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BackgroundTo analyze pathologic and perioperative outcomes of laparoscopic vs. open resections for rectal cancer performed over the last 10 years.MethodsA systematic literature search of the following databases was conducted: Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus. Only articles published in English from January 1, 2008 to December 31, 2018 (i.e. the last 10 years), which met inclusion criteria were considered. The review only included articles which compared Laparoscopic rectal resection (LRR) and Open Rectal Resection (ORR) for rectal cancer and reported at least one of the outcomes of interest. The analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist. Only prospective randomized studies were considered. The body of evidence emerging from this study was evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Outcome measures (mean and median values, standard deviations, and interquartile ranges) were extracted for each surgical treatment. Pooled estimates of the mean differences were calculated using random effects models to consider potential inter-study heterogeneity and to adopt a more conservative approach. The pooled effect was considered significant if p ResultsFive clinical trials were found eligible for the analyses. A positive involvement of CRM was found in 49 LRRs (8.5%) out of 574 patients and in 30 ORRs out of 557 patients (5.4%) RR was 1.55 (95% CI, 0.99-2.41; p = 0.05) with no heterogeneity (I2 = 0%). Incorrect mesorectal excision was observed in 56 out of 507 (11%) patients who underwent LRR and in 41 (8.4%) out of 484 patients who underwent ORR; RR was 1.30 (95% CI, 0.89-1.91; p = 0.18) with no heterogeneity (I2 = 0%). Regarding other pathologic outcomes, no significant difference between LRR and ORR was observed in the number of lymph nodes harvested or concerning the distance to the distal margin. As expected, a significant difference was found in the operating time for ORR with a mean difference of 41.99 (95% CI, 24.18, 59.81; p ConclusionDespite the spread of laparoscopy with dedicated surgeons and the development of even more precise surgical tools and technologies, the pathological results of laparoscopic surgery are still comparable to those of open ones. Additionally, concerning the pathological data (and particularly CRM), open surgery guarantees better results as compared to laparoscopic surgery. These results must be a starting point for future evaluations which consider the association between ''successful resection" and long-term oncologic outcomes. The introduction of other minimally invasive techniques for rectal cancer surgery, such as robotic resection or transanal TME (taTME), has revealed new scenarios and made open and even laparoscopic surgery obsolete.

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC.

BACKGROUND:There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. METHODS:The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. RESULTS:At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. CONCLUSIONS:An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.

BACKGROUND:Primary central nervous system (CNS) solitary fibrous tumour/hemangiopericytoma (SFT/HPC) is a rare neoplasm and its classification criteria have been redefined by the latest WHO Classification of CNS Tumours. Outcome can vary significantly among patients, thus reliable prognostic markers are warranted. METHODS:Primary CNS SFT/HPC diagnosed at the Pathology Unit of our Institution between 2006 and 2016 were retrospectively collected. Tumour grade along with immunohistochemistry for Ki67, STAT6, PHH3, CD34 and Bcl-2 were assessed. TERT promoter status was evaluated by Sanger sequencing. RESULTS:Fifteen SFT/HPC were analysed: 9/15 (60%) female, median age at diagnosis 60 (range: 10-67). Six (40%) cases showed a SFT phenotype and mean H&E-mitotic count was 4.8/10 HPF. Tumour grade was I in 6, II in 4 and III in 5 cases. Mean PHH3-mitotic count was higher than H&E count (8.4 versus 4.8/10 HPF), but it would have determined a change in tumour grade in a sole case. Nuclear staining for STAT6 was present in 14/15 (93.3%). CD34 and Bcl-2 expression rates were lower in higher grade tumours. TERT promoter was mutated in two cases. Median follow up time was 2.4 years (6 months-7.4 years) and 5/15 (33%) patients developed local disease recurrence. Partial resection (p = 0.0185), higher WHO grade (p = 0.038), lower CD34 (p = 0.038) and Bcl-2 (p = 0.010) expressions were significantly associated with a poorer disease-free interval. CONCLUSIONS:WHO grade is the main prognostic tool in CNS SFT/HPC, but it could be integrated by other markers, like CD34 and Bcl-2, in the clinical practice. The relevance of TERT promoter mutations in this subset of CNS tumours needs further evaluation.

BACKGROUND:Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. MATERIAL AND METHODS:A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. RESULTS:A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. CONCLUSION:c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Atmospheric pressure cold plasma (APCP) might be considered a novel tool for tissue disinfection in medicine since the active chemical species produced by low plasma doses, generated by ionizing helium gas in air, induces reactive oxygen species (ROS) that kill microorganisms without substantially affecting human cells.In this study, we evaluated morphological and functional changes in human corneas exposed for 2 minutes (min) to APCP and tested if the antioxidant n-acetyl l-cysteine (NAC) was able to inhibit or prevent damage and cell death.Immunohistochemistry and western blotting analyses of corneal tissues collected at 6 hours (h) post-APCP treatment demonstrated no morphological tissue changes, but a transient increased expression of OGG1 glycosylase that returned to control levels in 24 h. Transcriptome sequencing and quantitative real time PCR performed on different corneas revealed in the treated corneas many differentially expressed genes: namely, 256 and 304 genes showing expression changes greater than ± 2 folds in the absence and presence of NAC, respectively. At 6 h post-treatment, the most over-expressed gene categories suggested an active or enhanced cell functioning, with only a minority of genes specifically concerning oxidative DNA damage and repair showing slight over-expression values (

ObjectiveTo estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.DesignWith this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.MethodologyA Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer's perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.ResultsThe average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.ConclusionsUsing real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

ObjectiveStevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.MethodsA multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child's use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.ResultsTwenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1(st) November 1999 and 31(st) October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0-6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4-86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5-7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8-9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5-6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3-2.8).DiscussionOur study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.

Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programs.

BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP) precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France), Vigo (Spain) and Venice (Italy). To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore) and wild (lagoon) Venice mussels, both injected with 10(7) Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC) minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related to geographical origin or Vibrio injection emerged. Whether or not the contact with potential pathogens can increase the amount of AMP transcript variants in mussels requires additional study.