One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study

( Yuichi Matsuno ),( Takehiro Torisu ),( Junji Umeno ),( Hiroki Shibata ),( Atsushi Hirano ),( Yuta Fuyuno ),( Yasuharu Okamoto ),( Shin Fujioka ),( Keisuke Kawasaki ),( Tomohiko Moriyama ),( Tomohiro 대한장연구학회 2022 Intestinal Research Vol.20 No.2

Background/Aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤4), mucosal healing (MES ≤1), and histological healing (GS ≤1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. Conclusions: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered. (Intest Res 2022;20:260-268)

Endoscopic features of gastrointestinal stromal tumor in the small intestine

Yutaro Ihara,Takehiro Torisu,Tomohiko Moriyama,Junji Umeno,Atsushi Hirano,Yasuharu Okamoto,Yoshifumi Hori,Hidetaka Yamamoto,Takanari Kitazono,Motohiro Esaki 대한장연구학회 2019 Intestinal Research Vol.17 No.3

Background/Aims: Gastrointestinal stromal tumor (GIST) is one of the most common types of submucosal tumors (SMTs). Because of GIST’s malignant potential, it is crucial to differentiate it from other SMTs. The present study aimed to identify characteristic endoscopic findings of GISTs in the small intestine. Methods: We reviewed the clinicopathological and endoscopic findings of 38 patients with endoscopically or surgically resected SMTs in the small intestine. SMTs were classified into GIST and non-GIST groups, and clinicopathological and endoscopic findings were compared between the 2 groups. Results: Fifteen patients had GIST and 23 patients had other types of SMTs in the small intestine. Comparison of the endoscopic findings between the 2 groups revealed that dilated vessels in the surrounding mucosa were significantly more in number in the GIST group than in the non-GIST group (P<0.05). However, there were no other differences in endoscopic findings between the 2 groups. Among patients with GISTs, the presence of dilated vessels in the surrounding mucosa was not associated with bleeding risk, tumor size, or metastasis rate at diagnosis. Conclusions: Dilated vessels in the surrounding mucosa, identified during balloon-assisted endoscopy, may be a diagnostic indicator for GIST in the small intestine. However, its clinical significance should be further analyzed.

Risk of surgery in patients with stricturing type of Crohn’s disease at the initial diagnosis: a single center experience

Yuji Maehata,Yutaka Nagata,Tomohiko Moriyama,Yuichi Matsuno,Atsushi Hirano,Junji Umeno,Takehiro Torisu,Tatsuya Manabe,Takanari Kitazono,Motohiro Esaki 대한장연구학회 2019 Intestinal Research Vol.17 No.3

Background/Aims: It remains uncertain which patients with stricturing-type Crohn’s disease (CD) require early small bowel surgery after the initial diagnosis. We aimed to clarify clinical characteristics associated with the intervention in such condition of CD. Methods: We retrospectively evaluated the clinical course of 53 patients with CD and small bowel strictures who were initially treated with medications after the initial diagnosis. We investigated possible associations between small bowel surgery and the following: clinical factors and radiologic findings at initial diagnosis and the types of medications administered during follow-up. Results: Twenty-eight patients (53%) required small bowel resection during a median follow-up period of 5.0 years (range, 0.5–14.3 years). The cumulative incidence rates of small bowel surgery at 2, 5, and 10 years were 26.4%, 41.0%, and 63.2%, respectively. Univariate analysis indicated that obstructive symptoms (P=0.036), long-segment stricture (P<0.0001), and prestenotic dilation (P<0.0001) on radiography were associated with small bowel surgery, and immunomodulatory (P=0.037) and biological therapy (P=0.008) were significant factors during follow-up. Multivariate analysis revealed that long-segment stricture (hazard ratio [HR], 4.25; 95% confidence interval [CI], 1.78–10.53; P=0.001) and prestenotic dilation (HR, 3.41; 95% CI, 1.24–9.62; P=0.018) on radiography showed a positive correlation with small bowel surgery, and biological therapy (HR, 0.40; 95% CI, 0.15–0.99; P=0.048) showed a negative correlation. Conclusions: CD patients with long-segment stricture and prestenotic dilation on radiography seem to be at a higher risk of needing small bowel surgery. For such patients, early surgical intervention might be appropriate, even at initial diagnosis.

Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn’s Disease

Shunichi Yanai,Satoko Yamaguchi,Shotaro Nakamura,Keisuke Kawasaki,Yosuke Toya,Noriyuki Yamada,Makoto Eizuka,Noriyuki Uesugi,Junji Umeno,Motohiro Esaki,Eiko Okimoto,Shunji Ishihara,Tamotsu Sugai,Takayu 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.1

Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1 ) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn’s disease (CD). Methods: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. Results: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (p<0.001). The three patients with CEAS without SLCO2A1 expression had a homozygous splice-site mutation in SLCO2A1, c.1461+1G>C (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. Conclusions: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.

Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score- Matched Study

( Yuji Maehata ),( Shotaro Nakamura ),( Motohiro Esaki ),( Fumie Ikeda ),( Tomohiko Moriyama ),( Risa Hida ),( Ema Washio ),( Junji Umeno ),( Minako Hirahashi ),( Takanari Kitazono ),( Takayuki Matsum 대한간학회 2017 Gut and Liver Vol.11 No.5

Background/Aims: Gastric cancers develop even after suc-cessful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. Methods: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dis-section were included. After matching the propensity score, we retrospectively investigated the clinicopathological fea-tures of 192 patients, including 96 patients who had under-gone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). Results: In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive pa-tients, Hp-eradicated patients showed a more frequently de-pressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. Conclu-sions: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow- up endoscopies are necessary after H. pylori eradication. (Gut Liver 2017;11:628-634)

Immunohistochemical differentiation between chronic enteropathy associated with SLCO2A1 gene and other inflammatory bowel diseases

Satoko Yamaguchi,Shunichi Yanai,Shotaro Nakamura,Keisuke Kawasaki,Makoto Eizuka,Noriyuki Uesugi,Tamotsu Sugai,Junji Umeno,Motohiro Esaki,Takayuki Matsumoto 대한장연구학회 2018 Intestinal Research Vol.16 No.3

Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic enteropathy associated with SLCO2A1 (CEAS). The aim of this study was to evaluate SLCO2A1 protein expression in the intestinal tissues of patients with CEAS, intestinal Behçet’s disease (BD), simple ulcer (SU), and Crohn’s disease (CD). Methods: Immunohistochemical staining using a polyclonal anti-SLCO2A1 antibody was performed on the resected intestinal specimens from 13 cases of CD, 9 cases of intestinal BD/SU, and 3 cases of CEAS. The extent of SLCO2A1 expression was determined by counting positively-staining vascular endothelial cells and scored as 0 (no cells), 1 (1%−30% cells), 2 (31%−60%), or 3 (>60%). The intensity of SLCO2A1 expression was scored either as 0 (negative), 1 (intermediate), or 2 (strong). The extent score and intensity score were summed for the final score of 0, 2, 3, 4, or 5. Results: SLCO2A1 protein expression was observed in 1 of 3 cases of CEAS (33%), all 13 cases of CD (100%), and all 9 cases of BD/SU (100%). The mean final expression scores of CEAS, CD, and BD/SU were 1.6 (range, 0−5), 4.8 (range, 4−5), and 4.3 (range, 4−5), respectively. The final expression score in CEAS was significantly lower than in CD (P=0.03). Conclusions: Immunohistochemical staining of the SLCO2A1 protein is considered useful to distinguish CEAS from other inflammatory bowel diseases.