Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Iron overload in patients with Crohn's disease with short bowel syndrome who received long-term parenteral nutrition with trace elements.

Crohn's disease patients often need regular home parenteral nutrition (HPN) for intestinal failure due to multiple intestinal resections. Trace elements are necessary for long-term HPN but the requirement volume of iron is undetermined. We describe three patients with Crohn's disease with short bowel syndrome (SBS) who had iron overload as a result of long-term HPN including iron. Serum ferritin level was significantly decreased through depleting intravenous iron administration in all cases. One patient needed regular insulin injection and phlebotomy for diabetes mellitus due to hemochromatosis, and intravenous iron administration had a significant impact on the patient's health. Long-term routine intravenous iron administration should be cautious in SBS patients to avoid the overload.

Disproportionate cancer worries in ultra-short-segment Barrett's esophagus in Japan.

Objectives: Although Barrett's esophagus (BE), especially ultra-short-segment BE (USSBE), is very frequently diagnosed in Japan, how subjects feel about receiving a diagnosis of BE is unclear. We therefore prospectively investigated cancer worry in subjects who received a BE diagnosis. Methods: Self-administered questionnaires were sent to subjects who were diagnosed with BE at three health checkup institutes in Akita Prefecture, Japan. The cancer worry scale (CWS) was used to quantitatively assess the fear of developing cancer. The BE subjects were classified into USSBE <1 cm and non-USSBE ≥1 cm groups. Factors associated with the CWS were investigated using logistic regression analyses. Results: A total of 325 (31%) subjects, comprising 229 USSBE and 96 non-USSBE patients were included in this study. Compared with the USSBE group, the non-USSBE group had a significantly higher frequency of a history of a BE diagnosis and perception of carcinogenesis. However, the CWS was similar between the USSBE and non-USSBE groups, with a median CWS of 12.5 (3.75) versus 12.7 (3.65). A multivariate logistic regression analysis revealed that while positive reflux symptoms were significantly associated with a positive CWS, the BE length was not significantly associated with it, with an odds ratio (95% confidence interval) of 1.3 (0.75-2.2). Conclusions: A BE diagnosis promotes a similar level of worry about cancer among subjects, irrespective of the length of BE. In Japan, since USSBE poses a much lower cancer risk than non-USSBE, the former may frequently be associated with a disproportionate cancer worry relative to the latter. (UMIN000044010).

[A case of severe inflammatory bowel disease triggered by vaccination with SARS-CoV-2 mRNA].

A 64-year-old woman received a third dose of SARS-CoV-2 mRNA vaccine. On the next day, she developed fever, diarrhea, and abdominal pain and had bloody stools. Total colonoscopy revealed deep ulceration on the whole colon. She was treated with corticosteroid and infliximab and her symptoms improved. She was diagnosed with severe enteritis resembling ulcerative colitis triggered by SARS-CoV-2 mRNA vaccination.

DR3 Regulates Intestinal Epithelial Homeostasis and Regeneration After Intestinal Barrier Injury.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) superfamily member tumor necrosis factor-like protein 1A (TL1A) has been associated with the susceptibility and severity of inflammatory bowel diseases. However, the function of the tumor necrosis factor-like protein 1A and its receptor death receptor 3 (DR3) in the development of intestinal inflammation is incompletely understood. We investigated the role of DR3 expressed by intestinal epithelial cells (IECs) during intestinal homeostasis, tissue injury, and regeneration. METHODS: Clinical phenotype and histologic inflammation were assessed in C57BL/6 (wild-type), Tl1a-/- and Dr3-/- mice in dextran sulfate sodium (DSS)-induced colitis. We generated mice with an IEC-specific deletion of DR3 (Dr3ΔIEC) and assessed intestinal inflammation and epithelial barrier repair. In vivo intestinal permeability was assessed by fluorescein isothiocyanate dextran uptake. Proliferation of IECs was analyzed by bromodeoxyuridine incorporation. Expression of DR3 messenger RNA was assessed by fluorescent in situ hybridization. Small intestinal organoids were used to determine ex vivo regenerative potential. RESULTS: Dr3-/- mice developed more severe colonic inflammation than wild-type mice in DSS-induced colitis with significantly impaired IEC regeneration. Homeostatic proliferation of IECs was increased in Dr3-/- mice, but blunted during regeneration. Cellular localization and expression of the tight junction proteins Claudin-1 and zonula occludens-1 were altered, leading to increased homeostatic intestinal permeability. Dr3ΔIEC mice recapitulated the phenotype observed in Dr3-/- mice with increased intestinal permeability and IEC proliferation under homeostatic conditions and impaired tissue repair and increased bacterial translocation during DSS-induced colitis. Impaired regenerative potential and altered zonula occludens-1 localization also were observed in Dr3ΔIEC enteroids. CONCLUSIONS: Our findings establish a novel function of DR3 in IEC homeostasis and postinjury regeneration independent of its established role in innate lymphoid cells and T-helper cells.

A Follow-up Report on the Diagnosis of Gastrointestinal Cancer during the COVID-19 Pandemic in Akita Prefecture, Japan in 2021.

We recently reported the decrease in the number of gastrointestinal (GI) cancer diagnoses in 2020 due to disturbance of the healthcare system by the coronavirus disease 2019 (COVID-19) pandemic, using a hospital-based cancer registration system in Akita prefecture, Japan. In this study, we extended the research by showing the latest data (2021) on the number of cancers and examinations. Information on the occurrence and stage of esophageal, gastric, and colorectal cancers was collected from the same database. The number of GI examinations (cancer screening procedures and endoscopic examinations) was also investigated. Following the immediate decrease in the numbers of both GI examinations and GI cancer diagnoses in 2020, a rebound increase in the numbers of GI cancer diagnoses-especially colorectal cancers-was observed in 2021, resulting from an increased number of GI examinations i.e., the total number of colorectal cancers in 2021 increased by 9.0% and 6.8% in comparison to 2020 and pre-pandemic era, respectively. However, the rebound increase in 2021 was largely due to an increase in early-stage cancers, and there was no apparent trend toward the increased predominance of more advanced cancers. It therefore seems that we managed to escape from the worst-case scenario of disturbance of the healthcare system due to pandemic (i.e., an increase in the number of more advanced cancers due to delayed diagnoses). We need to continue to watch the trends in Akita prefecture, which has the highest rate of mortality from the 3 major GI cancers in Japan.

Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Diverse contributions of the visceral fat area to the etiology of two distinct subtypes of esophago-gastric junctional adenocarcinoma.

BACKGROUND: There are two distinct etiologies of esophago-gastric junctional adenocarcinomas (EGJACs): one associated with extensive gastric mucosal atrophy (GA), resembling non-cardiac gastric cancers; and the other related to gastro-esophageal reflux disease, resembling esophageal adenocarcinoma. In this study, we investigated the associations between the visceral fat area (VFA) and EGJACs separately in the two subtypes of EGJACs, depending on the extent of background GA. METHODS: Sixty-four consecutive patients with EGJACs (Siewert type 2) were enrolled from a population-based database in Akita Prefecture, Japan, between 2014 and 2019. Two age- and sex-matched healthy controls were randomly assigned to each EGJAC case. The extents of GA were evaluated endoscopically, and the VFA values were measured based on computed tomography images. Logistic regression analyses were performed to investigate the associations between EGJACs and the VFA. RESULTS: Study subjects were classified into 2 subgroups depending on the extent of endoscopic GA: 29 (45.3%) without and 35 (54.7%) with extensive GA. Multivariable regression analyses revealed that a VFA of ≥100 cm2 was significantly associated with EGJACs in subjects without extensive GA [odds ratio (95% confidence interval): 2.65 (1.08-6.54)], while there was no such association in subjects with extensive GA [odds ratio (95% confidence interval): 1.52 (0.60-3.83)]. CONCLUSIONS: The contribution of the VFA to the etiology of EGJACs seems to differ depending on the extent of background GA, with the VFA more prominently associated with EGJACs in subjects without extensive GA than in those with it, providing further rationale concerning the heterogeneous nature of EGJAC etiology.

The risk of antibiotics and enterocolitis for the development of inflammatory bowel disease: a Japanese administrative database analysis.

Previous studies have shown that antibiotic use and enterocolitis increase the risk of developing inflammatory bowel disease (IBD) in western countries. However, these risk factors have not yet been identified in Asian populations. This study aimed to investigate the risk of IBD development associated with antibiotic use and enterocolitis in Japan. A Japanese health insurance claims database was used to identify patients recently diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) along with five matched participants without IBD. Episodes of antibiotic use and enterocolitis for 1 and 2 years before the date of diagnosis were analyzed using a conditional regression test. A total of 371 patients with CD and 2420 with UC were included. The adjusted odds ratio (AOR) increased in association with antibiotic use to 1.61 (95% confidence interval [CI] 1.26-2.05) and 1.20 (95% CI 1.09-1.31) and enterocolitis to 3.40 (95% CI 2.60-4.44) and 2.14 (95% CI 1.88-2.43) in 1 year in CD and UC, respectively. The risk associated with antibiotics was independent of the number or type of antibiotics, and the risk associated with enterocolitis did not differ with the pathogen that caused the disease. However, prior exposure to antibiotic use and enterocolitis was associated with an increased risk of developing IBD.

Leucine-Rich Alpha-2 Glycoprotein in Monitoring Disease Activity and Intestinal Stenosis in Inflammatory Bowel Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 µg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Disturbance of Gastrointestinal Cancers Diagnoses by the COVID-19 Pandemic in a Depopulated Area of Japan: A Population-Based Study in Akita Prefecture.

Disruption of cancer screening programs and diagnoses of gastrointestinal cancers by the COVID-19 pandemic has been reported; however, little attention has been paid to the situation in depopulated areas with low infection rates. Akita Prefecture is one of the most depopulated areas of Japan and has the lowest COVID-19 infection rate per capita; at the same time, the prefecture has been top-ranked for mortality due to gastrointestinal cancer for years. In this population-based study in Akita Prefecture, we investigated the occurrence of gastrointestinal cancers and the number of cancer screening procedures over the five-year period of 2016-2020, employing a database from the collaborative Akita Prefecture hospital-based registration system of cancers. The occurrence of gastrointestinal cancers, especially esophago-gastric cancers, declined by 11.0% in 2020, when the COVID-19 pandemic affected the overall healthcare system, compared with the average of 2016-2019. Nonetheless, the occurrence of advanced-stage (stage IV) esophago-gastric cancers increased by 7.2% in 2020. The decrease in the gastrointestinal cancer diagnosis rate in 2020 coincided with a 30% decline in the total number of regular population-based screening programs. Under the ongoing COVID-19 pandemic, cancer screening was uniformly suspended throughout Japan. Accordingly, the COVID-19 pandemic has substantially disrupted the cancer screening system, leading to delays in diagnoses of gastrointestinal cancer, even in depopulated areas (Akita Prefecture) of Japan with a low prevalence of infection. Suspension of cancer screening procedures during an infectious disease pandemic should be thoroughly considered for each region based on the cancer incidence and infection status in that area.

Visceral obesity is associated with an increased risk of developing esophago-gastric junctional adenocarcinoma in Japan: a population-based case-control study in Akita Prefecture.

BACKGROUND: While an association between esophago-gastric junctional adenocarcinomas (EGJACs) and obesity, especially visceral obesity, has been suggested in Western countries, the association remains unclear in Asia, including Japan. In this population-based case-control study, we investigated the association between EGJACs and obesity. METHODS: To perform near-population-based data collection for all early-stage EGJACs occurring in Akita Prefecture from 2014 to 2019, clinical data, including endoscopic and computed tomography (CT) findings, were collected from 11 cancer treatment base hospitals in the area. Age- and gender-matched controls were extracted at a case-to-control ratio of 1:2 from healthy subjects who received health checkups in the same area. The visceral fat area (VFA) was calculated using CT images. Logistic regression analyses were performed to investigate the associations between EGJACs and obesity-related parameters. RESULTS: In total, 74 EGJAC cases (62 males, median age of 70 years old) and 148 controls were extracted. Multivariable analyses showed a significantly negative association between the BMI and EGJACs and a significantly positive association between the VFA and EGJACs with odds ratios (ORs) (95% confidence intervals [CIs]) of 0.65 (0.53-0.80) and 1.01 (1.01-1.02), respectively. These findings were confirmed in another dataset (40 EGJACs and 80 controls). In addition, as a categorical variable, VFA ≥ 100 cm2 showed a significantly positive association with EGJACs (OR [95% CI] 1.96 [1.02-3.76]). CONCLUSIONS: We found paradoxical associations between EGJACs and obesity-related parameters (BMI vs. VFA) in a Japanese population, suggesting a potentially pivotal role of the VFA rather than the BMI as a risk factor for EGJACs.

Low risk of esophageal adenocarcinoma among patients with ultrashort-segment Barrett's esophagus in Japan.

OBJECTS: Ultrashort-segment Barrett's esophagus (USSBE; length of <1 cm) is very frequently diagnosed in Japan, but the cancer risk of USSBE is unknown. In this study, by retrieving endoscopic images, we retrospectively investigated the incidence of esophageal adenocarcinoma (EAC) by the grade of Barrett's esophagus (BE) and compared the findings with those of gastric cancer by the degree of endoscopic gastric atrophy in the same population. METHODS: Among consecutive participants who had undergone endoscopy for an annual health checkup in 2014, the 9121 who had received at least one follow-up endoscopy by December 2020 were enrolled in this study. Using the retrieved endoscopic images, we retrospectively evaluated BE and gastric atrophy. Information on the subsequent occurrence of EAC and gastric cancer as of December 2020 was also collected. The incidence of cancer by the extent of BE and gastric atrophy was calculated and expressed as the percentage per year. RESULTS: On reviewing the endoscopic image in 2014, 4190 (45.9%) were found to have been diagnosed with BE, of whom 3318 (36.4%) were judged to have USSBE. During an observation period of 54.1 (17.9) months, 89 gastric cancers and only two EACs were identified. The incidence of EAC in USSBE was 0.0068%/year, which was nearly as low as the incidence of gastric cancer in atrophy-free patients (0.0068% vs. 0.0059%/year). CONCLUSIONS: Although the prevalence of USSBE is quite high (36.4%), the incidence of EAC in USSBE is very low (0.0068%/year). Accordingly, USSBE can be excluded from targets for endoscopic surveillance in Japan.

Limited endoscopic mucosal inflammation on equivalent to Mayo endoscopic subscore of 0 unaffect clinical relapse of ulcerative colitis.

BACKGROUND AND AIM: Mayo endoscopic subscore is a simple and validated endoscopic score for ulcerative colitis but the range of inflammation was not considered for scoring. There were few reports analyzing the range of inflammation for clinical relapse using Mayo endoscopic subscore (MES). The aim of this study is to investigate the relapsing potential of limited mucosal inflammation on endoscopic remission equivalent to MES of 0. METHODS: For this retrospective observational study, ulcerative colitis patients underwent total colonoscopy were enrolled. Small mucosal lesion (SML) was defined as limited inflammation of range less than 3 cm. Clinical relapse was analyzed using the Kaplan-Meier curve with log-rank test, and factors associated with clinical relapse was analyzed using the cox proportional hazard regression model. RESULTS: A total of 102 periods with mucosal healing or modified MES of 0 with SML were analyzed. In 12-months observation periods, clinical relapse occurred more frequently in MES of 1 than in MES of 0 or modified MES of 0 with SML, but it was comparable between MES of 0 and modified MES of 0 with SML. When compared to patients with modified MES of 0 with SML, the hazard ratio in patients with MES of 1 (6.55; p = .028) was significantly high but similar in those with MES of 0 (2.59; p = .29). CONCLUSIONS: Small mucosal inflammation in UC does not affect the clinical relapse if most of the mucosa achieved a score similar to MES of 0.

Clinical Course of Ulcerative Colitis Associated with an Age at Diagnosis: A Recent Japanese Database Survey.

The onset age of ulcerative colitis has been increasing in several countries. Furthermore, the number of elderly patients with ulcerative colitis has been increasing in an aging society. We investigated the incidence of ulcerative colitis patients in Japan using a large-scale health insurance claims database to survey the ulcerative colitis incidence ratio and the clinical characteristics in late-onset ulcerative colitis patients. Newly diagnosed 2,791 ulcerative colitis between 2015 and 2018 was investigated. Medical treatment within 12 months of diagnosis was analyzed among 0-19, 20-39, 40-59 and 60-75 age groups. The mean age at diagnosis was 40.3 years (SD: 12.9), and the incidence ratio peaked in the 40's. Most of patients received 5-aminocylitic acid (91.7%), a subset of patients received prednisolone (20.1%), and a small number of patients took immunomodulator (6.8%), cytapheresis (3.3%), anti-TNFα therapy (4.3%), and colectomy (1.0%) within 12 months after diagnosis. All treatments except colectomy were most frequent in the 0-19 age group; however, colectomy was most frequent in 60-75 age group. The clinical course of ulcerative colitis that developed in adults did not differ significantly in terms of medical treatment within 12 months from the onset; meanwhile, the surgery rate was high in elderly patients. It is necessary to pay close attention to future trends regarding the aging of the onset age and the treatment, especially for late-onset ulcerative colitis patients.

Anti-IL-4Ralpha monoclonal antibody dupilumab mimics ulcerative colitis: a case report.

BACKGROUND: Various molecular-targeted therapeutic agents that inhibit cytokines and immune checkpoints are used in clinical practice. Some of these biologics that control immunity, such as anti-interleukin-17, anti-programmed cell death protein-1, and anti-cytotoxic T-lymphocyte-associated protein antibodies, affect intestinal immune homeostasis and cause intestinal inflammation. Development of enteritis due to dupilumab (an anti-IL-4Ralpha monoclonal antibody) therapy is not yet reported in the literature. CASE PRESENTATION: A 17-year-old man was administered an injection of dupilumab and continued to receive it for refractory atopic dermatitis. After 3 months of initiating dupilumab therapy, he developed intermittent abdominal pain, tenesmus, and had diarrhea. Colonoscopy examination showed decreased vascularity, mild friability, and erythema in the cecum, part of the ascending colon, sigmoid colon, and rectum without any pathogenic bacteria. Histological examination revealed moderate mixed inflammatory cell infiltration, cryptitis, destruction of the crypt, decreased goblet cells, mucosal erosions, and edema. He was diagnosed with UC and was prescribed oral mesalazine (4800 mg/day) treatment. Within a month of the treatment, his diarrhea improved and the frequency of defecation decreased. CONCLUSIONS: This is a first report that dupilumab mimicked ulcerative colitis. Careful monitoring for adverse effects with the onset of an intestinal inflammation will be recommended after dupilumab administration.

Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis.

BACKGROUND: It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM: To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS: We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS: The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION: Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study.

OBJECTS: Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. METHODS: A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. RESULTS: Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC. CONCLUSION: This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).