Complete Endoscopic Remission Research Articles

Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial

BackgroundThe primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial.Design and methodsThe ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life.DiscussionThe ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients.Trial registrationDutch Trial Register (NTR) NTR2883. Registered May 3, 2011. ISRCTN, ISRCTN60945764. Registered August 12, 2019.

The role of granulocyte-macrophage colony-stimulating growth factor in inflammatory bowel diseases

Inflammatory bowel diseases, which include ulcerative colitis and Crohn's disease, are chronic immune-inflammatory diseases of the intestine that are increasing in prevalence and incidence worldwide. They are progressive, with the need for lifelong therapy, a high risk of surgical interventions and a decrease in the quality of life of patients. The results of clinical and population studies indicate that the possibilities of modern therapy for inflammatory bowel diseases have reached their maximum. Its effectiveness in achieving complete clinical and endoscopic remission, despite the use of genetically engineered biological drugs, is estimated at 35-40%, which is obviously insufficient. A possible solution to this problem could be the inclusion of granulocyte-macrophage colony-stimulating factors in treatment regimens for inflammatory bowel diseases in combination with glucocorticosteroids, cytostatics and biological therapy drugs. A review of a number of experimental and clinical studies that confirmed the clinical effectiveness of macrophage growth factors is the subject of this article.

Multi-modal conservative management of intra-abdominal collections in fistulising Crohn’s disease

Background and Objectives: The management of intra-abdominal collections in fistulising Crohn’s disease (CD) has traditionally involved surgery. However, conservative management is a potential alternative. In this study, we report our experience with multi-modal conservative management of intra-abdominal collections secondary to perforating CD. Methods: Medical records of CD patients with a history of intra-abdominal collections or fistulas over the past five years were reviewed retrospectively. Patients were included if they were initially managed conservatively using any combination of antibiotics, exclusive enteral nutrition (EEN), percutaneous drainage of collections, endoscopic dilatation of associated strictures and medical therapy for IBD with steroids, immunomodulators and/or biologics. Results: Eleven participants were included. All participants had penetrating CD affecting the terminal ileum. Nine participants had intra-abdominal collection on cross-sectional imaging whilst the remaining two participants had fistulising disease and sepsis without a discrete collection. Eight participants completed a 6–8 weeks course of EEN. All participants were treated with antibiotics and a thiopurine. Steroids were used in eight participants and biological agents in six. Six participants underwent endoscopic dilatation of small bowel strictures. After a median follow up of 20 months [range: 3–210] nine participants had evidence of adequate clinical, biochemical, radiological and endoscopic improvement. Complete resolution of abscess was seen in 4/7 participants and a significant reduction in abscess size was seen in 2/7. Two participants had complete endoscopic and histological remission and complete resolution of abscess. Both participants with fistulising disease (without a collection) had evidence of healed fistula tract on progress imaging and endoscopy. Two participants underwent surgery after failure of initial conservative management. Conclusion: Intra-abdominal collections in fistulising CD can be managed successfully in appropriately selected patients using a multi-modal approach incorporating antibiotics, EEN, endoscopic dilatations of culprit strictures and optimised medical management using steroids (for induction of remission), immunomodulators and biologics.

P955 The effect of appendicectomy on the clinical course of Ulcerative Colitis: Preliminary results

Abstract Background Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies have suggested a beneficial effect of appendicectomy in inducing and maintaining remission. Therefore, appendicectomy may be considered as an alternative or adjunctive treatment in UC. Aim To evaluate the efficacy of appendicectomy in maintaining remission in UC patients. Methods Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score &amp;lt;3 with endoscopic subscore of 0 or 1) following medical induction treatment for disease relapse within 12 months prior to randomisation, were enrolled in the Netherlands and United Kingdom. Patients were randomised (1:1) to undergo appendicectomy (intervention group) or continue maintenance medical therapy (control group). The primary outcome was the one-year UC relapse rate (defined as a total Mayo-score score ≥5 with endoscopic subscore of ≥2). To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed to achieve 80% power. The last patient was included in September 2022, so analysis of the primary outcome parameter is expected to start soon. Trial progress, including the accumulated number of (serious) adverse events (SAE) in both groups, were presented annually to the Data Safety Monitoring Board. Therefore safety data is available. Results In total, 99 patients were included in the intervention group and 99 patients in the control group. There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having proctitis (38.9%) or left sided colitis (35.9%). Three SAEs were reported in the appendicectomy group, 2 of which were related to the surgical procedure (reintervention for obstructive ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). The one-year reported colitis-associated adverse event rate was significantly lower in the appendicectomy group when compared to the control group (46.4% vs. 63.9%, P=0.02). During follow up there were no colectomies in the appendicectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group. Conclusion Appendicectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events. These results suggest that the final analysis of the primary outcome parameter (relapse rate) could demonstrate that appendicectomy is superior to standard medical therapy alone in maintaining remission in these patients.

A novel artificial intelligence–assisted “vascular healing” diagnosis for prediction of future clinical relapse in patients with ulcerative colitis: a prospective cohort study

Background and AimsImage-enhanced endoscopy (IEE) has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)-assisted IEE may help non-experts to provide objective accurate predictions using optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose “vascular-healing” and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC. MethodsThis open-label, prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histological assessment were recorded for six colorectal segments from each patient. Patients were followed-up for 12 months. Clinical relapse was defined as a partial Mayo score >2 ResultsThe clinical relapse rate was significantly higher in the AI-based vascular-active group [23.9% (16/67)] compared with the AI-based vascular-healing group [3.0% (1/33)] (P=0.01). In a sub-analysis predicting clinical relapse in patients with MES ≤1, the area under the curve for the combination of complete endoscopic remission and vascular-healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65). ConclusionsAI-based vascular healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable.

Эффективность и безопасность пантопразола в лечении пациентов с кислотозависимыми заболеваниями в России: многоцентровое наблюдательное исследование

The aim – evaluate the clinical effect and adherence to pantoprazole (Nolpaza®) therapy in patients with acid-dependent diseases in real clinical practice. Pantoprazole occupies a special place among various representatives of proton pump inhibitors (PPI) due to the peculiarities of its pharmacokinetics and pharmacodynamics. Thus, the area under the curve (AUC), correlating with the severity of acid-suppressive effect, is significantly higher for pantoprazole than for other PPIs. In addition, pantoprazole has a longer-lasting antisecretory effect because it is the only PPI that binds to both cysteine 813 and deep-lying cysteine 822. Of all PPIs, pantoprazole least blocks the CYP2C19 isoenzyme involved in multidrug metabolism, ensuring minimal drug interactions. Material and methods. Data collection for further analysis was performed using specially designed electronic individual registration cards of two groups of patients: the first – patients with gastroesophageal reflux disease (GERD), receiving therapy with Nolpaza®; the second – patients with peptic ulcer disease (PU) / erosive gastritis and patients with an indication for Helicobacter pylori eradication, receiving therapy with Nolpaza® as part of the eradication therapy regimen. Conclusion. According to the results of the conducted study it was possible to evaluate the clinical effect and tolerability of Nolpaza® therapy using the data of more than 14 thousand patients with GERD, gastritis, duodenitis, gastric and duodenal ulcer, drug-induced gastropathy, 98% of whom had gastrointestinal complaints before the beginning of treatment, while by the end of therapy the complaints remained in full in less than 1% of patients. The results of esophagogastroduodenoscopy at the end of therapy with Nolpaza® confirmed positive dynamics in 99.8% of cases, and the vast majority of patients achieved complete endoscopic remission. Positive dynamics was also observed in the majority of patients who were tested for H. pylori infection. The efficacy of eradication therapy with Nolpaza® amounted to 88.2%. The study provided a high assessment of patient adherence throughout the follow-up period.

Helicobacter pylori eradication treatment for primary gastric diffuse large B-cell lymphoma: A single-center analysis.

Unlike the already established effect of Helicobacter pylori (H. pylori) eradication on gastric mucosa-associated lymphoid tissue (MALT) lymphoma, its therapeutic effect on primary gastric diffuse large B-cell lymphoma (DLBCL) is still unclear. To clarify the efficacy of H. pylori eradication treatment for primary gastric DLBCL. We reported on 3 new cases, and added them to 3 previously reported cases. We analyzed the usefulness of H. pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center. Of the 6 patients (27-90 years old, 3 males and 3 females), all 3 patients with single lesions (one transformed from MALT lymphoma) achieved complete remission (CR) after H. pylori eradication. Regarding the 2 newly reported cases, CR was maintained for more than 6 years with eradication treatment alone. In contrast, none of the 3 patients with 2 lesions achieved CR. In 1 newly reported case, endoscopic CR was achieved in one lesion, while stable disease was obtained in the other lesion. Two patients with progressive disease responded to standard chemotherapy ± radiation and remained in CR for more than 6 years. We believe it is worthwhile to attempt H. pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Inflammatory Bowel Diseases: Does One Histological Score Fit All?

Mucosal healing (MH) is the main treatment target in ulcerative colitis (UC) and Crohn’s disease, and it is defined by the combination of complete endoscopic and histologic remission. The complete resolution of mucosal inflammation should be confirmed by histology but its assessment is not always univocal. Neutrophil infiltration represents the unique histological marker in discriminating the active vs. quiescent phases of the disease, together with crypt injuries (cryptitis and crypt abscesses), erosions, and ulcerations. On the contrary, basal plasmacytosis is not indicative of activity or the remission of inflammatory bowel diseases (IBDs) but instead represents a diagnostic clue, mostly at the onset. Several histological scoring systems have been developed to assess grade severity, particularly for UC. However, most are complex and/or subjective. The aim of this review was to summarize available scores, their characteristics and limitations, and to present the advantages of a simplified mucosa healing scheme (SHMHS) based on neutrophils and their distribution in the gut mucosa. Finally, we overview future developments including artificial intelligence models for standardization of disease assessments and novel molecular markers of inflammation with potential application in diagnostic practice.

Association of the ILR1 and FAS gene variants with primary nonresponse to anti-tumor necrosis factor therapy in patients with Crohn disease.

Crohn disease (CD) is a chronic inflammatory disease characterized by an uncontrolled immune response of the intestinal mucosal cells to antigens derived from the gut lumen. Specifically, the introduction of anti-tumor necrosis factor (TNF) drugs has changed the approach to the treatment of inflammatory bowel disease, and set new therapeutic goals, such as that of controlling clinical symptoms while simultaneously achieving complete endoscopic and mucosal remission. The mechanisms of action of anti-TNF drugs-and consequently the mechanisms of resistance to anti‑TNF therapy-are unknown. Our study was an attempt to discover whether the potential mechanism of nonresponse may be conditioned by polymorphisms in the genes involved in independent inflammatory or apoptotic pathways. The study included 196 diagnosed and clinically characterized Polish patients with CD treated with anti‑TNF therapy. Variants rs7539036, rs2041747, rs5746053, rs5746054, rs1061624, rs1143634, rs7896789, and rs55790676 of the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes were genotyped using Sanger sequencing, and analyzed in the context of response to biologic treatment. We observed that 33 patients (16.8%) did not respond to the therapy, which was associated with carrying the rs2041747 G allele variant of the ILR1 gene (odds ratio [OR], 3.72; P = 0.009). Moreover, the presence of the FAS rs7896789 homozygous CC genotype correlated with increased susceptibility to the lack of response to the anti‑TNF therapy (OR, 15.22; P = 0.003), whereas TT was identified as a potentially protective genotype. In patients with CD treated with anti‑TNF drugs, complex pathways with multigene conditioning participate in the mechanism underlying treatment resistance. The genes involved in apoptosis, FAS and ILR1, seem to play an essential role in the lack of response to the treatment, and would be interesting objects of further population and functional research.

VEDOLIZUMAB, USTEKINUMAB AND TOFACITINIB AS TRIPLE THERAPY FOR ULCERATIVE COLITIS

Abstract BACKGROUND Therapies for ulcerative colitis include mesalamine, immunomodulators, biologics, and small molecules. Unfortunately, patient response is not universal, and efficacy can diminish with time, postulated to be from increased drug clearance, anti-drug antibodies with biologics, and immune mediated pathogenesis changes. Biologic combinations have been investigated for producing synergistic drug effects and extending targeted therapy in patients lacking monotherapy response, with promise shown in two drug combinations (1), but not investigated using three. CASE A 20-year-old Caucasian male with UC presented in August 2015 following 1 month hospitalization for Clostridium difficile infection. He had 2 infusions of infliximab 10 mg/kg continued post-discharge, and started mesalamine 4.8gm qd, 6-mercaptopurpine (6MP) 100mg qd, and prednisone taper. By November 2015, colonoscopy showed severe Mayo 3 pancolitis. Due to insufficient response 6MP and infliximab were discontinued and he started vedolizumab. August 2016 colonoscopy had chronic colitis with Mayo 2 inflammation of the ascending, transverse, descending and rectosigmoid colon so prednisone 40mg was initiated and vedolizumab increased to vedolizumab q4 weeks. He responded well clinically and was tapered off prednisone by October 2016. November 2016 colonoscopy had right sided colitis resolution with residual proctosigmoiditis (Mayo 2); May 2017 colonoscopy still had rectosigmoid inflammation (Mayo 2) with chronic active colitis, so ustekinumab q8 weeks was added. December 2017 colonoscopy was unimproved so ustekinumab increased to q4 weeks, prednisone was increased, and he requested addition of budesonide and mesalamine. With clinical improvement, prednisone was tapered by February 2020. However, December 2020 colonoscopy showed severe (Mayo 3) recto-sigmoiditis with mild colitis in the descending to transverse colon, so tofacitinib XR 22 mg qd was added. He improved clinically, so budesonide was discontinued in February 2021. November 2021 colonoscopy showed complete endoscopic remission (Mayo 0) so he initiated de-escalation with initially discontinuing mesalamine and increasing ustekinumab initially to q8 week intervals and later vedolizumab to q8 weeks with maintenance of clinical remission. Given marginal effect, ustekinumab was discontinued initially and later, tofacitinib was discontinued. He remains in remission on vedolizumab q8 weeks monotherapy. CONCLUSION Combination therapies may be considered for suitable patients experiencing severe, refractory disease. Although patients with multiple comorbidities, frailty, immunosuppression or certain contraindications may not be well suited, this patient presents as an ideal candidate with no comorbidities and few other therapeutic options. REFERENCES (1) Privitera G et al. Combination therapy in IBD. Autoimmunity Reviews. 2021 Jun 1;20(6):102832.

S66 Leukocytoclastic Vasculitis in a Crohn’s Disease patient with recent Sars-CoV2 infection

Case: Prior to the COVID-19 pandemic, leukocytoclastic vasculitis (LCV) had been described in association with a variety of chronic infections, autoimmune disorders, and medications. In the inflammatory bowel diseases (IBD) population, LCV has been reported as a rare cutaneous, extraintestinal manifestation, which may be related to the disease itself or associated with the use of biologic medications, particularly those that target tumor necrosis factor. Several cases of LCV related to infection with SARS-CoV2, not related to IBD, have been reported. We present a case of LCV in a woman with Crohn’s Disease (CD) who was on long-term maintenance infliximab and presented with purpuric papules on bilateral lower extremities shortly after infection with SARS-CoV2. A 37-year-old female with a 26-year history of ileocolonic CD in remission for at least 2 years presents to our IBD clinic with concern of rash on both lower extremities, accompanied by significant ankle pain. She had been on infliximab for 10 years. The symptoms began 1 month prior, 2 months after being diagnosed with COVID-19. She denied any concurrent GI symptoms that were new or worsened from her baseline. Lab evaluation was notable for positive ANA, elevated to 1:160. She had normal ANCA, anti-myeloperoxidase antibody, anti-dsDNA antibody, total IgG and total IgM, and rheumatoid factor. Skin punch biopsy showed fibrinoid necrosis of capillary walls within the dermis with surrounding neutrophils and karyorrhectic debris, findings consistent with LCV. Colonoscopy showed complete endoscopic remission of CD. An oral steroid taper lead only to temporary improvement and symptoms recurred at a dose of 10 mg prednisone. Due to suspicion of infliximab-associated LCV, infliximab was discontinued, and ustekinumab therapy was initiated. She was able to taper off steroids, and the rash completely resolved. LCV falls within a general category of cutaneous small vessel vasculitis; it is limited specifically to the skin, with no systemic or renal involvement. Patients typically present with palpable purpura, at times associated with urticaria. When IBD patients present with these findings, providers should review recent infectious symptoms, medication changes or drug exposure. Direct immunofluorescence should be performed on skin biopsy for lesions lasting >= 4 weeks. For symptoms < 4 weeks, conservative therapy with oral anti-histamine, and compression stockings have been effective. Implicated drugs should be stopped. For severe cases, systemic therapy with prednisone is recommended; dapsone or colchicine have also been used. When LCV has been discovered in the setting of COVID infection, treatment approaches have been varied, including topical and oral steroids, low molecular weight heparin, and intravenous immunoglobulin (IVIG). Prior to this case, there has been one case describing successfully treatment of LCV in CD with IVIG. Because this is a rare entity, no randomized controlled trials have been performed to evaluate safety or efficacy of specific therapies. While rare, LCV is an important pathology that IBD providers should be comfortable diagnosing and may only increase as COVID-19 remains common. Importantly, we must be aware that management of LCV will likely involve change in therapy for IBD, as medications are often implicated.

Two-Stage Phase II Study of Envafolimab Combined with Endostar and Concurrent Chemoradiotherapy in Treatment of Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: Preliminary Results of Stage 1

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CRT) is the standard of care for patients with unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). In the era of immunotherapy, we performed a single-center, open-label phase II study of CRT combined with endostar (inhibitor of tumor angiogenesis) and envafolimab (PD-L1 checkpoint inhibitor) in patients with LA-ESCC. <h3>Materials/Methods</h3> Treatment-naïve patients with LA-ESCC were enrolled. Radiologists evaluated each patient to exclude the risk of esophageal fistula before enrollment. Involved field radiotherapy at doses of 50.4 Gy (1.8Gy QD), two cycles of paclitaxel liposome (150 mg /m²) and carboplatin (AUC=5) Q4W and 5 cycles of endostar (75mg × 48h, QW) were delivered. Envafolimab at 400 mg subcutaneous injection Q4W was started concurrently with CRT and continued for up to 12 cycles. In Stage 1, the primary endpoint was safety and tolerability. Secondary endpoint was objective response rate and the rate of endoscopic complete remission (EsCR) defined as absence of invasive cells in esophagoscopic biopsy. Responses were assessed by positron emission tomography-computed tomography (PET-CT) at baseline, 12 weeks after the CRT, and computed tomography (CT) at 4 weeks after the CRT, every 12 weeks thereafter. The esophagoscopic examination and biopsy were monitored at baseline, after 41.4 Gy radiation, and 1 month after the CRT To evaluate the efficacy. <h3>Results</h3> Between Sep. 8, 2021 and Nov. 15, 2022, 10 patients were enrolled in Stage-1. Treatment-related adverse events (TRAE) occurred in 9 (90%) patients, the most common of which was fatigue (30%), nausea (40%), thrombocytopenia (20%), leucopenia (60%), acute esophagitis (40%), thyroid dysfunction (10%), and Rash (20%). These occurred predominantly at grade 1 or 2 severity. The most frequent TRAE of grade 3 or worse was leucopenia (40%). No patient had pneumonitis, esophageal fistula. There were no deaths or treatment discontinuations due to serious adverse events. CT scan was completed in 10 patients, esophagoscopic examination biopsy in 9 of them, at 4 weeks after the CRT. All patients had a decrease in target lesion size on CT. The objective response rate was 100%. The pathology report of 8 patients revealed no cancerous cells was observed, resulting in an EsCR rate of 88.9%. <h3>Conclusion</h3> In the stage-1, Envafolimab combined with endostar and CRT was well tolerated with manageable toxicity for unresectable LA-ESCC patients. The preliminary results provide a basis for the ongoing stage 2 study. This trial is registered with ClinicalTrials.gov, number ChiCTR2100051606.

S2709 Rituxan-Induced Colitis

Introduction: Rituximab is a monoclonal antibody which is increasingly being used to treat autoimmune disorders and certain cancers. With this, we are also coming across Gastrointestinal toxicities. These are, however, usually self limited diarrhea and abdominal pain requiring supportive management. We present a case of a patient who developed Crohn’s disease after use of Rituximab requiring long term immunosuppressive therapy. Case Description/Methods: 67-year-old lady came in with 6 months of generalized lower abdominal pain and 7-9 episodes of watery diarrhea, along with unintentional weight loss. She had a history of well controlled Rheumatoid Arthritis/ Mixed connective tissue disease on Rituximab, failing multiple therapies in the past. CT abdomen showed Mural thickening in Terminal ileum, Cecum, and Ascending colon with enteric lymphadenopathies. The patient underwent colonoscopy for further evaluation which showed Ulceration, erythema and friable mucosa in terminal Ileum. The rest of the examined colon appeared normal. Pathology showed severe active ileitis and mild active colitis in transverse colon, while rest of segments were normal. Rituximab was stopped as a therapeutic trial which significantly improved the patient's symptoms. Her CDAI score improved from 289 points to 177 points. However Inflammatory markers, Imaging and endoscopic disease, despite improving, did not resolve completely. Ustekinumab was started after extensive discussion. After 6 months she had a complete clinical, endoscopic and histopathologic remission. (Figure) Discussion: Gastrointestinal toxicities of Rituximab are a well-known entity. The exact pathophysiology of rituximab induced colitis however, remains unclear. B and T lymphocytes interact in the intestinal wall and are responsible for mucosal immunoregulation, which increases immune tolerance. With Rituximab induced depletion of CD20+ B cells there is an increase infiltration of T lymphocytes in the intestinal mucosa which can potentially cause an immunogenic response resulting in IBD like colitis. A rare disease, drug induced IBD is mild uncomplicated and short lived requiring only supportive management and discontinuation of offending agent. Only a few cases are reported where patient fails to improve and require Immunosuppressive therapy. More data is needed on how to differentiate between primary vs drug induced IBD in addition to finding the ideal agent to treat drug induced IBD and long term outcomes of this disease sub set.Figure 1.: Ulceration/inflammation in terminal Ileum.

Clinical implication of radiologic complete remission on Crohn’s Disease: Compared with endoscopic remission

ObjectivesTo determine the clinical implications of radiologic complete remission (CR) in Crohn’s disease (CD) evaluated by computed tomography (CT) or magnetic resonance enterography (MRE) in comparison with endoscopic CR. MethodsTwenty-five CD patients who achieved endoscopic CR after medical treatment were retrospectively enrolled in this study. All patients underwent ileocolonoscopy, CT, or MRE at baseline, at the time of endoscopic CR, and during follow-up. Two radiologists assessed the mural and perienteric abnormalities on pre- and post-treatment CT or MRE in consensus. Patients were divided into radiologic CR and non-CR groups at the time of endoscopic CR. CD recurrence during subsequent follow-up periods was evaluated using clinical, laboratory, and CT/MRI findings. Statistical analysis was performed to assess whether there were significant differences in patient outcomes between the groups. ResultsAt the time of endoscopic CR, nine patients (mean age, 36.6 years) showed normalization of all radiologic features and were designated as the radiologic CR group. However, 16 patients (mean age: 32.9 years) showed residual CT/MRE abnormalities, suggesting persistent active inflammation, and were designated as the radiologic non-CR group. During follow-up, there was a significant difference between the groups regarding clinical outcomes (deep CR, 8/9 vs 5/16, P = 0.011; CD recurrence, 1/9 vs 14/16, P < 0.001). The mean fecal calprotectin level was significantly lower in the radiologic CR group (287.5 ug/g) than in the non-CR group (652.4 ug/g) (P = 0.023). ConclusionsRadiologic CR can represent a better therapeutic endpoint in CD, showing superiority over endoscopic CR in predicting both clinical and biochemical outcomes.

Appendiceal Orifice Inflammation Is Associated with Lower Rate of Complete Endoscopic Remission in Patients with Ulcerative Colitis.

Appendiceal orifice inflammation (AOI) is commonly considered a skip lesion in ulcerative colitis (UC). However, the clinical significance of AOI in UC patients remains controversial. This study aimed to evaluate the clinical feature and long-term outcomes of AOI by comparing UC patients with and without AOI. This study was conducted as a retrospective design of patients who were newly diagnosed or referred within 3 months after diagnosis at Seoul St. Mary’s Hospital from 1 January 2001 to 31 December 2020. All patients underwent index and follow-up colonoscopies. The long-term outcomes involved achieving complete endoscopic remission (ER), use of biologics, hospitalization, and proximal disease extension. Complete ER was defined as Mayo endoscopic subscore 0. In total, 318 UC patients were included, of which 140 had AOI. The baseline characteristics were not significantly different between AOI and non-AOI groups. The cumulative risk of complete ER was a significant difference between AOI and non-AOI groups (p = 0.041). The other cumulative risks of disease outcomes were not significantly different between AOI and non-AOI groups (use of biologics, p = 0.542; hospitalization, p = 0.795; proximal disease extension, p = 0.403). The multivariate Cox regression analysis also revealed that AOI was the significant factor of complete ER (hazard ratio, 0.656; 95% confidence interval, 0.462–0.932; p = 0.019) in UC patients. AOI shows a significant association with lower rate of complete ER in UC patients. Therefore, a meticulous treatment strategy may be recommended to achieve complete ER in UC patients with AOI.

Top-down Versus Step-up Strategies to Prevent Postoperative Recurrence in Crohn's Disease.

The best management after ileocolonic resection is still unknown in Crohn's disease (CD). We compared step-up and top-down approaches to prevent short and long-term postoperative recurrences in CD patients. From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014-2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at 6 months) were performed with systematic colonoscopy at 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis was applied for each comparison. Among 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (46.8% vs 65.9%, P = .042) and to achieve complete endoscopic remission (Rutgeerts index = i0; 45.3% vs 19.3%; P = .004) at 6 months. We did not observe any significant difference between the 2 groups regarding clinical postoperative recurrence (hazard ratio [HR], .86 [0.44-1.66], P = .66) and progression of bowel damage (HR, 0.81 [0.63-1.06], P = .12). Endoscopic postoperative recurrence at 6 months was associated with increased risk of clinical postoperative recurrence (HR, 1.97 [1.07-3.64], P 0.029) and progression of bowel damage (HR, 3.33 [1.23-9.02], P = .018). Among the subgroup without endoscopic postoperative recurrence at 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group (HR, 0.59 [0.37-0.94], P = .025; and HR, 0.73 [0.63-0.83], P < .001, respectively). Top-down strategy should be the preferred management to prevent short and long-term postoperative recurrence in CD.

COMBINATION USTEKINUMAB AND VEDOLIZUMAB THERAPY FOR REFRACTORY INFLAMMATORY BOWEL DISEASE: A SINGLE INSTITUTION CASE SERIES

Abstract INTRODUCTION Over the past 20 years, there have been great strides in the medical management of Inflammatory Bowel Disease (IBD). The advent of anti-TNF mAb therapy was transformative in the management of IBD and the positive effects are well documented1,2,3. While anti-TNF mAb biologics induce and maintain remission in IBD, a substantial portion of patients are refractory4. Newer biologic agents such as ustekinumab (UST) and vedolizumab (VDZ) have expanded therapeutic options for patients; however, obtaining deep remission in a subset of IBD patients remains challenging. We previously reported a successful case of deep remission in a patient with refractory stricturing Crohn’s Disease (CD) treated with maximum dosage UST + VDZ therapy5. Since this report, we have expanded our use of this combination in refractory IBD with encouraging results. METHODS Fifteen refractory IBD patients (12 CD, 3 UC) at the University of Kentucky were selected to initiate dual biologic therapy (DBT) with UST and VDZ. All patients previously failed other therapies, but demonstrated partial response to escalated dosing (Q4 week) of either VDZ or UST monotherapy. To determine DBT response, we analyzed fecal calprotectin (FC), C-reactive protein (CRP), albumin, BMI, hemoglobin, Harvey Bradshaw Index (HBI)/Mayo scores, endoscopic and histologic appearance. Steroid-free remission was defined by one or more of the following: 1) endoscopic and histologic remission, 2) normalization of biomarkers (FC and CRP) or 3) clinical remission defined by normalization of clinical scores AND normalization of albumin, hemoglobin, and BMI. Clinical remission was only used when endoscopic or biomarker data was not available. RESULTS Among the 12 CD patients receiving dual biologic therapy, 11 met criteria for remission (91.6%). Six of these CD patients had complete endoscopic and histologic remission. Three CD patients did not have follow-up endoscopic or FC data, but did have normalization of albumin, CRP, hemoglobin, and HBI scores. Two CD patients were initiated on DBT for spikes in biomarkers (FC and CRP) despite clinical remission. These biomarkers normalized after initiation of DBT. One of the CD patients did not achieve response, and no one with UC (3 patients) responded. Among the successful cases, the average time to remission was 14.9 weeks. There were no adverse events or safety concerns. CONCLUSION Dual biologic therapy with combination ustekinumab and vedolizumab is a promising and safe option for patients with refractory CD, particularly in those who demonstrate a partial response to monotherapy of either agent. This combination was not successful in our UC patients. This case series adds further support for the effectiveness of VDZ+ UST combination therapy in CD. Continued investigation is merited to support routine clinical use and improve access to this combination therapy.

THE MICROBIAL LANDSCAPE OF ULCERATIVE COLITIS IN ENDOSCOPIC REMISSION

Abstract BACKGROUND Achieving endoscopic remission (Mayo endoscopic score of 1 or 0) appears to be the optimal clinical target in ulcerative colitis, reducing risk of relapse, hospitalizations, complications, and need for surgery. While attaining complete endoscopic remission (MES 0) appears to reduce these risks further over mild endoscopic activity (MES 1), the etiologic factors for why MES 0 might be the superior target is poorly understood. Given the putative role of the gut microbiome in driving underlying endoscopic activity and subsequent relapse risk, we sought to define the microbial landscape of UC among patients who achieve either MES 0 vs MES 1 endoscopic remission, especially since the colonic microbial constituents of UC in remission remain uncharacterized. METHODS We performed a retrospective cohort study, utilizing data from The Study of a Prospective Adult Research Cohort with IBD (SPARC IBD), part of the IBD Plexus network established by the Crohn’s and Colitis Foundation. SPARC IBD is a national, multi-center, longitudinal cohort study enrolling eligible (&amp;gt;= 18 years) patients with IBD that includes demographic and disease specific clinical data, endoscopic scores, and stool metagenomics. To examine the microbiome, we evaluated beta-diversity (Bray-curtis dissimilarity), and phylum and genera-level differential taxal abundance, utilizing linear models (limma), between patients with UC in either MES 1 vs MES 0 endoscopic remission. Statistical analysis was performed using phyloseq and limma packages in R (ver 4.1). RESULTS Within the SPARC cohort, we identified 77 patients in endoscopic remission (48 with MES 0, 29 with MES 1), of which 52% were female and 91% white, with median age of 48. Patients in MES 0 or MES 1 had no significant differences in exposure to anti-TNF therapy (50% vs 50%), vedolizumab (25% vs 19%) or mesalamine (69% vs 72%). Beta-diversity was similar between MES 0 and MES 1 remission [Figure 1]. Both MES 1 and MES 0 remission were dominated by Bacteroidetes and Firmicutes, and were specifically abundant for Bacteroides uniformis, unclassified Subdoligranulum, and Akkermansia mucuniphila. Compared to MES 1 remission, patients with MES 0 remission had increased abundance of Bacteroidetes, Firmicutes, and Actinobacteria, but reduced levels of Proteobacteria and Verrucomicrobia, although after adjusting for multiple comparisons, differential abundance at the phylum and taxa-level between both groups were comparable [Figure 2]. CONCLUSIONS The microbial landscape of ulcerative colitis in MES 1 vs MES 0 endoscopic remission is comparable with respect to beta-diversity, phylum and genera-level differential taxal abundance. Further investigation will include comparison of UC in remission to healthy controls, and whether the presence of specific microbial groups in remission can predict subsequent relapse.

P228 Appendiceal Orifice Inflammation Is Associated with Lower Rate of Complete Endoscopic Remission in Patients with Ulcerative Colitis

Abstract Background Appendiceal orifice inflammation (AOI) is commonly considered a skip lesion in ulcerative colitis (UC). However, the clinical significance of AOI in UC patients remains controversial. This study aimed to evaluate the clinical feature and long-term outcomes of AOI by comparing UC patients with and without AOI. Methods This study was conducted as a retrospective design of patients who were newly diagnosed or referred within 3 months after diagnosis at Seoul St. Mary’s Hospital from January 1, 2001 to December 31, 2020. All patients underwent index and follow-up colonoscopies. The long-term outcomes involved achieving complete endoscopic remission (ER), use of biologics, hospitalization, and proximal disease extension. Complete ER was defined as Mayo endoscopic subscore 0. Results In total, 318 UC patients were included, of which 140 had AOI. The baseline characteristics were not significantly different between AOI and non-AOI groups. The cumulative risk of complete ER was a significant difference between AOI and non-AOI groups (p=0.041). The other cumulative risks of disease outcomes were not significantly different between AOI and non-AOI groups (use of biologics, p=0.542; hospitalization, p=0.795; proximal disease extension, p=0.403). The multivariate Cox regression analysis also revealed that AOI was the only significant factor of complete ER (hazard ratio, 0.636; 95% confidence interval, 0.446–0.906; p=0.012) in UC patients. Conclusion AOI shows a significant association with lower rate of complete ER in UC patients. Therefore, a meticulous treatment strategy may be recommended to achieve complete ER in UC patients with AOI.