RESUMEN
BACKGROUND: Ex vivo confocal microscopy using fusion mode and digital staining (EVCM) scans unfixed fresh tissue and produces rapidly digitally stained images of very similar quality to classical pathology. We investigated whether EVCM could represent an alternative to the standard histological examination of the pretherapeutic basal cell carcinoma (BCC) punch biopsies. OBJECTIVES: The objective of the study was to assess diagnostic accuracy of EVCM versus traditional histopathological examination for diagnosing and subtyping clinically suspicious lesions of BCC in 3-mm fresh and nonfixed punch biopsies. METHODS: In this prospective monocentric observational study, patients with clinically suspected BCC were consecutively enrolled. Punch biopsies were imaged using EVCM and subsequently processed for standard histologic examination (gold standard). EVCM images were examined by a dermatopathologist blinded to clinical aspect of the lesion and histopathological results. Concordance between the EVCM and histology analysis was calculated with Cohen's kappa (κ) statistic. RESULTS: Sixty-six patients were recruited, and 106 biopsies were analyzed. EVCM correctly diagnosed 70/73 BCCs and 31/33 non-BCC lesions, corresponding to a sensitivity of 96% and a specificity of 94% (positive predictive value = 97%, negative predictive value = 91%). The EVCM assessment led to over-staging and under-staging of BCC subtypes in 5% and 11% of cases, respectively. It led to over-staging and under-staging of BCC depths in 5% and 15%, respectively. The kappa coefficient for concordance was 0.78 (95% confidence interval [CI]: 0.69-0.88) when considering BCC subtypes and 0.81 (95% CI: 0.72-0.90) when considering BCC depths. CONCLUSIONS: These results render EVCM as a promising option for "real-time" pretreatment evaluation of clinically suspected BCC lesions. Further larger randomized studies are needed to assess the efficiency of EVCM versus standard care in patients with clinically suspected BCC.
RESUMEN
BACKGROUND AND AIM: Adenocarcinoma of the Pancreas is a leading cause of cancer-related mortality, accounting for an estimated 30,000 deaths per year in the United States. Multiple studies have indicated that specific cyclooxygenase-2 (COX-2) inhibitors may serve in the prevention and treatment of a variety of malignancies including pancreatic adenocarcinoma. Recent studies had shown that the long-term use of high concentration of COX-2 inhibitors is not toxic free and may be limited due to serious gastrointestinal and cardiovascular side effects. The chemopreventive efficacy of the phytochemical, curcumin has been demonstrated in several in vitro and animal models. In this study we investigated whether curcumin potentiates the growth inhibition effect of a COX-2 inhibitor (celecoxib, Pfizer, NY, USA) in human pancreatic cancer cells. METHODS: P-34 (expressing high levels of COX-2), and MIAPaCa (expressing low levels of COX-2) and Panc-1 (no expression of COX-2) evaluated cell lines were exposed to different concentrations of celecoxib (0-40 microM), curcumin (0-20 microM) and their combination. Cell viability was by XTT assay. Apoptosis was assessed by flow cytometry and COX-2 expression was measured by Western blotting analysis. RESULTS: In P-34 cells, curcumin synergistically potentiated the inhibitory effect of celecoxib on cell growth. The growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Western blot analysis showed that COX-2 expression was down-regulated by the combination therapy. CONCLUSION: Curcumin synergistically augments the growth inhibition inserted by celecoxib in pancreatic cancer cells expressing COX-2. The synergistic effect was mediated through inhibition of COX-2. This may enable the use of celecoxib at lower and safer concentrations and may pave the way for a more effective treatment in this devastating disease.