Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-α induction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-α expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-α expression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.

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e15146 Background: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated. Methods: Chemotherapy-naive patients confirmed histologic colorectal cancer with liver metastases, adequate born morrow, renal and hepatic function, measurable diseases were considered eligible for the study. Treatment: Six cycles of oxaliplatin 85 mg/m2 day1 plus capecitabine 1250 mg/m2 twice daily days 1–14 every 21 days Results: Twenty six patients were evaluated for safety and efficacy (male/female, 12/14). Median age was 53 years (range 32–75 years). A total of 142 cycles have been administered: median per patient 4 (range 3–6 courses). In an intent-to-treat efficacy analysis, One complete and ten partial responses were achieved [overall objective response rate (ORR): 42, 3%; whereas 7 patients had stable disease and eight patients had progressive disease. Seven patients from 11 with objective response underwent major liver resection: 2 bisegmentectomy, 1 left lobectomy, 4 segmentectomy, and receive the same regimen of chemotherapy (Six cycles) as an adjuvant treatment and still alive without recurrence. The overall survival (OS) was 19, 2 months. The median response duration was 7 months. The median time to progression (TTP) was 8 months. The grade 3 toxicities were diarrhea (7%), fatigue (4%), neurotoxicity (2%), neutropenia (2%), and thrombocytopenia 4%). Conclusions: The combination of oxaliplatin and capecitabine is safe and has a promising activity in patients with liver metastatic colorectal carcinoma. No significant financial relationships to disclose.

Background: Trifluridine/tipiracil hydrochloride has shown to improve progressionfree survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Exploratory analysis suggested that patients with good prognostic characteristics GPC (18 months since first diagnosis) carry better prognosis vs. poor prognostic characteristics (PPC). We report the Greater Manchester experience of the use of TFT.Methods: All consecutive patients who received TFT between August 2016 and August 2019 were included. Data were collected from electronic records. Univariate survival analysis was performed with Kaplan-Meier curve and log-rank test. Cox regression was used for multivariable analysis. Conclusion:Capecitabine associated with mitomycin and SIB-IMRT is a treatment as effective and safer than 5-FU-based chemotherapy for locally SCCAC.

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