Clinical and Translational Gastroenterology最新文献

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.

Introduction: The Toronto Inflammatory Bowel Disease (IBD) Global Endoscopic Reporting (TIGER) score was developed to provide 1 endoscopic scoring index for patients with both Crohn's disease (CD) and ulcerative colitis (UC). The goal of this study was to assess the predictive validity the TIGER score for daily-life disease burden (IBD Disk) and disease complications.

Methods: A prospective 12-month study was conducted in 1 tertiary IBD center. Baseline colonoscopy was performed. Moderate-to-severe mucosal involvement was defined as a TIGER score ≥100, Simple Endoscopic Score for CD >6, Mayo Endoscopic Score >1, and was used as a predictor for clinical outcomes. At each visit, IBD Disk questionnaires, disease complications, hospitalizations, surgeries, and medications were documented.

Results: A total of 107 adults, 52 with CD and 55 with UC, were included. Patients with a baseline TIGER score ≥100 had a significantly higher prevalence of an IBD Disk score ≥40 after the 12-month follow-up period despite receiving advanced therapy (33.9% vs 7.8%, P < 0.001). There were significantly more patients with a baseline TIGER score ≥100 who experienced at least 1 hospitalization (39.3% vs 2.0%, P < 0.001), underwent surgery (14.3% vs 0.0%, P < 0.005), had IBD-related complications (41.1% vs 9.8%, P < 0.001), and required steroids (67.9% vs 5.9%, P < 0.001) or advanced therapy (85.7% vs 7.8%, P < 0.001). Similar significant results were obtained with Simple Endoscopic Score for CD and Mayo Endoscopic Score as predictors of outcomes over the 12 months.

Discussion: The TIGER score is a simple endoscopic score for patients with CD and UC with an adequate predictive validity for worse clinical outcomes while having noninferiority to the current best-referenced endoscopic scores.

Autoimmune pancreatitis (AIP) is a distinct inflammatory pancreatic disorder characterized by its responsiveness to glucocorticoid therapy and association with autoimmune features. AIP primarily consists of type 1 and type 2, with relapse being a significant problem mainly associated with type 1 AIP, which has a high relapse rate of approximately 40%, whereas type 2 AIP has significantly lower relapse rates. This narrative review comprehensively examines the multifaceted factors influencing AIP relapse, particularly focusing on type 1 AIP. Dynamic changes in serum IgG4 levels-particularly insufficient decline, relative increase, or persistently elevated levels after steroid therapy-consistently correlate with relapse risk. Other serological markers including immunoglobulin E and autotaxin may serve as potential relapse predictors. Imaging features associated with relapse include diffuse pancreatic swelling, persistent post-treatment pancreatic enlargement, and elevated fluorodeoxyglucose positron emission tomography metabolic parameters. Extrapancreatic involvement, especially proximal biliary and renal manifestations, significantly increases relapse risk. Therapeutic considerations reveal that prolonged maintenance of glucocorticoid therapy reduces relapse rates, whereas immunosuppressants and rituximab show promise in managing refractory cases. This review synthesizes current evidence to guide clinicians in developing effective management strategies for this challenging pancreatic disorder.

Introduction: Rectal neuroendocrine tumors (rNETs) are subepithelial lesions with potential of malignancy. Despite the guidelines recommending that rNETs measuring 10-20 mm should be removed either endoscopic submucosal dissection (ESD) or transanal endoscopic microsurgery (TEM), the management with these entities is still a clinical dilemma. We performed a meta-analysis to compare ESD and TEM regarding method effectiveness and safety in the treatment of rNETs.

Methods: PubMed/MEDLINE/Embase/EBSCO/CINAHL was searched up for observational studies analyzing the efficacy and safety of both methods in the treatment of rNETs.

Results: A total of 59 observational studies with a total of n = 2,804 participants were included. In a subgroup analysis, we demonstrated that the R0 resection rate was significantly ( P = 0.002) lower for ESD (rate: 0.854) than for TEM (0.924). The recurrence rate differed significantly ( P = 0.008); the lowest (event rate [ER] = 0.015) was found for ESD and the highest for TEM (ER = 0.035). The overall bleeding rate was 0.046 and perforation rate was 0.023 and no significant differences ( P = 0.274 for bleeding, P = 0.808 for perforation) were found by intervention type. The rate of other complications (wound dehiscence, soilage, incontinence, rectovaginal fistula, pelvic pain, retroperitoneal emphysema, coagulation syndrome) was significantly ( P = 0.000) higher for TEM (ER = 0.107) than ESD (ER = 0.013). We also included 4 comparative studies with 490 patients. Using random-effects analysis, we found that the risk ratio for R0 resection was approximately 10% lower for ESD. Our analysis showed significantly greater size ( P = 0.01) and follow-up ( P = 0.03) in the group treated with TEM.

Discussion: The efficacy of TEM is higher than ESD with a higher risk of complications in this method. Lesions with a greater size are treated with TEM, and recurrence rate is greater for this procedure. Long follow-up is needed after the treatment of rNETs to detect the recurrence early.