Narrow band imaging in the intra-operative definition of resection margins in oral cavity and oropharyngeal cancer

Objectives: In oncological surgery, a three-dimensional resection 1.5\u20132 cm from the gross tumour edge is currently considered appropriate, and the status of resection margins is the most reliable indicator of radicality. Awareness of \u2018\u2018field cancerization\u2019\u2019 calls for a re-evaluation of the benchmarks of tumour resection; however, its identification is not simple because the dysplastic areas may be far from the main lesion and difficult to recognize macroscopically. New technologies such as narrow band imaging (NBI) could improve the detection of neoplastic and pre-neoplastic areas, ensuring more precise resections. The main purpose of this study was to investigate the value of NBI in detecting pre-cancerous areas and/or cancer around the tumour bulk intra-operatively, to achieve adequate resection of the tumour. Materials and Methods: The resection margins of 8 oral cavity and 8 oropharyngeal cancers were first drawn by macroscopic evaluation and then re-defined using NBI. Resections were performed following the NBI-drawing if extemporaneous histological examinations of the NBI-defined enlargements were positive for dysplasia or cancer. The number of clear margins was evaluated. Results: Resections margins were free of tumour or dysplasia at extemporaneous examination; on definitive histology, two patients had a margin positive for cancer and dysplasia, respectively. Among the NBI-defined enlargements, 25% were positive for dysplasia and 75% for cancer. The sensitivity, specificity, positive and negative predictive values were 100%, 88.9%, 100% and 87.5%, respectively. Conclusion: The method we propose could be useful for obtaining free surgical margins and reducing the potential development of tumour foci resulting from incomplete resection

Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells

Introduction: Progressive Tau deposition in neurofibrillary tangles and neuropil threads is the hallmark of tauopathies, a disorder group that includes Alzheimer’s disease. Since Tau is a microtubule-associated protein, a prevalent concept to explain the pathogenesis of tauopathies is that abnormal Tau modification contributes to dissociation from microtubules, assembly into multimeric β-sheets, proteotoxicity, neuronal dysfunction and cell loss. Tau also localizes in the cell nucleus and evidence supports an emerging function of Tau in DNA stability and epigenetic modulation.Methods: To better characterize the possible role of Tau in regulation of chromatin compaction and subsequent gene expression, we performed a bioinformatics analysis of transcriptome data obtained from Tau-depleted human neuroblastoma cells.Results: Among the transcripts deregulated in a Tau-dependent manner, we found an enrichment of target genes for the polycomb repressive complex 2. We further describe decreased cellular amounts of the core components of the polycomb repressive complex 2 and lower histone 3 trimethylation in Tau deficient cells. Among the de-repressed polycomb repressive complex 2 target gene products, IGFBP3 protein was found to be linked to increased senescence induction in Tau-deficient cells.Discussion: Our findings propose a mechanism for Tau-dependent epigenetic modulation of cell senescence, a key event in pathologic aging

Determination of Enantioselectivity and Enantiomeric Excess by Mass Spectrometry in the Absence of Chiral Chromatographic Separation: An Overview

This review describes the principles and instrumentation for the screening of asymmetric reactions by mass spectrometry. These techniques witnessed a significant advancement in the last few years. Although some of them are still at the proof-of-concept development stage, several applications might be foreseen in the field of combinatorial, high-throughput parallel catalyst screening

Erratum to: Open questions and novel concepts in oral cancer surgery

The persistence of cancerous cells after surgery in oral squamous cell carcinoma (OSCC) represents a major challenge, as it often leads to local recurrences and secondary primary tumors, which are eventually responsible for a large proportion of deaths. This persistence is currently evaluated by histological analyses. In this review we discuss some important pitfalls of the histopathological analysis, such as margin evaluation, specimen shrinkage and T staging. In addition, we critically analyze the appropriateness of current surgical techniques in relation to the concept of field cancerization. Finally, we describe some novel imaging and molecular approaches, which might be useful in tailoring surgical resections and encourage the use of OSCC animal models to explore and provide proof of concept of the feasibility and potential clinical utility of innovative surgical protocols

Open questions and novel concepts in oral cancer surgery

The persistence of cancerous cells after surgery in oral squamous cell carcinoma (OSCC) represents a major challenge, as it often leads to local recurrences and secondary primary tumors, which are eventually responsible for a large proportion of deaths. This persistence is currently evaluated by histological analyses. In this review we discuss some important pitfalls of the histopathological analysis, such as margin evaluation, specimen shrinkage and T staging. In addition, we critically analyze the appropriateness of current surgical techniques in relation to the concept of field cancerization. Finally, we describe some novel imaging and molecular approaches, which might be useful in tailoring surgical resections and encourage the use of OSCC animal models to explore and provide proof of concept of the feasibility and potential clinical utility of innovative surgical protocols

An assessment of chemotherapy-induced nausea and vomiting direct costs in three EU countries

Background: Chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as one of the most distressing adverse effects among treated patients with cancer. Inadequately treated, CINV can lead to increased resource utilization and severely impair patients’ daily functioning and quality of life. Direct costs include acquisition cost of antiemetic drugs and rescue medication, administration devices, add-on treatments, such as hydration, and additional patient care, that is, nursing and physician time, unscheduled office visits, emergency room admissions, and, in some cases, extended hospitalization or readmission. There are many reports on the cost-effectiveness of antiemetic drugs, but information on the total cost per patient associated with CINV is limited. The costs associated with severe CINV episodes are considered responsible for the most significant part of the expenditures. Scope: The aim of this study was to investigate the management of CINV episodes in three European health-care environments and to estimate direct costs associated with severe CINV episodes. Methods: An online survey addressed to Italian, German, and French oncologists and oncology nurses was performed. The survey included 41 questions about the management and the resource utilization for patients experiencing any CINV episode during the 6-month period preceding the survey. Furthermore, the cost associated with severe CINV episode management was estimated by adopting the National Health Service’s perspective. Findings: A large proportion of patients receiving chemotherapy experienced a CINV episode (34.4% in Italy, 50.2% in France, and 40.4% in Germany); among those, 8.8% in Italy, 11.6% in France, and 19.2% in Germany experienced a severe CINV episode. Compared with Italy, Germany and France presented a greater hospitalization rate following an unplanned visit to the oncology ward or an emergency room access due to CINV. In Italy, the mean cost per patient with a severe CINV episode resulted in approximately €389, about half of the mean cost in France (€750) and a third of the mean cost in Germany (€1,017). Conclusions: Severe CINV episodes requiring hospitalization, day hospital, or hospitalization extension involve a significant cost for the National Health Services; additional studies should be conducted in order to evaluate potential ways to offset these expenses

Is NBI-Guided Resection a Breakthrough for Achieving Adequate Resection Margins in Oral and Oropharyngeal Squamous Cell Carcinoma?

5noObjectives: Obtaining free resection margins is the main goal of oncological surgeons. Narrow-band imaging (NBI) has been recently used to help define resection margins in transoral laser microsurgery for laryngeal carcinoma. The aim of this study was to evaluate the effect of intraoperative NBI in defining the surgical resection margins of oral and oropharyngeal cancers. Methods: Between January 2014 and March 2015, NBI was used intraoperatively after an initial definition of resection margins with white light in 26 patients (group A). The rate of superficial positive margins at definitive histology was compared with that of a historical cohort of 44 patients (group B) previously managed without the use of intraoperative NBI. Results: A statistically significant reduction in the rate of positive superficial margins was observed at definitive histology in group A (P =.028). NBI helped to identify the presence of dysplasia and cancer around the visible tumor not otherwise detectable with visual examination alone. Conclusions: NBI could be a useful tool for obtaining free resection margins in oral and oropharyngeal carcinomapartially_openopenTirelli, Giancarlo; Piovesana, Marco; Gatto, Annalisa; Torelli, Lucio; Nata, Francesca BoscoloTirelli, GIAN CARLO; Piovesana, Marco; Gatto, Annalisa; Torelli, Lucio; Nata, Francesca Boscol

Unsaturated beta-ketoesters as versatile electrophiles in organocatalysis

beta-Ketoesters, which have widely been employed as nucleophiles, are also useful electrophiles in organocatalytic quinine mediated cascade reactions, leading to the formation of products bearing multiple stereocenters in high stereoselectivity

Follow-up of oral and oropharyngeal cancer using narrow-band imaging and high-definition television with rigid endoscope to obtain an early diagnosis of second primary tumors: a prospective study

6noNarrow-band imaging (NBI) is an optical technique enhancing mucosal vasculature. The aim of this study is to assess the effectiveness of rigid NBI endoscopy in the early detection of second primaries or local recurrences after treatment for oral (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), its advantage over standard white-light (WL) endoscopy, and the influence of previous radiotherapy, the learning curve, and lesion site. Between January 2013 and June 2015, 195 patients treated for OSCC or OPSCC with surgery alone (group A) or radiotherapy with or without surgery and/or chemotherapy (group B) underwent additional follow-up assessments using NBI. Sensitivity, specificity, positive/negative predictive values (PPV and NPV), and accuracy for detecting second primaries or local recurrences were calculated for patients with at least two NBI assessments. The effect of previous radiotherapy was determined by test of proportions and that of the learning curve and lesion site with Fisher's exact test. 138/195 patients were included in the analysis. NBI sensitivity, specificity, PPV, NPV, and accuracy for groups A and B were 89.5 vs 100%, 85.2 vs 81.5%, 65.4 vs 69.7%, 96.3 vs 100%, and 86.3 vs 87%, respectively. The diagnostic gain of NBI was 88.2% in group A and 69.6% in group B. The learning curve was the main source of false positives (p = 0.025), whereas radiotherapy and lesion site were uninfluential (p = NS). NBI appears useful for follow-up after treatment for OSCC or OPSCC, its performance being affected only by the learning curve and not by previous treatment or lesion site.reservedmixedTirelli, Giancarlo; Piovesana, Marco; Bonini, Pierluigi; Gatto, Annalisa; Azzarello, Giuseppe; Boscolo Nata, FrancescaTirelli, GIAN CARLO; Piovesana, Marco; Bonini, Pierluigi; Gatto, Annalisa; Azzarello, Giuseppe; BOSCOLO NATA, Francesc