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1.  Performance of EUS-FNA for mediastinal lymphadenopathy: impact on patient management and costs in low-volume EUS centers 
Surgical Endoscopy  2010;24(9):2260-2267.
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymphadenopathy has been shown to be a valuable diagnostic tool in high-volume EUS centers (≥50 mediastinal EUS-FNA/endoscopist/year). Our goal was to assess the diagnostic accuracy of EUS-FNA and its impact on clinical management and costs in low-volume EUS centers (<50 mediastinal EUS-FNA/endoscopist/year).
Consecutive patients referred to two Dutch endoscopy centers in the period 2002–2008 for EUS-FNA of mediastinal lymphadenopathy were reviewed. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. The impact of EUS-FNA on clinical management was subdivided into a positive impact by providing (1) adequate cytology that influenced the decision to perform surgery or (2) a diagnosis of a benign inflammatory disorder, and a negative impact which was subdivided into (1) false-negative or inconclusive cytology or (2) an adequate cytological diagnosis that did not influence patient management. Costs of an alternative diagnostic work-up without EUS-FNA, as established by an expert panel, were compared to costs of the actual work-up.
In total, 213 patients (71% male, median age = 61 years, range = 23–88 years) underwent EUS-FNA. Sensitivity, specificity, and negative and positive predictive values were 89%, 100%, 80%, and 100%, respectively. EUS-FNA had a positive impact on clinical management in 84% of cases by either influencing the decision to perform surgery (49%) or excluding malignant lymphadenopathy (35%), and a negative impact in 7% of cases because of inadequate (3%) or false-negative (4%) cytology. In 9% of cases, EUS-FNA was performed without an established indication. Two nonfatal perforations occurred (0.9%). Total cost reduction was €100,593, with a mean cost reduction of €472 (SD = €607) per patient.
Mediastinal EUS-FNA can be performed in low-volume EUS centers without compromising diagnostic accuracy. Moreover, EUS-FNA plays an important role in the management of patients with mediastinal lymphadenopathy and reduces total diagnostic costs.
PMCID: PMC2939341  PMID: 20177920
EUS-FNA; Costs; Accuracy; Mediastinal lymphadenopathy
2.  Predictors of malignancy in EUS-guided FNA for mediastinal lymphadenopathy in patients without history of lung cancer 
Annals of Thoracic Medicine  2011;6(3):126-130.
Mediastinal lymphadenopathy (ML) poses a great diagnostic challenge.
To investigate the predictors of malignancy in endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of ML in patients without known lung cancer.
Retrospective study.
Tertiary referral center.
One hundred eight patients without known lung cancer who underwent EUS guided-FNA for ML between 2000 and 2007. All subjects underwent EUS-guided FNA. Data was collected on patients′ demographics, and lymph node (LN) characteristics. Diagnosis of LN malignancy was based on FNA findings and clinical follow-up.
One hundred eight patients were analyzed; 58 (54%) were men and 87 (79%) were Caucasian. Mean age was 55 years. Prior malignancy was present in 48 (43%) patients. A total of 126 FNA samples from 126 distinct LNs were performed. Twenty-five (20%) LNs were positive for malignancy. Mean short and long-axis for LNs were 13 and 29 mms respectively. Round shape and sharp borders were found in 29 (15%) and 25 (22%) LNs, correspondingly. Independent predictors of a malignant FNA were: Prior cancer (OR 13.10; 95% CI 2.7-63.32; P = 0.001), short axis (OR 1.10; 95% CI 1.00-1.22; P = 0.041) and sharp LN borders (OR 5.47; 95% CI 1.01-29.51; P = 0.048). Age, race, gender, long axis, round shape were not associated with cancer in our cohort.
Retrospective design and lack of surgical gold standard.
Increased risk of malignancy was associated with prior history of cancer, larger LN short axis and presence of LN sharp borders. These predictors may help guide endoscopists perform FNA in malignant LNs, increasing the overall efficiency of EUS-FNA for ML.
PMCID: PMC3131754  PMID: 21760843
Endoscopic ultrasound; lung cancer; mediastinal lymphadenopathy; staging; fine needle aspiration
3.  Endoscopic Ultrasonograpic Findings of Benign Mediastinal and Abdominal Lymphadenopathy Confirmed by EUS-guided Fine Needle Aspiration 
Gut and Liver  2007;1(1):68-73.
Distinguishing benign and malignant lymph nodes by the findings of endoscopic ultrasonography (EUS) is still controversial. We tried to evaluate EUS findings of benign mediastinal and abdominal lymphadenopathy (BLAP) confirmed by EUS-guided fine needle aspiration (FNA).
A total of 37 patients with enlarged mediastinal or abdominal lymph nodes (diameter ≥1 cm) were enrolled and EUS-FNA was performed. Final diagnosis was based on FNA cytology and follow up imaging studies (CT scans or EUS).
Thirteen patients were confirmed to have BLAP by EUS-FNA. Causes of BLAP were as follows; (i) extrapulmonary tuberculosis in six cases including patients with postoperative states due to cervical cancer and advanced gastric cancer, (ii) Kikuchi disease in one case, (iii) hypereosinophilic syndrome in one case, (iv) reactive hyperplasia in five cases including patients with postoperative states due to thyroid cancer, lung cancer, and EGC with ESD. EUS findings of BLAP revealed that median lymph node size was 24.7 mm. Lymph nodes were oval or round shaped in 9 cases, sharp borders in 9 cases, hypoechoic echo pattern in 7 cases, heterogenous internal echo pattern in 7 cases. Other findings included internal septation, calcification, multiplicity, attachment to the gastrointestinal tract wall, and conglomeration.
EUS findings of BLAP were not different from those of malignant lymphadenopathy previously reported in other studies.
PMCID: PMC2871653  PMID: 20485661
Lymphadenopathy; Endoscopic ultrasonography, Fine needle aspiration
4.  Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry 
Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA) cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.
PMCID: PMC3214475  PMID: 22090704
Fine needle aspiration cytology; metastasis; pancreas; small cell lung carcinoma; trans-bronchial biopsy
5.  Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on patient management 
Thorax  2002;57(2):98-103.
Background: A study was undertaken to evaluate the clinical impact of endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) in patients with mediastinal masses suspected of malignancy.
Methods: From April 1993 to December 1999, 84 patients were referred for EUS-FNA. In all patients CT scanning had shown a lesion of the mediastinum suspected of malignancy located adjacent to the oesophagus. In order to evaluate the clinical impact of EUS-FNA, the history of each patient up to referral for EUS-FNA was reviewed. A board of thoracic specialists was asked to decide the further course of the patient if EUS-FNA had not been available, and this diagnostic strategy was compared with the actual clinical course after EUS-FNA.
Results: For the 79 patients in whom sufficient verification was obtained, EUS-FNA had a sensitivity of 92%, specificity of 100%, PPV of 100%, NPV of 80%, and an accuracy of 94% for cancer of the mediastinum. In 18 of 37 patients (49%) a thoracotomy/thoracoscopy was avoided as a result of EUS-FNA, and in 28 of 41 patients (68%) a mediastinoscopy was avoided. The direct result of the cytological diagnosis obtained by EUS-FNA was that a final diagnosis of small cell lung cancer was made in eight patients resulting in referral for chemotherapy, and in another three patients with benign disease specific treatment could be initiated (sarcoidosis, mediastinal abscess, and leiomyoma of the oesophagus).
Conclusions: EUS-FNA is a safe and sensitive minimally invasive method for evaluating patients with a solid lesion of the mediastinum suspected by CT scanning. EUS-FNA has a significant impact on patient management and should be considered for diagnosing the spread of cancer to the mediastinum in patients with lung cancer considered for surgery, as well as for the primary diagnosis of solid lesions located in the mediastinum adjacent to the oesophagus.
PMCID: PMC1746251  PMID: 11828036
6.  Rescue Endoscopic Ultrasound (EUS)-Guided Trucut Biopsy Following Suboptimal EUS-Guided Fine Needle Aspiration for Mediastinal Lesions 
Gut and Liver  2013;7(2):150-156.
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and Trucut biopsy (TCB) are sensitive techniques for diagnosing mediastinal lesions, but it is unclear how either one or both should be used to obtain a pathologic diagnosis. The objective of our study was to evaluate whether EUS-TCB impacts the diagnosis of mediastinal lesions after the initial on-site review of EUS-FNA specimen suggests a suboptimal result.
We enrolled consecutive patients with mediastinal lesions who underwent EUS-TCB during the same procedure if the initial EUS-FNA demonstrated an inadequate FNA sample or suggested that histopathology was required for diagnosis. Diagnostic accuracies between procedures were compared as the main outcome.
Twenty-seven patients (14 men; median age, 56 years; range, 19 to 82 years) underwent EUS-FNA and EUS-TCB to evaluate a mediastinal lymphadenopathy or mass (n=17), to determine the cancer stage (n=3) or to exclude tumor recurrence or metastasis (n=7). The overall diagnostic accuracies of EUS-FNA and EUS-TCB were 78% and 67%, respectively (p=0.375). The combined diagnostic accuracy of EUS-FNA plus EUS-TCB was 82%. In six patients with nondiagnostic EUS-FNA, EUS-TCB provided a final diagnosis in one patient (17%).
In the current series of patients with mediastinal masses or adenopathy, the administration of EUS-TCB following suboptimal results for the on-site cytology review did not increase the diagnostic yield.
PMCID: PMC3607767  PMID: 23560149
Endoscopic ultrasound; Endoscopic ultrasound-guided fine needle aspiration; Endoscopic ultrasound-guided Trucut biopsy; Mediastinum
7.  Diagnosis of metastatic fibrolamellar hepatocellular carcinoma by endoscopic ultrasound-guided fine needle aspiration 
CytoJournal  2011;8:2.
The fibrolamellar variant of hepatocellular carcinoma (FL-HCC) is distinguished from other hepatocellular carcinomas (HCC) by its unique clinical and pathologic features. Cytological features for this tumor on fine needle aspiration (FNA) of primary tumors have been described earlier. We present here a unique case of metastatic FL-HCC diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal adenopathy. A 32-year-old woman with a history of oral contraceptive use presented with nausea and severe abdominal pain but no ascites or stigmata of cirrhosis. She had a past history of resection of a liver lesion. Serial computed tomography scans revealed mediastinal lymphadenopathy and the patient was referred for endoscopic ultrasound (EUS). A transesophageal EUS-FNA was performed and tissue was collected for cytological evaluation by an on-site pathologist with no knowledge of prior history. Based on morphology correlated with prior history received later, a final diagnosis of metastatic FL-HCC in the retrocardiac lymph node was rendered on the EUS-FNA samples. There are very few reports in the literature where a diagnosis of FL-HCC is rendered at unusual sites. This case highlights that EUS-FNA is a relatively non-invasive, rapid, accurate and effective modality in obtaining tissue from otherwise hard-to-reach areas. It also suggests that metastasis of FL-HCC can be observed in mediastinal nodes and that diagnosis based on cytological features can be rendered even when the tumor is identified at unusual locations.
PMCID: PMC3045764  PMID: 21369523
Metastatic fibrolamellar variant of hepatocellular carcinoma; endoscopic ultrasound guidance; fine needle aspiration
8.  Diagnostic difficulties and pitfalls in rapid on-site evaluation of endobronchial ultrasound guided fine needle aspiration 
CytoJournal  2010;7:9.
One of the novel techniques utilizing fine needle aspiration (FNA) in the diagnosis of mediastinal and lung lesions is the endobronchial ultrasound (EBUS)-guided FNA. In this study, we describe five cases which had a discrepancy between on-site evaluation and final diagnosis, or a diagnostic dilemma when rendering the preliminary diagnosis, in order to illustrate some of the diagnostic difficulties and pitfalls that can occur in EBUS FNA.
A total of five EBUS FNA cases from five patients were identified in our records with a discrepancy between the rapid on-site evaluation (ROSE) and final diagnosis, or that addressed a diagnostic dilemma. All of the cases had histological confirmation or follow-up. The cytomorphology in the direct smears, cell block, and immunohistochemical stains were reviewed, along with the clinical history and other available information.
Two cases were identified with a nondefinitive diagnosis at ROSE that were later diagnosed as malignant (metastatic signet-ring cell adenocarcinoma and metastatic renal cell carcinoma (RCC)) on the final cytological diagnosis. Three additional cases were identified with a ROSE and final diagnosis of malignant (large cell neuroendocrine carcinoma (LCNEC) and two squamous cell carcinomas), but raised important diagnostic dilemmas. These cases highlight the importance of recognizing discohesive malignant cells and bland neoplasms on EBUS FNA, which may lead to a negative or a nondefinitive preliminary diagnosis. Neuroendocrine tumors can also be difficult due to the wide range of entities in the differential diagnosis, including benign lymphocytes, lymphomas, small and nonsmall cell carcinomas, and the lack of immunohistochemical stains at the time of ROSE. Finally, the background material in EBUS FNAs may be misleading and unrelated to the cells of interest.
This study illustrates the cytomorphology of five EBUS FNA cases that address some of the diagnostic challenges witnessed while examining these specimens during ROSE. Many of the difficulties faced can be attributed to the baseline cellularity of the aspirates, the bronchial contamination, the difficulty identifying neoplasms with bland cytology, the wide spectrum of diseases that can occur in the mediastinum with overlapping cytomorphologic features, the mismatch between the background material and the cell populations present, and the overall unfamiliarity with these types of specimens.
PMCID: PMC2895875  PMID: 20607094
Cytopathology; EBUS; endobronchial ultrasound; fine needle aspiration
9.  Endobronchial ultrasound guided fine needle aspiration versus transcervical mediastinoscopy in nodal staging of non small cell lung cancer: a prospective comparison study 
At present only few studies directly compare the diagnostic yield of endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) and transcervical video-assisted mediastinoscopy (TM) for mediastinal lymph node staging in patients with NSCLC. If and when EBUS-FNA may replace TM as Gold Standard remains controversial.
From April 2008 to December 2009, 36 patients with mediastinal lymphadenopathy underwent simultaneous EBUS-FNA/ TM at our institution. Among them were 26 patients with confirmed or suspected NSCLC.
A total of 133 samples were obtained by EBUS-FNA and 157 samples by TM. EBUS-FNA achieved significantly less conclusive, but more indeterminate pathological results in comparison to TM (78.7% vs. 98.6%, p < 0.001; 14.9% vs. 1.4%, p = 0.007). Less paratracheal nodes were sampled by EBUS-FNA (right: 46.2% vs. 88.5%, p = 0.003; left: 23.1% vs. 65.4%, p = 0.005), while sampling rates in the subcarinal localisation were comparable (96.2% vs. 80.8%, p = NS). Among patients with confirmed NSCLC and conclusive EBUS-FNA/ TM findings (n = 18), the prevalence of N2/N3 disease was 66.7% (n = 12) according to TM findings. Diverging nodal stages were found in five patients (27.8%). Three patients who were N2 negative in EBUS-FNA were upstaged to N2 or N3 by TM, two patients with N2 status in EBUS-FNA were upstaged to N3 by TM.
Compared to TM, EBUS-FNA had a lower diagnostic yield and resulted in systematic mediastinal nodal understaging. At this point we suggest corroborating negative EBUS-FNA results by transcervical mediastinoscopy.
PMCID: PMC3408361  PMID: 22672731
EBUS-FNA; Mediastinoscopy; NSCLC; Nodal staging
10.  Is endosonography guided fine needle aspiration (EUS-FNA) for sarcoidosis as good as we think? 
Thorax  2004;59(9):794-799.
Background: Preliminary data show that endosonography guided fine needle aspiration (EUS-FNA) may be an accurate method for diagnosing sarcoidosis. However, these data were obtained in a small selected group of patients with a very high pretest probability of sarcoidosis. This retrospective study reports on the use of EUS-FNA in an unselected group of patients with mediastinal lymphadenopathy of unknown origin.
Methods: The EUS database of a single tertiary referral centre was reviewed for patients who underwent EUS-FNA for mediastinal lymphadenopathy of unknown origin. Clinical presentation and imaging studies of each case were carefully reviewed and the diagnosis "sarcoidosis" or "no sarcoidosis" attributed if possible. The diagnoses were compared with the result of EUS-FNA.
Results: One hundred and twenty four patients were investigated. In 35 cases EUS-FNA identified granulomas (group 1); in the other 89 cases (group 2) no granulomas were detected. The definite diagnoses in group 1 were sarcoidosis (n = 25), indefinite (n = 7), no sarcoidosis (n = 3). The definite diagnoses in group 2 were sarcoidosis (n = 3), indefinite (n = 9), no sarcoidosis (n = 77). Of the 77 cases with no sarcoidosis, 44 were diagnosed with other diseases. The other 33 showed non-specific changes in the FNA and sarcoidosis was excluded by negative non-EUS pathology (n = 17) and clinical presentation. The sensitivity and specificity for EUS-FNA were 89% (95% CI 82 to 94) and 96% (95% CI 91 to 98), respectively, after exclusion of the indefinite cases in both groups.
Conclusions: EUS-FNA is an accurate method for diagnosing sarcoidosis in an unselected group of patients with mediastinal lymphadenopathy. The reported sensitivity and specificity must be appreciated in the context of the difficult and often incomplete clinical diagnosis of sarcoidosis.
PMCID: PMC1747124  PMID: 15333858
11.  First endoscopic procedure for diagnosis and staging of mediastinal lymphadenopathy 
AIM: To compare a first diagnostic procedure of transbronchial needle aspiration (TBNA) with selection of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or TBNA for mediastinal lymphadenopathy.
METHODS: Sixty-eight consecutive patients with mediastinal lymphadenopathy on computed tomography (CT), who required cytopathological diagnosis, were recruited. The first 34 underwent a sequential approach in which TBNA was performed first, followed by EUS-FNA if TBNA was unrevealing. The next 34 underwent a selective approach where either TBNA or EUS-FNA was selected as the first procedure based on the CT findings.
RESULTS: The diagnostic yield of TBNA as the first diagnostic procedure in the sequential approach was 62%. In the selective approach, the diagnostic yield of the first procedure was 71%. There was no significant difference in the overall diagnostic yield, but there were significantly fewer combined procedures with the selective approach.
CONCLUSION: Selecting either EUS-FNA or TBNA as the first diagnostic procedure achieved a comparable diagnostic yield with significantly fewer procedures than performing TBNA first in all patients.
PMCID: PMC2797668  PMID: 20027684
Aspiration biopsy; Needle biopsy; Endoscopy; Ultrasound; Mediastinum; Lymphadenopathy; Lung neoplasms; Diagnosis; Neoplasms staging
12.  Economic Analysis of Combined Endoscopic and Endobronchial Ultrasound in the Evaluation of Patients with Suspected Non-Small Cell Lung Cancer 
Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non–small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis ($18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA ($18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pretest probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.
PMCID: PMC2822087  PMID: 19473723
Ultrasonography; Endobronchial ultrasound; Non-Small Cell Lung Cancer; Medical Economics
13.  Oesophageal endoscopic ultrasound with fine needle aspiration improves and simplifies the staging of lung cancer 
Thorax  2004;59(7):596-601.
Background: Positron emission tomography (PET) is accurate for mediastinal staging of lung cancer but has a moderate positive predictive value, necessitating pathological verification. Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) is a technique for tissue verification of mediastinal and upper retroperitoneal abnormalities. The use of EUS-FNA may decrease the number of surgical procedures and thereby staging costs.
Methods: EUS-FNA was used prospectively for the cytological assessment of mediastinal and/or upper retroperitoneal PET hot spots in patients with suspected lung cancer. Only if EUS-FNA was positive for malignancy was subsequent mediastinoscopy or exploratory thoracotomy cancelled. The cost effectiveness of EUS-FNA was determined.
Results: Of 488 consecutive patients with suspected lung cancer, 81 were enrolled with mediastinal and/or upper retroperitoneal PET hot spots. EUS-FNA was positive in 50 (62%) patients, negative in six, and inconclusive in 25. Of the 31 negative or inconclusive patients, 26 underwent surgical staging (resulting in 14 patients with and 12 without mediastinal malignancy), while five patients had mediastinal metastases during follow up. No EUS-FNA related morbidity or mortality was encountered. The accuracy of the decision to proceed to surgery (or not) on the basis of EUS-FNA was 77% (95% CI 68 to 86). EUS-FNA detected more mediastinal abnormalities than PET except for the upper mediastinal region. Addition of EUS-FNA to conventional lung cancer staging reduced staging costs by 40% per patient, mainly due to a decrease in surgical staging procedures.
Conclusion: EUS-FNA can replace more than half of the surgical staging procedures in lung cancer patients with mediastinal and/or upper retroperitoneal PET hot spots, thereby saving 40% of staging costs.
PMCID: PMC1747056  PMID: 15223868
14.  Endoscopic ultrasound-guided biopsies for mediastinal lesions and lymph node diagnosis and staging 
Clinics  2011;66(9):1579-1583.
To disseminate transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) as an alternative to investigate mediastinal tumoral lesions because it is an underused modality that has been available in Brazil for more than 15 years.
Descriptive analysis of a single endoscopy service's experience since 1997 in the accomplishment of EUS-FNA for mediastinal staging of previously known malignancies (Group 1) or diagnostic definition of suspect lymph nodes and masses (Group 2).
EUS-FNA was performed in 51 patients between 26 and 87 years of age. The diameter of the lesions ranged between 1.1 and 9.8 cm (mean 3.9 cm). Their location corresponded to the following stations: higher paratracheal (4 cases), lower paratracheal (7), aortic window (12), para-aortic (6), subcarinal (9), paraesophageal (8), and hilar (5). In Group 1, 17 patients had previously diagnosed primary lung (9), breast (4), kidney (2), colon (1), and bladder (1) cancer. Fifteen of these punctures were positive for malignity. Two others were later submitted to mediastinoscopy, which identified metastases not detected by EUS-FNA. Group 2 comprised 34 patients. Among these patients, EUS-FNA diagnosed 22 neoplasms, five cases of tuberculosis and two duplication cysts. Cytology was inconclusive or without a specific diagnosis in five other cases. Mediastinoscopy identified two undiagnosed cases of oat-cell carcinoma, one lymphoma and one cryptococcosis, and confirmed one reactive lymphadenitis. There were no complications related to the method.
EUS-FNA obviated the need for surgical procedures in 86.3% of cases. Therefore, oncologists, pulmonologists, and thoracic surgeons should always remember the technique's potential and availability.
PMCID: PMC3164408  PMID: 22179163
Endoscopic ultrasound; Mediastinoscopy; Mediastinal Lymphadenopaty; Lung cancer, Staging; Mediastinal Tumor
15.  Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance 
AIM: To evaluate the safety and diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a cohort of pancreatic cancer patients.
METHODS: Of 213 patients with pancreatic cancer evaluated between April 2007 and August 2011, 82 were thought to have resectable pancreatic cancer on the basis of cross-sectional imaging findings. Of these, 54 underwent EUS-FNA before surgery (FNA+ group) and 28 underwent surgery without preoperative EUS-FNA (FNA- group).
RESULTS: All 54 lesions were visible on EUS, and all 54 attempts at FNA were technically successful. The diagnostic accuracy according to cytology and histology findings was 98.1% (53/54) and 77.8% (42/54), respectively, and the total accuracy was 98.1% (53/54). One patient developed mild pancreatitis after EUS-FNA but was successfully treated by conservative therapy. No severe complications occurred after EUS-FNA. In the FNA+ and FNA- groups, the median relapse-free survival (RFS) was 742 and 265 d, respectively (P = 0.0099), and the median overall survival (OS) was 1042 and 557 d, respectively (P = 0.0071). RFS and OS were therefore not inferior in the FNA+ group. These data indicate that the use of EUS-FNA did not influence RFS or OS, nor did it increase the risk of peritoneal recurrence.
CONCLUSION: In patients with resectable pancreatic cancer, preoperative EUS-FNA is a safe and accurate diagnostic method.
PMCID: PMC3974530
Pancreatic cancer; Diagnosis; Biopsy; Endoscopic ultrasound-guided fine-needle aspiration; Preoperative diagnosis
16.  Suspected oesophageal cancer in a 33 year old lady 
A previously healthy 33 year old lady presented with acute dysphagia with endoscopic and CT features of oesophageal carcinoma. Endoscopic ultrasound (EUS) revealed a large subcarinal lymph node compressing at the mid-oesophagus. Fine-needle aspiration (FNA) showed a single well-formed epithelioid granuloma with no evidence of malignancy. Molecular analysis showed the aspirate to be positive for Mycobacterium tuberculosis. She continues to improve with standard anti-TB medication without surgery.
This is a rare case of acute dysphagia secondary to primary tuberculous mediastinal lymphadenopathy. EUS and FNA have completely altered the clinical management of this lady.
PMCID: PMC3199616  PMID: 22096676
Oesophageal cancer; Endoscopic ultrasound; Fine-needle aspiration; Tuberculous lymphadenopathy
17.  Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience 
Gut  1999;44(5):720-726.
BACKGROUND—Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) is a recent innovation in the evaluation of gastrointestinal and pulmonary malignancies. 
AIMS—To review the experience with EUS-FNA of a large single centre. 
METHODS—333 consecutive patients underwent EUS-FNA. Follow up data were available on 327 lesions in 317 patients, including 160 lymph nodes, 144 pancreatic lesions, 15 extraintestinal masses, and eight intramural tumours. 
RESULTS—A primary diagnosis of malignancy was obtained by EUS-FNA in 62% of patients with clinically suspicious lesions. The overall accuracy of EUS-FNA for the diagnosis of malignancy was 86%, with sensitivity of 84% and specificity of 96%. With respect to lesion types, the sensitivity, specificity, and accuracy were 85%, 100%, and 89% for lymph nodes; 82%, 100%, and 85% for pancreatic lesions; 88%, 100%, and 90% for perirectal masses; and 50%, 25%, and 38% for intramural lesions, respectively. Compared with size and sonographic criteria, EUS-FNA in the evaluation of lymph nodes provided superior accuracy and specificity, without compromising sensitivity. Inadequate specimens were obtained from only six patients, including 3/5 with stromal tumors. Only one complication occurred. 
CONCLUSIONS—EUS-FNA is safe and can readily obtain tissue specimens adequate for cytopathological diagnoses. Compared with size and sonographic criteria, it is a superior modality for the detection of nodal metastases. While providing accurate diagnosis of pancreatic and perirectal malignancies, results suggest the technique is less useful for intramural lesions. 

Keywords: endoscopic ultrasound; endosonography; fine needle aspiration biopsy
PMCID: PMC1727480  PMID: 10205212
18.  Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy 
AIM: To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy.
METHODS: Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy.
RESULTS: Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70).
CONCLUSION: Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.
PMCID: PMC3004042  PMID: 21173913
Endoscopic ultrasound; Fine needle aspiration; Pancreatic cancer; p53; Ki-67; Immunohistochemistry
19.  Endoscopic Ultrasound Guided Fine Needle Aspiration Biopsy in Diagnosis of Pancreatic and Peripancreatic Lesions: A Single Center Experience in Korea 
Gut and Liver  2009;3(2):116-121.
Although endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has been introduced and its use has been increasing in Korea, there have not been many reports about its performance. The aim of this study was to assess the utility of EUS-FNA without on-site cytopathologist in establishing the diagnosis of solid pancreatic and peripancreatic masses from a single institution in Korea.
Medical records of 139 patients who underwent EUS-FNA for pancreatic and peripancreatic solid mass in the year 2007, were retrospectively reviewed. By comparing cytopathologic diagnosis of FNA with final diagnosis, sensitivity, specificity, and accuracy were determined, and factors influencing the accuracy as well as complications were analyzed.
One hundred twenty out of 139 cases had final diagnosis of malignancy. Sensitivity, specificity, and accuracy of EUS-FNA were 82%, 89%, and 83%, respectively, and positive and negative predictive values were 100% and 46%, respectively. As for factors influencing the accuracy of FNA, lesion size was marginally significant (p-value 0.08) by multivariate analysis.
EUS-FNA performed without on-site cytopathologist was found to be accurate and safe, and thus EUS-FNA should be a part of the standard management algorithm for pancreatic and peripancreatic mass.
PMCID: PMC2852702  PMID: 20431733
EUS-FNA; Pancreatic neoplasms; Peripancreatic mass; Diagnostic accuracy
20.  Combined Endobronchial and Transesophageal Approach of an Ultrasound Bronchoscope for Mediastinal Staging of Lung Cancer 
PLoS ONE  2014;9(3):e91893.
We evaluated the utility of a combined approach using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) for mediastinal staging of lung cancer.
An EBUS-TBNA database was analyzed retrospectively. EUS-FNA-B/E was performed after EBUS-TBNA when mediastinal lymph nodes were not accessible using EBUS-TBNA or when tissue sampling using EBUS-TBNA alone was inadequate.
During the study period, 44 patients were enrolled. EBUS-TBNA and EUS-FNA-B/E were performed on 79 and 52 lymph nodes, respectively. The sensitivity, specificity, and accuracy of mediastinal N-staging using EBUS-TBNA alone were 79%, 100%, and 84%, respectively. The sensitivity, specificity, and accuracy of mediastinal N-staging using a combination of EBUS-TBNA and EUS-FNA-B/E were 100%, 100%, and 100%, respectively. Significant differences in sensitivity (P = 0.008) and accuracy (P = 0.004) of mediastinal N-staging were evident when EBUS-TBNA alone and the combined procedure were compared. The nodal stage shifted higher after use of the EUS-FNA-B/E procedure in six cases (13%). No serious complication associated with the procedures was noted.
Use of a combination of EBUS-TBNA and EUS-FNA-B/E can afford better sensitivity and accuracy of mediastinal N-staging compared with use of EBUS-TBNA alone. Such combined procedures should be considered for examination of lesions that are inaccessible or difficult to access by EBUS-TBNA.
PMCID: PMC3954842  PMID: 24632834
21.  Two smalls in one: Coincident small cell carcinoma and small lymphocytic lymphoma in a lymph node diagnosed by fine-needle aspiration biopsy 
CytoJournal  2012;9:5.
B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) is one of the most common lymphoproliferative disorders in western countries. Patients with SLL / CLL are at increased risk of site-specific secondary cancers. We present a unique case of a 71-year-old male, with a history of SLL / CLL, who presented with pulmonary symptoms and a mediastinal mass. Fine needle aspiration (FNA) of the mediastinal lymph node revealed synchronous SLL / CLL and small cell carcinoma (SCC).
Materials and Methods:
The patient underwent a computed tomography (CT) scan of the chest and endobronchial ultrasound-guided transbronchial fine needle aspiration of the mediastinal lymph node (4R). The sample was submitted for cytopathology, immunohistochemical stains, and flow cytometry evaluation.
Fine needle aspiration of the mediastinal lymph node revealed neoplastic cells, in clusters and singly, with cytological features suggestive of small cell carcinoma. The immunohistochemistry results confirmed this diagnosis. Small-to-medium, mature-appearing lymphocytes were also present in the background. Flow cytometry analysis revealed that these lymphocytes possessed an immunophenotype consistent with CLL / SLL.
This case illustrates the importance of a pathologist's awareness of the possibility of concurrent lymphoma and metastatic carcinoma in a lymph node. When evaluating lymph nodes, pathologists must strive to identify both foreign cells and subtle lymphoid changes. As demonstrated by our case, ancillary techniques (such as immunohistochemistry and flow cytometry) can be critical to making a complete and accurate diagnosis. The diagnosis of small cell carcinoma in the enlarged lymph node, primarily harboring CLL / SLL, is of critical importance for decision-making and treatment purposes, in addition to having a significant adverse impact on the overall survival.
PMCID: PMC3307210  PMID: 22438859
Small cell carcinoma; lymphoma; FNA
22.  Endobronchial Ultrasound-guided Transbronchial Needle Biopsy for Diagnosis of Mediastinal Lymphadenopathy in Patients with Extrathoracic Malignancy 
Journal of Korean Medical Science  2011;26(2):274-278.
Mediastinal lymphadenopathy associated with extrathoracic malignancy or a metastasis of unknown origin (MUO) requires pathological verification. Surgical exploration or endoscopic ultrasound-guided fine needle aspiration is limited to application. We investigated the effectiveness of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) for evaluating mediastinal lymphadenopathy in patients with an extrathoracic malignancy. We retrospectively analyzed data from 59 patients who underwent EBUS-TBNA with a core biopsy because of a suspected mediastinal metastasis between September 2008 and August 2010. All patients had previously been diagnosed with an extrathoracic malignancy (n = 39, 66.1%) or a suspected MUO without a thoracic lesion (n = 20, 33.9%). A total of 88 lymph nodes was analyzed. EBUS-TBNA findings indicated malignancies in 34 patients (57.6%). The EBUS-TBNA sensitivity and specificity for the detection of mediastinal malignancy in patients with a previous extrathoracic malignancy were 96.3% and 100%, respectively. For MUO patients without a thoracic lesion, the sensitivity and specificity were 61.5% and 100%, respectively. The overall sensitivity and specificity were 81.0% and 100%, respectively (P = 0.053). EBUS-TBNA is a safe and effective modality for evaluating mediastinal lymphadenopathy in patients with a previous extrathoracic malignancy or a MUO without a thoracic lesion. The application of this diagnostic tool is likely to have significant clinical implications.
PMCID: PMC3031014  PMID: 21286021
EBUS; Extrathoracic Malignancy; Mediastinal Adenopathy; Metastatic Cancer of Unknown Primary Site; MUO
23.  Endoscopic ultrasound fine-needle aspiration characteristics of primary adenocarcinoma versus other malignant neoplasms of the pancreas 
Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic).
To compare and characterize primary pancreatic adenocarcinoma versus other malignant neoplasms, hereafter referred to as nonprimary pancreatic adenocarcinoma (NPPA), diagnosed by EUS-guided FNA.
The present study was a retrospective analysis of a prospectively maintained database. The setting was a tertiary care, academic medical centre. Patients referred for suspected pancreatic neoplasms were evaluated. Based on EUS-FNA characteristics, primary pancreatic adenocarcinoma was differentiated from other malignant neoplasms. The subset of other neoplasms was defined as malignant lesions that were ‘NPPAs’ (ie, predominantly solid or solid/cystic based on EUS appearance and primary malignant lesions or metastatic lesions to the pancreas). Pancreatic masses that were benign cystic lesions (pseudocyst, simple cyst, serous cystadenoma) and focal inflammatory lesions (acute, chronic and autoimmune pancreatitis) were excluded.
A total of 230 patients were evaluated using EUS-FNA for suspected pancreatic mass lesions. Thirty-eight patients were excluded because they were diagnosed with inflammatory lesions or had purely benign cysts. One hundred ninety-two patients had confirmed malignant pancreatic neoplasms (ie, pancreatic adenocarcinoma [n=144], NPPA [n=48]). When comparing adenocarcinoma with NPPA lesions, there was no significant difference in mean age (P=0.0675), sex (P=0.3595) or average lesion size (P=0.3801). On average, four FNA passes were necessary to establish a cytological diagnosis in both lesion subtypes (P=0.396). Adenocarcinomas were more likely to be located in the pancreatic head (P=0.0198), whereas masses in the tail were more likely to be NPPAs (P=0.0006). Adenocarcinomas were also more likely to exhibit vascular invasion (OR 4.37; P=0.0011), malignant lymphadenopathy (P=0.0006), pancreatic duct dilation (OR 2.4; P=0.022) and common bile duct dilation (OR 2.87; P=0.039).
Adenocarcinoma was more likely to be present in the head of the pancreas, have lymph node and vascular involvement, as well as evidence of pancreatic duct and common bile duct obstruction. Of all malignant pancreatic lesions analyzed by EUS-FNA, 25% were NPPA, suggesting that FNA is crucial in establishing a diagnosis and may be helpful in preoperative planning.
PMCID: PMC3472907  PMID: 23061060
Adenocarcinoma; Endoscopic ultrasound; Fine-needle aspiration; Malignant neoplasm; Nonprimary pancreatic adenocarcinoma; Pancreas
24.  CT-guided fine-needle aspiration of lung nodules: effect on outcome of using coaxial technique and immediate cytological evaluation. 
The Ulster Medical Journal  2004;73(1):32-36.
PURPOSE: To evaluate the risk of pneumothorax during CT-guided fine-needle aspiration (FNA) of lung nodules with single needle and coaxial needle techniques and to assess the effect on diagnostic accuracy of immediate cytological examination of lung FNA samples. MATERIALS AND METHODS: This prospective study analysed 53 patients undergoing transthoracic FNA biopsy of lung. 36 cases were performed by a radiologist using a coaxial technique, with 17 cases performed by a radiologist using a direct single-needle method. Effect of technique on occurrence of pneumothorax was recorded. FNA samples from all the patients in the study were examined immediately on-site by a cytologist or MLSO to determine whether sufficient aspirate had been obtained. Provisional diagnosis at immediate examination was compared to final diagnosis following full pathological evaluation. RESULTS: Coaxial and non-coaxial groups were comparable for age and gender. Number of pleural passes was significantly lower in coaxial group (P < 0.01). Pneumothorax occurred in six (17%) of the 36 patients biopsied by coaxial technique, compared to four (24%) of the 17 patients by non-coaxial method (P = 0.55). Chest tube placement was required in four patients (11%) in the coaxial group, and two patients (12%) in the non-coaxial group (P = 0.85). A provisional cytological diagnosis was recorded for 74% of the patients in the study. 83% of the provisional reports were accurate on comparison with full pathology report. Specimen size was sufficient in 81% of cases. CONCLUSIONS: The use of coaxial technique for CT-guided lung FNA biopsy reduced the number of pleural passes but did not significantly reduce the occurrence of pneumothorax. Immediate cytological examination of FNA specimens provided an accurate provisional diagnosis in the majority of cases, and should be routinely employed.
PMCID: PMC2475445  PMID: 15244123
25.  Dynamic telecytopathology of on site rapid cytology diagnoses for pancreatic carcinoma 
CytoJournal  2006;3:27.
Diagnosis of pancreatic lesions can be accurately performed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) with onsite cytopathologists to assess specimen adequacy and to determine a preliminary diagnosis. Considerable time is needed to perform on-site assessments. This takes away work time of cytopathologists and prohibits them from serving remote locations. It is therefore logical to ask if real-time telecytopathology could be used to assess specimen adequacy and if telecytopathology diagnosis has the same level of agreement to the final diagnosis as that of onsite evaluation. In this study, we compare agreement between cytodiagnoses rendered using telecytopathology with onsite and final interpretations.
40 Diff-Quik-stained EUS-FNA were re-evaluated retrospectively (patient ages 31–62, 19:21 male:female, 15 non-malignant lesions, 25 malignant lesions as classified by final diagnosis). Each previously assessed by a cytopathologist and finally reviewed by the same or different cytopathologist. Blinded to the final diagnosis, a resident pathologist re-screened all slides for each case, selected a slide and marked the diagnostic cells most representative of the lesion. Blinded to the diagnosis, one cytopathologist assessed the marked cells through a real time remotely operated telecytopathology system (MedMicroscopy). Diagnosis and time spent were recorded. Kappa statistic was used to compare agreements between telecytopathology vs. original onsite vs. final diagnoses.
Time spent for prescreening ranged from 1 to 5 minutes (mean 2.6 +/- 1.3 minutes) and time spent for telecytopathology diagnosis ranged from 2–20 minutes (mean 7.5 +/- 4.5 minutes). Kappa statistics, K, was as follows: telecytopathology versus onsite diagnosis K, 95% CI = 0.65, 0.41–0.88, for telecytopathology versus final K, 95% CI = 0.61, 0.37–0.85 and for onsite diagnosis versus final K, 95% CI = 0.79, 0.61–0.98. There is no significant difference in agreement between onsite and telecytopathology diagnoses. Kappa values for telecytopathology were less than onsite evaluation when compared to the final diagnosis; however, the difference was not statistically significant.
This retrospective study demonstrates the potential use of telecytopathology as a valid substitute for onsite evaluation of pancreatic carcinoma by EUS-FNA.
PMCID: PMC1713251  PMID: 17156485

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