Intestinal Research

Comments on “Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study”: Sidharth Harindranath; Received May 21, 2024 Accepted July 17, 2024 Published online September 6, 2024; DOI: https://doi.org/10.5217/ir.2024.00072 [Epub ahead of print]

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Clinical characteristics and long-term disease course in patients with Crohn’s disease as diagnosed by video capsule endoscopy: a multicenter retrospective matched case-control study: June Hwa Bae, Su Hyun Park, Jung-Bin Park, Ji Eun Baek, Seung Wook Hong, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Kyeong Ok Kim, Byung Ik Jang, Mi Rae Lee, Eun Soo Kim, Sang Hyoung Park; Received April 18, 2024 Accepted July 15, 2024 Published online August 29, 2024; DOI: https://doi.org/10.5217/ir.2024.00056 [Epub ahead of print]

Abstract PDF: Background/Aims
Video capsule endoscopy is rarely used to diagnose Crohn’s disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases.
Methods
This multicenter study included patients with Crohn’s disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis.
Results
Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn’s disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393–1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn’s disease-related hospitalization, and surgeries (log-rank test P< 0.05).
Conclusions
Patients with Crohn’s disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

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Combined eosinophilic gastroenteritis and ulcerative colitis successfully treated by vedolizumab: a case report: Hironobu Takedomi, Kayoko Fukuda, Suma Inoue, Nanae Tsuruoka, Yasuhisa Sakata, Shigehisa Aoki, Motohiro Esaki; Received January 22, 2024 Accepted April 1, 2024 Published online August 29, 2024; DOI: https://doi.org/10.5217/ir.2024.00013 [Epub ahead of print]

Abstract PDF: A 47-year-old man with over 10 years’ duration of ulcerative colitis treated by 5-aminosalicylic acid and intermittent topical steroids complained of acute epigastric pain. Esophagogastroduodenoscopy revealed diffuse mucosal edema with patchy redness, multiple erosions and nodularity of the stomach. Bioptic examination revealed marked eosinophilic infiltration, confirming the diagnosis of eosinophilic gastroenteritis. Systemic steroid therapy was initiated, whereas his ulcerative colitis and eosinophilia recurred when tapering the steroid. Addition of azathioprine was ineffective, and we subsequently started vedolizumab for eosinophilic gastroenteritis and ulcerative colitis. The medication effectively improved his abdominal symptoms and esophagogastroduodenoscopy and ileocolonoscopy 1 year later revealed endoscopic improvement of both diseases with histologically decreased level of eosinophilic infiltration. Considering that eosinophils also express α4β7 integrins, vedolizumab can be a possible therapeutic candidate for eosinophilic gastroenteritis as well as ulcerative colitis.

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Tuberculosis risk in patients with Crohn’s disease on biologics: a retrospective analysis of the Japanese Medical Claims Database: Koji Fujimoto, Shuhei Hosomi, Yumie Kobayashi, Rieko Nakata, Yu Nishida, Masaki Ominami, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Satoko Ohfuji, Yasuhiro Fujiwara; Received May 27, 2024 Accepted July 17, 2024 Published online August 19, 2024; DOI: https://doi.org/10.5217/ir.2024.00076 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn’s disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database.
Methods
We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates.
Results
We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020).
Conclusions
TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.

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Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn’s disease during biological remission: Naohiro Nakamura, Yusuke Honzawa, Yuka Ito, Yasuki Sano, Naoto Yagi, Sanshiro Kobayashi, Mamiko Aoi, Takashi Tomiyama, Tomomitsu Tahara, Norimasa Fukata, Toshiro Fukui, Makoto Naganuma; Received March 15, 2024 Accepted June 11, 2024 Published online August 19, 2024; DOI: https://doi.org/10.5217/ir.2024.00042 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn’s disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD.
Methods
This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD.
Results
Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=–0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification.
Conclusions
LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.

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Bowel movement alterations predict the severity of diverticular disease and the risk of acute diverticulitis: a prospective, international study: Antonio Tursi, Daniele Piovani, Giovanni Brandimarte, Francesco Di Mario, Walter Elisei, Marcello Picchio, Gisella Figlioli, Gabrio Bassotti, Leonardo Allegretta, Maria Laura Annunziata, Mauro Bafutto, Maria Antonia Bianco, Raffaele Colucci, Rita Conigliaro, Dan L. Dumitrascu, Ricardo Escalante, Luciano Ferrini, Giacomo Forti, Marilisa Franceschi, Maria Giovanna Graziani, Frank Lammert, Giovanni Latella, Daniele Lisi, Giovanni Maconi, Debora Compare, Gerardo Nardone, Lucia Camara de Castro Oliveira, Chaves Oliveira Enio, Savvas Papagrigoriadis, Anna Pietrzak, Stefano Pontone, Ieva Stundiene, Tomas Poškus, Giuseppe Pranzo, Matthias Christian Reichert, Stefano Rodino, Jaroslaw Regula, Giuseppe Scaccianoce, Franco Scaldaferri, Roberto Vassallo, Costantino Zampaletta, Angelo Zullo, Erasmo Spaziani, Stefanos Bonovas, Alfredo Papa, Silvio Danese, DICA International Group; Received March 22, 2024 Accepted May 8, 2024 Published online August 12, 2024; DOI: https://doi.org/10.5217/ir.2024.00046 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC).
Methods
An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up.
Results
Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]_constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04–1.27; P=0.004; and HR_diarrhea =1.14; 95% CI, 1.03–1.26; P=0.014, respectively).
Conclusions
In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

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The prevalence of pouch fistulas in ulcerative colitis following restorative proctocolectomy: a systematic review and meta-analysis: Sheng Wei Lo, Ishaan Dharia, Danujan Sriranganathan, Maia Kayal, Edward L. Barnes, Jonathan P. Segal; Received January 17, 2024 Accepted May 9, 2024 Published online August 9, 2024; DOI: https://doi.org/10.5217/ir.2024.00009 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
One complication of restorative proctocolectomy with ileo-anal pouch anastomosis is fistula formation in the pouch. Fistulas can be associated with significant morbidity and pouch failure. We conducted a systematic review with meta- analysis to try and understand the prevalence of pouch fistulas in patients with ulcerative colitis following restorative proctocolectomy.
Methods
The Embase, Embase Classic, and PubMed databases were searched between January 1979 and April 2022. Studies were included if there were cross-sectional, case-controlled, population-based or cohort studies reporting on prevalence of pouch fistulas in ulcerative colitis. Studies had to report the number of patients with pouch fistulas using either clinical, endoscopic, or radiological diagnosis in an adult population.
Results
Thirty-three studies screened met the inclusion criteria. The pooled prevalence of developing at least 1 fistula was 0.05 (95% confidence interval [CI], 0.04–0.07). The pooled prevalence of pouch failure in patients with pouch fistula was found to be 0.24 (95% CI, 0.19–0.30). The pooled prevalence of developing a pouch fistula at 3 years, 5 years and more than 5 years was 0.04 (95% CI, 0.02–0.07), 0.05 (95% CI, 0.02–0.07), and 0.05 (95% CI, 0.02–0.10), respectively.
Conclusions
This is the first systematic review and meta-analysis to report the prevalence of pouch fistula. It also provides a pooled prevalence of pouch failure in these patients. These results can help to shape future guidelines, power future studies, and help counsel patients.

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Perianal fistulizing lesions of Crohn’s disease are associated with long-term behavior and its transition: a Chinese cohort study: Wei Zhan, Xiaoyin Bai, Hong Yang, Jiaming Qian; Received February 1, 2024 Accepted April 22, 2024 Published online July 15, 2024; DOI: https://doi.org/10.5217/ir.2024.00021 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort.
Methods
Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months.
Results
A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011).
Conclusions
Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.

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Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study: Taku Kobayashi, Kei Moriya, Toshimitsu Fujii, Shigeki Bamba, Shinichiro Shinzaki, Akihiro Yamada, Takashi Hisabe, Shintaro Sagami, Shuji Hibiya, Takahiro Amano, Noritaka Takatsu, Katsutoshi Inagaki, Ken-ichi Iwayama, Toshifumi Hibi; Received January 11, 2024 Accepted April 29, 2024 Published online July 15, 2024; DOI: https://doi.org/10.5217/ir.2024.00005 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC.
Methods
This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed.
Results
Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%–71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%–76.4%). One adverse event not related to budesonide rectal foam occurred.
Conclusions
The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

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Filgotinib induction-study baseline characteristics of patients with ulcerative colitis who achieve sustained corticosteroid-free remission: post hoc analysis of the phase 2b/3 SELECTION study: Taku Kobayashi, Axel Dignass, Xavier Roblin, Yoshie Takatori, Toshihiko Kaise, Alessandra Oortwijn, Corinne Jamoul, Toshifumi Hibi; Received January 17, 2024 Accepted April 15, 2024 Published online June 14, 2024; DOI: https://doi.org/10.5217/ir.2024.00007 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Obtaining and maintaining corticosteroid-free remission are important goals of treatment for ulcerative colitis (UC). Characteristics associated with achieving corticosteroid-free remission were assessed in filgotinib-treated patients in SELECTION, a 58-week, phase 2b/3 trial in moderately to severely active UC.
Methods
This post hoc analysis used data from filgotinib-treated patients receiving corticosteroids at maintenance baseline in SELECTION. Univariate logistic regression was performed to assess induction baseline characteristics associated with 6 months of corticosteroid-free remission at week 58, defined as clinical remission without using corticosteroids for at least 6 months.
Results
At maintenance baseline, 92 and 81 patients were receiving corticosteroids in the filgotinib 200 mg and filgotinib 100 mg groups, respectively. Age, body mass index, history of pancolitis, disease duration, fecal calprotectin levels, C-reactive protein levels, Mayo Clinic Score, concomitant corticosteroids, immunomodulators, and aminosalicylates had no statistically significant effect on the likelihood of achieving corticosteroid-free remission. Baseline characteristics associated with increased odds of corticosteroid-free remission were Mayo Clinic Endoscopic Subscore of 2 (vs. 3) in the filgotinib 200 mg and filgotinib 100 mg groups, and female (vs. male) sex, current (vs. former or never) smoking, and being biologic‑naive (vs. experienced) in the filgotinib 200 mg group.
Conclusions
Steroid tapering can be achieved in patients with UC receiving filgotinib 200 mg independently of baseline characteristics such as clinical activity and duration of illness. However, the likelihood of achieving corticosteroid-free remission was higher among patients who were biologic-naive, current smokers, had low endoscopic inflammatory burden and who were female.

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Complex dichotomous links of nonalcoholic fatty liver disease and inflammatory bowel disease: exploring risks, mechanisms, and management modalities: Kanishk Aggarwal, Bhupinder Singh, Abhishek Goel, Durgesh Kumar Agrawal, Sourav Bansal, Sai Gautham Kanagala, Fnu Anamika, Aachal Gupta, Rohit Jain; Received December 31, 2023 Accepted April 15, 2024 Published online June 5, 2024; DOI: https://doi.org/10.5217/ir.2024.00001 [Epub ahead of print]

Abstract PDF PubReader ePub: Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.

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Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis: Ryo Karashima, Shintaro Sagami, Yoko Yamana, Masa Maeda, Aya Hojo, Yusuke Miyatani, Masaru Nakano, Takahisa Matsuda, Toshifumi Hibi, Taku Kobayashi; Received September 27, 2023 Accepted April 9, 2024 Published online June 5, 2024; DOI: https://doi.org/10.5217/ir.2023.00135 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated.
Methods
Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed.
Results
A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8.
Conclusions
LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.

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Predictors of histologic remission in patients with biologic-naïve, moderate-to-severe ulcerative colitis treated with first-line biologic agents and small-molecule drugs: a single-center, retrospective cohort study: Kijae Jo, Kwang Woo Kim, Hyun Jung Lee, Jong Pil Im, Joo Sung Kim, Seong-Joon Koh; Received March 20, 2024 Accepted April 15, 2024 Published online May 22, 2024; DOI: https://doi.org/10.5217/ir.2024.00044 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
The prevalence and incidence of ulcerative colitis (UC) in Korea is increasing. Each patient has a different disease course and treatment response. Recently, with the development of biologic agents, histological remission has become a treatment goal. In this study, we aimed to identify the predictors of histological remission after first-line biologic agent treatment in patients with biologic agent-naïve UC.
Methods
We retrospectively analyzed the medical records of 92 patients who had been diagnosed with UC and treated with first-line biologic agent treatment at our center, between 2015 and 2022. The clinical characteristics, laboratory test results, and endoscopic and biopsy findings were analyzed. Histological remission was defined as the absence of cryptitis, crypt abscesses, and inflammatory cells on histology. Univariate and multivariate logistic regression analyses were performed to identify the predictors of histological remission after first-line treatment.
Results
Of the total 92 patients, 25 (27.2%) achieved histological remission. Each cohort had a varied body mass index (BMI) distribution, with a statistically significant overweight ratio, as defined by the Asian-Pacific BMI category of 23–25 kg/m², of 48.0% in the histological remission cohort (P= 0.026). A causal correlation between the overweight category and histological remission was confirmed (odds ratio, 3.883; 95% confidence interval, 1.141–13.212; P= 0.030).
Conclusions
We confirmed that the overweight category was a predictor of histological remission after first-line treatment with a biological agent. However, as BMI does not account for skeletal muscle mass, future studies are required to confirm the correlation between skeletal muscle mass and histological remission.

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What to do when traditional rescue therapies fail in acute severe ulcerative colitis: Christopher F. D. Li Wai Suen, Matthew C. Choy, Peter De Cruz; Received January 7, 2024 Accepted March 22, 2024 Published online May 16, 2024; DOI: https://doi.org/10.5217/ir.2024.00003 [Epub ahead of print]

Abstract PDF PubReader ePub: Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies.

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Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy: Ryoya Sakakibara, Shinya Sugimoto, Kaoru Takabayashi, Hiroki Kiyohara, Yusuke Wakisaka, Yuta Kaieda, Miho Kawaida, Yusuke Yoshimatsu, Tomohisa Sujino, Naoki Hosoe, Motohiko Kato, Masayuki Shimoda, Yohei Mikami, Yasushi Iwao, Takanori Kanai; Received January 5, 2024 Accepted March 5, 2024 Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2024.00006 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

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Defining management strategies for acute severe ulcerative colitis using predictive models: a simulation-modeling study: Danny Con, Peter De Cruz; Received November 17, 2023 Accepted February 15, 2024 Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2023.00175 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Robust management algorithms are required to reduce the residual risk of colectomy in acute severe ulcerative colitis (ASUC) refractory to standard infliximab salvage therapy. The aim of this study was to evaluate the performance and benefits of alternative ASUC management strategies using simulated prediction models of varying accuracy.
Methods
This was a simulation-based modeling study using a hypothetical cohort of 5,000 steroid-refractory ASUC patients receiving standard infliximab induction. Simulated predictive models were used to risk-stratify patients and escalate treatment in patients at high risk of failing standard infliximab induction. The main outcome of interest was colectomy by 3 months.
Results
The 3-month colectomy rate in the base scenario where all 5,000 patients received standard infliximab induction was 23%. The best-performing management strategy assigned high-risk patients to sequential Janus kinase inhibitor inhibition and mediumrisk patients to accelerated infliximab induction. Using a 90% area under the curve (AUC) prediction model and optimistic treatment efficacy assumptions, this strategy reduced the 3-month colectomy rate to 8% (65% residual risk reduction). Using an 80% AUC prediction model with only modest treatment efficacy assumptions, the 3-month colectomy rate was reduced to 15% (35% residual risk reduction). Overall management strategy efficacy was highly dependent on predictive model accuracy and underlying treatment efficacy assumptions.
Conclusions
This is the first study to simulate predictive model-based management strategies in steroid-refractory ASUC and evaluate their effect on short-term colectomy rates. Future studies on predictive model development should incorporate simulation studies to better understand their expected benefit.

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Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn’s disease small bowel lesion in capsule endoscopy: Teppei Omori, Miki Koroku, Shun Murasugi, Ayumi Ito, Maria Yonezawa, Shinichi Nakamura, Katsutoshi Tokushige; Received October 6, 2023 Accepted February 26, 2024 Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2023.00139 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn’s disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE.
Methods
Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated.
Results
Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 μg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 μg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman’s rank correlation coefficient ρ = 0.681, P< 0.001).
Conclusions
An LRG cutoff value of 14 μg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 μg/mL may be useful in predicting the absence of SB inflammatory findings.

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Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease: Samridhi Lakhanpal, Kanishk Aggarwal, Harmanjit Kaur, Kunal Kanwar, Vasu Gupta, Jill Bhavsar, Rohit Jain; Received August 20, 2023 Accepted November 6, 2023 Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2023.00104 [Epub ahead of print]

Abstract PDF PubReader ePub: Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.

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The evolving understanding of histology as an endpoint in ulcerative colitis: Shintaro Akiyama, Yusuke Miyatani, David T. Rubin; Received September 13, 2023 Accepted January 24, 2023 Published online March 13, 2024; DOI: https://doi.org/10.5217/ir.2023.00120 [Epub ahead of print]

Abstract PDF PubReader ePub

A therapeutic goal for patients with ulcerative colitis (UC) is deep remission including clinical remission and mucosal healing. Mucosal healing was previously defined by endoscopic appearance, but recent studies demonstrate that histological improvements can minimize the risks of experiencing clinical relapse after achieving endoscopic remission, and there is growing interest in the value and feasibility of histological targets of treatment in inflammatory bowel disease, and specifically UC. In this review article, we identify remaining challenges and discuss an evolving role of histology in the management of UC.

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Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy
Shintaro Akiyama, Joëlle St-Pierre, Cindy Traboulsi, Alexa Silfen, Victoria Rai, Tina G. Rodriguez, Amarachi I. Erondu, Joshua M. Steinberg, Seth R. Shaffer, Britt Christensen, David T. Rubin
npj Gut and Liver.2024;[Epub] CrossRef

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Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study: Ying-Hsiang Wang, Chi-Hsiang Chung, Tien-Yu Huang, Chao-Feng Chang, Chi-Wei Yang, Wu-Chien Chien, Yi-Chiao Cheng; Received July 4, 2023 Accepted December 22, 2023 Published online February 21, 2024; DOI: https://doi.org/10.5217/ir.2023.00078 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.
Methods
This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.
Results
Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).
Conclusions
Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

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Multiomics analysis reveals the potential mechanism of high‐fat diet in dextran sulfate sodium‐induced colitis mice model
Yuyang Zhao, Zhimin Chen, Ruiyi Dong, Yufan Liu, Yixin Zhang, Yan Guo, Meiyi Yu, Xiang Li, Jiangbin Wang
Food Science & Nutrition.2024;[Epub] CrossRef

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Helminths in alternative therapeutics of inflammatory bowel disease: Himani Pandey, Daryl W. T. Tang, Sunny H. Wong, Devi Lal; Received May 25, 2023 Accepted November 1, 2023 Published online January 12, 2024; DOI: https://doi.org/10.5217/ir.2023.00059 [Epub ahead of print]

Abstract PDF PubReader ePub: Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.

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Risk of malignancies and chemopreventive effect of statin, metformin, and aspirin in Korean patients with ulcerative colitis: a nationwide population-based study: Eun Hye Oh, Ye-Jee Kim, Minju Kim, Seung Ha Park, Tae Oh Kim, Sang Hyoung Park; Received June 3, 2023 Accepted September 14, 2023 Published online November 9, 2023; DOI: https://doi.org/10.5217/ir.2023.00062 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
We investigated the incidences of overall and site-specific malignancies and chemopreventive effects of statin, metformin, and aspirin in patients with ulcerative colitis.
Methods
We collected data using the Health Insurance Review and Assessment claims database from January 2007 to April 2020.
Results
The overall malignancy risk among the 35,189 ulcerative colitis patients was similar to that of the general population (standardized incidence ratio, 0.94; 95% confidence interval, 0.88–1.00). In male patients, standardized incidence ratios were high for thyroid cancer and low for stomach cancer, colorectal cancer, liver cancer, and lung cancer. Concurrently, standard incidence ratios were high for liver cancer and central nervous system cancer in female patients. While 122 cases of colorectal cancer occurred in the study patients, the standardized incidence ratio was 0.83 (95% confidence interval, 0.69–0.99). Treatment for ulcerative colitis was not associated with an increased adjusted hazard ratio, while comorbidities increased it for all malignancies. Treatment for ulcerative colitis was associated with an increased adjusted hazard ratio, while comorbidities did not increase it for colorectal cancer. After adjusting for age, sex, comorbidities, and ulcerative colitis treatment, statins showed a dose-dependent chemopreventive effect for all malignancies (P=0.002), while metformin and aspirin did not show any.
Conclusions
In ulcerative colitis patients, standardized incidence ratios for all malignancies and colorectal cancer did not increase. Adjusted hazard ratios for all malignancies increased with comorbidities and those for colorectal cancer with ulcerative colitis treatment. Statins have a dose-dependent chemopreventive effect for all malignancies.

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