The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5 -29.2%) and 49% (95% CI, 42.2 -55.8%), respectively (P ¼ 0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the nonmucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27 -3.31; P ¼ 0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05 -2.40; P ¼ 0.0267), together with performance status ECOG 2, number of metastatic sites X2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20 -40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16 -2.77; P ¼ 0.008), haemoglobin p11.5 g l À1 (HR, 1.48; 95% CI, 1.06 -2.05; P ¼ 0.019), CEA level 450 ng ml À1 (HR, 1.86; 95% CI, 1.21 -2.88; P ¼ 0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16 -2.53; P ¼ 0.006), and time-toprogression under first-line chemotherapy p6 months (HR, 1.97; 95% CI, 1.39 -2.80; Po0.0001). A prognostic index was constructed dividing patients into low-(no risk factor), intermediate-(one to two risk factors), or high-(three to five risk factors) risk groups, and median survival times for each group were 12.7 months, 7.1 months, and 3.3 months, respectively (Po0.001). In the absence of data deriving from randomised trials, this analysis suggests that some easily available clinical factors may help to select patients with advanced gastric cancer who could derive more benefit from second-line chemotherapy.

The implementation of ISO 14000 certification in a company involves a set of costs and benefits that must be known in order to assess the investment effectively in terms of environmental quality. However, as will be shown, these figures can be difficult to calculate, mainly because of a lack of reference data or specific assessment criteria. Moreover, few companies have so far implemented an Environmental Management System. Investments in environment quality sometimes simply look like costs, but benefits do exist and these are often economically quantifiable. Such benefits depend on the choice and the pursuit of aims, on the respect of rules (e.g. no omissions) and on environmental efficiency (e.g. no waste), and can only be calculated following an in-depth analysis of the system. A first and approximate estimate of these costs and benefits has been obtained for a number of real industrial cases, mainly in the chemical field, and the survey results are given in this paper. The research was carried out in Italy in companies implementing an Environmental Management System in most cases in accordance with the ISO 14000 series

Preclinical and experimental data in vivo indicate that Lethal-7 (Let-7) microRNA downregulates KRAS with antitumor effects in the presence of activating KRAS mutations. We quantified the Let-7a isoform in KRASmutated colorectal carcinomas from patients who received salvage cetuximab plus irinotecan. The study population was retrospectively identified among metastatic colorectal cancer patients who underwent third-line therapy with cetuximab plus irinotecan in a period when only epidermal growth factor receptor (EGFR) expression was required for anti-EGFR therapy. In 59 patients harboring KRAS mutations, Let-7a levels were analyzed for association with overall survival (OS) and progression-free survival (PFS) times. An exploratory subgroup analysis was performed using the rs61764370 (LCS6 T>G) polymorphism that experimentally impairs Let-7 binding to KRAS mRNA. In the whole group, higher Let-7a levels were significantly associated with better survival outcomes. For the primary OS endpoint, the multivariate hazard ratio was 0.82 (95% confidence interval, 0.73-0.91; p ‫؍‬ .01). The same findings with an accentuated positive effect of high Let-7a levels on both OS and PFS times were observed in an exploratory analysis of the 45 wild-type LCS6 patients (excluding 14 carriers of the LCS6 G allele variant). All survival associations were confirmed after excluding patients with KRAS codon 13 mutations. Among the clinicopathologic features, high Let-7a levels were associated with grade 2-3 skin toxicity (p ‫؍‬ .002). In patients with KRAS mutations, Let-7a analysis may serve to identify subgroups of patients who may still benefit from EGFR inhibition and this may open up new perspectives for alternative treatment strategies.