Sherif Mohamed

Analysis of cell cycle-related proteins in mediastinal lymph nodes of patients with N2-NSCLC obtained by EBUS-TBNA: relevance to chemotherapy response

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate tool for lymph node staging of non-small cell lung cancer (NSCLC). Most patients with NSCLC require systemic chemotherapy during their treatment, with relatively poor responses. If the response to chemotherapy could be predicted, ideally at the time of the initial bronchoscopic examination, the therapeutic benefit could be maximised while limiting toxicity. A study was therefore undertaken to investigate the feasibility of EBUS-TBNA for obtaining tissue samples from mediastinal lymph nodes that can be used for immunohistochemical analysis, and to stratify patients with molecular-based pN2-NSCLC into chemo-responsive and chemoresistant subgroups who might benefit from tailoring of chemotherapy. Methods: The expression of six cell cycle-related proteins (pRb, cyclin D1, p16INK4A, p53, p21Waf1, Ki-67) in mediastinal lymph node specimens obtained by EBUS-TBNA was investigated by immunohistochemistry in 36 patients with pN2-NSCLC. Their predictive role(s) in the response to platinum-based chemotherapy was examined. Results: Immunostaining was feasible in all studied specimens. Univariate analysis revealed that p53 and p21Waf1 expressions were significantly related to the response to chemotherapy (p = 0.002 and p = 0.011, respectively). Multivariate logistic regression analysis revealed that only p53 overexpression was associated with a poor response to chemotherapy (p = 0.021). Conclusions: These results suggest that EBUS-TBNA is a feasible tool for obtaining mediastinal nodal tissue samples amenable for immunohistochemical analysis. Immunostaining of p53 in EBUS-TBNA-guided specimens may be useful in predicting the response to chemotherapy in patients with N2-NSCLC and helping in the selection of patients who might benefit from certain chemotherapeutic strategies.

Nuclear survivin in pN2 nonsmall cell lung cancer: prognostic and clinical implications

Patients with N2 nonsmall cell lung cancer (N2-NSCLC) represent heterogeneous groups. Survivin is a member of the inhibitor of apoptosis family. If N2-NSCLC patients could be stratified, based on survivin expression and/or its relation to cell cycle proteins, into homogeneous subgroups, certain therapies could be selected for those patients. Survivin expression in 78 surgically resected primary pathological N2-NSCLC tumours was evaluated using immunohistochemistry. Relationships of survivin expression to overall survival, clinical features and expression of six cell cycle-related proteins (pRb, cyclin D1, p16INK4A, p53, p21Waf1 and Ki-67) were analysed. Nuclear survivin and the number of mediastinal lymph node (LN) stations were independent prognostic factors. The patient group with combined negative survivin/single mediastinal LN station were the most favourable prognostic group, and was related to the clinical nodal factor. Indeed, patients with negative survivin/low Ki-67 labelling indices had the best survival, especially in nonsquamous histopathology. The current authors conclude that nuclear survivin is strongly related to lymph node metastasis and proliferative potentials in pathological N2 nonsmall cell lung cancer patients. Pre-operative N2 nonsmall cell lung cancer patients with combined negative nuclear survivin and a single mediastinal lymph node station, or low proliferative indices, particularly in clinical N0-1 disease and nonsquamous histopathology, respectively, are expected to have a favourable post-operative prognosis and may be candidates for primary resection.

Bronchial and Nonbronchial Systemic Artery Embolization in Management of Hemoptysis: Experience with 348 Patients

Background. We aimed to report our experience with bronchial artery embolization (BAE) in the management of moderate recurrent and/or life-threatening hemoptysis. Methods. We evaluated the demographics, clinical presentation, radiographic studies, short- and long-term efficacy, and complications in patients Who underwent BAE, at a tertiary university hospital, from 2003 to 2012. Results. Three hundred forty-one patients underwent BAE for the management of moderate recurrent or life-threatening hemoptysis. Pulmonary TB and bronchiectasis were the most common etiologies for hemoptysis in our locality. The most common angiographic signs for hemoptysis were hypervascularity and systemic-pulmonary artery shunt. BAE was successful in controlling hemoptysis immediately in 95% of patients and at 1 month in 90% of patients. Recurrence of hemoptysis was observed in 9.6% of patients, and reembolization was indicated in 85% of those cases. Complications of BAE were self-limited acute and subacute complications, while chronic complications were not recorded during this study. Conclusions. TB and bronchiectasis are the commonest etiologies for moderate recurrent or life-threatening hemoptysis in our locality. Hypervascular lesions from the bronchial arteries and nonbronchial systemic arteries represented the major vascular abnormalities. Bronchial and nonbronchial systemic artery embolizations were effective to control both acute and chronic hemoptyses, with no serious complications.

Diagnostic Utility of Transbronchial Needle Aspiration in Malignant Endobronchial Lesions: Relevance to Lesions’ Characteristics

In this prospective study, we aimed to report our experience with the diagnostic utility of transbronchial needle aspiration (TBNA) in patients with malignant endobronchial lesions detected during routine bronchoscopy. Ninety-four patients were enrolled. TBNA and conventional diagnostic techniques (CDTs: forceps biopsy, brushing, and washing) were performed in all patients. Endobronchial lesions were classified into exophytic mass lesions (EMLs), submucosal disease (SD), and peribronchial disease (PD). The diagnostic yields of TBNA and CDT alone and together were compared according to the lesions’ types, histopathology, and locations. During 3-year period, the addition of TBNA to CDT improved bronchoscopic sensitivity from 70.2% to 94.7% in all lesion types. Addition of TBNA to CDT increased the diagnostic success from 74% to 95% and from 50% to 94% in NSCLC and SCLC, respectively. The diagnostic success was increased in all localizations by the addition of TBNA to CDT, particularly for lesions located at the trachea, main bronchi, and upper lobes. We conclude that the addition of TBNA to CDT increases the diagnostic yield in patients with visible malignant endobronchial lesions, particularly in peribronchial disease, and improves the diagnostic yield of bronchoscopy, in both NSCLC and SCLC and in all bronchoscopic locations, particularly in central and upper lobar lesions.

Evaluation of pulmonary function changes in children with type 1 diabetes mellitus in Upper Egypt

Background: Diabetes mellitus is a leading cause of morbidity and mortality among children across the world and is responsible for a growing proportion of global healthcare expenditure. However, limited data are available on lung dysfunction in children with diabetes. Aim: The aim of this study was to evaluate the pulmonary function changes in children with type 1 diabetes mellitus (T1DM). Methods: We studied 60 children with T1DM (mean age 10.5 ± 2.32 years; disease duration 2.45 ± 0.6 years, and 50 healthy control children (mean age 9.9 ± 2.5 years). Spirometry was performed for all individuals to measure forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and peak expiratory flow rate (PEFR). Glycemic control was assessed on the basis of glycated hemoglobin (HbA1c), with HbA1c values <8% considered to indicate good glycemic control, and HbA1c values ⩾8% to indicate poor control. Results: There was significant reduction in all spirometeric parameters in diabetic children in comparison with healthy control children. Children with poor glycemic control had significant impairment in lung functions compared with those with good glycemic control. Conclusions: T1DM in children leads to impairment of lung functions and this impairment increases with poor glycemic control.