ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.

OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

OBJECTIVE: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). DESIGN: After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in the Netherlands. Patients with previous small-bowel surgery were excluded. After bowel preparation, VCE was performed. The videos were read by two independent investigators. If significant lesions were detected, an endoscopic procedure was subsequently performed to obtain histology and, if possible, remove the lesion. RESULTS: In total, 200 patients (mean age 50 years (range 35-69), M/F 88/112), with proven mutations were included. These concerned MLH1 (n = 50), MSH2 (n = 68), MSH6 (n = 76), PMS2 (n = 3) and Epcam (n = 3) mutation carriers. In 95% of the procedures, caecal visualisation was achieved. Small-bowel neoplasia was detected in two patients: one adenocarcinoma (TisN0Mx) and one adenoma, both located in the duodenum. In another patient, a duodenal cancer (T2N0Mx) was diagnosed 7 months after a negative VCE. This was considered a lesion missed by VCE. All three neoplastic lesions were within reach of a conventional gastroduodenoscope. All patients with neoplasia were men, over 50 years of age and without a family history of small-bowel cancer. CONCLUSIONS: The prevalence of small-bowel neoplasia in asymptomatic patients with LS was 1.5%. All neoplastic lesions were located in the duodenum and within reach of conventional gastroduodenoscopy. Although VCE has the potential to detect these neoplastic lesions, small-bowel neoplasia may be missed. TRIAL REGISTRATION NUMBER: NCT00898768.

Abdominal computed tomography in refractory coeliac disease and enteropathy associated T-cell lymphoma.

AIM: To evaluate computed tomography (CT) findings, useful to suggest the presence of refractory celiac disease (RCD) and enteropathy associated T cell lymphoma (EATL). METHODS: Coeliac disease (CD) patients were divided into two groups. Group I: uncomplicated CD (n = 14) and RCD type I (n = 10). Group II: RCD type II (n = 15) and EATL (n = 7). RESULTS: Both groups showed classic signs of CD on CT. Intussusception was seen in 1 patient in group I vs 5 in group II (P = 0.06). Lymphadenopathy was seen in 5 patients in group II vs no patients in group I (P = 0.01). Increased number of small mesenteric vessels was noted in 20 patients in group I vs 11 in group II (P = 0.02). Eleven patients (50%) in group II had a splenic volume < 122 cm3 vs 4 in group I (14%), 10 patients in group I had a splenic volume > 196 cm3 (66.7%) vs 5 in group II (33.3%) P = 0.028. CONCLUSION: CT scan is a useful tool in discriminating between CD and (Pre) EATL. RCD II and EATL showed more bowel wall thickening, lymphadenopathy and intussusception, less increase in number of small mesenteric vessels and a smaller splenic volume compared with CD and RCD I.

Duodenal histopathology and laboratory deficiencies related to bone metabolism in coeliac disease.

OBJECTIVES: Coeliac disease (CD) is a chronic immune-mediated small intestine enteropathy precipitated by gluten in genetically predisposed individuals. Adult presentation is often atypical and malabsorption of vitamins and minerals is common, with a consequent disturbance of bone metabolism. We aim to evaluate laboratory deficiencies related to bone metabolism and the relationship between severity of histological damage and degree of bone mass loss at diagnosis of CD. MATERIALS AND METHODS: A retrospective cross-sectional study of 176 adult coeliac patients was carried out. All patients fulfilled the histopathological criteria for CD. Biochemical data were analysed (calcium/phosphate/alkaline-phosphatase/vitamin D/parathormone). Duodenal histology was classified according to the Marsh classification. Bone mass density (BMD) at the lumbar and femoral regions measured by dual X-ray absorptiometry. A P-value of less than 0.05 was considered significant. RESULTS: No correlation was found between the presence of gastrointestinal symptoms and the Marsh histopathological stage (P>0.05). Vitamin D deficiency was most common (44.5%), whereas only 5.7% had hypocalcaemia. Calcium was lower (P<0.05) and parathormone was higher (P=0.01) in patients with Marsh III. These patients had lower lumbar T-score (P<0.05). Although low BMD occurred in all age groups, most osteoporotic patients were aged 45-49 years (81.8%). A multiple regression analysis showed that the Marsh histopathological stage could be a predictor of lower lumbar BMD (r=0.322, B=-1.146, P<0.05). CONCLUSION: Laboratory deficiencies and decreased BMD could be severe and unrelated to the presence of gastrointestinal symptoms. At diagnosis, the Marsh histopathological stage could predict the occurrence of low BMD, which carries a risk of developing into osteoporosis. In coeliac patients older than 30 years, evaluation of bone biomarkers and dual X-ray absorptiometry examination should be considered.

Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

BACKGROUND AND STUDY AIMS: Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE). The aim of this prospective study was to determine the incidence of SBN. PATIENTS AND METHODS: Asymptomatic LS patients who underwent a VCE were invited to undergo a second VCE procedure 2 years later. If abnormalities or polypoid lesions larger than 1 cm were detected, subsequent endoscopic procedures were performed. RESULTS: A total of 155 (78 %) of the initial 200 patients underwent a second VCE procedure after a mean of 2.2 (range 1 - 6) years. In 17 of the 155 (11 %) patients possibly significant lesions were detected, which required further investigation by means of gastroduodenoscopy (n = 8) or balloon-assisted endoscopy (n = 9). These procedures revealed no SBN. CONCLUSION: No SBN was found after 2 years. Surveillance of the small bowel by VCE does not seem to be warranted in asymptomatic LS patients.

Double-balloon endoscopy: an effective rescue procedure after incomplete conventional colonoscopy.

OBJECTIVE: A significant percentage of colonoscopies remain incomplete because of a failure to intubate the caecum. By double-balloon endoscopy (DBE), originally developed for deep enteroscopy, an otherwise incomplete examination of the colon might be completed. We evaluated the success rate of caecal intubation, the reasons for its failure and the therapeutic consequences of using DBE after incomplete conventional colonoscopy. METHODS: We report our single-centre experience of using DBE to complete an otherwise incomplete colonoscopy. A total of 114 consecutive patients, 45 male and 69 female, with a mean age of 64.8 years, who had undergone 116 procedures, were evaluated retrospectively by a review of their medical records. RESULTS: The main causes for failed caecal intubation using a conventional colonoscope were loop formation in 70 patients (61.4%) and an adhesive angulated sigmoid in 33 (28.9%). Caecal intubation by DBE was successful in 101 patients (88.6%). The rate of failure was not associated with the cause of failure of the previous colonoscopy. In 55 patients (48.2%) a relevant new diagnosis was made in the previously inaccessible part of the colon: carcinoma (n=4; 3.5%), one or more adenomas (n=48; 42.1%) and caecal flat hyperplastic polyps (n=4; 3.5%). Endoscopic polypectomy was performed in 51 patients (44.7%); two complications occurred, both being mild postpolypectomy bleedings. In seven patients (6.1%) a subsequent surgical resection was performed. CONCLUSION: Colonoscopy by DBE was useful in most patients in whom conventional colonoscopy was incomplete, irrespective of the cause of the failure. In nearly half the patients, a relevant new diagnosis was made with therapeutic consequences.

[Screening: management after incomplete colonoscopy could be improved]. / Screening: beleid na incomplete coloscopie kan beter.

In 2014 in the Netherlands a national screening programme for bowel cancer was started in which a colonoscopy is performed after a positive immunochemical faecal occult blood test. If colonoscopy is incomplete a CT colonography (CTC) is offered in order to visualize the remaining colon. Balloon endoscopy (BE), double- or single-balloon, is an effective and safe endoscopic alternative which has advantages over CTC, including the option of endoscopic polypectomy and histological examination. However, its cost and the need for an additional procedure on a different day are disadvantageous. BE deserves a place in the national screening programme for bowel cancer after an incomplete colonoscopy, as a possible alternative for CTC and certainly after finding polyps on CTC. Because expertise in BE and its availability are limited, in each screening region some centres should be appointed as designated referral centres to perform BE.

Evaluation of Cladribine treatment in refractory celiac disease type II.

AIM: To evaluate cladribine [2-chlorodeoxyadenosine (2-CdA)] therapy in refractory celiac disease (RCD) II. METHODS: An open-label cohort-study of RCD II patients treated with 2-CdA was performed between 2000 and 2010. Survival rate, enteropathy associated T-cell lymphoma (EATL) occurrence, clinical course, and histological and immunological response rates were evaluated. RESULTS: Overall, 32 patients were included with a median follow-up of 31 mo. Eighteen patients responded well to 2-CdA. Patients responsive to 2-CdA had a statistically significant increased survival compared to those who were unresponsive. The overall 3- and 5-year survival was 83% in the responder and 63% and 22% in the non-responder group, respectively. The overall 2-year clinical, histological and immunological response rates were 81%, 47% and 41%, respectively. Progression into EATL was reported in 16%, all of these patients died. CONCLUSION: Treatment of RCD II with 2-CdA holds promise, showing excellent clinical and histological response rates, and probably less frequent transition into EATL.

Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease.

BACKGROUND: Refractory celiac disease (RCD) patients with aberrant, often clonal, intraepithelial T-cells are at high risk for development of enteropathy associated T-cell lymphoma (EATL). Early detection of those patients that actually develop EATL is of utmost importance for curative intervention. AIM: First, to establish an optimal cut-off value for the percentage of aberrant lymphocytes, previously determined based on clinical observations, via reference ranges for aberrant T-cells in the duodenal mucosa of celiac disease patient and control groups. Secondly, to compare aberrancy with intestinal T-cell clonality as a prognostic parameter for EATL development in RCD. METHODS: Immunophenotyping using flow cytometry was performed on small intestinal biopsy-derived lymphocytes, obtained from distinct celiac disease (CD) patient and control groups (N=167 in total). T-cell clonality in duodenal biopsy specimens was assessed by PCR in RCD, ulcerative jejunitis and EATL patients (N=31 in total). RESULTS: In 95% of non-refractory CD patients, the highest percentage aberrant T-cells was 20%. Using this cut-off value, EATL development was exclusively seen in RCD with more than 20% aberrant T-cells (median 52% aberrant T-cells, range 27-94%). When compared with T-cell clonality analysis, >20% aberrancy showed a much higher negative predictive value and sensitivity (both 100%) for EATL development in RCD patients than T-cell clonality analysis (respectively 75% and 78%). CONCLUSIONS: Quantification of aberrant T-cells by flow cytometry is preferable to T-cell clonality analysis for identification of RCD patients at risk for EATL development. A cut-off value of 20% is of use in risk stratification, therapeutic options and subsequent follow-up of RCD patients.