Colorectal cancer (CRC) is one of the most common cancers in the western world. Early screening and detection could be highly preventative and therefore reduce mortality. Tight junctions (TJ) are well known for their function in controlling paracellular traffic of ions and molecules. It has become increasingly evident that TJs play a crucial role in maintaining cell-cell integrity, and the loss of cell junctional sealing could involve itself in the processes of carcinoma and cancer metastasis. If correlations between altered TJ proteins and CRC presence or invasiveness could be established, they may serve as important markers and guidelines for prophylactic and prognostic purposes, along with other screening methods. This review will present recent data from clinical and animal studies showing how altered TJ protein expression is a feature of certain CRCs. The up-regulation of claudin-1 in many CRCs is especially noteworthy. The focus of this article is simply on the association – however imperfect – between CRC and the major TJ transmembrane barrier proteins, namely claudins and occludin. Any causal relationship between TJ protein change and neoplasia remains conclusively unproven at present.

Background Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. Aims To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. Methods Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. Results Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1β, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. Conclusions When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Oral zinc administration can result in effective delivery of zinc to Barrett's epithelia with resulting effects on intracellular signal transduction.

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INTRODUCTION: Hepatocellular carcinoma is a decompensation of cirrhosis. We present a patient with HCC, presenting with anemia, found to have metastatic disease to the duodenum. CASE DESCRIPTION/METHODS: 67 y/o male with hepatitis C cirrhosis, complicated by HCC, presented with anemia and melena. HCC was diagnosed 1 year prior, with a 3.8 cm left lobe lesion, portal venous thrombus, and a LIRADS-4 right lobe lesion, initiated on palliative chemotherapy. Recent MRI demonstrated infiltrative HCC involving nearly the entire left lobe of the liver; tumor and bland thrombus within the portal system involving the confluence of the portal veins, left, and to a lesser extent, right portal vein. Exam revealed guaiac positive brown stool. Labs revealed hemoglobin 6.0 g/dL (baseline 12g/dL), MCV 93, BUN 17 mg/dL, Cr 1.2 mg/dL. Endoscopy demonstrated 3 superficial duodenal bulb ulcers, 2mm-3mm, with a visible vessel, treated; no varices seen. Repeat EGD demonstrated multiple closely associated pedunculated polypoid lesions with superimposed ulcerations with irregular appearing surrounding mucosa; biopsies without evidence of malignancy. Given the abnormal appearance, repeat EGD with biopsies was performed, revealing metastatic hepatocellular carcinoma in multiple fragments of the duodenal mucosa. DISCUSSION: Hepatocellular carcinoma is the most common primary liver malignancy. The most significant risk factor for HCC is pre-existing cirrhosis. Lung, bone and lymph nodes are the most common metastatic sites of HCC; metastatic disease to the duodenum is exceedingly rare (1). Of >7000 cases of HCC identified in Taiwan between 1996-2009, < 1%, or just 21 cases, revealed duodenal disease (1). GI involvement is most frequently a result of direct invasion by contiguous tumor, with right lobe disease most commonly extending to the duodenum and left lobe disease most commonly extending to the stomach (1). Rarely, as seen in our patient, duodenal disease can be a location of metastatic disease without direct contact. Wall thickening appreciated on imaging should prompt consideration of gastrointestinal involvement. It has been suggested that portal vein thrombosis may be an indication of hematogenous spread of tumor, in addition to being a poor prognostic indicator. Duodenal masses, ulcerations or bleeding should raise suspicion for duodenal metastasis, and portends a very poor prognosis.