecting mucosal permeability (MP) in ulcerative colitis (UC) are largely unknown. We aimed to investigate the difference in MP among patients with UC classified according to the colonic locations and to evaluate the correlations between local MP and endoscopic or histological activity of UC. METHODS: The transepithelial electrical resistance (TER), which is inversely proportional to permeability, of tissue samples from the mucosa of the ascending colon, descending colon, and rectum of patients with UC and healthy individuals (HIs) was measured by using the Ussing chamber. TERs were compared between patients with UC and HIs and evaluated according to colonic locations and disease activity of UC. RESULTS: Thirty-eight patients with UC and 12 HIs were included in this study. Both in HIs and patients with UC, MP tends to be higher in the anal side. TER in the ascending colon was significantly lower in patients with UC than in HIs (45.3 ± 9.0 Ω × cm 2 vs 53.5 ± 9.7 Ω × cm 2 , P = 0.01). The increased permeability in UC was observed also in the descending colon, only when the inflammation involved the location. A significant correlation between TER and endoscopic activity was found in the rectum only ( r = -0.49, P = 0.002). There were no significant correlations between TERs and UC histology. DISCUSSION: The MP in the colon differs according to the colonic location. The ascending colon among patients with UC showed disease-specific changes in MP, whereas the MP is increased in proportion to the endoscopic activity in the rectum.

Investigation of risk factors for metachronous recurrence in patients with early gastric adenocarcinoma by miRNA-mRNA integral profiling.

The mechanism of metachronous recurrence (MR) after performing endoscopic treatment for early gastric adenocarcinoma (GAC) and eradicating Helicobacter pylori (H. pylori) is unknown. To elucidate the mechanism and risk factors of MR, we analyzed gene expression at multiple locations of the gastric mucosa. We selected each five patients with MR and without MR (control), after early GAC treatment and eradication of H. pylori. Mucosal tissue was collected from four sites in the stomach of each patient as biopsy specimens for mRNA sequencing, gene set enrichment analysis, and microRNA (miRNA) sequencing. We also performed correlation analysis and target prediction on pathways. As a result, endoscopically, the MR group had more intestinal metaplasia and enlarged folds. A total of 384 mRNAs presented changes in expression and 31 gene sets were enriched in the MR group. Immune-related pathways were enriched in the entire stomach, and the IFN-α response had the highest enrichment score. Additionally, 32 miRNAs revealed changes in their expression. Correlation analysis and target prediction with genes in the gene set of IFN-α response revealed that 10 miRNA-mRNA pairs presented a significant correlation. Immune-related pathways with miRNAs in the gastric mucosa after H. pylori eradication may be a risk factor for MR.