Expert Review of Gastroenterology & Hepatology最新文献

Introduction: In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics.

Methods: We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group.

Conclusion: Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care.

Introduction: Hepatocellular carcinoma (HCC) presents a formidable challenge in oncology, demanding innovative treatment approaches. Both adjuvant and neoadjuvant therapies, thanks to the introduction of immunotherapy, have emerged as promising strategies in the management of HCC, aiming to reduce the risk of relapse and ultimately to improve survival.

Areas covered: This review considers current evidence, ongoing clinical trials, and future strategies to elucidate the evolving landscape of neoadjuvant and adjuvant treatments in HCC.

Expert opinion: Both adjuvant and neoadjuvant regimens, notably those incorporating immune checkpoint inhibitors, demonstrated encouraging safety profiles and efficacy outcomes in HCC.While significant challenges persist, including optimizing patient selection and endpoint definition, the evolving landscape of neoadjuvant and adjuvant therapy holds promise for maximizing the therapeutic potential of immunotherapy across all stages of HCC. Further insights into tumor biology and host immunity will shape the role of these approaches which are close to becoming reality in clinical practice.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of tumor-related deaths. The gut microbiota has gained attention in cancer treatment, due to its influence on the immune system and drug activity.

Areas covered: Tintelnot and collaborators highlight distinct gut microbiota composition in metastatic PDAC (mPDAC) patients responding versus non-responding to chemotherapy. In the context of chemotherapy treatment, the gut microbiota of responders can metabolize tryptophan from food into indole-3-acetic acid (3-IAA). The presence of neutrophil-derived myeloperoxidase facilitates the role of 3-IAA in promoting the accumulation of reactive oxygen species in tumor cells. This accumulation, in turn, inducing tumor cell cytotoxicity. Additionally, 3-IAA can inhibit tumor cell autophagy activity, diminishing tumor cells' ability to adapt to cell stress. This manuscript provides a comprehensive analysis of the latest research on microbiota, metabolites, and PDAC, sourced from PubMed, ScienceDirect, and Google Scholar.

Expert opinion: The evaluated study noted an elevation of the bacterial metabolite 3-IAA in responsive PDAC patients' serum, suggesting its potential to enhance chemotherapy sensitivity. Gaining a thorough comprehension of the impact of gut microbiota metabolites on drug activity is beneficial for broadening our strategies to mitigate chemotherapy resistance in tumors and identifying markers that predict chemotherapy outcomes.

Introduction: Disconnected pancreatic duct syndrome (DPDS) is a pathological condition that causes various symptoms due to the continuous secretion of pancreatic enzymes from the pancreas upstream, which has been separated due to disconnection of the pancreatic duct (DPD) for various reasons.Acute necrotizing pancreatitis includes a certain probability of DPDS appearance, which makes it necessary to provide various treatments for DPDS. Furthermore, DPDS can impact long-term results, such as recurrence and impaired pancreatic function. Although the development of various modalities has contributed to diagnosis and treatment, especially less invasive endoscopic therapy, DPDS is often overlooked, and the diagnosis can be delayed due to the lack of consensus on its definition and classification. This review summarizes the current knowledge and challenges of DPDS and discusses the optimal strategy for its diagnosis and treatment, as well as future perspectives.

Areas covered: Given the lack of established definition, diagnosis, and treatment of DPDS, we conducted a thorough review of the existing literature.

Expert opinion: It is emphasized that a standardized definition and classification of DPDS is essential for designing and conducting clinical studies to address current unmet needs in managing patients with DPDS.

Introduction: Remission rates for ulcerative colitis (UC) remain low despite significant progress in disease understanding and the introduction of novel therapeutic agents. Several challenges contribute to this, including the heterogeneity of the disease, suboptimal efficacy of current diagnostic and therapeutic tools, drug safety concerns, and limited access to newer treatment options.

Areas covered: This review evaluates current treatment targets in UC, assessing the effectiveness of various therapies and management strategies in achieving remission. We explore the potential role of personalized medicine, which tailors treatment based on clinical predictors, genetic factors, and immunologic profiles. Personalized approaches show promise in improving remission rates by addressing the unique characteristics of each patient. We also discussed the feasibility of adapting such management models and suggested solutions to some of the challenges in their implementation.

Expert opinion: Future efforts should prioritize the continued development of biologics, small molecules, and digital health solutions, alongside noninvasive monitoring techniques. These innovations could not only enhance patient outcomes by improving remission rates but also reduce healthcare costs by minimizing hospitalization and surgical interventions. Ultimately, a personalized, stratified approach to UC management is key to optimizing patient care and addressing the unmet needs in this field.

Introduction: Videocapsule endoscopy (VCE) may be a complementary tool in the diagnosis of celiac disease (CD) in cases with equivocal findings and in the follow-up of complicated cases. We aimed to summarize the literature on the utilization of VCE in CD diagnosis/follow-up.

Methods: A computerized literature search was performed to identify pertinent articles published between January 2010 and January 2024.

Results: Three studies focused on VCE in diagnosing CD, involving a total of 186 patients. VCE was performed due to small bowel atrophy with negative serology (19 patients), positive serology with negative histology (40 patients), contraindications/refusal to undergo esophagogastroduodenoscopy (6 patients), high clinical suspicion of CD despite negative serology and/or small bowel atrophy (99 patients), research purpose (22 patients). Twenty studies focused on the follow-up, involving a total of 1337 patients. VCE was performed due to positive serology despite GFD (64 patients), persistent symptoms (389 patients), known/suspected refractory CD-RCD (448 patients), not specified (436 patients). VCE revealed RCD in 243 patients, ulcerative jejunoileitis in 32, T-cell lymphoma in 18, small bowel tumor in one.

Conclusions: VCE may play a role in patients with equivocal CD diagnosis and in those with suspected complications, particularly RCD. Further studies are warranted to draw more solid conclusions.

Introduction: A proper sample size calculation enables to conduct adequately powered randomized controlled trials (RCTs) and to provide a valid assessment of a specific clinical question.

Areas covered: In the current manuscript, we tried to provide the reader with an easy guide on the principles of sample size calculation in RCTs, tailored specifically to the context of gastroenterology and hepatology. The basics of sample size calculation were commented with a description of some of the main methods, including the calculation of the non-inferiority margin for non-inferiority RCTs and the calculation of the minimum clinically important difference (MCID). Some examples from the gastroenterology literature were also provided.

Expert opinion: Collaborating with a biostatistician can provide valuable insights into the nuances of sample size calculation and study design. However, it is crucial that the clinicians understand the basics of calculating sample size, so they could provide valuable input in designing the study from a clinical point of view.

Introduction: Medication holidays in inflammatory bowel disease (IBD) offer a potential means to balance disease management, costs, and quality of life. This concept is increasingly relevant in light of the chronic nature of IBD, the cumulative side effects associated with long-term pharmacotherapy, and the evolving treatment landscape that now includes a large armamentarium of effective induction, maintenance, and rescue therapies paired with disease monitoring tools that enable early intervention.

Areas covered: This review critically examines the rationale, implementation, and risks of medication holidays in IBD. Recent evidence is reviewed to help guide the risks of relapse involved with cessation of therapy. The selection criteria for patients, the necessary monitoring protocols, and strategies for managing potential relapses are outlined.

Expert opinion: Despite the potential benefits, medication holidays in IBD involve significant risks and require careful patient selection and active management. Current research highlights a need for improved predictive models and a deeper understanding of patient-specific outcomes and consequences. The future of medication holidays will depend heavily on advancements in noninvasive monitoring technologies and more personalized approaches to therapy. Ultimately, establishing clearer guidelines for safely conducting medication holidays will be crucial in integrating this strategy into routine clinical practice.

Introduction: After years of treatment stagnation in biliary tract cancers (BTC), there has been a notable shift with the emergence of targeted therapies and immunotherapy, leading to substantial progress in tackling this aggressive disease.

Areas covered: We provide a comprehensive overview of the target therapies that are already part of the treatment algorithm for BTC, such as FGFR, IDH, and HER2 inhibitors. Additionally, we delve into some less known targets that are being explored, such as KRAS proto-oncogene, MAPK cascade, PI3K/AKT/mTOR pathway and novel molecules directed against P53, claudin, histones, and mitochondrial metabolism. Furthermore, we discuss agnostic drugs and analyze the efficacy data available for BTC specifically. We also examine the expanding world of immunotherapy, with an eye on predictive factors of response for immune checkpoint inhibitors, and on novel immune drugs such as chimeric antigen receptor (CAR)-T and vaccines.

Expert opinion: In the expert opinion, we discuss the problem of the scarcity of patients eligible for target therapies and how can clinical trials be designed to overcome this challenge. We also summarize the most promising trials that have the potential to change clinical practice both for immunotherapies and target drugs.