Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer.

Green synthesis of gold nanoparticles modulates lipopolysaccharide-induced lung inflammation in Wistar rats.

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

Medical treatment of hepatocellular carcinoma.

The management of hepatocellular carcinoma (HCC) has substantially changed in the past few decades, the introduction of novel therapies (such as sorafenib) have improved patient survival. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. Decision-making largely relies on evidence-based criteria, as showed in the US and European clinical practice guidelines, which endorse five therapeutic recommendations: resection; transplantation; radiofrequency ablation; chemoembolization; and sorafenib. However, areas still exist in which uncertainty precludes a strong recommendation, such as the role of adjuvant therapies after resection, radioembolization with yttrium-90 or second-line therapies for advanced HCC. Many clinical trials that are currently ongoing aim to answer these questions. The first reported studies, however, failed to identify novel therapeutic alternatives (that is, sunitinib, erlotinib or brivanib). Efforts that focus on the implementation of personalized medicine approaches in HCC will probably dominate research in the next decade.

Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Worldwide progressive population aging demands consensus development for decision making when treating elderly patients. Age itself might not be a critical determinant for the selection of a therapeutic option. In the past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and the involvement of a number of pathways, including angiogenesis, aberrant signal transduction, and dysregulated cell cycle control, have been demonstrated, leading to evaluation of the activity and toxicity of some of the new molecularly targeted agents. Sorafenib was demonstrated to significantly increase the survival of patients with advanced HCC in two prospective, randomized, placebo-controlled trials. Subsequently, a number of retrospective or prospective studies have indicated that the effectiveness of sorafenib therapy in the treatment of HCC is similar in elderly and non-elderly patients. The aim of this review is to describe the impact of age on the effects of sorafenib-targeted therapy in patients with HCC, and the next treatment options with new targeted agents (everolimus, tivantinib, linifanib, etc.).

Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST).

BACKGROUND: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G). METHODS: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets. RESULTS: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens. CONCLUSIONS: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

[Geografic epidemiology of soft tissue sarcomas, Trieste (1995 -2005)]. / Epidemiologia geografica dei tumori del connettivo a Trieste (1995-2005).

Exposure to dioxin has been associated with the development of various kind of cancer. In the town of Trieste there is a contaminated site of national interest (according to law) and the incidence rate of cancer is the highest in Friuli Venezia Giulia. Using "main residence" it was possible to map soft tissues sarcomas (ICD-IX-171), in order to detect possible clusters or incidence gradients. Available data do not point out any statistically significant difference between observed and expected cases, applying pooled means from North Italy Cancer Registers. This work did not highlighted a correlation between residence in supposed polluted areas and rates of incidence of Soft tissue sarcomas.

Identificação precoce de sinais neuromotores alterados em crianças nascidas pré-termo / Early identification of altered neuromotor signals in preterm infants

O objetivo deste estudo retrospectivo e descritivo foi identificar, em lactentes nascidos pré-termo, o período mais precoce em que foram observados sinais neurológicos motores comumente presentes em paralisia cerebral (PC) e discutir a rotina de retornos, com a finalidade de detecção e vigilância desses sinais. A amostra foi composta por 28 bebês nascidos com menos de 37 semanas e peso inferior a 2.500g, de ambos os sexos, internados na Unidade de Terapia Intensiva Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, no período de junho de 2006 a dezembro de 2007, e acompanhados no Ambulatório de Neurodesenvolvimento dessa instituição. Foram coletadas informações dos prontuários referentes à idade gestacional dos bebês, ao processo diagnóstico de PC, quando houvesse, e às idades das principais aquisições posturais. Os resultados mostraram que, em 19 das 28 crianças, foi observado algum sinal de risco ou sequela até o último retorno. Desses 19 pacientes, seis tiveram diagnóstico de PC definido, três pacientes, diagnóstico a definir, cinco apresentaram sinais transitórios de lesão corticoespinhal, e cinco lactentes apresentaram somente atraso postural. Concluiu-se que a rotina de retornos para detectar e vigiar os sinais indicativos de PC nessa amostra revelou a necessidade de um protocolo de avaliação específico e da criação de uma dinâmica de acompanhamento e estimulação de todas as crianças nascidas pré-termo até a idade de marcha sem apoio, independentemente de apresentarem sinais neurológicos perinatais.

This retrospective descriptive study was developed to identify the earlier stages when neuromotor signals commomnly found in cerebral palsy (CP) were registered for preterm infants, as well as to discuss the current follow-up practice I order to detect and monitor such signals. The sample consisted of 28 babies born at less than 37 weeks and weighing less than 2500g, of both genders, admitted to the Intensive Care Unit Neonatal Hospital of the Medical School of Ribeirão Preto, in the period from June 2006 to December 2007, and followed at Neurodevelopment Service of this institution. We collected the medical information regarding the gestational age of these babies, the diagnosis process of CP, when was the case, and the ages when major postural acquisitions occurred. In 19 out of 28 children, signs of risk or sequel were observed until the last follow-up consultation. Among these 19 patients, six were diagnosed with CP, three were to be diagnosed, five showed signs of transient corticospinal lesion, and five infants showed only postural delay. The routine follow-up to detect and monitor signals indicative of PC in this sample revealed need for a more specific assessment protocol, and for the creation of a monitoring and stimulation dynamics for all preterm infants up to the age of walking without support, regardless of presenting perinatal altered neurological signs.

Identificação precoce de sinais neuromotores alterados em crianças nascidas pré-termo / Early identification of altered neuromotor signals in preterm infants

O objetivo deste estudo retrospectivo e descritivo foi identificar, em lactentes nascidos pré-termo, o período mais precoce em que foram observados sinais neurológicos motores comumente presentes em paralisia cerebral (PC) e discutir a rotina de retornos, com a finalidade de detecção e vigilância desses sinais. A amostra foi composta por 28 bebês nascidos com menos de 37 semanas e peso inferior a 2.500g, de ambos os sexos, internados na Unidade de Terapia Intensiva Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, no período de junho de 2006 a dezembro de 2007, e acompanhados no Ambulatório de Neurodesenvolvimento dessa instituição. Foram coletadas informações dos prontuários referentes à idade gestacional dos bebês, ao processo diagnóstico de PC, quando houvesse, e às idades das principais aquisições posturais. Os resultados mostraram que, em 19 das 28 crianças, foi observado algum sinal de risco ou sequela até o último retorno. Desses 19 pacientes, seis tiveram diagnóstico de PC definido, três pacientes, diagnóstico a definir, cinco apresentaram sinais transitórios de lesão corticoespinhal, e cinco lactentes apresentaram somente atraso postural. Concluiu-se que a rotina de retornos para detectar e vigiar os sinais indicativos de PC nessa amostra revelou a necessidade de um protocolo de avaliação específico e da criação de uma dinâmica de acompanhamento e estimulação de todas as crianças nascidas pré-termo até a idade de marcha sem apoio, independentemente de apresentarem sinais neurológicos perinatais. (AU)

This retrospective descriptive study was developed to identify the earlier stages when neuromotor signals commomnly found in cerebral palsy (CP) were registered for preterm infants, as well as to discuss the current follow-up practice I order to detect and monitor such signals. The sample consisted of 28 babies born at less than 37 weeks and weighing less than 2500g, of both genders, admitted to the Intensive Care Unit Neonatal Hospital of the Medical School of Ribeirão Preto, in the period from June 2006 to December 2007, and followed at Neurodevelopment Service of this institution. We collected the medical information regarding the gestational age of these babies, the diagnosis process of CP, when was the case, and the ages when major postural acquisitions occurred. In 19 out of 28 children, signs of risk or sequel were observed until the last follow-up consultation. Among these 19 patients, six were diagnosed with CP, three were to be diagnosed, five showed signs of transient corticospinal lesion, and five infants showed only postural delay. The routine follow-up to detect and monitor signals indicative of PC in this sample revealed need for a more specific assessment protocol, and for the creation of a monitoring and stimulation dynamics for all preterm infants up to the age of walking without support, regardless of presenting perinatal altered neurological signs. (AU)

Gemcitabine combined with oxaliplatin (GEMOX) as salvage treatment in elderly patients with advanced ovarian cancer refractory or resistant to platinum: a single institution experience.

Both oxaliplatin (OXA) and gemcitabine (GEM) have shown single agent activity in patients with recurrent ovarian cancer. Response rates to second-line therapies remain low and there is a need to develop more effective regimens. In view of the synergistic effect of using GEM followed by OXA, we studied these agents in elderly patients with recurrent ovarian cancer refractory or resistant to first-line chemotherapy using platinum with or without paclitaxel. The aim of the study was to evaluate the efficacy and toxicity of combination GEM 1000 mg/m(2) Day 1 i.v. and OXA 100 mg/m(2) in 2h infusion Day 2; treatment was repeated every 2 weeks for 6 courses or until progression of disease or intolerable toxicity. The study was monoinstitutional and started in November 2002. 21 patients, median age 68.6 years (range 65-82) have been treated. Median Performance Status was 0-1, all had at least 1 prior platinum based chemotherapy and 11 had received also a taxane. Patients received a median of 6 cycles of treatment (range 4-11). There were 2 patient (9%) with complete response, 3 patients (14%) achieved a partial response. Low profile toxicity (grade 1-2, WHO criteria) was observed: nausea/vomiting 52%, thrombocytopenia 13%, neuropathy 28%. The GEMOX combination is well tolerated and even in this small group of patients, encouraging responses were documented.

Phase II trial of a biweekly regimen of fluorouracil and leucovorin plus irinotecan in patients with previously untreated advanced gastric cancer.

To investigate the therapeutic value and safety of the biweekly regimen of 5-fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F 35/15; median age = 65) with AGC, none of whom had received chemotherapy for advanced disease, were accrued in this trial. Fifteen patients (30%) were 70 years old or older. At the time of their accrual, cytotoxic chemotherapy, consisting of LV 100 mg/m(2) (2-hour i.v. infusion) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22-hour continuous infusion) on therapeutic days 1 and 2 plus CPT-11 180 mg/m(2) (1-hour infusion) on day 1, was initiated. Treatment courses were repeated every 2 weeks until evidence of progressive disease, unacceptable toxicity or withdrawal of consent. All patients were assessable for toxicity and 48 of 50 for response evaluation, having completed at least four courses of chemotherapy. Complete response was achieved in 2 patients (4%, intent to treat) and partial response in 16 (32%) (overall response rate, 36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had stable disease and 6 patients (16%) progressed. The median time to progression was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI: 6-22 months). Between the subgroups of patients <70 years old and 70 or older, there were no significant differences in efficacy. One toxic death occurred. Treatment tolerance was generally mild to moderate and easy to treat. The main grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%). Grade 3-4 neutropenia was the only treatment-related serious adverse event significantly more common in patients older than those aged <70 (53.3% vs 22.8%, respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5-FU plus CPT-11 in untreated patients with AGC is active and has an acceptable safety profile. Further evaluation of this regimen seems to be warranted in a phase III trial.

Reduced dose intensity of docetaxel plus capecitabine as second-line palliative chemotherapy in patients with metastatic gastric cancer: a phase II study.

BACKGROUND: A phase II study was conducted to evaluate the efficacy and safety of a combination regimen of a reduced dose intensity of docetaxel (Taxotere) plus capecitabine in pretreated patients with metastatic gastric cancer. PATIENTS AND METHODS: Twenty-eight patients with documented progression on or within 3 months of a cisplatin-based chemotherapy were enrolled between April 2004 and November 2006. Docetaxel (60 mg/m2 on day 1) plus capecitabine (1000 mg/m2 twice daily on days 1-14) were given every 3 weeks. RESULTS: All patients were assessable for safety and 25 (89%) for tumor response. Median age was 63 years, and median follow-up was 13.3 months. Overall response rate was 29% (95% confidence interval 11% to 46%), while an additional 36% had stable disease. The median time to progression and median overall survival was 4 and 6 months, respectively. The most common clinical adverse events (all grades) were neutropenia (78%), hand foot syndrome (HFS) (53%), fatigue and alopecia (50%) and diarrhea (43%). However, with the exception of grade 3-4 neutropenia, which was seen in 36% of patients, other severe adverse events were rare. There were no treatment-related deaths. Treatment delays or dose reductions were necessary in 18 out of 104 cycles. CONCLUSIONS: A reduced dose intensity of docetaxel plus capecitabine is a valuable regimen for second-line treatment in this setting of patients. This approach warrants further investigation as a promising chemotherapy option for chemonaive patients with metastatic gastric cancer.

Lapatinib in breast cancer.

Aberrant activation of some members of human epidermal growth factor receptor (HER) family plays a key role in breast carcinogenesis. Lapatinib is an oral dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. Clinical data have shown that lapatinib is active in HER2-positive breast cancer as monotherapy, in combination with trastuzumab, and in trastuzumab-resistant patients. Phase I clinical trials have shown also that lapatinib is well tolerated, with mild diarrhea and skin rush as common toxic effects and low incidence of cardiotoxicity. Phase II and III clinical trials' data provide encouraging evidence of the clinical effectiveness of lapatinib in advanced or metastatic breast cancer and for its potential in patients with brain metastases. Interim results from the large, phase III trial in 392 patients showed that in combination with capecitabine lapatinib almost doubled time to progression when compared with capecitabine alone. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents [paclitaxel (Taxol), capecitabine and platinoids], hormonotherapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes are allowing us to bring patient-specific novel therapies such as lapatinib to the clinic.

[Asthenopia in VDT users: our experience]. / Astenopia e lavoro al VDT: nostra esperienza.

The aim of this study was to investigate the relationship between asthenopia and work with video display terminals (VDT). 62 office workers (29 males and 33 females), that use VDT for more than 20 hours each week, were investigated by means of standardized questionnaires (elaborated by the Italian Society of Occupational Medicine and Industrial Hygiene). The authors analyzed the prevalence of occupational asthenopia and its correlation with the duration of weekly VDT use and the presence of refractive alterations. It was demonstrated a prevalence of asthenopia of 51% and a statistically significant correlation between the entity of asthenopic symptoms and number of weekly hours and years of work at VDT, in particular in subjects with presbyopia.

[Hand-arm vibration syndrome and upper limbs diseases in the forest workers of Italia meridionale]. / Sindrome da vibrazioni mano-braccio e patologie degli arti superiori in lavoratori forestali dell'Italia meridionale.

Vibration exposure of the hand-arm system is associated with an increased risk of upper-limb vascular, neurological and musculoskeletal lesions, or hand-arm vibration syndrome (HAVS). The prevalence of occupational HAVS and upper-limb disorders was studied among 278 Forestry Service workers in Sicily and Calabria. Subjects who used chain-saws (18 weeks/year) had a greater prevalence of peripheral sensory-neural disturbances (28%), upper-limb musculoskeletal disorders (33%) and carpal tunnel syndrome (19%) compared with 260 manual workers from the same Corps not exposed to hand-transmitted vibration. Raynaud's phenomenon was comparable in exposed and control subjects (5.3% vs. 4.7%.) Upper-limb neuropathies were significantly associated with energy-equivalent frequency-weighted acceleration; exposure duration; and cumulative vibration dose (m2/s4h). The variable "years of work with vibrating tools" was strongly associated with peripheral neuropathies; carpal tunnel syndrome; and upper-limb musculotendinous syndromes. Data suggest that in Sicily and Calabria, where the climate is milder than in other areas of Italy, forestry work with hand-held vibrating tools does not entail a greater prevalence of peripheral vascular disorders (Raynaud's phenomenon), while the prevalence of occupational upper-limb neurological and musculoskeletal disorders, in which combined ergonomic and mechanical risk factors have a large pathogenic role, is significantly increased.

[Air pollution in urban areas as a risk factor for health in the general population and in workers. Environmental and biologic monitoring of 1-3 butadiene]. / L'inquinamento atmosferico delle aree urbane come fattore di rischio per la salute della popolazione generale e lavorativa. monitoraggio ambientale biologico dell'1-3 butadiene.

Exposure to 1,3-butadiene (BD), a probable carcinogen to humans, was investigated in two groups of subjects working in a refinery plant: 28 occupationally exposed workers and 21 subjects non-occupationally exposed controls. BD in blood was higher in the exposed workers than in controls. Excretion of urinary mercapturic acids N-acetyl-S-(3,4-hydroxybutyl)-l-cysteine (MI), was not influenced by occupational exposure. The present study shows that unmetabolised BD in biological fluids, represents the biomarker of choice for assessing occupational exposure to low airborne concentrations of BD.

Evaluation of fitness for work: the most challenging situations.

Evaluation of fitness for work (FW) is the final task of both health surveillance and risk evaluation. It's aim is to protect the physical and psychological health of workers and respect their professional skills. The Occupational Physician faces several difficulties in the evaluation of FW. Moreover, Italian legislation on this topic can be variously interpreted and this can cause conflicting evaluations. In this session, the most challenging situations in FW evaluation will be taken into consideration.

Nipple reconstruction using the fleur-de-lis flap technique.

The authors propose a simple and reliable technique for nipple reconstruction characterized by minimal loss in vertical projection.

Affective correlates of occupational exposure to whole-body vibration. A case-control study.

BACKGROUND: Exposure to whole-body vibrations (WBV) represents a highly diffuse occupational risk. Some studies report that chronic exposure to WBV induces a significant increment in the modifications of the cognitive and emotional area. The aim of this study was to investigate the long-term effects of WBV exposure on the neuropsychic and behavioural system. METHODS: The study population consisted of 137 male subjects, mean age 45.7 years, working as drivers of mechanical trolleys and occupationally exposed to WBV of a frequency below 2 m/s2. The Profile of Mood States was administered to all subjects in a maximum time of 10 min and in the same operative conditions. The results were compared with those of a homogeneous control group by means of an innovative statistical technique. RESULTS: The results show a significant difference in the response to the neurobehavioural test. The exposed group showed, in fact, a higher score compared with the controls for all 6 factors. In particular, the scores for factors F (fatigue-inertia), D (depression-dejection) and T (tension-anxiety) were more elevated, expressing a significant alteration of the psycho-affective status. Moreover, statistical analysis showed a correlation between exposure time and the score obtained for all factors in the exposed group. CONCLUSION: This study indicates that occupational exposure to WBV is associated with alterations of mood status and that these modifications are directly proportional to exposure time. Furthermore, our results show that psychological tests commonly used in psychopathologic diagnostics can be useful in monitoring alterations of psycho-emotional status determined by physical stressors.

Stressful life events and fibrinogen level in middle-aged teachers.

BACKGROUND: Strong evidence has been reported that a high plasmatic level of fibrinogen plays a central role in the development of coronary heart disease. Many researches showed that stressful life events lead to an increase in plasmatic fibrinogen. The present investigation examined the relationship between plasmatic fibrinogen level and stressful life events. SAMPLING AND METHODS: A sample of 40 middle-aged women employed as teachers underwent a general objective examination, a venous puncture for plasma fibrinogen level evaluation, and completed a questionnaire regarding health behaviours, at baseline and 1-year follow-up. The stressful life events were recorded using the Paykel's interview for recent life events. RESULTS: At the baseline assessment, the distribution of teachers in the two stress exposure groups was 16 women for the non-exposed group of teachers, and 24 for the exposed teachers, while at the 1-year follow-up assessment, it was 10 for the non-exposed and 30 for the exposed group. The number of teachers exposed to stress was significantly higher at the 1-year follow-up than at the baseline assessment (30 and 24, respectively; p < 0.05). Average levels of plasmatic fibrinogen were significantly higher in stress-exposed women than in non-exposed women both at baseline assessment (p < 0.01) and at 1-year follow-up (p < 0.002). Moreover, the mean value of fibrinogen at the follow-up assessment showed a higher increase in stressed women compared with non-stressed women with an annual increase of 10.71 and 5.40%, respectively. CONCLUSIONS: Stress may trigger the hypercoagulable state evidenced by an increased plasmatic fibrinogen level. This mechanism may help explain the adverse impact of stress on the cardiovascular system.