bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma
Authors: Vos E L , Carr R A , Hsu M , Nakauchi M , Nobel T , Russo A , Barbetta A , Tan K S , Tang L , Ilson D , Ku G Y , Wu A J , Janjigian Y Y , Yoon S S , Bains M S , Jones D R , Coit D , Molena D , Strong V E 
Published: May 2021

Abstract

Background
Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively.

Methods
Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher’s exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray’s test.

Results
Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy.

Conclusion
In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.
DOP09 Mirikizumab-induced transcriptome changes in patient biopsies at Week 12 are maintained through Week 52 in patients with Ulcerative Colitis
Authors: Johnson T , Steere B , Zhang P , Zang Y , Higgs R , Gottlieb K , Reinisch W , Panés J , Krishnan G 
Published: May 2021

Abstract

Background
Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomised clinical trial in patients with moderate-to-severe ulcerative colitis (UC; NCT02589665). After 12 weeks (W) of treatment, miri was shown to down-regulate several transcripts correlated with increased UC disease activity as well as anti-TNF resistance. Here we show W52 gene expression analysis from the induction responder cohort at W12 for both miri and PBO treated patient biopsy samples to identify sustained changes in gene expression.

Methods
Miri-treated patients who achieved clinical response (decrease in 9-point Mayo subscore [rectal bleeding, stool frequency, endoscopy] of ≥2 points and ≥35% from baseline [BL] with either a decrease of RB subscore of ≥1 or an RB subscore of 0 or 1) or better at W12 were re-randomised to miri 200 mg administered subcutaneously (SQ) every 4 weeks or every 12 weeks through W52. Patients given placebo (PBO) in induction who achieved clinical response continued on PBO in the maintenance period. Colonic biopsies were obtained at W0, 12, and 52 from the most affected area at least 30 cm from the anal verge (miri N=31, PBO N=7). Transcript changes at W12 from BL in the PBO and miri arms were clustered into differentially expressed genes (DEGs) using the Bayesian Limma R-package. Among these DEGs, similarly expressed genes (SEGs) were identified as those which maintained their W12 expression level through W52.

Results
Analysis of transcript changes in W12 responders who continued to maintenance identified a profile of DEG-SEGs in responders (Fig 1A). Of these genes, 63 (70.8%) were present only in miri responders, 5 (5.6%) were present only in PBO responders, and 21 (23.6%) were present in both groups (Fig 1B, C). The magnitude of transcript changes was greater at W12, and more consistent through W52, in the group of miri responders compared to PBO responders (Fig 2). A separate cluster of DEG-SEGs correlated with to disease activity indeces (Robarts Histopathology Index [RHI], modified Mayo; both r&gt;0.5) were shown to be sustained in the miri treated patients but not in the placebo patients.

Conclusion
In this limited sample of W12 PBO and miri responders, miri responders showed broader, larger, and more sustained magnitude of changes at W52 compared to PBO responders. The qualitative description of transcripts suggests a distinct molecular healing pathway associated with miri treatment, as compared to the spontaneous healing that occurred in PBO responders. A cluster of transcripts that correlated with disease activity indices was identified, demonstrating consistency across molecular, endoscopic and clinical indices of healing in UC.
DOP12 Validation of a modified simple ultrasound activity Score for children with Crohn’s Disease
Authors: Ma H , Isaac D M , Petrova A , Almeida P , Parsons D , Kuc A , Carroll M W , Wine E , Huynh H 
Published: May 2021

Abstract

Background
Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess the bowel wall thickness (BWT) of children with Crohn’s disease (CD) due to its minimal invasiveness. Recently the Simple Ultrasound Activity Score for CD (SUS-CD) was developed and validated in adults using the Simple Endoscopic Score for CD (SES-CD). Our aim was to determine how the SUS-CD performed in children at diagnosis in comparison to endoscopy.

Methods
Pediatric patients (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled through the Edmonton Pediatric IBD Clinic in Alberta, Canada. Patients underwent a baseline TABUS to visualize the intestine (excluding rectum, which is difficult to see with TABUS), blood work and endoscopy. The weighted pediatric CD activity index (wPCDAI) assessed disease activity, and SES-CD assessed endoscopic disease. Modified SUS-CD (excluding rectal sub score) was calculated using BWT scores (0=&lt;3mm, 1=3–4.9mm, 2=5–7.9mm, 3=&gt;8mm) and colour doppler scores (0=no or 1 vessel, 1=2–5 vessels, 2=&gt;5 vessels per cm2) for each segment (terminal ileum, right colon, transverse colon, left colon) and compared to SES-CD. Modified SUS-CD was correlated to wPCDAI score, C-reactive protein (CRP) and fecal calprotectin (FCP). Using SPSS, anova and Chi square were used to assess for an association between TABUS parameters and wPCDAI. Spearman’s rank (rho) and Pearson’s correlation (r) were used to assess for a correlation between modified SUS-CD with SES-CD, wPCDAI, CRP and FCP.

Results
40 patients recruited, 35 had CD (mean age 12.6(2.85)) and 5 were normal and scanned for suspected IBD (mean age 12.2(3.75)). Median wPCDAI and SES-CD scores for CD patients were 61(IQR 35.6–77.5) and 15(IQR 7.5–21) respectively. Fat proliferation was associated with severe CD based on wPCDAI (p&lt;0.05). The modified SUS-CD score correlated well with the modified SES-CD score (rho=0.79,r=0.76,p&lt;0.001,R2 linear=0.465). When the BWT threshold was lowered by 0.5mm for each BWT category, correlation improved (rho=0.80,r=0.82,p&lt;0.001,R2 Linear=0.541). Using a similar lower threshold for BWT, a receiver operating characteristic curve analysis revealed an area under the curve of 0.87 and 0.90 for detecting mild endoscopic activity and moderate endoscopic activity, respectively. There was a significant correlation between SUS-CD and wPCDAI score (r=0.56,p&lt;0.01), CRP (r=0.55,p&lt;0.01) and FCP (r=0.56,p&lt;0.01).

Conclusion
Fat proliferation was associated with more severe CD. The modified SUS-CD correlated well with modified SES-CD score, wPCDAI, CRP and FCP. Correlation improved when BWT threshold in each category was dropped by 0.5mm. These data support the use of TABUS as an effective adjunct to the assessment of pediatric CD.
DOP60 Simplified rules to identify bio-naïve patients with Crohn’s Disease with higher likelihood of clinical remission when initiating vedolizumab versus anti-TNFα therapies: Analysis of EVOLVE study data
Authors: Mantzaris G , Yarur A , Wang S , Adsul S , Kamble P , Luo M , Guerin A , Billmyer E , Nguyen H , Bressler B 
Published: May 2021

Abstract

Background
Previously, we identified subsets of biologic-naïve patients (pts) with Crohn’s disease (CD) from the EVOLVE study who had higher rates of clinical remission (CR) [Fig 1] when initiating vedolizumab (VDZ) vs anti-TNFα treatment, using prediction models based on multiple baseline characteristics.1,2 To aid use in practice, we investigated whether these subsets could be identified using simpler rules based on fewer baseline characteristics.

Methods
Using data from EVOLVE, we used recursive partitioning and regression tree (RPART) classification to predict membership in the previously identified higher CR subsets for VDZ. The RPART algorithm repeatedly splits data, based on baseline predictors (demographics, prior treatments, clinical characteristics at treatment initiation, Charlson comorbidity index, prior extraintestinal manifestations [EIMs], and prior healthcare resource use). At each split, the predictor and its value as chosen by the algorithm to split the data were those that maximized the number of pts classified correctly. Simplified rules were developed from the resulting RPART decision trees. Analyses of the treatment effect of VDZ vs anti-TNFα were conducted in the subsets of pts identified by each rule.

Results
Pts with data on CR and candidate predictors were included (VDZ [n=195]; anti-TNFα [n=245]). Three simplified rules (A, B, & C) were identified (Table 1). Pt characteristics included in the rules (exacerbation ongoing at treatment initiation, no emergency department/emergency room (ED/ER) visits prior to treatment initiation, no fistulae at most recent assessment prior to treatment initiation, pre-initiation disease behaviour) were among the main predictors of CR in VDZ pts identified previously. Pts identified by Rule A comprised 32% of the EVOLVE population, and were those who 1) had an exacerbation ongoing at index, 2) did not have ED/ER visits prior to initiation and 3) had pre-initiation disease behaviour classified as other than stricturing with/without perianal disease. Among these pts, median time to CR for VDZ and anti-TNFα pts were 6.7 and 18.1 months, respectively (unadjusted log-rank p&lt;0.001), and the adjusted hazard ratio (HR) of CR for VDZ vs anti-TNFα was 2.9 (95% CI: 1.7, 5.0). Rules B & C identified larger subsets in which VDZ vs anti-TNFα treatment differences were smaller but still statistically significant.

Conclusion
Simple rules were developed to identify biologic-naïve, CD pts in whom VDZ initiation appeared to have a larger effect on CR relative to anti-TNFα initiation. Validation of these rules in other data sources is important to confirm these findings; if validated, these simplified rules can inform targeting of treatment and optimization of outcomes for pts with CD treated with VDZ.
DOP73 Antibiotic use differentially affects the risk of antidrug antibody formation during anti-TNFα therapy in Inflammatory Bowel Disease
Authors: Gorelik Y , Freilich S , Gerassy-Vainberg S , Blatt A , Pressman S , Focht G , Friss C , Loewenberg Weisband Y , Greenfeld S , Kariv R , Ledderman N , Iris D , Kashi Y , Turner D , Chowers Y 
Published: May 2021

Abstract

Background
Anti-drug antibodies (ADA) to anti-TNF therapy drive loss of response to treatment. Links between intestinal microbial composition and response to anti-TNF therapy were demonstrated, and antibiotic use during anti-TNF therapy reduced the risk of ADA formation. Here, we aimed to assess the possible implications of specific antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD) patients.

Methods
We performed a retrospective analysis of data from three health maintenance organizations, covering 89% of the Israeli population. All patients with IBD and available ADA levels were included. Survival analysis using Kaplan-Meier and multivariate Cox proportional hazards regression with drug use as time varying covariates methods were used to assess the association between specific antibiotic use and ADA development. C57BL and germ free mice were treated with respective antibiotics followed by immunization with infliximab. ADA were assessed after 14 days.

Results
We analyzed 1,946 patients treated with anti-TNF. Positive ADAs were detected in 363 patients (18.6%). Age, gender and concomitant use of immunomodulators where comparable in patients who eventually developed ADAs or not. However, infliximab and not adalimumab therapy, previous anti-TNF therapy and higher baseline C-reactive protein levels were significantly associated with ADA development in univariate analysis. Kaplan-Meier curves of prior antibiotic use demonstrated significant hazard of ADA development in patients who used cephalosporins or penicillins with beta-lactamase inhibitors (BLI) and reduced risk with prior use of fluoroquinolones, macrolides or metronidazole (Figure 1) with early risk divergence for most classes. Multivariable Cox proportional hazards model adjusted for multiple factors associated with ADA development was overall consistent with Kaplan-Meier estimates (Figure 2). In mice exposed to infliximab, increased ADA production by cefuroxime treatment and a non-significant reduction following azithromycin treatment was noticed (Figure 3). Germ free mice produced no ADA.
Figure 1: Kaplan-Meier curves of cumulative risk of ADA development for prior use of specific antibiotics. P value for the log rank test is presented in each plot.

Figure 2: Multivariable-adjusted HR with 95% CI of ADA for use of various antibiotic classes during anti-TNF therapy.

Figure 3: Mean ADA levels in mice treated with anti-TNF and prior cefuroxime, azithromycin, or no antibiotic

Conclusion
ADA production is microbial dependent. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillins with BLI, or possibly reduced by treatment with fluoroquinolones or macrolides.
DOP78 The differential diagnosis and clinicopathological spectrum of Inflammatory Bowel Disease: An interesting and informative ECCO topical review
Authors: Feakins R M , Torres J , Borralho-Nunes P , Burisch J , Cúrdia Gonçalves T , De Ridder L , Driessen A , Lobatón T , Menchén L , Mookhoek A , Noor N , Svrcek M , Villanacci V , Zidar N , Tripathi M 
Published: May 2021

Abstract

Background
A wide variety of intestinal and non-intestinal diseases can resemble chronic idiopathic inflammatory bowel disease (IBD) clinically and/or pathologically. The aim of the current Topical Review was to explore the differential diagnosis of IBD and to discuss clinical, histomorphological features and ancillary techniques that help distinguish between IBD and its mimics.

Methods
An open ECCO call led to the selection of 12 participants who formed three working groups (WG) to study the mimics of IBD. WG 1 comprised gastroenterologists, who explored mainly the clinical features. WG 2 consisted of histopathologists, who focused on macroscopic and microscopic pathological aspects. WG 3 was a mixed group of pathologists and clinicians who studied the value of additional investigative techniques such as imaging, serology and molecular markers. A systematic literature search allowed exploration of these topics and the identification of the most helpful and relevant distinguishing features. The process led to the development of Current Practice Position (CPP) statements and supporting text. Consensus meetings with voting by all participants facilitated modification and finalisation of CPP statements.

Results
The project highlighted several points. Firstly, there is a wide and sometimes overwhelming variety of potential mimics of new and established IBD, both in adults and in children.
Secondly, some mimics are more important clinically and others pathologically, meaning that the emphasis on the mimics of IBD is different for clinicians and pathologists. Thirdly, close attention to all clinical features, pathological findings and other evidence optimises accuracy. Finally, newer techniques sometimes have a role, e.g., in distinguishing monogenic IBD-like disorders from IBD in young children, and the value of many novel techniques is as yet uncertain. A practical message is that constant awareness by clinicians and pathologists of the possibility of mimics is particularly important.

Conclusion
Discussions between pathologists and clinicians were particularly useful during this process and were a reminder of the importance of clinicopathological correlation. There is a wide variety of mimics of IBD, including infections, diverticular disease, drug effect, radiation damage, immune disorders, vascular disorders and diversion proctocolitis. An important, relatively new, and sometimes very close mimic of IBD is immune checkpoint inhibitor colitis. In turn, reliable distinction between IBD and other entities requires a multidisciplinary approach with a full clinical history (including duration of disease), and with appropriate investigations that may include endoscopy, pathology, imaging, microbiological tests, serology, and newer molecular tests.
DOP87 Disease clearance as a new therapeutic target in patients with Ulcerative Colitis: A multicenter retrospective cohort study
Authors: D’Amico F , Fiorino G , Massarini E , Solitano V , Guillo L , Allocca M , Furfaro F , Zilli A , Bonovas S , Peyrin-Biroulet L , Danese S 
Published: May 2021

Abstract

Background
Symptom control and endoscopic endoscopic healing have been the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. We aimed to evaluate the impact of disease clearance on long-term outcomes in patients with UC.

Methods
A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between January 2014 and February 2021. All consecutive adult patients with confirmed UC undergoing colonoscopy with biopsies and available histological reports and clinical data within one month of colonoscopy were eligible for inclusion. Disease clearance was defined as clinical (partial Mayo score ≤2 with no subscore &gt;1), endoscopic (endoscopic Mayo score= 0), and histological (Nancy index= 0) remission of disease. The first available endoscopic procedure was considered as baseline. Disease clearance was measured at baseline and during follow-up by comparing the occurrence of negative disease outcomes in patients who achieved or not disease clearance.

Results
A total of 302 patients were included (46.4% female). Disease clearance was detected in 42 patients (13.9%) at baseline. Median follow-up was 32.2 ± 20.2 months. No patient achieving disease clearance underwent surgery during follow-up compared with 22 subjects in the non-disease clearance group (0.0% vs 8.5%, p=0.1). Similarly, a lower hospitalization rate was detected in patients with disease clearance at baseline compared with the control group (7.1% vs 25.4%, p=0.01). Interestingly, 51/302 patients (16.9%) achieved both endoscopic and histologic remission. This subgroup experienced a significantly lower rate of hospitalization (7.8% vs 25.9%, p=0.008) and surgery (0.0% vs 8.8%, p=0.05) compared with patients with endoscopic and/or histologic disease activity. The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk for surgery (p=0.04) and hospitalization (hazard ratio (HR)= 0.49, 95% confidence interval (CI) 0.08–2.29, p=0.009) (Figures 1–2).

Conclusion
Disease clearance is a new outcome that simultaneously takes into account remission of symptoms, endoscopy and histology. Patients with disease clearance are at significant lower risk for hospitalization and surgery and could be the ultimate therapeutic target for full disease control.
P124 Gastroenteropancreatic Neuroendocrine Neoplasms in patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series
Authors: Festa S , Zerboni G , Derikx L , Ribaldone D G , Dragoni G , Buskens C J , Nieveen van Dijkum E , Pugliese D , Panzuto F , Krela-Kaźmierczak I , Reiss H , Shitrit A B G , Chaparro M , Gisbert J P , Kopylov U , Teich N , Vainer E , Nagtegaal I , Hoentjen F , Garcia M J , Filip R , Foteinogiannopoulou K , Koutroubakis I , Argollo M , van Wanrooij R , Laja H , Truyens M , Lobaton Ortega T , Molnar T , Savarino E , Aratari A , Papi C , Goren I 
Published: May 2021

Abstract

Background
Neuroendocrine Neoplasms (NENs) are a heterogeneous group of tumours deriving from the diffuse endocrine system. NENs may occur almost everywhere in the body but are most common in the gastrointestinal tract, the pancreas, and the lungs, with gastroenteropancreatic (GEP) tumours representing 70% of all NENs. GEP-NENs have rarely been reported in association with inflammatory bowel diseases (IBDs) but no definitive relationship between these tumours and IBD has been established

Methods
This was an ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER). We included cases of GEP-NENs diagnosed in patients with IBD that met the diagnostic criteria for NEN according to the European Neuroendocrine Tumour Society. Data were retrospectively collected in a standardized case report form and analysed for event association with patient’s and IBD-related factors

Results
GEP-NEN was diagnosed in 100 patients with IBD [61% female, 55% Crohn’s disease, median age 48 years (IQR 37–59)]. Overall the most common location was the appendix (39/100) followed by the colon (22/100). Complete IBD-related data was available for 50 individuals with a median follow-up of 30.5 months (IQR 11.2–70) following NEN diagnosis. At the last follow-up data, 47/50 patients were alive. Three deaths occurred, of which 2 were related to NEN. Median duration of IBD at NEN diagnosis was 84 months (IQR 10–151), and in 18% of cases NEN and IBD were diagnosed concomitantly. 20/50 of NENs were at stage I (T1N0M0) and 28/50 graded G1 (ki 67 ≤2 %) at diagnosis.
Incidental diagnosis of NEN either during follow-up or during surgery as well as receiving diagnosis of NEN concomitantly with IBD was significantly associated with an earlier NEN stage (p&lt; 0.01 and p&lt;0.02, respectively). Exposure to immunomodulatory and/or biologic therapy was not associated with advanced NEN stage or grade. Interestingly, primary GEP-NEN sites significantly correlated to the segment affected by IBD (62% vs 38% p = 0.02)

Conclusion
In the largest case series to date, prognosis of patients with concomitant GEP-NEN and IBD seems favorable. Incidental NEN diagnosis correlates with an earlier NEN stage and IBD-related therapies are independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis