Clinical and Translational Gastroenterology最新文献

Introduction: Pharmacological therapies for chronic idiopathic constipation (CIC) are useful, but many patients report dissatisfaction from a lack of efficacy and occurrence of adverse events. The vibrating capsule (VC) is a US Food and Drug Administration approved nonpharmacologic treatment of CIC. However, its long-term usefulness in a community setting is unknown. The goal of this study was to assess the long-term efficacy and safety of VC treatment in a real-world community setting.

Methods: We conducted a postmarketing analysis of CIC patients prescribed VC who completed at least 3 or 6 months of treatment. The clinical utility was assessed by patient reported symptoms in an electronic stool diary. Safety data were also collected.

Results: One thousand seven hundred twenty-two patients were prescribed VC, and 491 and 298 took the VC and kept stool diaries for 3 and 6 months, respectively. Approximately 46% of patients were older than 55 years of age and 85% were women. Compared with baseline, complete spontaneous bowel movement rates increased significantly throughout the 3 and 6-month periods (average increase of >1 complete spontaneous bowel movement per week; P < 0.0001). Mean stool consistency (Bristol Stool Form Scale) improved from 2.9 (baseline) to 4.1 during treatment ( P < 0.0001), mean straining effort (1-4) decreased from 2.9 to 1.6 ( P < 0.0001), and toileting time also significantly decreased ( P < 0.0001). Safety analysis revealed that 4.6% of patients reported feeling a sensation of vibration, 1.8% reported abdominal pain and 0.64% reported diarrhea.

Discussion: In a community setting, the VC seems both effective and safe for long-term treatment of chronic constipation with diarrhea being notably uncommon.

Introduction: Intrapancreatic fat deposition is related to insulin resistance and type 2 diabetes mellitus. However, the association between intrapancreatic fat deposition and coronary artery disease has not been well studied. In this study, we investigated the associations between intrapancreatic fat deposition alone or in combination with triglyceride-glucose (TYG) index and the risk of coronary artery calcification (CAC) in a general population.

Methods: A total of 9,479 participants who underwent CT scans for lung cancer screening from 2018 to 2020 were included in this study. The TYG index was calculated through the following equation: Ln (fasting glucose [mg/dL] × fasting TG [mg/dL]/2). Pancreatic CT attenuation was used as a marker of intrapancreatic fat deposition. CAC was evaluated on noncardiogram-gated chest CT.

Results: CAC was detected in 2,447 of 9,479 participants. The prevalence of CAC was significantly lower in subjects with high pancreatic CT attenuation (37.8% in the first quartile [Q1] vs 17.8% in the fourth quartile [Q4], P < 0.001). Pancreatic CT attenuation was associated with the occurrence of CAC (odds ratio 0.82, 95% confidence interval 0.69-0.97, Q4 vs Q1). The area under the curve of the combination of pancreatic CT attenuation and the TYG index was significantly greater than that of TYG and pancreatic CT attenuation alone in identifying CACs (0.646 vs 0.596 and 0.612, P < 0.001).

Discussion: Intrapancreatic fat deposition was associated with CAC, and the combination of pancreatic CT attenuation and the TYG index performed better than TYG or pancreatic CT attenuation alone in identifying CACs.

Introduction: We examined whether the symptom expression of depression as assessed using the Patient Health Questionnaire-9 (PHQ-9) depression screening tool differs between patients with decompensated cirrhosis (DC) compared with primary care patients.

Methods: Study included 218 patients with DC (91% Child-Pugh Class B/C) recruited from a liver transplant center and a real-world cohort of 436 outpatients from 4 primary care clinics in a large tertiary academic health system who completed the PHQ-9. We calculated positive screening rates for depression (PHQ-9 cutoff score of 10) for both cohorts. We evaluated PHQ-9 items for differential item functioning (DIF) in both cohorts within an Item Response Theory framework. We compared DIF-adjusted and unadjusted Item Response Theory scores to characterize the impact of DIF on PHQ-9 total scores.

Results: Positive screening rates using a PHQ-9 cutoff score of 10 were 39% and 29% for DC and primary care patients, respectively. Three PHQ-9 somatic symptom items (sleep problems, low energy, psychomotor agitation, or retardation) showed significant DIF, with DC more likely than primary care patients with similar levels of depression severity to endorse these symptoms. DIF-adjusted scores suggested a 1-point increase (PHQ-9 cutoff score of 11) in the screening threshold for patients with DC.

Discussion: Equating for depression severity, we found differences in the symptom expression of depression for patients with DC relative to primary care patients. Our findings highlight the need for future clinical and basic research into the diagnostic performance of depression screening tests and the phenomenology of depression in patients with DC.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Electroporation-based therapies, such as electrochemotherapy (ECT) and irreversible electroporation (IRE), could be promising alternatives. ECT combines reversible electroporation with chemotherapy, enhancing intracellular drug uptake, while IRE leads to nonthermal tumor ablation. Both have been suggested as immunotherapy potentiators (electroimmunotherapy) in some tumor locations. We conducted a systematic review to evaluate the efficiency and safety of ECT, IRE, and immunoelectroporation in PDAC treatment.

Methods: We searched Medline, Embase, Cochrane, and Google-Scholar for ECT, IRE, and electroimmunotherapy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For ECT and electroimmunotherapy, regarding the scarcity of the data, we described independently each study protocol and results. For IRE, we collected protocol, efficiency, and safety data to provide a global analysis.

Results: Fifteen studies described the effects of ECT for PDAC treatment: Safety and efficiency were promising in both preclinical and human models. Thirty-eight clinical studies including 2,245 patients were analyzed for IRE, with patients mostly treated for locally advanced pancreatic cancer and a median overall survival of 17.2 months at the expanse of a 36% adverse event rate, half of which severe. Seven (preclinical and clinical) studies investigated electroimmunotherapy suggesting significant potentiation of immunotherapy in both preclinical and human models.

Discussion: In the largest systematic review to date regarding electroporation in PDAC treatment, analysis of study results plead against the use of IRE but highlight the potential benefits of ECT and electroimmunotherapy.

Introduction: Gastric cancer (GC) is a lethal malignant tumor necessitating high-sensitivity detection to improve diagnostic accuracy and the prognosis of patients. Alterations in long noncoding RNAs can influence cancer progression through various mechanisms. Our study tried to explore the potential of STARD4 antisense RNA 1 (STARD4-AS1) as a GC biomarker and its mechanism of action in GC development.

Methods: Pan-cancer analysis using The Cancer Genome Atlas database identified STARD4-AS1. Serum STARD4-AS1 levels in patients with GC were measured by quantitative real-time PCR, and diagnostic efficiency was assessed using receiver operating characteristic curves. Functional inactivation experiments and western blotting evaluated the biological role of STARD4-AS1 in GC cells. Bioinformatics analysis explored its potential role in GC immunotherapy and underlying mechanisms.

Results: Pan-cancer analysis revealed lower overall survival in GC patients with higher STARD4-AS1 expression. Quantitative real-time PCR confirmed the reproducibility and stability of STARD4-AS1 as a marker. Serum STARD4-AS1 levels in patients with GC were significantly higher than those in healthy subjects and gastritis patients. Receiver operating characteristic analysis demonstrated that STARD4-AS1 outperformed carcinoembryonic antigen, carbohydrate antigen 199 , and carbohydrate antigen 724 in differentiating GC from gastritis, with optimal diagnostic power when combined with these markers. Knockdown of STARD4-AS1 inhibited GC cell proliferation and metastasis and inhibited the epithelial-mesenchymal transition process. Biosignature prediction indicated that higher STARD4-AS1 expression could evaluate prognosis, as well as regulate GC progression through phosphatidylinositol-mediated signaling, and transmembrane receptor protein tyrosine phosphatase signaling pathway.

Discussion: Serum STARD4-AS1 may serve as a diagnostic biomarker and oncogene function for GC for improving diagnosis, monitoring progression, and evaluating prognosis of GC.

Introduction: Serrated polyposis syndrome (SPS) is clinically defined by the presence of multiple serrated polyps in the colon and rectum, and is associated with increased colorectal cancer risk. SPS is the most prevalent polyposis condition; however, its genetic basis remains poorly characterized. The British Society of Gastroenterology recommends gene panel testing for all patients with SPS to rule out other polyposis conditions. The aim of this study was to evaluate the diagnostic yield of genetic testing in patients with SPS.

Methods: We conducted a retrospective, cross-sectional analysis using the Polyposis Registry from St. Mark's Hospital, London, a national referral center in the United Kingdom. Patients with SPS who underwent genetic testing between April 4, 2009 and February 9, 2024, and met the SPS WHO criteria were included. Genetic variants were identified from test reports, and clinical data were extracted from medical records.

Results: In total, 573 people with SPS were identified in our registry, of whom 258 underwent genetic testing. Of these, 119 underwent target gene testing and 139 underwent multigene panel testing. No pathogenic variants were detected through targeted genetic testing. On multigene panel testing, pathogenic germline variants were found in 4 patients (2.9%), including 3 with Lynch syndrome (2 with PMS2 , one with MSH2 ) and one with an RNF43 variant.

Discussion: Genetic testing demonstrated a low diagnostic yield in this SPS cohort, suggesting undefined genetic risk or involvement of other pathophysiological factors. Therefore, genetic testing seems to have limited utility in patients with SPS and may primarily identify those with an incidental diagnosis of Lynch syndrome.

Introduction: Obesity and overweight are linked to increased postoperative issues in patients with colorectal cancer (CRC). However, the impact of obesity on outcomes of simultaneous colon and liver resections for colorectal liver metastasis (CRLM) is not well studied. This study was to assess the impact of obesity and overweight on outcomes of simultaneous colon/rectum and liver resection in patients with CRLM.

Methods: This retrospective study analyzed data from the US Nationwide Inpatient Sample between 2005 and 2020. Regression analysis evaluated associations between obesity/overweight and in-hospital outcomes.

Results: Of the 3,269 patients included, 413 were overweight or obese. Overweight and obese patients were younger and had higher rates of comorbidities such as heart failure, diabetes, hypertension, nonalcoholic fatty liver disease, and chronic pulmonary disease compared with nonobese patients. Overweight and obesity were associated with an increased risk of unfavorable discharge (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 1.00-2.07) and a greater likelihood of developing any complication (aOR 1.27, 95% CI 1.05-1.5). In addition, overweight and obese patients had significantly higher odds of experiencing acute kidney injury (aOR 1.61, 95% CI 1.15-2.25), with the effect being more pronounced in patients younger than 60 years (aOR 1.80, 95% CI 1.13-2.87).

Discussion: Overweight and obesity are associated with increased risks of complications, particularly acute kidney injury, and unfavorable discharge in patients undergoing simultaneous colon and liver resection for CRLM.

Despite an overall decline in the incidence and mortality of colorectal cancer, diagnosed cases of colorectal cancer in young adults are rising significantly. As more and more young patients with colorectal cancer survive their primary disease, there is an increasing concern about reproductive health associated with primary treatment. There is considerable controversy in the available literature regarding the outcomes of pregnancies in patients with colorectal cancer, including maternal and fetal/neonatal outcomes. The most commonly reported adverse events in labor were cesarean section, pre-eclampsia, preterm birth, and neonatal complications associated with preterm birth. The purpose of this review was to summarize the unmet reproductive needs of patients with early-onset colorectal cancer, the gonadal toxicity and fertility effects of treatment on patients with early-onset colorectal cancer, and the maternal and fetal/neonatal effects of pregnancy, to optimize the overall prognosis of patients with early-onset colorectal cancer.