United European Gastroenterology Journal最新文献

Background and aims: Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.

Methods: In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data.

Results: The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures.

Conclusions: TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.

Chronic pancreatitis is a severe disabling disease with persistent pain as the most prominent symptom often leading to significant quality of life (QoL) reduction. Current international guidelines propagate a step-up approach in which surgery should only be considered as a last resort in patients with failure of both medical and endoscopic interventions. Accumulating evidence, however, suggests that surgery is superior to endoscopic therapy and that early surgical intervention is beneficial in terms of pain relief, pancreatic function and QoL. Several surgical procedures are available with low morbidity and mortality rates, providing excellent long-term results. The purpose of this review was to present an overview of the surgical treatment options for chronic pancreatitis with a focus on the timing of surgery.

Background and aims: People with inflammatory bowel disease (IBD) often experience pain, fatigue and bowel incontinence and are at an increased risk of anxiety and depression. Our aim was to assess the impact of these symptoms on health-related quality of life (QoL) in IBD.

Methods: In the IBD-BOOST survey, over 26,000 people with IBD across the UK were approached; 8486 participant-completed surveys were returned. Participants' QoL was measured using the EQ-5D-5L questionnaire and their QoL was calculated on a scale ranging from 1 (perfect health) to -0.594 (worst health). Item non-response was imputed. Stages of linear regression models assessed the associations of symptoms with QoL controlling for IBD type, socio-demographic characteristics, co-morbidities and, in further analysis, for IBD activity and IBD control.

Results: The EQ-5D-5L questionnaire was fully completed by 8093 (95.4%) participants (mean age of 50 years [SD 15]; 49% with Crohn's disease). The mean QoL was 0.76 (SD 0.23). From the three IBD-related symptoms, pain was associated with the largest QoL decrement (-0.159), followed by fatigue (-0.140) and bowel incontinence (-0.048). Co-occurrence of pain and fatigue further reduced QoL. Clear graded associations were observed between symptom severity and QoL decrements (all trend p < 0.001). Depression and anxiety were also associated with significant QoL decrements (-0.102 and -0.110 for moderate-to-severe anxiety and moderately severe depression, respectively). Worse IBD control and higher IBD activity were associated with lower QoL.

Conclusions: We report strong associations between symptoms of pain, fatigue, bowel incontinence, anxiety, depression, and their severity and reduced QoL in IBD. These estimates could inform future IBD management interventions.

Background: Currently, there is still a lack of an accurate predictive model for delayed gastric emptying (DGE) following pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to develop a concise model that could effectively predict the risk of DGE.

Methods: This retrospective cohort study included a training cohort of 1251 consecutive PDAC patients who underwent PD from the US multicenter ACS-NSQIP database. Additionally, a validation cohort of 934 consecutive PDAC patients who underwent PD was included from the National Cancer Center in China. A total of 46 perioperative indicators were incorporated in the analysis. The DGE risk stratification (DGERS) model was then developed and validated using Lasso-logistic regression.

Results: After screening using Lasso-logistic regression, we identified four independent predictors that were significantly correlated with DGE: days to pancreatic drain removal (HR, 1.05; 95% CI, 1.02-1.08; p < 0.001), pancreatic fistula (HR, 2.61; 95% CI, 1.65-4.12; p < 0.001), sepsis/septic shock (HR, 2.46; 95% CI, 1.52-3.91; p < 0.001), and reoperation (HR, 4.16; 95% CI, 2.27-7.57; p < 0.001). Based on these factors, we developed a nomogram to predict postoperative DGE. The model demonstrated excellent calibration and optimal performance in the validation cohorts (AUC, 0.73; 95% CI, 0.67-0.73). In the validation cohort, the DGERS exhibited significant risk stratification ability, with AUC values of 0.7, 0.61, and 0.74 for the low-, moderate-, and high-risk groups, respectively.

Conclusions: This study identified four factors that independently increased the occurrence of DGE in patients with PDAC after PD, including days to pancreatic drain removal, pancreatic fistula, sepsis/septic shock, and reoperation. Based on these findings, we developed a personalized and straightforward DGERS that enables dynamic and precise prediction of DGE risk, allowing for effective stratification of individuals based on their risk profiles.

Background and aim: For branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WFs) or high-risk stigmata (HRS), current guidelines recommend surveillance. However, these intraductal papillary mucinous neoplasm (IPMNs), especially the small and stable-sized ones, carry a low risk of malignant transformation. Our aim was to assess whether small cyst size and absence of rapid growth provide reassurance against the development of WFs/HRS and malignancy (high-grade dysplasia (HGD) or pancreatic cancer (PC)).

Methods: PubMed/Medline, Embase, the Cochrane Library and the Web of Science Core Collection were systematically searched from inception to May 2023 to identify studies investigating surveillance outcomes of low-risk BD-IPMNs. Studies assessing baseline cyst size and/or growth in relation to WFs/HRS and/or HGD/PC were included. The Newcastle-Ottawa scale tool was used to assess study quality.

Results: Of the 1937 identified manuscripts, 21 studies were eligible for inclusion. The quality of these studies was considered reasonable. A negative association between cyst size and WFs/HRS development was found in 11 out of 13 relevant studies, but only one out of nine studies reported a negative association between size and malignancy. Regarding cyst growth, four out of six studies described a negative association with the development of WFs/HRS, and all six reported a negative association with malignancy. The pooled relative risk (RR) of developing WFs/HRS or malignancy for cysts ≤15 mm was 0.37 (95% CI 0.25-0.57) and the RR of developing malignancy for cyst growth <2-2.5 mm/year was 0.04 (95% CI 0.02-0.09)).

Conclusion: This systematic review and meta-analysis shows that small and stable-sized low-risk BD-IPMNs are associated with a markedly low progression rate, with stable cyst size being the most reassuring feature. Because of substantial heterogeneity in definitions and reported outcome measures, prospective studies are needed to confirm that surveillance of small and stable sized cyst can be de-intensified or even discontinued.

Background: Pancreatitis poses a growing public health concern among children and adolescents, yet comprehensive data on its prevalence, incidence, mortality, and disability-adjusted life years (DALYs) remain scarce. This study aims to analyze global, regional, and national trends in pancreatitis burden over the past 3 decades.

Methods: Using data from the Global Burden of Disease (GBD) 2019 database spanning 1990-2019, we assessed pancreatitis prevalence, incidence, mortality, and DALYs, reporting on numbers, rates, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized DALYs rate (ASDR), and average annual percentage changes (AAPCs). Trends were analyzed by age, sex, region, and socio-demographic index (SDI) using jointpoint analysis and predictive modeling.

Results: Globally, pancreatitis prevalence and incidence rates have increased (AAPC prevalence = 0.13, 95% CI: 0.11-0.16; AAPC incidence = 0.30, 95% CI: 0.28-0.32), while mortality and DALYs rates have decreased (AAPC mortality = -1.30, 95% CI: -1.53, -1.07; AAPC DALYs = -1.21, 95% CI: -1.41, -1.01). Both genders showed similar trends. Children under 5 and adolescents 15-19 had higher mortality and DALYs rates. Low SDI regions experienced the greatest increase in ASIR. Eastern Europe exhibited high and rising ASIR, ASMR, and ASDR. Projections indicate continued rise in prevalence with declining mortality and DALYs.

Conclusion: Pancreatitis burden in children and adolescents has surged globally, especially in lower SDI regions. These findings underscore the urgent need for targeted interventions and healthcare resources in affected areas.

Background: Local injection of darvadstrocel, a suspension of expanded adipose-derived allogenic mesenchymal stem cells, has been used for treatment-refractory perianal fistulas in Crohn's disease (CD).

Objective: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD.

Methods: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random-effects meta-analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I² value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted.

Results: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4-72.7) and 77.2% (95% CI 70.1-83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow-up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow-up time (p = 0.85). For effectiveness outcomes, between-study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient-years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively.

Conclusion: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile.

Background: The Japan Esophageal Society proposed the JES microvessel classification to assess eligibility of early esophageal squamous cell neoplasia (ESCN) for endoscopic resection based on intrapapillary capillary loop assessment. We aimed to assess its diagnostic reproducibility and accuracy in Western ESCN patients.

Methods: Intrapapillary capillary loops on endoscopic images of Western ESCN lesions (n = 113) collected between 2010 and 2022 were assessed by nine endoscopists, including three Japanese expert endoscopists, three Western expert endoscopists, and three residents-in-training, and graded according to the JES microvessel classification where microvessel type A corresponds with normality or low-grade intraepithelial neoplasia, and microvessel types B1, B2, and B3 correspond with high-grade intraepithelial neoplasia or invasion into the lamina propria, muscularis mucosae or superficial submucosa, and deep submucosa, respectively. Outcomes included overall accuracy in predicting ESCN invasion depth and interobserver agreement.

Results: Good interobserver agreement was observed among expert endoscopists (Krippendorf's alpha 0.64, 95% CI 0.57-0.70), while agreement was moderate among residents-in-training (Krippendorf's alpha 0.58, 95% CI 0.52-0.72). Overall accuracy of the JES microvessel classification was 53% (95% CI 42-63), 52% (95% CI 41-62), and 44% (95% CI 34-55) for Japanese endoscopists, Western endoscopists, and residents-in-training, respectively. Sensitivity and specificity for vessel type A, B1, B2, and B3 across assessors were 0%-50% and 89%-100%, 55%-64% and 66%-77%, 42%-71% and 60%-76%, and 10%-24% and 92%-97%, respectively. Negative predictive value ranged between 80% and 85% for B3 vessels.

Conclusion: Overall accuracy of the JES microvessel classification in Western ESCN patients is low, though absence of B3 vessels as assessed by experienced endoscopists may predict superficial ESCN amenable to endoscopic resection.

Trial registry: www.trialregister.nl; NL8897 (6-9-2020).