Thiopurine naivety at tacrolimus induction is a predictor of long-term remission in patients with intractable ulcerative colitis who responded to tacrolimus.

BACKGROUND: The short-term efficacy of tacrolimus (Tac) for steroid-dependent and steroid-resistant refractory ulcerative colitis (UC) has been demonstrated; however, its long-term outcomes have not been well documented. Thus, this study aimed to clarify the long-term outcomes of patients who achieved Tac-induced remission and identify its predictors. METHODS: This study included patients with moderate-to-severe active UC who started receiving Tac at our hospital between July 2004 and December 2016. Short-term treatment response was assessed using the Lichtiger index 3 months after starting Tac, and responding patients were further followed up to assess long-term outcomes. The primary endpoint was the relapse-free survival after Tac-induced remission, and the secondary endpoint was the identification of factors associated with relapse after Tac-induced remission. RESULTS: The cumulative relapse-free survival rate at 10 years after Tac-induced remission was 33.2%. Multivariate analysis revealed that being thiopurine naïve at Tac induction was associated with the absence of relapse (hazard ratio: 0.45; 95% confidence interval: 0.22-0.92). CONCLUSIONS: Approximately one-third of patients who achieved Tac-induced remission maintained long-term remission. Being thiopurine naïve at Tac induction was a predictor of the absence of relapse.

Long-term outcomes of endoscopic balloon dilation for intestinal strictures in patients with Crohn's disease during maintenance treatment with anti-tumor necrosis factor alpha antibodies.

BACKGROUND AND AIMS: Efficacy of endoscopic balloon dilation (EBD) for intestinal strictures in patients with Crohn's disease (CD) receiving anti-tumor necrosis factor alpha antibodies (anti-TNF) as maintenance therapy is unclear. We investigated the long-term efficacy and safety of EBD for intestinal strictures in patients with CD receiving anti-TNF. METHODS: We retrospectively analyzed data from patients with CD who received anti-TNF as maintenance therapy from 2008 to 2017, underwent EBD, and were followed up for ≥6 months. The primary endpoint was the cumulative surgery-free rate. The main secondary endpoints were technical success, repeat EBD rate, risk factors affecting surgical outcomes, and safety. RESULTS: Seventy-two patients with CD were assessed. The median observation period after EBD was 50 months. The technical success rate was 67%. The 3- and 5-year cumulative surgery-free rates were 81.1% and 73.5%, respectively. The repeat EBD rate was 74%. Multivariable analyses showed that risk factors affecting surgical outcomes were age at disease onset ≤16 years (hazard ratio 3.69; 95% confidence interval 1.36-10.01; P = 0.011). Serious complications requiring surgery developed in three patients. CONCLUSIONS: Endoscopic balloon dilation was an effective and safe short-term treatment and a useful long-term treatment for CD patients with intestinal strictures receiving anti-TNF as maintenance therapy.

Novel ultrathin double-balloon endoscopy for the diagnosis of small-bowel diseases: a multicenter nonrandomized study.

BACKGROUND: This study aimed to compare the markers of potential pancreatic injury during antegrade double-balloon endoscopy (DBE) using the newly developed ultrathin EN-580XP system and the conventional EN-580T system. METHODS: Patients who were scheduled for antegrade DBE during daily clinical practice were enrolled. Clinical background, adverse events, and laboratory data of patients were compared between those who underwent endoscopy using the EN-580XP system and those in whom the EN-580T system was used. The primary end points were pancreatic hyperamylasemia and hyperlipasemia after DBE. RESULTS: A total of 295 cases were registered. Pancreatic hyperamylasemia occurred in 2 of 92 patients (2.2 %) in the EN-580XP group and in 28 of 147 patients (19.1 %) in the EN-580 T diagnosis group (P < 0.001). Hyperlipasemia was significantly different between the two groups (1.1 % [EN-580XP] vs. 13.6 % [EN-580 T diagnosis]; P < 0.001). Acute pancreatitis occurred in four patients (7.1 %) in the EN-580 T therapy group. Multiple logistic regression analyses revealed that the endoscope type EN-580 T was significantly associated with pancreatic hyperamylasemia (adjusted odds ratio [OR] 8.63, 95 % confidence interval [CI] 1.97 - 37.70; P < 0.01) and hyperlipasemia (adjusted OR 13.10, 95 %CI 1.70 - 100.70; P = 0.01). CONCLUSIONS: The EN-580XP system seemed less harmful to the pancreas during antegrade DBE.

Comparison of Small Bowel Lesions Using Capsule Endoscopy in Ulcerative Colitis and Crohn's Disease: A Single-Center Retrospective Analysis.

BACKGROUND: Capsule endoscopy (CE) has allowed the characterization of small bowel lesions. However, small bowel lesions in ulcerative colitis (UC) have not been elucidated and no studies have compared between UC and Crohn's disease (CD). AIM: The objective of this study was to investigate the small bowel lesions in UC, and to characterize UC lesions by comparison with CD. METHODS: Subjects comprised 54 UC patients and 39 CD patients who underwent CE. We retrospectively investigated characteristics of small bowel lesions in UC. We also compared endoscopic findings and degree of inflammation between UC and CD. RESULTS: The incidence of small bowel lesions in UC was 27.8%. The group with small bowel lesions exhibited higher endoscopic activity in the colon than without small bowel lesions (p = 0.002). Comparing small bowel lesions between UC and CD, significantly more ulcerative lesions, notched appearance, longitudinal tendency of lesions, and cobblestone appearance were seen in CD. The Lewis score was significantly higher in CD than UC in the second and third tertiles (205 ± 379 vs. 73 ± 223, p = 0.01; 358 ± 449 vs. 105 ± 333, p < 0.001). CONCLUSIONS: Small bowel lesions in UC were linked to colonic activity. UC and CD differ in terms of the morphology and distribution of small bowel lesions.

[A case of a simple ulcer associated with ulcerative colitis that demonstrated a good clinical response to infliximab].

We present a case of a man in his 60s who had been in clinical remission of ulcerative colitis (UC) after treatment with 5ASA. Over the clinical course, he developed an isolated deep ulcer at the end of the ileum. There were moderate active UC findings in the rectum. We diagnosed a simple ulcer associated with UC and started treatment with azathioprine and infliximab (IFX). Shortly after the treatment, the ulcer began to scar. We report a rare case of a simple ulcer that accompanied UC, and for which IFX was effective.

Effectiveness of magnesium citrate as preparation for capsule endoscopy: a randomized, prospective, open-label, inter-group trial.

BACKGROUND AND AIM: Capsule endoscopy (CE) is effective in the detection of small bowel lesions. Many studies have been conducted on the effectiveness of preparations in improving diagnostic yield, but an effective method has yet to be confirmed. We used magnesium citrate as preparation for CE and evaluated its effectiveness. METHODS: 50 patients who underwent CE were randomly allocated to two groups - group A (preparation provided) and group B (no preparation). Group A were administered 34 g of magnesium citrate at 8 p.m. the night before the examination. Group B were not administered a laxative. RESULTS: The cleansing efficacy score was 24.4 ± 4.4 points for group A and 22.9 ± 4.4 points for group B, with no significant difference between groups. No significant difference was seen in the large bowel arrival rate between groups: 14 cases (63.6%) for group A and 16 cases (72.7%) for group B. CONCLUSION: In this study, superiority was not seen for cleansing efficacy, large bowel arrival rate for the preparation method involving administration of hypertonic MC solution 12 h prior to the procedure.

A review on the current status and definitions of activity indices in inflammatory bowel disease: how to use indices for precise evaluation.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn's disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Efficacy of enteral nutrition in patients with Crohn's disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis.

Enteral nutrition (EN) is effective in Crohn's disease (CD) patients and has been shown to have an inhibitory effect on loss of response to anti-tumor necrosis factor (TNF)-alpha antibody therapy; however, the current level of evidence is not sufficient. The objective of this meta-analysis was to determine whether EN in combination anti-TNF-alpha antibody therapy is useful in maintaining remission. PubMed was used to identify all relevant studies. A total of nine articles were identified including one randomized control trial, two prospective cohort studies, and six retrospective cohort studies. We performed a meta-analysis on all these articles to assess the remission maintenance effect of EN (n = 857). The remission or response maintenance effect in the EN group was 203/288 (70.5%), which was higher than 306/569 (53.8%) in the non-EN group. The odds ratio for long-term remission or response using fixed effects model and random effects model were 2.23 (95% CI 1.60-3.10) and 2.19 (95% CI 1.49-3.22), respectively. The usefulness of EN was unclear in two prospective studies that were conducted immediately after remission induction with anti-TNF-alpha antibody therapy was detected. Differences in the definition of relapse and the observation period among articles were considered to be limitations. This analysis suggests that EN is effective for maintaining remission in patients already in remission or response as a result of anti-TNF-alpha antibody maintenance therapy.

Systematic review with meta-analysis: efficacy of balloon-assisted enteroscopy for dilation of small bowel Crohn's disease strictures.

BACKGROUND: Evidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon-assisted enteroscopy is scarce. AIM: To evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon-assisted enteroscopy. METHODS: Citations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta-analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome-relevant risk factors. RESULTS: In the pooled per-study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short-term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow-up, 48.3% of patients reported symptom recurrence, 38.8% were re-dilated and 27.4% proceeded to surgery. On the per-patient-based multivariable analysis, that patients with disease activity in the small intestine had lower short-term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14-0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09-3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34-2.34, P < 0.001). CONCLUSIONS: Balloon-assisted enteroscopy for dilatation of CD-associated small intestinal strictures has high short-term technical and clinical efficacy and low complication rates. However, up to two-thirds of patients need re-dilation or surgery.

Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral center in Japan.

BACKGROUND: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. RESULTS: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Trough level of infliximab is useful for assessing mucosal healing in Crohn's disease: a prospective cohort study.

BACKGROUND/AIMS: Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn's disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2). METHODS: Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopically. RESULTS: In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 µg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 µg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating between the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 µg/mL vs. 0.5 µg/mL, P=0.032). CONCLUSIONS: TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH.

Risk factors for severity of colonic diverticular hemorrhage.

BACKGROUND/AIMS: Colonic diverticular hemorrhage (DH) was a rare disease until the 1990s, and its incidence has increased rapidly since 2000 in Japan. In recent years, colonic DH has been the most frequent cause of lower gastrointestinal bleeding (LGIB). Nearly all cases of DH are mild, with the bleeding often stopping spontaneously. Some cases, however, require surgery or arterial embolization. In this study, using a cohort at Fukuoka University Chikushi Hospital, we investigated factors associated with severe colonic DH. METHODS: Among patients with LGIB who underwent colonoscopy at our hospital between 1995 and 2013, DH was identified in 273 patients. Among them, 62 patients (22.7%) were defined as having severe colonic DH according to recurrence of bleeding in a short period, and/or the necessity of transfusion, arterial embolization, or surgery. We then evaluated risk factors for severe DH among DH patients in this retrospective cohort. RESULTS: Among the 273 patients with DH, use of non-steroidal anti-inflammatory drugs (NSAIDs) (odds ratio [OR], 2.801; 95% confidence interval [CI], 1.164-6.742), Charlson Risk Index (CRI) ≥2 (OR, 3.336; 95% CI, 1.154-7.353), right-sided colonic DH (OR, 3.873; 95% CI, 1.554-9.653), and symptoms of cerebral hypoperfusion (such as light-headedness, dizziness, or syncope) (OR, 2.926; 95% CI, 1.310-6.535) showed an increased risk of severe DH even after controlling for other factors. CONCLUSIONS: Severe DH occurred in 23% of DH patients, and NSAID use, CRI ≥2, right-sided colonic DH, and symptoms of cerebral hypoperfusion are suggested to be predictors of severe DH.

Endovascular Therapy for the Steal Phenomenon due to the Innominate Artery Severe Stenosis and Bilateral Internal Carotid Artery Severe Stenosis.

BACKGROUND: Symptomatic innominate artery stenosis presenting as hemodynamic bilateral cerebral ischemia is uncommon. We present a rare case of the severe stenosis of the origin of an innominate artery and severe stenosis of bilateral internal carotid artery that induced hemodynamic cerebral ischemia after ipsilateral axillary artery-bilateral femoral artery bypass and was treated with stent replacement of the innominate artery and right internal carotid artery. CASE REPORT: A 64-year-old woman who previously had undergone right axillary artery-bilateral femoral artery anastomosis for abdominal aorta high obstruction had been suffering from chronic dizziness and so visited our department. Findings of the examination included the severe stenosis of the origin of an innominate artery and severe stenosis of bilateral internal carotid artery, causing hemodynamic cerebral ischemia. She underwent stent replacement of the innominate artery and right carotid artery stenting via a right transbrachial approach. Her symptoms were relieved postoperatively. DISCUSSION: For the sake of improving the hemodynamic cerebral ischemia, we performed stent replacement for innominate artery stenosis and right carotid artery stenting. Endovascular treatment of subclavian and innominate artery disease is a safe procedure. In addition, for the protection of thromboembolic migration, we performed balloon protection of the external carotid artery and filter protection of the internal carotid artery. CONCLUSIONS: Stent replacement for these lesions can be performed safely with the right approach and protection methods, even when the only accessible route is the right brachial artery.

Endoscopic submucosal dissection of squamous cell carcinoma in the upper stomach 5 years after chemoradiotherapy for adenocarcinoma.

Primary squamous cell carcinoma is rarely observed, with a reported incidence of 0.04-0.07 % of all gastric cancers. An 81-year-old male underwent chemoradiotherapy for type 1 gastric cancer of the posterior wall of the cardiac region in 2005. The tumor disappeared after 1 year of therapy, following which an area of white epithelium, approximately 30 mm in diameter and continuous with the esophageal mucosa, became visible. Biopsy of the white epithelium indicated normal squamous epithelium. An elevated lesion was subsequently detected in the area of white epithelium on upper gastrointestinal endoscopy during a follow-up examination 5 years after therapy. As a biopsy of the same site indicated squamous cell carcinoma, we performed endoscopic submucosal dissection. Histopathological examination indicated high-grade fibrosis due to radiotherapy and showed a moderately differentiated squamous cell carcinoma invading the scarred portion. We describe a case where the developmental process of a squamous cell carcinoma was observed using endoscopy, including narrow band imaging with magnification. This carcinoma likely originated from squamous metaplasia that developed after chemoradiotherapy was administered for a gastric cancer.