Clinical and Translational Gastroenterology最新文献

Abstract: Pancreatic cancer represents the most lethal malignancy among all gastrointestinal tumors. Recent medical advances, such as targeted therapy and immunotherapy, increasingly rely on tumor molecular profiling to tailor treatment for patients with advanced cancer. Given the risks associated with invasive biopsy, circulating cell-free DNA (cfDNA) has emerged as a cutting-edge approach for the detection and monitoring of cancer. The minimally invasive operation, coupled with the sensitive and timely detection of cancer across multiple clinical application, makes cfDNA a potential solution to transform precision oncology. Despite the advances, the expected widespread application of liquid-biopsy is still limited due to a series of substantial challenges in technique and clinical settings. Here we discussed technologies and methodologies in the detection of cfDNA. The opportunities to address substantial challenges, including achieving clinical meaningful detection sensitivities, enhancing of assay accessibility, evaluating the clinical sensitivity of circulating tumor DNA (ctDNA) burden in clinical settings, were highlighted to support the integration of liquid biopsies into cancer treatment. The most recent ctDNA-associated studies were summarized to provide a whole picture of the application of ctDNA in the adaptive management and surveillance of pancreatic cancers.

Introduction: In Hungary, population-based colorectal cancer (CRC) screening was introduced shortly before the onset of COVID-19 pandemic. We aimed to assess the combined impact of these two factors on the incidence and characteristics of CRC.

Methods: The retrospective cohort study included all patients with newly diagnosed CRC between 2014 and 2023 and divided into pre-pandemic with screening (2015-2016, 2019), pre-pandemic without screening (2014, 2017-2018), pandemic (2020-2021), and post-pandemic (2022-2023) subgroups. CRC incidence, diagnostic patterns, and tumor stage were compared across subgroups.

Results: Crude CRC incidence in institution's care area was lower during pandemic (102.51 per 100,000) compared with the pre-pandemic with screening (117.92 per 100,000; p=0.060) and post-pandemic (120.60 per 100,000; p=0.044) subgroups. Age-standardized incidence differed significantly only between the pre-pandemic with screening and pandemic subgroups (125.30 vs. 105.88 per 100,000; p<0.001). During pandemic, the proportion of early-stage (AJCC 0-I) cancers was significantly reduced compared with the pre-pandemic with screening subgroup (18.74% vs. 25.08%; p=0.048) and the proportion of T1 cancers was also lower compared with the post-pandemic subgroup (6.90 vs. 12.2%; p=0.026). During pandemic, both the annual number of colonoscopies (2,706.00) and the mean number of colonoscopies required to detect one CRC (15.56) were markedly lower compared with the pre-pandemic with screening (4,590.67 and 13.97), pre-pandemic without screening (3,824.33 and 10.67), and post-pandemic (4,573.50 and 15.50) subgroups.

Conclusions: The COVID-19 pandemic was associated with unfavorable changes in CRC epidemiology. Organized screening may have mitigated the negative impact during the pandemic and post-pandemic periods.

Introduction: Some patients with chronic pancreatitis (CP) experience nociplastic pain due to central nervous system dysregulation, yet its recognition is limited by the lack of bedside tools. Self-reported body maps are used to assess pain widespreadedness and to differentiate pain mechanisms in chronic pain patients, but their utility in CP is unclear. This study aimed to determine whether pain widespreadedness, measured through a body map, is associated with features of nociplastic pain in CP.

Methods: We conducted a cross-sectional analysis of adults with definite CP enrolled in a single-center longitudinal cohort. Pain widespreadedness was assessed using the Michigan Body Map and categorized by the number of painful regions (0-7) and by the presence of localized vs widespread (≥3 regions) pain. Clinical features of nociplastic pain were measured using validated psychometric and pain surveys. Group comparisons were performed with multivariable regression models adjusted for demographics, comorbidities, and CP characteristics.

Results: Among 110 participants (mean age 54 years, 52% male), 93% reported abdominal pain. Of those with abdominal pain, 64% had widespread pain. Increasing the number of painful regions and widespread pain (vs localized) were independently associated with higher pain severity, pain interference, and neuropathic pain scores, as well as more fatigue, impaired physical functioning, greater chronic overlapping pain conditions, and poorer physical and mental health.

Discussion: Two-thirds of patients with CP had widespread pain assessed using a body map. This subgroup had more severe symptoms and features of nociplastic pain. This simple tool may facilitate targeted, mechanism-based pain management in CP.

Introduction: Ongoing surveillance after successful endoscopic eradication therapy (EET) for Barrett's esophagus (BE) related neoplasia is essential to detect and manage recurrence. Despite established surveillance interval recommendations after complete eradication of intestinal metaplasia (CE-IM), patient compliance with repeat endoscopy is frequently suboptimal. Understanding patient drivers to adherence is essential to inform interventions that address the high rates of overdue surveillance and loss to follow-up.

Methods: Patients with BE-related neoplasia who achieved CE-IM were eligible for inclusion and classified as delayed or on-time for endoscopic surveillance. Patients were prospectively enrolled and participated in structured virtual interviews designed to explore barriers and facilitators to on-time care. A rapid qualitative analysis approach was applied, continuing until thematic saturation was reached.

Results: Thirty-nine patients were interviewed: 22 (56.4%) were delayed, and 17 (43.6%) were on-time for surveillance. Patients in the delayed group had longer mean BE segment lengths and a higher prevalence of tobacco use. Geographic distance from the treatment center was the most frequently cited barrier to follow-up (n=17; 43.5%). Other common barriers were access limitations, financial concerns, misunderstanding of disease course, and test-related anxiety.

Discussion: Patient related drivers of delay in post-EET surveillance are largely logistical, socioeconomical, and psychological in nature. Solutions to reduce the significant burden on the patient and achieve timely surveillance may include transitioning patients back to their local endoscopists after CE-IM or incorporating non-endoscopic surveillance methods through patient centered approaches.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that increases susceptibility to chronic lung and liver diseases. There are limited data on testing rates in patients with cirrhosis. Guidelines recommend AATD testing in cryptogenic liver disease but not in patients with an established etiology. We aimed to quantify AATD testing patterns in a national cohort of patients with cirrhosis to inform guidelines.

Methods: In this retrospective cohort study of veterans with a new diagnosis of cirrhosis between January 1, 2008 and January 31, 2020, with follow-up until February 23, 2023, we identified predictors of testing, and of severe AATD (alpha-1 antitrypsin [AAT] < 57 mg/dL or PiSZ/PiZZ phenotype/genotype).

Results: Of the 126,210 patients with cirrhosis, 42,403 (33.6%) were tested, including 38,189 (30.3%) for AAT levels only, 1,103 (0.8%) for genotype/phenotype only, and 3,011 (2.4%) for both. Factors associated with higher AATD testing included specialist evaluation and White race, whereas patients with chronic obstructive pulmonary disease, hepatitis B/C, hepatocellular carcinoma, and hepatic decompensation were less likely to be tested. Only half of the patients with AAT levels of <57 mg/dL underwent genotype/phenotype testing. Most patients (94.7%) with severe AATD-associated liver disease also had an alternate etiology of liver disease, including metabolic dysfunction associated with steatotic liver disease (53.6%) or viral hepatitis (16.1%), and would be missed if testing only patients with cryptogenic liver disease.

Discussion: AATD testing rates in veterans with cirrhosis are low, and patients at high-risk are less likely to be tested. Guidelines are needed to emphasize universal AATD testing in patients with cirrhosis regardless of the presence of other risk factors.

Background: Patients with gastroesophageal reflux disease (GERD) are commonly instructed to reduce coffee intake. However, prior studies evaluating the effects of coffee on GERD yielded conflicting results. We aimed to perform a comprehensive systematic review and meta-analysis to assess the association between coffee use and risk of GERD and its complications.

Methods: A protocolized search strategy was developed for PubMed, EMBASE, and Web of Science databases in accordance with PRISMA and MOOSE guidelines. Measured outcomes for GERD were compared between coffee drinkers and non-drinkers. Dichotomous events between unmatched groups were used to calculate pooled proportions with rates estimated using random effects models and effect size. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot asymmetry and Egger regression.

Results: A total of 40 studies encompassing 122,074 patients were included (85,400 coffee drinkers vs 36,674 non-drinkers). GERD was more common among coffee users than non-users [34.9% (CI:28.5-41.8) vs 30.7% (CI:25.2-36.7); OR:1.18 (CI:1.03-1.36; I2=89.38)]. There was no significant association between coffee intake and Barrett's esophagus [22.1% (CI:12.8-35.4) users vs 17.6% (CI:5.5-43.8) non-users; OR:1.13 (CI:0.79-1.61; I2=55.5)]. There was no evidence of publication bias based on funnel plot and Egger regression testing (p>0.05 for all analyses).

Conclusion: Coffee use was associated with a small, statistically significant increased rate of GERD, but not Barrett's. The magnitude of this effect, however, is of unclear clinical significance. The role of routine avoidance/reduction of coffee intake as universal lifestyle modification for GERD needs further evaluation.

Introduction: Dairy consumption has been linked to the development of autoimmune diseases. We aimed to examine the association between dairy intake and risk of incident inflammatory bowel disease.

Methods: We conducted a prospective cohort study of 197,763 participants without a baseline diagnosis of inflammatory bowel disease in 1986 in Nurses' Health Study, 1991 in Nurses' Health Study II (NHSII), and 1986 in Health Professionals Follow-up Study. Data on dairy intake were collected every 2-4 years using a validated semi-quantitative food frequency questionnaire and modeled according to quintiles for total intake and quartiles for components of dairy. We used Cox proportional hazard modeling to estimate adjusted hazard ratios and 95% CIs.

Results: Through the end of follow-up in 2016 in Nurses' Health Study and Health Professionals Follow-up Study, and 2017 in Nurses' Health Study II, we documented 347 Crohn's disease cases and 428 cases of ulcerative colitis (UC). In our primary analysis, we observed an inverse association between baseline dairy intake (P trend = 0.04) and risk of UC (adjusted hazard ratio of 0.72 [95% CI 0.52-1.00 comparing extremes of quintiles]). Among dairy components, baseline yogurt consumption (hazard ratio = 0.70; 95%CI 0.5-0.99; P trend = 0.05) was most strongly associated with decreased risk of UC. There was no consistent association between dairy intake and risk of Crohn's disease.

Discussion: In 3 large prospective cohort studies, we observed a suggestive inverse association between baseline dairy intake, particularly from yogurt, and risk of UC. Future studies are needed to confirm these results.

Introduction: Disruptions to colorectal cancer (CRC) screenings occurred during the COVID-19 pandemic, but lingering effects and equity of this impact remain unclear. We evaluated local patterns and trends in CRC screening and cancer staging across 4 time periods and examined disparities by neighborhood social deprivation index (SDI).

Methods: Colonoscopies, fecal immunochemical test (FIT), fecal occult blood test, and sigmoidoscopies were identified at our institution through electronic medical records from March 2018 to February 2023 (n = 27,946). Screenings were linked to zip code-level SDI and aggregated by month across 4 periods: prepandemic (March 2018-February 2020), pandemic (March 2020-February 2021), postpandemic year 1 (March 2021-February 2022), and postpandemic year 2 (March 2022-February 2023). Analysis of variances compared monthly screening volumes and proportions from high-SDI areas across periods; χ 2 tests assessed differences in cancer staging.

Results: CRC screenings dropped during March-May 2020 but rebounded, resulting in no significant difference in monthly averages across periods ( P = 0.52). However, colonoscopies declined, whereas FIT use increased over time. The proportion of patients from high-SDI neighborhoods declined from 32.2% prepandemic to 28.9% by postpandemic year 2 ( P = 0.002), largely driven by reduced FIT screenings among individuals from these areas (30.9%-23.7%, P < 0.0001). Later-stage diagnoses increased during the pandemic and postpandemic year 1 but returned to baseline by year 2.

Discussion: Despite volume recovery, shifts in modality use and declining representation from high-SDI neighborhoods suggest growing disparities in CRC screening. Targeted outreach is needed to understand and address unmet screening needs, to support equitable prevention efforts moving forward.

Introduction: Gastric cancer (GC) is one of the most prevalent and lethal gastrointestinal malignancies. MutS homolog 2 (MSH2), a DNA mismatch repair protein, has emerged as a promising prognostic biomarker. However, traditional histopathological evaluation is limited by restricted fields compared with whole-slide imaging. This study aimed to investigate whether machine learning-derived digital pathomics features could predict MSH2 expression and clinical outcomes in GC.

Methods: Hematoxylin and eosin-stained whole-slide images from 234 patients were analyzed to extract quantitative pathological features. A pathomics score (PS) was developed to estimate MSH2 expression. The association between PS and overall survival (OS) was assessed using univariate and multivariate Cox regression. Survival differences between high-PS and low-PS groups were evaluated using Kaplan-Meier analysis. Functional enrichment and immune infiltration analyses were performed to explore potential biological mechanisms.

Results: Digital image analysis identified pathomics features associated with MSH2 expression. The PS served as a surrogate marker for MSH2 and effectively stratified patients into prognostic subgroups with significant different OS. High PS was associated with features suggestive of a stronger antitumor immune response, whereas low PS was linked to an immunosuppressive microenvironment.

Discussion: The machine learning-derived pathomics signature shows potential in predicting MSH2 expression. It can serve as a complementary research tool and provide clinically meaningful prognostic information for GC.

Introduction: US guidelines recommend surveillance colonoscopy after polyp removal, but stool testing may offer a more efficient, acceptable strategy for patients with nonadvanced lesions. We conducted exploratory analyses to evaluate the diagnostic accuracy of quantitative fecal immunochemical testing (FIT) results to diagnose advanced colorectal neoplasia in patients undergoing surveillance colonoscopy.

Methods: We classified patients by previous colonoscopy findings as having low, intermediate, or high risk polyps. We compared the diagnostic performance for detecting advanced colorectal neoplasia at an optimal cutoff identified by the Youden index vs the standard cutoff of 100 ng/mL. We also estimated cumulative sensitivity and specificity for serial FIT testing in patients with nonadvanced findings.

Results: Among the 449 participants (mean ± SD age 65.4 ± 7.1, 53.2% women, and 92.7% White), the median interval between colonoscopies was 5.0 years (IQR 3.5, 5.6); adequate or better bowel prep was achieved in 89.3%, and cecal intubation in 98.4%. We detected 55 advanced precancerous lesions, but no cancers. For patients with previous nonadvanced lesions (n = 378), the optimal cutoff was 26 ng/mL. Compared with the standard cutoff, the optimal cutoff increased sensitivity (14.3%-35.7%, P < 0.01) but reduced specificity (95.5%-79.2%, P < 0.01). Estimated cumulative sensitivity across 3 rounds of FIT testing was 73.4% at the optimal cutoff vs 37.1% with the standard cutoff.

Discussion: Lowering the FIT hemoglobin cutoff markedly improved sensitivity for detecting advanced precancerous lesions in patients without previous advanced polyps. Serial testing could further enhance detection. FIT-based surveillance should be further evaluated as a potential strategy to prioritize, delay, or replace colonoscopy.