BackgroundDespite 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.Methods/resultsIn 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.Data sourcesThe 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.ConclusionThe aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers.

Background/Aim: Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability. Materials and Methods: A total of 717 patients with CRLM who underwent hepatic resection +/-RFA at two tertiary institutions between 09/01/2000-12/01/2015 were eligible for inclusion in this study. Results: Among patients with <4 lesions (n=568), OS in the resection + RFA group (n=48) was significantly worse than in the resection alone group (n=520) (5-year OS: 34.4 % versus 58.9%, p=0.007). Conversely, in patients with ≥4 lesions, OS in the resection + RFA (n=68) and resection alone(n=81) groups were not significantly different (5-year OS: 31.9% versus 34.1%, p=0.48). In patients with <4 lesions, carcinoembryonic antigen (CEA) ≥30 ng/ml, extrahepatic metastasis, preoperative chemotherapy and resection + RFA were independently associated with poor prognosis. Interestingly, in patients with ≥4 lesions, positive primary lymph nodes, KRAS mutation, CEA ≥30 ng/ml and extrahepatic metastasis were independent predictors of poor prognosis; however, the combination of hepatic resection with RFA was not associated with worse survival (p=0.93). Conclusion: Although surgeons should always strive for R0 resection when feasible, combined resection and RFA may be a viable alternative for CRLM patients with a large number of tumors. Currently, the principal treatment strategy for patients with colorectal cancer liver metastasis (CRLM) is systemic chemotherapy, while hepatic resection can further improve survival in carefully selected patients (1-5). On the contrary, many reports concur that radio-frequency ablation (RFA) results in inferior outcomes than hepatic resection in patients with CRLM and should only be employed when surgical resection cannot be performed (6-9). Nonetheless, the presence of extensive metastatic tumor number in the liver, (especially four or more lesions) often precludes a curative hepatic resection due to either technical challenges or inadequate remnant liver function and is a wellknown poor prognostic factor (4, 5, 10-12). In fact, historically, specifically ≥4 CRLM, was considered to be a contraindication for liver resection (13, 14). Similarly, a study on a contemporary cohort (treated after 2005) demonstrated that the prognosis of patients with ≥4 CRLM who undergo surgery has not improved despite the development of modern chemotherapies (14). Interestingly, our group and others have demonstrated that hepatectomy + RFA may achieve long-term outcomes that are comparable to hepatectomy alone (15, 16). Nonetheless, the impact of combined resection and RFA on survival among patients with different levels of tumor number 6353 This article is freely accessible online.

Background: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.Methods: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.Results: 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P = 0.01) and wtKRAS status remained independently associated with a major response (P = 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P = 0.023).Conclusions: Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.