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Biomedical subjects

Mostafa Fraig

Publications and source records attributed to Mostafa Fraig.

7 recordsLinked to original sources

Multiple/bilateral renal tumors in patients with Birt-Hogg-Dubé syndrome.

OBJECTIVE: To describe our findings in four patients with multiple/bilateral renal cell carcinoma (RCC) and Birt-Hogg-Dubé (BHD) syndrome. PATIENTS AND METHODS: A series of four patients with BHD syndrome and RCC is analyzed. Patient charts were reviewed for age, sex, presentation, various clinical manifestations, imaging, management and outcome. RESULTS: Patients included 2 males and 2 females. Age ranged from 40 to 65 years (mean 56 years). The interval between the diagnosis of skin lesions characteristic of the disease and the development of renal tumors ranged between 1 and 35 years. Three of the patients had bilateral renal tumors (2 synchronous and one metachronous), one patient had multiple renal tumors in one kidney. In one patient the renal mass was diagnosed with a screening CT scan of the abdomen after the diagnosis of BHD syndrome. One patient had associated spontaneous pneumothorax and thyroid tumor. Only one of the 4 patients had prior family history of BHD syndrome. Renal tumors were clear cell type in 3 patients, and chromophobe tumor in one. Tumor size ranged from 2 to 9 cm. CONCLUSION: BHD syndrome is associated with multiple diseases and tumors. We describe four patients with BHD syndrome with multiple or bilateral RCC. Two of the patients were asymptomatic. A high index of suspicion should be present in patients who present with the characteristic skin lesions of BHD syndrome and screening for the presence of renal tumors should be done in those patients. Long term follow up is necessary after treating renal tumors in these patients.

Adult↗

Accurate molecular detection of non-small cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration.

OBJECTIVES: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases. METHODS: Patients with NSCLC were evaluated with chest CT and positron emission tomography scans. Those patients without evidence of metastases (87 patients) underwent EUS-guided FNA. Lymph nodes from levels 2, 4, 5, 7, 8, and 9 were sampled and evaluated by standard cytopathology and real-time RT-PCR. Normal control FNA specimens were obtained from patients without cancer who were undergoing EUS for benign disease (17 control specimens). For each sample, messenger RNA was extracted and real-time RT-PCR was used to quantitate the expression of six lung cancer-associated genes (ie, CEA, CK19, KS1/4, lunx, muc1, and PDEF) relative to the expression of an internal control gene (beta(2)-microglobulin). RESULTS: Clinical thresholds of marker positivity were set at 100% specificity, as determined by the receiver operating characteristic curve analysis. Of the cytology-positive lymph nodes (27 lymph nodes), the expression of the KS1/4 gene was above its respective clinical threshold in 25 of 27 samples (93%), making this the most sensitive marker for the detection of metastatic NSCLC. At least one of the six lung cancer-associated genes was overexpressed in 18 of 61 cytology-negative patients (30%), of which KS1/4 was overexpressed in 15 of 61 patients (25%). CONCLUSIONS: Based on the high accuracy of EUS-guided FNA/RT-PCR, we predict that some of the patients in the cytology-negative/marker-positive category will have high NSCLC recurrence rates. Among the genes used in our marker panel, KS1/4 appears particularly useful for the detection of overt or occult metastatic disease.

Biomarkers, Tumor↗

Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography.

BACKGROUND: Computed tomography (CT) is the most common method of staging lung cancer. We have previously shown endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) to be highly accurate in staging patients with nonsmall cell lung cancer (NSCLC) who have enlarged mediastinal lymph nodes on CT scan. In this study we report the accuracy and yield of EUS-FNA in staging patients without enlarged mediastinal lymph nodes by CT. METHODS: Patients with NSCLC and CT scan showing no enlarged mediastinal lymph nodes (> 1 cm for all nodes except > 1.2 cm for subcarinal) in the mediastinum underwent EUS. Fine needle aspiration was performed on at least one lymph node, if present, in the upper mediastinum, aortopulmonary window, subcarinal, and periesophagus regions. Each specimen was evaluated with on-site cytopathology and confirmed with complete cytopathologic examination. RESULTS: Sixty-nine patients without enlarged mediastinal lymph nodes were evaluated. Endoscopic ultrasound detected malignant mediastinal lymph nodes in 14 of 69 patients as well as other advanced (American Joint Committee on Cancer [AJCC] stage III/IV) in 3 others (1 left adrenal, and 2 with mediastinal invasion of tumor) for a total of 17 of 69 (25%, 95% confidence interval: 16% to 34%) patients. Eleven additional patients were found to have advanced disease by bronchoscopy (2), mediastinoscopy (2), and thoracotomy with mediastinal lymph node dissection (7). The sensitivity of EUS for advanced mediastinal disease was 61% (49% to 75%), and the specificity was 98% (95% to 100%). CONCLUSIONS: Endoscopic ultrasound guided fine needle aspiration can detect advanced mediastinal disease and avoid unnecessary surgical exploration in almost one of four patients who have no evidence of mediastinal disease on CT scan. In addition to previously reported results in patients with enlarged lymph nodes on CT, these data suggest that all potentially operable patients with nonmetastatic NSCLC may benefit from EUS staging.

Adenocarcinoma↗

Detection of telomerase expression in mediastinal lymph nodes of patients with lung cancer.

Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined.

Adenocarcinoma↗

Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex-smokers, and never-smokers.

The clinical and pathologic features of 109 cases of respiratory bronchiolitis (RB) identified from review of 156 consecutive surgical lung biopsy specimens were studied. A total of 107 of the 109 cases (98%) occurred in smokers, including all 83 current smokers and 24 of 49 ex-smokers (49%). RB persisted in some patients for many years after stopping smoking, occurring in one third of patients 5 years after quitting, and in one patient 32 years afterwards. A correlation was found between degree of cytoplasmic pigmentation of macrophages and number of pack-years smoked and also between the presence of peribronchiolar fibrosis and number of pack-years. No correlation was found between pulmonary function test results and pathologic findings. A desquamative interstitial pneumonia-like reaction was observed in six individuals. One patient each with a desquamative interstitial pneumonia-like reaction and one with RB were diagnosed based on clinical findings with desquamative interstitial pneumonia and RB-associated interstitial lung disease, respectively. No histologic features distinguished desquamative interstitial pneumonia from a desquamative interstitial pneumonia-like reaction or RB-associated interstitial lung disease from RB. Five cases of variant RB were encountered that resembled RB except that macrophage cytoplasm lacked pigment. All occurred in never-smokers, and their significance is unknown. RB is an accurate histologic marker of cigarette smoking, and it may be found many years after smoking ceases. There are no reliable histologic features to distinguish RB-associated interstitial lung disease from RB or desquamative interstitial pneumonia-like reactions from desquamative interstitial pneumonia.

Adolescent↗