Role of microRNAs in the predisposition to gastrointestinal malignancies

MicroRNAs(miRNAs)are highly deregulated in cancer and play a role in the initiation of tumorigenesis.Recently,miRNAs have attracted attention in gastrointestinal(GI)cancers.Single nucleotide polymorphisms(SNPs)could affect the genes involved in each step of miRNA biosynthesis.Several metaanalyses of case-control studies have assessed the association between miRNA“pathway”gene-SNPs(including biosynthesis regulators and binding sites)and susceptibility to GI cancers.We present in this mini-review the current knowledge on the association between miRNAs“pathway”genes and GI cancer predisposition.The interaction between miRNA/regulators/binding site-SNPs and environmental as well as genomic factors is an interesting field that should be exploited in future studies.     

Antibiotics and immunotherapy in gastrointestinal tumors: Friend or foe?

The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer patients with low immunity are vulnerable to all sorts of infections, such as respiratory tract infections and urinary tract infections. Moreover, cancer patients easily run into fever and neutropenia induced by myelosuppression. Therefore, antibiotics are used extensively and even overused in many conditions. However, because of the special anatomical location of the gastrointestinal tract, the antibiotic usage will bring changes to the intestinal flora. Besides, with the expanding popularity of immunotherapy, various factors affecting the efficacy of immune checkpoint inhibitors (ICIs) have been extensively explored, including cancer-associated inflammation and the local and systemic factors that lead to immunosuppression. Some biomarkers for ICIs, including the expression of PD-L1, tumor mutation load, and microbiota, also have been investigated, and many studies have confirmed that gut microbiota can affect the efficacy of immunotherapy. But further studies on the influence of antibiotics directly on immunotherapy are rare. In this review, we discuss the relationship between GI tumors and antibiotics, the current status of immunotherapy in GI tumors, and the influence of antibiotics on immunotherapy.     

Is endoscopic resection a correct treatment for atypical gastrointestinal lipomas?

We would like offering our experience about a very rare and underestimated type of gastrointestinal lipoma, which is the lipoma with precancerous or frankly malignant features of the mucosal epithelium, the so-called atypical lipoma. So far, only few cases have been described in the world literature. Recently, we grappled with what we think the first case of atypical colonic lipoma presenting with adenocarcinomatous transformation of the overlying epithelium, as discussed in more detail below. We propose a new definition and classification for this kind of lesions and discuss about their diagnosis, treatment and prognosis.     

How common is back pain in women with gastrointestinal problems?

OBJECTIVE: This study examined the relationship between back pain and gastrointestinal (GI) symptoms in a large scale population study with consideration of possible confounding factors. METHODS: Cross-sectional analysis of survey data from the Australian Longitudinal Study on Women's Health was conducted using multinomial logistic regression to model 4 frequencies of back pain in relation to number of GI symptoms (including constipation, hemorrhoids, and other bowel problems). A total of 38,050 women from 3 age cohorts were included in analysis. RESULTS: After adjustment for confounding factors, the number of GI symptoms was significantly associated with back pain among all age cohorts. Odds ratios for experiencing back pain "rarely," "sometimes," and "often" increased with the number of GI symptoms. Young, mid-age, and older women who experience 2 or 3 GI symptoms had adjusted odds ratios of 3.3 (2.5 to 4.4), 3.0 (2.5 to 3.7) and 2.8 (2.3 to 3.4), respectively, for "often" having back pain. DISCUSSION: This study has identified a strong association between back pain and GI symptoms in women. Possible factors that may account for this relationship include referred pain through viscerosomatic convergence, altered pain perception, increased spinal loading when straining during defecation, or reduced support of the abdominal contents and spine secondary to changes in function of the abdominal muscles.     

Blood transfusion for upper gastrointestinal bleeding: is less more again?

Background

The hemoglobin threshold for transfusion of red blood cells in patients with acute gastrointestinal (GI) bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy.

Methods

Objective: The objective was to prove that the restrictive threshold for red blood cell transfusion in patients with acute upper GI bleeding (UGIB) was safer and more effective than a liberal transfusion strategy.Design: A single-center, randomized controlled trial was conducted.Setting: Patients with GI bleeding were admitted to the de la Santa Creu i Sant Pau hospital in Barcelona, Spain.Subjects: The subjects were adult intensive care unit patients admitted with high clinical suspicion of UGIB (hematomemesis, melena, or both). Patients were excluded if they had massive exsanguinating bleeding, acute coronary syndrome, symptomatic peripheral vascular disease, stroke/transient ischemic attack, transfusion within the previous 90 days, recent trauma or surgery, lower GI bleeding, or a clinical Rockall score of 0 with hemoglobin higher than 12 g/dL.Intervention: A total of 921 patients with severe acute UGIB were enrolled. Of these, 461 were randomly assigned to a restrictive strategy (transfusion when the hemoglobin level fell to below 7 g/dL) and 460 to a liberal strategy (transfusion when the hemoglobin fell to below 9 g/dL). Random assignment was stratified according to the presence or absence of liver cirrhosis.Outcomes: The primary outcome was rate of death from any cause within the first 45 days. Secondary outcomes were further bleeding, defined as hematemesis or melena with hemodynamic instability or hemoglobin decrease of 2 g/dL or more, and in-hospital complications.

Results

In total, 225 patients assigned to the restrictive strategy (51%) and 65 assigned to the liberal strategy (15%) did not receive transfusions (P <0.001). The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% versus 91%; hazard ratio (HR) for death with restrictive strategy, 0.55; 95% confidence interval (CI) 0.33 to 0.92; P = 0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group and in 16% of the patients in the liberal-strategy group (P = 0.01), and adverse events occurred in 40% and 48%, respectively (P = 0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (HR 0.70, 95% CI 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (HR 0.30, 95% CI 0.11 to 0.85) but not in those with cirrhosis and Child-Pugh class C disease (HR 1.04, 95% CI 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P = 0.03) but not in those assigned to the restrictive strategy.

Conclusions

Compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute UGIB.     

Struggling with food and eating—life after major upper gastrointestinal surgery

Purpose

Few qualitative studies have explored patients' experience of food and eating following major upper gastrointestinal cancer surgery. The aim of this article was to explore the longer-term impact of different types of major upper gastrointestinal surgeries on people's relationship with food.

Methods

Twenty-six people having had major upper gastrointestinal cancer surgery greater than 6 months ago participated in semi-structured interviews. These interviews aimed to explore a person's physical, emotional and social relationship with food and eating following surgery. Interviews were tape-recorded, transcribed and analysed using an inductive thematic analysis approach.

Results

Interview findings revealed a journey of adjustment, grieving and resignation. The physical symptoms and experiences of people differed between types of surgery, but the coping mechanisms remained the same.

Conclusions

The grieving and resignation people experienced suggest adjustment and coping similar to that of someone with a chronic illness. Remodeling of health services is needed to ensure this patient group receives ongoing management and support.     

Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.Gastrointestinal (GI) helminths infect >10⁹ people worldwide (Anthony et al., 2007). Rodent studies demonstrate that IL-4, 5, 9, 13, 25, and 33 promote immunity against worm infections, with IL-4 and IL-13 serving a predominant role in host protection (Fallon et al., 2002, 2006; Humphreys et al., 2008). The IL-4 receptor α chain (IL-4Rα) is essential for both the type I (IL-4Rα/γ_c) and type II (IL-4Rα/IL-13Rα1) IL-4Rs and is responsible for nearly all known biological effects of IL-4 and IL-13 (Junttila et al., 2008). Indeed, IL-4Rα–deficient mice are highly susceptible to most GI nematode species because of impaired effector functions of bone marrow–derived and non–bone marrow–derived cell lineages (Finkelman et al., 1997; Urban et al., 2001).The niche inhabited by a particular worm species dictates the mechanism required for expulsion. IL-4/IL-13 stimulation of macrophage arginase production decreases survival of larvae of the hookworm Heligmosomoides polygyrus as they develop in the intestinal wall, but is not involved in IL-4/IL-13 expulsion of adult worms from the intestinal lumen (Anthony et al., 2006). Expulsion of Nippostrongylus brasiliensis adult worms from the intestinal lumen is mast cell, eosinophil, and antibody independent, but it requires IL-4/13–responsive non–bone marrow–derived cells (Urban et al., 2001), even though infected mice that express IL-4Rα only on bone marrow–derived cells develop strong IL-4/IL-13 responses. In contrast, protection against the human roundworm pathogen Trichinella spiralis, which resides in an intestinal epithelial cell (IEC) syncytium, is mast cell dependent and requires IL-4Rα expression by both bone marrow– and non–bone marrow–derived cells (Urban et al., 2000).The IL-4Rα–expressing cell type required for N. brasiliensis expulsion has been speculated to be smooth muscle (increased contractility) or intestinal epithelium (increased proliferation, permeability, and mucus production), but IL-4/IL-13''s effects on smooth muscle cells contribute only slightly to expulsion (Horsnell et al., 2007), and there has been no direct proof that IL-4/IL-13''s effects on IEC are required for expulsion. This study demonstrates that IL-4/IL-13 contributes importantly to expulsion of N. brasiliensis and H. polygyrus adults from the intestinal lumen by inducing IEC to differentiate into goblet cells that secrete resistin-like molecule (RELM) β, which interferes with worm nutrition.     

Unusual complication in patient with Gardner’s syndrome: Coexistence of triple gastrointestinal perforation and lower gastrointestinal bleeding: A case report and review of literature

Gardner’s syndrome (GS) is a rare syndrome with autosomal dominant inheritance, which is characterized by multiple intestinal polyps, dental anomalies, desmoid tumors, and soft tissue tumors. All gastrointestinal symptoms seen in GS are associated with the underlying familial adenomatosis polyposis and abdominal desmoid tumors, with the most common symptoms being anemia, lower gastrointestinal bleeding, abdominal pain, diarrhea, obstruction, and mucous defecation. To our best knowledge, no case of GS that has presented with gastrointestinal perforation and bleeding has ever been reported in the English language medical literature. A 37-year-old male who had been diagnosed with GS five years earlier was referred to our clinic for lower gastrointestinal bleeding. Despite the absence of a bleeding focus on conventional angiography, the patient was operated on with laparotomy, due to the persistence of both signs and symptoms of mild peritonitis. On the laparotomy, the patient was noted to have areas of perforation in the duodenum, splenic flexura, and mid-rectum. The third and fourth part of the duodenum, the proximal 15 cm segment of the jejunum, a 10 cm segment of the terminal ileum, the whole colon, and the upper and middle rectum were resected, and duodeno-jejunal side-to-side anastomosis and terminal ileostomy were performed. The histopathological analysis of the large mass measuring 30 cm × 20 cm was reported as a desmoid tumor. The pathological examination of the tumor foci detected in the colonic specimen revealed poorly differentiated adenosquamous carcinoma.     

Proposed risk stratification in upper gastrointestinal haemorrhage: Is hospitalisation essential?

Aims: Patients with upper gastrointestinal haemorrhage (UGIH) are usually admitted to hospital regardless of the severity of the bleed. The aim of this study was to identify patients who could be safely managed without hospitalisation and immediate inpatient endoscopy.

Methods: Based on a literature review, a protocol was devised using clinical and laboratory data regarded as being of prognostic value. A retrospective observational study of consecutive patients who attended the emergency department (ED) with UGIH was conducted during one calendar month.

Results: Fifty four patients were identified of whom 44 (81%) were admitted. Twelve suffered an adverse event. One of the 10 patients (10%) initially discharged from the ED was later admitted. Strict implementation of the protocol would have resulted in safe discharge of a further 15 patients, (34% of those admitted), and a saving of an estimated 37 bed days per month.

Conclusions: Patients at low risk from UGIH may be identified in the ED. If validated, this protocol may improve patient management and resource utilisation.