Expert Review of Gastroenterology & Hepatology最新文献

Introduction: Anorectal disorders, such as chronic constipation and fecal incontinence, significantly impact patients' quality of life. Accurate diagnosis is essential for effective treatment, and the balloon expulsion test (BET) has emerged as a simple yet valuable tool in evaluating anorectal function. Despite its simplicity, variations in technique and interpretation have led to ongoing debates regarding its diagnostic precision. To support this review, a PubMed search was conducted using the terms balloon, expulsion, test, evacuation, and disorders, focusing on the most relevant articles published over the past 25 years.

Areas covered: This review explores the evolution of the BET, highlighting its role in diagnosing defecatory disorders. It examines various methodologies, standardization efforts, and the test's sensitivity and specificity compared to other diagnostic modalities like anorectal manometry and defecography.

Expert opinion: The balloon expulsion test remains a cornerstone in the functional assessment of anorectal disorders due to its simplicity, cost-effectiveness, and accessibility. However, standardized protocols are essential to improve diagnostic accuracy and reproducibility. Future research should focus on refining BET techniques and integrating them with advanced diagnostic tools to enhance patient outcomes and guide personalized treatment strategies.

Introduction: Serrated polyps can progress to colorectal cancer (CRC), through a pathway that is distinct from the conventional adenoma-carcinoma sequence. This pathway includes hyperplastic polyps (HPs), sessile serrated polyps (SSPs), and traditional serrated adenomas (TSAs).

Areas covered: Our review includes the histology and pathological challenges, carcinogenesis, risk factors, detection, emerging technologies, resection, and surveillance.

Expert opinion: Serrated polyp management presents many detection, diagnosis, resection, and surveillance challenges. Missed serrated polyps contribute to preventable CRCs. A new SSP detection rate benchmark will guide endoscopists with a goal when improving detection. Furthermore, new SSP-specific surveillance strategies may also aid in reducing CRC burden. Histologic differentiation remains a challenge, underscoring the need for standardized pathology practices and exploring novel ways to stratify risk independent of histology, given interobserver variation. Moreover, the clinical significance of proximal HPs requires further clarification. Which HPs < 1 cm require closer surveillance intervals? Molecular profiling may help identify markers that separate proximal low risk from high-risk HP. The best approach for resection of serrated polyps also needs to be clarified. There is also a lack of robust longitudinal outcome data to guide surveillance recommendations since current guidelines are based on low quality of evidence.

Introduction: The liver is a central metabolic organ, but is also hosting a unique immune microenvironment to sustain homeostasis and proper defense measures against injury threats in healthy individuals. Liver macrophages, mostly represented by the tissue-resident Kupffer cells and bone marrow- or monocyte-derived macrophages, are intricately involved in various aspects of liver homeostasis and disease, including tissue injury, inflammation, fibrogenesis and repair mechanisms.

Areas covered: We review recent findings on defining the liver macrophage landscape and their functions in liver diseases with the aim of highlighting potential targets for therapeutic interventions. A comprehensive literature search in PubMed and Google Scholar was conducted to identify relevant literature up to date.

Expert opinion: Liver macrophages orchestrate key homeostatic and pathogenic processes in the liver. Thus, targeting liver macrophages represents an attractive strategy for drug development, e.g. to ameliorate liver inflammation, steatohepatitis or fibrosis. However, translation from fundamental research to therapies remains challenging due to the versatile nature of the liver macrophage compartment. Recent and major technical advances such as single-cell and spatially-resolved omics approaches deepened our understanding of macrophage biology at a molecular level. Yet, further studies are needed to identify suitable, etiology- and stage-dependent strategies for the treatment of liver diseases.

Introduction: Inflammatory bowel diseases (IBD) management extends beyond pharmacotherapy, incorporating psychosocial support, patient education, physical activity, and dietary strategies. These components are often overlooked despite their impact on quality of life (QoL) and treatment adherence. This review explores the role of non-pharmacological strategies in optimizing IBD care.

Areas covered: This article examines the significance of patient-physician communication, disease-specific education, mental health support, exercise, and diet in IBD management. A strong patient-physician relationship fosters trust and adherence to treatment. Knowledge empowers patients, improving long-term control. Psychosocial challenges, including anxiety, depression, and fatigue, further complicate disease management, highlighting the need for timely interventions. Physical activity and dietary interventions play essential roles in reducing sarcopenia and malnutrition, though standardized guidelines are lacking. Literature was reviewed to assess their effectiveness and clinical integration.

Expert opinion: Holistic, multidisciplinary care should be standard in IBD management. Education, mental health screening, and structured diet and exercise plans must be integrated into routine care. Medical training should emphasize communication skills and patient-centered strategies. Future research should establish evidence-based guidelines for implementing these approaches effectively, ensuring improved long-term outcomes for IBD patients.

Introduction: Information on rates of safety outcomes in patients with ulcerative colitis [UC] is helpful to better understand the benefit-risk profile of more recent therapies approved for UC.

Areas covered: This narrative review provides an updated examination of the incidence and prevalence of safety outcomes in the UC patient population. Incidence and prevalence estimates were determined for outcomes including cardiac conduction disorders, infections, and malignancies from published literature [2013-2023].

Expert opinion: While information for certain outcomes was more frequently recorded, such as herpes viral infection (incidence rate [IR] 0.0-4.47 per 100 person-years [PY]) and malignancies [all; IR 0.0-1.77 per 100 PY], rarer outcome estimates such as bradycardia [IR 0.2 per 100 PY] and macular edema [IR 0.2 per 100 PY] were limited. Our knowledge of certain, uncommon safety outcomes and concomitant medical conditions in the UC population remains limited given the lack of data available. Even though larger cohorts with longer follow-up are warranted, estimates provided in this review will contribute to an improved understanding of the safety profile of UC therapies.

Introduction: Investigative work in the treatment of hepatocellular carcinoma is rapidly growing with the advent of immunotherapy. Nonetheless, trial endpoints and, more importantly, clinically meaningful endpoints need to be accurately chosen depending on the phase of trial and the patient population studied. We provide a scoping review focusing on trial endpoints on the use of immunotherapy in hepatocellular carcinoma.

Areas covered: We searched PubMed and Google Scholar for prospective phase II and III trials using immunotherapy, whether in the neoadjuvant, adjuvant, bridging, downstaging, or palliative settings, while discussing the clinical implications of trial endpoints.

Expert opinion: The field of immune oncology is rapidly progressing and has become the standard of care in advanced hepatocellular carcinoma. However, the role of immunotherapy in the treatment of early and intermediate stage hepatocellular carcinoma is yet to be defined. Prospective trials for all stages of disease must strive for endpoints that are not only statistically significant but also clinically consequential. Whereas overall response rate may be a reasonable trial endpoint in phase II trials, phase III trials should rather aim for the improvement of overall survival or quality of life to have clinically meaningful impacts.

Introduction: A subset of gastrointestinal stromal tumors (GISTs) lacks the common mutations in KIT/PDGFRa genes. This is a rare and heterogeneous group of challenging GISTs due to their diversity and absence of sensitivity to the tyrosine kinase inhibitor (TKI) imatinib.

Areas covered: In this manscript, we review the pathogenesis, natural history, diagnostic features and management of KIT/PDGFRa wild-type (WT) GISTs, including SDH-deficient GISTs, GISTs with mutations in the RAS/RAF pathway, and quadruple WT GISTs which lack mutations in either KIT/PDGFRa and SDH genes or components of the RAS/RAF pathway, and syndromic GISTs as well as GISTs with rare KIT/PDGFRa mutations.

Expert opinion: Patients should be managed in reference centers. There has been progress in the understanding of the biology of these GISTs, and promising therapeutic targets have been identified. In SDH-deficient GISTs, the TKI olverembatinib has shown encouraging clinical activity but requires further clinical validation, while the HIF2a inhibitor bezultifan and temozolomide alone or in combination with the death receptor agonist 5 are under clinical investigation. Targeting the RAS/RAF pathway in RAS/RAF-mutated GISTs warrants evaluation in clinical trials. Rare molecular alterations in quadruple WT GISTs require investigation for their oncogenic potential. Collaborative research and patient advocacy is critical for these extremely rare tumors.

Introduction: Measurement of gastrointestinal (GI) transit is increasingly becoming a valuable tool in understanding the pathophysiology of symptoms of many digestive diseases, including irritable bowel syndrome (IBS). The objective of this article is to review the relevance of GI transit abnormalities for symptoms of IBS. These abnormalities relate to gastric emptying, small bowel transit, and colonic transit (whole gut transit).

Areas covered: The article briefly describes the current methods of assessment, factors that influence the result of these methods and the relationship of abnormalities of GI transit with symptoms that have been reported in IBS patients. Finally, a recommendation to guide the application of transit studies in IBS in both clinical practice and research is provided.

Expert opinion: Gastrointestinal transit is relevant to symptoms of bowel habits (stool frequency and form) and the relevance for other GI symptoms in IBS is not straightforward and needs further characterization. Intervention studies in IBS that incorporate objective measures of gut transit alongside symptom evaluation are warranted. Incorporating artificial intelligence into the methods of measuring transit could improve accuracy and simplify the measurements.

Introduction: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Photon radiotherapy shows efficacy in treating HCC but carries risks of high exit dose and radiation-induced liver disease. Additionally, HCCs with portal vein tumor thrombosis (PVTT) have a poor prognosis and are associated with higher risk of death. In recent years, proton beam therapy (PBT) has emerged as a novel treatment with the ability to downstage HCC for liver transplant (LT).

Areas covered: This review will provide an overview of dosimetric benefits of PBT, efficacy of PBT in treating HCC, downstaging HCC-PVTT for LT, and a comparison of PBT with other non-surgical techniques. A search of PubMed until 3 September 2024 was conducted using free search and the following keywords: hepatocellular carcinoma, proton beam therapy, portal vein tumor thrombosis, local ablative therapy, trans-arterial chemoembolization, stereotactic body radiotherapy, Y-90 radioembolization.

Expert opinion: Various clinical trials using PBT have shown promising tumor local control and overall survival rates. PBT is mostly safe and efficacious for downstaging HCC-PVTT for LT. PBT has also been shown to be non-inferior to various other treatment modalities. Future research should focus on combinations of PBT with other modalities.