Incomplete Intestinal Metaplasia of the Stomach Is more Related to Bile Reflux than Chronic Gastritis.

OBJECTIVE: Incomplete intestinal metaplasia (IIM) of the stomach is associated with higher risk of progression to dysplasia and gastric cancer than complete intestinal metaplasia (CIM). Whether the causative factors underlying IIM are different from those underlying CIM is currently unknown. In a recent study, bile acids were found to induce gastric intestinal metaplasia (IM) in mice by activating STAT3 signaling and accelerated the development of dysplasia. The aim of this study was to determine whether there are differences in associations between IIM and CIM and clinicopathologic features known to be associated with intestinal metaplasia, bile reflux, and activated STAT3. METHODS: Fifty-two consecutive gastric biopsies with IM were examined for the type of metaplasia, presence of inflammation, and Helicobacter pylori (H. pylori) status. Immunohistochemical staining was performed for phospho-STAT3 (p-STAT3) and evaluated by image analysis. The type of IM was then correlated with relevant clinicopathologic variables and p-STAT3 expression. RESULTS: Seven cases had IIM only, 31 had CIM only, and 14 had both CIM and IIM (CIIM). Significantly fewer cases with IIM had chronic gastritis than either CIM or CIIM (43%, 93%, 79%, respectively, p=0.005). H. pylori was not detected in any of the IIM cases but was positive in 29% of CIM and 29% of CIIM. Fifty-seven percent of patients with IIM had a history of cholecystectomy compared to 25% of those with CIM and 23% of those with CIIM. The mean BMI was 32.3 kg/m2 for patients with IIM compared to 28 kg/m2 for those with CIM and 31.2 kg/m2 for those with CIIM. Median p-STAT3 for biopsies with was IIM was 6.36 compared to 3.54 for CIM and 6.27 for CIIM. Reactive gastropathy was present in 57% of biopsies with IIM, 39% of CIM and 50% of CIIM. CONCLUSION: In contrast to CIM, IIM is significantly less likely to be associated with chronic gastritis. CIIM also tended to be less associated with H. pylori infection and more associated with reactive gastropathy, history of cholecystectomy, higher BMI, and higher median p-STAT3. These results tend to suggest that IIM is probably more likely to be associated with bile reflux than H. pylori-associated gastritis. Larger studies are needed to confirm these findings.Presented in part at Digestive Disease Week 2023, Chicago, IL, May 6, 2023.

Colonic Eosinophilia: Clinicopathologic Study of Paired Right and Left Colon Biopsies from 276 Patients.

OBJECTIVE: This study evaluated differences in eosinophil (Eos) count in the right colon (RC) and left colon (LC) relative to known clinical and pathologic features. METHODS: H&E slides from 276 subjects with biopsies taken from both RC and LC were reviewed. Eos/mm2 were counted in the area with highest concentration then correlated with clinical and pathologic findings for RC and LC. RESULTS: There were higher numbers of Eos/mm2 in RC than in LC (mean 177 vs 122, respectively p<0.0001), and there was significant positive correlation between Eos numbers in the two locations (r=0.57, p<0.001). In RC, the mean Eos/mm2 was 242 with active chronic colitis, 195 with inactive chronic colitis, 160 in microscopic colitis, 144 in quiescent IBD, and 142 with normal histology (p<0.001), and was higher in males (204 vs 164, p=0.022). In LC, mean Eos/mm2 was 186 with active chronic colitis, 168 with inactive chronic colitis, 154 in microscopic colitis, 82 in quiescent IBD, and 84 with normal histology (p<0.001), and was higher in males (154 vs 107, p<0.001). In biopsies with normal histology, RC showed higher mean Eos/mm2 in Asian patients (228 vs 139, p=0.019), and patients with history of UC (205 vs 136, p=0.004), but was not significantly different in patients with or without irritable bowel syndrome with diarrhea (IBS-D) or history of Crohn's disease (CD). In LC the mean Eos/mm2 was higher in males (102 vs 77, p=0.036), and history of CD (117 vs 78, p=0.007), but was not significantly different in patients with or without IBS-D or history of UC. The number of Eos/mm2 was greater in biopsies performed in the summer than during other seasons of the year. CONCLUSION: The mean number of Eos/mm2 in colorectal biopsies varies significantly by location, histopathologic changes, clinical diagnosis, season, gender and ethnicity. Of particular interest is the association between high Eos/mm2 in RC biopsies with otherwise normal histology and clinical history of UC, and in LC biopsies with clinical history of CD. Additional larger and prospective studies that include normal healthy volunteers are needed to establish a reliable cutoff for the histopathologic diagnosis of eosinophilic colitis, taking into consideration the biopsy site within the colon and rectum, as well as patient gender and ethnicity.Presented in part at the annual American College of Gastroenterology meeting, San Antonio, TX October 2019.

Alterations in MAdCAM1-Positive Mucosal Capillaries and Integrin a4b7-Positive Lymphocytes in Crohn's Disease Treated with Anti-TNFα Biologics.

OBJECTIVE: To elucidate the reasons for the decreased effectiveness of Vedolizumab (VDZ) treatment in patients with Crohn's disease (CD) previously treated (CD-T) with anti-TNF-α biologics. METHODS: Immunohistochemical staining was performed on sections of formalin-fixed paraffin-embedded ileocolonic biopsies using antibodies for the mucosal addressin molecule (MAdCAM-1) and Etrolizumab. RESULTS: The mean number of MAdCAM-1 positive capillaries (MAdCAM-1-C) was 3 in controls, 8.5 in CD, 5.37 in CD-T, 5.7 in ulcerative colitis (UC), and 3.1 in lymphocytic colitis (LC) (p=0.0032). When all biopsies with inflammatory bowel disease (IBD) in this series were considered together, the number of MAdCAM-1-C increased with an increased histologic activity score (HAS) (p<0.001). The mean MAd-CAM-1-C was lower in CD-T than CD (5.37 vs. 8.5, p=0.0362), even in cases with high HAS (6.46 vs. 9.5, p=0.073). Two of 6 (33%) controls, 4 of 6 (67%) CD, 9 of 16 (56%) CD-T, 6 of 7 (86%) UC, and 0 of 8 (0%) LC showed Etrolizumab-positive lymphocytes (E-Ly, p=0.0106). IBD biopsies positive for E-Ly were associated with higher HAS (p=0.0546). MAdCAM-1-C was heterogenous in some IBD cases. CONCLUSIONS: Our results suggest that treatment with anti-TNF-α reduces the number of MAdCAM-1-C in CD, even in biopsies with high HAS. This suggests that high inflammation in such cases obviously failed to respond to anti-TNF-α, may be less dependent on the migration of a4b7-lymphocytes to the inflamed mucosa, and therefore may not optimally respond to VDZ treatment.Presented in part at the Digestive Diseases Week meeting, San Diego, CA, May 2019. Supported by Takeda Pharmaceuticals.

Lymphocytic Esophagitis Is Not Similar to Eosinophilic Esophagitis Except for Seasonal Variation.

OBJECTIVE: Unlike eosinophilic esophagitis (EoE), there is no consensus on the minimum number of intraepithelial lymphocytes (IEL) that is diagnostic of lymphocytic esophagitis (LyE). The aim of this study was to determine whether significant correlations exist between the numbers of intraepithelial lymphocytes (IEL) in esophageal biopsies and clinical and endoscopic manifestations usually associated with EoE. METHODS: H&E slides from esophageal biopsies from 330 patients were reviewed. The number of IEL and intraepithelial eosinophils (IEE) per mm2 was counted in the area with the highest concentration in each biopsy. The numbers were then correlated with clinical and endoscopic findings. RESULTS: As expected, a higher number of IEE was significantly associated with food impaction (p=0.001), dysphagia (p=0.021), esophageal stricture (p=0.017), rings (P<0.0001), and furrows (p<0.0001). By contrast, there was no significant association between increased IEL and any of the aforementioned clinical and endoscopic features in the original 330 patients or in a subset of 233 patients with no IEE. Interestingly, the number of both IEE and IEL varied significantly by the season when the biopsy was obtained, being lowest in the fall and highest in the spring (p=0002 for IEE and p<0.0001 for IEL). CONCLUSION: In esophageal biopsies, increased IEL has no significant correlation with food impaction or dysphagia or with esophageal stricture, rings, or furrows. There is significant variation in the number of IEL depending on the season when the biopsy is obtained, which has not been previously reported.

Dilemma in post-IBD patients with IBS-D symptoms: A 2020 overview.

INTRODUCTION: Inflammatory bowel disease (IBD) patients in apparent clinical remission who present with irritable bowel syndrome (IBS)-like symptoms pose a diagnostic and therapeutic dilemma that is called post-IBD IBS. When associated with a diarrheal IBS presentation, this clinical syndrome is known as post-IBD IBS-D. AREAS COVERED: We review and describe the literature regarding the clinical overlap of IBD and IBS. We discuss prevalent theories regarding the pathophysiology of post-IBD IBS-D and whether this presentation represents coincident inherent IBS-D, IBS-D triggered by IBD, or an even more subtle level of IBD activity that is unrecognized by available laboratory modalities. We also discuss observations that post-IBD IBS-D patients harbor significantly increased colon mucosal eosinophils and appear to respond to a GI-hypoallergenic diet and budesonide therapy. EXPERT OPINION: The symptoms overlap between IBD and IBS complicates diagnosis and subsequent management of patients with post-IBD IBS-D. In addition to current theories regarding the pathophysiology of this condition such as alterations in mucosal inflammation, the microbiota, mucosal permeability, and gut-brain interactions. This new avenue of eosinophilic colopathy and therapy directed toward food-derived immune response in patients with post-IBD IBS-D deserves additional investigation.

Aquaporin-5 Expression Is Reduced in Lymphocytic Colitis.

OBJECTIVE: Aquaporin-5 (AQP5) is a member of a family of water channel proteins involved in the bidirectional transfer of water across cell membranes. Lymphocytic colitis (LC) and collagenous colitis (CC) are clinically similar diseases characterized by chronic watery diarrhea in patients with usually unremarkable colonic mucosa on colonoscopy. The aim of this study was to determine whether AQP5 expression in colonic epithelium is altered in LC and CC. METHODS: Sections of formalin-fixed and paraffin-embedded colorectal biopsies from three control patients (CTL), 8 patients with chronic non-bloody diarrhea with biopsies negative for active inflammation or significant distortion (CTL-D), 8 patients with LC, and 5 with CC were stained for AQP5 using immunohistochemistry. The staining intensity was scored as 3 (strong), 2 (intermediate), 1 (weak), or 0 (no staining). Statistical analysis was performed using Prism 7 Statistical Soft-ware. RESULTS: AQP5 was strongly expressed (score 3) in the epithelial cells in all three CTL cases and all 8 CTL-D cases. In the 5 cases of CC, 3(60%) had score 3 and 2(40%) had score 2, but none had a score of 1 or 0. Of the 8 LC cases, 2(25%) had score 3, 3 had score 2(37.5%), and 3 had score 1(37.5%) (p=0.0031). In the three cases of LC with markedly reduced AQP5 (score 1), enteric steroid treatment did not lead to significant improvement in diarrhea. CONCLUSIONS: Colorectal AQP5 expression is reduced in most cases of LC. Markedly reduced AQP5 expression in LC may identify a subset of patients with suboptimal response to enteric steroid treatment. Additional larger studies are needed to confirm these findings.This abstract was presented in part at Digestive Diseases Week in San Diego, CA, May 2019.

Anti-TNF-α Biologics Do Not Reverse CDX2 Downregulation in Patients with Crohn's Disease.

OBJECTIVE: The caudal-related homeobox transcription factor 2 (CDX2) plays an important role in intestinal epithelial differentiation, proliferation, migration, and adhesion. It has been previously reported that TNF-α reduces CDX2 expression in cultured colon epithelial cells in a dose-dependent manner, and that this effect was reduced by adding the anti-TNF-α drug infliximab to the culture medium. The aim of this study was to determine whether CDX2 expression is reduced in biopsies from patients with Crohn's disease (CD), and whether treatment with anti-TNF-α drugs reverses CDX2 downregulation in these patients. METHODS: Sections of ileocolonic biopsy tissues from patients with CD, CD treated with anti-TNF-α biologics (CD-T), and controls were stained for CDX2 and evaluated using OTMIAS digital image analysis. RESULTS: CDX2 expression in biopsies from patients with CD and CD-T was lower than in controls (p=0.0003). CDX2 expression in CD-T did not increase (p=0.3292) and remained significantly lower than controls (p=0.0002). CONCLUSIONS: Although CDX2 is downregulated in CD, it did not revert to normal in patients treated with anti-TNF-α biologics.

Downregulation of Estrogen Receptor Beta1 Expression in Sessile Serrated Adenomas.

OBJECTIVE: CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-ß1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-ß1 expression in SSA is unknown. The aim of this study is to determine ER-ß1 expression in SSA and its relation to CDX2 expression. METHODS: Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-ß1 and CDX2. SSA with ER-ß1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in <10% of SSA crypts as 1, 11-25% as 2, 26-50% as 3, 51-75% as 4, and CDX2 loss in >75% of the SSA crypts scored as 5. RESULTS: There is a significant correlation between a loss of CDX2 and the loss of ER-ß1 scores in SSA (p<0.001). The downregulation of CDX2 was greater in SSA arising from the right colon compared to the left colon and rectum (p=0.012). Similarly, downregulation of ER-ß1 was greater in SSA arising in the right colon compared to the left colon and rectum (p=0.014). CONCLUSIONS: Our findings show significant downregulation of both ER-ß1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-ß1 downregulation plays a significant role in the malignant progression of SSA.

The Significance of So-Called Equivocal Immunohistochemical Staining for Cytomegalovirus in Colorectal Biopsies.

CONTEXT.­: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV. OBJECTIVES.­: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies. DESIGN.­: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history. RESULTS.­: Fifty-two cases (24% of all tested, 63% of positive cases) showed equivocal staining for CMV, and of these, 41 had follow-up information. Polymerase chain reaction for CMV was performed largely on blood samples and was not found to be sensitive for the detections of CMV proctocolitis. Of 25 patients who received antiviral treatment, 21 (84%) had complete resolution of symptoms, compared with 8 of 16 (50%) who did not receive antivirals (P = .02). There was no statistically significant difference in response to antiviral drugs in patients with equivocal and unequivocal CMV staining (P = .17). CONCLUSIONS.­: Equivocal CMV staining likely represents true CMV proctocolitis. Prospective studies are needed to confirm these findings.

Pancreatic Acinar Metaplasia in Distal Esophageal Biopsies Is Associated With Chronic Nonsteroidal Anti-inflammatory Drug Use.

CONTEXT.­: The cause of pancreatic acinar metaplasia (PAM) at the distal esophagus/esophagogastric junction is still controversial. Whereas some authors believe it is congenital, others believe it is acquired because of inflammation of the gastric cardia, and more recently it was proposed to be due to chronic proton pump inhibitor use based on a study in rats. OBJECTIVE.­: To determine whether there is correlation between chronic proton pump inhibitor use and PAM in humans. We also investigated the correlation between several clinical and pathologic factors and PAM. DESIGN.­: Four hundred forty-four consecutive biopsies from the distal esophagus/esophagogastric junction were reviewed for the presence of PAM, which was then correlated with several clinical and pathologic findings. RESULTS.­: Pancreatic acinar metaplasia was found in 71 patients (16%). Pancreatic acinar metaplasia was significantly associated with patient age younger than 51 years ( P < .001), chronic carditis ( P = .01), and chronic proton pump inhibitor use ( P = .008). Surprisingly, we also found significant association between PAM and chronic nonsteroidal anti-inflammatory drug use ( P < .001). These associations, including that with chronic nonsteroidal anti-inflammatory drug use, remained significant in multivariate analysis. CONCLUSIONS.­: Our findings confirm the previous reports of significant association between PAM and chronic carditis and the findings from animal studies of association with chronic proton pump inhibitor use. The strong association with chronic nonsteroidal anti-inflammatory drug use has not been previously reported and warrants further studies.

In vitro comparison of an Er:YAG laser-activated bleaching system with different light-activated bleaching systems for color change, surface roughness, and enamel bond strength.

To compare an Er:YAG laser-activated bleaching system with different light-activated in-office bleaching systems for color change, surface roughness, and post-bleaching enamel bond strength. 51 enamel slabs were prepared from the sound buccal enamel of extracted bovine teeth. The teeth were randomly divided into three groups according to different light-activated office bleaching systems (n = 17): diode laser (Epic, Biolase) (940 nm, 7 W, continuous mode), Er:YAG laser (LightWalker, Fotona) (2940 nm, 50 mJ, 10 Hz, 1000 µs), and LED (Radii Plus) (440-480 nm, 1500 mW/cm2). All systems were used with their compatible bleaching agents according to manufacturers' recommendations. The tooth color and surface roughness (Ra) were assessed at baseline and after bleaching using a spectrophotometer and a surface profilometer, respectively. The color change was determined by the CIE L*a*b* system (ΔE, ΔL*, Δa*, Δb*). Kruskal-Wallis test was used for color change whereas Kruskal-Wallis and Wilcoxon tests were used to analyze the roughness data. For shear bond strength test (SBS), composite cylinders were bonded on bleached enamel samples 14 days after bleaching procedures and stored in water (37 °C). Specimens were then debonded with a universal testing machine at 1 mm/min and data were analyzed by using Kruskal-Wallis test. All the tested bleaching systems were effective on color change (ΔE > 3.3) and produced similar color change (p > 0.05). There were no significant differences among the Ra values of the groups neither at baseline nor after bleaching (p > 0.05). However, comparing the baseline and after bleaching Ra values, a significant increase was observed for all tested groups (p < 0.05). Significant differences were also found among all systems for SBS (p < 0.05). The highest values were obtained in Er:YAG group, whereas the LED group revealed the lowest values (p < 0.05). All tested bleaching systems were effective on tooth whitening, whereas they all led to an increase on surface roughness. Although the current Er:YAG laser-activated bleaching system did not differ from other tested bleaching systems according to color change and surface roughness, it appears to provide better results in terms of SBS.

Expression of estrogen receptor beta isoforms in pancreatic adenocarcinoma.

Limited studies have shown that some patients with pancreatic adenocarcinoma (PAC) may benefit from treatment with tamoxifen. PAC has been shown to be largely negative for estrogen receptor alpha (ER-alpha). The aim of this pilot study was to investigate ER-beta expression in human PAC. Sections of tissue microarray with 18 evaluable cases of human PAC were stained by immunohistochemistry (IHC) for ER-beta1, ER-beta2, ER-beta5, and Cyclin A. The levels of ER-beta isoform expression and the S-phase fraction (SPF) were determined using quantitative digital image analysis. Higher mean and median ER-beta2 levels correlated with male sex (p = 0.057 and p = 0.035, respectively), older age (p = 0.005 and p = 0.006, respectively), and lower pT stage (p = 0.008 and p = 0.009). Mean and median ER-beta5 levels correlated negatively with SPF (p = 0.021 and p = 0.047, respectively). Mean ER-beta1 expression did not correlate with any of the above mentioned clinicopathologic factors. The findings in this pilot study, although should be considered preliminary, suggest that some ER-beta isoforms may play a role in the biology of PAC. Additional larger studies are needed to confirm our findings, and to determine whether ER-beta may be considered for future targeted therapy.

p53 protein accumulation predicts malignant progression in Barrett's metaplasia: a prospective study of 275 patients.

AIMS: The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett's metaplasia (BM) is a predictor of malignant progression, without relying on dysplasia grading. METHODS AND RESULTS: Sections of formalin-fixed paraffin-embedded tissue from the initial biopsies of 275 patients with BM, who had no high-grade dysplasia (HGD) or oesophageal adenocarcinoma (EAC), were stained for p53 by immunohistochemistry. The mean follow-up was 41 months. p53-positive biopsies were divided into four groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan-Meier analysis with the log-rank test was used to determine the rate of progression to HGD/EAC. Of the 275 patients, 227 had initial biopsies that were completely negative for p53, and, of these, one (0.4%) progressed to HGD/EAC; none of 24 (0%) patients with scattered positive cells and none of four (0%) of patients with multifocal scattered positive cells progressed. In contrast, five of 16 (31.25%) patients with aggregates of positive cells and three of four (75%) of those with multifocal aggregates of positive cells progressed to HGD/EAC. Kaplan-Meier analysis with log-rank statistics showed the difference in progression rate between the five groups to be highly significant (P < 0.0001). CONCLUSIONS: We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.

The Effects of Desferroxamine on Bone and Bone Graft Healing in Critical-Size Bone Defects.

BACKGROUND: Autogenous bone grafts are still the criterion standard treatment option in critical-size bone defect reconstructions, and many therapies can affect its incorporation. In this study, it was aimed to research the effects of desferroxamine (DFO) application on bone and bone graft healing due to the effects of osteoblast and osteoclast regulation and stimulation of angiogenesis. METHODS: Rat zygomatic arch critical-size bone defect model (5 mm) was used as the experimental model. Thirty-two Sprague-Dawley rats (64 zygomatic arches) were divided into 4 groups (16 zygomatic arches in each). In groups 1 and 2, defects were reconstructed with the bone grafts harvested from the other side, and the right arc was named as group 1, and the left was group 2. At group 1, 200 µM/300 µL dosage of DFO was injected at the zygomatic arch region starting at the seventh day preoperatively and lasting until the 45th day postoperatively. Group 2 animals were defined as the control group of group 1, and 0.9% NaCl injection was applied. In groups 3 and 4, there was no repair after the formation of defects, and the right arc region was treated with DFO, and left was treated with 0.9% NaCl for postoperative 45 days, respectively. Radiological (computed tomography), histological (hematoxylin-eosin), and biomechanical (3-point bending test) tests were used for the evaluation. RESULTS: In radiological evaluation, there was a statistically significant decrease (P < 0.05) in bone defect size in group 3 animals at the 4th, 8th, and 12th weeks, and bone graft volume showed a statistical difference at all weeks (P < 0.05). In histological evaluation, it was observed that there was an increase in osteoblast number and vascularity rates (P < 0.05) in the DFO-treated groups at all weeks. Biomechanical evaluation of the subjects showed increase in bone strength in group 1 animals at 12 weeks. CONCLUSIONS: In this study, it was shown that DFO treatment increased bone graft incorporation and healing in critical-size bone defects. In this aspect, we suggest that DFO can be used to increase graft incorporation in risky areas and reduce the defect size in patients who are not suitable for vascularized bone graft transfer.

Rate and Predictors of Endoscopic Mucosal Healing in Biologic Naive Patients with Inflammatory Bowel Disease by Azathioprine Treatment: A Real World, 10 Years' Experience from a Single Centre in Turkey.

BACKGROUND: There is increasing evidence that endoscopic mucosal healing (EMH) is a key target in inflammatory bowel disease (IBD) therapy. However, there is limited evidence of EMH rates with conventional IBD therapy outside of Western population groups. AIM: To evaluate the role of azathioprine (AZA) in inducing EMH in IBD patients. METHODS: Patients with inflammatory bowel disease were evaluated in terms of endoscopic mucosal healing and the incidence of surgical interventions during the azathioprine treatment between 1995 to 2014. RESULTS: A total of 120 inflammatory bowel disease patients were enrolled. Endoscopic mucosal healing was found in 37% patients with inflammatory bowel disease (42% in chronic ulcerative colitis and 33% in Crohn's disease). Male gender had a negative impact on the efficacy of azathioprine (P<0.05). Responder inflammatory bowel disease patients were older (age at the IBD diagnose) than the nonresponder (P<0.05). Azathioprine therapy reduced the number of the surgical interventions (P<0.05). CONCLUSION: We showed that azathioprine therapy significantly induced endoscopic mucosal healing in biologic naïve patients with active inflammatory bowel disease as well as decreasing the surgical interventions, with negative predictive factors identified by a younger age at IBD presentation and male gender.