A major clinical challenge for patients with pancreatic cancer (PC) is metabolic adaptation. Neoplastic cells harboring molecular perturbations suffice for their increased anabolic demand and nucleotide biosynthesis to acquire chemoresistance. The mucin 5AC expressed de novo in malignant pancreas promotes cancer cell stemness and is significantly associated with poor patient survival. Identification of MUC5AC-associated drivers of chemoresistance through metabolic alterations may facilitate the sculpting of a new combinatorial regimen.

Significant progress has been made since the first report of inflammatory bowel disease (IBD) in 1859, after decades of research that have contributed to the understanding of the genetic and environmental factors involved in IBD pathogenesis. Today, a range of treatments is available for directed therapy, mostly targeting the overactive immune response. However, the mechanisms by which the immune system contributes to disease pathogenesis and progression are not fully understood. One challenge hindering IBD research is the heterogeneous nature of the disease and the lack of understanding of how immune cells interact with one another in the gut mucosa. Introduction of a technology that enables expansive characterization of the inflammatory environment of human IBD tissues may address this gap in knowledge.

This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs).

We performed a meta-analysis to investigate the efficacy of complete omentectomy (CO) in patients undergoing radical gastrectomy for gastric cancer.

Inactivation of the Apc gene is a critical early event in the development of sporadic colorectal cancer (CRC). Expression of serine-threonine kinase receptor-associated protein (STRAP) is elevated in CRCs and is associated with poor outcomes. We investigated the role of STRAP in Apc mutation-induced intestinal tumor initiation and progression.

Gastroparesis is a chronic functional disorder characterized by severe symptoms and objective documentation of delayed gastric emptying, in the absence of any mechanical obstruction. The pathogenesis of gastroparesis comprises abnormalities of gastric motility (corpus and fundus dysmotility and antral hypomotility), pyloric resistance to gastric outflow (pyloric lower compliance or hypertone), and lack of antroduodenal motor coordination. Several conditions have been correlated to gastroparesis: diabetes, post-surgical sequelae, medications, neurological/muscular disorders and collagen vascular diseases. Diabetes is the most frequent condition associated with gastroparesis, which has been reported in up to 50% of patients suffering from long-lasting disease. The therapy of gastroparesis is primarily medical, with prokinetic or antiemetic drugs, but response may be limited, and side effects can arise; if medical therapy fails, pyloromyotomy remains the main option, either surgical or endoscopic. Gastric peroral endoscopic myotomy (G-POEM) may be considered nowadays an effective potential therapeutic intervention in alternative to surgery, relatively easy to perform in experienced hands, with a technical success of 100%, a favorable safety profile, and positive outcomes in the short-term as documented in three meta-analyses. However, to date, the definition of clinical success in gastroparesis is still not standardized, the correlation between symptom improvement and the objective documentation of an improvement in gastric emptying remains in some cases uncertain, reliable data to help in predicting which categories of gastroparesis and which symptoms could benefit most from the intervention, and long-term outcomes are still lacking.

Esophageal diverticula (ED) are uncommon, mostly seen in elderly and can present with a multitude of symptoms. Of the three types of ED, epiphrenic and mid-esophageal diverticulum are still rare. These are often associated with esophageal motility disorder, which contributes to its development. The key step in the management of such symptomatic ED is the division of the septum and tackling the underlying motility dysfunction, if any. Traditional surgical options have high morbidity and mortality while flexible endoscopic septal division cannot adequately manage epiphrenic diverticulum with motility dysfunction. The technique of submucosal space creation and peroral endoscopic myotomy (POEM) has been used to treat a host of esophageal diseases such as achalasia. POEM has been recently described for the management of ED. Two different strategies have been described for tackling using POEM, namely, diverticular POEM (D-POEM) and salvage POEM (S-POEM). While D-POEM entails division of the septum and esophageal myotomy, S-POEM requires only esophageal myotomy without septum division. Multiple retrospective studies in the recent years have described use of POEM for the management of different types of ED with good safety and efficacy with low recurrence rate. This review encompasses a detailed account of the technical steps, pre- and post-procedure evaluation and literature review of safety, efficacy, adverse events, and recurrence rates of the use of POEM for ephiprenic and mid-esophageal diverticulum. We have also proposed a management algorithm based on the type of underlying motility dysfunction and the size of the diverticulum.

Gut microbiota plays a vital role in human health. The number of microorganisms inhabiting the gastrointestinal (GI) tract has been estimated to exceed 1013. The dominant genera in the human intestine are Firmicutes (more than 180 species of Lactobacillus), Actinobacteria (among others the Bifidobacteriae), Bacteroidetes (the most important is B. fragilis) and Proteobacteria (E. coli, Salmonella, Yersinia, Shigella, Vibrio, Haemophilus, etc.), but the composition of the flora varies individually, as well as in relation to factors such as host genetics, stress, diet, antibiotics and early childhood experiences. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGIDs), which has now been renamed disorders of gut-brain interaction, which affect a large number of people worldwide. It is characterized by abdominal pain and altered bowel habits in the absence of obvious anatomic or physiologic abnormalities. It poses a negative economic impact to the global health care system in addition to reducing the quality of life in patients. The pathophysiology of IBS is not fully understood. In IBS subjects gut microbiota relative to healthy controls was observed with an increase in Enterobacteriaceae, Ruminococcus, Clostridium, Dorea species and a decrease of Lactobacillus, Bifidobacterium, and Faecalibacterium species. IBS with diarrhea predominance (IBS-D) IBS with mixed bowel habits (IBS-M) share similarities in the microbial profile. Recent studies suggest that perturbations within "brain-gut-microbiota" axis may lead to IBS development. The aim of this review was to highlight the potential role of gut microbiota on pathophysiological mechanisms underlying IBS.

Intestinal microbiota-host interactions play a major role in health and disease. This has been documented at the microbiota level ("dysbiosis" in chronic immune-mediated diseases) and through the study of specific bacteria-host interactions but rarely at the level of intestinal ecosystem dynamics. However, understanding the behavior of this ecosystem may be key to the successful treatment of disease. We recently postulated that health and disease represent alternative stable states of the intestinal ecosystem (different configurations that can exist under identical external conditions), which would require adapted strategies in disease treatment. Here, we examine if alternative stable states indeed exist in this ecosystem and if they could affect remission from ulcerative colitis (UC).