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.

Learning Effect of Diagnosing Depth of Invasion Using Non-Extension Sign in Early Gastric Cancer.

BACKGROUND: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. METHODS: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). RESULTS: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). CONCLUSION: Nonexperts' diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

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.

Can we accurately diagnose minute gastric cancers (≤5 mm)? Chromoendoscopy (CE) vs magnifying endoscopy with narrow band imaging (M-NBI).

BACKGROUND: Chromoendoscopy (CE) is relatively ineffective at identifying the cancer-specific morphological characteristics of minute gastric cancers less than or equal to 5 mm in diameter, and on its own is insufficient to make an accurate diagnosis. The aim of this study is to assess the diagnostic performance of magnifying endoscopy with narrow band imaging (M-NBI) for minute gastric cancers. METHODS: The minute cancer group comprised consecutive endoscopic submucosal dissection-resected minute gastric cancers histologically measured as no larger than 5 mm in diameter. The non-cancer group comprised consecutive non-cancer lesions no larger than 5 mm in diameter. The two groups were subject to retrospective analysis to evaluate the diagnostic ability (sensitivity, specificity, and diagnostic accuracy) and reproducibility of CE and M-NBI. RESULTS: The results for CE versus M-NBI were as follows: sensitivity 43.7 % (95 % CI, 26.5-61.0 %) versus 78.0 % (95 % CI, 64.0-92.0 %); specificity 81.6 % (95 % CI, 72.6-90.6 %) versus 92.9 % (95 % CI, 87.0-98.9 %); and diagnostic accuracy 69.9 % (95 % CI, 61.0-78.6 %) versus 88.3 % (95 % CI, 82.0-94.5 %). The sensitivity and diagnostic accuracy were, therefore, significantly higher for M-NBI than for CE. The inter-observer variability was κ = 0.08 for CE and κ = 0.56 for M-NBI, while the intra-observer variability was κ = 0.38 and κ = 0.65, respectively. CONCLUSIONS: M-NBI has greater sensitivity and reproducibility than CE for the diagnosis of minute gastric cancers.

Long-term course of Crohn's disease in Japan: Incidence of complications, cumulative rate of initial surgery, and risk factors at diagnosis for initial surgery.

BACKGROUND AND AIMS: Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated. METHODS: This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery. RESULTS: (i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery. CONCLUSIONS: Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher.

Mucosal healing of ileal lesions is associated with long-term clinical remission after infliximab maintenance treatment in patients with Crohn's disease.

BACKGROUND AND AIM: The aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients. METHODS: This study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow-up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long-term follow up, correlations between mucosal healing and long-term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated. RESULTS: Ileal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long-term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044). CONCLUSIONS: Complete mucosal healing after 1-2 years was a predictive factor for long-term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long-term prognosis of Crohn's disease patients.

Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term remission in patients with ulcerative colitis treated with tacrolimus.

BACKGROUND AND AIM: The pharmacokinetics of tacrolimus (Tac) differ among individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and ABCB1 are thought to be involved. The aim of this study was to clarify whether these genetic polymorphisms affect the pharmacokinetics of Tac in patients with ulcerative colitis. METHODS: The subjects in this study were 45 patients with moderate-to-severe ulcerative colitis who were resistant to other therapies and were treated with Tac. The subjects were tested for genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1, and the relationship between Tac pharmacokinetics and the remission rate was investigated. RESULTS: Of the 45 subjects, 24 (53.3%) were CYP3A5 expressers (Exp), and 21 (46.7%) were non-expressers (Non-Exp). The trough level and the dose-adjusted trough level on days 2-5 were significantly higher in the Non-Exp group than in the Exp group (10.16 ± 5.84 vs 4.47 ± 2.50 ng/mL, P < 0.0001, 139.36 ± 77.43 vs 61.37 ± 41.55 ng/mL per mg/kg/day, P < 0.0001). The percentage of patients achieving the optimal trough level on days 2-5 was significantly higher in the Non-Exp group than in the Exp group (40.0% vs 4.3%, P = 0.01). This trend was also observed on days 7-10. On multivariate analysis, factors associated with achievement of the optimal trough level were food non-intake and Non-Exp of CYP3A5. The remission rate was significantly higher in the Non-Exp group than in the Exp group (47.6% vs 16.7%, P = 0.046). CONCLUSIONS: CYP3A5 genetic polymorphisms affected the pharmacokinetics of Tac, so that the short-term clinical remission rate was different between Exp and Non-Exp of CYP3A5.

Second peak in the distribution of age at onset of ulcerative colitis in relation to smoking cessation.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan. METHODS: A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital. RESULTS: Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10-20s, and small peaks were seen at age 40-44 years and then in 50-60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P < 0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93, 95% CI: 1.40-6.14, P < 0.01) on multivariate analysis. CONCLUSIONS: Similar to UC patients in Western countries, a bimodal distribution of onset age was also observed in Japanese UC patients, and smoking cessation may partly contribute to the increase in late-onset UC patients in recent years in Japan.

Long-term outcome of endoscopic balloon dilation for small bowel strictures in patients with Crohn's disease.

BACKGROUND AND AIM: Endoscopic balloon dilation (EBD) is an alternative to surgery for small bowel strictures of patients with Crohn's disease (CD). However, little is known about the long-term efficacy of EBD. The aim of the present study was to clarify the long-term outcome of EBD for small bowel strictures in patients with CD. METHODS: Subjects comprised 65 patients with CD who underwent EBD for small intestinal strictures and were followed up for at least 6 months. All subjects had obstructive symptoms as a result of small bowel strictures. Short-term success was defined as technical success and the disappearance of obstructive symptoms. The short-term success rate of EBD, its safety profile, the cumulative surgery-free rate and the cumulative redilation-free rate were investigated. RESULTS: Short-term success rate was 80.0% (52/65). Complications were encountered in six of the 65 patients (9.2%). Seventeen patients (26.2%) underwent surgery during the observation period of this study. Cumulative surgery-free rate after initial EBD was 79% at 2 years and 73% at 3 years, respectively. EBD successful cases showed significantly higher surgery-free rates than unsuccessful cases (P < 0.0001). In 52 of the successful cases, the cumulative redilation-free rate after initial EBD was 64% at 2 years and 47% at 3 years, respectively. CONCLUSION: EBD for small bowel strictures secondary to CD provides not only short-term success but also long-term efficacy. However, the high redilation rate is one of the clinical problems of this procedure.

Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study.

Background/Aims: Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC. Methods: This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed. Results: Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%-71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%-76.4%). One adverse event not related to budesonide rectal foam occurred. Conclusions: The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

Incidence, clinical characteristics, long-term course, and comparison of progressive and nonprogressive cases of aphthous-type Crohn's disease: a single-center cohort study.

BACKGROUND/AIMS: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. METHODS: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. RESULTS: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). CONCLUSION: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan.

A new endoscopic scoring system corresponding to histological healing using linked color imaging in ulcerative colitis: the SOUL study.

Background and study aims An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0-2), area of inflammation (A) (Grade 0-3), and lymphoid follicles (L) (Grade 0-3). Histological healing was defined as Geboes score < 2B.1. Endoscopic and histopathological scores were determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R ( P  = 0.013) and A ( P  = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD).

BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD]. RESULTS: Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities. CLINICAL TRIALS REGISTRY: University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

Value of concomitant endoscopic balloon dilation for intestinal stricture during long-term infliximab therapy in patients with Crohn's disease.

AIM: We assessed the long-term outcome of infliximab (IFX) therapy in patients with Crohn's disease (CD) and investigated the efficacy of concomitant endoscopic balloon dilation (EBD) for intestinal stricture during treatment. METHODS: The effectiveness of maintenance therapy with IFX was retrospectively evaluated in 185 patients with CD in a single center (median observation period 24 months). IFX effectiveness with and without immunomodulators (IMM) and enteral nutrition (EN), as well as cumulative surgery-free rates, were compared. The efficacy of concomitant EBD in patients with obstructive symptoms and high-level stricture was evaluated. RESULTS: In 185 patients receiving the maintenance therapy, the long-term efficacy rate was 84.9% at 24 months and 79.0% at 48 months. The cumulative surgery-free rate was significantly higher in the maintenance group (P < 0.001). Concomitant IMM and EN did not significantly affect the effectiveness of IFX. IFX was discontinued in only 18 cases (7.3%). Symptomatic high-level stricture occurred in 33 patients (17.8%) in the maintenance group and the cumulative surgery-free rate was significantly higher in the EBD combination compared with the non-EBD group (P < 0.05). If EBD were considered invasive intervention, the actual cumulative surgery rate in the maintenance group was significantly lower compared with the cumulative invasive intervention rate (P < 0.001). CONCLUSION: Long-term treatment with IFX is highly effective. The surgery-free rate was clearly higher in the maintenance group. Only concomitant EBD for intestinal stricture helped in the avoidance of surgery.

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.

Characteristics of adult patients newly diagnosed with Crohn's disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn's disease in Japan (iCREST-CD).

BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.

Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter, retrospective analysis in Japan.

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.

Carbon dioxide insufflation compared with air insufflation in double-balloon enteroscopy: a prospective, randomized, double-blind trial.

BACKGROUND: Few studies have evaluated the degree of pain, the amount of retained gas, and the safety of carbon dioxide (CO(2)) insufflation in patients undergoing double-balloon enteroscopy (DBE). OBJECTIVE: To clarify the usefulness and safety of CO(2) insufflation during DBE. DESIGN: Single-center, prospective, randomized, double-blind, controlled trial. SETTING: University hospital. PATIENTS: Forty eligible patients with small-bowel disease for whom DBE was indicated were randomized to a CO(2) insufflation (CO(2)) group or an air insufflation (air) group by means of sealed envelopes. INTERVENTION: DBE with insufflation of CO(2) or air. MAIN OUTCOME MEASUREMENTS: Efficacy evaluation was based on the degree of pain as assessed by use of a visual analog scale (VAS) and the amount of residual gas retention within the small and large bowels on radiography. The safety of CO(2) insufflation was evaluated by arterial blood gas analysis. RESULTS: Significantly fewer patients in the CO(2) group had severe pain of ≥ 50 mm on the VAS during DBE than in the air group (P = .02). Significantly less gas was retained in the small bowel just after and at 3 hours after DBE in the CO(2) group than in the air group (P = .003, P = .01, respectively). There was significantly less residual gas retention in the large bowel at 3 hours after DBE in the CO(2) group than in the air group (P = .02). There was no significant difference in pre-DBE and post-DBE partial pressure of oxygen in the blood (PaO(2)) and partial pressure of carbon dioxide in the blood (PaCO(2)) between groups. LIMITATIONS: Small sample size. CONCLUSION: CO(2) insufflation is a safe and useful procedure when performed during DBE.