Reviews
Application of histology-agnostic treatments in metastatic colorectal cancer
Cancer treatment is increasingly focused on targeting molecular alterations identified across different tumor histologies. While some oncogenic drivers such as microsatellite instability (MSI) and NTRK fusions are actionable with the very same approach regardless of tumor type (“histology-agnostic”), others require histology-specific therapeutic adjustment (“histology-tuned”) by means of adopting specific inhibitors and ad hoc combinations. Among histology-agnostic therapies, pembrolizumab or dostarlimab demonstrated comparable activity in MSI metastatic colorectal cancer (mCRC) as in other tumors with MSI status (ORR 38% vs 40% and 36% vs 39%, respectively), while entrectinib or larotrectinib proved effective in NTRK rearranged mCRC even though less dramatically than in the overall population (ORR 20% vs 57%, and 50% vs 78%, respectively).Systematic Review: esophageal motility patterns in patients with eosinophilic esophagitis
Eosinophilic esophagitis (EoE) is a chronic disorder of the esophagus characterized by an eosinophil-predominant inflammation and symptoms of esophageal dysfunction. Eosinophils can influence esophageal motility, leading to dysphagia worsening. The spectrum of esophageal motility in EoE is uncertain.Sarcopenia in chronic advanced liver diseases: A sex-oriented analysis of the literature
Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting.Exposed endoscopic full-thickness resection without laparoscopic assistance for gastric submucosal tumors: A systematic review and pooled analysis
Exposed endoscopic full-thickness resection (Eo-EFTR) is emerging as a promising minimally invasive alternative to surgery for the treatment of deep gastric submucosal tumors (G-SMTs). However, literature concerning this subject is heterogeneous and data mostly come from relatively small retrospective studies.Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective
Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.FAPI PET/CT research progress in digestive system tumours
18F-fluorodeoxyglucose positron emission tomography/computed tomography has been used in clinical practice for many years. This modality is of great value for tumour diagnosis, staging, and efficacy evaluations, but it has many limitations in the diagnosis and treatment of digestive system tumours. Fibroblast activation protein is highly expressed in gastrointestinal tumours. Various isotope-labelled fibroblast activation protein inhibitors are widely used in clinical research. These inhibitors have low background uptake in the brain, liver and oral/pharyngeal mucosa and show good contrast between the tumour and background, which makes up for the lack of fluorodeoxyglucose in the diagnosis of digestive system tumours.Intercellular crosstalk of liver sinusoidal endothelial cells in liver fibrosis, cirrhosis and hepatocellular carcinoma
Intercellular crosstalk among various liver cells plays an important role in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Capillarization of liver sinusoidal endothelial cells (LSECs) precedes fibrosis and accumulating evidence suggests that the crosstalk between LSECs and other liver cells is critical in the development and progression of liver fibrosis. LSECs dysfunction, a key event in the progression from fibrosis to cirrhosis, and subsequently obstruction of hepatic sinuses and increased intrahepatic vascular resistance (IHVR) contribute to development of portal hypertension (PHT) and cirrhosis.Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease
Hepatocellular carcinoma (HCC) is on the rise globally, causing more than 800 thousand deaths annually, with an estimated annual percent change of 0.51 for causes other than viral hepatitis, including nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD-related HCC is peaking in several Far East regions (6–12% vs. 2–3% in Western Europe and USA), HCC risk being mainly driven by the epidemic of obesity and diabetes, both favored by an unhealthy diet and sedentary lifestyle. Under inherited susceptibility outlined by such genetic markers as variants in PNPLA3, TM6SF2 and MBOAT7, neoplastic transformation of NAFLD is driven by sublethal lipotoxicity consequent to hepatocyte lipid overload, whereas a myriad of factors spanning from subverted circadian homeostasis and gut dysbiosis to alcohol abuse and tobacco may interact as risk modifiers.Cutting edge issues in juvenile sclerosing cholangitis
Sclerosing cholangitis (SC) is a rare chronic disorder characterised by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts. Diagnosis is based on cholangiogram showing bile duct dilatation, narrowing and obliteration of the biliary tree, and histologically, on the presence of inflammatory bile duct damage leading to periductal fibrosis. In children the most common SC is associated with strong autoimmune features, overlapping with those of autoimmune hepatitis (AIH); this form is known as autoimmune sclerosing cholangitis, ASC.The application of artificial intelligence in hepatology: A systematic review
The integration of human and artificial intelligence (AI) in medicine has only recently begun but it has already become obvious that intelligent systems can dramatically improve the management of liver diseases. Big data made it possible to envisage transformative developments of the use of AI for diagnosing, predicting prognosis and treating liver diseases, but there is still a lot of work to do. If we want to achieve the 21st century digital revolution, there is an urgent need for specific national and international rules, and to adhere to bioethical parameters when collecting data.A reasoned approach to the treatment of autoimmune hepatitis
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis on histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to analyse AIH therapeutic interventions with reference to our knowledge of the pathogenesis of AIH. Standard treatment, based on steroids and azathioprine, leads to disease remission in 80–90% of patients.Female reproductive health and inflammatory bowel disease: A practice-based review
Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause.Vaccinations in patients with inflammatory bowel disease
Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines.Treatment of primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive fibro-stenotic strictures and destruction of the biliary tree. Currently, there is no effective treatment which can delay its progression or ameliorate the transplant-free survival. Moreover, a major chontroversy in PSC is whether to use UDCA. More recently, novel pharmacological agents emerged aiming at: i) modulation of bile composition; ii) immunomodulation; iii) targeting the gut microbiome; iv) targeting fibrosis.Clinical usefulness of esophageal high resolution manometry and adjunctive tests: An update
High resolution manometry (HRM), developed from conventional manometry, is the gold standard for assessment of esophageal motor function worldwide. The Chicago Classification, now in its fourth iteration, is the modern standard for HRM categorization of esophageal motility disorders. The HRM protocol has expanded from the original 10 supine swallow standard, to include upright swallows, and provocative maneuvers such as multiple rapid swallows, rapid drink challenge and standardized test meal. Impedance has been incorporated into HRM for visualization of bolus clearance.Vaccinations and inflammatory bowel disease – a systematic review
Patients with inflammatory bowel disease(IBD) are at risk of infections, many of which are preventable with vaccinations. We performed a systematic review on various aspects of vaccination in IBD.Gastritis: The clinico-pathological spectrum
The inflammatory spectrum of gastric diseases includes different clinico-pathological entities, the etiology of which was recently established in the international Kyoto classification. A diagnosis of gastritis combines the information resulting form the gross examination (endoscopy) and histology (microscopy). It is important to consider the anatomical/functional heterogeneity of the gastric mucosa when obtaining representative mucosal biopsy samples. Gastritis includes self-limiting and non-self-limiting (long-standing) inflammatory diseases, and the latter are epidemiologically, biologically and clinically linked to the onset of gastric cancer (i.e.Quality of life in patients with moderate to severe ulcerative colitis and the impact of treatment: A narrative review
As a chronic inflammatory disease, ulcerative colitis has significant negative impact on the quality of life (QoL) of patients. Since the disease affects many aspects of QoL, comprising multiple domains, treatments that induce and maintain remission can provide benefits beyond hard clinical endpoints. Effective treatment of ulcerative colitis can restore QoL and return it to normal or near normal levels. Biological therapies have shown consistent improvement in the QoL of patients with ulcerative colitis during the induction phase, with benefits that are generally maintained in the long-term.Histopathology of non-IBD colitis practical recommendations from pathologists of IG-IBD Group
Pathologists are often called upon to diagnose colitides that differ from the two main forms of inflammatory bowel disease (IBD). These non-IBD colitides include infectious colitis, microscopic colitis, ischemic colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation colitis and diversion colitis. The diagnosis of these different disease entities relies on the histopathological examination of endoscopic biopsies of the gastrointestinal tract.Gastrointestinal endoscopy in children and adults: How do they differ?
Gastrointestinal endoscopy has grown dramatically over the past century, and with subsequent improvements in technology and anaesthesia, it has become a safe and useful tool for evaluation of GI pathology in children. There are substantial differences between paediatric and adult endoscopy beyond size, including: age-related patho-physiology and the different spectrum of diseases in children. Literature on endoscopic procedures in children is sparse but significant. The present review aims at describing the current knowledges on paediatric endoscopy practice and highlights the main areas of differences between paediatric and adult practice.Kidney function monitoring to prevent 5-aminosalicylic acid nephrotoxicity: What the gastroenterologist should know
The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic.Inflammatory bowel diseases and the risk of adverse health outcomes: Umbrella review of meta-analyses of observational studies
Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes.From inflammation to colitis-associated colorectal cancer in inflammatory bowel disease: Pathogenesis and impact of current therapies
The risk of colorectal cancer (CRC) is higher in patients with inflammatory bowel disease (IBD). Population-based data from patients with ulcerative colitis (UC) estimate that the risk of CRC is approximately 2- to 3-fold that of the general population; patients with Crohn's disease appear to have a similar increased risk. However, the true extent of colitis-associated cancer (CAC) in undertreated IBD is unclear. Data suggest that the size (i.e., severity and extent) and persistence of the inflammatory process is largely responsible for the development of CRC in IBD.Systematic assessment of environmental factors for gastroesophageal reflux disease: An umbrella review of systematic reviews and meta-analyses
Side effects of long-term acid suppression have increased the scholars’ interest in nonpharmacologic intervention.IBDs and the pediatric age: Their peculiarities and the involvement of the microbiota
Inflammatory Bowel Diseases (IBDs) are gastrointestinal disorders characterized by chronic, relapsing inflammation, with growing incidence worldwide over the last decades and distinctive features in the pediatric age. An increasing body of evidence indicates that gut microbiota plays a major role in inflammatory disorders, including IBDs. In this review we will discuss the most recent evidences on dysbiotic changes associated with gut inflammation, as well as environmental and genetic factors contributing to IBD pathogenesis, with a focus on the peculiarities of the pediatric age.
