Mediastinal adenopathy: finding the answer with endoscopic ultrasound-guided fine-needle aspiration biopsy

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS FNA) is a relatively new imaging modality that has been reported to be useful for mediastinal nodal staging of lung cancer and for the evaluation of mediastinal adenopathy of unknown cause. However, the technique is not commonly used in Australia. METHODS: A retrospective review of all patients who had mediastinal EUS FNA was undertaken. Of a total of 787 patients who had undergone endoscopic ultrasound (EUS) studies from November 1999 to March 2004, 27 patients were identified to have had mediastinal EUS FNA. Details were recorded including study indication, history of malignancy, source of referral, prior attempts for tissue diagnosis, EUS and EUS FNA findings, complications, surgical pathology if available and clinical outcome after diagnosis. RESULTS: Mediastinal EUS FNA was performed on an outpatient basis and no complications were recorded. Diagnostic material was obtained from all patients with a mean number of three passes. Nodal stations sampled included left paratracheal, subcarinal, aortopulmonary window and inferior mediastinum. Indications for the studies included mediastinal adenopathy of uncertain cause (17), lung cancer staging (7) and gastrointestinal cancer staging (3). EUS FNA confirmed malignancy in 16/27 patients, sarcoidosis in three patients, tuberculosis in one patient and seven patients were deemed to have reactive adenopathy. Primary cytopathological diagnosis of malignancy was determined by EUS FNA in nine patients. CONCLUSIONS: EUS FNA is a safe, efficient and effective modality for mediastinal staging of lung cancer and for the diagnosis of mediastinal adenopathy of uncertain origin. EUS FNA has the potential to significantly impact on patient management, avoiding more invasive procedures as well as unnecessary operations.     

Endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant subcarinal lymph node in a patient with lung cancer and a negative positron emission tomography scan

Transesophageal, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and positron emission tomography (PET) scanning are new modalities for staging non-small cell lung cancer (NSCLC), the roles of which are still being defined. A 78-year-old man with a right lower lobe (RLL) mass and mediastinal adenopathy seen on CT scan had a PET scan that revealed only a RLL hypermetabolic area. EUS/FNA cytology of a subcarinal lymph node (LN) revealed the presence of NSCLC. This is a case of a false-negative PET scan for nodal involvement in NSCLC that was diagnosed with EUS/FNA. Patients with NSCLC and suspicious lymphadenopathy may benefit from EUS/FNA of enlarged posterior mediastinal LNs, even with negative findings of PET scanning.     

Endoscopic transesophageal and endoscopic transbronchial real-time ultrasound-guided biopsy

The goal of preoperative staging of non-small-cell lung cancer is to identify patients who will benefit from surgical resection. Various imaging and less invasive modalities are now available to improve therapy decision-making, and with the introduction of multimodality treatment of lung cancer, proper staging of this disease is becoming more and more important. This staging process is therefore not only a question of determining the prognosis, but it is also necessary information for institution of the right treatment. Proper staging and restaging of lung cancer should also be a must in the evaluation of the different treatments of lung cancer in controlled clinical trials. In lung cancer, endoscopic ultrasound scanning (EUS) is emerging as an accurate, nonsurgical alternative to staging the mediastinum through EUS-fine-needle aspiration (EUS-FNA). The author presents publications on evaluating EUS in diagnosing lymph node involvement in lung cancer and tumor ingrowths in the mediastinum. With EUS it is possible to guide FNA with direct visualization of the needle path into the lymph nodes in real time. Although this method is only able to visualize the posterior path and the inferior parts of the mediastinum, it makes it possible to visualize the aortopulmonary window. The limitation of EUS is a sensitivity of about 90%; nonetheless, this method is more precise than other staging procedures except for mediastinoscopy, which is limited to only the anterior parts of the mediastinum.     

Malignant mediastinal lymphadenopathy detected by endoscopic ultrasound and guided fine needle aspiration in patients with resectable pancreaticobiliary cancer

Background

Resection surgery for pancreaticobiliary malignancies carries significant morbidity and mortality. Hence, preoperative assessment to exclude unresectable disease is mandatory. CT abdomen is the primary modality for staging of pancreaticobiliary cancers. However, some patients have malignant mediastinal lymphadenopathy (MML), which may be detected on endoscopic ultrasound (EUS) but not on CT scan.

Methods

We prospectively evaluated 75 consecutive patients (median age 54 years: 44 men) with a diagnosis of resectable pancreaticobiliary cancer (carcinoma gallbladder, carcinoma pancreas, cholangiocarcinoma, or periampullary carcinoma) for the presence of MML using EUS by an experienced endosonographer. If a lymph node had one or more features suggestive of malignancy, i.e. size exceeding 1 cm, hypoechoic appearance, a round shape, and regular margins, it was subjected to EUS-FNA.

Results

In seven (9.3%; 95% confidence intervals: 3.8% to 18.2%) of the 75 patients, EUS revealed enlarged mediastinal lymph nodes. The location of these lymph nodes was subcarinal in three, paraesophageal in two, and paratracheal in one patient; another patient had lymph nodes at two sites, i.e. the subcarinal and aortopulmonary window. In four of these seven patients, FNA documented the presence of MML. The overall rate of pathologically proven MML was 4/75 (5.3%; 95% CI [1.4% to 13%]).

Conclusion

EUS-FNA diagnosed MML in 5.3% of patients with pancreaticobiliary cancer. It may be useful to consider EUS assessment in patients with otherwise resectable pancreaticobiliary malignancy.

     

Defining the lymph node burden in a Northern European population without malignancy: the potential effect of geography in determining a need for FNA?

Data from the USA suggest that morphological specificity is insufficient to permit an assumption of malignancy in nodal staging with endoscopic ultrasound (EUS). This may not hold true elsewhere as the background lymph node burden may vary in different geographic regions. We aimed to assess the prevalence and features of mediastinal and abdominal lymph nodes at EUS in a Northern European population without malignant disease. A total of 129 consecutive patients without malignant disease referred for radial EUS were prospectively evaluated for the prevalence and echo features of lymph nodes in the mediastinum and upper abdomen. Sixty-two percent of patients had mediastinal lymph nodes and 17% had abdominal nodes at EUS. A mean of 1.4 (standard deviation 1.3, range 0–8) nodes were found per patient. No celiac nodes were seen. The majority of detected nodes were 0.5 cm or less in short axis, had oval shape, centrally echogenic pattern, and indistinct borders. The most common node locations were the subcarinal and paraesophageal areas, and the hepatoduodenal ligament. In multivariate analysis mediastinal lymphadenopathy was related to body mass index and abdominal lymphadenopathy to acute pancreatitis. The occurence of mediastinal lymphadenopathy is markedly lower in Northern Europeans than reported for US patients. Celiac nodes are extremely rare in patients without malignancy. The majority of nodes have a width of 0.5 cm or less, have oval shape, centrally echogenic pattern, and indistinct borders. The characterization of the background lymph node burden may improve the selection of lymph nodes for fine needle aspiration.     

EUS GUIDED FNA FOR MEDIASTINAL TUMORS (LUNG CANCER AND LYMPH NODES)

Trans‐esophageal endoscopic ultrasound‐guided fine needle aspiration biopsy (EUS‐FNA) has proven to be a safe and minimally invasive tissue‐sampling method which can be used to obtain a cytological diagnosis from mediastinal lesions. The aims of EUS‐FNA in the mediastinum are either to diagnose a lesion of unknown origin, to stage mediastinal lymph nodes in lung cancer patients or to diagnose other diseases involving lymph nodes of the mediastinum. In patients with non‐small cell lung cancer (NSCLC), surgery may be regarded as futile in up to 45% of patients operated, apparently because the stage of the disease is more advanced than expected preoperatively. This, combined with a stage‐dependent multimodality treatment, underlines the importance of exact staging of the disease. Conventional imaging and tissue sampling methods all have variable sensitivities. Twenty‐two studies concerning EUS‐FNA and mediastinal staging of lung cancer have been published with a total number of 1245 patients. The reported sensitivity for mediastinal malignancy range from 0.61–1.00 (median 0.90), and with specificities of 0.71–1.00 (median 1.00). The majority of the studies are retrospective and present the results of EUS‐FNA performed in lung cancer patients selected by computer tomography (CT). Recent data suggests that EUS‐FNA in addition can diagnose advanced mediastinal disease in 22–42% of NSCLC patients with normal sized lymph nodes (< 1 cm) on chest CT. EUS‐FNA may also be used as a re‐staging procedure after induction chemotherapy and it seems that EUS‐FNA is more accurate for mediastinal staging of NSCLC compared to positron emission tomography (PET). However, further studies are necessary before final conclusions can be made. At present, mediastinoscopy is still considered complementary to EUS‐FNA because EUS‐FNA cannot visualize structures anterior to the air‐filled trachea and main bronchi. Endoscopic trans‐bronchial real‐time ultrasound guided biopsy (EBUS‐TBNA) performed via the trachea and main bronchi seems to be an obvious solution. Preliminary experience with a prototype EBUS‐TBNA bronchoscope (Olympus, XBF‐UC40P, Tokyo, Japan) in 214 patients has shown promising results. Hopefully the combination of EUS‐FNA and EBUS‐TBNA will be able to replace more invasive and risky staging methods and improve the N‐staging accuracy of the mediastinum and lung hilar regions in the near future.     

Endoscopic ultrasound-guided elastography in the nodal staging of oesophageal cancer

AIM: To assess quantitative endoscopic ultrasound (EUS)-guided elastography in the nodal staging of oesophago-gastric cancers.METHODS: This was a single tertiary centre study assessing 50 patients with established oesophago-gastric cancer undergoing EUS-guided fine needle aspiration biopsy (FNAB) of lymph nodes between July 2007 and July 2009. EUS-guided elastography of lymph nodes was performed before EUS-FNAB. Standard EUS characteristics were also described. Cytological determination of whether a lymph node was malignant or benign was used as the gold standard for this study. Comparisons of elastography and standard EUS characteristics were made between the cytologically benign and malignant nodes. The main outcome measure was the accuracy of elastography in differentiating between benign and malignant lymph nodes in oesophageal cancers.RESULTS: EUS elastography and FNAB were performed on 53 lymph nodes. Cytological malignancy was found in 23 nodes, one was indeterminate, one was found to be a gastrointestinal stromal tumor and 25 of the nodes were negative for malignancy. On 3 occasions insufficient material was obtained for analysis. The area under the curve for the receiver operating characteristic curve for elastography strain ratio was 0.87 (P < 0.0001). Elastography strain ratio had a sensitivity 83%, specificity 96%, positive predictive value 95%, and negative predictive value 86% for distinguishing between malignant and benign nodes. The overall accuracy of elastography strain ratio was 90%. Elastography was more sensitive and specific in determining malignant nodal disease than standard EUS criteria.CONCLUSION: EUS elastography is a promising modality that may complement standard EUS and help guide EUS-FNAB during staging of upper gastrointestinal tract cancer.     

EUS-guided FNA of regional lymph nodes in patients with unresectable hilar cholangiocarcinoma

BACKGROUND: The clinical impact of EUS-guided FNA (EUS-FNA) in regional lymph-node staging in patients with unresectable hilar cholangiocarcinoma before liver transplantation has yet to be determined. OBJECTIVES: To determine the frequency of regional lymph-node detection, identify EUS features predictive of benign or malignant lymph nodes, compare EUS lymph-node detection rates to CT/magnetic resonance imaging and exploratory laparotomy, and evaluate the impact of EUS-FNA on patient selection for liver transplantation. DESIGN: Retrospective case series. SETTING: Tertiary referral EUS unit. PATIENTS: Clinical, radiographic, EUS, cytologic, and surgical data of 47 patients with unresectable hilar cholangiocarcinoma before liver transplantation were evaluated. INTERVENTIONS: EUS-FNA. MAIN OUTCOME MEASUREMENTS: Lymph-node morphology and echo features. RESULTS: EUS identified lymph nodes in all patients. FNA of 70 lymph nodes identified metastases in 9 nodes of 8 patients (17%), who were then precluded from transplantation before a staging laparotomy. Identified lymph nodes, irrespective of malignant involvement, were typically oval and geographic in shape, of mixed echogenicity, with a hypoechoic border. There were no morphologic criteria or echo features to correlate with nodal malignancy. The EUS finding of absent regional lymph-node metastases was confirmed in 20 of 22 by a subsequent exploratory staging laparotomy. LIMITATIONS: Single institution, retrospective analysis. CONCLUSIONS: EUS identified lymph nodes in all patients, and confirmation of malignant lymph nodes detected by FNA precluded 17% of patients from transplantation. EUS-FNA of visualized lymph nodes irrespective of appearance is advised because morphology and echo features do not predict malignant involvement.     

Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer

STUDY OBJECTIVE: Bronchoscopic methods fail to diagnose lung cancer in up to 30% of patients. We studied the role of transesophageal endosonography (EUS)-guided fine-needle aspiration (FNA; EUS-FNA) in such patients. DESIGN: Prospective study. The final diagnosis was confirmed by cytology, histology, or clinical follow-up. SETTING: University hospital. PATIENTS: Thirty-five patients (30 male and 5 female; mean age, 60.9 years; range, 34 to 88 years) with suspected lung cancer in whom bronchoscopic methods failed. Patients with a known diagnosis, recurrence of lung cancer, or mediastinal metastasis from an extrathoracic primary were excluded. INTERVENTIONS: EUS and guided FNA of mediastinal lymph nodes. RESULTS: The procedure was uneventful, and material was adequate in all. The final diagnosis by EUS-FNA was malignancy in 25 patients (11 adenocarcinoma, 10 small cell, 3 squamous cell, and 1 lymphoma) and benign disease in 9 patients (5 inflammatory, 2 sarcoidosis, and 2 anthracosis). Another patient with a benign result had signet-ring cell carcinoma diagnosed on pleural fluid cytology (probably false-negative in EUS-FNA). The sensitivity, specificity, accuracy, and positive and negative predictive values were 96, 100, 97, 100, and 90%, respectively. There were no complications. Reviewing the EUS morphology, the nodes were predominantly located in levels 7 and 8 of American Thoracic Society mediastinal lymph node mapping (subcarinal and paraesophageal region). In seven patients, the punctured nodes were < 1 cm (four malignant and three benign), which are difficult to sample by other methods. The malignant nodes had a hypoechoic, homogenous echotexture. CONCLUSIONS: EUS-FNA is a safe, reliable, and accurate method to establish the diagnosis of suspected lung cancer when bronchoscopic methods fail, especially in the presence of small nodes.     

Malignant mediastinal lymphadenopathy detected by staging EUS in patients with pancreaticobiliary cancer

BACKGROUND: In patients with pancreatic cancer, the presence of malignant mediastinal lymphadenopathy (MML) would preclude definitive resection. A recent study suggested routine evaluation for mediastinal lymph-node metastases in all patients being evaluated for pancreaticobiliary masses. In our practice, we routinely assess for mediastinal lymph-node metastases in all patients undergoing EUS for pancreaticobiliary cancer. METHODS: We retrospectively evaluated the presence of MML by EUS-guided FNA (EUS-FNA) in 160 consecutive patients with a definite diagnosis of pancreaticobiliary cancer (pancreatic and periampullary cancers) who underwent EUS-FNA by a single operator from 2000 to 2004. Lymph nodes that were round and hypoechoic with sharp margins were considered suspicious and were sampled by FNA. RESULTS: Of the 160 patients included in this study, 78 had peripancreatic lymph nodes (49%: 95% CI[41%, 58%]), 25 had celiac lymph nodes (16%: 95% CI[10%, 22%]), and 14 patients had mediastinal lymph nodes (9%: 95% CI[4%, 13%]) that were suspicious for malignancy by morphologic criteria. In 8 of 14 patients with suspicious mediastinal lymph nodes, FNA documented MML in 5%: 95% CI[2%, 8%]. Only one of these 8 patients with MML had other sites of documented distant metastases by CT and/or positron emission tomography scans. However, 7 of 8 patients had locally advanced cancers. CONCLUSIONS: MML is detected by staging EUS-FNA in 5% of patients with pancreaticobiliary cancer. Because of its important implications, endosonographers should routinely assess for MML in patients who undergo staging EUS for pancreaticobiliary malignancy.     

Central intranodal blood vessel: a new EUS sign described in mediastinal lymph nodes

BACKGROUND: The vascular architecture of normal lymph nodes is composed of prominent centrally located blood vessels. In malignant nodes, this pattern is distorted because of tumor infiltration and neovascularization. OBJECTIVE: To determine whether EUS imaging of central intranodal blood vessels (CIV) can be used to differentiate benign from malignant subcarinal lymph nodes in lung cancer. DESIGN: CIV was defined as a > or =1-mm-diameter tubular structure, with well-defined walls and blood flow. The diagnostic accuracy of CIV was compared with other lymph-node features in a retrospective cohort of patients who underwent EUS for lung cancer evaluation. Findings were then prospectively validated in a similar cohort. SETTING: Minneapolis Veterans Affairs Medical Center. PATIENTS: Patients who underwent EUS for lung cancer diagnosis or staging at the VA Medical Center from March 2003 to March 2005. RESULTS: Of 67 patients included in the retrospective analysis, CIV was noted in 17 of 35 patients with benign nodes (49%), compared with 5 of 32 patients with malignant nodes (16%) (P = .002). In lymph nodes > or =1 cm, CIV was noted in 14 of 16 patients with benign nodes (88%), compared with 2 of 27 with malignant nodes (7%) (P < .001). Forty-five patients were included in the prospective validation cohort, and 16 had malignant lymph nodes. For malignant lymph-node metastasis, the absence of CIV had a sensitivity of 75%, a specificity of 97%, and an accuracy of 89%. The accuracy of CIV was superior to that of lymph-node shape; margin; and internal echo pattern, singly or in combination. CONCLUSIONS: The absence of a central intranodal blood vessel was a strong and independent predictor of malignancy in lymph nodes of patients with lung cancer and can be used to select lymph nodes for FNA.     

Ultrasound techniques in the evaluation of the mediastinum,part I: endoscopic ultrasound (EUS), endobronchial ultrasound (EBUS) and transcutaneous mediastinal ultrasound (TMUS), introduction into ultrasound techniques

Ultrasound imaging has gained importance in pulmonary medicine over the last decades including conventional transcutaneous ultrasound (TUS), endoscopic ultrasound (EUS), and endobronchial ultrasound (EBUS). Mediastinal lymph node staging affects the management of patients with both operable and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography (EUS and EBUS) should be the initial tissue sampling test over surgical staging. Mediastinal nodes can be sampled from the airways [EBUS combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [EUS fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all mediastinal lymph nodes can be biopsied. Additionally endosonography has an excellent yield in assessing granulomas in patients suspected of sarcoidosis. The aim of this review, in two integrative parts, is to discuss the current role and future perspectives of all ultrasound techniques available for the evaluation of mediastinal lymphadenopathy and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part I is dealing with an introduction into ultrasound techniques, mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques and part II with the clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography.     

Mediastinal transthoracic needle and core lymph node biopsy: should it replace mediastinoscopy?

STUDY OBJECTIVES: Primary assessment of mediastinal lymph nodes (N2 or N3) for staging lung cancer by transthoracic needle with or without core biopsy. Mediastinoscopy only performed after FNA failed to yield a diagnosis. DESIGN AND SETTINGS: A retrospective study in a university setting. PATIENTS: Eighty-nine patients with mediastinal lymphadenopathy (> 1.5 cm in short-axis diameter) by CT. METHODS: Mediastinal transthoracic fine-needle aspiration (FNA) with or without core biopsy was performed prior to mediastinoscopy in 89 patients with mediastinal lymphadenopathy (lymph node > 1.5 cm in short-axis diameter) or masses by CT. RESULTS: Mediastinal transthoracic FNA was used alone in 39 of 89 patients, or with core biopsy in 50 of 89 patients. Mediastinal transthoracic FNA with or without core biopsy was diagnostic in 69 of 89 patients (77.5%) for cancer cell type, sarcoidosis, or caseating granulomas with or without tuberculosis. Transthoracic FNA with or without core biopsy of nodal stations (total, 94 biopsies) judged readily accessible by mediastinoscopy (n = 59) included paratracheal (n = 56) and highest mediastinal (n = 3); those more difficult (n = 26) included subcarinal (n = 20) and aorticopulmonary window (n = 6); and those impossible (n = 9) included paraesophageal and pulmonary ligament (n = 6), parasternal (n = 2), and para-aortic (n = 1). Innovative lung protective techniques for CT-guided biopsy access windows included "iatrogenic-controlled pneumothorax" (n = 10) or saline solution injection creating a "salinoma" (n = 11). Pneumothorax was detected in only 10% with a "protective" technique but 60% when traversing lung parenchyma. Transthoracic FNA with or without core biopsy failed to yield a diagnosis in 20 of 89 patients (22.5%); all then underwent mediastinoscopy, with 11 of 20 procedures (55%) diagnostic for cancer, and 9 of 20 procedures diagnostic of benign diagnosis or no cancer. CONCLUSION: Transthoracic FNA with or without core biopsy accesses virtually all mediastinal nodal stations is diagnostic in 78% of cases with mediastinal adenopathy or masses, and should precede mediastinoscopy in the staging of lung cancer or workup of mediastinal masses.     

Evaluation of metastatic celiac axis lymph nodes in patients with esophageal carcinoma: accuracy of EUS.

BACKGROUND: Endosonography (EUS) is the most accurate modality for assessing depth of tumor invasion and local lymph node metastasis. However, its accuracy in the identification of metastatic (celiac axis) lymph nodes is less well defined. Our objective in this study was to determine the accuracy of Eus in detecting celiac axis lymph node metastasis in patients with esophageal carcinoma. METHODS: Two hundred fourteen patients with esophageal carcinoma underwent preoperative EUS. Of these, 145 underwent attempted surgical resection and staging, and 4 underwent EUS-guided fine-needle aspiration of mediastinal and celiac lymph nodes. Local (mediastinal) and distant (celiac axis) lymph nodes were assessed for malignancy on the basis of four criteria (larger than 1 cm, round, homogeneous echo pattern, sharp borders). Accuracy of EUS was determined by means of correlating histopathologic findings for the resected lymph nodes or results of EUS-guided fine-needle aspiration cytologic examination. RESULTS: Surgical exploration (n = 145) and fine-needle aspiration cytologic examination (n = 4) revealed metastatic celiac axis lymph nodes in 23 and metastatic mediastinal (local) lymph nodes in 93 of 149 patients with esophageal carcinoma. According to defined criteria for malignant lymph nodes, there were 19 true-positive and 4 falsenegative results. Sensitivity for the diagnosis of celiac lymph node metastasis with EUS was 83% with a 98% specificity. For the diagnosis of mediastinal lymph node metastasis, sensitivity was 79% and specificity was 63%. All patients with malignant celiac axis lymph nodes had local T3 (tumor breaching adventitia) or T4 (tumor invading adjacent organs) disease. CONCLUSION: EUS is an excellent modality in the evaluation of metastatic celiac axis lymph nodes in patients with esophageal carcinoma. These findings should be used in selecting options for treatment. Sensitivity for detecting malignancy is consistent with that of prior studies, and local and regional lymph nodes and specificity is significantly higher.     

Impact of preoperative endoscopic ultrasound on non-small cell lung cancer staging

AIM: To determine if the addition of preoperative endoscopic ultrasound (EUS) to non-small cell lung cancer staging can reduce the proportion of patients in whom malignant mediastinal lymph nodes (inoperable disease) are discovered at surgery. METHODS: All patients with lung cancer who underwent mediastinoscopy or thoracotomy for cancer diagnosis, staging, or treatment from 1999 to 2005 were identified. Patients who had undergone preoperative EUS were designated as the EUS group. The control group was composed of similar patients who had not undergone preoperative EUS, and were frequency matched to those in the EUS group in a 3:1 ratio by preoperative cancer stage. The proportion of patients in whom malignant mediastinal lymph nodes were diagnosed at surgery was the primary outcome. RESULTS: Forty-four patients (average age, 67.8 years) met criteria for the EUS group, and 132 patients (average age, 67.4 years) were selected as control subjects. Overall, in the EUS group, 3 of 44 patients (6.8%) were found to have malignant mediastinal lymph nodes at surgery, compared with 41 of 132 patients (31.1%) in the control group (p = 0.003). In patients undergoing thoracotomy for cancer resection, 3% in the EUS group, compared with 20% in the control group, were found to have malignant mediastinal lymph nodes at surgery (p = 0.01). There was also a trend toward lower yield of mediastinoscopy done for cancer diagnosis or staging in the EUS group (p = 0.08). CONCLUSIONS: Preoperative EUS in lung cancer patients may reduce unnecessary surgery at which advanced inoperable disease is discovered.     

Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT,positron emission tomography,and endoscopic ultrasonography with and without fine-needle aspiration

PURPOSE: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection. PATIENTS AND METHODS: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as "gold standard" to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. RESULTS: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUS-guided FNA), which gave a tissue diagnosis including tumor type, without complications. CONCLUSIONS: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small mediastinal metastases of lung cancer. CT seems necessary additionally to evaluate the pretracheal region as well as the rest of the thorax, and PET may be valuable to detect distant metastases.     

Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma

BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.     

Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung cancer: analysis of false-positive FDG-PET findings

BACKGROUND: Accurate staging of mediastinal and hilar lymph nodes is a critical factor determining operability in patients with non-small cell lung cancer (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer (FDG-PET) has recently been reported to be more effective in detecting tumor involvement in mediastinal and hilar lymph nodes than computed tomography (CT). OBJECTIVE: In this study, we analyzed the accuracy of FDG-PET in mediastinal and hilar lymph node staging in patients with NSCLC and the factors associated with false-positive or false-negative FDG-PET findings in mediastinal and hilar lymph node staging. METHODS: Fifty-four patients with NSCLC who underwent preoperative analysis including chest CT and whole-body FDG-PET were evaluated retrospectively. Using FDG-PET, lesions were considered to be positive if a definite, localized area of higher uptake, excluding physiologic uptake, than in surrounding normal tissue was present. On CT findings, lymph nodes were considered to be positive if they were >10 mm in short-axis diameter, except subcarinal lymph nodes (#7), which were considered to be positive if they were >15 mm in short-axis diameter. All patients underwent surgical resection of primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our institute. Resected lymph nodes were histologically examined for the existence of tumor cells. RESULTS: A total of 306 lymph nodes were resected and used for analysis. The sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55, 96, 55 and 96%, respectively. When pre-operative nodal staging was compared with post-operative histopathological staging, 44 patients (81%) were correctly staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39 patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary complications, including interstitial pneumonitis (n = 2), previous pulmonary tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were also undetectable by CT. CONCLUSION: FDG-PET is superior to CT in mediastinal and hilar lymph node staging of patients with NSCLC. However, care should be taken in lymph node staging for patients who have other pulmonary complications, including interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.     

The value of mediastinoscopy in preoperative evaluation of mediastinal involvement in non-small-cell lung cancer patients with clinical NO disease

BACKGROUND: The efficacy of mediastinal lymph node examination using cervical mediastinoscopy in operable non-small cell lung cancer patients without radiological nodal involvement on computerized tomography (CT) has been elusive. METHODS: The value of mediastinoscopy as a staging modality for assessing the mediastinal lymph node status was evaluated in 79 patients with presumed resectable non-small-cell lung cancer (NSCLC) with mediastinal nodes smaller than 1 cm (NO) form the CT scan. Sixty-one patients who did not have nodal involvement at mediastinoscopy and had complete medical records underwent complete resection. RESULTS: Negative predictive value (NPV) of the CT scan according to mediastinoscopy was 92.4 %. Histopathological examination of the surgical specimen showed the NPV of mediastinoscopy to be 93.4 %. Only 4 patients (3 patients with N2, 1 patient with N3 disease) were not correctly staged using CT scanning and mediastinoscopy. According to the pathological examination, the NPV of CT was found to be lower (76.5 %) in patients with adenocarcinoma, but the difference was not statistically significant (p > 0.128) CONCLUSION: Although the likelihood of surgical-pathological N2 is slightly higher in patients with adenocarcinoma, radiological examination of patients with cNO NSCLC disease can be as accurate as mediastinoscopy in appropriately staging mediastinal lymph node involvement.     

Impact of staging transesophageal EUS on treatment and survival in patients with non-small-cell lung cancer

BACKGROUND: Transesophageal EUS-guided FNA (EUS-FNA) is safe, accurate, and cost effective in staging patients with non-small-cell lung cancer (NSCLC). However, the impact of EUS-FNA on patient survival has not been demonstrated. OBJECTIVE: To determine the impact of metastatic disease in mediastinal lymph nodes as determined by EUS staging on treatment choice and survival in patients with NSCLC. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Tertiary university-based referral center. PATIENTS: Patients with biopsy-proven NSCLC who underwent staging EUS-FNA. The relationship between the EUS nodal status and patient survival was evaluated. Cox proportional hazards models were used to determine the significance of EUS nodal status and patient characteristics on patient survival. MAIN OUTCOMES MEASUREMENTS: Impact of EUS-FNA on therapy and survival in patients with NSCLC. RESULTS: Of 125 patients with NSCLC, EUS-FNA confirmed metastatic disease in 46% of the patients. Patients who were node positive were more likely to receive chemotherapy and/or radiation therapy and were less likely to undergo surgery compared with patients who were node negative (P< .0001). Patients with N2 or N3 disease by EUS-FNA had a shorter survival time than patients who were node negative (P= .004). Adjusting for age, race, and sex, EUS-FNA was the most important predictor of survival of patients with NSCLC in this cohort of patients (hazard ratio 2.34, 95% CI 1.31-4.21). LIMITATIONS: Lack of surgical reference standard in all patients and referral to a tertiary center. CONCLUSIONS: Patients with node-positive NSCLC as detected by EUS-FNA have a shorter survival time compared with patients who were node negative. They are more likely to receive neoadjuvant therapy and less likely to receive surgery. Preoperative EUS-FNA is a minimally invasive technique that provides important prognostic information in patients with NSCLC.