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Funding Acknowledgements Type of funding sources: None. Background Present guidelines endorse complete removal of cardiovascular-implantable electronic devices (pacemakers/defibrillators), including extraction of intracardiac electrodes, not only for systemic infections but also for localized "pocket infections." Objectives We evaluated the efficacy of delivering "Continuous, In-situ-Targeted, ultra-high concentration of Antibiotics" (CITA) into the infected subcutaneous the device-pocket, obviating the need for device/lead-extraction. Methods The CITA-Group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, nine patients declined lead-extraction because of prohibitive operative risk, and six patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction but opted for CITA treatment, were compared to 81 patients with pocket infection and similar characteristics who underwent device/lead-extraction as primary therapy. Results Eighty patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (68/80) patients, who remained free of infection (median follow-up: 3 years, interquartile range 1 – 6.8 years). In the case-control study of CITA vs. device/lead extraction, cure rates were higher after device/lead-extraction than after CITA [96.2%; (78/81) vs. 84.6%; (55/65), p=0.027]. However, rates of serious complications were also higher after extraction [12 (14.8%) vs. 1 (1.5%), p=0.005]. All-cause 1-month and 1-year mortality were similar for CITA and device/lead-extraction (0% vs. 3·7%, p=0·25 and 12·3% vs. 13·6%, p=1·00, respectively). Extraction was avoided in 90·8% (59/65) extraction-eligible patients treated with CITA. Conclusions CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction.

In Italy, forest tree crops cover an area of about 100.000 hectares of farmland: more than half are represented by specialized poplar plantations, while the remaining consists mainly of hardwood broadleaves plantations. The profitability of poplar and hardwood broadleaved plantations, assessed by field data collected on a representative number of plantation sites, was evaluated in terms of net present value and equivalent annual value under different levels of wood prices and in presence or absence of financial public incentives. Under current market conditions the investment in specialized poplar plantations is usually positive, even without subsidies. On the contrary, hardwood broadleaves plantations usually do not provide positive financial results without public incentives, while better financial results can be obtained by polycyclic plantations including both hardwood broadleaves (medium-long rotation) and hybrid poplar (short rotation) on the same parcel.

This technical note describes a quick methodology to classify the phytodepurative potential of riparian forest stands. Some municipalities located within landscapes characterized by both intensive agricultural and industrial activities in Central Italy are considered as test areas. Starting from the on-screen interpretation of high-resolution digital aerial orthophotos, supported by accurate ground surveys and GIS operations, it has been possible to map the riparian forest stands and classify each of them based on factors representing their phytodepurative potential. The proposed mapping process, feasible and easily replicable, provides a support tool for analysis and planning related to phytoremediation and/or to identify conservation and environmental management priorities and, depending on the goals of the phytoremediation objectives, to define where to locate eventual specific technical interventions.

Objective The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. Design The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) 10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Conclusions Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. Lay summary NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD. ©

Os alimentos funcionais fazem parte de uma nova percepção de alimentos, pois além da alimentação suprir as necessidades básicas nutricionais, também proporciona benefícios para a saúde como a diminuição de riscos de doenças como hipertensão, diabetes entre outras. Existe um público específico que possuem restrições alimentares à açúcar, glúten e lactose por inúmeros fatores relacionados à saúde. Com isso, o objetivo do presente trabalho foi o desenvolvimento de um bolo funcional, isento de trigo, leite e açúcares adicionados e a elaboração de sua tabela de informação nutricional. Com a formulação final do bolo de maçã foi elaborada a tabela nutricional com base nas legislações RDC 359 e 360/2003 da Agência Nacional de Vigilância Sanitária (ANVISA), em vigor. As IN 75/2020 da ANVISA, que vigora em outubro de 2022, RDC 429/2020 e RDC 54/2012 também foram consultadas. Diante disso, foi possível elaborar um produto com teor de fibras de 2,6g na porção, suficiente para ser considerado “fonte de fibras”. O produto proposto torna-se uma opção para o público em geral, mas especificamente para pessoas com dietas restritivas, como diabetes, celíacos e intolerante à lactose/alérgicos à proteína do leite.

Osteoarthritis (OA) results from loss of cartilage in-tegrity in association with changes to the structure of the entire joint. Treatment of OA is based on different pharmaceutical and no phar-maceutical approaches and the latter include the use of spa-therapy. The biological effects of mud-bath therapy are mainly secondary to heat stimulation and to physic-chemical properties of mineral waters and mud-packs. Mud-bath therapy likely exerts its effects modulating several cytokines and other molecules involved in inflammation and cartilage degradation. Our aim was to perform an updated meta-analysis of the effectiveness of the mud-bath therapy on knee osteoarthritis and briefly to discuss the mechanisms of action of this treatment.A MEDLINE on PubMed for articles on knee OA and spa therapy published from 1995 through up to April 2019 was performed. Then, we checked the Cochrane Central Register of Controlled Trials to find additional references included up to April 2019. Articles were included if in accordance with the eligibility cri-teria. Sample size and effect sizes were processed with the MedCalc software package.Twenty one studies met the inclusion criteria and were included in meta-analysis. We examined WOMAC Index and VAS pain. We found significant improvements in function scores and painful symptoms after mud-bath therapy in patients with knee joint osteoarthritis.Spa therapy is a non-drug treatment modalities, non invasive, complication-free, and cost-effective alternative modality for the conservative treatment of knee osteoarthritis. It cannot substitute for conventional therapy but can integrated or alternated to it. Treatment with mud-bath therapy may relieve pain, stiffness and improve functio-nal status in patients with knee OA.

Aims To present the long term-results and complications of a large series of stapled ileal orthotopic neobladders. Materials and methods From 1992 to 2012 we performed 606 radical cystectomies with stapled orthotopic neobladder substitution in male patients. The median patient age was 65 years (interquartile range [IQR]: 58–71). Results Median operative time was 205 min (IQR: 180–225). The overall survival rates at 5, 10, 15, and 20 yr were 68% (336 of 494), 55% (207 of 376), 38% (98 of 259), and 23% (14 of 62), respectively, and the disease specific survival rates were 75% (371 of 494), 59% (222 of 376), 50% (130 of 259), and 35% (22 of 62), respectively. After a median follow-up of 81 months (IQR: 30–144), a total of 147 early (less than 90 days) complications (38 diversion related, 109 diversion unrelated) occurred in 144 patients (24%); 163 late complications (141 diversion related, 22 diversion unrelated) affected 141 patients (23%). At 60 months, daytime and nighttime continence was complete in 96% and 72% of cases, respectively. Urodynamic studies showed that maximum capacity, residual volume, maximum flow rate, pressure at maximum capacity, and maximum outlet closure pressure were not statistically different at 12 and 60 months postoperatively. Conclusions The use of a stapler when performing orthotopic neobladders significantly reduces the operating time, and offers good functional results with acceptable complication rates. Our results could encourage the use of a stapler when performing an ileal neobladder during laparoscopic and robotic radical cystectomies.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Poly (ɛ-caprolactone) (PCL) is a biodegradable polyester approved for applications in the human body such as drug delivery devices and sutures. Conventional synthesis of PCL involves metal catalysts and organic solvents that may leave toxic residues in the products and contribute to environmental pollution. Polymerization processes catalyzed by enzymes are becoming more attractive due to the importance of clean processes, which produces substances free of residues, ideal for pharmaceutical and food applications. The aim of this work was to investigate the enzymatic ring-opening polymerization (e-ROP) of PCL in supercritical carbon dioxide (scCO 2 ) solvent medium through a set of experiments assessing the influence of pressure (120–280 bar), solvent/monomer ratio (2:1–1:2 mass ratio) and enzyme percentage related to monomer (5–15 wt%) on the reaction yield, number-average molecular weight ( M n ), weight-average molecular weight ( M w ) and polydispersity index (P.I.). The results of these first experiments were used in the selection of the conditions for the kinetic experiments evaluating the influence of catalyst content and temperature on reaction yield, M n , M w , P.I. and on the characteristics of the polymer produced. This study also evaluates the enzyme reuse in order to reduce the impact of the enzyme cost on the process. Results for ANOVA statistical analysis for the first set of experiments show that the pressure or the solvent density has no significant influence over the parameters evaluated, while the solvent/monomer mass ratio presented significant effect on M n and on M w , with the best results obtained for the solvent/monomer mass ratio of 1:2. As expected, the enzyme content affects significantly all parameters evaluated. Polymerization results for the kinetic experiments indicate reaction yields up to 90 wt%, M n up to 13,700 Da and M w up to 22,200 Da, with P.I. ranging from 1.2 to 1.7. Taking into account the reaction productivity, the conditions for the reuse assays were chosen: 120 bar, 1:2 solvent/monomer ratio, 3 wt% of enzyme, 65 °C and 12 h of reaction. The enzyme recycling experiments suggested viability up to the second cycle as an alternative to improve the enzyme use. The variable-volume view reactor was adequate to provide simultaneous control of the process variables.

Supercritical fluid extraction from dried banana peel (Musa spp., subgroup Prata, genomic group AAB, popularly known in Brazil as Enxerto) was studied. The aspects investigated were: overall extraction curve (OEC), mass transfer modeling of the yield curves, economical analysis of the process and phase equilibrium data for the pseudo-ternary system of banana peel extract, carbon dioxide and ethanol. The extraction operating conditions evaluated were: pressure ranging from 100 bar to 300 bar, temperature from 40 to 50 °C and constant solvent flow rate of 5.0 gCO2/min. Experimental extraction data were correlated using three kinetic models based on mass transfer equations (logistic, diffusion and Esquivel models). Phase equilibrium measurements were performed using pressure from 64.9 bar to 239.9 bar and mass fraction of supercritical extract from 0.52 to 3.55 wt%. Yield results ranged from 0.6 to 6.9% d.b. (dry basis). The lowest deviation between experimental and correlated data was obtained by the Logistic model, except for the curve at 300 bar and 40 °C which was best represented by the Esquivel model. The economical analysis identified the possibility to apply the supercritical fluids to obtain extracts from banana peel in an industrial scale. Phase equilibrium for the supercritical extract from banana peel with carbon dioxide modified by ethanol exhibited liquid–liquid, vapor–liquid (bubble point) and vapor–liquid–liquid phase transitions. A crossover phenomenon for the systems evaluated was observed for pressures between 200 bar and 240 bar, for both groups of assays, i.e., supercritical extraction and phase equilibrium.

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 T cells (%CD38/CD8)] and lymphocyte proliferation to P. jiroveci, C. albicans, C. neoformans, A. fumigatus at a single time point after treatment, were selected. CD38 expression ≥2401 CD38 ABC and ≥85% CD38/CD8 cut-off points, accurately discriminates responders versus non-responders, both measures resulting in 75.0% (CI 42.8–94.5) sensitivity (identification of non-responder) and 93.8% (CI 69.8–99.8) specificity (identification of responder), when considered as single assays. The association ‘≥2401 CD38 ABC or ≥85% CD38/CD8’ improved sensitivity to 83.3% (CI 51.6–97.9), while the association ‘

This work reports phase equilibrium measurements for the ternary systems linoleic (acid + CO2 + ethanol) and (linolenic acid + CO2 + ethanol). The fatty acids present in the ternary systems were selected based on composition of banana peel oil extracted by supercritical CO2 at 20 MPa and 313 K. The motivation of this research relies on the fact that these unsaturated fatty acids are recognized to play an important role in lowering blood pressure and serum cholesterol and because they are present in high concentrations in banana peel extract. Besides that, equilibrium data of these compounds are scarce in literature. The phase equilibrium experiments were performed using a high-pressure variable-volume view cell over the temperature range of (303 to 343) K and pressures up to 19 MPa. For both systems, only vapour–liquid phase transitions were visually recorded for all data measured.

The aim of this work is to report phase equilibrium data for the binary systems (CO2 + α-humulene) and (CO2 + trans-caryophyllene), and for the ternary system (CO2 + α-humulene + trans-caryophyllene). Results from literature show that α-humulene and trans-caryophyllene are the main compounds responsible for the anti-inflammatory and anti-allergic characteristics attributed to the medicinal plant Cordia verbenacea D.C., hence giving importance to the phase behaviour investigation performed in this work. Phase equilibrium experiments were performed in a high-pressure, variable-volume view cell over the temperature range of T = (303 to 343) K and pressures up to 20 MPa. (Liquid + liquid) and (vapour + liquid + liquid) equilibrium were observed at T = 303 K, while (vapour + liquid) phase transitions were verified to occur from T = (313 to 343) K, for all systems studied. Thermodynamic modelling was performed using the Peng–Robinson equation of state and the classical quadratic mixing rules, with a satisfactory agreement between experimental and calculated values.

In 2001 the Italian Ministry of Agricultural and Forest Politics financed a forest research project (Ri.Selv.Italia), which included a study for testing arboreous species and cultivars for the production of energy biomass and for industrial purposes, in different sites of the country. The first results, here reported, were obtained for the SRF plantations of poplar and willow planted out in the period of 2001-2002 in two different sites (Casale Monferrato AL, in Northern Italy and Bagni di Tivoli Rome, in Central Italy). In each trials the soil was ploughed and harrowed before planting. In early spring, poplar and willow 20 cm long rootless cuttings were planted in single or in twin rows with a planting density of 10000 trees ha-1. Regular cultural practices, chemical and mechanical weed control in particular, were carried out during the first year and after coppicing. Irrigation and parasites control were done only in Casale M.to where the soil is sandy. At the present stage, in the Central Italy site, poplar seems to be more productive than willow, as the willow clones are very sensitive to the summer drought. In Northern Italy the annual mean of yield achieved by the best willow clone, with irrigation, was above 19 oven dry tons (ODt) ha-1 year-1; and the yield of the best poplar clone was slightly below 17.5 ODt ha-1 year-1. The selection tests for both poplars and willows are pointing out a good potential for genetic improvement of the species grown in SRF, especially in order to increase the productivity. In the trial of Casale Monferrato, moderate but significant differences of yield have been observed between single and twin lines - with unchanged planting density, in favour of the first layout.

Objetivo En Chile existe escasa informacion acerca de la neumonia adquirida en la comunidad de caracter grave manejada en las unidades de cuidados intensivos. En este trabajo se describen el cuadro clinico, los factores pronosticos y el tratamiento de pacientes adultos hospitalizados en la unidad de cuidados intensivos por neumonia adquirida en la comunidad grave. Pacientes y metodos Se ha realizado un estudio clinico prospectivo y descriptivo que ha incluido a 113 pacientes consecutivos. Resultados De los 113 pacientes incluidos (edad media ± desviacion estandar: 73 ± 15 anos), el 95% tenia comorbilidad asociada y un 81% pertenecia a las categorias de alto riesgo del indice de gravedad de la neumonia (Pneumonia Severity Index). Se demostro la etiologia en el 31% y los patogenos mas frecuentes fueron Streptococcus pneumoniae (40%), bacilos gramnegativos (17%) y Mycoplasma pneumoniae (6%). Las principales complicaciones fueron necesidad de ventilacion mecanica (45%), shock septico (26%), insuficiencia cardiaca (24%) y arritmias (15%). La mortalidad a los 30 dias fue del 16,8% y mediante un analisis multivariado se identificaron los siguientes factores asociados a mayor riesgo de muerte: insuficiencia renal aguda (odds ratio = 5,1) y glucemia mayor de 300 mg/dl (odds ratio = 7,2). Conclusiones Los pacientes con neumonia grave ingresados en la unidad de cuidados intensivos son de edad avanzada, con una alta tasa de comorbilidad y complicaciones, pero la mayoria sobrevive.

PCR (Polymerase Chain Reaction) has revolutionized molecular genetics and continues to be applied to many fields of medicine and biology. We used nested real time RT – PCR to detect circulating prostate cells in patients affected by prostate cancer, in order to evaluate a possible clinical role of this technique. We present our initial experience.

Objectives: To estimate the prevalence of and identify risk factors for lipodystrophy syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents. Design: Cross-sectional observational study. Methods: HIV-infected subjects aged 2-18 years were recruited from 15 HIV centers in Belgium Italy, and Poland between January 2007 and December 2008. Standardized assessments by the patient's long-term clinician were performed to establish the presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia). Results: Among 426 subjects (70% white), median age was 12.2 years (interquartile range: 9.0-15.0 years) and median duration of antiretroviral therapy was 5.2 years (interquartile range: 2.2-8.8 years). Prevalence was 57% (n = 235) for LS and 42% (n =176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n =117) of subjects and lipohypertrophy in 27% (n = 115), most commonly in the face and trunk, respectively. In multivariable analysis, white ethnicity, body mass index, ritonavir/lopinavir, and nonnucleoside reverse transcriptase inhibitors were each associated with an increased risk of LS (P

Background In order to improve our cisplatin–5-fluorouracil (5-FU)-based alternating chemo-radiotherapy regimen, in 1996 we started an investigational program to explore a modified alternating regimen including gemcitabine given both with radiosensitizing and cytotoxic intent. Materials and methods Based on our previous feasibility trial, we conducted a second study testing the feasibility and activity of the following schedule: gemcitabine 800 mg/m2 on day 1 and cisplatin 20 mg/m2 on days 2–5 (weeks 1, 4, 7 and 10) alternated with three courses of radiotherapy (RT) (weeks 2–3, 5–6 and 8–9) with conventional fractionation up to 60 Gy. Gemcitabine 300 mg/m2 was also administered on the Monday of each week of RT. Results Forty-seven patients with stage IV (41 patients) unresectable squamous cell carcinoma of the head and neck (SCC-HN) or who had relapsed after surgery (6 patients) were enrolled. None had previously received chemotherapy or radiotherapy. Eight patients (18%) did not complete the treatment. Main grade 3–4 toxicities were as follows: neutropenia (44%); neutropenia with fever (12%); thrombocytopenia (37%); anemia (30% grade 3). One patient died in therapy due to sepsis. Most patients needed hospitalization and tube-feeding or parenteral nutrition. However, 44% of patients had a weight loss >10%. Thirty-four patients had a complete response (72%). Three partial responders were rendered disease-free by surgery (final complete response rate, 79%). At a median follow-up of 38 months actuarial 3-year overall survival, progression-free survival and loco-regional control are 43%, 39% and 64%, respectively. Data of locoregional control favorably compare with those from our database of patients treated with alternating cisplatin–fluorouracil and radiation within controlled clinical trials (64% versus 40%). Conclusions The inclusion of gemcitabine into an alternating regimen seems to improve the results achievable with the original alternating program in stage IV patients. However, due to the high acute toxicity correlated, this intensive regimen should be managed by institutions well trained in multidisciplinary treatments.

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX (TM)/Doxil (R)) versus conventional doxorubicin for first-line treatment of metastatic breast cancer Background: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX(TM) [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first- line treatment of women with metastatic breast cancer (MBC). Patients and methods: Women (n = 509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m(2) (every 4 weeks) or doxorubicin 60 mg/m(2) (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. Results: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR) = 1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR = 3.16; 95%CI 1.58-6.31; P

Prostate cancer is, today, the most frequent cancer and the second most frequent cause of death for cancer in USA. The watchful waiting approach, that has been traditionally proposed by urological communities in Northern Europe, is still matter of debate. The following review will consider the clinical studies published in Literature and will discuss the most controversial issues.

Objectives: The aim of this study was to describe the patterns of breast cancer relapse and the factors influencing therapeutic choices in an unselected postmenopausal population. Methods: Five hundred and thirty-nine patients were enrolled between October 1999 and March 2001. The majority (92.6%) underwent surgery for the primary tumor: there was no difference between general and university hospitals in terms of the type of mastectomy, but a slight difference was found between Southern and Northern Centers. Results: At the time of first relapse, 61.6% of the patients had a good Karnofsky performance status. The median disease-free interval (DFI) was 34 months. More than half of the patients (62.3%) presented a single metastasis. Metastatic disease was treated with chemotherapy in 64.8% of cases (alone in 44.1%, and in combination with hormone therapy in 20.1%), hormone therapy alone was given in 30.8% of cases. The main reasons for choosing chemotherapy were age (31%), standard guidelines (19.4%) and the site of metastatic disease (14.3%), and those for selecting hormone therapy were age (26.6%), site of relapse (19.3%), standard guidelines (19.2%), biological tumor characteristics (14.3%) and the DFI (11.1%). Taxane-containing treatments accounted for 46.1% of the chemotherapies, whereas letrozole was the preferred hormone (41.2%). Conclusion: The first relapse of breast cancer is often single, at bone or viscera, and mainly diagnosed by instrumental screening examinations. The preferred chemo- and hormone therapies are taxane-containing regimens and letrozole, respectively.

Aims: To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma. Methods and results: A 70-year-old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, α1-antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In-situ hybridization for Epstein–Barr virus was negative. Conclusions: We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.

The aim of this study was to investigate the possible impact of the treating institution on the survival of patients with advanced squamous cell carcinoma of the head and neck treated with radiotherapy alone or concomitant alternating chemotherapy and radiation. The National Institute for Cancer Research of Genoa (IST) was the coordinator of two multicentre randomised trials comparing an alternating chemotherapy and radiation approach to radiotherapy alone with standard fractionation (HN-8 trial: 157 patients) or accelerated fractionation (HN-9 trial: 136 patients) in patients with advanced squamous-cell carcinoma of the head and neck. A single database of the two studies was created and a univariate analysis was performed. The Cox regression model, adjusted for the effect of other prognostic factors, was used to test the impact of the treating institution on survival. Three-year overall survival was 46% for patients treated with chemotherapy and radiation at the coordinating centre and 27% for those treated with the same approach at the affiliated centres (P=0.0001). No difference was detected between patients treated with radiation alone at the coordinating centre or outside (23% versus 21%: P=0.52). The hazard ratio of death for patients treated at the affiliated centres with concomitant alternating chemotherapy and radiation was 2.15 (95% Confidence Interval (C.I.) 1.45-3.18), while it was 1.003 (95% C.I. 0.65-1.55) for those treated with radiation alone. In our experience, the treating institution had a significant impact only on the prognosis of patients treated with the multidisciplinary approach. This finding has implications, both in terms of clinical research and clinical practice.

Background The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate (pCR) in patients with locally advanced breast cancer (LABC) treated with combined modality therapy. Patients and methods Stage IIIA/IIIB patients received three courses of induction chemotherapy (ICT) with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by local therapy (total mastectomy or segmental mastectomy with axillary nodes dissection) and adjuvant chemotherapy (ACT) with three courses of CEF alternated with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Patients were randomized to receive ICT and ACT every 3 weeks (arm A, ‘standard treatment’) or every 2 weeks with granulocyte–macrophage colony-stimulating factor (GM-CSF) support (arm B, ‘dose-dense treatment’). In both arms radiotherapy was administered after the end of chemotherapy (in selected cases) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years. Results A total of 150 patients were randomized (77 arm A and 73 arm B) and demographics were well balanced between the two arms. Compliance to treatment was excellent: 95% and 93% of patients in arms A and B, respectively, completed the treatment program with no modification or delay. Median duration of treatment (ICT+local+ACT) was 183 days (range 0–265) in arm A and 139 days (0–226) in arm B. The average relative dose intensity (ARDI) of chemotherapy was 1.3 with a 30% increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [62%; 95% confidence interval (CI) 49% to 73.2%] and pathological response rates to ICT was observed between the two arms. Median follow-up was 5 years (range 1–96 months); median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in standard therapy: this figure has not yet been reached in the dose-dense treatment. Conclusions In LABC a dose-dense regimen, while allowing a 30% increase in the dose intensity of chemotherapy, did not provide significant improvement in pathological response rates. However, accelerated chemotherapy reduced the duration of the combined-modality program (6.1 versus 4.6 months) with no additional toxicities.

Drought resistance was examined for 2-year-old saplings of Ceratonia siliqua L., Olea oleaster Hoffmgg. et Link., Quercus suber L. and Q. pubescens Willd. growing in the field in Sicily, with the aim of testing their possible use in the reforestation of degraded areas. To this purpose, leaf conductance to water vapour (gL), transpiration rate (EL), relative water content (RWC) and water potential (ΨL) were measured between pre-dawn and sunset, monthly from May to November. Parallel measurements of loss of hydraulic conductance of twigs of the current year (PLC) were made together with an estimate of whole-plant hydraulic conductance (KPLANT) on the basis of the ratio of maximum EL to (ΨPD-ΨMIN), where ΨPD is pre-dawn ΨL and ΨMIN is the minimum diurnal ΨL. C. siliqua saplings maintained high gL throughout the study period with high RWC (over 90%) and ΨL. They grew rapidly and increased their foliage area (AL) by over 60% from May to winter rest. This was accompanied by low twig PLC (about 20% in September) resulting in high KPLANT all through the study period. In contrast, O. oleaster saplings underwent distinct dehydration in July, i.e. they showed stomatal closure due to a drop in RWC (to 75%) and ΨL (to the turgor-loss point). This was apparently due to twig cavitation, resulting in a strong decrease of KPLANT. Plants, however, tolerated summer drought, and showed growth (AL increased by 15% from May to November). Saplings of Q. suber and Q. pubescens were much more vulnerable to twig cavitation (PLC was 35–48% from June to November) than the other two species, and their average KPLANT was lower. Saplings of Q. suber and Q. pubescens grew only during the wet spring period, and no new foliage was produced thereafter. Changes in twig hydraulic conductance played a dominant role in determining changes in KPLANT in that the two variables were well correlated to each other (r=0.68 for P=0.001). We conclude that C. siliqua is an ideal candidate for reforestation of Sicilian degraded areas as is O. oleaster that, however, requires some additional water supply in the summer, at least during the early years after plantation. In wetter locations of Sicily, to an altitude between 0 and 500 m, Q. suber and Q. pubescens can be used for reforestation with expected higher competitiveness of the latter over the former species.

Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer.Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1).The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients.The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.

Aims To report feasibility, safety and effectiveness of “zero-ischemia” laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. Methods We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Results Mean patients age was 68 years (range 56–74), mean tumor size was 3.5 cm (range 2.2–6.3 cm). STE was successfully completed in 16 patients 12–15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a “zero-ischemia” approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5–22). Mean operative time was 123 min (range 115–130) and mean intraoperative blood loss was 250 mL (range 20–450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. Conclusions STE is a viable option to perform “zero-ischemia” LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (P-het = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)(Q4-Q1) = 1.29 (95% confidence interval, CI, 1.05-1.58), P-trend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), P-trend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), P-trend = 0.80] (P-het = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), P-trend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.

Background Oral capecitabine was evaluated in terms of overall response rate, safety, and tolerability as first-line therapy in women aged > or = 55 years with advanced/metastatic breast cancer. Patients and methods Ninety-five patients were randomized (2:1) to either intermittent oral capecitabine 1,255 mg/m2 twice daily (two weeks' treatment followed by a one-week rest period) or intravenous CMF (cyclophosphamide. methotrexate, 5-fluorouracil [5-FU]) administered every three weeks. Results The overall response rate in the capecitabine group was 30% (95% confidence interval (95% CI): 19%-43%), including three complete responses (5%). The response rate observed in the CMF group was 16% (95% CI: 5%-33%), with no complete responses. Median time to disease progression was 4.1 months with capecitabine and 3.0 months with CME. Survival was similar in the two treatment groups (median 19.6 months with capecitabine. 17.2 months with CMF). The safety profiles were different for capecitabine and CMF. However, both regimens were generally well tolerated and treatment interruption and/or dose modification was effective in managing toxicities associated with capecitabine. Alopecia and myelosuppression were rare in patients receiving capecitabine while diarrhea and hand-foot syndrome were more common. Treatment interruption and/or individual dose adjustment of capecitabine was required in 34% of patients and was generally effective in managing adverse events. Treatment was stopped owing to toxicity in 16% of patients in the capecitabine arm. The incidence of deaths during or within 28 days of stopping study treatment was 8% and 6% in the capecitabine and CMF arms, respectively. Conclusions An oral, twice-daily regimen of capecitabine is effective and well tolerated when used as first-line chemotherapy in older patients (> or = 55 years) with advanced/metastatic breast cancer, and is suitable for outpatient therapy.

Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m−2 intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m−2 i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m−2 i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III–IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38–73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy. © 1999 Cancer Research Campaign