Expert Review of Gastroenterology & Hepatology最新文献

Introduction: The therapeutic landscape of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is rapidly evolving with the FDA approval of resmetirom, the first authorized molecule to treat metabolic dysfunction-associated steatohepatitis. Clinical trials are investigating other promising molecules. However, this focus on pharmacotherapy may overshadow lifestyle interventions, which remain the cornerstone of MASLD management. A significant percentage of patients with MASLD struggle with an underlying eating disorder, often a precursor to obesity. The obesity pandemic, exacerbated by the increasing prevalence of binge eating, underscores the need for a psychological approach to address their common roots.

Areas covered: We reviewed the current evidence on behavioral interventions for MASLD. Interventions such as self-monitoring, goal setting, and frequent counseling, have proven effective in achieving at least 5% weight loss. Cognitive behavioral therapy is the first-line treatment for eating disorders and has shown efficacy in treating binge eating and obesity. Further research is needed to establish the optimal behavioral therapy for MASLD, focusing on enhancing compliance and achieving sustained weight loss through diet and physical exercise.

Expert opinion: The treatment of MASLD should not rely solely on pharmacotherapy targeting a single-organ manifestation. Instead, we must consider behavioral interventions, emphasizing the pivotal role of a holistic approach to this multifaceted disorder. [Figure: see text].

Introduction: Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism.

Areas covered: In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated.

Expert opinion: Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.

Introduction: Functional constipation (FC) is a common childhood condition, diagnosed via the Rome IV criteria. Standard therapy includes lifestyle and dietary modification followed by initiation of osmotic laxative therapy. About 30% of children continue to experience symptoms related to FC despite appropriate management. New pharmacologic, surgical, and neuromodulatory therapies for FC are now available for use in adult and pediatric populations. In 2023, the first pharmacologic agent, linaclotide, obtained FDA approval for treatment of FC in children 6-17 years old.

Areas covered: This article reviews current and emerging pharmacologic, surgical, and neuromodulation therapies for the management of FC in pediatric patients. Efficacy and safety data regarding each of these modalities was reviewed and discussed.

Expert opinion: Advancements in therapeutics available for the management of FC necessitate further investigation on safety and efficacy in pediatric populations. Careful consideration should be taken in choosing an available treatment with limited pediatric evidence as adult and pediatric FC have different underlying pathophysiology and require a different therapeutic approach. Standardization of methodology and pediatric endpoints are needed to optimize ability to compare efficacy of different treatments. We predict the future of pediatric FC management will include a personalized approach to care, resulting in improved outcomes.

Introduction: Endoscopic retrograde pancreatography (ERP) has traditionally been the standard modality for pancreatic endotherapy. However, in certain situations, failure of retrograde ductal access may warrant an alternative modality of drainage. This can occur in various settings like difficult and/or surgically altered anatomy or duodenal obstruction. Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) is a relatively newer addition to the armamentarium for endoscopic access to the PD.

Areas covered: This comprehensive state-of-art review aims to give an overview of the indications, technical details, different approaches, and outcomes of EUS-PDD, with the latest evidence available in scientific literature.

Expert opinion: Akin to its biliary drainage counterpart, EUS-PDD enables an EUS-assisted-ERP using rendezvous technique or EUS-guided drainage through transmural stenting. The technique has evolved over the ensuing years with multitude of accessories, approaches, and devices to optimize the outcomes. However, the technical success and adverse events rates need to be further improved. Additionally, it has a steep learning curve with requirements of advanced technical skill and optimum infrastructure back-up. Meticulous patient selection, precise knowledge of ductal anatomy, appropriate approach, and carefully chosen accessories can improve its clinical outcomes.

Introduction: Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics.

Areas covered: We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms.

Expert opinion: We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Introduction: Although gastrointestinal (GI) comorbidities are experienced by over 90% of individuals with Rett syndrome (RTT), a neurodevelopmental disorder associated with mutations in the MECP2 gene, many neurologists and pediatricians do not rank the management of these comorbidities among the most important treatment goals for RTT. Trofinetide, the first approved pharmacologic treatment for RTT, confers improvements in RTT symptoms but is associated with adverse GI events, primarily diarrhea and vomiting. Treatment strategies for GI comorbidities and drug-associated symptoms in RTT represent an unmet clinical need.

Areas covered: This perspective covers GI comorbidities experienced by those with RTT, either with or without trofinetide treatment. PubMed literature searches were undertaken on treatment recommendations for the following conditions: constipation, diarrhea, vomiting, aspiration, dysphagia, gastroesophageal reflux, nausea, gastroparesis, gastritis, and abdominal bloating.

Expert opinion: The authors recommend a proactive approach to management of symptomatic GI comorbidities and drug-associated symptoms in RTT to enhance drug tolerance and improve the quality of life of affected individuals. Management strategies for common GI comorbidities associated with RTT are reviewed based on authors' clinical experience and augmented by recommendations from the literature.

Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory, disabling disorder characterized by prominent eosinophilic inflammation of the esophagus, leading to troublesome symptoms including dysphagia and food impaction. The natural history of EoE is poorly known, but it may lead to esophageal strictures. The therapeutic armamentarium is expected to grow in the near future, especially due to the availability of novel biological therapies targeting crucial inflammatory pathways of EoE.

Areas covered: In this review, we discuss the main clinical features and natural history of EoE, focusing on the current therapeutic strategies, as well as past and current trials investigating biologics for its treatment.

Expert opinion: Dupilumab has been the first approved biologic drug for the treatment of EoE; long-term studies assessing how it could change the natural history of EoE are awaited. Novel biological drugs or other molecules are currently under study and could change the current treatment algorithms in the near future. Proper drug positioning and long term 'exit strategies' are yet to be defined.

Introduction: Endoscopic full-thickness resection (EFTR) represents a pivotal advancement in the minimally invasive treatment of gastrointestinal lesions, offering a novel approach for the management of lesions previously deemed challenging or unreachable through conventional endoscopic techniques.

Areas covered: This review discusses the development, methodologies, applications, and clinical outcomes associated with EFTR, including exposed and device-assisted EFTR, the integration of endoscopic mucosal resection with EFTR in hybrid techniques, and the collaborative approach between laparoscopic and endoscopic surgery (LECS). It encapsulates a comprehensive analysis of the various EFTR techniques tailored to specific lesion characteristics and anatomical locations, underscoring the significance of technique selection based on the lesion's nature and situational context.

Expert opinion/commentary: The review underscores EFTR's transformative role in expanding therapeutic horizons for gastrointestinal tumors, emphasizing the importance of technique selection tailored to the unique attributes of each lesion. It highlights EFTR's capacity to facilitate organ-preserving interventions, thereby significantly enhancing patient outcomes and reducing procedural complications. EFTR is a cornerstone in the evolution of gastrointestinal surgery, marking a significant leap forward in the pursuit of precision, safety, and efficacy in tumor management.

Evaluation of: Araki H, Tazawa H, Kanaya N, et al. Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. Mol Ther Oncolytics. 2022;27:3-13.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. PDAC has a dense, desmoplastic stroma and immunosuppressive microenvironment, which impedes current treatment options. Immunotherapy delivered via oncolytic virotherapy is one potential solution to these barriers. Immune checkpoint inhibitors may facilitate immunogenic cell death by improving immune cell infiltration in cancer cells. PD-1 blockade shows better clinical outcomes for certain cancers. The addition of p53 to stimulate cell cycle arrest remains a novel field of research. The evaluated article by Araki et al. explores the efficacy of PD-1 blockade with oncolytic adenovirus platforms on immunogenic cell death and the possibility of combining PD-1 blockade and p53-activation. In vitro analysis showed increased cell death in multiple cell lines infected with AdV mediating p53 expression. The underlying process may attribute to apoptosis and autophagy, with evidence of increased immunogenic cell death. In vivo models demonstrated improved efficacy of p53-expressing AdV, particularly with the addition of PD-1 blockade which appears to be related to CD8+ cell infiltration.