Chronic inflammation, regardless of infectious agents, plays important roles in the development of various cancers, particularly in digestive organs, including Helicobacter pylori –associated gastric ...cancer, hepatitis C virus–positive hepatocellular carcinoma, and colitis-associated colon cancers. Cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations of various proto-oncogenes and tumor-suppressor genes. During chronic inflammation, infectious agents such as H pylori and hepatitis C virus as well as intrinsic mediators of inflammatory responses, including proinflammatory cytokines and reactive oxygen and nitrogen species, can induce genetic and epigenetic changes, including point mutations, deletions, duplications, recombinations, and methylation of various tumor-related genes through various mechanisms. Furthermore, inflammation also modulates the expressions of microRNAs that influence the production of several tumor-related messenger RNAs or proteins. These molecular events induced by chronic inflammation work in concert to alter important pathways involved in normal cellular function, and hence accelerate inflammation-associated cancer development. Among these, recent studies highlighted an important role of activation-induced cytidine deaminase, a nucleotide-editing enzyme essential for somatic hypermutation and class-switch recombination of the immunoglobulin gene, as a genomic modulator in inflammation-associated cancer development.
Specificity proteins (SPs) and Krüppel-like factors (KLFs) belong to the family of transcription factors that contain conserved zinc finger domains involved in binding to target DNA sequences. Many ...of these proteins are expressed in different tissues and have distinct tissue-specific activities and functions. Studies have shown that SPs and KLFs regulate not only physiological processes such as growth, development, differentiation, proliferation, and embryogenesis, but pathogenesis of many diseases, including cancer and inflammatory disorders. Consistently, these proteins have been shown to regulate normal functions and pathobiology in the digestive system. We review recent findings on the tissue- and organ-specific functions of SPs and KLFs in the digestive system including the oral cavity, esophagus, stomach, small and large intestines, pancreas, and liver. We provide a list of agents under development to target these proteins.
Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and ...pancreatic diseases in the United States.
We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids’ Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH).
Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020.
Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.
Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European ...Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21–22 September 2000.
A ‘test and treat’ approach is recommended in adult patients under the age of 45 years (the age cut‐off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro‐oesophageal reflux disease symptoms, non‐steroidal anti‐inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test.
As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low‐grade gastric mucosa‐associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first‐degree relatives of gastric cancer patients and according to patients’ wishes after full consultation.
It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long‐term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro‐oesophageal reflux disease in most cases, and does not exacerbate existing gastro‐oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non‐steroidal anti‐inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non‐steroidal anti‐inflammatory drugs.
Treatment should be thought of as a package which considers first‐ and second‐line eradication therapies together. First‐line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second‐line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second‐line therapy should be with proton pump inhibitor‐based triple therapy. If second‐line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case‐by‐case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradica‐ tion should always be confirmed by urea breath test or an endoscopy‐based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.
Covid‐19 and the digestive system Wong, Sunny H; Lui, Rashid NS; Sung, Joseph JY
Journal of gastroenterology and hepatology,
20/May , Volume:
35, Issue:
5
Journal Article
Peer reviewed
Open access
The novel coronavirus disease is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a member of the Betacoronavirus genus that also ...includes the SARS‐CoV and Middle East respiratory syndrome coronavirus. While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Studies have identified the SARS‐CoV‐2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS‐CoV‐2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease.
Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein ...families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation state expression, and association with >80 human diseases when mutated. Whereas most IF mutations cause disease, mutations in simple epithelial keratins 8, 18, or 19 or in lamin A/C predispose to liver disease with or without other tissue manifestations. Keratins serve major functions including protection from apoptosis, providing cellular and subcellular mechanical integrity, protein targeting to subcellular compartments, and scaffolding and regulation of cell-signaling processes. Keratins are essential for Mallory-Denk body aggregate formation that occurs in association with several liver diseases, whereas an alternate type of keratin and lamin aggregation occurs upon liver involvement in porphyria. IF-associated diseases have no known directed therapy, but high-throughput drug screening to identify potential therapies is an appealing ongoing approach. Despite the extensive current knowledge base, much remains to be discovered regarding IF physiology and pathophysiology in digestive and nondigestive organs.
Chronic digestive diseases, including irritable bowel syndrome, gastroesophageal reflux disease, and inflammatory bowel diseases, cannot be disentangled from their psychological context—the ...substantial burden of these diseases is co-determined by symptom and disease severity and the ability of patients to cope with their symptoms without significant interruption to daily life. The growing field of psychogastroenterology focuses on the application of scientifically based psychological principles and techniques to the alleviation of digestive symptoms. In this Clinical Practice Update, we describe the structure and efficacy of 2 major classes of psychotherapy—cognitive behavior therapy and gut-directed hypnotherapy. We focus on the impact of these brain–gut psychotherapies on gastrointestinal symptoms, as well as their ability to facilitate improved coping, resilience, and self-regulation. The importance of the gastroenterologist in the promotion of integrated psychological care cannot be overstated, and recommendations are provided on how to address psychological issues and make an effective referral for brain–gut psychotherapy in routine practice.
Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular ...carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.
Infection with the SARS-CoV-2 virus seems to contribute significantly to increased postoperative complications and mortality after emergency surgical procedures. Additionally, the fear of COVID-19 ...contagion delays the consultation of patients, resulting in the deterioration of their acute diseases by the time of consultation. In the specific case of urgent digestive surgery patients, both factors significantly worsen the postoperative course and prognosis. Main working hypothesis: infection by COVID-19 increases postoperative 30-day-mortality for any cause in patients submitted to emergency/urgent general or gastrointestinal surgery. Likewise, hospital collapse during the first wave of the COVID-19 pandemic increased 30-day-mortality for any cause. Hence, the main objective of this study is to estimate the cumulative incidence of mortality at 30-days-after-surgery. Secondary objectives are: to estimate the cumulative incidence of postoperative complications and to develop a specific postoperative risk propensity model for COVID-19-infected patients.A multicenter, observational retrospective cohort study (COVID-CIR-study) will be carried out in consecutive patients operated on for urgent digestive pathology. Two cohorts will be defined: the "pandemic" cohort, which will include all patients (classified as COVID-19-positive or -negative) operated on for emergency digestive pathology during the months of March to June 2020; and the "control" cohort, which will include all patients operated on for emergency digestive pathology during the months of March to June 2019. Information will be gathered on demographic characteristics, clinical and analytical parameters, scores on the usual prognostic scales for quality management in a General Surgery service (POSSUM, P-POSSUM and LUCENTUM scores), prognostic factors applicable to all patients, specific prognostic factors for patients infected with SARS-CoV-2, postoperative morbidity and mortality (at 30 and 90 postoperative days). The main objective is to estimate the cumulative incidence of mortality at 30 days after surgery. As secondary objectives, to estimate the cumulative incidence of postoperative complications and to develop a specific postoperative risk propensity model for SARS-CoV-2 infected patients.The protocol (version1.0, April 20th 2020) was approved by the local Institutional Review Board (Ethic-and-Clinical-Investigation-Committee, code PR169/20, date 05/05/20). The study findings will be submitted to peer-reviewed journals and presented at relevant national and international scientific meetings.ClinicalTrials.gov Identifier: NCT04479150 (July 21, 2020).
The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify ...diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve AUC = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P < .05). In addition, PIS provided a higher net benefit than TNM stage. A composite nomogram was built based on PIS and patients' clinical information with well‐fitted calibration curves (c‐index = 0.84). We further used other cohorts from Gene Expression Omnibus databases and obtained similar results, confirming the reliability and validity of the DIS and PIS. In addition, the unsupervised clustering analysis using immune cell proportions revealed 6 immune subtypes, suggesting that the immune types defined as having relatively high levels of M0 or/and M1 macrophages were the high‐risk subtypes of relapse. In conclusion, this study comprehensively analyzed the tumor immune microenvironment and identified DIS and PIS for digestive system cancers.
Our study comprehensively analyzed the utility of consideration of immune cells in the diagnosis and prognosis of digestive system cancers. The diagnostic immune score and prognostic immune score signature might serve as biomarkers for early diagnosis and predicting survival.
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