Martina Bonifazi

Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies

OBJECTIVES 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. METHODS We searched MEDLINE and Embase for all original articles of observational studies on cancer incidence in scleroderma patients without language restriction published up to December 2011. Two independent authors reviewed all titles/abstracts and retrieved detailed full-text of potentially relevant articles to identify studies according to predefined selection criteria. Summary estimates were derived using random-effects model and reported as relative risk (RR). Publication bias was evaluated by trim and fill analysis. RESULTS From articles initially identified, 16 original studies, involving more than 7000 patients, were included in the present review. Compared with the general population, the summary RR to develop all invasive cancers in scleroderma patients was 1.75 (95% CI 1.41, 2.18). The results for selected cancer sites indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08, 9.09), and a significant increased risk also for haematological neoplasms (RR 2.24; 95% CI 1.53, 3.29). The relation with breast cancer, suggested in some previous epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29). CONCLUSION The present meta-analysis, the first on scleroderma and cancer risk, provides definite estimates on the association between scleroderma and cancer.

Safety and Diagnostic Yield of Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Diseases: A Comparative Study versus Video-Assisted Thoracoscopic Lung Biopsy and a Systematic Review of the Literature.

Background: A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. Objectives: The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. Methods: We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). Results: A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11). Conclusion: Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.

Sarcoidosis and Cancer Risk : Systematic Review and Meta-analysis of Observational Studies

BACKGROUND An increased cancer risk in patients with sarcoidosis 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 a random-effects model and reported them as relative risk (RR). Publication bias was evaluated using a funnel plot and was quantified by the Egger test. RESULTS Sixteen original studies, involving > 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 significantly increased risk of skin (RR, 2.00; 95% CI, 1.69-2.36), hematopoietic (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 (RR, 1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (P = .9), nor for any specific cancer site. CONCLUSIONS The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.

Bronchoscopic Treatment of Emphysema: State of the Art

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.

Original Research: Diffuse Lung DiseaseSarcoidosis and Cancer Risk: Systematic Review and Meta-analysis of Observational Studies

BACKGROUND An increased cancer risk in patients with sarcoidosis 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 a random-effects model and reported them as relative risk (RR). Publication bias was evaluated using a funnel plot and was quantified by the Egger test. RESULTS Sixteen original studies, involving > 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 significantly increased risk of skin (RR, 2.00; 95% CI, 1.69-2.36), hematopoietic (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 (RR, 1.33; 95% CI, 1.07-1.67). There was no evidence of publication bias for all cancers (P = .9), nor for any specific cancer site. CONCLUSIONS The present meta-analysis suggests a significant, though moderate, association between sarcoidosis and malignancy.

Aspirin use and pancreatic cancer risk

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 ≥5 years (OR=0.53; 95% CI: 0.21–1.33) and for time since first use ≥10 years (OR=0.69; 95% CI: 0.25–1.93). The risk of pancreatic cancer was significantly below unity for current users of ≥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.

An Age-Period-Cohort Analysis of Gastric Cancer Mortality from 1950 to 2007 in Europe

PURPOSE To analyze the components of the favorable trends in gastric cancer in Europe. METHODS From official certified deaths from gastric cancer and population estimates for 42 countries of the European geographical region, during the period 1950 to 2007, age-standardized death rates (World Standard Population) were computed, and an age-period-cohort analysis was performed. RESULTS Central and Northern countries with lower rates in the 2005 to 2007 period, such as France (5.28 and 1.93/100,000, men and women respectively) and Sweden (4.49 and 2.21/100,000), had descending period and cohort effects that decreased steeply from the earliest cohorts until those born in the 1940s, to then stabilize. Former nonmarket economy countries had mortality rates greater than 20/100,000 men and 10/100,000 women, and displayed a later start in the cohort effect fall, which continued in the younger cohorts. Mortality remained high in some countries of Southern and Eastern Europe. CONCLUSIONS The decrease in gastric cancer mortality was observed in both cohort and period effects but was larger in the cohorts, suggesting that the downward trends are likely to persist in countries with higher rates. In a few Western countries with very low rates an asymptote appears to have been reached for cohorts born after the 1940s, particularly in women.

Trastuzumab-Related Cardiotoxicity in Early Breast Cancer: A Cohort Study

BACKGROUND 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. METHODS Through a record linkage between four regional health care databases, we identified the rate of severe cardiac adverse events among women treated with trastuzumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model. RESULTS Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity increased up to 2 years after starting treatment, reaching a plateau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged ≥70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence interval [CI]: 3.5-36.6) for women aged ≥70 years as compared with those <50 years of age. Hazard ratio was 4.4 (95% CI: 2.1-9.5) for women with a history of cardiac disease compared with those without a history of cardiac disease. CONCLUSIONS Cardiotoxicity of trastuzumab varies considerably across subgroups of patients. The long-term safety profile was less favorable than in the largest clinical trial. Strategies to reduce cardiotoxicity in high-risk women should be investigated.

The role of the pulmonologist in rapid on-site cytologic evaluation of transbronchial needle aspiration: a prospective study.

BACKGROUND Rapid on-site cytologic evaluation (ROSE) of cytologic specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions. ROSE is not a widespread technique, however, because of a 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. METHODS A pulmonologist and a cytopathologist, the latter deemed the gold standard, performed ROSE and classified specimens into five diagnostic categories. Agreement between clinicians was assessed through κ statistics. The accuracy of ROSE was established according to definitive cytologic assessment. RESULTS A total of 362 TBNAs were performed on 84 patients affected by hilar/mediastinal lymphadenopathies. There was an 81% overall substantial agreement between observers (κ, 0.73; 95% CI, 0.61-0.86; P , 0.001), which became excellent in cases of malignant disease (κ, 0.81; 95% CI, 0.70-0.90; P , 0.001). The accuracy of ROSE performed by the pulmonologist (80%; 95% CI, 77-90) was not statistically different from that provided by the cytopathologist (92%; 95% CI, 85-94). CONCLUSIONS Our study provides the first evidence, to our knowledge, that a trained pulmonologist can assess the adequacy of cytologic smears on-site. Training pulmonologists to have a basic knowledge of cytopathology could obviate most difficulties related to the involvement of cytopathologists in routine diagnostic activities and may reduce the costs of the procedure.

Transbronchial Needle Aspiration: A Systematic Review on Predictors of a Successful Aspirate

Background: 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. Objectives: We performed a systematic review to identify the main predictors of a successful transbronchial aspirate according to different clinical settings. Methods: We searched Medline and Embase for all studies evaluating predictors of TBNA diagnostic yield, published up to February 2012. Two authors reviewed all titles/abstracts and retrieved the full text of articles that are potentially relevant to identify studies according to predefined selection criteria. The methodological quality of studies was assessed through the revised Quality Assessment of Diagnostic Accuracy Studies tool. Evidence synthesis was graded according to overall number of studies, patients involved and methodological features. Results: Fifty-three studies, involving more than 8,000 patients and evaluating 23 potential predictive factors, were included. Major predictors in an unselected population, as well as in patients with suspected/known lung cancer, included lymph node size (short axis length ≥2 cm), presence of abnormal endoscopic findings, subcarinal and right paratracheal location, and the use of histological needle by an experienced bronchoscopist. Stage I and sampling of more than one lymph node stations were the only predictors of a successful TBNA result in patients with suspected sarcoidosis. Conclusions: The diagnostic yield of TBNA depends on selected clinical and procedural features. Knowledge of factors that predict a positive TBNA result may help optimize the diagnostic success of the procedure in different clinical settings.