Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. RESULTS: A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains. CONCLUSION: The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

Idiopathic terminal ileitis: myth or true entity?

PURPOSE OF REVIEW: Isolated terminal ileitis is an increasing phenomenon identified during colonoscopy. Idiopathic terminal ileitis (IDTI) is a diagnosis of exclusion, representing a significant challenge from a diagnostic and management point of view. This review provides an overview of the most recent and relevant evidence on idiopathic IDTI, focusing on its evolution, the natural history and the management strategies proposed in the literature. RECENT FINDINGS: IDTI is uncommon, with a reported prevalence between 0.5 and 7%. The main differential is with Crohn's disease and intestinal tuberculosis in endemic countries. A proportion of patients (0-50%) can progress and develop Crohn's disease; however, there are no reliable predictive factors to stratify IDTI patients. SUMMARY: IDTI is a challenging entity, with a small proportion of patients progressing to Crohn's disease over time thus requiring follow-up. Noninvasive modalities such as capsule endoscopy are useful for follow-up, but further research is required to better understand this entity.

The carbon cost of inappropriate endoscopy.

BACKGROUND AND AIMS: Digestive endoscopy is a resource-intensive activity with a conspicuous carbon footprint and an estimated rate of inappropriateness. However, the carbon costs of inappropriate endoscopic procedures still remain obscure. Here we evaluated the environmental impact of inappropriate endoscopic examinations. METHODS: We calculated the carbon cost of a standard endoscopic procedure (EGD and colonoscopy [CLS]), taking into account the items (eg, disposable materials, personal protective equipment) and energy required for the endoscopy procedure itself and the cleaning process. The rates of inappropriateness and the mortality cost of carbon (MCC) of endoscopic examinations in different scenarios were calculated. RESULTS: EGD and CLS presented a carbon cost of 5.43 kg and 6.71 kg of CO2, respectively. Different scenarios were evaluated, according to the number of endoscopic procedures performed in Italy per 1000 inhabitants and the reported data on their inappropriateness. The carbon cost of inappropriate EGD and CLS in Italy was 4133 CO2 metric tons per year (MCC, .93), ranging from 3527 to 4749, and equivalent to 1,760,446 L of gasoline consumed. Applying the same data to the European population, the estimated carbon footprint of inappropriate digestive endoscopy in Europe was 30,804 metric tons. CONCLUSIONS: The environmental impact of inappropriate endoscopic procedures in Europe is remarkable. These results highlight the need to adopt novel strategies aimed at reducing both the carbon footprint of digestive endoscopy and the rate of inappropriate procedures.

Treatment options for gastrointestinal bleeding blue rubber bleb nevus syndrome: Systematic review.

OBJECTIVES: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. METHODS: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. RESULTS: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow-up time (P = 0.19) or in the recurrence rate (P = 0.45). CONCLUSION: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported.

Reproducibility and diagnostic accuracy of pocket-sized ultrasound devices in ruling out compensated cirrhosis of mixed etiology.

OBJECTIVE: Fibrosis is the key prognostic factor in chronic liver disease patients. Liver surface nodularity (LSN) is the ultrasonographic sign with the highest accuracy to detect advanced liver fibrosis. The use of pocket-sized ultrasound devices (PUDs) has been assessed in several clinical settings but never as regards chronic liver disease (CLD) severity. Our study aimed at evaluating the feasibility, reproducibility, and diagnostic accuracy of PUD in LSN identification. METHODS: We enrolled all the consecutive adults referred for percutaneous liver biopsy. Two independent operators evaluated LSN by PUD; one sonographer used standard ultrasound (US). Transient elastography (TE) and liver biopsy were performed on all the patients. PUD reproducibility was evaluated by Cohen's k statistic. PUD, standard US, and TE results were compared with histology staging. RESULTS: A total of 104 consecutive patients (aged 54 ± 14 years) with mixed-etiology CLD were studied. Assessment by PUD was feasible in all the patients and showed very good inter-observer agreement with Cohen's k = 0.87 (95% CI 0.72-0.95). The diagnostic accuracy estimates for PUD in diagnosing compensated cirrhosis (F = 4) were 87.5% sensitivity, 76.8% specificity, positive likelihood ratio (LR) 3.78, and negative likelihood ratio (LR-) 0.16, while those for standard US and TE (> 12.5 kPa) were, respectively, 87.5% sensitivity, 72.6% specificity, LR+ 3.2, and LR- 0.17, and 87.5% sensitivity, 90.5% specificity, LR + 9.2, and LR- 0.13. CONCLUSIONS: PUD reproducibility in assessing LSN was excellent even with operators of different experience. PUD performed very well in excluding advanced CLD. PUD can be used as a first-line tool for screening patients to undergo more invasive techniques, thus shortening the time for clinical decision-making. KEY POINTS: • PUD is highly reproducible in assessing the sign of liver surface nodularity. • PUD showed high diagnostic accuracy in excluding the presence of advanced chronic liver disease. • PUD can be used as a first-line tool for screening patients with CLD who should undergo more invasive techniques.

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer.

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.

Cost-benefits and environmental impact of the no-biopsy approach for the diagnosis of coeliac disease in adults.

Objective: Recent evidence suggests that adult patients with IgA tissue transglutaminase levels of ≥10× the upper limit of normal could be accurately diagnosed with coeliac disease without undergoing endoscopy and biopsy. We aimed to evaluate the cost-benefits and the environmental impact of implementing the no-biopsy approach for diagnosing coeliac disease in clinical practice. Design: We calculated the overall direct and indirect costs of the conventional serology-biopsy approach and the no-biopsy approach for the diagnosis of coeliac disease based on the national average unit costs and the Office of National Statistics data. We further estimated the environmental impact of avoiding endoscopy based on the estimated greenhouse gas emissions from endoscopy. Results: Approximately 3000 endoscopies for suspected coeliac disease could be avoided each year in the UK. Implementing the no-biopsy approach for the diagnosis of coeliac disease in adults could save the National Health Service over £2.5 million in direct and indirect costs per annum and reduce endoscopy carbon footprint by 87 tonnes of CO2 per year, equivalent to greenhouse gas emissions from driving 222 875 miles, carbon emissions from charging over 10 million smartphones and the carbon sequestrated by 1438 trees grown for 10 years. Conclusion: The implementation of this non-invasive green approach could be an essential first step in the 'Reduce' strategy advocated by the British Society of Gastroenterology and other international endoscopy societies for sustainable endoscopy practice.

Incomplete small bowel capsule endoscopy: Risk factors and cost-effectiveness of real-time viewing.

Background and study aims International guidelines recommend real-time viewing (RTV) in capsule endoscopy for gastric emptying monitoring, yet it is often overlooked in clinical practice. We aimed to assess risk factors for incomplete small bowel capsule endoscopy (SBCE) and evaluate the clinical relevance and cost-effectiveness of RTV implementation. Methods We included consecutive SBCEs from 2013 to 2020. RTV was not applied per local protocol. We used multivariate logistic regression to identify risk factors for incomplete SBCE, including prolonged gastric transit time (GTT) and prolonged small bowel transit time (SBTT). Results Analyzing 858 SBCEs, we observed a completion rate of 94.6%. Prolonged GTT and SBTT were present in 4.9% and 18.2% of complete SBCEs, and in 13% ( P =0.03) and 10.8% ( P =0.24) of incomplete SBCEs, respectively. Only 0.7% (6 of 858) had incomplete SBCE with prolonged GTT. In both univariate and multivariate analysis, a modifiable (prolonged GTT odds ratio [OR] 2.9; 95% confidence interval [CI] 1.1-7.5) and two unmodifiable risk factors (inpatient status OR 2.3; 95% CI 1.1-4.5) and history of incomplete SBCE (OR 4.2; 95% CI 1.3-13.7) were independently linked to higher incomplete SBCE rates. The pretest completion probability was 90.5% and 95.8% in patients with and without unmodifiable risk factors, respectively ( P <0.01). The direct cost of systematic RTV adoption and prokinetics administration would be €5059, aiming to identify and treat each case of prolonged GTT associated with incomplete SBCE. Conclusions Modern devices make incomplete SBCE rare, usually not tied to prolonged GTT. In a low-incidence scenario, widespread RTV use brings high costs and uncertain effectiveness.

Narrow-band imaging for optical diagnosis of duodenal villous atrophy in patients with suspected coeliac disease: A systematic review and meta-analysis.

BACKGROUND: Narrow-band imaging (NBI) is a readily accessible imaging technique that enhances mucosal visualisation, allowing for a more accurate assessment of duodenal villi. However, its role in the diagnosis of coeliac disease (CD) in clinical practice remains limited. METHODS: We systematically searched several databases in June 2023 for studies evaluating the diagnostic accuracy of NBI for detecting duodenal villous atrophy (VA) in patients with suspected CD. We calculated the summary sensitivity, specificity, and likelihood ratios using a bivariate random-effects model. The study followed PRISMA guidelines and was registered at PROSPERO (CRD42023428266). RESULTS: A total of 6 studies with 540 participants were included in the meta-analysis. The summary sensitivity of NBI to detect VA was 93% (95% CI, 81% - 98%), and the summary specificity was 95% (95% CI, 92% - 98%). The area under the summary receiver operating characteristic curve was 0.98 (95% CI, 96 - 99). The positive and negative predictive values of NBI were 94% (95% CI, 92% - 97%) and 92% (95% CI, 90% - 94%), respectively. CONCLUSION: NBI is an accurate non-invasive tool for identifying and excluding duodenal VA in patients with suspected CD. Further studies using a validated classification are needed to determine the optimal role of NBI in the diagnostic algorithm for CD.

Clinical impact of videocapsule endoscopy and device-assisted enteroscopy in non-bleeding small bowel lesions.

Background: Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are part of the diagnostic and therapeutic work-up of indications other than suspected small bowel bleeding (OSBB). The literature is currently lacking studies describing these procedures in this particular setting. Objectives: We assessed the clinical impact of VCE and DBE in a large monocentric cohort of OSBB patients, as compared to a control group of suspected small bowel bleeding (SSBB) patients who underwent enteroscopy over the same period. Design: Monocentric, retrospective, cohort study. Methods: We collected the data of consecutive patients with OSBB undergoing VCE and/or DBE from March 2001 to July 2020. The demographic and clinical parameters of the patients, technical characteristics, and adverse events for each procedure were collected. The impact of VCE and DBE was defined in terms of diagnostic yield (DY). The patients were subdivided according to the main indication into four groups: celiac disease, Crohn's disease (CD), neoplasia, and persistent gastrointestinal symptoms. Results: A total of 611 VCEs and 387 DBEs were performed for OSBB. The main indications were complicated celiac disease and CD. The DYs of VCE and DBE overall were 53 and 61.7%, respectively, with some variance among the four groups. We report no statistical differences in the DY of VCE and DBE in SSBB vs OSBB (57.7% vs 53%, p = 0.0859 and 68.8% vs 61.7%, p = 0.0582, respectively). OSBB patients were significantly younger than those with SSBB. However, similarly to SSBB (k = 0.059), poor agreement between the enteroscopic techniques was found in the OSBB population (k = 0.109). The safety of both procedures in OSBB was comparable to that in SSBB patients. Conclusion: VCE and DBE are effective and safe in suspected OSBB, where their role is similar to that in SSBB, their main indication.

Effectiveness of double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (DBE-ERCP): A multicenter real-world study.

BACKGROUND AND AIMS: To investigate the effectiveness of double-balloon enteroscope-assisted retrograde cholangiopancreatography (DBE-ERCP) in patients with gastrointestinal surgically altered anatomy (SAA). METHODS: From May 2013 to October 2021, all consecutive patients undergoing DBE-ERCP in three gastroenterological referral centers in Northern Italy were enrolled in the study. Patients were assessed regarding their medical history, previous surgery, time from previous surgery to the DBE-ERCP procedure, and the success or failure of DBE-ERCP. RESULTS: Fifty-three patients (60% men, median age 65 (23-89) years) undergoing 67 DBE-ERCP procedures (1-3 DBE-ERCP per patient) were enrolled. Reasons for SAA included orthotopic liver transplantation (23%), ulcers (15%), malignancies (43%), difficult cholecystectomy (17%), and other causes (2%). Types of surgery included Roux-en-Y biliodigestive anastomosis (45%), Roux-en-Y gastrectomy (32%), pancreaticoduodenectomy (17%), and Billroth II gastrectomy (6%). The overall DBE-ERCP success rate was 86%. The type of surgery, indications, and the length of time between previous surgery and DBE-ERCP were not statistically associated with DBE-ERCP success. The DBE-ERCP success rate increased from 2018 to 2021. CONCLUSIONS: DBE-ERCP is a successful procedure in challenging patients with SAA. The improvement in results over time indicates the necessity of adequate training and of centralizing patients in referral centers.

Dual X-ray absorptiometry-derived bone status indexes and videocapsule intestinal aspects in celiac disease.

BACKGROUND AND AIM: Celiac disease is a risk factor for osteopenia and osteoporosis. Our aim was to evaluate the possible correlation between villous atrophy extension and dual-energy X-ray absorptiometry (DXA)-derived parameters of bone status. METHODS: We have retrospectively analyzed data of 47 celiac patients (36 women, 52 ± 14 years of age) who underwent video capsule endoscopy and DXA scans within 1 year of interval from 2006 to 2019. Quantitative, qualitative and geometric DXA parameters were collected only from the most recent DXA measurements. RESULTS: . Patients were divided into three categories; the first included those with no lesions at video capsule endoscopy (23 patients), the second those with typical lesions (mucosal atrophy, mosaicism and scalloping) in less than one-third of the small bowel (SB) (16 patients) and the third those with typical lesions in more than one-third of the SB (7 patients). In the third group, bone mineral density seemed to be lower in both the lumbar spine and the hip ( P = 0.026 and P = 0.011, respectively). The deterioration of bone structure in patients with severe and extended SB atrophy was statistically significant ( P = 0.032). Furthermore, bone density, structure and geometry did not correlate with the duration of the gluten-free diet. Notably, autoimmune comorbidities did not affect DXA results. CONCLUSION: Neither endoscopic nor histological atrophy itself can explain the deterioration of bone mineralization and structure, whereas atrophy extension appeared to be responsible for bone impairment.

Clinical features of type 1 and 2 refractory celiac disease: Results from a large cohort over a decade.

OBJECTIVES: Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up. METHODS: We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients. RESULTS: Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality. CONCLUSIONS: Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality.

Bleeding Lesion from Roux-en-Y Hepaticojejunostomy: A Successful Combined Hemostasis with Dual Emission Laser 1.9/1.5 µm.

A 28-year-old woman, with a history of liver transplantation with Roux-en-Y hepaticjejunostomy, was admitted for melena and severe anemia. Bidirectional endoscopy was normal. Capsule endoscopy demonstrated fresh blood in the efferent limb downstream of the jejuno-jejunostomy. Anterograde double-balloon enteroscopy (DBE) showed an adherent clot with a visible vessel oozing next to the hepaticojejunostomy. Bleeding was treated firstly with argon plasma coagulation and endoclips and further treated with dual emission laser, achieving complete hemostasis. At the 3 months follow-up, hemoglobin was stable without evidence of re-bleeding.

Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor ß cell-cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

The role of elastography in viral hepatitis and autoimmune hepatitis.

The prognosis of chronic liver diseases, which represent a major public health problem, is mainly linked to the extent and progression of liver fibrosis and the subsequent risk of developing cirrhosis and related complications, mainly hepatocellular carcinoma. During the past decade many noninvasive methods and in particular electrographic techniques, have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility and poor acceptance by patients. The aim of this review was to provide a comprehensive review of the role of elastography techniques in viral chronic liver diseases and autoimmune hepatitis, with the focus on the possible advantages and limitations of these techniques and on their diagnostic accuracy in predicting the stage of liver fibrosis.