Therapeutic Advances in Gastroenterology最新文献

Background: The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).

Objectives: We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival.

Design: In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed.

Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla^® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC).

Results: A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation.

Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC.

Background: Approval of the adalimumab (ADA) biosimilar ABP 501 for inflammatory bowel disease (IBD) indications was based on the principle of extrapolation, without indication-specific clinical trial data.

Objectives: To evaluate the real-world treatment patterns of ABP 501 in patients with IBD.

Design: Retrospective analysis of pharmacy claims data from Germany and France.

Methods: Continuously insured adult IBD patients who initiated ABP 501 between October 2018 and March 2020 were included. Treatment persistence, adherence, and post-ABP 501 switching patterns were evaluated for two mutually exclusive groups: ADA-naïve patients (i.e. no baseline use of ADA products) and ADA-experienced patients (i.e. previously treated with ADA products).

Results: A total of 3362 German patients and 733 French patients were included, with 54.4% and 65.3% being ADA-naïve patients, respectively. Median persistence (95% CI) on ABP 501 was 10.9 months (9.8-11.6) in ADA-naïve patients and 14.2 months (12.7-15.2) in ADA-experienced patients in Germany; for the French cohort, ADA-naïve and -experienced patients had median persistence of 12.8 months (10.2-14.7) and 11.5 months (8.8-14.4), respectively. During the first 12 months of ABP 501 initiation, 53.7% of German patients and 51.0% of French patients were adherent to the therapy. About 20% of patients in both countries switched from ABP 501 to another targeted therapy. In the German cohort, ADA-naïve patients most frequently switched to non-tumor necrosis factor inhibitor biologics, but ADA-experienced patients most commonly switched to reference product (RP); in the French cohort, patients most often switched to RP regardless of prior exposure to ADA products.

Conclusion: About 50% of patients persisted on and were adherent to ABP 501 therapy during the first 12 months after treatment initiation in two large European countries. Post-ABP 501, switching patterns varied between countries, indicating diversified treatment practices warranting further research on reason(s) for switching and potential overall treatment outcomes.

Background: Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma. It is critical to recognize the risk factors associated with BE.

Objectives: The present meta-analysis aims to systematically estimate the association of hiatal hernia with the risk of BE.

Design: A meta-analysis with trial sequential analysis.

Data sources and methods: The PubMed, EMBASE, and Cochrane Library databases were searched. The pooled odds ratios (ORs) and adjusted ORs (aORs) with their 95% confidence intervals (CIs) were calculated for the combined estimation of unadjusted data and data adjusted for confounders, respectively. Heterogeneity was quantified using the Cochrane Q test and I² statistics. Subgroup, meta-regression, and leave-one-out sensitivity analyses were employed to explore the sources of heterogeneity.

Results: Forty-seven studies with 131,517 participants were included. Based on the unadjusted data from 47 studies, hiatal hernia was significantly associated with an increased risk of any length BE (OR = 3.91, 95% CI = 3.31-4.62, p < 0.001). The heterogeneity was significant (I² = 77%; p < 0.001) and the definition of controls (p = 0.014) might be a potential contributor to heterogeneity. Based on the adjusted data from 14 studies, this positive association remained (aOR = 3.26, 95% CI = 2.44-4.35, p < 0.001). The heterogeneity was also significant (I² = 65%; p < 0.001). Meta-analysis of seven studies demonstrated that hiatal hernia was significantly associated with an increased risk of long-segment BE (LSBE) (OR = 10.01, 95% CI = 4.16-24.06, p < 0.001). The heterogeneity was significant (I² = 78%; p < 0.001). Meta-analysis of seven studies also demonstrated that hiatal hernia was significantly associated with an increased risk of short-segment BE (OR = 2.76, 95% CI = 2.05-3.71, p < 0.001). The heterogeneity was not significant (I² = 30%; p = 0.201).

Conclusion: Hiatal hernia should be a significant risk factor for BE, especially LSBE.

Registration: PROSPERO registration number CRD42022367376.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF.

Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients.

Design: Retrospective observational study.

Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially).

Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission.

Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Background: Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy.

Objectives: We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC.

Design: Monocentric, prospective study.

Methods: We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy.

Results: Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated.

Conclusion: Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies.

Trial registration: Not applicable.

Before the development of double-balloon enteroscopy (DBE), the standard management of small-bowel polyposis was surgical resection. This is an invasive procedure that could lead to short bowel syndrome. In the 21st century, several new enteroscopy techniques were distributed worldwide, including DBE, single-balloon enteroscopy, spiral enteroscopy, and motorized spiral enteroscopy. These devices enable the diagnoses and endoscopic interventions in the entire small bowel, even in patients with a history of laparotomy. In patients with Peutz-Jeghers syndrome (PJS), endoscopic ischemic polypectomy with clips or a detachable snare is the preferred method for managing pedunculated polyps because it is less likely to cause adverse events than conventional polypectomy. Although polyps in patients with PJS always recur, repeat endoscopic resection can reduce the total number and mean size of polyps in the long-term clinical course. Endoscopic reduction of small-bowel intussusception caused by PJS polyps can be successfully performed using DBE without surgery. A transparent hood is useful for securing a visual field during the treatment of small-bowel polyps, and minimal water exchange method is recommended to facilitate deep insertion. Familial adenomatous polyposis (FAP) is a genetic disorder that increases the risk of developing colorectal cancer. Because jejunal and ileal polyps in patients with FAP have the potential to develop into cancer via the adenoma-carcinoma sequence, periodical surveillance, and endoscopic resection are needed for them, not only polyps in the duodenum. In cases of multiple small-bowel polyps in patients with FAP, cold snare polypectomy without retrieval is an acceptable treatment option for polyps that are 10 mm or smaller in size. Additional good pieces of evidence are necessary to confirm these findings because this narrative review mostly includes retrospective observational studies from single center, case reports, and expert reviews.

Background: Exposure-response studies have shown that higher infliximab concentrations are associated with better outcomes in inflammatory bowel disease. There is little agreement about the optimal time to measure infliximab levels in children.

Objectives: We aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission. The secondary aim was to define target trough levels at weeks 6 and 14.

Design: We used routinely collected electronic healthcare data of 70 anti-tumour necrosis factor naïve children with inflammatory bowel disease treated with a standard infliximab induction- and variable maintenance scheme.

Methods: Trough levels and blood and faecal markers for disease activity were measured before every infliximab administration. Sustained remission was defined as the absence of symptoms and low inflammatory markers between weeks 26 and 52 after the start of infliximab therapy. Optimal infliximab levels at weeks 6 and 14 were determined using the receiver operating characteristic curve.

Results: The median infliximab level at week 6 was not significantly higher in children who achieved sustained remission compared to those who did not (16.9 mg/L versus 12.0 mg/L; p = 0.058) but the median infliximab level at week 14 was significantly higher in those with sustained remission (7.7 mg/L versus 3.8 mg/L; p = 0.006). The area under the receiver operating characteristics curves at weeks 6 and 14 to predict sustained remission was 0.67 (95% CI 0.51-0.83) and 0.75 (95% CI 0.60-0.90), respectively. Target trough levels at weeks 6 and 14 were ⩾13.2 and ⩾6.9 mg/L, respectively.

Conclusion: An infliximab measurement at week 14 with a target through level ⩾6.9 mg/L best predicted sustained remission.

Background: The integration of artificial intelligence (AI) into healthcare has opened new avenues for enhancing patient care and clinical research. In gastroenterology, the potential of AI tools, specifically large language models like ChatGPT, is being explored to understand their utility and effectiveness.

Objectives: The primary goal of this systematic review is to assess the various applications, ascertain the benefits, and identify the limitations of utilizing ChatGPT within the realm of gastroenterology.

Design: Through a systematic approach, this review aggregates findings from multiple studies to evaluate the impact of ChatGPT on the field.

Data sources and methods: The review was based on a detailed literature search of the PubMed database, targeting research that delves into the use of ChatGPT for gastroenterological purposes. It incorporated six selected studies, which were meticulously evaluated for quality using the Joanna Briggs Institute critical appraisal instruments. The data were then synthesized narratively to encapsulate the roles, advantages, and drawbacks of ChatGPT in gastroenterology.

Results: The investigation unearthed various roles of ChatGPT, including its use in patient education, diagnostic self-assessment, disease management, and the formulation of research queries. Notable benefits were its capability to provide pertinent recommendations, enhance communication between patients and physicians, and prompt valuable research inquiries. Nonetheless, it encountered obstacles in decoding intricate medical questions, yielded inconsistent responses at times, and exhibited limitations in generating novel content. The review also considered ethical implications.

Conclusion: ChatGPT has demonstrated significant potential in the field of gastroenterology, especially in facilitating patient-physician interactions and managing diseases. Despite these advancements, the review underscores the necessity for ongoing refinement, customization, and ethical regulation of AI tools. These findings serve to enrich the dialog concerning AI's role in healthcare, with a specific focus on ChatGPT's application in gastroenterology.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively interferes with the quality of life of the patients, on a physical, emotional, and social level. Its symptoms can vary including diarrhea, bleeding, abdominal pain, fever, and weight loss, depending on the type and location and severity of the disease. Despite evolving treatment, they do not always achieve control of the symptoms, so between 23% and 45% of people with idiopathic chronic ulcerative colitis, and up to 75% of those with Crohn's disease, eventually, will need surgery.

Objective: The increase in its incidence in Latin America has promoted a renewed interest on the part of the medical and scientific community in standardizing and unifying criteria for the proper diagnosis and management of the disease, which is part of the current discussions of various events; however, this interest has not yet been reflected in policies and initiatives by governments to address the disease. We decided to develop a consensus meeting in order to elucidate the actual situation of IBD care in our region.

Design: The methodology employed to build the consensus document derived from a review of literature, evidence, and policies on IBD, followed by a process of validation and feedback with a group of 10 experts in the field.

Methods: Nine experts from different countries in Latin America were reunited in web meetings on 2 days and voted on topics derived from the consensus document. A full agreement with 100% approval was needed, so topics were discussed to reach the consensus otherwise were removed.

Results: There is still a lack of information about IBD in Latin America, therefore IBD continues to be an 'invisible' disease and is little recognized by decision-makers.

Conclusion: This document describes the current situation of IBDs in the Latin American region, highlighting the main barriers and challenges in timely access to diagnosis and treatment, in order to demonstrate the need to promote the development and implementation of policies, in order to improve the quality of care of patients with IBD.

Background: Achieving endoscopic and histological remission is a critical treatment objective in ulcerative colitis (UC). Nevertheless, interobserver variability can significantly impact overall assessment performance.

Objectives: We aimed to develop a deep learning algorithm for the real-time and objective evaluation of endoscopic disease activity and prediction of histological remission in UC.

Design: This is a retrospective diagnostic study.

Methods: Two convolutional neural network (CNN) models were constructed and trained using 12,257 endoscopic images and biopsy results sourced from 1124 UC patients who underwent colonoscopy at a single center from January 2018 to December 2022. Mayo Endoscopy Subscore (MES) and UC Endoscopic Index of Severity Score (UCEIS) assessments were conducted by two experienced and independent reviewers. Model performance was evaluated in terms of accuracy, sensitivity, and positive predictive value. The output of the CNN models was also compared with the corresponding histological results to assess histological remission prediction performance.

Results: The MES-CNN model achieved 97.04% accuracy in diagnosing endoscopic remission of UC, while the MES-CNN and UCEIS-CNN models achieved 90.15% and 85.29% accuracy, respectively, in evaluating endoscopic severity of UC. For predicting histological remission, the CNN models achieved accuracy and kappa values of 91.28% and 0.826, respectively, attaining higher accuracy than human endoscopists (87.69%).

Conclusion: The proposed artificial intelligence model, based on MES and UCEIS evaluations from expert gastroenterologists, offered precise assessment of inflammation in UC endoscopic images and reliably predicted histological remission.