The role of bevacizumab in breast cancer

AbstractNeoangiogenesis and expression of the main angiogenic factor Vascular endothelial growth factor (VEGF) are critical steps already present at an early stage of breast cancer development. As tumor growth progresses other pro-angiogenic factors, including bFGF, TGFa and IL-8, are overexpressed and act in addition to VEGF. VEGF expression has been associated to poor prognosis and therapy outcome in breast cancer. Moreover, several studies have documented that HER-2 overexpression induces VEGF expression/secretion and neovascularization and that VEGF expression increases when tumors become resistant to treatment. On these bases the anti-VEGF drug Bevacizumab has been evaluated in the clinical setting in breast cancer patients. Recently, phase III studies have demonstrated that Bevacizumab in combination with taxanes produces a high rate of responses and increases the Progression Free survival of breast cancer patients. A large array of studies is currently ongoing with Bevacizumab in combination with chemotherapy and hormone-therapy in the metastatic, neoadjuvant and adjuvant setting

EXTRACELLULAR MIMETICS: A COMPARATIVE EVALUATION OF CELL ENCAPSULATION UTILIZING HYDROGELS AND SCAFFOLDS

An in vitro encapsulation platform utilizing hydrogels and bone matrix (BM) scaffolds to investigate the effects of microenvironmental parameters on encapsulated goat mesenchymal stem cells (gMSC) was presented. The base encapsulation matrix was composed of a biocompatible hydrogel formed through a photoinitiated polymerization process. Different polymer concentrations were used to compare the effects of hydrogel crosslinking density on physical properties, as well as on cell viability. The potential of BM to support the growth and differentiation of gMSC was also analyzed. Both methods were compared in order to analyze viability. Structures that better allow flow of oxygen showed more promising results, whereas BM structures require a better evaluation method for concrete results

Genesi, evoluzione e paleografia delle grotte costiere di marina di Camerota (parco nazionale del Cilento Vallo Di Diano, Italia Meridionale)

ItLa costa tra Marina di Camerota e P.to Infreschi (SA) presenta numerose grotte, già note per il loro valore preistorico. E’ stato condotto uno studio geomorfologico e stratigrafico, per delucidare la loro genesi ed evoluzione. Sono stati individuati 4 tipi di cavità: grotte sviluppate in depositi marini o continentali, grotte in substrato calcareo impostate su faglia o frattura, grotte associate all’emergenza di una falda in rete e relitti di cavità crollate. All’interno delle cavità sono stati riconosciuti diversi stazionamenti del livello del mare. Le grotte studiate contengono il registro delle oscillazioni eustatiche e climatiche tardo pleistoceniche, oltre che importanti tracce preistoriche. Esse possono dunque essere considerate geositi di rilevanza nazionale e come tali devono essere preservate e valorizzate in maniera adeguata.EnThe coastline between Marina di Camerota and the bay of Porto Infreschi (Province of Salerno) is characterized by several caves, known above all for their prehistoric records. We carried out a detailed study of these caves in order to better understand their genesis and evolution in function of the main middle and late Pleistocene eustatic sea level fluctuations.Along the coastal sector four different kind of cave have been identified. The first one includes caves developed into Pleistocene marine conglomerates or into slope breccias, located at altitude higher than the present see level and which are associated with ancient see level. The second one contains fault-guided or joint-guided caves developed into carbonate bedrock; some are active and some other are fossil. The third kind includes phreatic caves cut into carbonate bedrock. Generally, they are present in group and developed along front line(for example, the case of the bay of Porto Infreschi). The last one is represented by the remains of collapsed caves; which are visible for the presence of marine deposits, speleothems and remains of alluvial fan along the sea cliff (i. e. the case of the Riparo degli Infreschi cave). Into the caves the traces of at least three different high stands located at altitude of 8.5-8, 4.5, 3.5 m a.s.l. which can be referred to the Last Interglacial period have been observed (ESPOSITO et al., 2002). Moreover in the Porto Infreschi caves are clearly recorded moments of speleothems formations between the different phases of marine ingression.During the low stands of the isotopic stages 4 and 3 the most of the caves were abandoned by the sea and they became a safe refuge for the prehistoric man. The richness of their stratigraphical record, from a paleoclimatical and archaeological point of view, in addition to their prehistoric importance, allow many of these caves to be considered as important "geosites"

[¹⁸F]FMCH PET/CT biomarkers and similarity analysis to refine the definition of oligometastatic prostate cancer

Background:The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [18F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease.Methods:PCa patients eligible for [18F]FMCH PET/CT presenting biochemical failure after first-line curative treat-ments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions’ similarity analysis were performed.Results: [18F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions’ heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogene-ity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity.Conclusions:We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring dif-ferent cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometa-static PCa

Short-term clinical outcomes of robot-assisted intersphincteric resection and low rectal resection with double-stapling technique for cancer: a case-matched study

Background: Intersphincteric resection (ISR) with total mesorectal excision (TME) is an accepted technique for the surgical treatment of very low rectal cancer. Historically it is associated with a higher functional complication rate than the Double Stapling (DS) technique when performed with open or laparoscopic approach. The aim of this study was to compare the surgical, short-term oncologic and functional outcomes of robotic ISR TME (R-ISR-TME) with those of robotic low anterior resection TME with a double stapling technique (R-DS-TME). Methods: Between April 2010 and December 2013, 42 patients underwent robot-assisted rectal resection with TME at our General Surgery Unit, including 10 R-ISR-TME. The outcomes of the R-ISR-TME group were compared with a R-DS-TME group selected using a case-matched methodology. We evaluated the operative, pathological, short-term oncologic results and postoperative sexual, urinary and defecation functions using specific questionnaires. Results: The analyses of the data showed similar results for R-ISR-TME and R-DS-TME regarding the operative, pathological and oncologic results. Focusing on urinary and sexual function, no score values were significantly different at any time between the two groups. The daily frequency of defecation 1 year after surgery was 1.9±0.9 for RISR-TME and 1.8±0.3 for RDS-TME indicating no difference between the two groups. Moreover, there were no significant differences between the two groups in other defecation functions. The mean Wexner score 1 year after surgery was 3.0±1.1 in R-ISR-TME and 2.2±1.0 in R-DS-TME group (p=0.2) and defecation-related quality of life for R-ISR-TME and R-DS-TME was not significantly different (modified fecal incontinence quality of life score: 30.3±19.1 vs 27.5±14.5, respectively; p=0.2). Conclusions: These clinical and functional results suggest that R-ISR-TME could be a good sphincter-preserving surgery for patients with very low rectal cancer. Robotic assistance may overcome some intrinsic limitations of the ISR technique flattening the difference with the DS-TME procedure

Hand-assisted hybrid laparoscopic–robotic total proctocolectomy with ileal pouch–anal anastomosis

PURPOSE: Few studies have reported minimally invasive total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We herein report a novel hand-assisted hybrid laparoscopic-robotic technique for patients with FAP and UC. METHODS: Between February 2010 and March 2014, six patients underwent hand-assisted hybrid laparoscopic-robotic total proctocolectomy with IPAA. The abdominal colectomy was performed laparoscopically with hand assistance through a transverse suprapubic incision, also used to fashion the ileal pouch. The proctectomy was carried out with the da Vinci Surgical System. The IPAA was hand-sewn through a trans-anal approach. The procedure was complemented by a temporary diverting loop ileostomy. RESULTS: The mean hand-assisted laparoscopic surgery (HALS) time was 154.6 (±12.8) min whereas the mean robotic time was 93.6 (±8.1) min. In all cases, a nerve-sparing proctectomy was performed, and no conversion to traditional laparotomy was required. The mean postoperative hospital stay was 13.2 (±7.4) days. No anastomotic leakage was observed. To date, no autonomic neurological disorders have been observed with a mean of 5.8 (±1.3) bowel movements per day. CONCLUSIONS: The hand-assisted hybrid laparoscopic-robotic approach to total proctocolectomy with IPAA has not been previously described. Our report shows the feasibility of this hybrid approach, which surpasses most of the limitations of pure laparoscopic and robotic techniques. Further experience is necessary to refine the technique and fully assess its potential advantages

ANÁLISE CRÍTICA DA CONTABILIDADE GERENCIAL SOB A ÓTICA DO PROFISSIONAL CONTÁBIL: UM ESTUDO NAS EMPRESAS ATUANTES NO RAMO SUCROALCOOLEIRO DO INTERIOR DO ESTADO DE SÃO PAULO

Esta pesquisa apresenta uma análise crítica da contabilidade gerencial, a partir da ótica dos profissionais contábeis que desempenham suas atribuições junto às indústrias sucroalcooleiras instaladas no interior do estado de São Paulo O objetivo deste estudo consiste em demonstrar a visão destes profissionais sobre a importância do uso da contabilidade gerencial no processo de gestão e tomada de decisão. A metodologia empregada na elaboração desta pesquisa caracteriza-se como empírico-analítica de caráter descritivo, e a premissa adotada para a coleta de dados consistiu na aplicação de um questionário eletrônico (survey). Como resultados principais a pesquisa aponta que 80% dos participantes responsabilizam a falta de informações contábeis como causa do insucesso organizacional, e 100% concordam total e parcialmente que prejuízos crescentes e baixa competitividade estão atrelados ao uso incorreto das informações contábeis no processo de tomada de decisão nas empresas atuantes no setor. O trabalho contribui com a pesquisa na área, por demonstrar a importância da contabilidade gerencial na percepção dos profissionais como essencial à gestão dos negócios e à sobrevivência das organizações e por apresentar um perfil de profissional no setor, a maioria é pós-graduado e do gênero masculino

Effectiveness of sequential viscosupplementation in temporomandibular joint internal derangements and symptomatology : a case series

Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. +is case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. +is viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles

Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus

Preparations from Pimenta pseudocaryophyllus (Gomes) L.R. Landrum (Myrtaceae) have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR). The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1), followed by the essential oil of the citral chemotype (62.5–250 μg mL−1). Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1) and Cryptococcus spp. (3.9–15.6 μg mL−1). The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects