Language：Japanese   Publisher：(一財)日本消化器病学会  

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Publishing type：Research paper (scientific journal)   Publisher：Massachusetts Medical Society  

DOI： 10.1056/nejmoa2207940

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

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.

DOI： 10.1038/s41598-023-37145-6

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Other Link： https://www.nature.com/articles/s41598-023-37145-6

Language：English  

DOI： 10.1007/s00535-023-01998-5

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/den.14570

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.gie.2023.05.058

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Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

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Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00535-023-01972-1

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Other Link： https://link.springer.com/article/10.1007/s00535-023-01972-1/fulltext.html

Language：English  

DOI： 10.1093/ibd/izad023

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background and Aims

Perianal lesion is a refractory phenotype of Crohn’s disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD.

Methods

Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD].

Results

Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions.

Conclusions

At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities.

Clinical trials registry

University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

DOI： 10.1093/ecco-jcc/jjad038

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00535-022-01953-w

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Intestinal Behçet's disease (BD) is a relapsing-remitting disease typically associated with punched-out ulcers in the ileocecal region. Optimal monitoring of disease activity is necessary; however, ileocolonoscopy cannot be performed on a regular basis as it is invasive, resource-intensive and causes considerable patient discomfort. Furthermore, there are risks of intestinal bleeding and perforation caused by pretreatment laxatives and air insufflation during the examination. Hence, other follow-up examinations are required. Intestinal ultrasonography (IUS) is a minimally invasive imaging method, but there are no previous reports of comparisons between IUS and endoscopy for intestinal BD. This study aimed to evaluate the usefulness of IUS in assessing the activity of ileocecal ulcers in intestinal BD.

Methods

This retrospective single-centre study included patients with intestinal BD who underwent colonoscopy and IUS within 2 weeks, from 2007 to 2020. Correlations between the corresponding endoscopic activity using the Sakita–Miwa classification and six IUS variables (bowel wall thickness [BWT], vascularity, bowel wall stratification, intramural and extramural abscesses, fistulas and mesenteric lymphadenopathy) were assessed and used to select the variables that should be included in the new simple score. IUS findings were also compared with biomarker (C-reactive protein [CRP]) concentrations and clinical severity indices (Crohn’s disease activity index and disease activity index for intestinal BD [DAIBD]).

Results

Seventy-nine IUS examinations from 53 patients were included. Univariate analysis revealed that CRP and DAIBD and the IUS findings BWT, vascularity and bowel wall stratification and intramural and extramural abscesses differed significantly according to endoscopic ulcer activity. Multivariate analysis using a logistic regression model revealed that only BWT and vascularity were statistically different; therefore, a new simple score ([2*BWT] + [5*vascularity]) was constructed. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for detecting endoscopic activity, which was superior to those of CRP (0.80; P=0.069), Crohn’s disease activity index (0.69; P=0.002) and DAIBD (0.67; P<0.001).

Conclusion

A new simple ultrasound activity index for intestinal BD comprising BWT and vascularity was constructed and correlated well with endoscopic disease activity. This is the first report describing the usefulness of IUS for intestinal BD, and we believe the findings will have many implications in clinical practice.

DOI： 10.1093/ecco-jcc/jjac190.0313

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Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1093/ibd/izac270

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

DOI： 10.1080/00365521.2022.2107878

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1371/journal.pone.0282204

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Language：English   Publishing type：Research paper (scientific journal)  

Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.

DOI： 10.2169/internalmedicine.0839-22

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00535-022-01907-2

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Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1016/j.dld.2022.03.003

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Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.2147/ppa.s346309

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Language：English   Publishing type：Research paper (scientific journal)  

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the intestine. The incidence of IBD is increasing worldwide, including Japan, and in approximately 25% of all affected patients it is diagnosed before 18 years of age. For the health maintenance of such patients, planned transition to adult care systems is essential. Previous Japanese surveys have revealed gaps between adult and pediatric gastroenterologists with regard to their knowledge and perception of health-care transition for patients with childhood-onset IBD. In 2021-2022, several Web workshops to discuss issues related to the transitional care of IBD patients were held by the Ministry of Health, Labour and Welfare of Japan as part of their program for research on intractable diseases. Clinicians experienced in IBD treatment for pediatric and adult patients participated. As a result, this panel of adult and pediatric gastroenterologists developed five consensus statements on the issue of "transfer from pediatric to adult care" and nine statements on the issue of "addressing transitional care (transition program)." To address current gaps in health-care transition for childhood-onset IBD patients, a programmed approach to transition, and better partnerships between pediatric and adult gastroenterologists are indicated. It is hoped that this consensus statement will provide a basis for the development of appropriate guidelines for clinical practice.

DOI： 10.1111/ped.15241

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/ibd/izab222

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cgh.2020.07.067

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1111/jgh.15207

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

The Morisky Medication Adherence Scale is a clinically relevant tool used to evaluate medication adherence. In the current study, the validity and reliability of a Japanese version of the Morisky Medication Adherence Scale and factors related to low adherence were investigated in patients with ulcerative colitis. The original English version was translated into Japanese and then 3 institutions in Japan administered that Japanese version to 428 patients taking medication. Factor validity, internal consistency, and correlations between the Morisky Medication Adherence Scale and adherence were calculated on the basis of patients' own reports of skipped medication, and known group validity between clinically different groups was assessed. Logistic regression was used to assess relationships between low adherence and other factors. The Morisky Medication Adherence Scale identified 184 of 428 patients (43.0%) who exhibited low adherence. Confirmed factor analysis indicated one-dimensionality of the scale. Cronbach's α was 0.74. The Morisky Medication Adherence Scale score was significantly correlated with self-reported missed medication. Patients who were on concomitant induction therapy exhibited significantly better Morisky Medication Adherence Scale scores than those who were not. Patients with low adherence reported difficulty taking medicine, having proctitis, and ulcerative colitis duration of less than 5 years, and were of younger age. The Japanese Morisky Medication Adherence Scale yielded clinically relevant measures of adherence in patients with ulcerative colitis and may promote further international comparative studies.

DOI： 10.1097/SGA.0000000000000533

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIMS: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children. METHODS: This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data. RESULTS: A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn's disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturing/non-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01). CONCLUSIONS: Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.

DOI： 10.5217/ir.2019.00130

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

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 &gt
33 random biopsies in real-world settings under adequate observation by specialists.

DOI： 10.3390/jcm9072286

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00535-020-01690-y

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/ecco-jcc/jjaa105

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Other Link： http://academic.oup.com/ecco-jcc/article-pdf/14/12/1786/34665140/jjaa105.pdf

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/ecco-jcc/jjz161

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Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.3390/diagnostics10050267

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10620-020-06221-6

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Other Link： http://link.springer.com/article/10.1007/s10620-020-06221-6/fulltext.html

Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Institute of Anticancer Research  

Background/Aim: The present study examined the utility of serum p53 antibody (Ab) for detecting colitisassociated cancer (CAC) in the era of immunosuppressive therapy. Patients and Methods: Two hundred and fifty patients were analyzed, 219 had no carcinoma or dysplasia (Group non-CAC), and 31 had carcinoma or dysplasia (Group CAC). Serum p53 Abs were detected with an enzyme-linked immunosorbent assay. Immunohistochemical detection was performed in Group CAC. Results: Immunosuppressive therapy was performed in 98.1% of Group non-CAC and 80.6% of Group CAC. There were no differences in serum p53 Abs positivity between Groups non-CAC and CAC (8.7% vs. 3.2%, p=0.30). p53 staining positivity was noted in 90.3% of Group CAC, and the rate of serum p53 positivity was significantly lower in patients with immunosuppressive therapy than in those without in Group CAC (0.0% vs. 16.7%, p=0.04). Conclusion: The utility of serum p53 Ab for detecting CAC is dubious in the era of immunosuppressive therapy.

DOI： 10.21873/invivo.11830

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Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

小児クローン病は、診断時の病変範囲が成人より広範かつ重症で、肛門病変を合併することも少なくない。また、消化器症状にとどまらず、成長や学校生活、心理的問題を呈することもあり、小児の特性に配慮した治療指針の作成が望まれる。近年の炎症性腸疾患(IBD)診療の進歩に対応すべく、日本小児栄養消化器肝臓学会と日本小児IBD研究会により小児IBD治療指針作成委員会が立ち上げられ、2005年と2013年に報告された小児クローン病治療指針案・治療ガイドラインの改訂版を作成したので報告する。この改訂版では、成人患者に対する治療との整合性に配慮しながら、小児クローン病の治療原則、臨床的評価に基づいた治療方針、さらには、個々の治療法について、小児への適応承認の実際や小児用量も示しながら解説した。さらに、小児期特有の問題である成長障害、予防接種、心理社会的側面、成人診療科への移行期医療、超早期発症型IBDなどについても言及した。(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

小児潰瘍性大腸炎は、一般に成人に比して短期間で全大腸炎型へ進展しやすい。重症化しやすいなどの特徴があり、また成長障害など小児期特有の問題を有することから、小児の特性に配慮した治療指針の作成が望まれる。近年の炎症性腸疾患(IBD)診療の進歩に対応すべく、日本小児栄養消化器肝臓学会と日本小児IBD研究会により小児IBD治療指針作成委員会が立ち上げられ、2004年と2008年に報告された「小児潰瘍性大腸炎治療指針案」の改訂版を作成したので報告する。この改訂版では、成人患者に対する治療との整合性に配慮しながら、小児潰瘍性大腸炎の治療原則、臨床的評価と活動性指標に基づいた治療方針、個々の治療法と小児への適用承認の実際や小児用量について解説した。さらに、小児期特有の問題である成長障害、予防接種、心理社会的側面、成人診療科への移行期医療、超早期発症型IBDなどについても言及した。(著者抄録)

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Language：English  

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.

DOI： 10.1080/00365521.2019.1683224

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DOI： 10.1111/jgh.14690

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DOI： 10.1097/MEG.0000000000001595

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DOI： 10.1007/s00535-019-01582-w

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIMS: Tacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis. METHODS: We retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged < 17 years treated with tacrolimus between 2000 and 2012. Patients' characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score < 10; treatment response was defined as a PUCAI score reduction of ≥ 20 points compared with baseline. RESULTS: Patients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11-15] years). Thirty-nine patients were steroid-dependent and 26 were steroidrefractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05-0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P< 0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy. CONCLUSIONS: Tacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children.

DOI： 10.5217/ir.2019.00027

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Language：English   Publishing type：Research paper (scientific journal)  

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn’s disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab.

Methods

In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group.

Results

There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher’s exact test, p &lt;0.001]. Kaplan–Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group.

Conclusions

Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

DOI： 10.1093/ecco-jcc/jjz030

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

DOI： 10.5217/ir.2018.00021

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DOI： 10.1080/00365521.2018.1511825

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Publisher：Gastroenterological Endoscopy  

© 2018 Japan Gastroenterological Endoscopy Society. All righrts reserved. 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&#039; 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 resp

DOI： 10.11280/gee.60.1033

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DOI： 10.1007/s00535-018-1439-1

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

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

DOI： 10.1097/mib.0000000000001230

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

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 &lt
0.0001). Conclusion: A considerable proportion of the respondents did not follow the guidelines when selecting patients for surveillance and carrying out SCS.

DOI： 10.1111/den.12803

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background and AimChildhood-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).
MethodsA national survey of IFX, adalimumab, CYA, and FK506 use in pediatric IBD patients (&lt;17years 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.
ResultsThe 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.
ConclusionsInfliximab is reasonably safe and effective in pediatric CD patients and should therefore be administered in refractory cases.

DOI： 10.1111/jgh.13498

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER/PLENUM PUBLISHERS  

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.<br />
To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted.<br />
A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan.<br />
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.<br />
The RIC regimen and HLH control might be

DOI： 10.1007/s10875-016-0348-4

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BACKGROUND & AIMS: A random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC. METHODS: We performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups. RESULTS: The mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679-2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation. CONCLUSIONS: In a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608.

DOI： 10.1053/j.gastro.2016.08.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Massachusetts Medical Society  

BACKGROUND
Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.
METHODS
We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of = 100 points or a CDAI score &lt;150). The primary end point for the maintenance trial was remission at week 44 (CDAI score &lt;150).
RESULTS
The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P=0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P&lt;0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups.
CONCLUSIONS
Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.)

DOI： 10.1056/nejmoa1602773

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DOI： 10.5217/ir.2016.14.2.139

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Yokohama City University  

Although ulcerative colitis (UC) is a benign disease, cancer-associated colitis (CAC) or dysplasia complicated with long-term UC can be fatal. Sixteen (4.9%) of 324 patients with UC who underwent surgical intervention were diagnosed with CAC or dysplasia complicated with UC at our department. The clinicopathological features of these patients were juvenile-onset, long-term, cancer that was frequently located in the rectum and multiple cancers. All 14 patients who regularly attended our outpatient clinic, were on maintenance therapy, and underwent serial endoscopic examinations remained alive without disease recurrence. In contrast, curative surgery was impossible for two patients who did not regularly attend our clinic, were not on maintenance therapy, and did not undergo regular endoscopic assessment due to operative findings of distant (peritoneal) metastasis. Regular attendance at outpatient clinics and endoscopic surveillance are important because early detection and treatment might improve the prognosis of patients with CAC or dysplasia complicated with UC, the frequency of which is likely to increase in the future.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Japan  

Background Although attention has been focused for over 20 years on the possible increased risk for hematologic malignancies (HM) in patients with inflammatory bowel diseases (IBD) receiving immune-modulators or anti-TNF-alpha antibodies, the association is still controversial. To understand the actual conditions of HM in the Japanese patients with IBD, the research committee for IBD supported by the Ministry of Health, Welfare and Labor of Japan (IBD-MHWL) conducted a multi-center retrospective study. Methods Questionnaires for the development of HM in IBD patients were sent to the 70 facilities participating with IBD-MHWL in the first survey, followed by the second survey using a more detailed questionnaire, sent to the 27 members with HM patients. Results Out of a total of 36,939 IBD patients in 70 facilities, 28 cases of HM related with IBD [12 of 10,500 UC patients (0.11 %), 16 of 6,310 CD patients (0.25 %)] were analyzed. The numbers of UC patients who developed HM were 2 (0.15 %) from the group receiving and 10 (0.13 %) from the group non-receiving thiopurine, without significant differences. The numbers of CD patients who developed HM were 4 (0.39 %) from the group receiving and 12 (0.21 %) from the group non-receiving thiopurine, without significant differences. The odds ratios of developing HM by thiopurine were 1.37 (95 % CI 0.30–6.24) in UC patients and 1.86 (95 % CI 0.60–5.78) in CD patients. Conclusions Our results suggested that thiopurine therapy may not be a risk factor for HM in Japanese patients with IBD. Further accumulation of cases and prospective studies are necessary to conclude this important issue.

DOI： 10.1007/s00535-013-0873-3

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Background: Crohn&#039;s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. Methods. Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as &quot;hyper-flow&quot; and &quot;hypo-flow&quot; according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson&#039;s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). Results: There were no significant differences in disease features or laboratory findings between &quot;hypo-flow&quot; lesions (n = 4) and &quot;hyper-flow&quot; lesions (n = 8). Histopathologically, &quot;hyper-flow&quot; lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did &quot;hypo-flow&quot; lesions. There was no apparent association between the blood flow and CDAI. Conclusions: In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions. © 2014 Sasaki et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1756-0500-7-363

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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.

DOI： 10.3109/00365521.2013.871744

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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. © 2013 The Author(s).

DOI： 10.1007/s00535-013-0872-4

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DOI： 10.1016/j.crohns.2012.06.019

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Other Link： http://orcid.org/0000-0002-2323-1640

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1016/j.crohns.2011.02.003

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1038/ajg.2009.453

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Other Link： http://www.nature.com/articles/ajg2009453

Language：English   Publishing type：Research paper (scientific journal)  

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 © The American Society of Gene Therapy.

DOI： 10.1016/j.ymthe.2004.07.001

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Publishing type：Research paper (scientific journal)   Publisher：Cold Spring Harbor Laboratory  

tobis a member of antiproliferative family genes. Mice lackingtobare prone to spontaneous formation of tumors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher intob^−/−mice than in wild-type mice.tob^−/−p53^−/−mice show accelerated tumor formation in comparison with single null mice. Expression ofcyclin D1mRNA is increased in the absence of Tob and is reduced by Tob. Tob acts as a transcriptional corepressor and suppresses thecyclin D1promoter activity through an interaction with histone deacetylase. Levels oftobmRNA are often decreased in human cancers, implicatingtobin cancer development.

DOI： 10.1101/gad.1088003

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Language：Japanese   Publisher：日本小児栄養消化器肝臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：Japanese   Publisher：日本小児栄養消化器肝臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：日本小児栄養消化器肝臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese   Publisher：日本小児栄養消化器肝臓学会  

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Language：Japanese   Publisher：日本小児栄養消化器肝臓学会  

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Language：Japanese   Publisher：日本臨床免疫学会  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

DOI： 10.1111/j.1365-2036.2005.02400.x

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