Current Opinion in Gastroenterology最新文献

Purpose of review: A paraesophageal hernia (PEH) is the condition in which the fundus of the stomach protrudes through the diaphragmatic hiatus into the chest adjacent to the esophagus. Such hernias can result in serious complications such as bleeding, obstruction, ischemia, and perforation. There is considerable controversy regarding the optimal management of PEH and, in this report, we review recent publications that address this issue.

Recent findings: After surgical repair of PEH, the rate of recurrence remains high, and recent data do not document a clear advantage for the use of a mesh for crural buttressing in preventing recurrence. There also appears to be no significant difference among different types of mesh for preventing recurrence in the long term. The optimal shape, positioning, and material for mesh remain controversial topics. Recent reports suggest benefit for performing gastropexy routinely during PEH repair, and the addition of a fundoplication does not seem to reduce rates of recurrence or gastroesophageal reflux. Promising early results have been described for new techniques of PEH repair such as the use of posterior rectus sheath fascia for hiatal augmentation, and anterior crural reconstruction.

Summary: This report summarizes the most recent data on key issues in the management of PEH such as the use of mesh, gastropexy, fundoplication, the role of age, and novel techniques for PEH repair.

Purpose of review: Proton-pump inhibitor therapy does not provide complete relief of symptoms in up to 40% of patients with gastroesophageal reflux disease (GERD). Antireflux surgery (ARS) aims to reconstruct the natural antireflux barrier consisting of the diaphragmatic crura, the lower esophageal sphincter, and the gastroesophageal flap valve.

Recent findings: Although the 360° Nissen fundoplication combined with crural repair remains the gold-standard ARS treatment for GERD, the Toupet and Dor partial fundoplications and the magnetic sphincter augmentation (LINX) procedure have emerged as suitable alternative options with fewer side-effects. Randomized and observational clinical studies show that reflux control with partial fundoplications and LINX is acceptable and the risk of side-effects is minimal. Early results with the novel Refluxstop procedure show that restoration of distal esophageal length and the gastroesophageal flap valve, combined with anterior fundoplication and a silicon prosthesis to stabilize the esophagogastric junction below the diaphragm, can also provide excellent reflux control with minimal side-effects.

Summary: Laparoscopic ARS should be performed in centers offering a comprehensive diagnostic pathway and a spectrum of techniques tailored to the individual GERD patient's phenotype and expectations. Further research is needed to provide more personalized and durable ARS.

Purpose of review: This review explores the evolving landscape of inflammatory bowel disease (IBD) therapy, particularly through the lens of startups that are pushing the boundaries of current treatment paradigms. By discussing the challenges and opportunities faced by startups, this review seeks to provide insights for aspiring entrepreneurs and innovators in the IBD space.

Recent findings: The landscape of IBD is rapidly evolving, with innovative solutions ranging from novel therapeutics to digital health platforms. An analysis of recent SBIR award winners highlights emerging trends, including microbiome-based therapies, targeted small molecules, and advanced drug delivery systems like hydrogels. Digital health solutions, such as smart monitoring tools and AI-assisted treatment selection are gaining traction. IBD startups are playing a crucial role in cost reduction through competition, streamlining drug development, and treatment personalization. Despite regulatory, financial, and funding challenges, startups are driving the next phase of IBD innovation.

Summary: The future of IBD therapy is being driven by innovative start-ups that are challenging the status quo in IBD treatment. These companies are addressing critical gaps in therapy by focusing on novel drug targets, improved drug delivery, and precision medicine. While startups face many challenges including high research and development (R&D) costs, regulatory hurdles, and funding, they continue to be at the forefront of IBD innovation. Their success could potentially lead to more affordable and effective therapies. By drawing on examples like the nutraceutical company, Evinature, my own personal experience as technical lead of Edulis, a startup focused on localized IBD therapy, and perspective from the head of the Crohn's and Colitis Foundation's IBD Ventures, this review aims to provide insights for those looking to innovate in IBD.

Purpose of review: Tissue-directed therapies (TDTs) provide potential advantages, including improved tolerance, safety, and efficacy. This review provides a conceptual framework for understanding intestinal TDT and summarizes the current landscape of TDT in inflammatory bowel disease (IBD).

Recent findings: Vedolizumab, a mAb targeting the gut homing α4β7 integrin, served as revolutionary proof-of-principle for the power of advanced TDT in IBD. The development of other monoclonal antibodies targeting cell adhesion molecules followed including abrilumab (α4β7), etrolizumab (β7), and ontamalimab (MAdCAM-1). MORF-057, an oral small molecule inhibitor of α4β7, is now in development for ulcerative colitis. Efforts have also been made toward gut specific JAK inhibitors. Microbiome-based therapies, including engineered probiotics, bacteriophages, and postbiotics, are gaining interest. There are also a number of innovative drug delivery methods, including engineered yeast, hydrogels, and nanoparticles, and viral-based gene therapy.

Summary: Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or in combination with currently available therapies. Future directions should focus on the development of tried-and-true modalities (mAbs, small molecules) as well as the microbiome and more innovative delivery systems.

Purpose of review: The challenges in distinguishing reflux hypersensitivity (RH) from other functional esophageal disorders demand a comprehensive understanding of RH. This review aims to discuss the latest practices in diagnosis and management of RH, examining the pathophysiology, diagnostic criteria, and evolving treatment strategies for RH, with an emphasis on the role of effective patient-physician communication.

Recent findings: Esophageal hypersensitivity appears to play a significant role in symptoms generation for RH patients. Diagnostic algorithms have improved with updates from the Lyon consensus. Management strategies including treatments with neuromodulators, proton-pump inhibitors, behavioral interventions, and antireflux surgery are potential therapeutic options for patients with RH.

Summary: Effective RH management requires a patient-centered approach that considers possible pharmacologic, behavioral, and surgical strategies. Effective patient-physician communication is essential to educate patients and address their concerns about neuromodulators, and to reframe treatment strategies to target esophageal hypersensitivity rather than a psychiatric disorder.

Purpose of review: Chromatin plays a critical role in gene regulation and disease pathogenesis. In inflammatory bowel disease (IBD), alterations in chromatin structure contribute to disease heterogeneity and impact treatment responses. This review explores chromatin accessibility and chromatin-associated proteins as biomarkers for IBD and highlights recent technological advancements enabling targeted biomarker discovery and novel therapies.

Recent findings: Advancements in high-throughput sequencing have enabled genome-wide profiling of chromatin interactions in IBD. Studies have identified distinct chromatin landscapes in Crohn's disease (CD) and ulcerative colitis (UC), revealing stable regulatory shifts independent of inflammation.

Summary: Chromatin profiling offers a novel approach for identifying biomarkers and therapeutic targets in IBD. Integrating chromatin accessibility data with transcriptomic and epigenomic analyses can refine disease classification and guide personalized treatment strategies. Emerging techniques compatible with formalin-fixed paraffin-embedded (FFPE) samples enhance clinical applicability, bridging the gap between molecular research and precision gastroenterology.

Purpose of review: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, chronic cholestatic diseases associated with significant morbidity. While previously approved therapies for PBC, including ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have substantially altered the natural course of the disease and improved patient survival, they have several limitations including an incomplete therapeutic response, patient intolerance and a lack of symptom relief.

Recent findings: Peroxisome proliferator-activated receptor (PPAR) agonists have emerged as promising therapeutic agents capable of achieving biochemical remission and alleviating debilitating symptoms such as pruritus. Elafibranor and Seladelpar were recently granted accelerated approval by the FDA as second-line treatment option for PBC. Although no treatment has yet received approval for PSC, several PPAR agonists have been evaluated in clinical trials.

Summary: This review highlights the evolving role of PPAR agonists as second-line agents for PBC and investigational treatments for PSC.

Purpose of review: The management of esophageal perforation is a topic of debate, as there now are viable surgical and endoscopic options. Historically, surgical management had been considered the standard of care for these perforations, but such surgical management can be associated with considerable morbidity. In this report, we explore contemporary options for the care of patients with esophageal perforations.

Recent findings: Innovations in endoscopic therapies, including self-expanding metal and plastic stents, over-the-scope clips, vacuum therapy, and endoscopic suturing have expanded treatment options for esophageal perforations. These approaches are particularly beneficial for selected patients with early, contained perforations, offering reduced morbidity and shorter hospital stays. However, surgical intervention remains essential in cases of extensive contamination, necrosis, or delayed diagnosis. A growing body of evidence supports a patient-specific approach, integrating both traditional and emerging interventions.

Summary: The management of esophageal perforation is evolving with the increasing use of minimally invasive endoscopic techniques. However, surgical repair remains the definitive treatment in patients with hemodynamic instability or extensive contamination. Timely intervention is critical, as delayed diagnosis significantly increases morbidity and mortality. A tailored approach, incorporating patient-specific factors and nature of the disease, ensures optimal outcomes.

Purpose of review: Despite advances in medical therapies for the treatment of Crohn's disease (CD), 20-30% of patients fail to respond to these therapies (i.e. refractory CD). Medically refractory CD leads to significant disability increasing morbidity and mortality. To prevent the disability of refractory CD, hematopoietic stem cell transplantation (SCT) has emerged as a therapeutic strategy.

Recent findings: Autologous (auto-SCT) and allogeneic SCT (allo-SCT) have been explored in clinical trials for refractory CD patients. We will review the stem cell transplant process, how each part of stem cell transplantation affects clinical efficacy and safety, and how specific clinical trials advanced our understanding of the role of stem cell transplant in the treatment of refractory CD.

Summary: As multiple clinical trials using the same auto-SCT protocol demonstrated auto-SCT as clinically efficacious for refractory CD it supports that this treatment may be adopted as standard of care for select patients with refractory CD. To establish auto-SCT as a standard therapy will require the creation of international registries to track long-term SCT outcomes and translational studies to refine SCT protocols for CD patients as a cellular therapy that truly restores healthy intestinal immune cell populations from hematopoietic stem cells.

Purpose of review: The purpose of this review article is to: describe the clinical manifestations of esophageal lichen planus (ELP), understand its epidemiological risk factors, elaborate the common endoscopic and histopathologic findings of ELP, summarize current thinking on treatment and surveillance, and understand the long-term sequelae of ELP.

Recent findings: A combination of clinical, endoscopic, and histopathologic findings are required to make a diagnosis of ELP. While there is no consensus on management of ELP, there is evidence of clinical and endoscopic improvement with the use of topical steroids among other therapies. There is a known risk of malignant transformation of ELP to esophageal squamous cell carcinoma (ESCC).

Summary: ELP is an idiopathic condition that primarily affects Caucasian females ages 50-70 years. This review of current literature suggests that a combination of clinical, endoscopic, and histologic findings are required to make a diagnosis; topical steroids with or without esophageal dilation show overall improvement of ELP; and endoscopic surveillance to monitor for ESCC is recommended.