Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial.

INTRODUCTION: Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation. METHODS: This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics ( B. longum BB536, 5 × 10 10 colony-forming unit, n = 39) or placebo (n = 41) once daily for up to 4 weeks. The severity of constipation was evaluated using the Constipation Scoring System. The primary end point was the difference in the changes from baseline in the constipation scoring system total score between the 2 groups at week 4. RESULTS: A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary end point was not significant ( P = 0.074), although there was significant improvement ( P < 0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the stool frequency ( P = 0.008) and failure of evacuation ( P = 0.051) subscales, respectively, at week 4 between the 2 groups. Few adverse events related to the probiotics were observed. DISCUSSION: The primary end points were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals.

Transgastric Jejunostomy (PEG-J) for Continuous Infusion of Levodopa-Carbidopa Intestinal Gel: An Approach for Parkinson's Disease Treatment.

BACKGROUND Parkinson's disease (PD) is a neurodegenerative disorder that often requires long-term management of motor symptoms. Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) has shown promising results in alleviating motor fluctuations and improving quality of life. This study aimed to evaluate the efficacy and safety of transgastric jejunostomy (PEG-J) as a delivery method for LCIG in a cohort of 43 PD patients. MATERIAL AND METHODS Forty-three PD patients who were candidates for LCIG therapy underwent transgastric jejunostomy to facilitate continuous infusion of LCIG. The primary outcomes assessed were motor symptom improvement, reduction in motor fluctuations, and medication-related adverse events. Secondary outcomes included changes in quality of life, dyskinesia severity, and healthcare resource utilization. RESULTS The results of this study demonstrated significant improvements in motor symptoms, reduction in motor fluctuations, and enhanced quality of life following PEG-J for LCIG infusion. The treatment was generally well-tolerated, with a low incidence of procedure-related complications. Notably, the use of PEG-J allowed for precise and continuous delivery of LCIG, minimizing variations in drug absorption and ensuring consistent therapeutic levels. CONCLUSIONS Transgastric jejunostomy (PEG-J) offers an effective approach for the continuous infusion of LCIG in Parkinson's disease treatment. This method provides a stable and reliable delivery system, leading to improved symptom control and enhanced quality of life for PD patients.

The Multifaceted Role of Plasminogen in Cancer.

Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.

A Soluble Fiber Diet Increases Bacteroides fragilis Group Abundance and Immunoglobulin A Production in the Gut.

Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Previous studies have shown that Bacteroidetes, the major phylum of gut microbiota together with Firmicutes, impact IgA production. However, the relative abundances of species of Bacteroidetes responsible for IgA production were not well understood. In the present study, we identified some specific Bacteroidetes species that were associated with gut IgA induction by hsp60-based profiling of species distribution among Bacteroidetes The levels of IgA and the expression of the gene encoding activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were increased in soluble high-fiber diet (sHFD)-fed mice. We found that Bacteroides acidifaciens was the most abundant Bacteroidetes species in both sHFD- and normal diet-fed mice. In addition, the gut IgA levels were associated with the relative abundance of Bacteroides fragilis group species such as Bacteroides faecis, Bacteroides caccae, and Bacteroides acidifaciens Conversely, the ratio of B. acidifaciens to other Bacteroidetes species was reduced in insoluble high-fiber diet fed- and no-fiber diet-fed mice. To investigate whether B. acidifaciens increases IgA production, we generated B. acidifaciens monoassociated mice and found increased gut IgA production and AID expression. Collectively, soluble dietary fiber increases the ratio of gut Bacteroides fragilis group, such as B. acidifaciens, and IgA production. This might improve gut immune function, thereby protecting against bowel pathogens and reducing the incidence of inflammatory bowel diseases.IMPORTANCE Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Gut microbiota impact IgA production, but the specific species responsible for IgA production remain largely elusive. Previous studies have shown that IgA and Bacteroidetes, the major phyla of gut microbiota, were increased in soluble high-fiber diet-fed mice. We show here that the levels of IgA in the gut and the expression of activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were correlated with the abundance of Bacteroides fragilis group species such as Bacteroides faecis, Bacteroides caccae, and Bacteroides acidifaciensB. acidifaciens monoassociated mice increased gut IgA production and AID expression. Soluble dietary fiber may improve gut immune function, thereby protecting against bowel pathogens and reducing inflammatory bowel diseases.

Linked color imaging improves visibility of reflux esophagitis.

BACKGROUND: With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE). METHODS: Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21-39 points was comparable to white light, and < 20 points equaled decreased visibility. Inter- and intra-rater reliabilities (Intra-class Correlation Coefficient [ICC]) were also evaluated. Images showing color differences (ΔE*) and L* a* b* color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system. RESULTS: The mean age of patients was 67.1 years (range: 27-89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was "moderate" for LA grade M and "substantial" for erosive RE. The LCI intra-rater reliability was "moderate-substantial" for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE (P < 0.001 for WLI vs. LCI). CONCLUSION: LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.

Effectiveness of Cytapheresis for Ulcerative Colitis in Special Situations: Delayed Onset of Optimum Efficacy in Elderly Patients.

BACKGROUND: Cytapheresis is a non-pharmacologic treatment option in which depleting elevated/activated leucocytes is known to exacerbate and perpetuate ulcerative colitis (UC) by releasing inflammatory cytokines. Therefore, it is a relevant treatment for elderly patients who wish to avoid pharmacologicals. METHODS: The efficacy of Cytapheresis for remission induction in 72 patients who received Cytapheresis for active UC at our hospital was retrospectively evaluated. Patients included 11 elderly cases, patients on steroids, biologics, calcineurin inhibitor, and 13 with extra-intestinal complications. Lichtiger's UC clinical activity index ≤4 meant remission was assessed at the end of therapy and then 1 month later. The efficacy on extra-intestinal manifestations meant improvement of the main morbidity. RESULTS: At the end of Cytapheresis therapy, the remission rate in the elderly was 36.4%, and 54.2% in the non-elderly patients. One-month post Cytapheresis, the remission rate in the elderly had increased to 72.7% (p = 0.042), but to 58.3% in the non-elderly, suggesting a delayed response phenomenon in the elderly. The efficacy of Cytapheresis in 4 cases with loss of response to biologics was 75%, and 84.6% in the 13 patients with extra-intestinal complications, indicating a dramatic efficacy on dermatitis and arthralgia. CONCLUSIONS: Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.

Linked Color Imaging and the Kyoto Classification of Gastritis: Evaluation of Visibility and Inter-Rater Reliability.

BACKGROUND/AIMS: To compare white light imaging (WLI) with linked color imaging (LCI) and blue LASER imaging (BLI) in endoscopic findings of Helicobacter pylori presently infected, previously infected, and uninfected gastric mucosae for visibility and inter-rater reliability. METHODS: WLI, LCI and BLI bright mode (BLI-bright) were used to obtain 1,092 endoscopic images from 261 patients according to the Kyoto Classification of Gastritis. Images were evaluated retrospectively by 10 experts and 10 trainee endoscopists and included diffuse redness, spotty redness, map-like redness, patchy redness, red streaks, intestinal metaplasia, and an atrophic border (52 cases for each finding, respectively). Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Visibility was assessed from totaled scores. The inter-rater reliability (intraclass correlation coefficient) was also evaluated. RESULTS: Compared with WLI, all endoscopists reported improved visibility with LCI: 55.8% for diffuse redness; LCI: 38.5% for spotty redness; LCI: 57.7% for map-like redness; LCI: 40.4% for patchy redness; LCI: 53.8% for red streaks; LCI: 42.3% and BLI-bright: 80.8% for intestinal metaplasia; LCI: 46.2% for an atrophic border. For all endoscopists, the inter-rater reliabilities of LCI compared to WLI were 0.73-0.87. CONCLUSION: The visibility of each endoscopic finding was improved by LCI while that of intestinal metaplasia was improved by BLI-bright.

Does Endoscopic Retrograde Cholangiopancreatography Carry Higher Risk for Patients 90 Years and Older? A Single-Institution Retrospective Study.

BACKGROUND Endoscopic retrograde cholangiography (ERCP) for patients aged ≥90 years is often required. The safety of ERCP for super-elderly patients is a major concern for gastrointestinal endoscopists. We retrospectively examined the safety of ERCP for super-elderly patients by comparison with patients in their 70s. MATERIAL AND METHODS We reviewed 66 patients aged ≥90 years (Group A) and 43 patients in their 70s (Group B) who underwent ERCP in our institution from January 2012 to October 2019. Data were collected on patients' backgrounds, corresponding procedures, and clinical outcomes, including adverse events. RESULTS Patients in Group A (mean age: 92.3±2.1 years) had significantly poorer performance status (median: 3 vs. 0; P<0.001) and American Society of Anesthesiologists classification (median: III vs. II; P<0.001) when compared to Group B (mean age: 75.1±2.7 years). Underlying cardiovascular, cerebrovascular, renal, and orthopedic comorbidity occurrence was significantly higher in Group A than in Group B (87.88% vs. 67.44%; P=0.0094). Group A comprised more patients with benign disease than Group B (90.91% vs. 76.74%; P=0.040). Group B comprised more patients with malignant disease (31.82% vs. 53.54%; P=0.041). Emergency ERCP was higher in Group A than in Group B (71.70% vs. 29.73%; P<0.0001). No significant between-group differences in adverse events (15.15% vs. 11.63%; P=0.602) and mortality rate (1.52% vs. 2.33%; P=0.758) were noted. CONCLUSIONS Indications for ERCP should not be determined simply based on the super-elderly age of patients. ERCP may not necessarily carry higher risks if endoscopists practice maximal caution against gastrointestinal perforation.

Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study.

BACKGROUND: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS: This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS: A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS: The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

Budesonide Foam for Ulcerative Colitis Patients Experiencing Inadequate Response to Biological Therapy.

BACKGROUND In recent years, a plethora of therapeutic agents for ulcerative colitis (UC), especially novel biologics (Bio), have become available. Although it is now possible to use biological drugs, there should be no need for frequently changing medications. To avoid first-pass metabolism in the liver, thus reducing systemic bioavailability, budesonide foam has been applied as a topical steroid. We therefore evaluated whether budesonide foam has therapeutic value in UC patients who responded inadequately to Bio or to tacrolimus. MATERIAL AND METHODS We enrolled 10 patients who were experiencing an inadequate response to Bio (n=7) or to tacrolimus (n=3) at Juntendo University. We used Lichtiger's index to assess UC activity and clinical response. RESULTS Of the study patients, 4 were receiving adalimumab, 3 golimumab, and 3 tacrolimus. The average Lichtiger's index before budesonide administration was 7.1 (range 13-3), which improved to 3.4 (range 7-0) after budesonide therapy (p=0.01). Notably, 4 of the 6 cases with a Lichtiger's index >4 before budesonide administration achieved improvement of ≥3 points or remission. CONCLUSIONS Although the number of patients was small, budesonide foam had significant efficacy when added to the treatment of patients having an inadequate response to Bio or to tacrolimus. These results suggest that in cases responding poorly to Bio, adding budesonide foam as combination therapy can achieve a clinical remission.

Improved Visibility of Barrett's Esophagus with Linked Color Imaging: Inter- and Intra-Rater Reliability and Quantitative Analysis.

BACKGROUND/AIMS: To evaluate the usefulness of linked color imaging (LCI) and blue LASER imaging (BLI) in Barrett's esophagus (BE) compared with white light imaging (WLI). METHODS: Five expert and trainee endoscopists compared WLI, LCI, and BLI images obtained from 63 patients with short-segment BE. Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and one (decreased). Scores were evaluated to assess visibility. The inter- and intra-rater reliability (intra-class correlation coefficient) of image assessments were also evaluated. Images were objectively evaluated based on L* a* b* color values and color differences (ΔE*) in a CIELAB color space system. RESULTS: Improved visibility compared with WLI was achieved for LCI: 44.4%, BLI: 0% for all endoscopists; LCI: 55.6%, BLI: 1.6% for trainees; and LCI: 47.6%, BLI: 0% for experts. The visibility score of trainees compared with experts was significantly higher for LCI (p = 0.02). Intra- and inter-rater reliability ratings for LCI compared with WLI were "moderate" for trainees, and "moderate-substantial" for experts. The ΔE* revealed statistically significant differences between WLI and LCI. CONCLUSION: LCI improved the visibility of short-segment BE compared with WLI, especially for trainees, when evaluated both subjectively and objectively.

Efficacy and Acceptability of 1 Liter of Polyethylene Glycol with Ascorbic Acid vs. 2 Liters of Polyethylene Glycol Plus Mosapride and Sennoside for Colonoscopy Preparation.

BACKGROUND [color=black]Bowel preparation is an important factor for an optimal outcome of colonoscopy. Recently, polyethylene glycol (PEG) solution has been in common use for bowel cleansing for colonoscopy, but some patients are intolerant of PEG because of taste or volume. A low-volume PEG administered with ascorbic acid solution (PEG-Asc) was designed to improve tolerability, but the administration of this method is more complex than that with PEG alone. This study aimed to compare bowel cleansing efficacy, safety, and tolerability of 1 L PEG-Asc with a 2 L PEG preparation with use of sennosides and mosapride.[/color] MATERIAL AND METHODS [color=black]This was a prospective, single-center, non-inferiority trial that included 112 patients (PEG-Asc group, 68; PEG group, 44). The primary endpoint was the efficacy of colon cleansing assessed by endoscopists using a validated 4-point scale according to the Aronchick scale and was verified by a blinded investigator. Acceptability, tolerability, and adenoma detection rate (ADR) of these 2 regimens were secondary endpoints.[/color][color=black] [/color] RESULTS [color=black]We found no statistically significant differences between the groups in colon-cleansing efficacy or in the adenoma detection rate (ADR). Moreover, overall, patients significantly favored PEG-Asc over PEG, reflecting better acceptance of PEG-Asc. Additionally, more patients favored PEG-Asc over PEG for a hypothetical future colonoscopy. [/color] CONCLUSIONS [color=black]The alternate 1 L PEG-Asc regimen and standard 2 L PEG regimen were clinically equivalent with respect to cleansing efficacy, safety, and ADR, and more patients favored PEG-Asc than PEG. This alternate regimen may improve patient compliance and acceptance of surveillance colonoscopy.[/color].

Efficacy of cytapheresis for remission induction and dermatological manifestations of ulcerative colitis.

BACKGROUND: In ulcerative colitis (UC) patients, cytapheresis depletes elevated and activated leucocytes, which are known to release inflammatory cytokines including tumor necrosis factor (TNF)-α. Further, there are UC patients who develop erythema nodosum (EN) or pyoderma gangrenosum (PG) as extra-intestinal manifestations of UC. METHODS: Between 2008 and 2015, 181 consecutive patients with active UC received cytapheresis with either a granulocyte and monocyte apheresis (GMA) column or with a leucocyte removal filter (LCAP) as remission induction therapy. Each patient received weekly or intensive (2-3 sessions/week) cytapheresis up to 10 sessions. In 13 patients, UC was complicated by EN or PG. Lichtiger's clinical activity index (CAI) ≤4 meant remission, while ≥3 decrease in CAI meant response to therapy. Prednisolone sparing and the changes in the extra-intestinal manifestations were factored for assessing treatment efficacy. RESULTS: The overall remission and response rates were 52.5% and 71.8%, respectively, CAI fell from 9.4 ± 3.3 to 4.9 ± 3.5 (P < 0.001). The efficacy rates in subgroups on concomitant corticosteroid, anti-TNF or tacrolimus, and those without concomitant medications were not significantly different (P > 0.05). However, in 84 patients on prednisolone, the average daily prednisolone dose was reduced from 18.15 to 12.43 mg/day (P < 0.001) with 21.7% being corticosteroid free. All patients with EN or PG showed favorable response to cytapheresis, notably 2 EN patients achieving remission after just 2 cytapheresis sessions without concomitant medication. CONCLUSIONS: In this retrospective efficacy evaluation, cytapheresis was effective as remission induction therapy with steroid sparing effect and desirable safety profile. Further, patients with EN or PG responded favorably to cytapheresis.

Distinct endoscopic characteristics of sessile serrated adenoma/polyp with and without dysplasia/carcinoma.

BACKGROUND AND AIMS: Sessile serrated adenoma/polyp (SSA/P) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSA/P can be difficult to detect. This study aimed to clarify the endoscopic characteristics of SSA/P with advanced histology. METHODS: We examined 462 endoscopically or surgically resected lesions that were pathologically diagnosed as SSA/P, including 414 without and 41 with cytologic dysplasia, and 7 with invasive carcinoma. We retrospectively studied the clinicopathologic and endoscopic characteristics and performed pit pattern analysis. RESULTS: A stepwise increase in the size of the SSA/P series was identified along with their dysplastic progression, although 19 of 48 (39.6%) SSA/Ps with dysplasia/carcinoma were ≤10 mm in size. Most lesions were covered with a mucus cap. Macroscopically, (semi)pedunculated morphology, double elevation, central depression, and reddishness were found more frequently in SSA/P with cytologic dysplasia and invasive carcinoma ([semi]pedunculated morphology, 17.1%/28.6%; double elevation, 63.4%/57.1%; central depression, 9.8%/28.6%; reddishness, 39.0%/85.7%) than in those without dysplasia (4.6%, 4.6%, 3.9%, and 3.4%, respectively). Furthermore, the presence of at least 1 of these 4 markers had high sensitivity (91.7%) for identifying the dysplasia/carcinoma within a SSA/P, with a specificity of 85.3%. In the pit pattern analysis, all SSA/Ps without dysplasia exhibited type II pit pattern only, whereas 94.4% of SSA/Ps with dysplasia/carcinoma showed type II in addition to type IIIL, IV, VI, or VN pit patterns. CONCLUSIONS: In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, in addition to the use of magnifying endoscopy, may be useful to accurately diagnose advanced histology within an SSA/P.

Continuation of antithrombotic therapy may be associated with a high incidence of colonic post-polypectomy bleeding.

BACKGROUND AND AIM: Post-polypectomy bleeding (PPB) is the most common complication of endoscopic procedures. To reduce the risk of thromboembolic incidents, Japanese guidelines for gastroenterological endoscopy were revised to indicate that antithrombotic agents were not to be discontinued for endoscopic treatment. However, carrying out endoscopic procedures under antithrombotic medication potentially increases the incidence of hemorrhagic complications. The present study investigated the impact of the revised guidelines on the frequency of complications after colonoscopic procedures. METHODS: The surveillance period comprised the year before the initiation of the new guidelines (2012), which served as a control period, and 2 years after initiation of the new guidelines (2013 and 2014). During the control period, 3955 cases were examined colonoscopically and 1601 lesions were treated endoscopically. During the 2-year period under the new guidelines, 8749 colonoscopies and 3768 endoscopic treatments were carried out. Changes in treatment methods and rates of complications were compared. RESULTS: PPB rate was not significantly different before and after the revision (0.87% vs 1.01%). With the new guidelines, PPB rates in antithrombotic non-users and users were 0.60% and 3.13%, respectively (OR 5.11, P = 0.000). Multivariable analysis showed that the risks for PPB were as follows: heparin bridging therapy (OR 6.34, P = 0.0002); low-dose aspirin (LDA) continuation (OR 5.30, P = 0.0079); and lesion size (OR 1.06, P < 0.0001). CONCLUSION: The present study showed that the overall PPB rate under the new guidelines was not significantly higher when compared with the previous data obtained before the new guidelines were introduced.

Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: a study of 29 cases.

BACKGROUND: Gastric adenocarcinoma with enteroblastic differentiation (GAED) has been recognized as a variant of alpha-fetoprotein (AFP)-producing gastric carcinoma, although its clinicopathologic and immunohistochemical features have not been fully elucidated. METHODS: To elucidate the clinicopathologic and immunohistochemical features of GAED, we analyzed 29 cases of GAED, including ten early and 19 advanced lesions, and compared these cases with 100 cases of conventional gastric adenocarcinoma (CGA). Immunohistochemistry for AFP, glypican 3, SALL4, and p53 was performed, and the phenotypic expression of the tumors was evaluated by immunostaining with antibodies against MUC5AC, MUC6, MUC2, CD10, and caudal-type homeobox 2 (CDX2). RESULTS: Lymphatic and venous invasion was more frequent in GAED (76 and 72 %) than in CGA (41 and 31 %; P ≤ 0.001). Lymph node metastasis was more frequently observed in GAED (69 %) than in CGA (38 %; P = 0.005), as were synchronous or metachronous liver metastases (GAED, 31 %; CGA, 6 %; P ≤ 0.001). Immunohistochemically, all GAED were positive for at least one of three enteroblastic linage markers (AFP, glypican 3, and SALL4). Glypican 3 was the most sensitive marker (83 %) for GAED, followed by SALL4 (72 %) and AFP (45 %), whereas no CGA was positive. Furthermore, the rate of positive p53 staining was 59 % in GAED. Regarding the mucin phenotype, CD10 and CDX2 were diffusely or focally expressed in all GAED cases. Invasive areas with hepatoid or enteroblastic differentiation were negative for CD10 and CDX2. CONCLUSIONS: Clinicopathologic features of GAED differ from those of CGA. GAED shows aggressive biological behavior, and is characteristically immunoreactive to AFP, glypican 3, or SALL4.

MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis.

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory disorder of the large intestine. Mucosal associated invariant T (MAIT) cells are a member of innate-like lymphocytes found abundantly in the mucosal tissue. The contribution of MAIT cells in the pathogenesis of UC is still unclear; therefore, this study aimed at investigating the role of these cells in patients with UC. METHODS: The frequency of MAIT cells, as well as the production of cytokines and expression levels of activation markers by these cells in the peripheral blood of UC patients and healthy controls, was analyzed by flow cytometry. MAIT cells were also quantified in colon biopsies of UC patients using a confocal microscope. RESULTS: There was a significant reduction in MAIT cell frequency in the peripheral blood of UC patients compared with healthy controls (P < 0.0001). MAIT cells from UC patients secreted more interleukin (IL)-17 than healthy controls (P < 0.05). The expression levels of CD69 on these cells were correlated with disease activity and endoscopic scores and plasma levels of IL-18. Furthermore, MAIT cells increased in the inflamed mucosa, and their frequency was correlated with clinical and endoscopic disease activity in UC patients. CONCLUSIONS: The findings from this study indicate that MAIT cells could be associated with UC and may serve as potential biomarkers or therapeutic targets in UC.

Closure with clips to accelerate healing of mucosal defects caused by colorectal endoscopic submucosal dissection.

BACKGROUND: Most mucosal defects that occur with endoscopic submucosal dissection (ESD) can be closed completely using endoscopic clips. However, benefits of such closure in wound healing are unknown. A randomized controlled study evaluated the efficacy of closure with clips compared with no closure. METHOD: Twenty-eight patients who had undergone ESD were randomly divided into two groups: closure (n = 14) and non-closure groups (n = 14). In the closure group, the mucosal defect resulting from ESD was closed using endoscopic clips. Four weeks after ESD, defects in both groups were observed by colonoscopy. Efficacy was based on change in the area of the defect, percentage of complete healing in each group, and complications. RESULT: Data were analyzed for 26 of the 28 patients (13, closure group; 13, non-closure group). All tumors were resected en bloc by ESD without bleeding or perforation. In the closure group, the area of the defect just after ESD was 677 ± 306 mm(2) (mean ± SD) as determined by the size of the removed lesion and had decreased to 2.17 ± 4.51 mm(2) at 4 weeks after ESD (reduction, 99.7 %), but in the non-closure group that area was 790 ± 221 mm(2) and had decreased to 27.42 ± 25.72 mm(2) at 4 weeks post-ESD (reduction, 96.2 %). The reduction rate was significantly higher in the closure than in the non-closure group (99.7 vs. 96.2 %, p = 0.010). Complete healing was 69.2 % in the closure group vs. 7.7 % in the non-closure group (p = 0.005). Multivariate analysis showed that closure of the mucosal defect (OR 24.029, 95 % CI 2.09-276.15, p = 0.011) was an independent factor associated with complete healing at 4 weeks after ESD. Delayed perforation or post-ESD bleeding was not observed in any participant. CONCLUSION: Use of endoscopic clips for closure of defects after ESD is safe and efficacious in accelerating wound healing. TRIAL REGISTRATION: UMIN-CTR UMIN000009112.

An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/µL to 6950/µL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.