Clinical and Experimental Gastroenterology最新文献

Etrasimod is a sphingosine 1 phosphate (S1P) receptor modulator approved for the treatment of moderate to severely active ulcerative colitis (UC). Etrasimod selectively activates S1P_1,4,5 receptors with no detectable activity on S1P_2,3. The ELEVATE clinical trials evaluated the efficacy and safety of etrasimod for UC. Etrasimod showed clinically significant improvement in clinical remission at weeks 12 and 52 compared to placebo. Etrasimod showed greater efficacy in patients who were biologic naive. Etrasimod was also effective in a subgroup of patients with isolated proctitis. The medication should be avoided in pregnancy and lactation, certain cardiac conditions including brady-arrythmias, and those with a history of skin cancer. Etrasimod has a shorter half-life and fewer drug-drug and food interactions as compared to the S1P receptor modulator ozanimod. In addition, no dosing titration is required. Etrasimod is a promising treatment option for UC patients with moderate to severe inflammation, particularly those who have no prior biologic exposure, are not considering pregnancy, and prefer oral therapy.

Aim: Correlation of Survivin expression levels in tumor tissues and degree of tumor outgrowth with colorectal cancer characteristics.

Methods: The pathological tissues of 90 cases of colorectal cancer were observed by HE staining, and the tumor budding was judged by Ueno standard, and the expression of Survivin was detected by immunohistochemistry (IHC) technique (EnVision method), so as to analyze the correlation between tumor budding, the expression level of Survivin and the degree of tumor budding, and the correlation between the tumor budding and the patients' clinical characteristics.

Results: The expression level of Survivin was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer; tumor outgrowth was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer (P < 0.05); the expression level of Survivin was significantly correlated with the degree of tumor budding in patients with colorectal cancer (P < 0.05).

Conclusion: In this paper, we tested the relationship between Survivin and tumor budding in colon cancer, and analyzed its relationship with clinicopathological features, with a view to providing a reference for the mechanism related to colorectal cancer.

Purpose: Colorectal cancer is the second leading cause of cancer-related death in the United States. A multi-omics approach has contributed in identifying various cancer-specific mutations, epigenetic alterations, and cells response to chemotherapy. This study aimed to determine the factors associated with colorectal cancer survival and develop and validate a polygenic survival scoring system (PSS) using a multi-omics approach.

Patients and methods: Data were obtained from the Cancer Genome Atlas (TCGA). Colon Adenocarcinoma (TCGA-COAD) data were used to develop a survival prediction model and PSS, whereas rectal adenocarcinoma (TCGA-READ) data were used to validate the PSS. Cox proportional hazards regression analysis was conducted to examine the association between the demographic characteristics, clinical variables, and mRNA gene expression.

Results: Overall accuracy of PSS was also evaluated. The median overall survival for TCGA-COAD patients was 7 years and for TCGA-READ patients was 5 years. The multivariate Cox proportional hazards model identified age, cancer stage, and expression of nine genes as predictors of colon cancer survival. Based on the median PSS of 0.38, 48% of TCGA-COAD patients had high mortality risk. Patients in the low risk group had significantly higher 5-year survival rates than those in the high group (p <0.0001). The PSS demonstrated a high overall accuracy in predicting colorectal cancer survival.

Conclusion: This study integrated clinical and transcriptome data to identify survival predictors in patients with colorectal cancer. PSS is an accurate and valid measure for estimating colorectal cancer survival. Thus, it can serve as an important tool for future colorectal cancer research.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

This article explores the potential benefits and challenges of incorporating Patient-Generated Images (PGIs) into the clinical practice for perianal conditions. PGIs refer to photographs (and video) captured by patients themselves of affected areas of their own bodies to illustrate potential pathologies. It facilitates remote patient assessments and swift evaluation for coloproctologist. They potentially reduce the need for in person follow-up particularly after operation if the patient is asymptomatic. However, concerns with PGI include quality of images, risk of misinterpretation, ethical, legal, and practical problems, especially when imaging private or sensitive body regions. Any platform transmitting and storing PGIs should prioritize data protection with advanced encryption. Comprehensive guidelines should be developed by collaboration between healthcare administrators, regulators, and professionals, and a thorough framework formulated to ensure that quality care is delivered always while respecting patient privacy and dignity. It should be considered as complementary to, rather than a replacement for, traditional clinical consultations. However, patient awareness and education regarding the limitations are key to ensuring that this modality is not misinterpreted or misused.

Irritable bowel syndrome (IBS) is a common disorder of the gut-brain axis. IBS with constipation (IBS-C) accounts for approximately one-third of IBS cases and is associated with substantial burden of illness and decreased quality of life. This narrative review provides an overview of the current and upcoming treatment options and disease management for IBS-C from a US perspective and discusses the importance of the relationship between patient and health care provider in diagnosis and treatment. A positive diagnostic strategy for IBS-C is recommended, based on clinical history, physical examination, and minimal laboratory tests. An effective communication strategy between patients and health care professionals is essential to ensure early diagnosis and reduce both health care costs and overall disease burden. Treatment typically begins with lifestyle interventions and nonpharmacologic options, such as dietary interventions, fiber supplements, and osmotic laxatives. In patients with inadequate response to these therapies, 4 currently available therapies (lubiprostone, linaclotide, plecanatide, and tenapanor) approved by the US Food and Drug Administration may relieve IBS-C symptoms. These agents are generally well tolerated and efficacious in improving IBS-C symptoms, including constipation and abdominal pain. In patients with persistent abdominal pain and/or psychological symptoms, brain-gut behavioral therapy or neuromodulator therapy may be beneficial.

Introduction: For patients with locally advanced pancreatic cancer (LAPC), who are candidates for radiation therapy, dose-escalated radiation therapy (RT) offers unique benefits over traditional radiation techniques. In this review, we present a historical perspective of dose-escalated RT for LAPC. We also outline advances in SBRT delivery, one form of dose escalation and a framework for selecting patients for treatment with SBRT.

Results: Techniques for delivering SBRT to patients with LAPC have evolved considerably, now allowing for dose-escalation and superior respiratory motion management. At the same time, advancements in systemic therapy, particularly the use of induction multiagent chemotherapy, have called into question which patients would benefit most from radiation therapy. Multidisciplinary assessment of patients with LAPC is critical to guide management and select patients for local therapy. Results from ongoing trials will establish if there is a role of dose-escalated SBRT after induction chemotherapy for carefully selected patients.

Conclusion: Patients with LAPC have more therapeutic options than ever before. Careful selection for SBRT may enhance patient outcomes, pending the maturation of pivotal clinical trials.

This case report provides data on unique challenges related to amoebiasis diagnostics and treatment in non-endemic regions. The presented case report is focused a 28-year-old male patient of Indian origin, temporarily living in Poland, who was diagnosed with an amoebic liver abscess. The patient presented with a range of non-specific symptoms including shortness of breath, chest pain, and fever. The differential diagnosis included cardio-pulmonary diseases, a range of tropical diseases such as malaria or typhoid fever, bacterial abscesses, and malignancies, necessitating a comprehensive, multi-modal diagnostic approach. This approach included an extensive review of patient history, physical examination, and various laboratory and imaging investigations. A further challenge in this case was the unavailability of standard cysticidal treatments in Poland, which required individualized therapeutic strategy. Despite these obstacles, the patient was successfully treated using an alternative regimen of intravenous metronidazole, ceftriaxone, doxycycline, chloroquine, and finally, trimethoprim/sulfamethoxazole (treatment with metronidazole was used as a base drug, due to the lack of typical cysticidal treatment, an alternative treatment was added: chloroquine is a recommended drug used in the treatment of pregnant patients, in addition, doxycycline showed in vitro activity against Entamoeba histolytica). This therapeutic journey underscored the value of adaptability in treatment protocols, particularly in regions where certain resources may not be readily available. This case report underlines the importance of broadening the differential diagnosis in non-endemic regions to include tropical diseases, particularly in the context of increasing global travel and migration. It also highlights the significance of employing comprehensive diagnostic strategies and adaptable treatment protocols in such scenarios. In addition, the report reiterates the need for global collaboration and education among healthcare providers to effectively manage tropical diseases, especially in non-endemic regions. Through its exploration of the complexities associated with diagnosing and managing amebiasis in a non-endemic region, this report offers valuable insights to clinicians worldwide.

Increased intestinal permeability has been identified as one of the many pathophysiological factors associated with the development of irritable bowel syndrome (IBS), a common disorder of gut-brain interaction. The layer of epithelial cells that lines the intestine is permeable to a limited degree, and the amount of paracellular permeability is tightly controlled to enable the absorption of ions, nutrients, and water from the lumen. Increased intestinal permeability to macromolecules can be triggered by a variety of insults, including infections, toxins from food poisoning, or allergens, which in turn cause an inflammatory response and are associated with abdominal pain in patients with IBS. This review article discusses increased intestinal permeability in IBS, focusing on IBS with constipation (IBS-C) through the lens of a patient case with a reported prior diagnosis of "leaky gut syndrome" upon initial contact with a gastrointestinal specialist. We review advantages and disadvantages of several methods of measuring intestinal permeability in patients and discuss when measuring intestinal permeability is appropriate in the therapeutic journey of patients with IBS-C. Furthermore, we discuss a possible mechanism of restoring the intestinal barrier to its healthy state through altering intracellular pH by inhibiting sodium-hydrogen exchanger isoform 3 (NHE3). Tenapanor is a minimally absorbed, small-molecule inhibitor of NHE3 that has been approved by the US Food and Drug Administration for the treatment of IBS-C in adults. Preclinical studies showed that tenapanor may restore the intestinal barrier in IBS-C by affecting the conformation of tight junction proteins via NHE3 inhibition to block the paracellular transport of macromolecules from the intestinal lumen. Testing for increased permeability in patients with IBS-C who experience abdominal pain may help inform the choice of therapeutics and alter patients' misconceptions about "leaky gut syndrome".

Purpose: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease.

Patients and methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane's Q value, to detect and correct the effects of horizontal pleiotropy.

Results: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis.

Conclusion: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.