The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first-line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting.
Background.An increased cancer risk in sarcoidosis patients has been suggested, although results are conflicting in a number of case-control and cohort studies. We conducted a systematic review of all available data and performed a meta-analysis to better define and quantify the association between sarcoidosis and cancer. Methods.We searched Medline and Embase for all original articles on cancer and sarcoidosis published up to January 2013. Two independent authors reviewed all titles/abstracts to identify studies according to predefined selection criteria. We derived summary estimates using random effects model and reported as relative risk (RR). Publication bias was evaluated by using funnel plot and was quantified by Egger's test. Results.Sixteen original studies, involving more than 25,000 patients, were included in the present review. The summary RR to develop all invasive cancers was 1.19 (95% CI, 1.07-1.32). The results for selected cancer sites indicated a significant increased risk of skin (RR 2.00; 95% CI, 1.69-2.36), haematopoietic (RR 1.92; 95% CI, 1.41-2.62), upper digestive tract (RR 1.73; 95% CI, 1.07-2.79), kidney (RR 1.55; 95% CI, 1.21-1.99), liver (RR 1.79; 95% CI, 1.03-3.11) and colorectal cancers (1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (p=0.8), nor for any specific cancer site. Conclusions.The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.
Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ?70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.
Indication for the use of trastuzumab was given in Italy in 2000 for the treatment of HER-2 metastatic breast cancer and in 2006 for early stage breast cancer. Information on trastuzumab use and on its possible variation with age in Italy is however limited. Using health care administrative databases, we evaluated the prevalence of the use of trastuzumab, and the probability for administration since the first hospitalization for breast cancer in various age groups, in two series of Italian women diagnosed with breast cancer in the Lombardy region (2004-2009) and in the Palermo district. The ratio between trastuzumb users and patients with a hospitalization for breast cancer increased from 2.9% in 2004 up to 17.2% in 2009 in Lombardy. Patients aged <65 years were more frequent users (9.6%) compared to those aged ? 75 years (1.3%). Similarly, in the Palermo district the ratio increased from 10.6% in 2006 to 28.5% in 2008, with subjects aged <65 years more frequently using trastuzumab (19.1%), than subjects aged ? 75 years (6.2%). The age ratio between younger and older patients decreased over time in both settings (from 15 in 2004 to 10.2 in 2006, and 5.2 in 2009 in Lombardy, and from 4.0 in 2006 to 2.3 in 2009 in the Palermo district). The proportion of breast cancer patients using trastuzumab increased over time both in Lombardy and in Palermo district, though geographical differences persisted. Younger breast cancers patients were more likely to receive a trastuzumab treatment than elderly ones, but the difference declined over calendar period.
Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed trastuzumab-related cardiotoxicity and its predictors in a large cohort of Italian women.
Transbronchial needle aspiration (TBNA) is a safe and useful sampling technique for the diagnosis of mediastinal adenopathies/masses, but its accuracy seems to be influenced by selected clinical and procedural aspects.
Bullous pemphygoid is the most common blistering skin disease, characterized by an autoantibody response against two major hemidesmosomal antigens within the dermo-epidermal junction. We describe a proven case of bullous pemphigoid with extensive tracheobronchial involvement and with the only bronchoscopic images available in the published literature, to our knowledge. The patient, a 73-year-old woman with a medical history of bullous pemphigoid, was admitted to our hospital for dyspnea, productive cough, and blood-streaked sputum. She underwent bronchoscopy, which showed ulcerative tracheitis with fibrinous exudates. After antibiotic therapy, a repeat bronchoscopy revealed hemorrhagic vesciculobullous lesions in the subglottic area and at the level of the main bronchi. Pathologic evaluation, direct immunofluorescence microscopy examination, and enzyme-linked immunosorbent assay led to a definitive diagnosis of bullous pemphigoid. Due to the potential confounding presence of bacterial superinfection, the real prevalence of such manifestation of this disease is still unknown. Our experience should alert clinicians about this possible localization of bullous pemphigoid.
The aim of this study was to describe the clinical use of bevacizumab in Lombardy (9.5 million inhabitants), Italy, during 2006-2007 in patients with metastatic colorectal cancer (mCRC) to evaluate compliance with the Italian Medicine Agency (AIFA) indications, the incidence of adverse events, and the survival rate. We performed computerized record linkage among three different Lombardy health care databases: File F registry, Regional discharge database, and Registry Office records. Patients were classified into approved and off-label uses according to the AIFA indications. Treatment with bevacizumab was administered to 780 patients, of whom 81.7% (n = 637) had mCRC. Among these, 37.8% (n = 241) of patients received the drug in observance of AIFA indications. Overall, ?10% of patients had serious treatment-related toxicities (fistula, 3.5%; venous thromboembolism, 2.8%; hemorrhage, 1.9%; intestinal perforation and arterial thromboembolism, <1%). The 1-year survival rate was 74.3% and the 2-year survival rate was 39.2%. The median survival time was 20.5 months, and there were no meaningful differences between gender and age groups. There was a gap between the bevacizumab approved indication and clinical practice pattern: overall, less than one half of the patients received bevacizumab in observance with the regulatory indication. The main reason for nonadherence to the indication was use as a second-line or advanced line of therapy. The incidence of serious adverse events and the survival rates of mCRC patients were similar to those reported in clinical trials.
Over the last decade, mortality from oral and pharyngeal cancer has been declining in most European countries, but it had been increasing substantially in Hungary, Slovakia and a few other countries of central Europe, reaching rates comparable to those of lung cancer in several western European countries in males. To update trends in oral cancer mortality and further analyse the recent epidemic in central Europe, official death certifications for oral and pharyngeal cancer for 37 European countries were derived over the period 1970-2007, and an age-period-cohort model was fitted for selected countries. Male oral cancer mortality continued to decline in most European countries, including the Russian Federation, and, more importantly, it also started to decline in some of the countries with the highest male rates, i.e. Hungary and Slovakia; persisting rises were, however, observed in Belarus, Bulgaria and Romania. Oral cancer mortality rates for women were lower than in men and showed no appreciable trend over recent periods in the EU overall. Estimates from the age-period-cohort analysis for most selected countries showed a fall in effects for the cohorts born after the 1950s. For the period effect displayed a rise for the earlier periods, an inversion in the 1990 s and a continuous fall up to the last studied period. Only some former non-market economy countries, like Romania, Ukraine and Lithuania, had rising cohort effect trends up to most recent generations. The major finding of this updated analysis of oral cancer mortality is the leveling of the epidemic for men in most European countries, including Hungary and other central European countries, where mortality from this cancer was exceedingly high. These trends essentially reflect the changes in alcohol and tobacco consumption in various populations.
Preclinical findings suggest that aspirin might inhibit pancreatic carcinogenesis, but epidemiological data are scanty and controversial. The role of aspirin use in pancreatic cancer is further analyzed in a multicentric hospital-based case-control study conducted in Italy between 1991 and 2008. Cases were 308 patients with incident pancreatic cancer and controls were 477 patients admitted to the same hospitals as cases for acute conditions, not related to risk factors for pancreatic cancer. A total of 22 cases (7%) and 37 controls (8%) reported regular aspirin use, with a corresponding adjusted odds ratio (OR) of 0.87 [95% confidence interval (CI): 0.47-1.61]. A slight protection, although not significant, was observed for duration of use > or =5 years (OR=0.53; 95% CI: 0.21-1.33) and for time since first use > or =10 years (OR=0.69; 95% CI: 0.25-1.93). The risk of pancreatic cancer was significantly below unity for current users of > or =5 years (OR=0.23; 95% CI: 0.06-0.90), but the risk was based on three cases and 16 controls only. We observed no association between regular aspirin use and pancreatic cancer risk, although our results suggested a possible protective effect for long-term current users.
A higher incidence of cancer in scleroderma patients compared with the general population has been suggested by several observational studies, reporting, however, different estimates. Therefore, we aimed to perform a systematic review and meta-analysis to definitely assess this association.
In recent years, different bronchoscopic techniques have been proposed for the treatment of emphysema, with the aim of obtaining the same clinical and functional advantages of lung volume reduction surgical techniques while reducing risks and costs. Such techniques can be classified into: methods employing devices that block the airways (e.g. spigots and unidirectional valves), methods that have a direct effect on the lung parenchyma (polymeric lung volume reduction, coils and thermal vapor ablation) and procedures that facilitate the expiration of trapped air from the emphysematous lung (airway bypass). This review aimed to evaluate the indications, outcomes and safety of the different techniques, based on the evidence from the available literature. Results obtained by these methods are encouraging, but they are still based mainly on studies with small groups of patients. However, several trials are ongoing and in the near future we will acquire more knowledge which should lead to a better optimization of these procedures. Meanwhile, the bronchoscopic treatment of emphysema cannot yet be considered a standard of care and patients should be treated in the context of clinical trials or controlled registries, with well-defined programs of evaluation and follow-up.
The role of alcohol intake in the risk of Hodgkin lymphoma (HL) is still largely unclear. To summarize the evidence on the issue, we carried out a meta-analysis of the available studies. We identified eight case-control and two cohort studies, including a total of 1488 cases of HL. We derived meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and carried out a dose-risk analysis using nonlinear random-effects metaregression models. Compared with nondrinkers, the relative risk for alcohol consumers was 0.70 [95% confidence interval (CI), 0.60-0.81] overall, 0.66 (95% CI, 0.56-0.78) among case-control, and 0.92 (95% CI, 0.63-1.33) among cohort studies. Compared with nondrinkers, the pooled relative risks were 0.71 (95% CI, 0.57-0.89) for light (i.e. ?1 drink/day) and 0.73 (95% CI, 0.60-0.87) for moderate-to-heavy (i.e. >1 drink/day) alcohol drinking. This meta-analysis suggests a favourable effect of alcohol on HL, in the absence, however, of a dose-risk relationship. The inverse association was restricted to--or greater in--case-control as compared with cohort studies. This indicates caution in the interpretation of results.
In this study, we compared a purified aqueous extract and the corresponding nonpurified aqueous preparation under the same build-up protocol in bee venom allergic patients with a normal baseline mast cell tryptase concentration. Eighty patients with a history of a systemic reaction were enrolled for immunotherapy using a 5-day rush protocol. Patients treated with the purified extract and those treated with the non purified aqueous extract who developed a systemic reaction underwent maintenance therapy with the purified aluminium hydroxide adsorbed preparations. Patients treated with the nonpurified aqueous extract who did not experience a systemic reaction during the rush phase underwent the maintenance phase with that extract. Systemic reactions during the build-up phase occurred significantly more often in patients treated with nonpurified aqueous extract than in those treated with the corresponding purified aqueous preparations. During the one-year maintenance phase, no systemic reactions occurred in either of the groups. Neither age nor baseline mast cell tryptase concentration presented a significant correlation with the occurrence of a systemic reaction during the treatment, while the type of extract did. In conclusion, nonpurified aqueous extracts induced more frequent systemic reactions than the purified aqueous preparations, during the same rush protocol. The efficacy seemed to be comparable.
Rapid on-site evaluation (ROSE) of cytological specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions. ROSE is not a widespread technique, however, because of lack of time and resources. Our aim was to verify whether, in comparison with a board-certified cytopathologist, a pulmonologist could evaluate the adequacy of transbronchial needle aspiration (TBNA) specimens on-site to diagnose hilar/mediastinal adenopathies/masses after receiving training in cytopathology. Our secondary aim was to assess and compare the accuracy of ROSE as performed by both physicians.
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