Annals of Gastroenterology最新文献

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The presence of the KRAS G12C mutation in patients with CRC is associated with poor responses to standard therapies and worse outcomes. This study systematically reviewed and analyzed the existing evidence on the efficacy of KRAS G12C inhibitors.

Methods: PubMed, Scopus, and ISI Web of Knowledge were searched, along with conference proceedings, posters, and major oncology journals. Eligibility criteria included clinical trials involving adult patients with KRAS G12C-mutant CRC. Data on treatment outcomes, study design, and patient demographics were extracted and analyzed using a random-effects model, with heterogeneity assessed via I2 statistics.

Results: Seventeen trials, comprising 663 patients with KRAS G12C-mutant metastatic CRC, were included. Monotherapy with KRAS G12C inhibitors demonstrated an objective response rate of 23%, while combination therapies with agents such as cetuximab and panitumumab showed a higher response rate of 43%. Stable disease rates were also higher in monotherapy (62%) compared to combination therapy (44%). The highest disease control rates were observed with combination therapies (96%). The overall progressive disease rate was lower with combination therapies (1%) than with monotherapies (10%).

Conclusions: The results indicate that KRAS G12C inhibitors, particularly in combination with other agents, show promising efficacy in treating metastatic CRC. High heterogeneity across studies suggests variability due to small sample sizes and early-phase trial designs. While preliminary data are promising, further large-scale phase III trials are essential to establish these inhibitors as a standard treatment for KRAS G12C-mutant CRC.

Background: Liver cirrhosis is characterized by major circulatory dysregulation, related to an imbalance between several vasoactive agents. Although alterations in intrahepatic and systemic vasculature have been rather well described, the peripheral microcirculation and endothelial function are less well studied. Our aim was to evaluate peripheral microcirculatory function in patients with cirrhosis via nailfold video-capillaroscopy.

Methods: We enrolled 60 patients with cirrhosis and 20 controls. All participants underwent nailfold video-capillaroscopy. Capillary density was measured at rest (baseline), after 4-min arterial occlusion (post-occlusive reactive hyperemia) and after 2-min venous congestion.

Results: Cirrhotic patients presented lower capillary density than controls at baseline (35.8±3.6 vs. 38±1.1 capillaries/mm², P=0.01), during post-occlusive reactive hyperemia (40.0±4.4 vs. 45.3±1.5 capillaries/mm², P<0.001), and after venous congestion (43.3±4.2 vs. 47.2±1.5 capillaries/mm², P<0.001). Capillary density decreased significantly with deterioration of Child-Pugh class at baseline (Child-Pugh A: 38.0±3.9 vs. Child-Pugh B: 35.6±2.7 vs. Child-Pugh C: 33.9±3.2 capillaries/mm², P<0.001), during post-occlusive reactive hyperemia (43.5±3.4 vs. 39.8±3.0 vs. 36.8±3.9 capillaries/mm², respectively, P<0.001), and after venous congestion (46.7±3.1 vs. 43.0±2.7 vs. 40.1±3.8 capillaries/mm², respectively, P<0.001).

Conclusions: Capillary density in all phases was significantly lower in cirrhotic patients compared to controls. Moreover, a lower capillary density was associated with deteriorating Child-Pugh stages, suggesting that increasing severity of cirrhosis is associated with more impaired peripheral microcirculatory function.

Background: Patients with metabolic dysfunction-associated steatohepatitis (MASH; nonalcoholic fatty liver disease activity score ≥4) and significant fibrosis (≥F2; at-risk MASH) are at increased risk for disease progression. Magnetic resonance elastography (MRE) combined with the fibrosis-4 (MEFIB) index enables the noninvasive diagnosis of at-risk MASH and significant fibrosis. We assessed the performance of the MEFIB index for ruling in/out both target conditions.

Methods: We analyzed studies up to February 2025 assessing the performance of MEFIB index for ruling in (MRE≥3.3 kPa plus FIB-4≥1.6) and out (MRE<3.3 kPa plus FIB-4<1.6) at-risk MASH or significant fibrosis, using liver biopsy as the reference standard. We calculated pooled diagnostic accuracy estimates using bivariate random-effects models.

Results: We included 7 studies with 3356 participants. For ruling in at-risk MASH, the MEFIB index yielded a pooled specificity of 0.94 (95% confidence interval [CI] 0.74-0.99), and a positive likelihood ratio (LRp) of 5.3 (95%CI 1.8-15.7). For ruling out at-risk MASH, the MEFIB index had a pooled sensitivity of 0.77 (95%CI 0.62-0.88) and a negative likelihood ratio (LRn) of 0.34 (95%CI 0.23-0.52). For ruling in significant fibrosis, the MEFIB index achieved a summary specificity of 0.93 (95%CI 0.85-0.97) with LRp 8.2 (95%CI 4.5-14.9). For excluding significant fibrosis, the pooled sensitivity and LRn of the MEFIB index were 0.88 (95%CI 0.79-0.94) and 0.16 (95%CI 0.08-0.31), respectively.

Conclusions: MEFIB index has acceptable accuracy for diagnosing at-risk MASH and significant fibrosis. Proposed thresholds can be used to identify both target conditions in high prevalence settings and facilitate patient recruitment in clinical trials.

Background: Iron deficiency anemia (IDA) commonly complicates patients with decompensated cirrhosis (DC). We investigated the efficacy of intravenous ferric carboxymaltose (FCM) over oral iron in treating IDA in these patients, the circulatory and renal effects of each treatment, and the prognostic impact of FCM.

Methods: We prospectively evaluated non-acutely anemic patients with DC and hemoglobin levels 8-10 g/dL: 58 with IDA (serum ferritin <30 ng/mL) and 90 without IDA. Patients with IDA received oral iron polymaltose (IP) for 3 months and those not achieving hemoglobin increases ≥2 g/dL switched to FCM. Systemic vascular resistance (SVR) as mean arterial pressure/cardiac output ratio, plasma renin activity (PRA), plasma aldosterone, glomerular filtration rate (GFR) and renal blood flow (RBF) were evaluated 3 months after each treatment. All patients with recurrent IDA during follow up received FCM. New/recurrent decompensation and survival rates were assessed in patients with and without IDA.

Results: Hemoglobin increased by ≥2 g/dL in 6/51 (11.7%) patients who tolerated IP, compared to 34/45 (75.5%; P<0.001) FCM-treated patients. FCM use was safe and, unlike IP, it significantly increased SVR, GFR and RBF, while significantly reducing PRA and plasma aldosterone (P<0.001). Percentage hemoglobin changes correlated with changes in SVR (r=0.533; P<0.001), GFR (r=0.775; P<0.001) and RBF (r=0.803; P<0.001). FCM-treated patients showed lower 5-year risk of decompensation (P=0.002) and mortality (P=0.006), and lower incidence of hepatorenal syndrome (n=0.03), than patients without IDA.

Conclusions: FCM outperforms oral iron in ameliorating IDA in DC patients with DC. Addressing IDA yields positive circulatory, renal and prognostic outcomes.

Background: Most echoendoscopes are oblique viewing instruments, potentially limiting their value in mucosal evaluation during upper endoscopic ultrasound (EUS) examinations. This raises at least the potential for missed mucosal lesions. While esophagogastroduodenoscopy (EGD) prior to EUS may mitigate this, performing EGD adds both cost and time to upper EUS. This study evaluated the utility of routine EGD before EUS in asymptomatic patients.

Methods: We performed a retrospective, single-center, cohort study including 626 patients undergoing EUS for pancreaticobiliary/mediastinal indications over a 5-year period (2017-2022). Exclusion criteria included luminal symptoms or prior upper gastrointestinal surgery. Clinically significant EGD findings and their impact on management were analyzed.

Results: Among 568 patients who underwent EGD before EUS, 16.8% (n=95) had clinically significant lesions, including reflux esophagitis (32.7%), Barrett's esophagus (12.7%) and gastritis (17.3%). Additionally, 16.6% (n=94) exhibited findings affecting the feasibility of EUS (e.g., strictures, large hiatal hernias). Management changes occurred in 54.3% of cases, primarily biopsies (54.3%) and medication initiation (36.6%). Only 4.6% had a prior EGD within 6 months of their EUS.

Conclusions: Routine EGD before EUS can detect clinically significant mucosal lesions in asymptomatic patients, as well as anatomical factors influencing EUS performance. These findings support considering the incorporation of routine EGD into pre-EUS evaluations to optimize diagnostic accuracy and patient management.

Background: Epidemiological data on metabolic syndrome (MetS) in patients with inflammatory bowel disease (IBD) are limited.

Methods: A retrospective cohort study was conducted using the United States (US) Collaborative Network (TriNetX) to obtain data for patients with IBD between 2010 and 2023. The primary aim of the study was to estimate the prevalence of MetS in ulcerative colitis (UC) and Crohn's disease (CD). Prevalence was further characterized by age, sex, race, disease location, IBD medications, history of surgery, and IBD phenotype.

Results: Among 100,890 patients with IBD, metabolic syndrome (MetS) affected 34.4% overall (UC 32.4%, CD 34.3%). Prevalence rose sharply with age (12-14% at 18-39 to 47-50% at ≥65) and was higher in men than women. Rates were greatest among American Indian (CD 45.2%), Black (40%) and Hispanic (38-39%) populations, and lowest in Asian patients (26%). MetS clustered with more severe phenotypes (stricturing CD, prior CD surgery) and was not elevated among patients receiving advanced therapy. MetS was associated with greater systemic corticosteroid use and higher surgery/colectomy risk, while stricture and fistula risks in CD were similar; advanced therapy was not initiated more frequently in CD.

Conclusion: Our study provides updated epidemiological estimates of MetS in patients with IBD in the US.

Background: Knowledge of the local prevalence of Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) is imperative in screening the population for gastric cancer. The aim of our study was to estimate the histopathological prevalence of H. pylori infection and GIM in Greek patients.

Methods: This was a single-center retrospective study. The age, sex, endoscopic diagnosis, the presence of H. pylori gastritis and the presence of either complete or incomplete GIM, were extracted from the medical reports of our study group and stored in Microsoft Excel. The analysis was focused on the epidemiologic behavior of 2 histologic diagnoses: the presence of H. pylori gastritis and GIM.

Results: H. pylori gastritis was recorded in 910 of the 2343 patients studied (38.8%, 95% confidence interval [CI] 36.8-40.8%). GIM was found in 601 of 2317 patients (25.9%, 95%CI 24.2-27.8%). The prevalence of incomplete GIM was 15.2%. These results are consistent with those observed in other European countries.

Conclusions: This study is the first large Greek study to estimate the histopathological prevalence of H. pylori infection and GIM in a population from a primary care gastrointestinal unit. There was a strong association between H. pylori infection and the development of GIM. H. pylori were more prevalent in non-operated stomachs compared with operated. There was no difference in the prevalence of GIM between operated and non-operated stomachs.

Background: Improving Crohn's disease (CD) management requires a comprehensive understanding of the disease's full impact. Τhis real-world, patient-reported survey investigated the disease burden and unmet medical needs among Greek patients with CD.

Methods: Between October 2023 and January 2024, members of the Hellenic Society of Crohn's Disease and Ulcerative Colitis Patients (HELLESCC) completed a structured questionnaire. The questionnaire captured demographics, disease and treatment characteristics, as well as patient-reported outcomes: Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Work Productivity and Activity Impairment (WPAI), Patient Health Questionnaire-9 (PHQ-9), treatment satisfaction, and treatment adherence. To determine associated factors, both univariate and multivariate logistic regression analyses were carried out.

Results: Among 240 CD patients, 52.9% had active disease and 83.7% were treated with advanced therapies (biological/small molecule agents). Approximately 73.1% reported impaired quality of life (QoL) (SIBDQ <60), 30.9% reduced work productivity, and 36.0% limitations in daily activities. Nearly half (46.1%) reported moderate-to-severe depressive symptoms (PHQ-9 ≥10). Four of 10 patients expressed dissatisfaction with their treatment and 9.9% reported reduced adherence. Higher disease activity was associated with poorer QoL, reduced work productivity, worse mental health, and lower treatment satisfaction. Notably, 76.3% of patients on advanced therapies reported impaired QoL. Of these, 30.9% were in clinical remission.

Conclusions: In Greece, CD patients continue to bear a substantial disease burden, evidenced by reduced QoL, impaired work productivity and daily activity, high rates of depression, and persistent disease activity. A significant proportion also reported dissatisfaction with their treatment, underscoring ongoing unmet needs in disease management.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease affecting ~1.5 million individuals, causing significant impairment in quality of life, psychological well-being, and healthcare burden. Using indirect meta-analysis, this study compared the efficacy and safety of anti-interleukin (IL)-12/23 and IL-23 agents vs. placebo and each other, during induction and maintenance in moderate-to-severe UC.

Methods: A systematic search of PubMed, Cochrane, Scopus, Web of Science, and ClinicalTrials. gov was conducted on October 1, 2024. The randomized controlled trials (RCTs) included evaluated ustekinumab, mirikizumab, risankizumab, and guselkumab. The primary outcomes were clinical remission and endoscopic improvement at both induction and maintenance endpoints. Odds ratios (ORs) with 95% confidence intervals (CIs) and surface under the cumulative ranking (SUCRA) values were used to rank treatment efficacy.

Results: Six RCTs (n=3808) were analyzed for induction and 5 RCTs (n=1697) for maintenance. During induction, risankizumab demonstrated the highest clinical remission rates (OR 3.89, 95%CI 2.24-6.75; SUCRA 80.7%) and endoscopic improvement rates (OR 4.21, 95%CI 2.12-8.35; SUCRA 87.6%) compared to placebo. In maintenance, guselkumab showed the highest clinical remission (OR 4.28, 95%CI 1.58-11.59; SUCRA 81.6%) and endoscopic improvement (OR 4.21, 95%CI 2.12-8.35; SUCRA 93.1%), and was superior to risankizumab (OR 2.05, 95%CI 1.09-3.84) for endoscopic outcomes.

Conclusions: Risankizumab was most effective in induction, while guselkumab was more effective in maintenance. Head-to-head trials are warranted.