Despite recent advances the pathogenesis of Crohn's disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature. In this review, we sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction. The MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohn's disease, animal model. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Additional articles were gathered and evaluated. The aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers.

Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably Double Strand Breaks (DSBs). The epithelial host cell responds by activation of DNA Damage Repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection.

The aim of this study was to evaluate the safety and effectiveness of percutaneous cholecystostomy without interval cholecystectomy as definitive treatment for acute cholecystitis in elderly or critically ill patients with various coexisting diseases who were unfit for surgery under general anesthesia. Between July 2004 and June 2006, 24 consecutive elderly and critically ill patients unfit for surgery, suffering from acute cholecystitis, and in whom significant comorbid factors were present, underwent percutaneous cholecystostomy as an emergency procedure at Laiko General Hospital. The diagnosis and the severity of acute cholecystitis were based on the Tokyo Guidelines, whereas the American Society of Anesthesiologists' (ASA) physical status classification was used for the perioperative risk stratification for cholecystectomy. There were 14 male and 10 female patients with a median age of 79 years. Acute cholecystitis was classified as grade 2 in 20 patients and as grade 3 in 4 patients; 17 patients were classified as ASA score III and 7 as ASA score IV, whereas a total of 52 comorbid factors were present. Gallstones were disclosed as the underlying etiology in 23 patients, whereas one patient was diagnosed as suffering from acalculous cholecystitis. Percutaneous cholecystostomy was technically feasible in all patients (100%). Clinical improvement was noticed in 14 patients within 24 hours and in all patients within 72 hours. Statistically significant reduction in the values of white blood cells, C-reactive protein, and axillary body temperature were observed within 72 hours. The procedure-related mortality was 4%, whereas within a median follow-up of 17.5 months, definitive and effective control of symptoms was achieved in 90.5% of the patients. For the subgroup of extremely high-risk and unfit for surgery patients, percutaneous cholecystostomy might be considered as the definitive treatment since it controls the local symptoms and the systemic inflammatory response.

Advanced glycation end products (AGEs) and their receptor RAGE emerge as important pathogenic contributors in colorectal carcinogenesis. However, their relationship to the detoxification enzyme Glyoxalase (GLO)-I and Adiponectin receptors (AdipoR1, AdipoR2) in colorectal carcinoma (CRC) is currently understudied. In the present study, we investigated the expression levels of the above molecules in CRC compared to adjacent non-tumoral tissue and their potential correlation with clinicopathological characteristics and patients’ survival. We analyzed the immunohistochemical expression of AGE, RAGE, GLO-1, AdipoR1 and AdipoR2 in 133 primary CRC cases, focusing on GLO-I. The tumour MSI status was further assessed in mucinous carcinomas. Western immunoblotting was employed for validation of immunohistochemical data in normal and tumoral tissues as well in three CRC cell lines. An independent set of 55 patients was also used to validate the results of univariate survival analysis regarding GLO-I. CRC tissue showed higher intensity of both AGE and RAGE expression compared with normal colonic mucosa which was negative for GLO-I in most cases (78 %). Western immunoblotting confirmed AGE, RAGE and GLO-I overexpression in tumoral tissue. GLO-I expression was directly related to RAGE and inversely related to AGE immunolabeling. There was a trend towards higher expression of all markers (except for RAGE) in the subgroup of mucinous carcinomas which, although of borderline significance, seemed to be more prominent for AdipoR1 and AGE. Additionally, AGE, AdipoR1 and Adipo R2 expression was related to tumor grade, whereas GLO-1 and AdipoR1 to T-category. In survival analysis, AdipoR2 and GLO-I overexpression predicted shortened survival in the entire cohort and in early stage cases, an effect which for GLO-I was reproduced in the validation cohort. Moreover, GLO-I emerged as an independent prognosticator of adverse significance in the patients’ cohort. We herein provide novel evidence regarding the possible interactions between the components of AGE-RAGE axis, GLO-I and adiponectin receptors in CRC. AGE and AdipoR1 are possibly involved in colorectal carcinogenesis, whereas AdipoR2 and GLO-I emerged as novel independent prognostic biomarkers of adverse significance for patients with early disease stage. Further studies are warranted to extend our observations and investigate their potential therapeutic significance.

The incidence of colorectal cancer (CRC) is expected to increase by 80% in year 2035. Even though advantages in treatment of CRC have being made over the last decades, the outcome remains poor. Recently, several inflammatory markers including pretreatment neutrophil to lymphocyte ratio (NLR), have being used as prognostic factors, since host inflammatory response to cancer is believed to determine disease progression. The aim of this study is to evaluate the prognostic significance of pretreatment NLR, in terms of overall survival (OS), 5-year survival, disease-free survival (DFS) and recurrence, in CRC patients who underwent curative resection. We retrospectively reviewed 296 patients, who were submitted to elective surgery as first therapeutic option in curative intent, between January 2010 and December 2015. Pretreatment NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS, 5-year survival, DFS and recurrence. The cutoff point of NLR was calculated with Kaplan-Meier curves and log-rank test to 4.7. Univariate and multivariate analyses disclosed elevated NLR as a significant dismal prognostic factor for DFS (HR 1.88; 95% CI 1.01–3.52; p = 0.048), 5-year survival (HR 2.14; 95% CI 1.12–4.10; p = 0.021) and OS (HR 2.11; 95% CI 1.11–4.03; p = 0.023). In a subgroup analysis, in patients with stage II CRC, NLR > 4.7 was a stronger poor predictor for DFS (HR 2.76; 95% CI 1.07–7.13; p = 0.036), 5-year survival (HR 3.84; 95% CI 1.39–10.63; p = 0.01) and OS (HR 3.62; 95% CI 1.33–4.82; p = 0.012). After adjusting stage for gender, age, location of the primary tumor, differentiation, as well as the presence of perineural, vascular, and lymphovascular invasion, the significance of NLR > 4.7 became more prominent for DFS (HR 2.85; 95% CI 1.21–6.73; p = 0.0176), 5-year survival (HR 4.06; 95% CI 1.66–9.93; p = 0.002) and OS (HR 4.07; 95% CI 1.69–9.91; p = 0.002) in stage II patients. Pretreatment NLR > 4.7 is a poor prognostic factor for DFS, 5-year survival and OS in CRC patients undergoing curative resection. The dismal prognostic effect of NRL is magnified in Stage II CRC patients.

Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. National Institute for Health and Care Research.