Andrea Imperatori

Lung cancer in Teesside (UK) and Varese (Italy): a comparison of management and survival

Background: The survival of lung cancer patients in the UK is lower than in other similar European countries. The reasons for this are unclear. Methods: Two areas were selected with a similar incidence of lung cancer: Teesside in Northern England and Varese in Northern Italy. Data were collected prospectively on all new cases of lung cancer diagnosed in the year 2000. Comparisons were made of basic demographic characteristics, management, and survival. Results: There were 268 cases of lung cancer in Teesside and 243 in Varese. Patients in Teesside were older (p<0.05), were more likely to have smoked (p<0.001), had a higher occupational risk (p<0.001), higher co-morbidity (p<0.05), and poorer performance status (p<0.001). Fewer patients in Teesside presented as an incidental finding (p<0.001) and the histological confirmation rate was lower than in Varese (p<0.01). In Teesside there were more large cell carcinomas (p<0.001), more small cell carcinomas (p<0.05), and fewer early stage non-small cell lung cancers (p<0.05). The resection rate was lower in Teesside (7% v 24%; p<0.01) and more patients received no specific anti-cancer treatment (50% v 25%; p<0.001). Overall 3 year survival was lower in Teesside (7% v 14%; p<0.001). Surgical resection was the strongest multivariate survival predictor in Varese (HR = 0.46) and Teesside (HR = 0.31). Co-morbidity in Teesside resulted in a significantly lower resection rate (p<0.001). Conclusions: Patients with lung cancer in Teesside presented at a later stage, with more aggressive types of tumour, and had higher co-morbidity than patients in Varese. As a result, the resection rate was significantly lower and survival was worse.

The role of the bronchial microvasculature in the airway remodelling in asthma and COPD

In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.

Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.

BackgroundAtrial fibrillation (AF) after thoracic surgery is a continuing source of morbidity and mortality. The effect of postoperative AF on long-term survival however has not been studied. Our aim was to evaluate the impact of AF on early outcome and on survival > 5 years after pulmonary lobectomy for lung cancer.MethodsFrom 1996 to June 2009, 454 consecutive patients undergoing lobectomy for lung cancer were enrolled and followed-up until death or study end (October 2010). Patients with postoperative AF were identified; AF was investigated with reference to its predictors and to short- and long-term survival (> 5 years).ResultsHospital mortality accounted for 7 patients (1.5%), while postoperative AF occurred in 45 (9.9%). Independent AF predictors were: preoperative paroxysmal AF (odds ratio [OR] 5.91; 95%CI 2.07 to 16.88), postoperative blood transfusion (OR 3.61; 95%CI 1.67 to 7.82) and postoperative fibro-bronchoscopy (OR 3.39; 95%CI 1.48 to 7.79). Patients with AF experienced higher hospital mortality (6.7% vs. 1.0%, p = 0.024), longer hospitalization (15.3 ± 10.1 vs. 12.2 ± 5.2 days, p = 0.001) and higher intensive care unit admission rate (13.3% vs. 3.9%, p = 0.015). The median follow-up was 36 months (maximum: 179 months). Among the 445 discharged subjects with complete follow-up, postoperative AF was not an independent predictor of mortality; however, among the 151 5-year survivors, postoperative AF independently predicted poorer long-term survival (HR 3.75; 95%CI 1.44 to 9.08).ConclusionAF after pulmonary lobectomy for lung cancer, in addition to causing higher hospital morbidity and mortality, predicts poorer long-term outcome in 5-year survivors.

CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation

Recent studies suggested that human CD56brightCD16− NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56dimCD16+ and CD56brightCD16− NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56brightCD16− than in CD56dimCD16+ NK cells. CD57 was mostly expressed by CD56dimCD16+ NK cells. CD203a/PC-1 expression was restricted to CD56brightCD16− NK cells. CD56brightCD16− NK cells produce ADO and inhibit autologous CD4+ T cell proliferation. Such inhibition was 1) reverted pretreating CD56brightCD16− NK cells with a CD38 inhibitor and 2) increased pretreating CD56brightCD16− NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56brightCD16− NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4+ T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56brightCD16− NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56brightCD16− NK cells act as “regulatory cells” through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune/inflammatory diseases.

Risk Factors in Surgery

Abstract Improved surgical and anesthetic techniques and postoperative care have not significantly changed wound infection rates over the last 30 years. Many risk factors, related both to the host and to the surgical practice, have been identified in different studies. Control of nosocomial infections has become more challenging recently, due to a widespread bacterial resistance to antibiotics and to more frequent surgical indications in elderly patients at increased risk. A change in the microbiology of postoperative infections has also been noticed, characterized by a greater incidence of infections caused by methicillin-resistant Staphylococcus aureus, by polymicrobic flora and by fungi. This paper reviews the most important risk factors encountered in general surgery, that we observed during a 6-year prospective study of wound infection carried out in our Department of Surgery at the University of Insubria in Varese. Furthermore, the epidemiologic data on wound infections recorded in 4,002 patients undergoing general surgical procedures (mostly gastrointestinal operations), are presented and discussed.

High-Dose Intravenous IgG for Treatment of Severe Surgical Infections

113 severely septic surgical patients, with an initial sepsis score ≧ 17 (mean: 23 ± 4) were prospectively randomized to receive either high-dose intravenous IgG (IVIG group) or placebo (control group

Peri-operative complications of video-assisted thoracoscopic surgery (VATS)

Video-assisted thoracoscopic surgery (VATS) has multiple indications for diagnosis and treatment of many different thoracic diseases; the commonest are lung wedge resection, pleural and mediastinal biopsy, treatment of pneumothorax, and pleurectomy. Moreover, in recent years a few surgeons have performed routinely major lung anatomic resections by VATS approach, including segmentectomy, lobectomy and pneumonectomy. In our experience VATS constitutes about one-third of all thoracic surgical procedures. In the reviewed literature as in the most frequent complications after VATS procedures are: prolonged air leak, bleeding, infection, postoperative pain, port site recurrence and the need to convert the access in thoracotomy. The complication and mortality rates are generally very low and VATS procedures are considered safe and effective. It is recommended that all thoracic surgery departments audit their VATS procedures for peri-operative morbidity and mortality to compare results and outcomes.

Infections in 346 Consecutive Video-Assisted Thoracoscopic Procedures

BACKGROUND Postoperative infections, as related to risk factors, in patients undergoing video-assisted thoracoscopic surgery (VATS) procedures have been studied infrequently. MATERIALS AND METHODS We evaluated 346 consecutive patients who underwent VATS procedures between October 1996 and June 2002 at our center. Patients preoperatively were free of chest infections and were divided into two groups: Group A (n = 139) who underwent lung wedge resection; group B (n = 207), who underwent pleural biopsy (n = 183) or biopsy of a mediastinal mass (n = 24). We recorded prospectively the following preoperative infection risk parameters: Hemoglobin concentration, hematocrit, serum albumin concentration, lymphocyte count, length of preoperative stay, duration of surgery, blood transfusion, age, comorbidity, and chronic obstructive pulmonary disease specifically (COPD, measured as FEV(1) <70% of expected). Short-term antibiotic prophylaxis was given to 94% of patients in group A and to 90% of patients in group B. As outcome measures we recorded the occurrence of postoperative infections within 30 days (surgical site infection, pneumonia, empyema) and the final patient outcome. RESULTS Patients who developed postoperative infections (all the above types included) were 17/346 (4.9%), the difference between group A (5.0%) and group B (4.8%) being not significant. The overall surgical site infection rate was 1.7%. Groups A and B showed a similar incidence of surgical site infection (2.8% vs. 1.0%; p = NS), of pneumonia (2.8% vs. 3.4%; p = NS), and of empyema (0.7% vs. 2.0%; p = NS). Among assessed infection risk parameters, a FEV(1) <70% of expected was the only parameter associated with a significantly increased incidence of surgical site infection (p < 0.05). CONCLUSIONS This prospective study confirms that the wound infection rate is low (1.7%) after minimally invasive VATS procedures. The cumulative incidence of postoperative infections (including wound infection, pneumonia, empyema) was similar after lung wedge resection and after pleural or mediastinal mass biopsy procedures. Among the infection risk parameters, COPD was the only parameter associated with a significantly increased incidence of postoperative infection. Our results suggest that patients with COPD who undergo VATS for lung wedge resections and for pleural/mediastinal biopsy should receive antibiotic prophylaxis to prevent surgical site infection.

Microwave ablation therapy for treating primary and secondary lung tumours: technical note

PurposeThe purpose of our study was to retrospectively evaluate the feasibility, safety and effectiveness of microwave ablation (MWA) in nine patients with unresectable lung tumour.Materials and methodsTen lesions were treated in ten ablation sessions in nine patients. The treatments were performed with a microwave generator with 45 W and 915 MHz connected to a 14.5-gauge antenna for 10 min. Antenna placement was performed with computed tomography (CT) fluoroscopy guidance or XperGuide. All patients underwent CT follow-up at 1, 3 and 6 months from the procedure.ResultsTechnical success was obtained in all cases; mortality at 30 days was 0%.ConclusionsThis study shows that in selected patients, MWA is a valid alternative to other ablative techniques. Further studies are required to demonstrate the short- and long-term effects of this technique and to make a comparison with other available ablation systems, especially with radiofrequency.RiassuntoObiettivoLo scopo dello studio è stato quello di valutare il successo tecnico, la sicurezza, l’efficacia della metodica del trattamento ablativo mediante microonde (MW) in 9 pazienti affetti da neoplasia polmonare non trattabile chirurgicamente.Materiali e metodiSono state trattate 10 masse polmonari in 10 sessioni d’ablazione in 9 pazienti. È stato utilizzato un sistema ablativo costituito da un generatore di MW a 45 W e 915 MHz connesso ad un antenna 14,5 G, per un tempo di ablazione totale di 10 minuti. Il posizionamento dell’antenna è stato eseguito sotto guida fluoro-tomografia computerizzata (TC) o XperGuide. I pazienti sono stati sottoposti a follow-up mediante TC a 1, 3, 6 mesi dalla procedura.RisultatiSi è ottenuto un successo tecnico in tutti i casi; il tasso di mortalità a 30 giorni è stato dello 0%.ConclusioniQuesto studio dimostra che, in pazienti selezionati, la termoablazione con microonde rappresenta una valida alternativa ad altre tecniche ablative. Sono tuttavia necessari ulteriori studi per confermare a breve e lungo termine l’efficacia di questa metodologia e permettere un confronto con altri sistemi ablativi, in particolare rispetto alla radiofrequenza.

Self-Selection Effects in Smokers Attending Lung Cancer Screening: A 9.5-Year Population-Based Cohort Study in Varese, Italy

Background: We hypothesize that mortality risk profile of participants and nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be different. Methods: In 1997, a population-based cohort of 5815 smokers of Varese Province was invited to nonrandomized LC screening by annual chest x-ray examination for 4 years. LC risk factors and screening participation rate were recorded. Except for screening, the whole cohort received usual care. After 9.5-year observation, we compared mortality of participants versus nonparticipants by assessing age-standardized all-cause mortality rate ratio (MRR) and disease group-specific MRR with 95% confidence intervals (95% CI). Results: Self-selected screening participants were 21% of cohort. Participants were younger (p < 0.001), were more frequently current smokers (p = 0.019), had more pack-years of smoking (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic regression analysis familial LC, occupational risk and pack-years smoked were significant predictors of participation in screening and of developing LC. Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95% CI, 0.53–0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41–0.91), cardiovascular diseases MRR = 0.38 (95% CI, 0.22–0.63), and noncancer disease other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34–0.92). The LC mortality (MRR = 1.40; 95% CI, 1.03–1.91) was higher in participants relative to nonparticipants (p = 0.031). Conclusion: The selection effect in LC screening participants was dual: healthy effect and higher LC mortality. In assessing the overall effectiveness of LC screening on a population level, a higher LC mortality risk in participants should be considered.