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1.
Phys Chem Chem Phys ; 24(4): 1993-2003, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35018901

RESUMO

We have investigated the frontier orbitals of persistent organic radicals known as nitroxyls by resonant photoelectron spectroscopy (ResPES) under inner shell excitation. By means of this site-specific technique, we were able to disentangle the different atomic contributions to the outer valence molecular orbitals and examine several core-hole relaxation pathways involving the singly occupied molecular orbital (SOMO) localized on the nitroxyl group. To interpret the ResPES intensity trends, especially the strong enhancement of the SOMO ionized state at the N K-edge, we computed the Dyson spin orbitals (DSOs) pertaining to the transitions between the core-excited initial states and several of the singly ionized valence final states. We found that the computed vertical valence ionization potentials and norms of the DSOs are reasonably reliable when based on the long-range corrected CAM-B3LYP density functional. Thanks to their unpaired electrons, nitroxyls have recently found application in technological fields implying a spin control, such as spintronics and quantum computing. The present findings on the electronic structure of nitroxyl persistent radicals furnish important hints for their implementation in technological devices and, more in general, for the synthesis of new and stable organic radicals with tailored properties.

2.
Phys Chem Chem Phys ; 21(32): 17959-17970, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31384854

RESUMO

The starburst π-conjugated molecule 4,4',4''-tris(N-3-methylphenyl-N-phenyl-amino)triphenylamine (C57H48N4, m-MTDATA), based on triphenylamine (TPA) building blocks, is widely used in optoelectronic devices due to its good electron-donor characteristics. The electronic structure of m-MTDATA was investigated for the first time in the gas phase by means of PhotoElectron Spectroscopy (PES) and Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. The combination of Density Functional Theory (DFT) calculations with the experimental spectra provides a comprehensive description of the molecular electronic structure. Moreover, by comparing the results with previous TPA measurements, we could shed light on how the electronic structure evolves when the molecular size is increased. We found that the C 1s photoelectron spectra of m-MTDATA and TPA are similar, due to the balance of the counter-acting effects of the electronegativity of the N atoms and the delocalization of the amine lone-pair electrons. In contrast, the increased number of N atoms (i.e. N lone pairs) in m-MTDATA determines a three-peak feature in the outermost valence binding energy region with strong contributions by the N 2pz orbitals. We also obtained a decrease of the HOMO-LUMO gap for m-MTDATA, which points to improved electron donating properties of m-MTDATA with respect to TPA.

3.
J Phys Chem A ; 122(44): 8745-8761, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30351097

RESUMO

The near-edge x-ray-absorption fine-structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS) spectra of benzo[ b]thiophene (BBT) and dibenzothiophene (DBT) in the gas phase have been measured at the carbon K-edge and sulfur LII,III-edge regions. The assignment of the spectral features has been provided by theoretical calculations based on density functional theory (DFT) and its time-dependent generalization (TDDFT) in the linear response regime. Observed trends in computed C 1s and S 2p ionization potentials (IPs) have been rationalized in terms of both the inductive effects due to the presence of S and the increased π-electrons delocalization arising from the benzo-annulation process. The analysis of the NEXAFS carbon K-edge and sulfur LII,III-edge regions provided information on both low-lying delocalized virtual π orbitals, and higher-lying localized σ*(C-S) states. The evolution of the NEXAFS carbon K-edge spectral features along the series thiophene (T) and derivatives, BBT and DBT, is informative of a stabilizing effect due to increased aromaticity. This effect is however more pronounced in going from T to BBT compared to the introduction of a second annulated phenyl ring in DBT. The nature of the most intense sulfur LII,III-edge NEXAFS spectral features is instead conserved along the series reflecting thus the localized nature of the virtual states involved in the S 2p core-excitation process.

4.
Proc Natl Acad Sci U S A ; 114(48): 12797-12802, 2017 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29133396

RESUMO

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.


Assuntos
Linfócitos B/imunologia , Ligante de CD40/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/genética , Linfócitos T Auxiliares-Indutores/imunologia , Imunidade Adaptativa , Animais , Linfócitos B/citologia , Ligante de CD40/imunologia , Diferenciação Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Centro Germinativo/citologia , Centro Germinativo/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , Cultura Primária de Células , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-6/imunologia , Transdução de Sinais , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/imunologia , Especificidade da Espécie , Linfócitos T Auxiliares-Indutores/citologia
5.
J Chem Phys ; 146(5): 054705, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28178795

RESUMO

Photoelectron Spectroscopy (PS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy have been used to investigate the occupied and empty density of states of biphenylene films of different thicknesses, deposited onto a Cu(111) crystal. The obtained results have been compared to previous gas phase spectra and single molecule Density Functional Theory (DFT) calculations to get insights into the possible modification of the molecular electronic structure in the film induced by the adsorption on a surface. Furthermore, NEXAFS measurements allowed characterizing the variation of the molecular arrangement with the film thickness and helped to clarify the substrate-molecule interaction.

6.
J Chem Phys ; 146(5): 054303, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28178810

RESUMO

The electronic structure of short-chain thiophenes (thiophene, 2,2'-bithiophene, and 2,2':5',2″-terthiophene) in the gas phase has been investigated by combining the outcomes of Near-Edge X-ray-Absorption Fine-Structure (NEXAFS) and X-ray Photoemission Spectroscopy (XPS) at the C K-edge with those of density functional theory (DFT) calculations. The calculated NEXAFS spectra provide a comprehensive description of the main experimental features and allow their attribution. The evolution of the C1s NEXAFS spectral features is analyzed as a function of the number of thiophene rings; a tendency to stabilization for increasing chain length is found. The computation of the binding energy allows to assign the experimental XPS peaks to the different carbon sites on the basis of both the inductive effects generated by the presence of the S atom as well as of the differential aromaticity effects.

7.
Med Biol Eng Comput ; 55(7): 1123-1127, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28078482

RESUMO

In recent years, many local ablation technologies based on thermal damage have been used in the treatment of locally advanced pancreatic carcinoma (LAPC) and borderline resectable pancreatic carcinoma (BLRPC). However, they are associated with major complications because of possible vascular and ductal damage. Irreversible electroporation (IRE) is a nonthermal ablation technology that seems safe near vital vascular and ductal structures. IRE could be used as exclusive treatment of LAPC (en situ to IRE) after induction chemotherapy In BLRPC, surgery is not really radical in 6% of patients (microscopic residual) and local recurrences occur in 11-42% of apparent radical resections. IRE could be used as margin accentuation to increase posterior margin during radical surgery in BLRPC. Our outcomes are safety, time to progression. Secondary outcomes are overall survival, pain control and quality of life. We are performing a prospective evaluation of patients undergoing IRE for LAPC or BLRPC since July 2014. We have included patients with non-metastatic LAPC with maximum size ≤4 cm (en situ to IRE) and patients with BLRPC (complementary IRE). We have performed induction chemotherapy in both groups. After treatment, patients were evaluated on days 1, 2, 4, 7, 14, 21, 30, 60 and 90 with amylase and lipase serum and abdominal drainage test. Based on Ethics Committee's request, follow-up imaging was performed at the 10th day for safety evaluation, at 30, 60 and 90 days for response evaluation and then every 3 months. Seven patients (two women and five men) underwent IRE. Two patients had LAPC and received en situ to IRE. In five patients affected by BLRPC we performed IRE and pancreatic head resection. In all patients, intraoperative imaging confirmed that the treatment of the whole tumor volume was complete. All seven patients demonstrated nonclinically relevant elevation of their amylase and lipase, which returned normal at 5 days postprocedure. No patient showed evidence of clinical pancreatitis or fistula. No major complications were recorded. Patients with LAPC died of distant metastases 6 month after treatment. At 3- and 6-month follow-up, all patients with BLPRC were alive and disease free. Only one patient has already reached 9-month follow-up and is alive and disease free. Our results are only preliminary. However, IRE ablation of LAPC and BLRPC seems a safe and feasible treatment.


Assuntos
Adenocarcinoma/terapia , Eletroporação/métodos , Neoplasias Pancreáticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
8.
J Chem Phys ; 147(24): 244301, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29289119

RESUMO

The Near-Edge X-ray-Absorption Fine-Structure (NEXAFS) and X-ray Photoemission Spectroscopy (XPS) of short-chain oligothiophenes (thiophene, 2,2'-bithiophene, and 2,2':5',2″-terthiophene) in the gas phase have been measured in the sulfur L2,3-edge region. The assignment of the spectral features is based on the relativistic two-component zeroth-order regular approximation time dependent density functional theory approach. The calculations allow us to estimate both the contribution of the spin-orbit splitting and of the molecular-field splitting to the sulfur binding energies and give results in good agreement with the experimental measurements. The deconvolution of the calculated S2p NEXAFS spectra into the two manifolds of excited states converging to the LIII and LII edges facilitates the attribution of the spectral structures. The main S2p NEXAFS features are preserved along the series both as concerns the energy positions and the nature of the transitions. This behaviour suggests that the electronic and geometrical environment of the sulfur atom in the three oligomers is relatively unaffected by the increasing chain length. This trend is also observed in the XPS spectra. The relatively simple structure of S2p NEXAFS spectra along the series reflects the localized nature of the virtual states involved in the core excitation process.

9.
Oncogene ; 36(9): 1200-1210, 2017 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-27524418

RESUMO

Amplification of the MET oncogene occurs in 2-4% of gastroesophageal cancers and defines a small and aggressive subset of tumors. Although in vitro studies have given very promising results, clinical trials with MET inhibitors have been disappointing, showing few and short lasting responses. The aim of the work was to exploit a MET-amplified patient-derived xenograft model to optimize anti-MET therapeutic strategies in gastroesophageal cancer. We found that despite the high MET amplification level (26 gene copies), in the absence of qualitative or quantitative alterations of EGFR, MET inhibitors induced only tumor growth inhibition, whereas dual MET/EGFR inhibition led to complete tumor regression. Importantly, the combo treatment completely prevented the onset of resistance, which quite rapidly appeared in tumors treated with MET monotherapy. We found that this secondary resistance was due to EGFR activation and could be overcome by dual MET/EGFR inhibition. Similar results were also obtained in a MET-addicted, established gastric cancer cell line. In vitro experiments performed on tumor-derived primary cells confirmed that MET inhibitors were not able to abrogate the activation of downstream transducers and that only the combined MET/EGFR treatment completely shut off the signaling. Previously reported cases, as well as those described here, showed only partial and transient sensitivity to anti-MET therapy. The finding that combined anti-MET/EGFR therapy-even in the absence of EGFR genetic alterations-induced complete and durable response, represents a proof of concept and guarantees further investigations, opening a new perspective of treatment for these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Esofágicas/tratamento farmacológico , Amplificação de Genes , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Proliferação de Células/efeitos dos fármacos , Cetuximab/administração & dosagem , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/efeitos dos fármacos , Humanos , Lapatinib , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fosforilação , Quinazolinas/administração & dosagem , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Artigo em Espanhol | LILACS | ID: biblio-964404

RESUMO

Se presenta un aspecto del programa de investigación que este grupo viene realizando desde el año 2000 en el marco de las diferentes programaciones UBACyT. En esta etapa nos proponemos realizar articulaciones entre nuestro quehacer como psicoanalistas clínicos especializados en primera infancia y la labor de investigación basada en observaciones minuciosas de interacciones video-filmadas. Ejemplificamos, a partir de las viñetas de situaciones lúdicas video-filmadas en el marco de la investigación, la superposición de análisis posibles de las mismas desde tres sistemas, desarrollados por el equipo, descriptos también en este artículo. Un primer sistema estudia la modalidad afectiva de interacción, los indicadores de desregulación y el nivel de simbolización. Un segundo sistema se centra en los temas más frecuentes que se despliegan en la situación de juego libre. El tercero se basa en conceptualizaciones psicoanalíticas, con énfasis en la teoría de desarrollo de la libido. Tenemos en cuenta una visión que contempla la complejidad y la heterogeneidad de nuestro objeto de estudio y el aporte que la investigación observacional de interacciones lúdicas progenitor-niño puede realizar al estudio del desarrollo y a la clínica en primera infancia.


This paper presents one aspect of the research program that this group has been conducting since 2000 under UBACyT research programme. At this stage, we intend to make links between our clinical work as psychoanalysts specialized in early childhood and our research work, based on detailed observations of video-filmed interactions obtained in the research program. We offer some vignettes in order to exemplify the different possible analysis of the play situation, based on three observational systems, developed by the team, that are also described in this article. One system studies the affective mode of interaction, signs of affective deregulation and the level of symbolization in the play situation. A second system focuses on the description of play themes. The third system is based on psychoanalytical conceptualizations, with emphasis on the the theory of the development of the libido. Our view includes the complexity and heterogeneity of the play situation as object of study for developmental psychology and the contribution that observational research of parent-child play interactions can offer to the research and clinical interventions in early childhood.


Assuntos
Humanos , Jogos e Brinquedos , Simbolismo , Desenvolvimento Infantil , Relações Pai-Filho
11.
Rev Esp Med Nucl Imagen Mol ; 35(4): 232-7, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26907833

RESUMO

AIM: Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography ((18)F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal(18)F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. METHODS: Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery (18)F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. RESULTS: 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by (18)F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased (18)F-FDG uptake, were recognized. CONCLUSIONS: PP+IPCH of patients selected by (18)F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Fluordesoxiglucose F18 , Hipertermia Induzida , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
12.
Eur J Gynaecol Oncol ; 37(5): 638-643, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29787001

RESUMO

INTRODUCTION: The best treatment for relapsed platinum sensitive epithelial ovarian cancer (EOC) is controversial. The aim of the study was to compare progression-free survival (PFS) and overall survival (OS) in platinum-sensitive EOC patients treated with chemotherapy alone (CTA), secondary cytoreductive surgery (SCR) or SCR plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective analysis of the clinical outcome of 46 EOC patients with at least 30 months of follow-up. RESULTS: Median follow-up time was 32 months for the CTA group, 30 months for the SCR group, and 45 months for the SCR + HIPEC group. Fifteen recurrences were observed in the CTA group, seven in the SCR group, and 16 in the SCR + HIPEC group. The median time elapsed between first and second recurrence (PFI-2) was significantly higher among patients treated with SCR + HIPEC, in comparison with patients treated with CTA (p = 0.012 andp = 0.017, respectively). On the contrary, PFI-2 did not significantly differ between the SCR and SCR + HIPEC groups (p = 0.877). A statistically significant difference in OS favouring SCR + HIPEC in comparison with CTA (p = 0.04) was observed. CONCLUSIONS: SCR HIPEC compared with CTA improves PFI-2 in patients with platinum-sensitive EOC recurrence. SCR + HIPEC might also improve OS in comparison with CTA. No improvement in favor of SCR + HIPEC vs SCR was observed,. These results further support the need of a randomized trial comparing chemotherapy with SCR ± HIPEC in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidade , Platina/uso terapêutico , Estudos Retrospectivos
13.
Eur J Surg Oncol ; 41(4): 478-83, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25633642

RESUMO

BACKGROUND: Laparoscopic trans-abdominal total mesorectal excision is technically demanding. Transanal Total Mesorectal Excision (taTME) is a new technique which seems to provide technical advantages. This study describes the results of taTME in a consecutive series of patients with low rectal cancer. METHODS: From January 2012 to December 2013, a consecutive series of 26 patients with low rectal cancer underwent laparoscopic taTME with coloanal anastomosis. cT4 or Type II-III rectal cancer (according to Rullier's classification) were contraindications to taTME. After anal sleeve mucosectomy, the rectal wall was transected at the ano-rectal junction. A single-access multichannel port was inserted in the anal canal. taTME was performed from down to up until the sacral promontory posteriorly and the Pouch of Douglas anteriorly were reached. A laparoscopic trans-abdominal approach was used to complete the left colon mobilization. RESULTS: Sixteen patients (61.5%) were male. The mean distance of the rectal cancer from the anal verge was 4.4 cm (range 3-6). Nineteen patients (73.1%) received long-course neoadjuvant radiotherapy. At final pathology, resection margins were negative in all the patients: the mean distal and radial resection margins were 19 mm and 11.2 mm, respectively. TME was complete in 23 patients (88.5%) and nearly complete in three. Postoperative mortality was 3.8%. The overall morbidity rate was 26.9% (7 patients): two patients (7.7%) had an anastomotic leakage (Dindo I-d). After a mean follow up of 23 months, no patients have developed a local recurrence. CONCLUSIONS: laparoscopic taTME allow wide resection margins and good quality TME.


Assuntos
Adenocarcinoma/cirurgia , Canal Anal/cirurgia , Colo/cirurgia , Endoscopia Gastrointestinal/métodos , Neoplasias Retais/cirurgia , Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Intervalo Livre de Doença , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasia Residual , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Reto/patologia , Retenção Urinária/etiologia
14.
Appl Opt ; 53(26): 5879-88, 2014 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25321666

RESUMO

We present the design and characterization of a double-configuration grating monochromator for the spectral selection of extreme-ultraviolet ultrafast pulses. Two grating geometries are joined in an instrument with two interchangeable diffracting stages, both used at grazing incidence: one with the gratings in the off-plane mount (OPM), the other in the classical diffraction mount (CDM). The use of two stages gives great flexibility: the OPM stage is used for sub-50 fs time response and low spectral resolution, while the CDM stage is for 100-200 fs time response and high spectral resolution. The monochromator spectral and temporal performances have been experimentally demonstrated on a high-order laser-harmonics beam line.

15.
Eur J Surg Oncol ; 40(8): 925-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24726786

RESUMO

AIMS: Aim of this study was to assess operators' safety while performing a semi-closed HIPEC procedure for peritoneal carcinomatosis using cisplatin drugs. METHODS: Environmental air, theater personnel urine, operators' gloves and hand skin contamination were assessed during two non-consecutive working days. Six operating surgeons, two anesthesiologists and two theater nurses were included in the study. Glove samples were collected from the inner surface of the external glove and from the external surface of the inner glove from operating surgeons wearing a double pair of gloves. Personnel urine samples were collected before, after and 24 h from the procedure. RESULTS: Air and urine samples permanently resulted below detectable levels for cisplatin presence on all the tested sources and sessions. Cisplatin contamination was detected on the inner surface of the external gloves and on the outer surface of the inner gloves, but in a lower concentration for the latter. Skin wipe samples were below detectable levels for platinum presence. CONCLUSION: The results suggest that two pairs of gloves are adequate to protect the skin from antiblastic drugs. No sign of direct contact or systemic absorption of drugs was ever detected from the inspected samples. Semi-closed HIPEC technique appears to be a safe procedure for operators.


Assuntos
Poluentes Atmosféricos/análise , Antineoplásicos/análise , Carcinoma/cirurgia , Quimioterapia do Câncer por Perfusão Regional , Cisplatino/análise , Luvas Cirúrgicas , Pessoal de Saúde , Hipertermia Induzida , Exposição Ocupacional , Neoplasias Peritoneais/cirurgia , Adulto , Antineoplásicos/urina , Quimioterapia do Câncer por Perfusão Regional/métodos , Cisplatino/urina , Falha de Equipamento , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Saúde Ocupacional , Médicos , Risco , Segurança
16.
Minerva Chir ; 69(1): 9-15, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24675242

RESUMO

AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival. RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively. CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Laparotomia , Neoplasias Pulmonares/cirurgia , Mesotelioma/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Hipertermia Induzida , Infusões Parenterais , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Laparoscopia , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mesotelioma/química , Mesotelioma/diagnóstico , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno , Pessoa de Meia-Idade , Seleção de Pacientes , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Cuidados Pré-Operatórios , Resultado do Tratamento , Adulto Jovem
17.
Minerva Chir ; 69(1): 27-35, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24675244

RESUMO

AIM: Ovarian cancer may be considered as an "intraperitoneal disease" by itself. When surgical removal associated with systemic chemotherapy fails, usually, the history of the patients is characterized by poor prognosis. Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this article was to evaluate the survival benefit and the morbidity of patients with ovarian cancer treated at our institution by cytoreductive surgery associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: Between October 1995 and December 2012 more than 600 operations for PC were performed; in 308 cases surgical cytoreduction associated with HIPEC was carried out. Eighty-five patients treated by cytoreduction associated with HIPEC were affected by recurrent epithelial ovarian cancer (EOC). Statistical analysis was performed on 70 patients (last 15 patients were too recent for evaluation). Two trials were applied: 1) patients presenting first peritoneal relapse after surgery and systemic chemotherapy (CT), 6 months later from last CT administration; 2) multiple relapse patients. RESULTS: On 70 patients, morbidity and mortality rates were 35.7% and 7.1%, respectively. Overall median survival was 42.0 months, but in primary EOC was 48.0 months and in recurrent EOC was 28 months (P=0.12). Statistical analysis revealed that the completeness of cytoreduction was the most statistically significant factor related to survival: in completely citoreduced patients, overall survival was 48 months. CONCLUSION: Citoreductive surgery associated to platinum compounds HIPEC is feasible and relatively safe in recurrent and primary PC from ovarian cancer. Better selection of patients and second-look surgery in high risk-patients have to be investigated to improve those encouraging results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/secundário , Hipertermia Induzida , Laparotomia/métodos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Omento/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Peritônio/cirurgia , Cuidados Pré-Operatórios , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Intern Emerg Med ; 9(4): 455-62, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24214335

RESUMO

Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.


Assuntos
Angioedema/induzido quimicamente , Angioedema/epidemiologia , Emergências , Serviço Hospitalar de Emergência , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Cidade de Roma
19.
Minerva Chir ; 68(6): 551-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24193287

RESUMO

AIM: Peritoneal carcinomatosis (PC) is one of the routes of spread of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results on overall survival (OS) and disease-free survival (DFS) with surgical cytoreduction associated with hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this article is to evaluate the survival benefit and the morbidity in patients affected by colorectal PC treated at our institution by cytoreductive surgery associated with HIPEC. METHODS: In our institution, from October 1995 to June 2012, about 550 operations for PC were performed; in 300 cases cytoreduction plus HIPEC was carried out. Out of 90 operations for colonic cancer: 50 cytoreduction plus HIPEC, 12 cytoreduction and EPIC (early postoperative intraperitoneal chemotherapy) and 28 debulking or explorative laparoscopies/laparotomies were performed. For the present study, 50 patients who had undergone cytoreduction and HIPEC for PC of colorectal cancer origin (CRC) were considered. RESULTS: The morbidity and mortality rates were 34% (17/50) and 2% (1/50), respectively. The patients were divided in two groups according to PCI (peritoneal cancer index, range 0-39) and CC score (completeness of cytoreduction): in Group A (23 patients, PCI>16, CC-2) the median survival time was 15 months compared to 48.1 months for Group B (27 patients, PCI≤16, CC-0/1). The poor survival of Group A seemed to be related to higher PCI and CC score. CONCLUSION: Patient selection based on a maximum PCI of 16 associated with a complete cytoreduction (CC-0) produced encouraging results.


Assuntos
Carcinoma/secundário , Carcinoma/terapia , Quimioterapia do Câncer por Perfusão Regional , Neoplasias do Colo/patologia , Hipertermia Induzida , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/cirurgia , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
Minerva Chir ; 68(6): 569-77, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24193289

RESUMO

AIM: Pseudomyxoma peritonei (PMP) is a rare form of peritoneal carcinomatosis characterized by abnormal quantity of extracellular mucinous material. It almost originates from a primary appendiceal tumor with different malignancy degrees. The purpose of this study was to evaluate outcome and long-term survival on 80 patients affected by PMP after cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From October 1995 to June 2012, about 550 operations for PC were performed; in 300 cases surgical cytoreduction in association with HIPEC was carried out. Regarding PMP, 80 procedures of CRS and HIPEC were performed. This approach is based on surgical removal of the primitive cancer, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC performed with cisplatinum and C mytomicin. The rationale of this treatment is to obtain, after macroscopic disease removal, an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. RESULTS: The complication rate was 52.5% (42/80) with no postoperative deaths. The median overall and progression-free survival were 144 and 88 months, respectively. Not complete cytoreductive surgery (P<0.001), tumor histology (P=0.02) and previous systemic chemotherapy (p = 0.03) were identified in the univariate analysis as independent predictors for a poorer long-term survival. In the multivariate analysis, the completeness of cytoreduction was the only significant variable influencing the outcome. Incomplete cytoreduction (P<0.01) resulted the only statistically significant variable associated with a higher incidence of postoperative complications. CONCLUSION: PMP can be treated with curative intent in a large percentage of cases by cytoreductive surgery associated with HIPEC. This new approach could be performed safely with acceptable morbidity and mortality in selected patients treated in specialized centers. Completeness of cytoreduction allows to achieve the best results.


Assuntos
Quimioterapia do Câncer por Perfusão Regional , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia
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