Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

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.

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

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

[Preoperative diagnosis of small intestinal cancer associated with Crohn's disease: a case report].

The patient was a 46-year-old woman with a history of Crohn's disease for several years. At 45 years of age, a colonoscopy was performed, and a protruding lesion in the terminal ileum was detected. Pathological analysis of a biopsy specimen noted high suspicion for a well differentiated adenocarcinoma. The patient underwent ileocecal resection, and histological examination of the specimen revealed that infiltration of the well differentiated adenocarcinoma was limited to the mucosa. To the best of our knowledge, this is the first known case of early small intestinal cancer associated with Crohn's disease in Japan. Both endoscopy and a biopsy of any protruding lesions may be useful for making a preoperative diagnosis of small intestinal cancer associated with Crohn's disease.

Comparison of the histopathological characteristics of large colorectal laterally spreading tumors according to growth pattern.

OBJECTIVES: Colorectal laterally spreading tumors (LSTs) are widely recognized owing to their structural characteristics. This study aims to clarify the histopathological characteristics of large colorectal LSTs according to growth pattern. METHODS: We studied 297 colorectal LSTs measuring ≥20 mm in diameter. The LSTs were classified into four types: granular homogenous type (LST-G-H), granular nodular mixed type (LST-G-M), non-granular flat elevated type (LST-NG-F), and non-granular pseudo-depressed type (LST-NG-PD). Retrospectively collected data were examined to compare the histopathological characteristics of LSTs according to the growth pattern. RESULTS: LST-G-M lesions (142 lesions) were most common, followed by LST-NG-F (74 lesions), LST-G-H (61 lesions), and LST-NG-PD (20 lesions). The mean tumor diameter of LST-G lesions (38.5 ± 17.2 mm) was significantly greater than that of LST-NG lesions (26.3 ± 7.0 mm, P < 0.001). In particular, 45% of LST-G-M lesions were ≥40 mm in diameter. Adenomas accounted for 54% of LST-G-H lesions compared with only 10% of LST-NG-PD lesions. Pathological T1 carcinomas accounted for 55% of LST-NG-PD lesions and were not found among LST-G-H lesions. CONCLUSIONS: The biological malignancy of colorectal LSTs differs considerably depending on the growth pattern even among large lesions and therefore should be considered when selecting treatment regimens.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

The 5C Concept and 5S Principles in Inflammatory Bowel Disease Management.

BACKGROUND AND AIMS: The international Inflammatory Bowel Disease [IBD] Expert Alliance initiative [2012-2015] served as a platform to define and support areas of best practice in IBD management to help improve outcomes for all patients with IBD. METHODS: During the programme, IBD specialists from around the world established by consensus two best practice charters: the 5S Principles and the 5C Concept. RESULTS: The 5S Principles were conceived to provide health care providers with key guidance for improving clinical practice based on best management approaches. They comprise the following categories: Stage the disease; Stratify patients; Set treatment goals; Select appropriate treatment; and Supervise therapy. Optimised management of patients with IBD based on the 5S Principles can be achieved most effectively within an optimised clinical care environment. Guidance on optimising the clinical care setting in IBD management is provided through the 5C Concept, which encompasses: Comprehensive IBD care; Collaboration; Communication; Clinical nurse specialists; and Care pathways. Together, the 5C Concept and 5S Principles provide structured recommendations on organising the clinical care setting and developing best-practice approaches in IBD management. CONCLUSIONS: Consideration and application of these two dimensions could help health care providers optimise their IBD centres and collaborate more effectively with their multidisciplinary team colleagues and patients, to provide improved IBD care in daily clinical practice. Ultimately, this could lead to improved outcomes for patients with IBD.

Accuracy of cervical auscultation in detecting the presence of material in the airway.

Several studies have investigated the accuracy of cervical auscultation (CA). However, both the sensitivities and the specificities of CA in detecting dysphagic conditions varied widely among these studies. These wide variations of the accuracy of CA might be caused by differences of the targeted sounds, such as the expiratory sound (ES) and/or swallowing sound (SS). Forty-six dysphagic patients were served as subjects. Patients who had unoccluded tracheostoma and patients who could not follow the instructions were excluded. During the videofluorographic swallowing study (VFSS), the subjects swallowed 3 ml of yogurt containing barium sulfate. The VFSS images were recorded with acoustic signals including both the swallowing and respiratory sounds detected by our method. Classification of the VFSS images was decided by consensus of the three dentists using a penetration-aspiration scale (PAS). Recorded VFSS images were classified into the following 2 groups based on PAS: "no or minimum risk group": PAS1-2; and "possible risk group": PAS3-8. As a result of the classification of VFSS findings, 30 samples were evaluated as no or minimum risk group and 16 as possible risk group. Twelve observers including 10 dentists other than 3 dentists who evaluated VFSS images and 2 speech pathologists auditorily diagnosed "negative" and "positive." Sensitivity, specificity, and intra-rater reliability was calculated for the 3 types of acoustic samples. The sensitivity of the intra-rater reliability was 60.3% for ES, 76.6% for SS, and 89.9% for ES + SS. The sensitivity of intra-rater reliability of ES + SS samples was significantly higher than that of ES (p < .01) and SS (p < .05). The sensitivity of intra-rater reliability of SS was significantly higher than that of ES (p < .01). The specificity of the intra-rater reliability was 53.7% for ES, 50.3% for SS, and 44.5% for ES + SS. ES + SS might be most useful for detecting the presence of material in the airway.

A Retrospective Claims Database Study on Drug Utilization in Japanese Patients with Crohn's Disease Treated with Adalimumab or Infliximab.

INTRODUCTION: Crohn's disease (CD) is a chronic and progressive disease in which the long-term management is important. This study sought to assess treatment persistence and dose escalation in the maintenance phase with adalimumab (ADA) or infliximab (IFX) in a Japanese real-world setting. METHODS: A retrospective analysis was conducted using the Japan Medical Data Center database. CD patients with either ADA or IFX prescriptions between January 2012 and February 2015 were included. Outcomes of interest were (1) failure in the induction phase (defined as switch or discontinuation) and (2) persistence in the maintenance phase (defined as the absence of switch or discontinuation over 12 months since maintenance initiation). RESULTS: Overall, 133 patients (53 ADA; 80 IFX) were included. Of them, treatment failed in 26 patients (19.6%) in the induction phase. During the induction phase, there was a trend towards fewer treatment failures with ADA than IFX (88.7% vs. 75.0%; p = 0.051). Of those who completed induction, 64 patients (33 ADA; 31 IFX) had at least 12 months of valid insurance enrolment after the initiation of maintenance and 13 (5 ADA; 8 IFX) had either switch or discontinuation within 12 months after the initiation of maintenance. Probabilities of switch or discontinuation over 12 months after the maintenance date were 15.2% and 20.9% for ADA and IFX groups, respectively (p-log rank = 0.7764). CONCLUSION: Japanese patients have a high primary response to anti-tumor necrosis factor therapy in the real-world setting, in line with the results of clinical trials. This initial therapeutic advantage can be lost during the maintenance phase, leading to dose escalation, treatment switch, or discontinuation. This study suggests that those events occurred in comparable proportions of patients treated with either ADA or IFX. However, these findings should be considered with caution given the retrospective nature and small size of the study. FUNDING: Abbvie GK, Tokyo, Japan.

Clinical usefulness of endoscopic ultrasonography for the evaluation of ulcerative colitis-associated tumors.

AIM: To evaluate the clinical usefulness of endoscopic ultrasonography (EUS) for the diagnosis of the invasion depth of ulcerative colitis-associated tumors. METHODS: The study group comprised 13 patients with 16 ulcerative colitis (UC)-associated tumors for which the depth of invasion was preoperatively estimated by EUS. The lesions were then resected endoscopically or by surgical colectomy and were examined histopathologically. The mean age of the subjects was 48.2 ± 17.1 years, and the mean duration of UC was 15.8 ± 8.3 years. Two lesions were treated by endoscopic resection and the other 14 lesions by surgical colectomy. The depth of invasion of UC-associated tumors was estimated by EUS using an ultrasonic probe and was evaluated on the basis of the deepest layer with narrowing or rupture of the colonic wall. RESULTS: The diagnosis of UC-associated tumors by EUS was carcinoma for 13 lesions and dysplasia for 3 lesions. The invasion depth of the carcinomas was intramucosal for 8 lesions, submucosal for 2, the muscularis propria for 2, and subserosal for 1. Eleven (69%) of the 16 lesions arose in the rectum. The macroscopic appearance was the laterally spreading tumor-non-granular type for 4 lesions, sessile type for 4, laterally spreading tumor-granular type for 3, semi-pedunculated type (Isp) for 2, type 1 for 2, and type 3 for 1. The depth of invasion was correctly estimated by EUS for 15 lesions (94%) but was misdiagnosed as intramucosal for 1 carcinoma with high-grade submucosal invasion. The 2 lesions treated by endoscopic resection were intramucosal carcinoma and dysplasia, and both were diagnosed as intramucosal lesions by EUS. CONCLUSION: EUS provides a good estimation of the invasion depth of UC-associated tumors and may thus facilitate the selection of treatment.

Diagnostic performance of EUS for evaluating the invasion depth of early colorectal cancers.

BACKGROUND: EUS is one technique used to estimate the invasion depth of early colorectal cancer (CRC), but its diagnostic accuracy remains a matter of debate. OBJECTIVE: To assess the accuracy of EUS for estimating the invasion depth of early CRC. DESIGN: Retrospective analysis. SETTING: Tertiary-care academic medical center. PATIENTS: The invasion depth of early CRC was estimated by EUS from 1989 through 2012. INTERVENTIONS EUS MAIN OUTCOME MEASUREMENTS: Accuracy of EUS diagnosis, risk factors for misdiagnosis, and characteristics of lesions that were difficult to image. RESULTS: We estimated the invasion depth of 714 cases of early CRC on EUS. Of the lesions able to be visualized on EUS, the overall diagnostic accuracy of EUS for differentiating between lesions that could be resected endoscopically (Tis and T1a cancers), and those that required colectomy (T1b cancers) was 89%. Submucosal cancer and a macroscopic classification of superficial type were independent risk factors for misdiagnosis. Ninety lesions (13%) were difficult to image. Risk factors for difficulty in imaging were protruding-type morphology and tumor location in the sigmoid colon or from the descending colon to the cecum. LIMITATIONS: Single center, retrospective. Experienced endoscopists performed EUS. CONCLUSIONS: Although some lesions that were protruding or located in the proximal colon were difficult to visualize, EUS is considered a useful technique for the diagnosis of invasion depth and the selection of treatment in patients with early CRC.

Clinical Study of the Relation between Mucosal Healing and Long-Term Outcomes in Ulcerative Colitis.

Background and Objectives. Mucosal healing (MH) is considered an important therapeutic goal in ulcerative colitis (UC). We evaluate the severity of intestinal inflammation and clarify the relation between MH and long-term outcomes. Methods. The study group comprised 38 patients with UC in clinical remission on total colonoscopy who were followed up for at least 5 years. Clinical remission was defined as a Mayo score of 0 for both stool frequency and rectal bleeding. Colonoscopic findings were evaluated into 4 grades according to the Mayo endoscopic subscore (MES). Results. During clinical remission, the MES was 0 in only 24% of the patients, 1 in 40%, 2 in 26%, and 3 in 10%. Seventy-six percent of the patients thus had active disease on colonoscopy. After initial colonoscopy, the cumulative rate of remission maintenance was 100% in MES 0, 1 in 93%, 2 in 70%, and 3 in 50% at 6 months and 78%, 40%, 10%, and 0%, respectively, at 5 years (P < 0.001). Conclusion. Many patients with UC in clinical remission have active lesions. Patients with a higher MES have a higher rate of recurrence. To improve long-term outcomes, an MES of 0 should be the treatment goal.

Clinical usefulness of single-balloon endoscopy in patients with previously incomplete colonoscopy.

AIM: To evaluate the clinical usefulness of single-balloon endoscopy (SBE) in patients in whom a colonoscope was technically difficult to insert previously. METHODS: The study group comprised 15 patients (8 men and 7 women) who underwent SBE for colonoscopy (30 sessions). The number of SBE sessions was 1 in 7 patients, 2 in 5 patients, 3 in 1 patient, 4 in 1 patient, and 6 in 1 patient. In all patients, total colonoscopy was previously unsuccessful. The reasons for difficulty in scope passage were an elongated colon in 6 patients, severe intestinal adhesions after open surgery in 4, an elongated colon and severe intestinal adhesions in 2, a left inguinal hernia in 2, and multiple diverticulosis of the sigmoid colon in 1. Three endoscopists were responsible for SBE. The technique for inserting SBE in the colon was basically similar to that in the small intestine. The effectiveness of SBE was assessed on the basis of the success rate of total colonoscopy and the presence or absence of complications. We also evaluated the diagnostic and treatment outcomes of colonoscopic examinations with SBE. RESULTS: Total colonoscopy was successfully accomplished in all sessions. The mean insertion time to the cecum was 22.9 ± 8.9 min (range 9 to 40). Abnormalities were found during 21 sessions of SBE. The most common abnormality was colorectal polyps (20 sessions), followed by radiation colitis (3 sessions) and diverticular disease of the colon (3 sessions). Colorectal polyps were resected endoscopically in 15 sessions. A total of 42 polyps were resected endoscopically, using snare polypectomy in 32 lesions, hot biopsy in 7 lesions, and endoscopic mucosal resection in 3 lesions. Fifty-six colorectal polyps were newly diagnosed on colonoscopic examination with SBE. Histopathologically, these lesions included 2 intramucosal cancers, 42 tubular adenomas, and 2 tubulovillous adenomas. The mean examination time was 48.2 ± 20.0 min (range 25 to 90). Colonoscopic examination or endoscopic treatment with SBE was not associated with any serious complications. CONCLUSION: SBE is a useful and safe procedure in patients in whom a colonoscope is technically difficult to insert.

Comparison of diagnostic accuracies of various endoscopic examination techniques for evaluating the invasion depth of colorectal tumors.

This study was designed to assess the clinical value of magnifying endoscopy combined with EUS for estimating the invasion depth of colorectal tumors. We studied 168 colorectal adenomas and carcinomas that were sequentially examined by conventional endoscopy followed by magnifying endoscopy and EUS in the same session to evaluate invasion depth. Endoscopic images obtained by each technique were reassessed by 3 endoscopists to determine whether endoscopic resection (adenoma, mucosal cancer, or submucosal cancer with slight invasion) or colectomy (submucosal cancer with massive invasion or advanced cancer) was indicated. The accuracy of differential diagnosis was compared among the examination techniques. The rate of correct differential diagnosis according to endoscopic examination technique was similar. The proportion of lesions that were difficult to diagnose was significantly higher for EUS (15.5%) than for conventional endoscopy and magnifying endoscopy. Among lesions that could be diagnosed, the rate of correct differential diagnosis was the highest for EUS (89.4%), but did not significantly differ among three endoscopic examination techniques. When it is difficult to evaluate the invasion depth of colorectal tumors on conventional endoscopy alone, the combined use of different examination techniques such as EUS may enhance diagnostic accuracy in some lesions.

Rectal granular-cell tumor difficult to distinguish from carcinoid tumor.

A 60-year-old man had a positive fecal occult-blood test on a medical check-up. Colonoscopy revealed a yellowish-white submucosal tumor 8 mm in diameter in the rectum. Endoscopic ultrasonography showed a well-demarcated mass with a homogeneous, low-level, internal echo in the second to third layers of the rectal wall. A carcinoid tumor was suspected, and the mass was resected endoscopically. Histopathological examination revealed a granular-cell tumor. Gastrointestinal granular-cell tumors rarely arise in the rectum, and the preoperative diagnosis of small lesions is often difficult. In our patient, granular-cell tumor was difficult to differentially diagnose because the endoscopic and endoscopic ultrasonographic findings closely resembled those of carcinoid tumor. Interestingly, the endoscopic characteristics of the rectal granular-cell tumor in our patient resembled those of a carcinoid tumor.

P21WAF1/CIP1 expression in colorectal carcinomas is related to Kras mutations and prognosis.

BACKGROUND/AIM: P21WAF1/CIP1 is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest. A consensus has not been reached concerning the prognostic value of p21WAF1/CIP1 expression in colorectal cancers. PATIENTS/METHODS: P21WAF1/CIP1 expression was determined immunohistochemically in a series of 211 cases of colorectal carcinomas, together with its relation to p53, bcl-2, cell turnover (as assessed by Ki67 expression and apoptotic counts) and the Kras gene status. The expression of p21WAF1/CIP1 was also compared with reference to clinicopathological parameters and patient survival. RESULTS: The median value for nuclear p21WAF1/CIP1 expression was 31% (interquartile range, 13-47%) and the fraction of cases considered to be high expressers (>20%) was 66%. Expression of p21WAF1/CIP1 was not associated with immunoreactivity for p53 or bcl-2, or cell turnover. P21WAF1/CIP1 high-expressing tumors were more often well differentiated (P<0.001), node-negative (P=0.037), Dukes' B (P=0.027) and Kras gene-mutated cases (P=0.04). On univariate analysis, low p21WAF1/CIP1 expressers (

Contribution of TIA-1+ and granzyme B+ cytotoxic T lymphocytes to cryptal apoptosis and ulceration in active inflammatory bowel disease.

In spite of the clinicopathological differences between Crohn's disease (CD) and ulcerative colitis (UC), they share the fundamental feature of destructive inflammatory processes involving the intestinal wall. The aim of the present study was to investigate the contribution of cell-mediated cytotoxicity to mucosal damage in CD and UC. Colonic mucosal biopsy specimens from patients with active CD (n=25) and UC (n=26) and normal controls (n=12) were immunohistochemically analyzed for the expression of CD3, CD4, CD8, and T cell-restricted intracellular antigen (TIA)-1, which promotes apoptosis by alternative splicing of pre-messenger RNA of the Fas receptor, and granzyme B (GrB), which leads to apoptosis through induction of perforin. Histological scores for cryptal apoptosis and ulceration were assessed in hematoxylin- and eosin-stained sections. In patients with CD and UC, CD3+(P<0.001), CD4+(P<0.001), CD8+(P<0.01), TIA-1+(CD, P<0.01; UC, P<0.001), and GrB+(CD, P<0.01; UC, P<0.001) intraepithelial lymphocytes (IELs) were significantly increased as compared with controls. Positive relationships were found between the histological scores for apoptosis or ulceration and the numbers of CD8+or TIA-1+IELs. In conclusion, cytotoxic T lymphocytes are present in increased numbers in the mucosa of patients with active CD and UC, and local activation of IELs may contribute to mucosal damage with these diseases.