Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals.

AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls 179/137 and 30/15, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (NSCLC) sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. CONCLUSIONS: Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.

Morbidity and mortality after major pulmonary resections in patients with locally advanced stage IIIA non-small cell lung carcinoma who underwent induction therapy.

BACKGROUND: The optimal treatment for patients with locally advanced stage IIIA non-small cell lung carcinoma (NSCLC) remains controversial, but induction therapy is increasingly used. The aim of this study was to evaluate mortality, morbidity, hospital stay and frequency of postoperative complications in stage IIIA NSCLC patients that underwent major pulmonary resections after neoadjuvant chemotherapy or chemoradiation. METHODS: We conducted a retrospective analysis of all patients who underwent major pulmonary resections after induction therapy for locally advanced NSCLC from October 2009 to February 2014. Forty-one patients were included in the study. RESULTS: Complete resection was achieved in 40 patients (97.5%). A complete pathologic response was seen in 10 patients (24.4%). Mean hospital stay was 17.7 days (ranged 5-129 days). Early (in-hospital) mortality occurred in 2.4% (one patient after bilobectomy), late (six months) mortality in 4.9% (two patients after right pneumonectomy and bilobectomy), and overall morbidity in 58.5% (24 patients). Postoperative complications included: bronchopleural fistula (BPF) with empyema - three patients, empyema without BPF - five patients, air leak - eight patients, atrial fibrillation - eight patients, pneumonia - eight patients, and lobar atelectasis - four patients. CONCLUSION: Following neoadjuvant therapy for stage IIIA NSCLC, pneumonectomy can be performed with low early and late mortality (0% and 5.8%, respectively), bilobectomy is a high risk operation (16.7% early and 16.7% late mortality); and lobectomy a low risk operation (0% early and late mortality). The need for major pulmonary resections should not be a reason to exclude patients from a potentially curative procedure if it can be performed with acceptable morbidity and mortality rates at an experienced medical centre.

Lobectomy for non-small cell lung cancer: differences in morbidity and mortality between thoracotomy and thoracoscopy.

OBJECTIVE: Until the last decade, lobectomy by thoracotomy (TL) was the "gold standard" for treatment of patients with operable lung carcinoma. Today, video-assisted thoracic surgery lobectomy (VATS-L) has become accepted as a safe and effective procedure to treat early-stage lung cancer. We analyzed and compared postoperative complications, hospital stay, morbidity, and mortality after TL and VATS-L in patients with non-small cell lung carcinoma (NSCLC). METHODS: Between February 1998 and December 2007, we performed 326 TLs in patients with NSCLC. From December 2007, VATS-L was preferentially performed, and 63 cases of NSCLC patients underwent surgery using this method. Comorbidities were scaled according to the Charlson Comorbidity Index, and propensity scores between the TL and VATS-L patients were compared. RESULTS: Postoperative complications occurred in 142 TL patients (43.6%) and 17 VATS-L patients (27%), with 3.6% and 1.6% intrahospital mortality, respectively. There were no significant differences between the TL and VATS-L patients in Charlson Comorbidity Index or propensity scores, which led us to compare complications between TL and VATS-L groups and discovered that VATS-L patients had a shorter median length of stay (P < 0.001) and VATS-L was associated with a reduction in the occurrence of atrial fibrillation (P = 0.011) and offered benefits for patients with more significant comorbidities, for example, congestive heart failure patients (P = 0.042). CONCLUSIONS: Our clinical impression is that VATS-L offers advantages over TL in terms of lower morbidity, fewer and less serious complications, shorter hospital stays, and the possibility to operate on patients with more comorbidities.

Normal and elevated HbA1C levels correlate with severity of hypoxemia in patients with obstructive sleep apnea and decrease following CPAP treatment.

PURPOSE: Sleep apnea is associated with higher HbA1C levels in patients with and without diabetes but whether its severity correlates with HbA1C levels ranging from normal to abnormal is less clear. Also, the effect of continuous positive airway pressure (CPAP) treatment on HbA1C levels in patients with sleep apnea is controversial. METHODS: Thirty consecutive patients with obstructive sleep apnea were studied. None of the patients was previously diagnosed with diabetes. All patients underwent overnight polysomnography and HbA1C levels were determined. Patients were subdivided into three groups according to their HbA1C levels: <6% (n = 10), 6-6.5% (n = 10), and ≥6.5% (n = 10). Polysomnography and determination of HbA1C level were repeated in patients with severe sleep apnea (n = 12) following 3-5 months of CPAP treatment. RESULTS: HbA1C levels across the spectrum from normal to abnormal correlated with severity of hypoxemia (average SpO(2), r = -0.43, p = 0.019 and percent time with SpO(2) < 90%, r = 0.48, p = 0.007). HbA1C levels decreased from a mean of 6.47 ± 0.67% to a mean of 6.28 ± 0.51%, p = 0.038 in 12 patients with severe sleep apnea following 3-5 months of CPAP treatment. CONCLUSIONS: The severity of hypoxemia in patients with sleep apnea correlates with HbA1C levels ranging from normal to pre-diabetes and diabetes. CPAP treatment for 3-5 months decreases HbA1C levels in patients with severe sleep apnea.

Thoracic empyema in high-risk patients: conservative management or surgery?

We retrospectively analyzed the data of 119 patients who were treated for empyema thoracis from 1999 to 2007. There were 87 men with a mean age of 63.9 years (range, 19-79 years) and 32 women with a mean age 55.2 years (range, 26-78 years). The empyema was right-sided in 73 patients and left-sided in 46. The etiology was parapneumonic in 43.7% of cases, postoperative in 42.0%, posttraumatic in 11.8%, and due to other causes in 2.5%. Eight (6.7%) patients underwent surgery on admission because of unstable clinical status; all 8 survived. Fibrinolysis was used in 111 (93.3%) patients; of these, 88 (73.9%) were successfully treated by intrapleural urokinase instillation, and 23 (19.4%) failed treatment and underwent surgery. All 88 patients who had successful fibrinolytic therapy survived, they accounted for 1.8% of the morbidity. In the 23 patients who underwent surgery after failed treatment, there were 3 deaths, accounting for 2.7% overall mortality and 6.3% morbidity. Treating thoracic empyema in patients with significant comorbidities is challenging. Intrapleural urokinase administration might be beneficial in high-risk patients, but in those without significant comorbidities, early surgery may be considered.

Cervical mediastinoscopic lymphadenectomy for accurate staging in lung cancer.

Accurate preoperative staging of the mediastinum is important in the treatment of non-small-cell lung cancer. Enlarged mediastinal lymph nodes on chest computed tomography are positive for malignancy on mediastinoscopy in only half of these patients. After negative mediastinoscopy, some positive nodes are found at thoracotomy. The aim of this study was to attempt to remove all lymph nodes accessible by cervical mediastinoscopic lymphadenectomy and reevaluate the same mediastinal stations at thoracotomy for missed lymph nodes. Between 1999 and 2003, 30 patients with operable non-small-cell lung cancer and enlarged mediastinal lymph nodes (>1 cm in diameter on computed tomography) that were negative on cervical mediastinoscopy underwent pulmonary resection with complete lymph node dissection. The total number of lymph nodes dissected in these 30 patients was 329 (143 at mediastinoscopy and 186 at thoracotomy); the mean numbers of nodes dissected were 4.8 at mediastinoscopy and 6.2 at thoracotomy. Ten (6.5%) residual lymph nodes were detected at thoracotomy in mediastinal stations R4, L4, and 7. The low number of missed lymph nodes demonstrates the accuracy of the technique of cervical mediastinoscopic lymphadenectomy.

Three years of pulmonary rehabilitation: inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients. To date, however, there is no agreement for how long a rehabilitation program should be implemented. In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients. The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI). METHODS: A matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months. Eighty patients with moderate to severe COPD (age 63 +/- 7 years; FEV1 48% +/- 14) were recruited. The control group received standard care only, while in addition, the case study group received PR for duration of three years. These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked. RESULTS: The decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001). Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01). A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05). CONCLUSION: Three years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients.

Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study.

BACKGROUND: FEV(1) is used for the classification of disease severity and is a good predictor of COPD mortality. However, it is a poor predictor of clinical symptoms, exercise tolerance, and response to bronchodilators in COPD. Progressive reduction in inspiratory capacity (IC) during exercise reflects dynamic hyperinflation and is a good predictor of decreased exercise ability as well as increased exertional dyspnea. In animal models of COPD, N-acetylcysteine (NAC), an antioxidant/mucous modifier, has been shown to modify small airways, which mainly causes lung hyperinflation. OBJECTIVE: Our goal was to examine the effect of 1,200 mg/d of NAC on lung hyperinflation at rest and after exercise in patients with moderate-to-severe COPD. METHODS: This was a randomized, double-blind, cross-over study that included 24 eligible patients > 40 years of age with a diagnosis of COPD, a FEV(1) < 70% of predicted, FEV(1)/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to placebo treatment or NAC treatment twice daily for 6 weeks. This was followed by a 2-week washout period, and then patients were crossed over to alternate therapy for an additional 6 weeks. Evaluation was performed after each 6 weeks of each treatment. RESULTS: IC and FVC were higher especially after exercise after NAC treatment compared with placebo treatment. In addition, the relationship of residual volume to total lung capacity was reduced in a similar pattern. Furthermore, endurance time was longer after NAC treatment compared with placebo treatment. CONCLUSIONS: NAC treatment of patients with stable, moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00476736.

Gene expression subtraction of non-cancerous lung from smokers and non-smokers with adenocarcinoma, as a predictor for smokers developing lung cancer.

BACKGROUND: Lung cancer is the commonest cause of cancer death in developed countries. Adenocarcinoma is becoming the most common form of lung cancer. Cigarette smoking is the main risk factor for lung cancer. Long-term cigarettes smoking may be characterized by genetic alteration and diffuse injury of the airways surface, named field cancerization, while cancer in non-smokers is usually clonally derived. Detecting specific genes expression changes in non-cancerous lung in smokers with adenocarcinoma may give us instrument for predicting smokers who are going to develop this malignancy. OBJECTIVES: We described the gene expression in non-cancerous lungs from 21 smoker patients with lung adenocarcinoma and compare it to gene expression in non-cancerous lung tissue from 10 non-smokers with primary lung adenocarcinoma. METHODS: Total RNA was isolated from peripheral non-cancerous lung tissue. The cDNA was hybridized to the U133A GeneChip array. Hierarchical clustering analysis on genes obtained from smokers and non-smokers, after subtracting were exported to the Ingenuity Pathway Analysis software for further analysis. RESULTS: The genes subtraction resulted in disclosure of 36 genes with high score. They were subsequently mapped and sorted based on location, cellular components, and biochemical activity. The gene functional analysis disclosed 20 genes, which are involved in cancer process (P = 7.05E-5 to 2.92E-2). CONCLUSION: Detected genes may serve as a predictor for smokers who may be at high risk of developing lung cancer. In addition, since these genes originating from non-cancerous lung, which is the major area of the lungs, a sample from an induced sputum may represent it.

[Ophthalmoplegia and blindness associated with necrotizing sarcoid granuloma].

A 65 year old male, presented with ophthalmoplegia and reduced vision in his left eye. The magnetic resonance imaging (MRI) of the brain revealed three hyperintensity areas located in the left parasellar area, left lacrimal gland and right frontal bone. Chest CT revealed bilateral pulmonary masses. The pathological diagnosis was necrotizing granuloma and vasculitis. Nine months after the diagnosis, the right eye was involved. This case report presents a rare manifestation of blinding necrotizing sarcoid granulomatosis that had responded to steroid therapy, but had a relapsing clinical course.

Prevalence of chronic obstructive pulmonary disease among smokers aged 45 and up in Israel.

BACKGROUND: Chronic obstructive pulmonary disease is an increasing cause of chronic morbidity and mortality around the world. The major cause of the disease is smoking. Despite the gravity of the problem there is no knowledge of its rate in the Israeli smoking population. OBJECTIVES: To assess the prevalence of COPD and early lung cancer among smokers. METHODS: People aged 45 up to 75 with a history of at least 20 pack-years cigarette smoking, including quitters, were screened for COPD. They were interviewed and a spirometry was performed. RESULTS: Of the 1150 people recruited 92% underwent and performed acceptable spirometry; 22% of these subjects had airflow limitation and were diagnosed with COPD according to the GOLD classification. Only 4% had been diagnosed as COPD prior to this screening. The majority of those tested were unaware of or unconcerned about developing the disease. There was no correlation between pack-years smoking and development of COPD, but there was a relative correlation of pack-years smoking and severity of COPD, particularly in the older group (r = 0.42). CONCLUSIONS: About one-fifth of the smokers aged 45 and up developed COPD. There is a significant gap between the disease distribution and its awareness in the population at risk. The need for a national screening program and early diagnosis of COPD in people at risk is needed.

Large solitary fibrous tumour of the pleura: analysis of six cases.

BACKGROUND: A large solitary fibrous tumour of the pleura (SFTP) is a very rare occurrence. The aim of this study was to retrospectively review the clinical characteristics, surgical treatment and outcome of patients with a large SFTP operated on in our General Thoracic Surgery Unit. METHODS: We conducted a retrospective analysis of the clinical records of six patients who underwent surgery for a huge SFTP between 1998 and 2004. RESULTS: Six patients (four men and two women, mean age 73.3 years) with a large SFTP (mean diameter 20.3 and mean weight 1265 g) underwent surgery during this period with full excision of the tumour. Five tumours were excised together with the implantation basis, and in one case extended resection with pneumonectomy was performed. The presentation symptoms resolved in all cases after surgery. CONCLUSIONS: Despite the huge size of these tumours (giant SFTP), surgical resection is an acceptable method of treatment in elderly patients with low morbidity and mortality rates.

A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack.

STUDY OBJECTIVE: Noninvasive ventilation has been shown to be effective in patients with acute respiratory failure due to pulmonary edema and exacerbations of COPD. Its role in an acute asthmatic attack, however, is uncertain. The purpose of this pilot study was to compare conventional asthma treatment with nasal bilevel pressure ventilation (BPV) [BiPAP; Respironics; Murrysville, PA] plus conventional treatment in patients with a severe asthmatic attack admitted to the emergency department. DESIGN: A prospective, randomized, placebo-controlled study. SETTING: An emergency department at a university hospital. PATIENTS: Thirty patients with a severe asthma attack were recruited from a larger group of 124 asthmatic patients seen in the emergency department. Fifteen patients were randomly assigned to BPV plus conventional therapy and 15 patients to conventional therapy alone. The two groups had similar clinical characteristics on hospital admission. Mean (+/- SD) FEV(1) on recruitment was 37.3 +/- 10.7% in the BPV group and 33.8 +/- 10.2% in the control group (p = not significant). INTERVENTIONS AND MEASUREMENTS: BPV with predetermined inspiratory and expiratory pressures was applied for 3 h in the BPV group; in the control group, a similar sham device with subtherapeutic pressures was applied for 3 h. Bedside lung function test results and vital signs were obtained at baseline, and during and at the completion of the study protocol. RESULTS: The use of BPV significantly improved lung function test results. Eighty percents of the patients in the BPV group reached the predetermined primary end points (an increase of at least 50% in FEV(1) as compared to baseline), vs 20% of control patients (p < 0.004). Mean rise in FEV(1) was 53.5 +/- 23.4% in the BPV group and 28.5 +/- 22.6% in the conventional treatment group (p = 0.006). The intention-to-treat analysis of the secondary end point rate of hospitalization included 33 patients. Hospitalization was required for 3 of 17 patients (17.6%) in the BPV group, as compared with 10 of 16 patients (62.5%) in the control group (p = 0.0134). CONCLUSION: In selected patients with a severe asthma attack, the addition of BPV to conventional treatment can improve lung function, alleviate the attack faster, and significantly reduce the need for hospitalization.