Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO.

Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results: NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.

A review on microbiological decontamination of fresh produce with nonthermal plasma.

Food safety is a critical public health issue for consumers and the food industry because microbiological contamination of food causes considerable social and economic burdens on health care. Most foodborne illness comes from animal production, but as of the mid-1990s in the United States and more recently in the European Union, the contribution of fresh produce to foodborne outbreaks has rapidly increased. Recent studies have suggested that sterilization with nonthermal plasma could be a viable alternative to the traditional methods for the decontamination of heat-sensitive materials or food because this technique proves capable of eliminating micro-organisms on surfaces without altering the substrate. In the last 10 years, researchers have used nonthermal plasma in a variety of food inoculated with many bacterial species. All of these experiments were conducted exclusively in a laboratory and, to our knowledge, this technique has not been used in an industrial setting. Thus, the purpose of this review is to understand whether this technology could be used at the industrial level. The latest researches using nonthermal plasma on fresh produce were analysed. These evaluations have focused on the log reduction of micro-organisms and the treatment time.

Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial.

BACKGROUND: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. PATIENTS AND METHODS: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and ß error of 0.05 and 0.20, respectively, 262 patients were required. RESULTS: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. CONCLUSIONS: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. ClinicalTrials.gov number: NCT00720512.

The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer.

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.

Analysis of environmental endocrine disrupting chemicals using the E-screen method and stir bar sorptive extraction in wastewater treatment plant effluents.

Endocrine disrupting chemicals (EDCs) have become a major issue in the field of environmental science due to their ability to interfere with the endocrine system. Recent studies show that surface water is contaminated with EDCs, many released from wastewater treatment plants (WWTP). This pilot study used biological (E-screen assay) and chemical (stir bar sorptive extraction-GC-MS) analyses to quantify estrogenic activity in effluent water samples from a municipal WWTP and in water samples of the recipient river, upstream and downstream of the plant. The E-screen assay was performed on samples after solid phase extraction (SPE) to determine total estrogenic activity; the presence of estrogenic substances can be evaluated by measuring the 17-beta-estradiol equivalency quantity (EEQ). Untreated samples were also assayed with an acute toxicity test (Vibrio fischeri) to study the correlation between toxicity and estrogenic disruption activity. Mean EEQs were 4.7 ng/L (+/-2.7 ng/L) upstream and 4.4 ng/L (+/-3.7 ng/L) downstream of the plant, and 11.1 ng/L (+/-11.7 ng/L) in the effluent. In general the WWTP effluent had little impact on estrogenicity nor on the concentration of EDCs in the river water. The samples upstream and downstream of the plant were non-toxic or weakly toxic (0

Application of semipermeable membrane device for assessing toxicity in drinking water.

Semipermeable membrane devices (SPMDs) mimic passive diffusive transport of bioavailable hydrophobic organic compounds through biological membranes and their partitioning between lipids and environmental levels. Our study was developed on a surface water treatment plant based in Turin, Northern Italy. The investigated plant treats Po River surface water and it supplies about 20% of the drinking water required by Turin city (about one million inhabitants). Surface water (input) and drinking water (output) were monitored with SPMDs from October 2001 to January 2004, over a period of 30 days. The contaminant residues, monthly extracted from SPMDs by dialysis in organic solvent, were tested with the Microtox acute toxic test and with the Ames mutagenicity test. Same extracts were also analyzed with gas chromatography--mass spectrometry technique in order to characterise the organic pollutants sampled, especially Polycyclic Aromatic Hydrocarbons (PAHs). Although the PAHs mean concentration is about one hundred times lower in the output samples, the mean toxic units are similar in drinking and surface water. Our data indicate that the SPMD is a suitable tool to assess the possible toxicity in drinking water.

Toxicity and estrogenic activity of a wastewater treatment plant in Northern Italy.

Many xenobiotics, widely diffused in the environment, have the potential to disrupt the delicate endocrine system balance of wildlife and humans. Substances showing hormone-like actions in living organisms are defined endocrine-disruptor chemicals and they may mimic, block, or interfere with the synthesis, release, transport, elimination, and binding of natural hormones. Different ecotoxicologic studies were applied to screen for the discharge of estrogenic and toxic substances into the aquatic environment from a small industrial wastewater treatment plant based in Northern Italy. Samples of wastewater (3 L) were taken at three different periods during the year from different points of the plant's process: three phases of treatment, and effluent. Untreated samples (1 L) were assayed with two toxicity tests: Microtox and Daphnia magna. A simplified proliferation test using human estrogen receptor-positive MCF-7 breast cancer cells (E-screen assay) was performed on 2-L samples after solid-phase extraction for the determination of total estrogenic activity; the presence of estrogenic substances was evaluated by measuring the proliferation rate in cells exposed to samples. The results of the Microtox assay employing the marine bacterium Vibrio fischeri were compared with data obtained from whole-effluent toxicity testing methods employing D. magna. Toxicity was found only for the influent point. The proliferative effect of the five points, relative to the positive control 17beta-estradiol (relative proliferation effect), was between 2.4% and 39%, and the 17beta-estradiol equivalent concentrations were between 0.06 and 3.94 ng/L. A first comparison between results from toxicity load and estrogenic activity was performed. At all process points, the effluent samples were considered acceptable (taking only toxicity into account), but we demonstrated that they had estrogenic activity in the river water indicating an input of estrogenic substances by way of the treatment plant.

p53 evaluation in gastric mucosa of patients with chronic Helicobacter pylori infection.

Gastric cancer is often associated with p53 over-expression and Helicobacter pylori (HP) infection. In this study we have investigated the production of the p53 protein and mutation of its gene in precancerous gastric lesions with HP infection. For this purpose 130 patients who underwent endoscopy for dyspepsia were enrolled in the study. To assess p53 production and mutation of the p53 gene we employed an immunoluminometric assay and polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis, respectively. Histologically, 52 of the 130 enrolled patients showed intestinal metaplasia type I (IM) (90.4% of these were also HP positive), 47 had HP-related gastritis and 31 were normal. p53 cytosol levels were significantly higher in patients with IM or HP-related gastritis than in normal patients (p = 0.0137 and p = 0.0411, respectively). All DNAs extracted from gastric mucosa samples with higher p53 values and examined for p53 mutations by PCR-SSCP analysis were characterized by a normal run. Our data indicate, that irreversible genetic changes in the p53 protein has not yet occurred in morphologically non-neoplastic gastric mucosa with IM and HP-related chronic gastritis. In conclusion, the increase in p53 cytosolic levels found in our study is due to an increased production of the wild-type protein probably related to an inflammatory response induced by HP infection.

[Common variable hypogammaglobulinemia associated with intestinal lymphoid hyperplasia].

A case of adult common variable hypogammaglobulinemia with nodular lymphoid hyperplasia characterized by malabsorption and enteric protein loss, probably due to bacterial overgrowth, is reported. This clinical condition is of particular interest because of the unusual pathology and the lack of an efficient treatment. The association between common variable hypogammaglobulinaemia and nodular lymphoid hyperplasia must be considered in young adults with recurrent respiratory tract infection, gastrointestinal symptoms, diarrhoea, hypogammaglobulinemia and low serum albumin.

Serological evidence of Cryptosporidium infections in southern Europe.

Although cryptosporidiosis outbreaks have been frequently reported in the United States, Canada and the United Kingdom, few outbreaks have been reported on the European continent. The reasons for this are unclear. To ascertain whether a European population has been previously exposed to Cryptosporidium, we conducted a survey of 100 resident blood donors in a northern Italian city for IgG serological response to two oocyst antigen groups. A serological response to the 15/17-kDa antigen group was detected in 83% of blood donors and response to the 27-kDa antigen group in 62%. Donors who traveled outside of Italy during the prior 12 months were less likely to have had a response to the 15/17-kDa antigen group (p < 0.04) and to have a less intense response (p < 0.05). Older age was predictive of a more intense response to each antigen group (p < 0.01). The fraction of Italian blood donors with a serological response to either antigen group was higher than in four United States blood donor populations, with differences more pronounced for response to the 15/17-kDa antigen group (p < 0.01). A lower fraction of Italian donors had a serological response to either antigen group than persons tested at the time of a cryptosporidiosis outbreak in the United States or blood donors tested six months after that outbreak (p < 0.05). Since the presence of serological responses to these antigen groups predicts a reduced risk of cryptosporidiosis, the high prevalence of serological responses in these Italian blood donors may explain the infrequent occurrences of clinically detectable cryptosporidiosis in this city.

Biological activity of particle exhaust emissions from light-duty diesel engines.

Whole diesel exhaust has been classified recently as a probable carcinogen, and several genotoxicity studies have found particulate exhaust to be clearly mutagenic. Moreover, genotoxicity of diesel particulate is greatly influenced by fuel nature and type of combustion. In order to obtain an effective environmental pollution control, combustion processes using alternative fuels are being analyzed presently. The goal of this study is to determine whether the installation of exhaust after treatment-devices on two light-duty, exhaust gas recirculation (EGR) valve-equipped diesel engines (1930 cc and 2500 cc) can reduce the mutagenicity associated with particles collected during U.S.A. and European driving cycles. Another interesting object was to compare the ability of alternative biodiesel and conventional diesel fuels to reduce the mutagenic activity associated with collected particles from two light duty diesel engines (both 1930 cc) during the European driving cycle. SOF mutagenicity was assayed using the Salmonella/microsome test (TA 98 and TA 100 strains, +/- S9 fraction). In the first part of our study, the highest mutagenicity was revealed by TA98 strain without enzymatic activation, suggesting a direct-acting mutagenicity prevalence in diesel particulate. The 2500 cc engine revealed twofold mutagenic activity compared with the 1930 cc engine (both EGR valve equipped), whereas an opposite result was found in particulate matter amount. The use of a noncatalytic ceramic trap produced a decrease of particle mutagenic activity in the 2500 cc car, whereas an enhancement in the 1930 cc engine was found. The catalytic converter and the electrostatic filter installed on the 2500 cc engine yielded a light particle amount and an SOF mutagenicity decrease. A greater engine stress was obtained using European driving cycles, which caused the strongest mutagenicity/km compared with the U.S.A. cycles. In the second part of the investigation, even though a small number of assays were available, exhaust emission generation by biodiesel fuel seemed to yield a smaller environmental impact than that of the referenced diesel fuel. The results point out the usefulness of mutagenicity testing in the research of both newer, more efficient automotive aftertreatment devices and less polluting fuels.

[Presence of aflatoxin in products intended for human consumption: the choice of methods and the results obtained]. / La presenza di aflatossine in prodotti diretti al consumo umano: scelte dei metodi e risultati ottenuti.

The contamination of food resources by aflatoxin is a major problem for those countries where the meteorological and sanitary conditions allow the growth of Aspergillus Flavus and the contaminated food is not discarded because of the critical economical and social situation. However this phenomenon is also recorded in those Nations where the environmental and meteorological conditions are not favourable to Aspergillus Flavus growth. In Europe it has been possible to measure low aflatoxin (M1) concentrations in milk destined to humans. This kind of contamination may represent a source of chronic exposure to an important risk factor for hepatocancerogenesis. In Italy an appropriate law regulating the maximum aflatoxin concentration in the food destined to human nutrition is lacking, therefore the purpose of this paper is to contribute to the knowledge of a possible human exposure from the milk consumed in the Turin area (north western Italy). The results obtained display a lower (but more diffused) contamination in milk sampled after processing treatments (1.9-15 ppt), than in raw milk (5.3-94 ppt). Moreover it has been possible to show a positive relationship between dry animal feed and aflatoxin concentrations in milk.