DIAGNOSTIC ACCURACY OF INTESTINAL ULTRASOUND IN THE DETECTION OF INTRA-ABDOMINAL COMPLICATIONS IN CROHN'S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Crohn's disease (CD) is frequently associated with the development of strictures and penetrating complications. Intestinal ultrasound (IUS) is a non-invasive imaging modality ideal for point-of-care assessment. In this systematic review and meta-analysis we provide a current overview on the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, cross-sectional imaging, surgery and pathology. METHOD: We conducted a literature search for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. Meta-analysis was performed for both conventional IUS (B-mode) and oral contrast IUS (SICUS). RESULTS: Of the 1498 studies we identified, 68 were included in this review and 23 studies (3863 patients) were used for the meta-analysis. Pooled sensitivities and specificities for strictures, inflammatory masses and fistulas by B-mode IUS were 0.81 and 0.90, 0.87 (sensitivities) and 0.95, and 0.67 and 0.97 (specificities), respectively. Pooled overall log diagnostic odds ratios were 3.56, 3.97 and 3.84 respectively. Pooled sensitivity and specificity of SICUS were 0.94 and 0.95, 0.91 and 0.97 (sensitivities), and 0.90 and 0.94 (specificities), respectively. Pooled overall log diagnostic odds ratio of SICUS were 4.51, 5.46 and 4.80, respectively. CONCLUSION: IUS is accurate for the diagnosis of intra-abdominal complications in CD. As a non-invasive, point-of-care modality, IUS is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.

Anti-drug antibodies against anti-TNF in patients with inflammatory bowel disease: an evaluation of possible strategies.

OBJECTIVE: Immunogenicity against anti-TNF antibodies usually leads to loss of response. We aimed to evaluate the efficacy of clinical strategies to improve clinical remission and pharmacokinetics upon detection of anti-drug antibodies (ADA). METHODS: Inflammatory bowel disease (IBD) patients with ADA against infliximab or adalimumab were identified through a single centre database search covering 2004-2022. Criteria for successful intervention upon ADA detection (baseline) were clinical remission after 1 year without further change in strategy. RESULTS: Two-hundred-and-fifty-five IBD patients (206 Crohn's disease) were identified. At baseline, median ADA level was 77 AU/ml; 50.2% of patients were in clinical remission. Implemented strategies were: (1) 81/255 (32%) conservative management, (2) 102/255 (40%) anti-TNF optimisation, (3) 72/255 (28%) switch within or out of class. Switching was the most successful strategy for clinical remission (from 19% at baseline to 69% at 1 year, p < 0.001). Patients that continued the same dose anti-TNF or discontinued biological therapy were often in clinical remission, but deteriorated significantly (-22.7%, p = 0.004). Anti-TNF dose intensification with immunomodulator optimisation was the fastest (median 3.0 months, p = 0.009) and most effective (65% ADA suppression, p < 0.001) strategy to suppress ADA compared to solely anti-TNF or immunomodulator optimisation. CONCLUSIONS: Switching therapy, within or out of class, is the most successful strategy to regain and maintain clinical remission upon immunogenicity. When switching to another anti-TNF, concomitant immunomodulatory therapy should be started or continued to prevent repeated immunogenic loss of response. Anti-TNF dose escalation with concomitant immunomodulator optimisation is the fastest and most effective strategy to suppress ADA.

Immunogenicity against anti-TNF antibodies is associated with loss of response in patients with inflammatory bowel diseases and remains a clinical challenge. We investigated potential therapeutic strategies in a retrospective patient cohort focusing on clinical efficacy and pharmacokinetics.

Early recapture of response with tofacitinib 10 mg twice daily in patients with ulcerative colitis in OCTAVE Open following dose reduction or treatment interruption in OCTAVE Sustain.

BACKGROUND AND AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. METHODS: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. RESULTS: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. CONCLUSIONS: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial.

Background: The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms. Methods: Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data. Findings: Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm. Interpretation: This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped. Funding: None.

Positioning intestinal ultrasound in a UK tertiary centre: significant estimated clinical role and cost savings.

Objective: Intestinal ultrasound (IUS) is an inexpensive, non-invasive method of diagnosing and monitoring inflammatory bowel disease (IBD). We aimed to establish the proportion of lower gastrointestinal endoscopies (LGIEs) and magnetic resonance enterographies (MREs) that could have been performed as IUS, the potential pathology miss-rates if IUS was used and the associated cost savings. Methods: All MREs and LGIEs performed for either assessment of IBD activity or investigation of possible IBD, performed at a single UK tertiary centre in January 2018, were retrospectively reviewed against predetermined criteria for IUS suitability. Case outcomes were recorded and cost of investigation if IUS was performed instead was calculated. Results: 73 of 260 LGIEs (28.1%) and 58 of 105 MREs (55.2%) met the criteria for IUS suitability. Among potential IUS-suitable endoscopy patients, one case each of a <5 mm adenoma and sessile serrated lesion were found; no other significant pathology that would be expected to be missed with IUS was encountered. Among IUS-suitable MRE patients, no cases of isolated upper gastrointestinal inflammation likely to be missed by IUS were found, and extraintestinal findings not expected to be seen on IUS were of limited clinical significance. The predicted cost saving over 1 month if IUS was used instead was £8642, £25 866 and £5437 for MRE, colonoscopy and flexible sigmoidoscopy patients, respectively. Conclusion: There is a significant role for IUS, with annual projected cost savings of up to almost £500 000 at our centre. Non-inflammatory or non-gastrointestinal pathology predicted to be missed in this cohort was of limited clinical significance.

Disc-like lesions in the intestinal tract after renal transplantation.

We report a case of intestinal lesions in a patient with a history of lupus nephritis and renal transplantation. Biopsy revealed an EBV-driven post-transplant lymphoproliferative disease (PTLD). An EBV-driven PTLD is a major complication after renal transplantation and is an important differential diagnostic consideration in the follow-up of renal transplant recipients.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial.

BACKGROUND: Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. METHODS: The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. FINDINGS: Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. INTERPRETATION: Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. FUNDING: Netherlands Organisation for Health Research and Development and Broad Medical Research Program.

A Healthcare Physician Can Be Trained to Perform Intestinal Ultrasound in Children With Inflammatory Bowel Disease.

OBJECTIVES: Training healthcare physicians to perform intestinal ultrasound (IUS) during outpatient visits with equal accuracy as radiologists could improve clinical management of IBD patients. We aimed to assess whether a healthcare-physician can be trained to perform IUS, with equal accuracy compared with experienced radiologists in children with iBD, and to assess inter-observer agreement. METHODS: Consecutive children, 6 to 18 years with IBD or suspicion of IBD, who underwent ileo-colonoscopy were enrolled. iUS was performed independently by a trained healthcare-physician and a radiologist in 1 visit. Training existed of an international training curriculum for IUS. Operators were blinded for each other's IUS, and for the ileocolonoscopy. Difference in accuracy of IUS by the healthcare-physician and radiologist was assessed using areas under the ROC curve (AUROC). Inter-observer variability was assessed in terminal ileum (TI), transverse colon (TC) and descending-colon (DC), for disease activity (ie, bowel wall thickness [BWT] >2 mm with hyperaemia or fat-proliferation, or BWT >3 mm). RESULTS: We included 73 patients (median age 15, interquartile range [IQR]:13-17, 37 [51%] female, 43 [58%] with Crohn disease). AUROC ranged between 0.71 and 0.81 for the healthcare-physician and between 0.67 and 0.79 for radiologist (P  > 0.05). Inter-observer agreement for disease activity per segment was moderate (K: 0.58 [SE: 0.09], 0.49 [SE: 0.12], 0.52 [SE: 0.11] respectively for TI, TC, and DC). CONCLUSIONS: A healthcare- physician can be trained to perform IUS in children with IBD with comparable diagnostic accuracy as experienced radiologists. The interobserver agreement is moderate. Our findings support the usage of IUS in clinical management of children with IBD.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease: Results of the HOT-TOPIC trial after 1-year follow-up.

BACKGROUND: Previously published short-term results (week 16) of this trial showed a significant improvement in clinical, radiologic and biochemical outcomes in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen therapy. OBJECTIVE: To assess the long-term (week 60) efficacy, safety and feasibility of hyperbaric oxygen therapy in perianal fistula in Crohn's disease. METHODS: Crohn's disease patients with high perianal fistula(s) failing conventional treatment >6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received 40 hyperbaric oxygen sessions and outcomes were assessed at week 16 and week 60. RESULTS: Twenty patients were included (median age 34 years). At week 16, median scores of the perianal disease activity index and modified Van Assche index (co-primary outcomes) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, p < 0.001) and 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, p = 0.004), respectively. At week 60, the respective scores remained significantly lower than baseline: 4 (95% CI 3-7, p < 0.001) and 7.7 (95% CI 5.2-10.2, p = 0.003). Perianal disease activity index score of 4 or less (representing inactive perianal disease) was observed in 13 patients at week 16 and 12 patients at week 60. Using fistula drainage assessment, 12 and 13 patients showed a clinical response at week 16 and 60, respectively, and clinical remission was achieved in four patients for both time points. At week 16, a statistically significant biochemical improvement (C-reactive protein and faecal calprotectin levels) was found, but this effect was no longer significant at week 60. CONCLUSIONS: The clinical and radiologic improvement of perianal fistula in Crohn's disease, that was found at week 16 after treatment with hyperbaric oxygen therapy, is maintained at 1-year follow-up.

Appropriateness of Medical and Surgical Treatments for Chronic Pouchitis Using RAND/UCLA Appropriateness Methodology.

BACKGROUND AND AIMS: The treatment of chronic pouchitis remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in chronic pouchitis. METHODS: Appropriateness of medical and surgical treatments in patients with chronic pouchitis was considered in 16 scenarios incorporating presence/absence of four variables: pouchitis symptoms, response to antibiotics, significant prepouch ileitis, and Crohn's disease (CD)-like complications (i.e., stricture or fistula). Appropriateness of permanent ileostomy in patients refractory to medical treatments was considered in eight additional scenarios. Using the RAND/UCLA appropriateness method, international IBD expert panelists rated appropriateness of treatments in each scenario on a 1-9 scale. RESULTS: Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and inappropriate in all other scenarios. Ileal-release budesonide was rated appropriate in 6/16 scenarios including patients with significant prepouch ileitis but no CD-like complications. Probiotics were considered either inappropriate (14/16) or uncertain (2/16). Biologic therapy was considered appropriate in most scenarios (14/16) and uncertain in situations where significant prepouch ileitis or CD-like complications were absent (2/16). In patients who are refractory to all medications, permanent ileostomy was considered appropriate in all scenarios (7/8) except in asymptomatic patients with no CD-like complications. CONCLUSIONS: In the presence of significant prepouch ileitis or CD-like complications, chronic antibiotics and probiotics are inappropriate. Biologics are appropriate in all patients except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most medically refractory patients.

Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients.

BACKGROUND AND AIMS: Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas. METHODS: Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis. RESULTS: Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]. CONCLUSIONS: Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure. EUDRACT: 2013-002932-25 and 2018-002064-15.

Endoscopic tissue sampling - Part 2: Lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.

Endoscopic tissue sampling - Part 1: Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence.

Population pharmacokinetics of subcutaneous infliximab CT-P13 in Crohn's disease and ulcerative colitis.

BACKGROUND: Infliximab is a chimeric monoclonal antibody against tumour necrosis factor-alpha for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of CT-P13, an infliximab biosimilar, was approved for clinical use. AIMS: To characterise CT-P13 pharmacokinetics (PK) and its clinically relevant determinants after subcutaneous administration through population PK modelling. METHODS: Data from a two-part Phase I study with intravenous (5 mg/kg) and variable maintenance subcutaneous dosing of CT-P13 with frequent PK sampling in patients with CD or UC were used. Population PK analysis was conducted by non-linear mixed effects modelling. Covariates affecting PK parameters were chosen based on their clinical relevance (effect size of ≥20%) using a full fixed-effect modelling approach. RESULTS: CT-P13 PK was described by a two-compartment model with linear elimination. The half-life in a typical 70 kg patient with serum albumin of 44 g/L was 10.8 days. The typical value for clearance was 0.355 L/d, absorption constant 0.273/d, bioavailability 79.1%, central volume of distribution 3.10 L and peripheral volume of distribution 1.93 L. Clinically relevant covariates affecting clearance were body weight (+43.2% from 70 to 120 kg), the presence of anti-drug antibodies (+39%) and serum albumin concentration (+30.1% from 44 to 32 g/L). Simulated drug exposure was comparable between routes of administration for patients weighing 50 or 70 kg, but lower with subcutaneous dosing in patients weighing 120 kg. CONCLUSIONS: This first population PK model for subcutaneous CT-P13 supports fixed subcutaneous maintenance dosing, although heavy patients had lower cumulative drug exposure.

Work productivity loss is determined by fatigue and reduced quality of life in employed inflammatory bowel disease patients: a prospective multicentre cohort study.

OBJECTIVE: Inflammatory bowel disease (IBD) patients experience problems at work resulting in work productivity loss driving indirect healthcare costs. We aimed to find determinants for work productivity loss in employed IBD patients while correcting for disease severity according to prior and active maintenance treatment. METHODS: In this longitudinal multicentre cohort study, 510 employed IBD patients completed online questionnaires during 18 months follow-up. Work productivity, fatigue and health-related quality of life (HRQL) were measured using the Work Productivity and Activity Impairment questionnaire, the Multidimensional Fatigue Inventory (score 20-100) and Short-Inflammatory Bowel Disease Questionnaire (score 10-70). Linear mixed model analyses including random, repeated and fixed effects were performed. RESULTS: Fatigue (ß 0.22; 95% CI, 0.12-0.32) and reduced HRQL (ß -1.15; 95% CI, -1.35 to -0.95) were the strongest determinants for work productivity loss in employed IBD patients. Clinical disease activity (ß 9.50, 95% CI 6.48-12.51) and corticosteroid use (ß 10.09, 95% CI 5.25-15.84) were associated with work productivity loss in the total IBD group and ulcerative colitis subgroup, but not in Crohn's disease patients. History of IBD-related surgery (ß 9.41; 95% CI, 2.62-16.20) and vedolizumab use (ß 12.74; 95% CI, 3.63-21.86) were significantly associated with work productivity loss in the ulcerative colitis subgroup. CONCLUSIONS: Fatigue and reduced HRQL were the strongest determinants for work productivity loss in employed IBD patients while correcting for disease severity and activity. These results underline the importance of monitoring fatigue and HRQL in routine care to reduce work productivity loss and indirect costs.

Patients Undergoing Ileoanal Pouch Surgery Experience a Constellation of Symptoms and Consequences Representing a Unique Syndrome: A Report from the Patient-Reported Outcomes After Pouch Surgery (PROPS) Delphi Consensus Study.

BACKGROUND: Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research. OBJECTIVE: The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function. DESIGN: This was a Delphi consensus study. SETTING: Three rounds of surveys were used to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement. PATIENTS: Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients, including patients, colorectal surgeons, and gastroenterologists or other clinicians. MAIN OUTCOME MEASURES: A consensus statement was the main outcome. RESULTS: patients, 62 colorectal surgeons, and 48 gastroenterologists or nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement. LIMITATIONS: The study was limited by online recruitment bias. CONCLUSIONS: This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function. See Video Abstract at http://links.lww.com/DCR/B571. LOS PACIENTES SOMETIDOS A CIRUGA DE RESERVORIO ILEOANAL EXPERIMENTAN UNA CONSTELACIN DE SNTOMAS Y CONSECUENCIAS QUE REPRESENTAN UN SNDROME UNICO: Un Informe de los Resultados Reportados por los Pacientes Posterior a la Cirugía de Reservorio (PROPS) Estudio de Consenso DelphiANTECEDENTES:Los resultados funcionales después de la creación del reservorio ileoanal han sido estudiados; sin embargo, existe una gran variabilidad en la forma en que se definen y reportan los resultados relevantes. Más importante aún, la perspectiva de los pacientes no se ha representado a la hora de decidir qué resultados deberían ser el foco de investigación.OBJETIVO:El objetivo principal era crear en el paciente una definición centrada de los síntomas principales que debería incluirse en los estudios futuros de la función del reservorio.DISEÑO:Estudio de consenso Delphi.ENTORNO CLINICO:Se emplearon tres rondas de encuestas para seleccionar elementos de alta prioridad. La votación de la encuesta fue seguida por una serie de reuniones de consulta de pacientes en línea que se utilizan para aclarar las tendencias de votación. Se realizo una reunión de consenso final en línea con representación de los tres paneles de expertos para finalizar una declaración de consenso.PACIENTES:Se eligieron partes interesadas expertas para correlacionar con el escenario clínico del equipo multidisciplinario que atiende a los pacientes con reservorio: pacientes, cirujanos colorrectales, gastroenterólogos / otros médicos.PRINCIPALES MEDIDAS DE VALORACION:Declaración de consenso.RESULTADOS:Ciento noventa y cinco pacientes, 62 cirujanos colorrectales y 48 gastroenterólogos / enfermeras especialistas completaron las tres rondas Delphi. 53 pacientes participaron en grupos focales en línea. 161 interesados participaron en la reunión de consenso final. Al concluir la reunión de consenso, siete síntomas intestinales y siete consecuencias de someterse a una cirugía de reservorio ileoanal se incluyeron en la declaración de consenso final.LIMITACIONES:Sesgo de reclutamiento en línea.CONCLUSIONES:Este estudio es el primero en identificar resultados funcionales claves después de la cirugía de reservorio con información directa de un gran panel de pacientes con reservorio ileoanal. La inclusión de pacientes en todas las etapas del proceso de consenso permitió un verdadero enfoque centrado en el paciente para definir los dominios principales en los que debería centrarse los estudios futuros de la función del reservorio. Consulte Video Resumen en http://links.lww.com/DCR/B571.

Real-world clinical and endoscopic outcomes after one year tofacitinib treatment in ulcerative colitis.

OBJECTIVE: Tofacitinib, an oral Janus kinase inhibitor, is approved for the treatment of moderate to severe ulcerative colitis (UC). We evaluated clinical and endoscopic efficacy, safety and drug survival of tofacitinib up to one year in a real-world cohort. METHODS: In this retrospective cohort study, 36 UC patients were included who received tofacitinib. The primary outcome was combined with steroid-free clinical remission [Simple Clinical Colitis Activity Index (SCCAI) ≤2] and endoscopic improvement (Mayo score ≤1) at 52 weeks. Secondary outcomes included clinical (SCCAI drop ≥3) and endoscopic response (Mayo score drop ≥1), biochemical remission [fecal calprotectin (FC) ≤150 mg/kg and C-reactive protein ≤5 mg/L), safety and drug survival. RESULTS: Median disease duration was 7 (3-14) years and 89 and 42% of patients failed prior anti-tumor necrosis factor (anti-TNF) and vedolizumab treatment, respectively. Combined corticosteroid-free clinical remission and endoscopic improvement were observed in 8/36 patients (22%), 6/35 (17%) and 12/31 (39%), at 16, 36 and 52 weeks, respectively. Corresponding combined clinical and endoscopic response rates were 15/36 (42%), 12/35 (34%), 15/31 (48%) and biochemical remission rates were 11/33 (33%), 10/32 (31%) and 10/29 (34%). Nine infections (two herpes zoster) led to dose reduction or (temporary) drug withdrawal. Permanent withdrawal occurred in 14/36 patients (33%) after a median duration of 9 (5-30) weeks. Drug survival at 1 year was 60%. Patients that failed anti-TNF were less likely to discontinue tofacitinib treatment early compared to patients without prior anti-TNF use (hazard ratio 0.20, 95% confidence interval 0.06-0.65). CONCLUSION: In a refractory UC population, combined steroid-free clinical remission and endoscopic improvement were found in 39% of patients at 1 year.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease.

BACKGROUND: Positive effects of hyperbaric oxygen on perianal fistulas in Crohn's disease have been reported. AIM: To assess efficacy, safety and feasibility of hyperbaric oxygen in Crohn's disease patients with therapy-refractory perianal fistulas. METHODS: Twenty consecutive patients were recruited at the out-patient fistula clinic of the Amsterdam UMC. Crohn's disease patients with high perianal fistula(s) failing conventional treatment for over 6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received treatment with 40 hyperbaric oxygen sessions and outcome parameters were assessed at Week 16. RESULTS: Seven women and 13 men were included (median age 34 years). At Week 16, median scores of perianal disease activity index and modified van Assche index (co-primary outcome parameters) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, P < 0.001), and from 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, P = 0.004) respectively. Perianal disease activity index scores ≤4 (representing inactive perianal disease) were observed in 13/20 patients (65%). Twelve patients showed a clinical response (60%) and four (20%) clinical remission, assessed with fistula drainage assessment. Median C-reactive protein and faecal calprotectin levels decreased from 4.2 mg/mL (95% CI 1.6-8) to 2.2 (95% CI 0.9-4.3, P = 0.003) and from 399 µg/g (95% CI 52-922) to 31 (95% CI 16-245, P = 0.001), respectively. CONCLUSIONS: We found significant clinical, radiological and biochemical improvement in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen. CLINICAL TRIAL REGISTRATION: www.trialregister.nl/trial/6489.

Impaired Quality of Working Life in Inflammatory Bowel Disease Patients.

BACKGROUND: Work-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients. AIMS: We aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL. METHODS: Employed IBD patients of two tertiary and two secondary referral hospitals were included. QWL (range 0-100) was measured using the Quality of Working Life Questionnaire (QWLQ). Work productivity (WP), fatigue, and health-related quality of life (HRQL) were assessed using the Work Productivity and Activity Impairment questionnaire, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire, respectively. Active disease was defined as a score > 4 for the patient-reported Harvey-Bradshaw index in Crohn's disease (CD) or Simple Clinical Colitis Activity Index in ulcerative colitis patients. RESULTS: In total, 510 IBD patients were included (59% female, 53% CD, mean age 43 (SD 12) years). The mean QWLQ score was 78 (SD 11). The lowest subscore (54 (SD 26)) was observed for "problems due to the health situation": 63% reported fatigue-related problems at work, 48% agreed being hampered at work, 46% had limited confidence in their body, and 48% felt insecure about the future due to their health situation. Intermediate/strong associations were found between QWL and fatigue (r = - 0.543, p < 0.001), HRQL (r = 0.527, p < 0.001), WP loss (r = - 0.453, p < 0.001) and disease activity (r = - 0.331, p < 0.001). Independent predictors of impaired QWL in hierarchical regression analyses were fatigue (B = - 0.204, p < 0.001), WP loss (B = - 0.070, p < 0.001), and impaired HRQL (B = 0.248, p = 0.001). CONCLUSIONS: IBD-related problems at work negatively influence QWL. Fatigue, reduced HRQL, and WP loss were independent predictors of impaired QWL in IBD.