Complete Histological Remission Research Articles

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.

Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease: A 13 Center Correlative Study.

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated. The aim of this study was to rigorously assess patterns of histologic mucosal recovery at follow-up in celiac disease and to correlate findings with clinical data. Gastrointestinal pathologists from 13 centers evaluated initial and follow-up duodenal biopsies from 181 celiac disease patients. Marsh scores and intraepithelial lymphocytes (IELs)/100 enterocytes were assessed blindly. Histology at follow-up was correlated with symptoms, immunoglobulin A anti-tissue transglutaminase titers and gluten-free diet adherence. Fifty-six/181 (31%) patients had persistent villous blunting and 46/181 (25%) patients had just persistently elevated IELs at follow-up, with only 79/181 (44%) patients having complete histologic remission. IEL normalization (82/181; 45%) lagged villous recovery (125/181;69%). In a minority of patients, villous blunting was limited to proximal duodenal biopsies. No correlation was found between Marsh scores and symptoms, normalization of immunoglobulin A anti-tissue transglutaminase serology, or diet adherence. Children showed greater recovery of Marsh score (P<0.001) and IELs (P<0.01) than adults. Persistent mucosal injury is common in celiac disease, with discordant villous/IEL normalization. Pathologist awareness of expected findings in celiac disease follow-up biopsies, including their frequent lack of correlation with clinical data, is important for patient management, and has implications for eligibility criteria for therapeutics currently in development.

Endoscopic Submucosal Dissection for Treatment of Localized Gastric Mucosa-associated Lymphoid Tissue Lymphoma: A Case Series

Background/Aims: The treatment for gastric mucosa-associated lymphoid tissue lymphoma (MALToma) generally involves eradication of &lt;i&gt;Helicobacter pylori&lt;/i&gt;. However, MALToma lesions may recur even without &lt;i&gt;H. pylori&lt;/i&gt; re-infection. Furthermore, the remission rate of &lt;i&gt;H. pylori&lt;/i&gt;-negative MALToma after eradication is low. Therefore, herein, we report on endoscopic submucosal dissection (ESD) as a treatment strategy for gastric MALToma.Methods: We retrospectively reviewed the data of all patients of gastric MALToma who underwent endoscopic resection at our institution between January 2000 and December 2021. Clinical remission was defined as complete histological remission or probable minimal residual disease according to the GELA grading system for post-treatment evaluation of gastric MALToma.Results: Six patients with gastric MALToma underwent ESD. Two patients were diagnosed with gastric MALToma, which improved after eradication treatment and relapsed approximately 36 and 41 months later, respectively. These patients had singular lesions localized to the mucosa and did not experience &lt;i&gt;H. pylori&lt;/i&gt; re-infection. The lesions were successfully removed via ESD. The remaining four patients had &lt;i&gt;H. pylori&lt;/i&gt;-negative gastric MALToma. These patients also had single, localized lesions that were removed via ESD. All the patients remained in clinical remission until the final follow-up.Conclusions: ESD is a safe and effective intervention for &lt;i&gt;H. pylori&lt;/i&gt;-negative gastric MALToma when the lesion is single and confined to the mucosal layer.

Prospective study of an amino acid–based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial

Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically. We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE. Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome. Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P= .002) and duodenum (P= .001). Scores improved in overall PhGA (P= .002); EGREFS (P= .003); EGDP (P= .002); SODA pain intensity (P= .044), non-pain (P= .039), and satisfaction (P= .0024); and PROMIS depression (P= .0078) and fatigue (P= .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject. An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis. gov Identifier: NCT03320369.

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.

One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial

Empirical elimination diets are effective for achieving histological remission in eosinophilic oesophagitis, but randomised trials comparing diet therapies are lacking. We aimed to compare a six-food elimination diet (6FED) with a one-food elimination diet (1FED) for the treatment of adults with eosinophilic oesophagitis. We conducted a multicentre, randomised, open-label trial across ten sites of the Consortium of Eosinophilic Gastrointestinal Disease Researchers in the USA. Adults aged 18-60 years with active, symptomatic eosinophilic oesophagitis were centrally randomly allocated (1:1; block size of four) to 1FED (animal milk) or 6FED (animal milk, wheat, egg, soy, fish and shellfish, and peanut and tree nuts) for 6 weeks. Randomisation was stratified by age, enrolling site, and gender. The primary endpoint was the proportion of patients with histological remission (peak oesophageal count <15 eosinophils per high-power field [eos/hpf]). Key secondary endpoints were the proportions with complete histological remission (peak count ≤1 eos/hpf) and partial remission (peak counts ≤10 and ≤6 eos/hpf) and changes from baseline in peak eosinophil count and scores on the Eosinophilic Esophagitis Histology Scoring System (EoEHSS), Eosinophilic Esophagitis Endoscopic Reference Score (EREFS), Eosinophilic Esophagitis Activity Index (EEsAI), and quality of life (Adult Eosinophilic Esophagitis Quality-of-Life and Patient Reported Outcome Measurement Information System Global Health questionnaires). Individuals without histological response to 1FED could proceed to 6FED, and those without histological response to 6FED could proceed to swallowed topical fluticasone propionate 880 μg twice per day (with unrestricted diet), for 6 weeks. Histological remission after switching therapy was assessed as a secondary endpoint. Efficacy and safety analyses were done in the intention-to-treat (ITT) population. This trial is registered on ClinicalTrials.gov, NCT02778867, and is completed. Between May 23, 2016, and March 6, 2019, 129 patients (70 [54%] men and 59 [46%] women; mean age 37·0 years [SD 10·3]) were enrolled, randomly assigned to 1FED (n=67) or 6FED (n=62), and included in the ITT population. At 6 weeks, 25 (40%) of 62 patients in the 6FED group had histological remission compared with 23 (34%) of 67 in the 1FED group (difference 6% [95% CI -11 to 23]; p=0·58). We found no significant difference between the groups at stricter thresholds for partial remission (≤10 eos/hpf, difference 7% [-9 to 24], p=0·46; ≤6 eos/hpf, 14% [-0 to 29], p=0·069); the proportion with complete remission was significantly higher in the 6FED group than in the 1FED group (difference 13% [2 to 25]; p=0·031). Peak eosinophil counts decreased in both groups (geometric mean ratio 0·72 [0·43 to 1·20]; p=0·21). For 6FED versus 1FED, mean changes from baseline in EoEHSS (-0·23 vs -0·15; difference -0·08 [-0·21 to 0·05]; p=0·23), EREFS (-1·0 vs -0·6; difference -0·4 [-1·1 to 0·3]; p=0·28), and EEsAI (-8·2 vs -3·0; difference -5·2 [-11·2 to 0·8]; p=0·091) were not significantly different. Changes in quality-of-life scores were small and similar between the groups. No adverse event was observed in more than 5% of patients in either diet group. For patients without histological response to 1FED who proceeded to 6FED, nine (43%) of 21 reached histological remission; for patients without histological response to 6FED who proceeded to fluticasone propionate, nine (82%) of 11 reached histological remission. Histological remission rates and improvements in histological and endoscopic features were similar after 1FED and 6FED in adults with eosinophilic oesophagitis. 6FED had efficacy in just less than half of 1FED non-responders and steroids had efficacy in most 6FED non-responders. Our findings indicate that eliminating animal milk alone is an acceptable initial dietary therapy for eosinophilic oesophagitis. US National Institutes of Health.

Diagnosis and Treatment for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first reported in 1984, shows an indolent clinical course. However, the detailed clinicopathological characteristics of gastric MALT lymphoma have not been fully elucidated. We performed a literature search concerning the clinical features and treatment for gastric MALT lymphoma using PubMED. MALT lymphomas develop in single or multiple extranodal organs, of which the stomach is one of the most frequent sites; gastric MALT lymphoma accounts for 7% to 9% of all B-cell lymphomas, and 40% to 50% of primary gastric lymphomas. The eradication of Helicobacter pylori (H. pylori) is the first-line treatment for patients with gastric MALT lymphoma, regardless of the clinical stage. Approximately 60-90% of cases with stage I/II1 disease only achieve a complete histological response via H. pylori eradication. In patients who do not respond to H. pylori eradication therapy, second-line treatments such as watch-and-wait, radiotherapy, chemotherapy, rituximab immunotherapy, and/or a combination of these are recommended. Thus, H. pylori plays a causative role in the pathogenesis of gastric MALT lymphoma, and H. pylori eradication leads to complete histological remission in the majority of cases.

TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN.

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy.

To assess the short- and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in real-world practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness. We collected data regarding the efficacy of PPIs during this cross-sectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of <15 eosinophils (eos)/high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis. After induction therapy, histological and clinico-histological remission were observed in 51.4% (n = 346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility [odds ratio (OR), 9.20; 95% confidence interval (CI), 2.10-40.16], and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n = 108) and 16 months (n = 34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild. We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a step-down strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.

Measurable residual disease in childhood B-cell acute lymphoblastic leukemia.

Measurable residual disease in childhood B-cell acute lymphoblastic leukemia.

Efficacy of Topical Corticosteroid Monotherapy in Inducing and Maintaining Clinical and Histologic Remission in Adolescent and Adult Patients with Eosinophilic Esophagitis: a Systematic Review and Meta-Analysis

Background: Eosinophilic esophagitis (EoE) is the second most common cause of esophagitis. Topical steroids represent a promising group of drugs for inducing and maintaining clinical and histological remission in these patients.Objective. To evaluate the effectiveness of topical steroids in inducing and maintaining clinical and histological remission in adolescent and adult patients with EoE.Methods. A systematic literature search using defined keywords was performed up to March 20, 2021 in the MEDLINE / PubMed, EMBASE (Excerpta Medica), and Cochrane Central Register of Controlled Trials, ClinicalTrial.gov databases.Results. 390 patients from 5 studies were included in this systematic review with meta-analysis. The meta-analysis showed that topical steroids, compared with placebo, was more effective in inducing (odds ratio (OR) 75.77; 95 % confidence interval (CI): (21.8; 263.41), p &lt; 0.001) and maintaining complete histological remission (OR 103.65; 95 % CI: (36.05; 298.01), p &lt; 0.001) in patients with EoE. Also, topical steroids significantly relieved disease symptoms compared with placebo in inducing and maintaining clinical remission (OR 4.86; 95 % CI: (1.4; 16.86), p = 0.01) and (OR 11.06; 95 % CI: (4.62; 26.45), p &lt; 0.001) respectively.Conclusions. Topical steroids represent an effective group of drugs for inducing and maintaining histologic and clinical remission in adolescent and adult patients with EoE.

Characterization and clinical management of abnormal cytology findings in pregnant women: a retrospective analysis

PurposeThe diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women.MethodsData of pregnant patients with suspected cervical dysplasia who presented to the University Women’s Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated.Results142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred.ConclusionsWatchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated.

Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial

ObjectiveIn a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL. MethodsPhase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates. ResultsWithin 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ. ConclusionIn women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.

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.

Effect of amino acid-based formula added to four-food elimination in adult eosinophilic esophagitis patients: A randomized clinical trial.

BackgroundElimination of key foods restricts dietary options in eosinophilic esophagitis (EoE) patients. Addition of amino acid‐based formula (AAF) to an elimination diet might facilitate adherence and, therefore, enhance efficacy of dietary management.AimTo evaluate whether addition of AAF to a four‐food elimination diet (FFED) is more effective than FFED alone in decreasing eosinophilia, endoscopic signs, and clinical outcomes.MethodsThis randomized controlled trial enrolled 41 adult patients with active EoE (≥15 eosinophils (eos) per high power field (hpf)) at baseline biopsy. Subjects were randomized (1:1 ratio) to groups given a FFED or FFED with addition of AAF providing 30% of their daily energy needs (FFED + AAF). Histological disease activity, endoscopic signs, symptoms, and disease‐related quality of life (EoEQoL) were measured at baseline and after 6 weeks of intervention.ResultsPatients (60% male, age 34.5 (interquartile range (IQR) 29–42.8 years)) were randomized to FFED (n = 20) or FFED + AAF (n = 21); 40 participants completed the diet. Complete histological remission (<15 eos/hpf) was achieved in 48% of FFED + AAF subjects (n = 21) vs. 25% of FFED subjects (n = 20), respectively (p = 0.204). Peak eosinophil counts (PEC) decreased significantly in both groups between baseline and week 6, but the change in PEC between groups was not different (p = 0.130). A significant but similar endoscopic and symptomatic reduction was observed in both groups (all; p<0.05). Total EoEQoL scores significantly improved in the FFED + AAF group between baseline and week 6 (p = 0.007), and not in the FFED group.ConclusionThe addition of AAF to a FFED did not lead to a larger decrease in PEC between baseline and 6 weeks, but may result in a significant improvement of QoL in adult EoE patients NL6014 (NTR6778).

S433 Topical Steroids for Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis

Introduction: Eosinophilic Esophagitis (EoE) is the most common cause of food impaction with an estimated prevalence of 0.5-1 cases/1000 persons. Pharmacologic therapy consists of trial of PPI (Proton Pump Inhibitors) or topical steroids. Fluticasone and budesonide are the 2 most commonly used steroids and believed to decrease inflammation. The most recent meta-analysis with 2 studies concluded that budesonide viscous is the most effective steroid treatment for complete histologic remission. However, reporting analyses of one or 2 studies is not the best integration approach for a meta-analysis. Methods: We performed a literature search using PubMed and CINAHL from inception through December 22, 2019. The following search strategy was used (eosinophilic oesophagitis OR eosinophilic esophagitis) AND (steroid OR steroids). All articles were individually reviewed by 2 people and disagreements were agreed upon by consensus. We included clinical trials which reported data on clinical or histological change after the use of topical steroids. Results: In the absence of head-to-head comparisons of fluticasone and budesonide, we performed an indirect analysis with the available studies. The meta-analysis for budesonide versus placebo clinical remission showed that budesonide had increased odds for clinical remission (OR:6.15, 95% CI: 1.63, 23.15) with 5 of 6 studies favoring budesonide. Comparisons for budesonide versus placebo histological response showed that budesonide had increased odds for histological change (OR: 41.96, 95% CI: 13.09, 134.51) with all 5 studies favoring budesonide. Our comparisons for fluticasone versus placebo histological response showed that fluticasone had increased odds for histological change (OR: 26.37, 95% CI: 5.69, 122.29) with all 3 studies favoring fluticasone. Conclusion: Overall, we found that budesonide has increased odds for clinical remission and histological change. Fluticasone had increased odds for histological change. One of the limitations of our study is that there were no head-to-head comparison trials for comparison of budesonide with fluticasone. The trials included in our study were limited to the effect of budesonide or fluticasone to a placebo. Topical steroids including budesonide and fluticasone are effective for inducing histological change. Fluticasone is effective at bringing histological change but further trials are needed to study fluticasone and clinical response.Figure 1.: Flowchart of studies selection at each stageTable 1.: Data Extraction

Effectiveness of PPI treatment and guideline adherence in 236 patients with eosinophilic oesophagitis-Results from the population-based DanEoE cohort shows a low complication rate.

BackgroundProton pump inhibitors (PPIs) are often the first drug of choice in the treatment of eosinophilic oesophagitis (EoE), and in Denmark 8 weeks of high‐dose PPI therapy is recommended as first‐line treatment followed by rebiopsying, reflecting international recommendations.AimsTo assess the population‐based effectiveness of PPIs in the treatment of EoE and evaluate whether patients were treated and followed according to the regional guideline.MethodsThis is a retrospective, registry‐based, DanEoE cohort study of 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. After patient file revision, the EoE diagnosis was defined according to the AGREE 2 consensus. Symptomatic PPI response was defined as complete symptom resolution and histological remission (<15 eosinophils per high‐power field).ResultsPPI treatment was initiated in 92% of the EoE patients. High‐ and low‐dose PPIs were prescribed in 55% and 45% of the cases, respectively. When treated with high‐dose PPIs, 68% of the patients were completely symptom‐free, and 49% were in histological remission. In 39% of high‐dose PPI‐treated patients, the symptomatic and histological responses were conflicting. While treated with PPIs, complications were rare, with <5% strictures in responders and <10% in non‐responders. Rebiopsying was done in 67% of the EoE patients started on PPIs.ConclusionsHigh‐dose PPI treatment was effective in half of the EoE patients started on PPIs, but conflicting symptomatic and histological PPI responses were common. Complications were rare when PPIs were started. One‐third of the patients were not rebiopsied as recommended.

Effectiveness of photodynamic therapy in women of reproductive age with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2)

ObjectiveTo evaluate the histologic response rate of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia 2 (CIN2) of the cervix after photodynamic therapy (PDT) treatment in women with fertility requirements. Materials and methodsA retrospective study was carried out comprising 31 female patients aged 20–38 years with histologically confirmed HSIL/CIN2 with high-risk human papillomavirus (hrHPV) infection. Patients were treated with three sessions of 20% 5-aminolevulinic acid (5-ALA) PDT at intervals of 7–14 days. All patients had a follow-up including cytology, HPV testing and colposcopy-directed biopsy after PDT treatment at the 6-month and 12-month follow-up points. The main outcome measure was efficacy, defined as complete histologic remission 12 months after PDT. Secondary outcomes were the remission of HPV infection and the adverse effects of PDT treatment. ResultsAt the 12-month follow-up, 21 out of 27 patients (77.78%) and 4 out of 27 patients (14.81%) showed histologic disappearance and histologic regression, respectively. Only 7.41% (2/27) patients persisted with HSIL/CIN2. In addition, no patients progressed to CIN3 or carcinoma. The total baseline HPV remission rate was 62.96% (17/27). The remission rate of HPV16/18 was statistically significant compared to the other hrHPV (57.14% vs. 100%, p = 0.016) in the group with HISL/CIN2 disappearance. Adverse events were mild, with increased vaginal secretion and abdominal pain being the most common complaints. There was no report of adverse events such as vaginal bleeding, colporrhagia, ulcer, or abdominal pain after PDT treatment. Conclusions5-ALA-PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with HSIL/CIN2 who have fertility requirements.

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant

Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.