Background and Objective: Environmental factors interact with host cells, primarily during specific vulnerable periods in a genetically predisposed individual. These factors can act as triggers of an exaggerated immune response contributing to the development of inflammatory bowel disease (IBD). The connection between host genome, gut microbiome, and environmental exposures in the development of IBD requires further clarification. The objective of this review is to explore air pollution as a possible risk factor for the development of IBD. Methods: We searched PubMed, Embase, and Cochrane Library databases to identify studies published up to September 15, 2023. We also analyzed references from relevant original articles and literature reviews to identify additional studies that were not encompassed in the initial database searches. For all eligible studies, we provided a narrative analysis of the findings. Key Content and Findings: The onset of IBD results from the association of various risk factors including genetic susceptibility, diet, immune dysregulation, and environmental factors that could potentially trigger the disease. Although there are conflicting results regarding the impact of air pollution on IBD pathogenesis, it appears that its role in increasing the expression of pro-inflammatory cytokines, disturbances in microbiota composition and colonic function is associated with a higher risk of incident ulcerative colitis (UC). Conclusions: Besides conflicting and inconsistent results from previous studies and notable knowledge gaps, there is a plausible chance that the development of IBD can be affected by air pollution. Future prospective studies are required to gain comprehensive insight into this correlation.
Epigenetic mechanisms maintain gene expression states within a cell and through cellular generations and involve DNA methylation and chromatin changes, such as histone modifications. These mechanisms play roles in inflammatory processes. Here we review recent advances about what we know about their impact in inflammatory bowel disease (IBD). The incidence and prevalence of IBD have significantly increased in recent decades, establishing it as one of the most common gastrointestinal disorders. Lifestyle changes, including dietary factors, have been identified as potential contributors to this phenomenon. Although the heritability of IBD cannot be solely attributed to common genetic variants, their examination has shed light on the involvement of epigenetic and chromatin factors, such as DNMT3A and SP140, in the development of IBD. Studies focusing on SP140 have provided a paradigm by demonstrating the association between genetic alterations in this gene and changes in chromatin structure, gene expression, and the composition of the microbiome, ultimately resulting in abnormal inflammation. Genetic deletion coupled to experimental colitis studies in mice have highlighted roles of additional important factors linked to DNA methylation, MBD2 and UHRF1, and histone methylation, such as SETD2, in regulating the inflammatory processes in the gut. Further research is needed to investigate how environmental factors contribute to the predisposition of IBD through epigenetic mechanisms. This line of inquiry holds the potential to pave the way for new intervention strategies.
Background and Objective: Esophagectomy and subsequent gastrointestinal tract reconstruction provide treatment for both benign and malignant diseases. It can be performed by open and minimally invasive esophagectomy (MIE) techniques with either trans-thoracic (TT) or trans-hiatal (TH) approaches. Regarding the intrinsic differences of each procedure, some postoperative complications are highly common in all types of esophagectomy. Gastroesophageal reflux disease (GERD) is one of the most common postoperative complications of esophageal resection. This review aims to discuss reflux after esophagectomy and its correlation to the surgical technique adopted, the pathophysiological mechanisms involved, its clinical impact, as well as the strategies for diagnosis, preventing measures and clinical or surgical treatment options. Methods: The authors performed a narrative review evaluating the reflux after esophagectomy. Key Content and Findings: The causes for its occurrence are multifactorial, including loss of anti-reflux mechanisms and other hypothetical mechanisms. There is no consensus regarding the diagnostic methods and when to start the reflux investigation after esophagectomy. Nevertheless, the initial assessment should be performed with endoscopy. Further diagnostic evaluation with pH-metry or impedance monitoring is not routinely indicated, given the absence of standardization of the positioning of the pH-metry catheter. In order to avoid its occurrence, both intraoperative and postoperative measures should be adopted to mitigate the risks of postoperative gastroesophageal reflux. Understanding risk factors and aspects of surgical technique may decrease the impact of this complication. This review discusses reflux after esophagectomy and its correlation to the surgical technique adopted, the pathophysiological mechanisms involved, its clinical impact, the strategies for investigating this condition, and the measures to prevent and treat it. Conclusions: Gastroesophageal reflux after esophagectomy is a common complication, demanding complex management. Understanding the pathophysiological mechanisms, the clinical impact, its diagnosis and prevention and treatment options may help reduce its morbidity.
First-line treatment for gastroesophageal reflux disease (GERD) consists of lifestyle modifications and anti-reflux medication with proton pump inhibitors (PPI) being the most common. Approximately 30% of patients continue to suffer despite these medications. New surgical and endoscopic techniques have been developed to treat medically refractory GERD. Nontraditional surgical therapies include magnetic sphincter augmentation (MSA) and transoral incisionless fundoplication (TIF). Initial studies with each of these approaches have demonstrated promising results and their roles in treating reflux are still evolving. Studies for both procedures have demonstrated promising long-term results in regards to reduced PPI usage, symptom relief, and improvement in quality of life. In addition, these procedures have been shown to be safe with a low incidence of adverse events. Although initial studies with each of these approaches have demonstrated promising results, their roles in treating reflux are still evolving. As their roles in anti-reflux surgery continue to expand, this also opens up the potential for complications including dysphagia and persistent reflux disease. The purpose of this review article is to discuss the mechanism of action and outcomes for both MSA and TIF. In addition, we will discuss the evaluation and management of patients who require re-operation for complications following each procedure.
Background and Objective: Tumor treating fields (TTFields) therapy have emerged as a potentially effective treatment for various malignancies by delivering low-intensity, intermediate-frequency electrical fields that disrupt many processes inside cells, resulting in the interruption of cell division in cancer cells. Additionally, TTFields therapy has been found to be synergistic with existing therapeutic approaches. In this review, we provide an introduction and background to the primary mechanisms of TTFields and discuss the emerging preclinical and clinical outcomes of this novel cancer treatment technology.Methods: We performed a literature search on PubMed, ClinicalTrials.Gov, and Google Scholar using the terms 'TTFields' and 'cancer'. We included studies, review articles, and editorials published in English from 1st January 2000 to 1st October 2023. All obtained publications were reviewed and their key references are cross-checked to ensure a balanced and high-quality review.Key Content and Findings: Clinical studies reported to date have demonstrated the survival advantage of TTFields therapy in newly diagnosed glioblastoma (GBM), non-small cell lung cancer (NSCLC), and meaningful clinical activity in recurrent GBM (rGBM) and malignant pleural mesothelioma. Moreover, TTFields therapy has exhibited promising safety profiles across a diverse range of cancers including pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, NSCLC, and gastric cancer, when combined with cytotoxic chemotherapy and/or immunotherapy regimens, suggesting broad applicability as an added treatment modality.Conclusions: Based on preclinical and clinical studies, TTFields therapy show promise as a potential treatment option for patients with a number of different malignancies, offering a favorable safety profile and the potential for significant clinical benefit. Further research is warranted to establish the optimal treatment parameters and identify specific patient subgroups that may derive the greatest advantage from this treatment modality.
Biliary reflux refers to the ascent of duodenal fluid, biliary and pancreatic secretions into the stomach and esophagus. It is a primitive phenomenon or it can be secondary to gastric or biliary surgery. In particular, biliary reflux seems common after bariatric surgeries with, however, unknown incidence. Current data show that the prevalence of biliary reflux was higher after minigastric bypass as compared to the other bariatric surgeries. Nevertheless, biliary reflux resulted to be a relevant risk factor for the development of reflux-related complications, such as erosive esophagitis and Barrett esophagus, and its persistence over time seems to be an independent risk factor for gastric cancer. Its evaluation is challenging, and several methods have been proposed to date. Hepatobiliary iminodiacetic acid (HIDA) assessment is a non-invasive technique which showed a good correlation with gastric bile acids in several clinical investigations. Impedance-pH monitoring has been shown to correctly identify non-acidic reflux, but it is not considered a valid tool to diagnose the occurrence of bile reflux episodes in the esophagus since its inability to distinguish bile from other non-acidic components of the refluxate like food. Fibreoptic spectrophotometric probe (Bilitec) was proposed to quantify bile reflux in an ambulatory setting and over a prolonged period, using bilirubin as a marker for the presence of duodenal contents. Only few studies have addressed the impact of anti-reflux surgeries on treating biliary reflux, although these procedures appear to be effective to improve clinical and objective outcomes of this complication.
: To minimize the postoperative pulmonary complications after esophagectomy, transhiatal esophagectomy has been a choice of surgical procedure but regarded as oncologically insufficient surgery for esophageal squamous cell carcinoma, because it omits the mediastinal lymph node dissection, especially in the upper mediastinum. In the past decade, non-transthoracic radical esophagectomy with the combination of transcervical and transhiatal video-assisted surgery have been increasingly reported. This procedure, referred as mediastinoscopic esophagectomy, enables the retrieval of the whole posterior mediastinal regional lymph nodes via cervical and abdominal small incisions. Mediastinoscopic esophagectomy would be advantageous in the prevention of postoperative pulmonary complications because it can be completed without any manipulations on the lungs or the chest wall. However, transcervical part of the mediastinoscopic esophagectomy allows limited assistance from a second surgeon owing to the small skin incision and the narrow operative field. In addition, surgeons have to overcome technical issues, such as unfamiliar surgical view and susceptibility to the recurrent nerve injury. Nowadays, studies on the safety and the feasibility of mediastinoscopic surgery have been accumulated reporting its surgical outcome. A review of literatures on short term outcome was conducted here to clarify the feasibility of mediastinoscopic esophagectomy as an oncologic surgery. Fourteen studies and four review articles hit the PubMed search. Tracheal injury was reported in three studies with a frequency of 3.3–6.3% and no other type of intraoperative adverse event was reported. In-hospital mortality was rarely reported. The reported frequency of the pulmonary complication was less than 10% in the majority of the studies. The mediastinoscopic radical esophagectomy has been demonstrated as safe and feasible. However, its superiority in the short term outcome remains unknown.
After sleeve gastrectomy (SG), patients may develop gastroesophageal reflux disease (GERD), leading to severe complications like erosive esophagitis (EE), long-term use of proton-pump inhibitors, Barrett's esophagus (BE), and in rare cases, esophageal adenocarcinoma. Therefore, conducting regular surveillance through endoscopy is essential to detect any potential issues, even if there are no apparent symptoms. Upper gastrointestinal endoscopy (UGE) and contrast studies are recommended to diagnose GERD after SG. Identifying anatomical complications is crucial for patients experiencing reflux symptoms after SG. If no anatomical issues are detected, the first course of treatment is medical management with proton-pump inhibitors. If symptoms persist, the dose may escalate, and de-escalation may occur if symptoms improve. pHmetry and manometry can be utilized to identify underlying issues if proton-pump inhibitors are ineffective. When necessary, Roux-en-Y gastric bypass is the preferred treatment. Though emerging techniques like the Stretta procedure and Linx system are being evaluated for their less invasive approach to managing GERD after SG, their data still needs to be conclusive. Even in asymptomatic patients, continuous screening, including routine upper endoscopy, is necessary for long-term follow-up of GERD after SG. Management may require a combination of medical and surgical interventions, and less invasive approaches still require further research.
Background and Objective: Inflammatory bowel disease (IBD) is an immune-mediated disease of the gastrointestinal (GI) tract. Its pathophysiology is influenced by environmental and epigenetic factors such as diet, microbiota, genetics, and DNA modifications. Omics analysis has provided valuable insights into the role of these factors in IBD pathogenesis and the identification of potential biomarkers. Methods: To interpret the evidence on the association of environmental factors, such as diet, with IBD onset and their impact on the genome, a literature review using the MEDLINE database within the National Library of Medicine (PubMed) was performed. Key Content and Findings: IBD is a multifactorial disease involving genetic and epigenetic factors, and understanding its etiology has been challenging to many researchers. Different elements of the exposome may induce epigenetic changes related to IBD. One of the most scrutinized in the last few years is diet and how it can modulate the microbiome. Conclusions: Genomics does not explain the disease in its entire pathophysiology, and this opened the possibility of investigating other pathways and factors, such as the epigenome, microbiome, diet, and exposome, to better understand IBD. We emphasized in this review the relevance of researching IBD more broadly, mainly looking at association studies, although mechanistic ones still need to be improved in the literature. This review highlights the need for a comprehensive investigation of the Exposome-Diet-Epigenome axis to enhance our understanding of IBD and its outcomes.
: Histone post-translational modifications are reversible epigenetic mechanisms that regulate chromatin structure and gene transcription. In recent years, in addition to the well-characterized histone acetylation, new acylations such as propionylation, crotonylation, butyrylation and beta-hydroxybutyrylation have been described and explored in different cell types at contexts of health and disease. Understanding how histone acylations contribute to gene expression regulation is especially important in intestinal epithelial cells (IECs) because they receive many different signals from other cells and the external environment and must adapt to maintain essential functions such as nutrient and water absorption, maintenance of tolerance and protection against pathogens. In this review, we describe how cells regulate these modifications, how they are recognized by other proteins and impact gene expression. We summarize recent studies that explored the role of these distinct epigenetic marks in the regulation of IECs and discuss their biological importance for the intestinal epithelium's adaptations to changes in metabolism and to respond to environmental signals provided, for example, by the diet, components of the intestinal microbiota and pathogens. Finally, we discuss how the histone acylations are affected by inflammatory signals and how this knowledge may provide new targets for treatment of pathologies such as the inflammatory bowel diseases.
Background: Inflammatory cloacogenic polyps (ICPs) are rare anorectal tumours considered part of the spectrum of mucosal prolapse manifestations. They can mimic various anorectal pathologies and are known to be associated with other colorectal pathologies. Current recommendations mandate complete excision for malignant transformation concerns, even though the chance of this occurring is infrequent. Case Description: An 88-year-old lady presented to our unit for colonoscopy following a year’s complaints of intermittent haematochezia previously attributed to internal haemorrhoids, for which she underwent bedside hemorrhoidal banding. Rectal examination revealed a soft, fleshy mass at the anterior rectal wall and index colonoscopy demonstrated a large, 30 mm sessile polyp in the anorectal junction. Lesion characterisation did not show neoplastic features, and targeted biopsies revealed an inflammatory picture. Following a discussion with the patient, the polyp was resected without complications 2 weeks later through the hybrid endoscopic submucosal dissection (ESD) technique. The subsequent histopathology was consistent with ICP: hyperplastic tubulovillous glands with elongated and irregular crypts with fibromuscular proliferation within the lamina propria. On surveillance colonoscopy 3 months later, the resected site has healed with no evidence of recurrence. Our patient remains well with no further complaints. Conclusions: Despite the low incidence of ICPs, clinicians need to familiarise themselves with this benign entity as they can be mistaken for haemorrhoids (in our case), benign ulcers or even anorectal cancers. Careful antegrade and retrograde colonoscopic examination complemented with narrow-band imaging (NBI) and targeted biopsies are practical strategies for improving specimen yield. In terms of endoscopic treatment for lesions larger than 20 mm, hybrid ESD can be a viable alternative for centres that do not possess the technical expertise required of conventional ESD. Here, we described novel approaches to how NBI and hybrid ESD could complement current diagnostic and therapeutic strategies for ICPs.
