Performance measures for the SACRED team-centered approach to advanced gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology have defined performance measures for upper and lower gastrointestinal, pancreaticobiliary, and small-bowel endoscopy. Quality indicators to guide endoscopists in the growing field of advanced endoscopy are also underway. We propose that equal attention is given to developing the entire advanced endoscopy team and not the individual endoscopist alone.We suggest that the practice of teams intending to deliver high quality advanced endoscopy is underpinned by six crucial principles concerning: selection, acceptance, complications, reconnaissance, envelopment, and documentation (SACRED).

In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis.

BACKGROUND AND AIMS: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis. METHODS: We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients. RESULTS: In both animal models, the course of colitis was associated with increased interleukin-1ß [IL-1ß] and tumour necrosis factor-α [TNF-α] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1ß expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated with TNF-α and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKCζ expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkcζ, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients. CONCLUSIONS: Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.

Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD. METHODS: We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium. In searches of IBD pathology databases, we identified 813 lesions (616 low-grade dysplasias [LGDs], 64 high-grade dysplasias [HGDs], and 133 CACs) in 410 patients with IBD: 299 had dysplasia (73%) and 111 had CAC (27%). The primary aim was to determine the risk of more-advanced lesions after diagnosis of LGD or HGD. RESULTS: Of the 287 patients with LGD, 21 (7%) developed more-advanced lesions (HGD or CAC) after a median time period of 86 months (interquartile range, 34-214). Of the 28 patients with HGD, 4 (14%) developed CAC after a median time period of 180 months (interquartile range, 23-444). The overall cumulative incidence of CAC at 10 years after an initial diagnosis of HGD was 24.3% and after an initial diagnosis of LGD was 8.5% (P < .05). Metachronous lesions, non-polypoid lesions, and colonic stricture were associated with risk of occurrence of more-advanced lesions after LGD (P < .05). Of the 630 dysplastic lesions identified during endoscopy, 545 (86%) were removed during the same procedure or during a follow-up endoscopy or by surgery. Of 111 patients with CAC, 95 (86%) did not have prior detection of dysplasia and 64 of these 95 patients (67%) developed CAC outside of the screening or surveillance period recommended by the European Crohn's and Colitis Organisation. CONCLUSIONS: In an analysis of pathology data from 7 medical centers in Belgium, we found a low rate of detection of more-advanced lesions following detection of LGD or HGD-taking into account that most of the lesions were removed. Main risk factors for development of more-advanced lesions after LGD were metachronous lesions, non-polypoid lesions, and colon strictures.

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study.

BACKGROUND: Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse. AIMS: To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies. METHODS: A retrospective multicentre case-control observational study was performed. RESULTS: VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live-born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups. CONCLUSION: No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation.

Post-colonoscopy colorectal cancer in Belgium: characteristics and influencing factors.

Background and study aims Post-colonoscopy colorectal cancer (PCCRC) is an important quality parameter of colonoscopy. Most studies have shown that the risk for colorectal cancer is reduced after an index colonoscopy for screening or diagnostic purposes with or without polypectomy. In this study, we aimed to quantify and describe PCCRC in Belgium, including the possible relationships with patient, physician, and colonoscopy characteristics. Patients and methods Reimbursement data on colorectal related medical procedures from the Intermutualistic Agency (IMA-AIM) were linked with data on clinical and pathological staging of colorectal cancer (CRC) available at the Belgian Cancer Registry (BCR) over a period covering 9 years (2002 - 2010). Results In total, 63 518 colorectal cancers were identified in 61 616 patients between 2002 and 2010. We calculated a mean PCCRC rate of 7.6 %. PCCRC was significantly higher in older people and correlated significantly with polyp detection rate and the number of resections and procedures performed per year per physician. Conditional observed survival, given still alive 3 years since first colonoscopy, for PCCRC was worse than for CRC. Older patients and patients with invasive carcinomas had a worse outcome. Conclusions Although no quality register exists in Belgium, we were able to demonstrate that PCCRC in Belgium is directly related to the experience of the physician performing the procedure. In the absence of a quality register, utilization of population-based data sources proved to be a valuable tool to identify quality parameters.

Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study.

BACKGROUND: Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn's disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics. METHODS: This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52. RESULTS: Data from 152 patients were analysed. All patients were exposed to at least one anti-TNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients. CONCLUSIONS: This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab.

BACKGROUND AND AIMS: Vedolizumab is an IgG1 anti-α4ß7 integrin antibody approved for the treatment of inflammatory bowel diseases [IBD], but without clear safety data during conception, pregnancy and nursing. Animal studies showed that mucosal vascular addressin cell adhesion molecule 1 [MAdCAM-1] is expressed by maternal vessels in the placenta and recruits α4ß7-expressing cells that are considered important for maternal/fetal tolerance. Blocking this interaction by vedolizumab might affect this process. We aimed to evaluate pregnancy outcomes in vedolizumab-treated female IBD patients. METHODS: We conducted a retrospective, multicentre Belgian observational study. Details on disease activity, prenatal complications, delivery and neonatal outcome were collected through a case report form. RESULTS: Twenty-four pregnancies were reported. Five women had active disease at conception and one patient flared during pregnancy. There were 23 live births. Complications were observed in 25% of pregnancies [premature rupture of membranes, pre-eclampsia, miscarriage, elective termination and stillbirth] and in 35% of infants [prematurity, intra-uterine growth retardation, small for gestational age and congenital malformations including hip dysplasia, pulmonary valve stenosis and Hirschprung's disease]. Vedolizumab was continued throughout pregnancy in two females and stopped in the 1st and 2nd trimester in five and 16 patients, respectively. For live born children, the median [interquartile range] gestational age, weight and Apgar score 5 min after birth were 39 [37-39.6] weeks, 3270 [3080-3585] grams and 10 [9-10], respectively. CONCLUSIONS: Although several complications were observed, both in mothers and in newborns, no firm conclusions can be drawn. Awaiting prospective and controlled registries, vigilance and strict follow-up of pregnant patients treated with vedolizumab seems mandatory.

Efficacy and safety of radiofrequency ablation of Barrett's esophagus in the absence of reimbursement: a multicenter prospective Belgian registry.

BACKGROUND: Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS: Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS: 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS: Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

BACKGROUND: Vedolizumab is a recently available monoclonal antibody targeting α4ß7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). OBJECTIVE: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. METHODS: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. RESULTS: Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. CONCLUSION: Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Next generation of biologics for the treatment of Crohn's disease: an evidence-based review on ustekinumab.

The limited efficacy of the currently available medical therapies in a proportion of patients with Crohn's disease has led to the research and development of molecules that can block new inflammatory pathways. Ustekinumab is a fully human IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17 inflammatory responses are inhibited. Ustekinumab has been recently approved for its use in patients with Crohn's disease. Its efficacy and safety was initially proved in patients with psoriasis and psoriatic arthritis. More recently, three Phase III trials have confirmed its efficacy in patients with Crohn's disease refractory to anti-tumor necrosis factor therapy. This biologic agent appears safe, with no increased risk of infectious or malignant complications, and a low immunogenic profile.

Colonoscopy in patients with liver cirrhosis : success and safety issues.

BACKGROUND: Patients with liver cirrhosis undergo screening colonoscopy before liver transplantation. Screening colonoscopy is subject to specific quality criteria, among which caecal intubation rate. Several factors associated with failed caecal intubation have been identified. AIMS: We investigated whether liver cirrhosis influenced success and safety of screening colonoscopy. METHODS: Caecal intubation and complication rate of 93 candidates for liver transplantation due to liver cirrhosis were compared with the control rates of our endoscopy unit. Several patient and colonoscopy variables were taken into account. RESULTS: In patients with liver cirrhosis caecal intubation rate was only 83%, whereas in the control group it was 94% (P<0.0001). The presence of high volume ascites tends to compromise a successful colonoscopy. Serious complication rate was 0,4% in controls without colonoscopy-related mortality. In the cirrhotic population two severe complications were encountered (2,2%, P<0.05) and one patient died due to colonic perforation and sepsis (mortality 1.1%). CONCLUSIONS: Caecal intubation rate is significantly lower in patients with liver cirrhosis undergoing screening colonoscopy, possibly related to the presence of ascites. Complication and mortality rate of screening colonoscopy is significantly higher in patients being screened for liver transplantation.

Renewed attention for overtube-assisted colonoscopy to prevent incomplete endoscopic examination of the colon.

BACKGROUND: Colonoscopy is the standard examination to detect mucosal pathology in the colon. However, failure to complete colonoscopy may reach more than 10% in population-based endoscopy practices. The reasons for incomplete conventional colonoscopy are diverse and result in missed diagnosis of colonic polyps and carcinoma. OBJECTIVE: Recent endoscopic developments have shown that the use of specialized overtubes may help to reach the cecum in the case of a difficult colonoscopy, even with less discomfort. Several types of overtubes are currently available, whereas other types are being developed and clinically evaluated. The current review highlights the development of overtubes for colonoscopy and the available clinical data on overtube-assisted colonoscopy in the case of incomplete conventional colonoscopy. DATA SOURCES: Data were derived from a PubMed search through November 2012. STUDY SELECTION: Available clinical literature data on recent developments in overtube-assisted colonoscopy were studied. INTERVENTION: A descriptive comparison was made of currently available endoscopy systems used for overtube-assisted colonoscopy. MAIN OUTCOME MEASURES: The primary outcomes measured were the feasibility and safety of different endoscopy systems to perform overtube-assisted colonoscopy. RESULTS: Several overtube-assisted colonoscopy systems have recently been developed to complete colonoscopy in the case of difficult conventional colonoscopy. Literature data show excellent feasibility to reach the cecum with very low complication rates and good patient tolerance for the different overtube systems. LIMITATIONS: The majority of available studies are uncontrolled case series describing 7 to 110 patients undergoing overtube-assisted colonoscopy with only 1 direct comparison between 2 overtube systems. CONCLUSIONS: Overtube-assisted colonoscopy has been shown to be useful in performing colonoscopy by increasing the cecal intubation rate and patient tolerance and by decreasing the need for sedation. There is no standardized superior overtube system at this moment.

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis: first case.

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting. Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution, although the clinical and radiological picture was not typical and the response to corticosteroids was poor. We performed a single-balloon enteroscopy showing a short, ulcerous stenosis 50 cm proximal from Bauhin's valve. The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). High dose corticosteroids were again started, without effect. The monoclonal tumor necrosis factor-α (TNF-α) antibody infliximab was added to the medical therapy. After induction therapy, both clinical and endoscopic amelioration was obtained. Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.

Safety of pull-type and introducer percutaneous endoscopic gastrostomy tubes in oncology patients: a retrospective analysis.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) allows long-term tube feeding. Safety of pull-type and introducer PEG placement in oncology patients with head/neck or oesophageal malignancies is unknown. METHODS: Retrospective analysis of 299 patients undergoing PEG tube placement between January 2006 and December 2008 revealed 57 oncology patients. All patients with head/neck or oesophageal malignancy were treated with chemo- and radiotherapy. In case of high-grade stenosis introducer Freka® Pexact PEG tube was placed (n = 24) and in all other patients (n = 33) conventional pull-type PEG tube. Short-term complications and mortality rates were compared. RESULTS: Patients' characteristics and clinical status were comparable in both groups. Short-term complications were encountered in 11/24 (48%) introducer PEG patients as compared to only 4/33 (12%) pull-type PEG patients (P < 0.05). Accidental removal of the introducer PEG tube occurred in 4/24 (17%) with need for surgical intervention in 1 vs. 0/33 (0%, P < 0.05). Wound infection occurred in 3/24 (12%) leading to septic shock and admission to intensive care unit (ICU) in 1 vs. 3/33 (9%, NS). Finally, 3/24 gastrointestinal perforations (12%) resulted from a difficult placement procedure vs. 1/33 (3%), leading to urgent surgical intervention and admission to ICU. Two introducer PEG patients died at ICU, resulting in an overall mortality rate of 8% vs. 0% (P = 0.091). CONCLUSION: The introducer Freka® Pexact PEG procedure for long-term tube feeding may lead to significantly higher complication and mortality rates in patients with head/neck or oesophageal malignancies treated with chemo- and radiotherapy. It is suggested to use the conventional pull-type PEG tube placement in this group of patients, if possible.

Cecal intubation rate with the double-balloon endoscope after incomplete conventional colonoscopy: a study in 45 patients.

BACKGROUND AND AIM: Conventional colonoscopy is the gold standard for colorectal cancer screening. However, a failure rate to complete conventional colonoscopy of more than 10% is reported in the literature. We evaluated whether the therapeutic Fujinon double-balloon endoscope EN-450T5/20 is a valuable tool to intubate the cecum and to carry out all conventional endoscopic procedures after incomplete conventional colonoscopy. METHODS: Forty-five consecutive patients with prior incomplete conventional colonoscopy were prospectively enrolled. All but three procedures were carried out under conscious sedation with the patient in the left lateral decubitus position without fluoroscopic guidance. RESULTS: The cecum was reached in 42 of 45 patients (93%) and in 62% additional therapeutic interventions were carried out. Double-balloon colonoscopy required less conscious sedation compared to conventional colonoscopy. No external abdominal compression nor fluoroscopic control was used. The insertion depth of the double-balloon endoscope did not exceed the working length of a conventional colonoscope. CONCLUSIONS: The present study illustrates that the concept of double-balloon endoscopy is a valuable alternative to reach the cecum after prior incomplete conventional colonoscopy, especially due to redundant colon and colonic loop formation. The procedure requires less conscious sedation and no fluoroscopic control, but allows all conventional endoscopic interventions.

Capsule endoscopy in paediatrics: multicentric Belgian study.

BACKGROUND AND STUDY AIMS: Capsule Endoscopy (CE) is a noninvasive procedure for evaluating small bowel disease. Data concerning children are scarce. The aim of the present report was to review all paediatric cases investigated by CE in Belgium. PATIENTS AND METHODS: The seven Belgian academic hospitals using the CE device (Given) were asked to collect information on CE performed in patients < or = 18 years. Main indications for performing VCE, former radiological and endoscopic procedures were collected, as well as final diagnosis and clinical impact of VCE findings. RESULTS: From November 2002 until December 2005, VCE was performed in 17 children (mean age : 11.9 years, range : 5-18). Indications were occult gastro-intestinal bleeding (OGIB) and/or iron deficiency anaemia (IDA) (10 cases) and chronic and/or recurrent abdominal pain (7 cases). Mean duration of symptoms was 8.6 months. The mean number of endoscopic and radiological procedures before performing CE was 4.2 per patient. Detected lesions were ulcerations (6 cases), jejunal varices (1), ileo-ileal invagination (2), active bleeding (1), and normal findings (7). In the indication of OGIB/IDA, relevant findings having an impact on the diagnosis were found in 60% of the cases. In the group with chronic and recurrent abdominal pain, CE brought relevant findings in 43%. CE findings had an impact on therapy in 44% of the patients. CONCLUSIONS: CE could be a useful tool for clinical work-up of difficult paediatric cases, not only in the indication of IDA/OGIB, but also for selected cases of recurrent abdominal pain, but prospective controlled trials including emerging techniques like CT enterography are mandatory.