The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

Background/Aims: The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. Methods: A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. Results: In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Background/Aims: Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors’ opinions and test equipment in hospitals are unclear. The aim of the study was to investigate these issues to improve the prognosis of IBD patients. Methods: This retrospective, multicenter study was conducted by 83 investigators who were members of the Asian Organization for Crohn’s and Colitis. Data on opportunistic infection were collected from hospital databases between January 2017 and December 2017. The survey con sisted of 11 items. Results: Most physicians appreciated the diagnostic value of tissue cytomegalovirus (CMV) DNA, accounting for 86.1% of members in China, 37.5% in Japan, 52.9% in South Korea, and 66.7% in Southeast Asia. Only 83.1% of hos­pitals had the ability to test for CMV immunohistochemistry in Asia. Hepatitis B surface antigen (HBsAg) screening was recommended by all members. However, only 66.7% in China, 70.6% in South Korea, and 66.7% in Southeast Asia agreed to routinely vaccinate IBD patients when HBsAg tested negative. Most members preferred metro nidazole (74.7%) as the first choice for patients with Clostridium difficile infection. However, the proportion of stool C. difficile toxin test was lower in China than in other areas (75.0% in China vs 95.8% in Japan and 100% in South Korea and Southeast Asia, p<0.05). Conclusions Opportunistic infection from CMV, hepatitis B virus, and C. difficile should be of high concern for IBD patients. More efforts are needed, such as understanding consensus in clinical practice and improving testing facilities in hospitals.

Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.

Objective:To investigate the risk factors of dysplasia in patients with ulcerative colitis (UC) in China.Methods:From March 1st, 2012 to December 30th, 2013, a total of 154 UC patients were prospectively enrolled from the following 11 hospitals, Xijing Hospital of Digestive Diseases, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Peking Union Medical College Hospital, Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Nanfang Hospital affiliated to Southern Medical University, China-Japan Friendship Hospital, The Second Hospital of Hebei Medical University, West China Hospital affiliated to Sichuan University, The Seventh Medical Center of PLA General Hospital, Zhongshan Hospital affiliated to Xiamen University, and the First Affiliated Hospital of Anhui Medical University. The patients were followed up till December 1st, 2017. All the UC patients underwent colon endoscopy and histopathological evaluation. T test and Chi-square test were used for statistical analysis. Cox proportional risk model was used for identifying the risk factors of dysplasia in UC patients. Results:Finally, 133 UC patients were enrolled, the age was (50.0±11.9) years, the diagnosis age was (35.5±11.6) years, the course of disease was (14.5±6.7) years, and the number of endoscopic examinations was (3.4±1.6) times. A total of 21 patients were detected with dysplasia. No patients were detected with colorectal cancer. The results of univariate analysis revealed that the diagnosis age (hazard ratio ( HR)=1.05, 95% confidence interval ( CI) 1.01 to 1.10, P=0.009) and extensive colitis ( HR=2.92, 95% CI 0.97 to 8.79, P=0.057) were factors with statistically significant difference. The results of multivariate analysis revealed that the old age at diagnosis ( HR=1.06, 95% CI 1.02 to 1.11, P=0.003) and extensive colitis ( HR=3.68, 95% CI 1.21 to 11.19, P=0.022) were independent risk factors of dysplasia in UC patients. The cumulative incidence of dysplasia of UC patients with extensive colitis was higher than that of patients with left-sided colitis (24.3%, 17/70 vs. 6.3%, 4/63), and the difference was statistically significant ( χ2=8.023, P=0.005). Conclusions:Extensive colitis and older age at diagnosis are two independent risk factors of dysplasia in UC patients of our country. The cancer monitoring should be strengthened in UC patients with long course of disease and extensive colitis.

[Abstract] Objective: To investigate the effect of 18H12, a functional monoclonal antibody that can target gastric cancer stem cells, on the self-renewal and invasion ability of gastric cancer cells. Methods: The gastric cancer cell line PAMC-82 was used as cell model, the expression of ENO1 (enolase-1) on the membrane surface of its parental cells and enriched stem cells by sphere culture was detected by Flow cytometry. Flow cytometry was used to separate ENO1+ cells and ENO1- cells to detect their self-renewal ability and invasion ability. With the commercial ENO1 antigen and antibody as the samples, CoIP (co-immunoprecipitation) was used to verify whether 18H12 antibody targeting ENO1 could able to accurately recognize ENO1. After being treated with 18H12 for 12 h, 24 h and 48 h, the selfrenewal and invasion ability of PAMC-82 cells were detected by methylcellulose pelletization experiment and Transwell chamber assay, respectively. Results: Flow cytometry showed that the expression of ENO1 on the membrane surface of PAMC-82 sphere cells was significantly higher than that of its parental cells (P<0.01), so ENO1 could be a potential target for targeting gastric cancer stem cells. The self-renewal ability and invasion ability of the sorted ENO1+ cells were significantly stronger than those of the ENO1- cells and the parental cells (P<0.05 or P<0.01). 18H12 antibody could accurately recognize ENO1, which was consistent with the commercial antibody recognition band. 18H12 could significantly inhibit self-renewal ability and invasion ability of PAMC-82 cells (P<0.01). Conclusion: Monoclonal antibody 18H12 can significantly inhibit the self-renewal and invasion of gastric cancer stem cells and is expected to be a candidate antibody drug targeting gastric cancer stem cells.

Objective: To investigate the expression of programmed death ligand 1 (PD-L1) in liver cancer tissues and its clinical significance. Methods: The expression levels of PD-L1 in 110 liver cancer tissues, including 95 cases of hepatocellular carcinoma and 15 cases of cholangiocarcinoma were detected by using immunohistochemical staining method, and the relationship between PD-L1 expression and the clinicopathological characteristics of patients with hepatocellular carcinoma was analyzed. Results: Immunohistochemistry results showed that the positive rate of PD-L1 in liver cancer tissues was 69.1% (76/110), and the positive rate of membrane and cytoplasm was 46.4% (51/110) and 22.7% (25/110), respectively. The positive rate of PD-L1 expression in hepatocellular carcinoma was higher than that in cholangiocarcinoma [78.9% (75/95) vs. 6.7% (1/15)], and the difference was statistically significant (χ ² = 31.693, P < 0.01). The positive expression of PD-L1 was closely associated with the depth of invasion and TNM stage of hepatocellular carcinoma (both χ² = 4.629, both P = 0.031), but there was no relationship with the patients'age, gender and pathological grade (all P > 0.05). Further analysis showed that protein expression localization of PD-L1 was closely related to the pathological grade in hepatocellular carcinoma (P = 0.013). Conclusion The positive expression of PD-L1 in hepatocellular carcinoma is closely associated with depth of invasion and TNM stage, which provides a theoretical basis for the immunotherapy of liver cancer targeting PD-L1.

Objective The objectives of this study were to screen and identify monoclonal antibodies against hepatoma stem cells by screening for hepatoma spheroid cells,and to provide candidate therapeutic monoclonal antibodies for targeting cancer stem cells to treat hepatic cancer. Methods Hepatic cancer stem cells were enriched by serum-free suspension culture. Immunofluores-cence,cisplatin resistance assay, Real -time qPCR, subcutaneous tumor formation in nude mice, and other methods were used to screen and identify anti-hepatocarcinoma stem cell monoclonal antibodies. Immunohistochemistry was used to identify the expression of antigen recognized by monoclonal antibody in liver cancer tissues. The antigen was identified by mass spectrometry. Results MH-CC97L cells were able to form cell spheres in serum -free suspension culture and were labeled with PKH26 dye. Flow cytometry showed that the expression of CD90 + in MHCC97L spheroid cells was 3. 4 times higher than that in the parental cells. In the inhibition experiment of serum-free spheroid,6 monoclonal antibodies significantly inhibited MHCC97L cells in serum-free medium,and in-hibitory rates were 54. 67% ,50. 33% ,45. 73% ,42. 26% ,39. 11% ,and 37. 63% ,respectively. The results of immunofluorescence showed that monoclonal antibodies 28C10 and CD90 were colocalized in MHCC97L cells. The results of real-time qPCR showed that the expression of Sox-2 and Oct-4 in MHCC97L 28C10 + cells was significantly higher than those of MHCC97L 28C10 - cells. Flow cytometry showed that the ratio of 28C10 + in MHCC97L cells and its sphere cells were 7. 98% and 10. 7% ,respectively. The ratio of 28C10 + cells was increased by 1. 34 times. The in vitro globing ability and invasive ability of 28C10 + cells obtained by flow cytometry were significantly higher than those of 28C10 - cells. The results of CCK-8 assay showed that 28C10 + cells were resistance to cispla-tin in 28C10 - cells,which are 1. 96 g/ml and 1. 16 g/ml,respectively. Tumorigenic assay showed that 28C10 + cells were inoculated subcutaneously with 2×104 cells into the nude mice,and tumors were formed in 2 months,with 40% of tumor formation rate. Another nude mouse that did not form a tumor had formed a lung metastasis(1/5). Immunohistochemistry showed that the target antigen posi-tive rate of monoclonal antibody 28C10 in hepatic cancer tissues was about 72. 0% (77/107),while it was lowly expressed in adjacent tissues,and the difference was significant. Mass spectrometry showed that the antigen recognized by 28C10 was HSP90α. Conclusion The MHCC97L spheroid cell model is successfully used to identify a monoclonal antibody that specifically recognizes hepatoma stem cells,which provides a foundation for antibody therapy targeting hepatic cancer stem cells.