Mark I. Block

Accuracy of EUS in staging of T4 lung cancer

BACKGROUND Increasingly, EUS is being used to stage lung cancer. Direct mediastinal invasion (T4) by lung cancer is stage IIIb disease. Patients in this stage have a 5-year survival of less than 5% and generally are offered chemotherapy without surgery. This study evaluated the accuracy of EUS in detecting T4 lung cancer. METHODS The study included all patients with lung cancer who had EUS staging and subsequent staging at surgery, or for whom there was unequivocal confirmation of unresectability (T4) by thoracoscopy, thoracotomy or presence of malignant pleural effusion, or definite invasion of great vessels/adjacent organs on CT. RESULTS A total of 175 of 308 patients with lung cancer who underwent EUS over a 5-year period (1997-2002) had subsequent confirmatory tumor staging. Ten patients were found by EUS to have stage T4 tumors; 7 were confirmed to be T4 by either surgical exploration (2), CT demonstration of aortic invasion (3), or documentation of malignant pleural effusion (2). Three of the 10 (30%) patients found to have stage T4 tumors by EUS had T2 disease at surgery and underwent curative resection. Of the remaining 165 patients without evidence of T4 disease at EUS, only one was found to have aortic invasion (T4) at surgery. EUS had a sensitivity of 87.5%, specificity of 98%, positive predictive value of 70%, and a negative predictive value of 99% for detecting T4 disease. CONCLUSIONS Caution is warranted when unresectability of lung cancer is based solely on tumor invasion into mediastinal soft tissue at EUS. Overstaging occurs when a tumor appears to invade the pleural layer without mediastinal organ invasion. Confirmation of unresectability by other diagnostic modalities is warranted in such instances.

Lunx Is a Superior Molecular Marker for Detection of Non-Small Lung Cell Cancer in Peripheral Blood

The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.

Real-Time Reverse Transcription-PCR Detects KS1/4 mRNA in Mediastinal Lymph Nodes from Patients with Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most common cancer-related cause of death for both men and women in the US. Standard therapies for patients with NSCLC include surgery, chemotherapy, and radiation therapy, and the stage of disease dictates choice of therapy. The current staging system for lung cancer uses the American Joint Committee on Cancer TNM system, and its goal is to classify patients into groups based on the extent of disease. This system relies heavily on the pathologic evaluation of the primary tumor (T), regional nodes (N), and distant metastases (M). Patients in whom mediastinal lymph nodes (MLNs) are involved (N2 or N3) are classified with stage III disease (1) and are generally considered inoperable. The recent identification of genes overexpressed in lung cancer (2)(3)(4) combined with advances in real-time reverse transcription-PCR (RT-PCR) provide the opportunity to establish sensitive and specific ways to analyze MLNs. In addition, molecular biology approaches using real-time RT-PCR are well suited to the analysis of lymph node tissue procured through minimally invasive procedures such as endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This technique enables reliable biopsy of MLNs without the need for general anesthesia or surgery (5). Given the advantages of EUS-FNA, we investigated the possibility that metastatic disease could be reliably detected in MLNs of NSCLC patients by real-time RT-PCR. To define the ability of real-time RT-PCR to detect metastatic NSCLC in MLNs, we procured by EUS-FNA nine MLNs containing metastatic NSCLC (five adenocarcinomas, one large cell carcinoma, one squamous cell carcinoma, and two uncharacterized carcinomas). For negative controls, we collected 30 cervical lymph nodes obtained by surgical resection. Protocols for tissue procurement and patient consent governing all aspects of this study were reviewed and approved by the Medical University of South Carolina Institutional Review Board. For EUS-FNA, a …

Accuracy of EUS criteria and primary tumor site for identification of mediastinal lymph node metastasis from non-small-cell lung cancer

BACKGROUND EUS with FNA is useful for staging non-small-cell lung cancer. However, benign mediastinal adenopathy is common. The aims of this study were to identify clinical factors, especially primary tumor location, and EUS lymph nodal characteristics predictive of aortopulmonary window and subcarinal lymph node metastases of non-small-cell lung cancer. METHODS Patients with known or suspected non-small-cell lung cancer underwent EUS staging at which EUS-FNA was performed for all identified mediastinal lymph nodes. Clinical characteristics, primary tumor data, EUS findings, and histopathology were reviewed. Exact tests were performed for both aortopulmonary window and subcarinal lymph nodes to identify factors predictive of malignant cytology. RESULTS Ninety-two patients with non-small-cell lung cancer were included. Fifty-one had aortopulmonary window, and 73 had subcarinal lymph nodes on EUS. The EUS with FNA specimens were interpreted as suspicious or diagnostic for malignancy for 9 aortopulmonary window and 9 subcarinal lymph nodes. When comparing benign vs. malignant EUS with FNA findings for aortopulmonary window and subcarinal lymph nodes, only lymph node size of 1 cm or greater and sharp lymph nodal edges were associated with malignancy in lymph nodes at both sites, whereas primary tumor site, lymph node shape, and echogenicity were associated with malignant subcarinal nodes. When 4 classic lymph nodal features of malignancy were evaluated, the presence of 3 or more typical features had positive and negative predictive values of, respectively, 41% and 96%. CONCLUSIONS Although tumor location and EUS lymph nodal characteristics are associated with malignant involvement of lymph nodes, the accuracy of these predictors does not obviate the need for cytologic evaluation. EUS with FNA should be performed for all lymph nodes when an abnormal finding will alter management.

Reversal of laryngotracheal separation: a detailed case report with long-term followup.

Chronic aspiration is a difficult and potentially lethal problem. Patients who have persistent soilage of the upper respiratory tract despite discontinuing oral intake may be offered surgical intervention to avoid life-threatening pulmonary infections. The Lindeman procedures (tracheoesophageal diversion and laryngotracheal separation) have gained popularity as surgical treatments for intractable aspiration because of their efficacy in preventing aspiration and their technical simplicity. A major downside of these procedures is the necessity for a tracheostoma and the loss of speech following surgery. Rarely, patients recover from the neurologic deficits which led to their intractable aspiration and desire reversal of their Lindeman procedure. While few “successful” reversals have been reported, detailed accounts of the long-term results of such patients are lacking. We describe a patient who underwent a laryngotracheal separation for intractable aspiration following a brainstem stroke. In the following six months he experienced significant neurologic recovery and, after careful evaluation, underwent surgical restoration of laryngotracheal continuity. Five years later he speaks fluently and has no dietary restrictions. Videofluooroscopic examination and quantitative voice analysis reveal near-normal laryngeal function.

Control of Traumatic Chylothorax with EUS-Guided Thoracic Duct Injection Sclerotherapy

Control of Traumatic Chylothorax with EUS-Guided Thoracic Duct Injection Sclerotherapy David H. Robbins, Mark Block, David Lewin, Michael Wallace, Brenda Hoffman Chylothorax due to thoracic duct (TD) trauma is traditionally treated with duct ligation at thoracotomy.We describe a novel endoscopic approach to this difficult management dilemma using endoscopic ultrasound (EUS) and fine needle injection (FNI) of the TD. A 41 year-old male was involved in a high-speed motor vehicle accident resulting in ejection from the vehicle and severe chest injuries. During his hospitalization refractory hiccups and nausea prompted a chest CT scan. A 4.9 3 3.1 cm focal fluid collection was identified between the esophagus and aorta in the subcarinal region. Bilateral pleural effusions were seen but no pulmonary mass or adenopathy was present. Rupture of the thoracic duct was considered and anEUS confirmed a 6 cmfluid collection under the aortic arch. A dilated 2.2 mm thoracic duct could be tracked into the collection and 35 ml of milky, straw colored fluid was aspirated; pathology confirmed a chyloma. In preparation for thoracic duct occlusion the following day and to optimize TD visualization, the patient was fed 2 canisters of high fat Ensure. The next day the fluid had fully re-accumulated and the thoracic duct was again identified. Color flow Doppler interrogation of surrounding structures confirmed its relation to the azygous vein. Twenty ml was again aspirated, fully collapsing the collection. Because of its safety profile and sclerosant properties, 1.5 ml of sodiummorrhuate (NaM) was directly into the TD under EUS control. There were no complications. The nausea and hiccups resolved and the patient was discharged uneventfully. No surgical intervention or chest tube placement was required. To our knowledge, this represents a novel and minimally invasive approach to manage traumatic chylothorax. We have replicated this approach in swine models and will present gross and histopathologic proof of principle. *T1552 A Prospective Multi-centre Study of the Safety and Accuracy of Combined Endoscopic Ultrasound (EUS) guided Fine Needle Aspiration (FNA) and Trucut Needle Biopsy (TNB) William Tam, Guru Aithal, Jeremy Dean, Stephen P. Pereira Background: There are few data on the specimen yield, safety and accuracy of EUS-guided TNB using a novel 19G needle (Quick-Core, Wilson-Cook) compared with standard 22GEUS-guided FNA (Echo-Tip,Wilson-Cook). Aims: To prospectively evaluate the safety and accuracy of combined EUS-FNA and TNB, and to determine the additional benefit of EUS-TNB. Methods: 59 patients (34M: 25F, median age 61 yrs) with mediastinal (n=23), gastric (n=3) or pancreaticobiliary (transgastric approach in 20, transduodenal approach in 13) mass lesions underwent EUS-FNA and EUS-TNB. Twenty patients had had previous negative biopsy and/or cytology results obtained percutaneously or at ERCP. Tissue sampling was defined as adequate if i) five cellular smears following EUS-FNA and ii) two cores after EUS-TNB, were obtained. An on-site cytopathologist was not available. Results: The diagnostic accuracy of combined EUS-FNA and EUS-TNB was 95%, with a prevalence of malignancy of 69% (median follow-up 29 weeks, IQR 11-40). Both EUS techniques had comparable sensitivity, specificity and predictive values (Table). In 8 patients, EUS-TNB allowed further tumour characterisation. Optimal tissue sampling was achieved in 88% of target lesions by EUS-FNA and in 76% by EUS-TNB (p>0.05). Five needle failures were encountered during transduodenal EUS-TNB. There were no immediate or late complications. Conclusions: EUS-guided FNA and TNB have equivalent safety profiles and both are effective means of obtaining tissue for the diagnosis ofmediastinal and gastrointestinalmass lesions.Histological assessment of core biopsies obtained from EUS-TNB may improve tumour characterisation. Transduodenal EUS-TNB is associated with a higher technical failure rate than either the mediastinal or transgastric approach.