EUS-guided Trucut needle biopsy: is more tissue really better?
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Biomedical subjects
Publications and source records attributed to Michael B Wallace.
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This article outlines the basic principals of lung cancer staging and EUS-FNA techniques and suggests appropriate and inappropriate indications of EUS-FNA for lung cancer.
New techniques have expanded the role of endoscopy in the diagnosis, staging, therapy, and palliation of malignancies. Three major areas of emerging technologies--endoscopic ultrasound (EUS), luminal stent technology, and photodynamic therapy (PDT)--are discussed in this article. Although EUS and PDT have been used for more than two decades, they have only recently emerged as established integral methods in the armamentarium of the gastrointestinal endoscopist.
Barrett's esophagus is the most important risk factor in the development of adenocarcinoma of the esophagus. Barrett's esophagus is generally regarded as the most significant complication of gastroesophageal reflux disease. Adenocarcinoma occurs more frequently in the setting of high-grade dysplasia. The prognosis of adenocarcinoma of the esophagus is strongly correlated with the stage of disease. The prognosis of late stage disease is extremely poor. Cure may be achieved when disease is found at an early stage. Esophagectomy has been the definitive treatment of limited stage adenocarcinoma of the esophagus. The morbidity and mortality rate for esophagectomy is high. Therefore, alternative endoscopic methods for curative treatments have gained popularity. The two main endoscopic therapies, photodynamic therapy and endoscopic mucosal resection, are both effective when applied to early-stage disease. Traditional evaluation of the patient with Barrett's esophagus with high-grade dysplasia includes esophago-gastro-duodenoscopy (EGD) with biopsy and computed tomography of the chest. Endoscopic ultrasound (EUS) has gained popularity in the evaluation of the patient with Barrett's esophagus and high-grade dysplasia because it is the only imaging technique capable of delineating the separate histologic layers of the gastrointestinal tract. The principal role of EUS in evaluating patients with Barrett's-associated dysplasia is to identify patients who may be candidates for endoscopic ablative (endoscopic mucosal resection, photodynamic therapy) therapies. EUS has been shown to be superior to computed tomography (including high resolution spiral CT) or magnetic resonance imaging for preoperative staging in patients with high-grade dysplasia and carcinoma. This review of the literature summarizes the ability of EUS to evaluate patients with Barrett's esophagus and high-grade dysplasia.
OBJECTIVES: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases. METHODS: Patients with NSCLC were evaluated with chest CT and positron emission tomography scans. Those patients without evidence of metastases (87 patients) underwent EUS-guided FNA. Lymph nodes from levels 2, 4, 5, 7, 8, and 9 were sampled and evaluated by standard cytopathology and real-time RT-PCR. Normal control FNA specimens were obtained from patients without cancer who were undergoing EUS for benign disease (17 control specimens). For each sample, messenger RNA was extracted and real-time RT-PCR was used to quantitate the expression of six lung cancer-associated genes (ie, CEA, CK19, KS1/4, lunx, muc1, and PDEF) relative to the expression of an internal control gene (beta(2)-microglobulin). RESULTS: Clinical thresholds of marker positivity were set at 100% specificity, as determined by the receiver operating characteristic curve analysis. Of the cytology-positive lymph nodes (27 lymph nodes), the expression of the KS1/4 gene was above its respective clinical threshold in 25 of 27 samples (93%), making this the most sensitive marker for the detection of metastatic NSCLC. At least one of the six lung cancer-associated genes was overexpressed in 18 of 61 cytology-negative patients (30%), of which KS1/4 was overexpressed in 15 of 61 patients (25%). CONCLUSIONS: Based on the high accuracy of EUS-guided FNA/RT-PCR, we predict that some of the patients in the cytology-negative/marker-positive category will have high NSCLC recurrence rates. Among the genes used in our marker panel, KS1/4 appears particularly useful for the detection of overt or occult metastatic disease.
Since its development and introduction to clinical practice, endoscopic ultrasonography (EUS) has progressed rapidly from being a purely imaging modality with limited use in the detection of small pancreatic cancers to one that can provide a tissue diagnosis by fine-needle aspiration (FNA) and deliver therapy. EUS has now firmly established a place as the investigation of choice in the diagnosis, locoregional staging and management of a wide range of gastrointestinal cancers. With the increasing use of FNA, the accuracy of EUS has substantially improved and may become a stand-alone investigation in some situations. However, it is recommended that a combination of information obtained from other imaging modalities and EUS is needed to maximize the accuracy, in particular to complete staging beyond locoregional stage. In addition to well-established indications, newer applications of EUS are emerging and are no longer limited to the gastrointestinal system. In lung cancer, EUS combined with endobronchial ultrasonography is emerging as an accurate, minimally invasive, nonsurgical alternative to staging of the mediastinum. Furthermore, the ability of EUS to acquire tissue safely and conveniently results in a potential role of the molecular diagnostics to enhance the performance of EUS-guided FNA. Besides a diagnostic role of EUS, there continues to be technological advances in the field of interventional EUS, with many potential applications under investigation. This review focuses on the current and future roles of EUS in the diagnosis and management of cancers.
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BACKGROUND: Computed tomography (CT) is the most common method of staging lung cancer. We have previously shown endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) to be highly accurate in staging patients with nonsmall cell lung cancer (NSCLC) who have enlarged mediastinal lymph nodes on CT scan. In this study we report the accuracy and yield of EUS-FNA in staging patients without enlarged mediastinal lymph nodes by CT. METHODS: Patients with NSCLC and CT scan showing no enlarged mediastinal lymph nodes (> 1 cm for all nodes except > 1.2 cm for subcarinal) in the mediastinum underwent EUS. Fine needle aspiration was performed on at least one lymph node, if present, in the upper mediastinum, aortopulmonary window, subcarinal, and periesophagus regions. Each specimen was evaluated with on-site cytopathology and confirmed with complete cytopathologic examination. RESULTS: Sixty-nine patients without enlarged mediastinal lymph nodes were evaluated. Endoscopic ultrasound detected malignant mediastinal lymph nodes in 14 of 69 patients as well as other advanced (American Joint Committee on Cancer [AJCC] stage III/IV) in 3 others (1 left adrenal, and 2 with mediastinal invasion of tumor) for a total of 17 of 69 (25%, 95% confidence interval: 16% to 34%) patients. Eleven additional patients were found to have advanced disease by bronchoscopy (2), mediastinoscopy (2), and thoracotomy with mediastinal lymph node dissection (7). The sensitivity of EUS for advanced mediastinal disease was 61% (49% to 75%), and the specificity was 98% (95% to 100%). CONCLUSIONS: Endoscopic ultrasound guided fine needle aspiration can detect advanced mediastinal disease and avoid unnecessary surgical exploration in almost one of four patients who have no evidence of mediastinal disease on CT scan. In addition to previously reported results in patients with enlarged lymph nodes on CT, these data suggest that all potentially operable patients with nonmetastatic NSCLC may benefit from EUS staging.
BACKGROUND: EUS is commonly used in the staging of GI, thoracic, and other malignancies. Studies suggest EUS can detect occult liver metastases, but the frequency with which this occurs is unknown. METHODS: Records were reviewed for all patients seen during a 3-year period who underwent EUS of the upper-GI tract for staging of known or suspected malignancy. Patients were included if there was histopathologic evidence of malignancy, they had undergone noninvasive liver imaging within 6 weeks of EUS, and liver surveillance was specifically mentioned in the report of the EUS procedure. RESULTS: A total of 222 patients were included. Liver lesions were seen in 27 patients, 17 of whom had an abnormal noninvasive liver imaging test. EUS-guided FNA of the liver was performed in 21 patients and was diagnostic of malignancy in 15 (6.8%), 5 of whom (2.3%) had normal noninvasive imaging. In 6 patients, the EUS-guided FNA result was benign. EUS missed liver lesions in 4 patients known to have abnormalities by other imaging modalities. CONCLUSIONS: EUS can detect occult liver metastases in patients in whom noninvasive hepatic imaging studies are normal, although the frequency at which such lesions are detected is low. Liver surveillance during EUS is worthwhile for patients in whom there is another indication for the procedure; but, at present, EUS should not replace traditional imaging modalities.
BACKGROUND: Flexible endoscopy plays an important role in digestive health. However, access to endoscopy is limited in many rural areas throughout the world. Training non-physician personal to perform diagnostic endoscopy and to transmit images to a central hospital, where experienced endoscopists can review the procedures, may improve digestive health for patients in remote areas. The aim of this study was to evaluate the diagnostic quality and accuracy of upper-GI tele-endoscopy. METHODS: Fifty patients scheduled for EGD underwent upper-GI tele-endoscopy. The procedures were observed simultaneously by the endoscopist and a gastroenterologist observing from a remote station connected by 4 integrated services digital network telephone lines. The interpretation of the findings by both were compared and concordance for diagnosis of major and minor lesions was analyzed. RESULTS: Tele-endoscopic image quality was adequate to support diagnosis of abnormal lesions by the remote observer. Technical issues included worsening image quality caused by mild pixelation during rapid endoscope movement and rare loss of the telephone lines. The endoscopist identified 47 different major and 44 minor findings in the 50 patients. The observer missed one major lesion (columnar-lined esophagus) because of suspected inflammation and described 10 non-existing major lesions (sensitivity 98%: 95% CI[89%, 99%], specificity 80%: 95% CI[66%, 90%]). Some of the differences were because of interobserver variability. CONCLUSIONS: Upper-GI tele-endoscopy by using telephone lines has good diagnostic quality and is highly sensitive with regard to major findings. The misinterpretation of certain findings (esophageal ring, gastric erosions) may be caused by interobserver variability. The data strongly suggest that endoscopist and observer see similar endoscopic views.
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.
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.
BACKGROUND: Unsedated esophagoscopy with ultrathin endoscopes is a valuable screening modality for Barrett's esophagus, but the stomach and the duodenum cannot be examined completely with the smallest and best tolerated of these endoscopes. There are no data as to how often disease in the stomach and the duodenum would be missed when using this screening strategy. Our hypothesis is that patients with reflux symptoms, in the absence of daily abdominal pain, nausea, or history of ulcer, were unlikely to have clinically significant gastroduodenal disease. METHODS: Patients scheduled for upper endoscopy at a single outpatient endoscopy unit in a tertiary referral center were screened. The inclusion criterion was reflux symptoms as the primary indication for upper endoscopy. Patients with another valid indication were excluded. A detailed history was recorded and symptom questionnaire completed for each patient before endoscopy; these data were compared with the endoscopy findings. RESULTS: A total of 175 patients were included. Indications for upper endoscopy were the following: worsening symptoms (n=74), ongoing reflux despite therapy (n=27), and long-standing reflux (n=74). Major esophageal findings were discovered in 95 patients. In 10 patients, major gastric or duodenal findings were detected as follows: erosive gastritis (n=8), gastric ulcer (n=2), duodenal ulcer (n=2), erosive duodenitis (n=2), and duodenal polyp (n=1). Daily abdominal pain (p=0.014) or possibly daily nausea (p=0.028 unadjusted, 0.197 adjusted) was associated with major gastric/duodenal disease. Patients without daily abdominal pain, nausea, or a history of gastric/duodenal ulcer were much less likely to have major disease (0.9%) than patients with one of these predictors (13.2%, p=0.00097). CONCLUSIONS: Daily abdominal pain and nausea, in combination with a history of ulcer disease, are strong predictors of major gastric or duodenal disease. Patients with reflux without these predictors are highly unlikely to have a major disease involving the stomach or duodenum, and are suitable candidates for esophagoscopy alone.
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OBJECTIVES: The goals of this study were to compare women and men's understanding of screening flexible sigmoidoscopy (FS) and to identify predictors of endoscopic colorectal cancer (CRC) screening. METHODS: We mailed a 36-item questionnaire to asymptomatic patients aged 50 years or older who were scheduled for routine health assessments at a large multispecialty health-care group. Data collection included demographics, health behaviors, psychosocial factors, and CRC screening compliance. We followed participants for 1 year and assessed completion of endoscopic CRC screening. Both cross-sectional results examining previous screening and prospective results examining screening 1 year later were evaluated. RESULTS: 554 (54%) of 998 patients responded to the survey. Responses of 13 patients were excluded in the analyses due to unverifiable screening outcome. The majority of the respondents were white, and their average age was 62 years. Women reported significantly more embarrassment and fear about having FS than men. Women were more willing to consider having a FS if a female endoscopist performed the procedure. Of the 334 participants who were eligible to have endoscopic CRC screening, 53 (16%) had the procedure within a year. The odds of having the endoscopic procedures increased with the length of time the patients were under the care of their primary care providers and how strongly patients believed that one should have an FS even without symptoms. CONCLUSION: Our findings suggest some unique gender-specific attitudes and beliefs that act as potential barriers for CRC screening and further support the important role of primary care providers in facilitating timely completion of screening.
OBJECTIVES: Palliation of terminal conditions such as malignant dysphagia must take into account individual preferences for aggressive or nonaggressive care, with a focus on quality of life. Despite this, there are very few data on patients' preferences for palliative therapy. This study is designed to quantitatively determine individual preferences for palliation of malignant dysphagia using health state utilities (HSU). METHODS: HSU were measured using three methods: time trade-off (TTO), visual analog scale (VAS), and the EQ-5D. Patients with esophageal cancer were asked to rate their own state of health and of three standardized scenarios of local, regional, and metastatic disease. RESULTS: Fifty patients with esophageal cancer were enrolled. Using the TTO method, the utilities of their own health state were 0.80 (95% CI 0.59-0.99) for localized, 0.54 (0.37-0.70) for regional, and 0.52 (0.32-0.71) for metastatic cancer showing no significant difference in mean utility scores for the three staging groups. VAS and EQ5D gave statistically similar values to TTO. Patients consistently rated their own utility better than the utility of standardized scenarios with similar stage and prognosis. Independent of their staging, patients with high dysphagia scores rated their utility worse than patients with low dysphagia scores. CONCLUSIONS: These results confirm the perceived poor state of health of patients with esophageal cancer and are substantially lower than previous estimates in operated patients. Cost-effectiveness models must take into account significant differences between patients' assessment of their own state of health, and that of a "societal" perspective of others with a similar disease. All three methods provided similar estimates. Given the ease of use of VAS and EQ-5D, these methods may be preferable to TTO.
The diagnosis of chronic pancreatitis at an early stage is a clinical challenge. A major limitation is the inability of clinicians to obtain a tissue or histological sample to confirm the clinical diagnosis. Currently available imaging modalities have limited sensitivity or specificity for diagnosing early chronic pancreatitis. Endoscopic ultrasonography (EUS), introduced in the early 1980's, was first developed to image the pancreas. It overcame many of the limitations (abdominal gas and fat) of transabdominal ultrasonography when evaluating patients for possible pancreatic diseases. To date, EUS represents the most promising imaging modality for diagnosing chronic pancreatitis. Contrary to endoscopic retrograde pancreatography (ERCP), EUS has a very low risk of complications and can detect abnormalities suggestive of chronic pancreatitis in the pancreatic parenchyma and ductal system which are not visible on any other imaging modality. The minimal changes in echotexture are difficult to interpret because there is no reliable gold standard confirmatory test. There is now some evidence in the literature suggesting that these early changes detected by EUS correlate with the histological changes of chronic pancreatitis and may predict progression to more advanced disease. The EUS diagnosis of chronic pancreatitis relies on quantitative (more than qualitative) parenchymal and ductal criteria found during evaluation of the pancreas. It is generally accepted that, in the absence of any criteria, chronic pancreatitis is unlikely, whereas in the presence of 5 or more criteria (out of 9-11) chronic pancreatitis is likely although ERCP and pancreatic function tests may still be normal. The diagnostic significance of patients with fewer (1-4) criteria found on EUS is currently unclear, particularly when other diagnostic tests such as ERCP and function testing are normal. In these cases, there is a potential for "over-diagnosis" of chronic pancreatitis, since the EUS changes cannot be confirmed by other modalities. How can we better understand the implications of EUS detected changes when other tests are normal?
Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined.