Predictors of severe submucosal fibrosis during endoscopic submucosal dissection in patients with ulcerative colitis: Retrospective cohort study.

OBJECTIVES: Severe submucosal fibrosis is a crucial technical difficulty encountered during endoscopic submucosal dissection (ESD) in patients with ulcerative colitis (UC). We aimed to identify predictors of severe submucosal fibrosis in patients with UC. METHODS: We retrospectively included 55 tumors resected using ESD from 48 consecutive patients with UC. We analyzed the clinicopathological characteristics and treatment outcomes between the F0/1 (none to mild submucosal fibrosis) group (n = 28) and F2 (severe submucosal fibrosis) group (n = 27). RESULTS: No significant difference was found between the F0/1 and F2 groups in en bloc resection rate (100% vs. 96%, P = 0.49), the R0 resection rate (100% vs. 93%, P = 0.24), and the dissection speed (0.18 vs. 0.13 cm2 /min, P = 0.07). Intraoperative perforation was more common in the F2 group (30%) than in the F0/1 group (8%; P = 0.01). Multivariable analysis showed that a longer duration of UC (≥10 years; odds ratio [OR] 6.11; 95% confidence interval [CI] 1.20-31.03; P = 0.03) and scarring of background mucosa of the tumor (OR 39.61; 95% CI 3.91-400.78; P < 0.01) were independent predictors of severe submucosal fibrosis. CONCLUSION: Long UC duration and scarring background mucosa were predictors of severe submucosal fibrosis associated with perforation during ESD.

Serrated polyps in patients with ulcerative colitis: Unique clinicopathological and biological characteristics.

BACKGROUND: Serrated polyps have recently been reported in patients with ulcerative colitis (UC); however, their prevalence and detailed characteristics remain unclear. METHODS: The prevalence and clinicopathological and biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease center in Japan from 2000 to 2020. RESULTS: Among 2035 patients with UC who underwent total colonoscopy, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was 1.8% (36/2035). Serrated polyps in colitis-affected segments were common with extensive colitis (88%), history of persistent active colitis (58%), and long UC duration (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of the 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion-like dysplasia, traditional serrated adenoma-like dysplasia, and serrated dysplasia not otherwise specified, respectively. Sessile serrated lesion-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas traditional serrated adenoma-like dysplasia and serrated dysplasia not otherwise specified were common in the distal colon (100% and 80%, respectively) and with KRAS mutations (100% and 75%, respectively). CONCLUSIONS: Serrated polyps comprised 14% of the neoplasias in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting chronic inflammation in the development of serrated polyps in patients with UC.

Appropriate Preconception Corticosteroid-Free Remission Period in Pregnant Women With Ulcerative Colitis.

BACKGROUND: In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). METHODS: We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to <3 months, and non-CFREM). We also investigated disease activity during pregnancy and postpartum and adverse pregnancy outcomes in each group. RESULTS: During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to <3 months CFREM groups compared with that in the non-CFREM group (P < .001 and P = .0257, respectively). Postpartum, the rate of active disease was significantly lower in the ≥3 months CFREM group compared with that in the non-CFREM group (P = .0087). The preconception CFREM period of ≥3 months was an independent inhibitory factor for active disease during pregnancy and postpartum (adjusted odds ratio, 0.15; P = .0035; and adjusted odds ratio, 0.33; P = .027, respectively). Adverse pregnancy outcomes were less common in the >3 months CFREM group compared with those in the other groups, but this difference was not significant. CONCLUSIONS: A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

In women with ulcerative colitis, a preconception corticosteroid-free remission period for at least 3 months may be appropriate. This period could reduce disease activity during pregnancy and postpartum and reduce the incidence of adverse pregnancy outcomes.

Vonoprazan and high-dose amoxicillin dual therapy for Helicobacter pylori first-line eradication: A single-arm, interventional study.

Background: To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high-dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first-line treatment. Methods: This prospective, dual-center, single-arm interventional study was performed in Japan. Twenty H. pylori-positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). Results: The intention-to-treat and per-protocol eradication rates were 90% (95% confidence interval [CI] 68.3-98.8%, n = 20) and 94.4% (95% CI 72.7-99.9%, n = 18) respectively. No significant adverse event was recorded. Conclusion: Vonoprazan/high-dose amoxicillin dual therapy can be a safe standard first-line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan-based triple therapy.

Magnifying endoscopy is useful for tumor border diagnosis in ulcerative colitis patients.

BACKGROUND AND AIMS: Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC. METHODS: We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes. RESULTS: We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99). CONCLUSIONS: ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Consistency of Trans-Abdominal and Water-Immersion Ultrasound Images of Diseased Intestinal Segments in Crohn's Disease.

The aim of this study is to clarify whether trans-abdominal ultrasound (TAUS) can reflect actual intestinal conditions in Crohn's disease (CD) as effectively as water-immersion ultrasound (WIUS) does. This retrospective study enrolled 29 CD patients with 113 intestinal lesions. Five ultrasound (US) parameters (distinct presence/indistinct presence/disappearance of wall stratification in the submucosal and mucosal layers; thickened submucosal layer; irregular mucosal surface; increased fat wrapping around the bowel wall; and fistula signs) that may indicate different states in CD were determined by TAUS and WIUS for the same lesion. Using WIUS as a reference standard, the sensitivity, specificity, and accuracy of TAUS were calculated. The degree of agreement between TAUS and WIUS was evaluated by the kappa coefficient. All US parameters of TAUS had an accuracy >70% (72.6-92.7%). The highest efficacy of TAUS was obtained for fistula signs (sensitivity, specificity, and accuracy values were 63.6%, 96.0%, and 92.7%, respectively). All US parameters between TAUS and WIUS had a definitive (p ≤ 0.001) and moderate-to-substantial consistency (kappa value = 0.446-0.615). The images of TAUS showed substantial similarity to those of WIUS, suggesting that TAUS may function as a substitute to evaluate the actual intestinal conditions of CD.

Correlation between the macroscopic severity of Crohn's disease in resected intestine and bowel wall thickness evaluated by water-immersion ultrasonography.

Objectives: Transabdominal ultrasonography is a common and accurate tool for managing Crohn's disease (CD); however, the significance of the resulting data is poorly understood. This study was performed to determine the association between bowel wall thickness evaluated by water-immersion ultrasonography and macroscopic severity, namely, refractory inflammation and subsequent fibrosis in CD surgical specimens.Materials and methods: We retrospectively evaluated 100 segments of colon and small intestine from 27 patients with CD. The resected specimens were placed in saline postoperatively, and bowel wall thickness was measured by water-immersion ultrasonography and compared with macroscopic findings. Correlations between bowel wall thickness and macroscopic findings were assessed using analysis of variance and receiver operating characteristic curves.Results: According to the progression of macroscopic severity, the mean bowel wall thickness was increased as follows: macroscopically intact: 4.1 mm, longitudinal ulcer scars: 5.4 mm, longitudinal open ulcers: 6.0 mm, large ulcers: 6.4 mm, cobblestone-like lesions: 7.1 mm, and fibrotic strictures: 7.4 mm. For all lesions except longitudinal ulcer scars, the bowel wall thickness was significantly thicker than that of macroscopically-intact areas (p < .001). According to receiver operating characteristic curves, bowel wall thickness >4.5 mm was associated with CD lesions, and thickness >5.5 mm was associated with more severe lesions.Conclusions: The bowel wall thickness of CD lesions was evaluated by water-immersion ultrasonography correlated with macroscopic disease severity.

Remission induction, maintenance, and endoscopic outcome with oral 5-aminosalicylic acid in intestinal Behçet's disease.

BACKGROUND AND AIM: Oral 5-aminosalicylic acid (5-ASA) is recommended for the therapy of mild to moderate intestinal Behçet's disease (BD). However, the induction remission efficacy and endoscopic outcomes of 5-ASA are unknown. We investigated remission induction at 8 weeks, endoscopic outcomes until 52 weeks, and event-free survival at 52 weeks in patients with intestinal BD treated with 5-ASA. METHODS: Forty-one patients with intestinal BD were treated with oral 5-ASA. Clinical remission was evaluated with the Crohn's disease activity index (CDAI). The endoscopic response was evaluated using the modified global gastrointestinal endoscopic assessment scores. Rescue therapy-free survival and surgery-free survival at 52 weeks were estimated, and predictive factors for a clinical response at weeks 8 and 52 were identified. RESULTS: Seven patients (17%) withdrew 5-ASA early (≤ 8 weeks) because of adverse events. At week 8, clinical efficacy could be accurately evaluated in 28 patients, and the response and remission rates were 61% and 57%, respectively, using the CDAI. Endoscopic evaluation was achieved in 17 patients up to 52 weeks, and the endoscopic response and remission rates were 71% and 35%, respectively. The probabilities of rescue therapy-free survival and surgery-free survival were 73% and 100%, respectively, at 52 weeks in all 41 patients. The predictive factors for therapeutic effectiveness at week 8 were a higher baseline C-reactive protein level and CDAI, but they were negative predictive factors for a 52-week response. CONCLUSIONS: 5-ASA is effective for clinical and endoscopic induction and maintaining a response in patients with mild to moderate intestinal BD.

Patient self-reported symptoms using visual analog scales are useful to estimate endoscopic activity in ulcerative colitis.

BACKGROUND/AIMS: In clinical practice, colonoscopy has been regarded as the gold standard for the evaluation of disease severity as well as mucosal healing in ulcerative colitis (UC). Some activity indices incorporating patient symptoms as parameters have been shown to reflect the endoscopic activity of UC. The aim of this study was to examine whether self-reported symptoms with visual analog scales (VAS) can predict endoscopic activity. METHODS: A cross-sectional study of 150 UC patients who underwent colonoscopy with submission of VAS scores of 4 symptoms: general condition, bloody stools, stool form, and abdominal pain (0: no symptoms, 10: the most severe symptoms). Each VAS score was compared with colonoscopic activity assessed with the Mayo endoscopic subscore (MES). RESULTS: All VAS scores were significantly correlated with the endoscopic severity (Spearman correlation coefficients of general condition, bloody stools, stool form, and abdominal pain: 0.63, 0.64, 0.58, and 0.43, respectively). Mucosal healing defined as MES 0 alone was predicted by VAS score <1.5 on general condition or 0 on bloody stools with sensitivity of 0.84 and 0.76 and specificity of 0.66 and 0.76, respectively. Additionally, VAS score <2.5 on stool form predicted active lesions in distal colorectum alone with sensitivity of 0.67 and specificity of 0.66, suggesting that this item could predict the indication of topical therapy. CONCLUSIONS: Self-reported VAS scores on symptoms were correlated with endoscopic activity of UC. To clarify the relationship between VAS and mucosal healing, further validation studies are needed.

Short- and long-term efficacy of adalimumab salvage therapy after failure of calcineurin inhibitors in steroid-refractory ulcerative colitis.

OBJECTIVE: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC. MATERIALS AND METHODS: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan-Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered. RESULTS: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis. CONCLUSIONS: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.

Incidence and Outcomes of Central Venous Catheter-related Blood Stream Infection in Patients with Inflammatory Bowel Disease in Routine Clinical Practice Setting.

BACKGROUND: Patients with inflammatory bowel disease (IBD) occasionally require central venous catheter (CVC) placement to support a therapeutic plan. Given that CVC can predispose patients to infection, this investigation was undertaken to assess the incidence, risk factors, and outcomes of CVC-related blood stream infection (CRBSI) in patients with IBD during routine clinical practice. METHODS: Data were compiled using retrospective chart reviews of 1367 patients treated at our IBD center between 2007 and 2012 during routine clinical practice. Among the 1367 patients, 314 who had received CVC placements were included. Patients with positive blood culture were considered as "definite" CRBSI, whereas "possible" CRBSI was defined as patients in whom fever alleviated within 48 hours post-CVC without any other infection. Patients' demographic variables including age, body mass index, serum albumin, duration of CVC placement, use of antibiotics, medications for IBD, and perioperative status between CRBSI and non-CRBSI subgroups were compared by applying a multivariate Poisson logistic regression model. RESULTS: Among the 314 patients with CVC placement, there were 83 CRBSI cases (26.4%). The average time to the onset of CRBSI was 22.5 days (range 4-105 days). The jugular vein access was found to be the most serious risk of CRBSI (risk ratio 2.041 versus subclavian vein). All patients with CRBSI fully recovered. CONCLUSIONS: In this investigation, regardless of the patients' demographic features including immunosuppressive therapy, up to 30% of febrile IBD patients with CVC showed CRBSI. It is believed that CVC placement per se is a risk of CRBSI in patients with IBD.