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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. [ABSTRACT FROM AUTHOR]

Background: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove–Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. Methods: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. Results: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002–0.198), higher PRO2 (OR 0.306; 95% CI 0.144–0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019–1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853–0.995) was a negative factor to predict surgery within 28 days. Conclusions: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy. [ABSTRACT FROM AUTHOR]

Background: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). Methods: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. Results: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. Conclusion: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients. [ABSTRACT FROM AUTHOR]

Aims: To determine the risk factors of surgical complications and the optimal timing of surgery for patients with severe ulcerative colitis (UC). Methods: One hundred one UC patients who had undergone surgery for a severe indication were retrospectively reviewed. Indications included severe disease unresponsive to medical therapy, massive bleeding, toxic megacolon, and colon perforation. Outcomes were compared based on the occurrence or absence of surgical complications. Patients with severe disease unresponsive to medical therapy were investigated separately to determine the optimal timing of surgery. Results: There was no significant difference regarding the use of rescue therapy. The duration of all medical therapy for a severe attack was the only significant factor associated with a surgical complication (p = 0.032). In patients with severe disease unresponsive to medical therapy, the receiver operating characteristic curve analysis showed that 30.5 days was the length of medical therapy after which the risk of surgical complications significantly increased. Conclusions: In patients with severe UC, rescue therapy itself was not related to an increased risk of surgical complications. However, prolonged medical therapy increased the risk of surgical complications. Patients should undergo surgery within 30 days from the institution of medical therapy for a severe attack. [ABSTRACT FROM AUTHOR]

Background: Double-stapled ileal pouch-anal anastomosis (DS-IPAA) is easy to construct and has a good functional outcome in patients with ulcerative colitis (UC). However, retention of the anorectal mucosa may lead to a subsequent risk of inflammation and neoplasia. This study aimed to identify factors associated with the retention of a large amount of anorectal mucosa after DS-IPAA. Methods: The medical records of 163 patients who had undergone one-stage total proctocolectomy and DS-IPAA for UC between 2007 and 2020 were retrospectively reviewed. The patients were divided into two groups according to the length of the retained mucosa. The high anastomosis group was defined as having a retained mucosal length of ≥ 30 mm in the anterior or posterior wall. Clinical factors were compared between the high and low anastomosis groups. Results: The high anastomosis group showed a significantly higher body mass index (BMI) (high vs. low: 23.2 vs. 19.0), longer operation time (304 vs. 263) and greater blood loss (357 vs. 240). In the multivariate analysis, high BMI was the only factor significantly associated with high anastomosis (odds ratio 1.32). There was a positive correlation between BMI and the length of the retained mucosa. Conclusions: In DS-IPAA, BMI showed the strongest association with the retention of a large amount of the anorectal mucosa. In high BMI patients, although the risk of inability of anastomosis is little than that of IPAA with mucosectomy, the possible retention of a large amount of mucosa should be considered. [ABSTRACT FROM AUTHOR]

Objective. Ultrasonography (US) is a simple, inexpensive and minimally invasive method. We evaluated the vascularity of small intestinal lesions in Crohn's disease using color Doppler US (CD-US) and retrospectively compared them with endoscopic and surgical macroscopic findings. Material and methods. In order to compare CD-US and endoscopic findings, 108 Crohn's disease patients who underwent examination of the terminal ileum by both colonoscopy and CD-US were included in the study. Vascularity was evaluated in CD-US using a semiquantitative method, the Limberg score. We analyzed correlations between Limberg score and simple endoscopic score for Crohn's disease (SES-CD), an index reflecting endoscopic activity. Scores of SES-CD 3 and higher were defined as endoscopically active. For comparison with surgical macroscopic findings, 22 Crohn's disease patients who received CD-US and subsequent iliectomies were included. Lesions with apparent open ulcers were defined as active, and those without as non-active. These findings were compared with the Limberg score. Results. A substantial positive correlation was observed between Limberg scores and SES-CD (ρ = 0.709 [ p < 0.001]). Notably, all 27 cases with a Limberg score of 3 or 4 were classified as endoscopically active. Compared to surgical macroscopic activity, Limberg scores of active lesions were significantly higher than those of non-active lesions ( p = 0.005). In particular, all 11 cases with a Limberg score of 3 or 4 were classified as active lesions. Conclusion. Vascularity of small intestinal lesions of Crohn's disease evaluated by CD-US with Limberg score is well correlated with endoscopic and surgical macroscopic findings. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressants lead to an increased risk of infection, but few prospective studies have assessed the incidence of opportunistic infections in inflammatory bowel disease (IBD) patients, a high proportion of whom are treated with immunosuppressants. The aim of this study was to assess the age distribution of Japanese IBD patients with opportunistic infections and the risk factors associated with these infections. Methods: A multicenter, prospective study of 570 IBD patients was conducted. The patients were followed for up to 12 months to identify any new infections. The incidence of opportunistic infections and the age distribution of patients with these infections were analyzed. We carried out a case-control study in which 2 non-infected IBD patients were selected as controls for each case (infected IBD patient); the effect of medications on the infection rate was also examined. Results: Fifty-two (9.1 %) of 570 IBD patients developed opportunistic infections. Herpes simplex virus and herpes zoster virus infections were observed in 29 and 16 patients, respectively. No cases of active tuberculosis were observed. The incidence of opportunistic infections in patients aged 50 years or over was significantly higher than that in the other age groups ( p = 0.01). The use of steroids ( p = 0.02), thiopurine ( p < 0.01), and immunosuppressant combination therapy ( p < 0.01) was associated with an increased rate of opportunistic infections. However, the use of infliximab was not associated with an increased rate of opportunistic infections ( p = 0.62). Multivariate analysis indicated that the use of thiopurine was an independent risk factor for opportunistic infections ( p < 0.01). Conclusions: Age ≥50 years and the use of immunosuppressants are risk factors for opportunistic infections in patients with IBD. In our cohort, tuberculosis was not seen as a complication of immunosuppressant therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients. Methods: We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (<2500g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed. Results: A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1–25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5–15.0) were significantly higher in Crohn''s disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2–7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7–10.1) and LBW (OR 3.5, 95% CI: 1.3–9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery. Conclusion: In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection. [Copyright &y& Elsevier]

Behçet's disease (BD) is a multisystem immune-mediated inflammatory disorder that involves the gastrointestinal tract. Although intestinal BD chiefly affects the ileocecum and colon, it may involve the entire alimentary tract. Upper gastrointestinal involvements of BD are not common, and its treatment has been rarely reported. Mesalazine is known to be an effective anti-inflammatory agent for treatment of distal intestinal lesions of inflammatory bowel disease by its delayed drug release system. Here we show a case of chronic active, steroid-dependent BD involving the upper gastrointestinal tract who was treated with ground mesalazine powder. Endoscopy performed 8 weeks after the treatment showed marked improvement of the gastric ulcers. This is the first report of intestinal BD treated with oral administration of mesalazine powder, and our results suggest that it may be a beneficial and effective new therapy for the upper gastrointestinal lesion of BD. [ABSTRACT FROM AUTHOR]

Purpose: To determine the selection criteria, postoperative complications, bowel function, and prognosis of stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA for ulcerative colitis (UC). Methods: We defined our surgical indications and strategy, and compared the postoperative complications, bowel function, and prognoses between patients who underwent stapled and hand-sewn IPAA for UC at the Yokohama City University Medical Center between 2004 and 2017. Results: Among 320 patients enrolled, 298 patients underwent stapled IPAA while 22 underwent hand-sewn IPAA. There was no significant difference in the postoperative complications between the two groups. Regarding postoperative bowel function, stapled IPAA caused significantly less soiling (stapled vs hand-sewn: 9.1% vs 41.0%, odds ratio (OR) = 0.14, p < 0.0002), spotting (stapled vs hand-sewn: 23.2% vs 63.6%, OR = 0.17, p < 0.0001), and difficulty in distinguishing feces from flatus (stapled vs hand-sewn: 39.9% vs 63.6%, OR = 0.36, p < 0.026). No postoperative neoplasia was observed at the final follow-up in all patients. Conclusion: In this study, there was no clear difference in the postoperative complications between stapled and hand-sewn IPAA, but stapled IPAA resulted in better postoperative bowel function. Postoperative oncogenesis from the residual mucosa is rare. However, future cancer risk remains; thus, careful follow-up is required. [ABSTRACT FROM AUTHOR]

Background and Aim: Even with increasing numbers of biologic agents available for management of ulcerative colitis (UC), infliximab (IFX) retains an important place in treatment of pediatric patients with this disease. As few reports have addressed outcomes in pediatric UC patients who had to discontinue IFX, we examined clinical course and prognosis after IFX failure in pediatric UC. Methods: A prospective cohort study of pertinent cases enrolled in the Japanese Pediatric Inflammatory Bowel Disease Registry between 2012 and 2020 was conducted to determine outcomes for pediatric UC patients who received IFX but required its discontinuation during follow‐up (IFX failure). Results: Of the 301 pediatric UC patients in the registry, 75 were treated with IFX; in 36 of these, IFX was discontinued during follow‐up. Severity of UC at onset and absence of concomitant immunomodulator therapy were significant risk factors for IFX failure (P = 0.005 and P = 0.02, respectively). The cumulative colectomy rate after IFX failure was 41.3% at 1 year and 47.5% at 2 years. Colectomy was significantly more frequent when IFX was discontinued before June 1, 2018, than when IFX was discontinued later (P = 0.013). This difference likely involves availability of additional biologic agents for treatment of UC beginning in mid‐2018 (P = 0.005). Conclusion: In pediatric UC patients, approximately 50% underwent colectomy during a 2‐year interval following IFX failure. Prognosis after IFX failure appeared to improve with availability of new biologic agents and small‐molecule drugs in mid‐2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn's disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596).Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, "continue" (Con) or "discontinue" (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety.Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group.Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6–16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method. [ABSTRACT FROM AUTHOR]

Background: As best practices for treating children with severe-onset ulcerative colitis remain controversial in the era of biologic agents, we prospectively investigated treatments and outcomes in a multicenter cohort. Methods: Using a Web-based data registry maintained in Japan between October 2012 and March 2020, we compared management and treatment outcomes in an S1 group defined by a Pediatric Ulcerative Colitis Activity Index of 65 or more points at diagnosis with those in an S0 group defined by an index value below 65. Results: Three hundred one children with ulcerative colitis treated at 21 institutions were included, with follow-up for 3.6 ± 1.9 years. Among them, 75 (25.0%) were in S1; their age at diagnosis was 12.3 ± 2.9 years, and 93% had pancolitis. Colectomy free rates in S1 were 89% after 1 year, 79% after 2, and 74% after 5, significantly lower than for S0 (P = 0.0003). Calcineurin inhibitors and biologic agents, respectively, were given to 53% and 56% of S1 patients, significantly more than for S0 patients (P < 0.0001). Among S1 patients treated with calcineurin inhibitors when steroids failed, 23% required neither biologic agents nor colectomy, similarly to the S0 group (P = 0.46). Conclusions: Children with severe ulcerative colitis are likely to require powerful agents such as calcineurin inhibitors and biologic agents; sometimes colectomy ultimately proves necessary. Need for biologic agents in steroid-resistant patients might be reduced to an extent by interposing a therapeutic trial of CI rather than turning to biologic agents or colectomy immediately. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice. [ABSTRACT FROM AUTHOR]

Background and Aim The risk of developing colorectal cancer is higher in patients with ulcerative colitis ( UC) than in the general population. Guidelines recommend surveillance colonoscopy ( SCS) to reduce mortality; however, few studies have assessed physicians' adherence to guidelines. This study was aimed to clarify the current status of SCS and adherence to guidelines through the characteristics of cancer/dysplasia surveillance for UC patients in Japan. Methods A questionnaire was mailed to 541 physicians who attended meetings on inflammatory bowel disease. Results The respondents encountered a median of 100 UC cases. Thirty percent of the respondents had never managed a UC patient with cancer. Fifty-one percent of the respondents had never diagnosed colorectal cancer with UC. Forty-seven percent of the respondents considered extensive colitis and left-sided colitis as indications for SCS, and 38% carried out SCS regardless of the disease extent. Sixty-three percent of the respondents started SCS at 7-10 years after UC onset, whereas 20% started SCS at 3 years or less. Fifty-two percent of the respondents obtained targeted biopsies only, and chromoendoscopy was used by 49% of the respondents as a special technique for surveillance. Median number of biopsies at SCS was five per patient; it was three among patients whose biopsy was carried out by physicians who obtained targeted biopsies only and seven among those carried out by physicians who obtained step biopsies and targeted biopsies ( P < 0.0001). Conclusion A considerable proportion of the respondents did not follow the guidelines when selecting patients for surveillance and carrying out SCS. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the frequency and grade of anastomotic leakage (AL) in stapled ileal pouch-anal anastomosis (IPAA) and its long-term impact on the pouch functions. Methods: A longitudinal cohort study was conducted on UC patients who underwent stapled IPAA at Yokohama City University Medical Center between 2007 and 2018. The diagnosis and grading of AL were performed in accordance with the recommendations of the International Study Group of Rectal Cancer. We assessed the functional pouch rate, late complication, pouch survival rate, bowel function (bowel movements per day, soiling, spotting, difficulty in distinguishing feces from flatus) and pouch inflammation (pouchitis disease activity index; PDAI) in the long-term period. Results: Two hundred seventy-six patients were analyzed. Twenty-three (8.3%; grade B/C; 13/10) patients were diagnosed with AL, but a functional pouch was achieved in all the twenty-three patients. Anastomotic stricture was significantly more common in patients with AL (AL group) than in patients without AL (non-AL group; AL/non-AL: 13.0/3.2%, p = 0.020). There were no differences in other late complications. Furthermore, the pouch survival rate did not differ between the AL and non-AL groups (100.0/97.9%/10 years, p = 0.494). There were no differences between the groups in bowel movements per day, spotting, soling, difficulty in distinguishing feces from flatus, or PDAI postoperatively. Conclusions: Curable AL may not affect late complications (except anastomotic stricture), pouch survival, the bowel function, or pouch inflammation over the long term. Perioperative management to prevent the severity of AL is as important as preventing its occurrence. [ABSTRACT FROM AUTHOR]

Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD. An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia. The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (p =.16). In HGD cases, six metachronous dysplasia lesions (two LGD and four HGD) were detected 11.6–40.5 months after ER. However, these patients did not progress to CRC. All metachronous lesions were well-circumscribed and with no invisible dysplasia surrounding them; they were 'endoscopically resectable' lesions. Two of the four metachronous HGD lesions were treated endoscopically and two, by colectomy. No synchronous HGD or CRC was detected in the colectomy specimens. Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved. [ABSTRACT FROM AUTHOR]

Why inflammation is common in ileal pouches with ulcerative colitis (UC) is unclear. We therefore clarified the morphological changes in pouches and afferent limbs (AL) of patients with UC and explored the relationship between these findings. We evaluated the morphological findings (histological and endoscopic inflammation as the Pouchitis Disease Activity Index [PDAI] histology subscore [hPDAI] and endoscopy subscore [ePDAI], inflammatory bowel disease [IBD]-specific findings using the IBD score [SIBD], colonic metaplasia using the colonic metaplasia score [CMS], and goblet cell [GC] ratio) in the pouch and AL of patients with UC. A total of 261 pouchoscopies were analyzed. The pouch body had a higher hPDAI (p < 0.001), SIBD (p < 0.001), CMS (p < 0.001), GC ratio (p < 0.001), and ePDAI (p < 0.001) than the AL. The hPDAI was correlated with the SIBD (Spearman's coefficient r = 0.538; p < 0.001), CMS (r = 0.687; p < 0.001), and the ePDAI (r = 0.552; p < 0.001), but not with GC ratio (r = 0.175; p < 0.001) or the pouch usage duration (r = −0.057; p = 0.107). The incidence of histological inflammation was higher in specimens showing basal plasmacytosis with severe mononuclear cell infiltration (BP) than in those without BP (odds ratio [OR] 6.790, p < 0.001), BP was commonly found with crypt hyperplasia (OR 3.414, p < 0.001) and the crypt length correlated with neutrophil infiltration (r = 0.469; p < 0.001). Histological inflammation, colonic metaplasia, the GC ratio, endoscopic inflammation, and IBD-specific findings were commonly present in the pouch than in the AL. Histological inflammation occurs with IBD-specific findings and colonic metaplasia, and these signify endoscopic inflammation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Non-adherence to medication was reported by 28% of Japanese patients with ulcerative colitis, but in the United Kingdom, patients with inflammatory bowel disease have lower medication adherence, which increases clinical relapse risk. The objective of this study was to compare medication adherence among patients with ulcerative colitis in Japan with previously reported results and patients in the United Kingdom. Patients and Methods: This cross-cultural comparison study investigated medication adherence among 100 ulcerative colitis patients in the United Kingdom and 432 ulcerative colitis patients in Japan. Adherence was assessed using The Morisky Medication Adherence Scale-8 questionnaire. Patient clinical features were collected from medical records and the questionnaire. Distribution of responses for each item, questionnaire total score, difference in ratio for each item between Japanese and UK patients, and difference in percentage of low/medium/high adherence between Japanese and UK patients were compared. Results: The proportion of low/medium or high adherence was significantly different between countries (42.6% and 7.4% [Japan] vs 24.0% and 76.0% [United Kingdom]; p< 0.01). Significantly more Japanese patients reported taking medication correctly the day before the questionnaire compared with UK patients. Conclusion: UK patients were more likely to not take medication when they felt their symptoms were under control compared with Japanese patients. UK patients perceived it was more difficult to remember to take the medication than Japanese patients. This study highlights culturally sensitive medication-taking behaviors in Japanese and UK patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Purpose: The present study explored preoperative risk factors (predictors) of incisional surgical site infection (I-SSI) in severe or intractable ulcerative colitis (UC). Methods: This was a retrospective study of 230 consecutive patients who underwent primary surgery for UC. Patients whose surgical indications were UC with cancer or dysplasia were excluded. SSI was defined as an infection according to the Centers for Disease Control and Prevention Guidelines. Preoperative variables were examined by univariate, receiver operating characteristic curve, and multivariate analyses. Results: We analyzed 208 patients in this study. In a multivariate logistic analysis, C-reactive protein (CRP) ≥ 1.7 mg/dl [odds ratio (OR) 5.35; 95% confidence interval (CI) 1.50–19.06; p = 0.01), albumin ≤ 2.4 g/dl (OR 5.77; 95% CI 1.41–23.57; p = 0.02), and preoperative blood transfusion (OR 3.21; 95% CI 1.04–9.96; p = 0.04) were predictors of I-SSI. Patients with all predictors had a more than 50% incidence of I-SSI, a higher incidence of all severe complications (13.6% vs. 3.2%; p = 0.02), and a longer postoperative hospital stay (19.5 vs. 17.0 days, p = 0.04) than the other patients. Conclusions: CRP ≥ 1.7 mg/dl, albumin ≤ 2.4 g/dl, and transfusion are predictors of I-SSI in severe or intractable UC. Clinician should carefully evaluate the surgical options before these predictors appear. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to clarify the perioperative deep-vein thrombosis (DVT) prevalence and its risk factors in surgical ulcerative colitis (UC) patients by comparing the results with those in surgical colorectal cancer (CRC) patients at a high risk of perioperative venous thrombosis. Methods: This retrospective, observational study included patients who underwent surgery for UC or CRC between January 2013 and October 2019. Consecutive surgical patients with a positive D-dimer assay result (≥ 1.0 µg/ml) underwent lower-extremity venous ultrasonography. The prevalence and risk factors for preoperative DVT were examined in UC patients. Results: A total of 101 UC patients and 593 CRC patients were deemed eligible. Among the D-dimer positive cases, there were no significant differences between the two groups in the preoperative DVT prevalence (UC: 21.8% vs. CRC: 28.8%, p = 0.151), distal type (18.8% vs. 27.2%, p = 0.086), or proximal type (5.9% vs. 4.2%, p = 0.434). Furthermore, multivariate analyses showed that an older age, overweight status, poor ASA status, and a high preoperative dose of steroid were independent risk factors for preoperative DVT in UC surgical patients. Conclusions: The risk of perioperative thrombosis in UC patients was considered similar to that in CRC, so active thromboprophylaxis should be administered to UC patients while paying attention to bleeding. Trial registration: This study was registered with the Japanese Clinical Trials Registry as UMIN000042004 (http://www.umin.ac.jp/ctr/index.htm). [ABSTRACT FROM AUTHOR]

Abstract: Background: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009–2010. Methods: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections. Results: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20years was significantly higher than that among patients in other age groups (p<0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group. Conclusion: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed. [Copyright &y& Elsevier]

Background: Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting system without physician interference. Methods: Sixty-eight pregnant UC women were recruited from 17 institutions between 2013 and 2019. During the course of pregnancy, questionnaires were collected separately from patients and physicians, to investigate the true adherence to medications, disease activity, and birth outcomes. Multivariable logistic regression analysis was performed to identify the risk factors for the relapse or adverse pregnancy outcomes. Results: Of 68 pregnancy, 15 adverse pregnancy outcomes occurred in 13 patients. The rate of self-reported non-adherence was the greatest to mesalamines in the first trimester, which was significantly higher than physicians' estimate (p = 0.0116), and discontinuation was observed in 42.1% of non-adherent group. Logistic regression analysis revealed non-adherence as an independent risk factor for relapse [odds ratio (OR) 7.659, 95% CI 1.928–30.427, p = 0.038], and possibly for adverse pregnancy outcome (OR 8.378, 95% CI 1.350–51.994, p = 0.023). Among the subgroup of patients treated with oral mesalamine alone, the non-adherence was confirmed to be an independent risk factor for relapse (p = 0.002). Conclusion: Non-adherence to mesalamine was underestimated by physicians in pregnant UC patients and contributed to disease relapse and possibly on pregnancy outcomes. Preconceptional education regarding safety of medications and risk of self-discontinuation is warranted. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic resection is feasible for superficial tumors in patients with ulcerative colitis; however, endoscopic resection options have not been evaluated comprehensively. We evaluated the efficacy and safety of endoscopic submucosal dissection and endoscopic mucosal resection, and decision making regarding endoscopic resection options for patients with ulcerative colitis. Methods: Endoscopically treated tumors from patients with ulcerative colitis were analyzed retrospectively. We evaluated en bloc and R0 resection, adverse events, local tumor recurrence, and metachronous lesion occurrence rates. Results: We examined 102 tumors (mean size, 12 mm; non‐polypoid, 55 tumors) from 74 patients with ulcerative colitis, of whom, 39 and 63 underwent endoscopic submucosal dissection and endoscopic mucosal resection, respectively. The R0 resection rate was significantly higher for endoscopic submucosal dissection (97%) than for endoscopic mucosal resection (80%) (P = 0.0015). For 11–20‐mm tumors, the R0 resection rate was significantly higher for endoscopic submucosal dissection (94%) than for endoscopic mucosal resection (55%) (P = 0.0027); the endoscopic submucosal dissection and endoscopic mucosal resection R0 rates did not differ for ≤ 10‐mm tumors. The non‐polypoid tumor R0 resection rates were significantly higher for endoscopic submucosal dissection (100%) than for endoscopic mucosal resection (65%) (P < 0.001) and did not differ regarding the polypoid tumor R0 resection rates (75% vs 86%, P = 0.49). Four patients experienced intraoperative perforation during endoscopic submucosal dissection. No local recurrences occurred. Metachronous high‐grade dysplasia occurred in three patients during surveillance. Conclusions: In patients with ulcerative colitis, endoscopic submucosal dissection is suitable for ≥ 11‐mm and non‐polypoid tumors, whereas endoscopic mucosal resection is acceptable for ≤ 10‐mm tumors. [ABSTRACT FROM AUTHOR]

Background: In 2019 we reported the results of a Japanese national survey designed to explore the views of adult gastroenterologists regarding transitional care for patients with childhood‐onset inflammatory bowel disease (IBD). For the present study, we conducted a similar survey of pediatric gastroenterologists to compare the views of the two sets of specialists. Methods: The survey conducted in 2019 involved 48 representative members of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition. They were contacted by conventional mail and their answers were not anonymized. Respondents who had already referred patients with IBD to adult gastroenterologists were asked in a questionnaire to rank the importance of specific statements on a Likert scale. Results: The response rate was 79% and 29 (60%) of the respondents had experienced transitional care for patients with IBD. Transfer to adult care was considered by 90% of the respondents to be the ideal form of medical care for adolescents/young adults with IBD. However, 59% of the respondents had experienced some degree of difficulty when making referrals for such care. The majority of pediatric gastroenterologists considered that the ideal age for transfer was 18–22 years. Among the respondents, physicians at municipal hospitals considered that the presence of diseases other than IBD and a shortage of manpower were significantly more important issues than other practice settings. Conclusions: The present survey revealed that the general views regarding transitional care for IBD between pediatric and adult gastroenterologists were similar, except for the appropriate time for transfer. The results underline the importance of preparing a transition program appropriate to practice settings. [ABSTRACT FROM AUTHOR]

Also, an Appendix listing iCREST-CD Study Group collaborators is included in this correction. Appendix: iCREST-CD Study Group Collaborators Masakazu Nagahori: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University; Tatsu Yukawa: Inflammatory Bowel Disease Center Yokohama City University Medical Center; Daisuke Saito: Department of Gastroenterology and Hepatology, Kyorin University School of Medicine; Mikio Kawai: Department of Intestinal Inflammation Research, Hyogo College of Medicine; Atsushi Masamune: Division of Gastroenterology, Tohoku University Graduate School of Medicine; Mitsuo Nagasaka: Department of Gastroenterology, Fujita Health University School of Medicine; Tomoe Kazama: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine. [Extracted from the article]

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In 2018, Japanese guidelines for autonomy support of patients with inflammatory bowel disease (IBD) in the transitional period were published. These guidelines, however, were prepared mainly by pediatric gastroenterologists. In order to improve such supportive guidelines, it is necessary for pediatric gastroenterologists to be aware of the attitudes and expectations of adult gastroenterologists. Accordingly, the first Japanese national survey designed to explore the views of adult gastroenterologists regarding successful transitional care was conducted. Methods: The survey involved institutions at which adult gastroenterologists in the Ministry of Health, Labor and Welfare of Japan's Inflammatory Bowel Diseases Study Group, were working. Physicians were contacted by conventional mail, and their answers were not anonymized. A total of 100 eligible adult institutions were identified. Further specific subgroup analysis was conducted. Results: A response rate of 34% was achieved. Seventy‐six percent of the respondents had experienced some degree of difficulty when accepting patients with childhood‐onset IBD referred from pediatric gastroenterologists. With regard to the ideal form of medical care for adolescent patients with IBD, transfer to adult care was supported by 94% of the respondents. Only 27% of respondents, however, stated they would have no hesitation in accepting patients referred from pediatric care centers. Two crucial areas requiring improvement were identified: inadequate clinical summaries and lack of patient independence from their parents/caregivers. Conclusions: The present survey results reinforce the importance of a transitional program of education for childhood‐onset IBD patients and the need to improve communication between adult and pediatric gastroenterologists. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.Aims: To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC.Methods: This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC).Results: An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient).Conclusions: BFM had no effect on time to relapse in UC patients compared with placebo.Study Registration: UMIN000007593. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese. [ABSTRACT FROM AUTHOR]

Background and Aim: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells during cytapheresis therapy in a short duration. Methods: Endoscopy was performed in 26 patients with UC in multicentre hospitals, and biopsy specimens were collected from the rectum before and within two weeks after leukocytapheresis (LCAP). The expression of representative proteins in intestinal epithelial cells and pathological findings was compared before and after LCAP. Results: The expression of caudal type homeobox 2 (CDX2) and a hes family bHLH transcription factor 1(HES1) markedly increased after LCAP. Patients with endoscopic improvement after LCAP showed the expression of CDX2 before LCAP. Moreover, the number of goblet cells significantly increased after LCAP. Patients without endoscopic improvement after LCAP did not show the expression of CDX2 before LCAP. However, the expression of CDX2 markedly increased after LCAP. Conclusion: This study suggests that cytapheresis might induce CDX2 expression without affecting the cell proliferation, thus resulting in mucosal healing with goblet cell restoration. [ABSTRACT FROM AUTHOR]

Background and Aim Childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression. Infliximab (IFX), cyclosporin (CYA), and tacrolimus (FK506) are increasingly used to treat pediatric IBD; however, their long-term effects and adverse events have not been properly investigated in pediatric patients. The aim of this study was to characterize the effects of these biologics and immunomodulators on pediatric IBD patients in Japan. Additionally, we assessed IFX use in pediatric patients with Crohn's disease (CD). Methods A national survey of IFX, adalimumab, CYA, and FK506 use in pediatric IBD patients (< 17 years of age) was sent to 683 facilities in Japan from December 2012 to March 2013. Secondary questionnaires were sent to pediatric and adult practitioners with the aim of assessing the effectiveness and safety of IFX for pediatric CD patients. Results The response rate for the primary survey was 61.2% ( N = 418). Among 871 pediatric CD patients, 284 (31.5%), 24, 4, and 15 received IFX (31.5%), adalimumab, CYA, and FK506, respectively, from 2000 to 2012. According to the secondary survey, extensive colitis (L3, Paris classification) was diagnosed in 69.4% of pediatric CD patients who received IFX. Regarding the effectiveness of IFX in this population, 54.7% (99/181) of patients were in remission, and 42.0% (76/181) were on maintenance therapy. However, 32.0% (58/181) of patients experienced adverse events, and one patient died of septic shock. Conclusions Infliximab is reasonably safe and effective in pediatric CD patients and should therefore be administered in refractory cases. [ABSTRACT FROM AUTHOR]

Background: Overall, 30%-45% of patients with ulcerative colitis (UC) are non-adherent and have difficulties taking their medications; this non-adherence increases the risk of clinical relapse 1.4- to 5.5-fold. This study aimed to clarify the strategies patients employ to facilitate adherence and determine whether the strategies had an impact on good adherence. Methods: This was a cross-sectional survey using a self-administered questionnaire and review of medical records. Patients diagnosed as having UC and attending one of the outpatient clinics of four urban hospitals from June 2009 to December 2012 were enrolled. A questionnaire was developed to identify the strategies patients employ to facilitate adherence and then administered to patients with UC. Adherence to 5-aminosalicylic acid was calculated, and univariate and multiple logistic regression analyses were performed to determine the strategies that were associated with good adherence. Results: The final analyses included 671 participants (mean age 40.2 years; 54.3% males). The valid response rate was 96.9%; 186 (27.7%) participants were classified as non-adherent, the mean adherence rate being 86.1% (standard deviation [SD] 17.9). Seven strategies that patients employ to facilitate adherence were identified, the following two being significantly associated with good adherence: "I keep my medicines where I eat meals" and "I keep each day's medicine in a pill case or something similar to make sure I have taken them". Conclusion: The identified strategies might be used to develop a program to improve medication adherence in patients with UC. [ABSTRACT FROM AUTHOR]

Background: X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and splenomegaly and sometimes associated with refractory inflammatory bowel disease (IBD). Although hematopoietic stem cell transplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory compared with those for SLAM-associated protein deficiency and familial HLH. Aim: To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted. Methods: A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan. Results: Up to the end of September 2016, 10 patients with XIAP deficiency had undergone HSCT in Japan, 9 of whom (90%) had survived. All surviving patients had received a fludarabine-based reduced intensity conditioning (RIC) regimen. Although 5 patients developed post-HSCT HLH, 4 of them survived after etoposide administration. In addition, the IBD associated with XIAP deficiency improved remarkably after HSCT in all affected cases. Conclusion: The RIC regimen and HLH control might be important factors for successful HSCT outcomes, with improved IBD, in patients with XIAP deficiency. [ABSTRACT FROM AUTHOR]

Background: Clinical evidence regarding intestinal Behçet's disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs.Methods: An expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted.Results: Fifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized.Conclusions: In addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies. [ABSTRACT FROM AUTHOR]

Background: Clinical evidence regarding intestinal Behçet's disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs. Methods: An expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted. Results: Fifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized. Conclusions: In addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC.METHODS:This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups.RESULTS:Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1±16.9 days in the weekly GMA treatment group and 14.9±9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects.CONCLUSIONS:Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects. [ABSTRACT FROM AUTHOR]

Reported herein is a case of hepatocellular carcinoma (HCC) occurring in a 25-year-old Japanese man who was diagnosed with Crohn's disease (CD) at 14 years of age; treatment included predonisolone, azathioprine, and infliximab. The tumor was located in right upper lobe and the size was 8 cm in diameter; histology was poorly differentiated HCC with pleomorphic cellular changes. Adjacent normal liver showed no evidence of cirrhosis or viral hepatitis. Until now, only six cases of HCC arising in patients with CD have been reported in the English-language literature. Most of these patients had early onset of CD and HCC: none had cirrhosis or virus hepatitis. Most patients had a long disease history of CD and were being medicated with several immunosuppressive agents. Some factors associated with CD might indirectly or directly be related to the development of HCC in CD patients, although the possibility that these HCC occurred coincidentally in CD patients, including the present patient, cannot be ruled out. Accumulation of cases is necessary to evaluate the relationship between CD and HCC precisely. [ABSTRACT FROM AUTHOR]

We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 × 108 to 3.7 × 108 cells on 6–17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4+ T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor β-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study. [Copyright &y& Elsevier]

Focuses on a study which analyzed the risk of cancer development in mice lacking Tob, an antiproliferative family genes. Tumor development in mice lacking Tob; Involvement of Tob in the regulation of cyclin D1 transcription; Suppression of Tob in human cancers.

We previously performed a randomized controlled trial (RCT) comparing targeted and random biopsy in neoplasia detection in patients with ulcerative colitis (UC), which showed the short-term effectiveness of targeted biopsy with one-time colonoscopy. In this retrospective cohort study, we investigated the long-term effectiveness of targeted biopsy in tertiary care hospitals, using the follow-up data from patients with UC for ≥ 8 years who had enrolled in the initial RCT. The primary outcome was death from colorectal cancer (CRC). Secondary outcomes were advanced neoplasia (CRC or high-grade dysplasia) and colectomy due to neoplasia after the RCT. We compared these outcomes between target and random groups. Data on 195 of the 221 patients (88.2%) enrolled in the previous RCT were collected from 28 institutions between 2008 and 2019. No patients died of CRC in either group, with a median 8.8-year follow-up demonstrating a robustness for targeted biopsy in terms of CRC death prevention. Advanced neoplasia was detected in four and three patients in the target and random groups, respectively. Colectomy was required due to neoplasia in three patients in each group. The chance of developing CRC in patients with a negative colonoscopy was low, and the targeted biopsy appeared effective in this population. Conversely, patients found with low-grade dysplasia at initial RCT have 10-fold higher risk of progression to high-grade dysplasia and/or CRC. Ten extracolonic malignancies were observed during the follow-up, resulting in four deaths. Panchromoendoscopy was used only in 4.6% and targeted biopsy was only performed in 59.1% of colonoscopies. We recommend targeted biopsy rather than > 33 random biopsies in real-world settings under adequate observation by specialists. [ABSTRACT FROM AUTHOR]