- Email: [email protected]
Transesophageal Endoscopic Ultrasound-Guided Mediastinal Lymph Node Aspiration
ronment for thrombus formation. This delayed LAA “myopathy” may be responsible for the continued risk of stroke in patients with AF. The higher incidence of stroke in elderly patients with AF may be a function of the longer duration of AF and delayed LAA “myopathy,” rather than age per se. The finding that AF-induced LAA “myopathy” may develop gradually over time has important implications relative to anticoagulation. It suggests that a “one-time” decision regarding anticoagulation in patients with AF is not justified. Perhaps such patients should have TEE performed at 1- or 2-year intervals to monitor LAA function; if and when a LAA “myopathy” develops, eg, when LAA emptying velocities fall ⬍ 20 cm/s, then warfarin should be started. Serial TEE may also be justified in patients with sinus rhythm and demand ventricular pacing in whom deterioration of LAA function has been recently reported.15 A recent study16 and editorial17 have emphasized the role of TEE in the decision-making process concerning anticoagulation in AF. The TEE appearance of poor LAA function, spontaneous contrast, or thrombus are indications for warfarin.15 The current paper by Tsai et al underscores the importance of assessing the LAA at regular intervals, as a one-time decision seems inappropriate, given the decline in LAA function over time leading to the development of a delayed LAA “myopathy,” and the known persistent risk of stroke in patients with AF. Charles Pollick, MD Los Angeles, CA Dr. Pollick is Director, Non-Invasive Cardiology, Good Samaritan Hospital, and Associate Clinical Professor, UCLA School of Medicine. Correspondence to: Charles Pollick, MD, Los Angeles Cardiology Associates, 1245 Wilshire Blvd, Suite 703, Los Angeles, CA 90017; e-mail: [email protected]
References 1 Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA 1994; 271:840 – 844 2 Wolf PA, Abbott RD, Kannel WB, et al. Atrial fibrillation: a major contributor to stroke in the elderly; the Framingham study. Arch Intern Med 1987; 147:1561–1564 3 Wolf PA, Dawber TR, Thomas HE, et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28:973–977 4 Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population based estimates. Am J Cardiol 1998; 82(Suppl 8A):2N–9N 5 Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Arch Intern Med 1994; 154:1449 –1457 6 Aberg H. Atrial fibrillation: 1. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969; 185:373–379 298
7 Yamanouchi H, Tormonaga M, Shimada H, et al. Nonvalvular atrial fibrillation as a cause of fatal massive cerebral infarction in the elderly. Stroke 1989; 20:1653–1656 8 Fisher CM. Reducing the risks of cerebral embolism. Geriatrics 1979; 34:59 – 66 9 Aschenberg W, Schluter M, Kremer P, et al. Transesophageal two-dimensional echocardiography for the detection of LAA thrombus. J Am Coll Cardiol 1986; 7:163–166 10 Sullivan H, Pollick C. Incomplete LAA ligation that simulates mitral regurgitation. J Am Soc Echo 1990; 3:75–77 11 Pollick C, Taylor D. Assessment of LAA function by transesophageal echocardiography. Circulation 1991; 84:223–231 12 Kamp O, Verhorst PM, Welling RC, et al. Importance of LAA flow as a predictor of thromboembolic events in patients with atrial fibrillation. Eur Heart J 1999; 20:979 –985 13 Wolf PA, Kannel WB, McGee DL, et al. Duration of atrial fibrillation and imminence of stroke: the Framingham study. Stroke 1983; 14:664 – 667 14 Zipes DP. Atrial fibrillation. a tachycardia-induced atrial cardiomyopathy. Circulation 1997; 95:562–564. 15 Sparks PB, Mond HG, Vohra JK, et al. Mechanical remodeling of the left atrium after loss of atrioventricular synchrony. A long-term study in humans. Circulation 1999; 100:1714 –1721. 16 Stollberger C, Chnupa P, Kronik G, et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation: ELAT Study Group; embolism in left atrial thrombi. Ann Intern Med 1998; 128:630 – 638 17 Silverman DI, Manning WJ. Role of echocardiography in patients undergoing elective cardioversion of atrial fibrillation. Circulation 1998; 98:479 – 486
Transesophageal Endoscopic Ultrasound-Guided Mediastinal Lymph Node Aspiration Does the End Justify the Means? ultrasonography (EUS) is a unique E ndoscopic imaging modality where a high-frequency ultra-
sound transducer is incorporated into the tip of an endoscope to provide high-resolution images of the GI wall and structures in close proximity to the GI tract above and below the diaphragm. EUS is the most accurate method for local tumor and lymph node staging of the GI cancers, with many other applications as well in the GI tract. The development of echoendoscopes that can image parallel to the long axis of the instrument allows visualization of a needle along its length, making EUS-guided intervention a clinical reality. Endosonography has evolved from a technological accomplishment to a clinically useful procedure for sampling peri-GI lymph nodes, pancreatic masses, and submucosal GI lesions, etc.1– 6 EUS-guided injection of therapeutic substances has also begun.7–10 Since EUS during transesophageal imaging provides high-resolution images of the posterior mediastinum, considerable interest and investigation have Editorials
occurred over the last few years about its utility in the detection of mediastinal lymphadenopathy in lung cancer and other malignancies. Initially, before the development of interventional EUS techniques, the focus was on studying echo features of lymph nodes to predict malignant invasion. Lymph nodes seen by EUS that were larger than 1 cm, round, hypoechoic, and with distinct margins were considered to be malignant.11 These criteria during EUS were initially described for GI cancers, eg, esophageal,11 and were later applied to mediastinal lymph nodes in lung cancer. These EUS echo features of mediastinal lymph nodes in lung cancer have been shown in one study to have accuracy of 84% compared to CT scan accuracy of 49%.12 However, the reliance on EUS echo features to diagnose malignant lymph node invasion in lung cancer has problems of interobserver variability, lack of standardization of frequencies used to study the lymph nodes, as well as lack of uniform criteria to label a lymph node as hypoechoic or with sharp, distinct margins.13 In addition, it has also been shown in the study by Bhutani et at13 that although the presence of echo features described above could predict malignant invasion about 80% of the time; however, only 25% of nodes that had malignant invasion had all four echo features. This study that included enlarged lymph nodes in patients with esophageal, lung, and pancreatic cancers also compared the accuracy of echo features of lymph nodes with EUS-guided fine-needle aspiration (FNA) and found that EUSguided FNA was a more reliable method for predicting lymph node invasion than echo features. Transesophageal EUS-guided real-time FNA of mediastinal lymph nodes has become a clinically useful minimally invasive method for detecting malignant lymph node invasion, as shown in this issue of CHEST (see page 339) by Fritscher-Ravens and colleagues. The accuracy of EUS-guided mediastinal lymph node FNA in this series was 97%, which is comparable to the accuracy in studies from other centers.12–15 In addition, this procedure appears to be safe in expert hands, with no significant complications occurring in the current series. This procedure is performed under conscious sedation, similar to any other endoscopy, and the patient can be discharged from the hospital after observation in the recovery room for 45 to 60 min. Following is a summarization of the advantages and limitations of this technique, so that EUS-guided FNA of mediastinal lymph nodes could be used in the appropriate clinical setting. (1) In patients with known non-small cell lung cancer who have mediastinal lymph nodes on CT scan and who have a negative transbronchial FNA, EUS-guided FNA can be used as an accurate,
minimally invasive method to stage the mediastinum. The accuracy of EUS-guided FNA in this setting is about 96%.12 A positive result by FNA for cancer would then obviate the need for more invasive staging modalities such as mediastinoscopy. (2) EUS-guided FNA also appears to have a cost advantage over mediastinal lymph node staging in lung cancer. Cost data in a study12 on EUS-guided FNA for staging lung cancer revealed that the total cost for EUS was $1,975, with mediastinoscopy and thoracotomy significantly more expensive at $7,759 and $26,028, respectively. As mentioned before, if a EUS-guided FNA result is positive for cancer, it would obviate the need for more expensive and invasive procedures, such as mediastinoscopy and thoracotomy. A decision model analysis has also been performed to calculate the average cost per year of survival in patients with lung carcinoma. This model resulted in an average cost per year of survival of EUS-guided FNA to be $3,810 and $9,757 for mediastinoscopy.16 (3) When a primary lung mass is suspected on CT and mediastinal lymph nodes are seen, if bronchoscopic and transbronchial methods fail to acquire a primary diagnosis, EUS-guided mediastinal FNA in these patients could potentially provide a primary diagnosis (as well as staging information). These were the inclusion criteria for the current study by Fritscher-Ravens et al, and a final diagnosis of malignancy was achieved in 25 of 35 patients. Furthermore, EUS can also play a significant role in evaluating mediastinal lymphadenopathy of unknown origin with no primary lung mass on CT. If transbronchial FNA results are negative in these patients, EUS-guided FNA can provide a diagnosis of malignancy.13 (4) Lymph nodes that are located in the subcarina, aortopulmonary window, and the paraesophageal area are difficult to approach during procedures such as mediastinoscopy.12,14 However, these locations are best suited and the most accessible for puncture during transesophageal EUS.12,14 (5) Previous studies on the utility of EUS-guided FNA have only included patients who have enlarged mediastinal lymph nodes by CT scan. Generally by CT scan criteria, lymph nodes that are ⱖ 1 cm in size are considered to be enlarged. However, using size alone as a criteria for malignant invasion of lymph nodes by CT may not be ideal, since lymph nodes ⬍ 1 cm can potentially have malignant invasion. In a series of patients who underwent CT scan and EUS, we found a significant number of patients with thoracic malignancies who had posterior mediastinal lymphadenopathy by EUS with negative CT criteria for enlarged lymph nodes. Only 50% of patients in this series who underwent EUS-guided transesophCHEST / 117 / 2 / FEBRUARY, 2000
299
ageal FNA had enlarged nodes by CT scan.17 Early data from another group also suggest that EUSguided FNA can diagnose malignant invasion in small mediastinal lymph nodes that are negative by CT criteria.18 This concept is further strengthened by FritscherRavens and colleagues. It is noteworthy that seven patients who underwent EUS-guided mediastinal lymph node FNA had lymph nodes that were ⬍ 1 cm in diameter and would not have been classified as enlarged by CT scan. Four of these aspirates revealed malignant cells. Thus, in suspected or known pulmonary malignancies, even if small (⬍ 1 cm) lymph nodes are seen in the posterior mediastinum, it might be worthwhile to perform EUS imaging and possible FNA of these lymph nodes. However, further studies in this area are needed to establish the utility of EUS in patients who do not have enlarged nodes by CT criteria. EUS with FNA also has some limitations. Endosonography is the newest advance in GI endoscopy, with a long learning curve. Currently, this technique is generally performed by experts at some (but not all) tertiary referral centers, and the procedure is not uniformly available throughout the United States as well as around the world (although the number of centers offering EUS with FNA is steadily increasing). In contrast, transbronchial FNA and other invasive methods such as mediastinoscopy are more established modalities and more uniformly available worldwide. EUS is unable to image and sample lymph nodes that are anterior and lateral to the trachea. Early data on endobronchial ultrasound have been reported19 and may be a prelude to endobronchial real-time ultrasound-guided transbronchial FNA of lymph nodes, and further development in this area may significantly improve the yield of transbronchial mediastinal sampling techniques, and potentially decrease the indications for a transesophageal approach. In conclusion, in patients with known or suspected lung cancer with mediastinal lymph nodes or in patients with mediastinal lymphadenopathy of unknown etiology, EUS-guided transesophageal FNA is a safe and minimally invasive method with high accuracy. When EUS is available, it should be used as the next logical step for mediastinal lymph node sampling if transbronchial methods are nondiagnostic, provided the lymph nodes are not located anterior and lateral to the trachea. Locations such as subcarina, aortopulmonary window, and paraesophageal area are especially suited for EUS-guided FNA, as these locations are hard to access during mediastinoscopy. Physicians performing EUS-guided transesophageal FNA can play an important role in helping pulmonary and thoracic surgery colleagues in the workup 300
of mediastinal lymphadenopathy. Even with the development of endobronchial ultrasound-guided FNA, certain lymph node locations may be best approached transesophageally. Future research in this area should focus on the cost, complications, and technical feasibility based on the location of the lymph nodes and accuracy of current and evolving techniques for mediastinal lymph node sampling. This will allow physicians to select the most appropriate sequential application of technology on a case-to-case basis. Manoop S. Bhutani, MD Gainesville, FL Dr. Bhutani is Director, Center for Endoscopic Ultrasound; Director, Center for Experimental Endoscopy; and Associate Professor of Medicine, University of Florida, Gainesville, FL. Correspondence to: Manoop S. Bhutani, MD, Director, Center for Endoscopic Ultrasound, PO Box 100214, University of Florida, Gainesville, FL 32610-0214; e-mail: [email protected]
References 1 Bhutani MS, ed. Interventional endoscopic ultrasonography. Amsterdam, Holland: Harwood Academic Publishers, 1999 2 Wiersema MJ, Vilmann P Giovannini M, et al. Endosonography guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997; 112:1087–1095 3 Chang K J, Nguyen P, Erickson RA, et al. The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma. Gastrointest Endosc 1997; 45:387–393 4 Giovannini M, Seitz J-F, Monges G, et al. Fine needle aspiration cytology guided by endoscopic ultrasonography: results in 141 patients. Endoscopy 1995; 27:171–177 5 Vilmann P, Hancke S, Henriksen FW, et al. Endoscopic ultrasonography with guided fine needle aspiration biopsy of malignant lesions in the upper gastrointestinal tract. Endoscopy 1993; 25:523–527 6 Bhutani MS, Hawes RH, Baron PL, et al. Endoscopic ultrasound guided fine needle aspiration of malignant pancreatic lesions. Endoscopy 1997; 29:854 – 858 7 Hoffman BJ, Knapple W, Bhutani MS, et al. Treatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidance. Gastrointest Endosc 1997; 45:77–79 8 Wiersema MJ, Wiersema LM. Endosonography-guided celiac plenus neurolysis. Gastrointest Endosc 1996; 44:656 – 662 9 Gress F, Ciaccia D, Kiel J, et al. Endoscopic ultrasound guided celiac plexus block for management of pain due to chronic pancreatitis: a large single center experience [abstract]. Gastrointest Endosc 1997; 45:594 10 Chang KJ, Nguyen PT, Thompson JA, et al. Phase I clinical trial of local immunotherapy (Cytoimplant) delivered by endoscopic ultrasound (EUS) guided fine needle injection (FNI) in patients with advanced pancreatic carcinoma [abstract]. Gastrointest Endosc 1998; 47:AB144 11 Catalano MF, Sivak MV Jr, Rice T, et al. Endosonographic features predictive of lymph node metastases. Gastrointest Endosc 1994; 40:442– 446 12 Gress F, Savides TJ, Sandler A, et al. Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative Editorials
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14 15
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staging of non-small cell lung cancer: a comparison study. Ann Intern Med 1997; 127:604 – 616 Bhutani MS, Hawes RH, Hoffman BJ. A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion. Gastrointest Endosc 1997; 45:474 – 479 Silvestri GA, Hoffman BJ, Bhutani MS, et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61:1441–1446 Huhnerbein M, Ghadimi BM, Haensch W, et al. Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance. J Thorac Cardiovasc Surg 1998; 116:554 –559 Aabaken L, Silvestri G, Hawes R, et al. Cost effectiveness of endoscopic ultrasonography with fine needle aspiration vs mediastinoscopy in the staging of patients with lung cancer [abstract]. Gastrointest Endosc 1996; 43:414 Bhutani MS, Nadella P. Comparison of endoscopic ultrasound (EUS) and EUS-guided FNA with computed tomography for detection of mediastinal lymphadenopathy [abstract]. Gastrointest Endosc 1998; 93:1664 Ciaccia D, Imperiale T, Kim J, et al. Operating characteristics and clinical utility of endoscopic ultrasound (EUS) guided FNA in the preoperative staging of non-small cell lung cancer (NSCLCA) in computerized tomographic patients preliminary results [abstract]. Gastrointest Endosc 1999; 49:AB155 Kurimoto N, Murayama M, Yoshioka S, et al. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest 1999; 115:1500 –1506
Disorders of Ventilation Weakness, Stiffness, and Mobilization article by Misuri et al, “Mechanism of CO T heRetention in Patients With Neuromuscular Dis2
ease,” in this issue of CHEST (see page 447) points out something concerning the lungs of patients with neuromuscular disorders that has long been recognized concerning their limbs: the loss of function results from a combination of weakness and increases in soft tissue elastance. The latter is caused by the failure to fully mobilize the soft tissues and joints because of muscle weakness.1 Muscle strength also diminishes as soft tissues adaptively shorten over time. As muscle loses its normal flexibility and weaker muscles are stretched by their stronger antagonists, changes in their length-tension relationships result in decreased peak tensions, strength, and endurance.2,3 When a foreshortened position of a muscle is maintained for ⬎ 5 to 7 days, the loose connective tissue in the muscle belly shortens and then gradually changes into dense connective tissue.1 These tissues lose their normal elasticity and plasticity, resulting in the loss of range of motion (ROM) and joint contractures.2 A joint is contracted when it lacks full passive ROM. The muscle and other soft
tissue limitations that result in joint contractures can also cause bony deformities, particularly in young, growing patients.1 Upper limb contractures cause discomfort and diminish the ability to perform activities of daily living.4 Lower limb contractures cause the premature loss of the ability to walk.5 For example, contractures of hip flexors reduce hip extension, thereby shortening stride and requiring the patient to walk on the balls of the feet with increased lumbar lordosis and a consequent increase in energy consumption.1 Knee flexion contractures of 30° increase the work of the calf muscles and the knee extensors by 50%. It has been demonstrated that while the combination of moderate leg weakness and contractures can result in frequent falls and wheelchair dependence, when leg contractures are prevented by ROM mobilization or surgery, the same patients can walk longer without assistance and without falls despite worsening weakness.5 Flexibility exercises performed three times a week for 10 to 15 min in healthy but inactive subjects are sufficient to maintain the optimal resting lengths of the long muscles that would otherwise not be put through full ROM during normal daily activities. However, the independent performance of flexibility exercises requires that the subjects have normal strength. When strength is diminished, passive ROM with a sustained terminal stretch can be effective in preventing contractures if applied for 20 to 30 min bid.1 Normally, people take deep breaths or sigh regularly. These actions stretch the respiratory structures. Patients with chronic respiratory muscle weakness have reductions in lung volumes and vital capacity (VC) and can develop hypercapnia that greatly exceeds what might be anticipated from the loss of muscle force; and they may have decreases in lung distensibility that contribute to the disproportionate hypercapnia from lung volume restriction.6,7 As shown by Mizuri et al, failure to fully expand the lungs causes increases in lung tissue and chest wall elastance and decreases in compliance. The total mechanical work of breathing (WOB) is the sum of the work of overcoming both the elastic and frictional forces opposing inflation. In healthy adults, about two thirds of the WOB can be attributed to elastic forces opposing ventilation. The remaining third is due to frictional resistance to gas and tissue movement. In diseased states, the WOB can dramatically increase. In patients with restrictive lung disease, work is the integration of the volumepressure breathing curve. The increase in the WOB is a function of tissue elastance and an inverse function of pulmonary compliance.8,9 Failure to take periodic deep breaths can change CHEST / 117 / 2 / FEBRUARY, 2000
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References 1 Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA 1994; 271:840 – 844 2 Wolf PA, Abbott RD, Kannel WB, et al. Atrial fibrillation: a major contributor to stroke in the elderly; the Framingham study. Arch Intern Med 1987; 147:1561–1564 3 Wolf PA, Dawber TR, Thomas HE, et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28:973–977 4 Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population based estimates. Am J Cardiol 1998; 82(Suppl 8A):2N–9N 5 Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Arch Intern Med 1994; 154:1449 –1457 6 Aberg H. Atrial fibrillation: 1. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969; 185:373–379 298
7 Yamanouchi H, Tormonaga M, Shimada H, et al. Nonvalvular atrial fibrillation as a cause of fatal massive cerebral infarction in the elderly. Stroke 1989; 20:1653–1656 8 Fisher CM. Reducing the risks of cerebral embolism. Geriatrics 1979; 34:59 – 66 9 Aschenberg W, Schluter M, Kremer P, et al. Transesophageal two-dimensional echocardiography for the detection of LAA thrombus. J Am Coll Cardiol 1986; 7:163–166 10 Sullivan H, Pollick C. Incomplete LAA ligation that simulates mitral regurgitation. J Am Soc Echo 1990; 3:75–77 11 Pollick C, Taylor D. Assessment of LAA function by transesophageal echocardiography. Circulation 1991; 84:223–231 12 Kamp O, Verhorst PM, Welling RC, et al. Importance of LAA flow as a predictor of thromboembolic events in patients with atrial fibrillation. Eur Heart J 1999; 20:979 –985 13 Wolf PA, Kannel WB, McGee DL, et al. Duration of atrial fibrillation and imminence of stroke: the Framingham study. Stroke 1983; 14:664 – 667 14 Zipes DP. Atrial fibrillation. a tachycardia-induced atrial cardiomyopathy. Circulation 1997; 95:562–564. 15 Sparks PB, Mond HG, Vohra JK, et al. Mechanical remodeling of the left atrium after loss of atrioventricular synchrony. A long-term study in humans. Circulation 1999; 100:1714 –1721. 16 Stollberger C, Chnupa P, Kronik G, et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation: ELAT Study Group; embolism in left atrial thrombi. Ann Intern Med 1998; 128:630 – 638 17 Silverman DI, Manning WJ. Role of echocardiography in patients undergoing elective cardioversion of atrial fibrillation. Circulation 1998; 98:479 – 486
Transesophageal Endoscopic Ultrasound-Guided Mediastinal Lymph Node Aspiration Does the End Justify the Means? ultrasonography (EUS) is a unique E ndoscopic imaging modality where a high-frequency ultra-
sound transducer is incorporated into the tip of an endoscope to provide high-resolution images of the GI wall and structures in close proximity to the GI tract above and below the diaphragm. EUS is the most accurate method for local tumor and lymph node staging of the GI cancers, with many other applications as well in the GI tract. The development of echoendoscopes that can image parallel to the long axis of the instrument allows visualization of a needle along its length, making EUS-guided intervention a clinical reality. Endosonography has evolved from a technological accomplishment to a clinically useful procedure for sampling peri-GI lymph nodes, pancreatic masses, and submucosal GI lesions, etc.1– 6 EUS-guided injection of therapeutic substances has also begun.7–10 Since EUS during transesophageal imaging provides high-resolution images of the posterior mediastinum, considerable interest and investigation have Editorials
occurred over the last few years about its utility in the detection of mediastinal lymphadenopathy in lung cancer and other malignancies. Initially, before the development of interventional EUS techniques, the focus was on studying echo features of lymph nodes to predict malignant invasion. Lymph nodes seen by EUS that were larger than 1 cm, round, hypoechoic, and with distinct margins were considered to be malignant.11 These criteria during EUS were initially described for GI cancers, eg, esophageal,11 and were later applied to mediastinal lymph nodes in lung cancer. These EUS echo features of mediastinal lymph nodes in lung cancer have been shown in one study to have accuracy of 84% compared to CT scan accuracy of 49%.12 However, the reliance on EUS echo features to diagnose malignant lymph node invasion in lung cancer has problems of interobserver variability, lack of standardization of frequencies used to study the lymph nodes, as well as lack of uniform criteria to label a lymph node as hypoechoic or with sharp, distinct margins.13 In addition, it has also been shown in the study by Bhutani et at13 that although the presence of echo features described above could predict malignant invasion about 80% of the time; however, only 25% of nodes that had malignant invasion had all four echo features. This study that included enlarged lymph nodes in patients with esophageal, lung, and pancreatic cancers also compared the accuracy of echo features of lymph nodes with EUS-guided fine-needle aspiration (FNA) and found that EUSguided FNA was a more reliable method for predicting lymph node invasion than echo features. Transesophageal EUS-guided real-time FNA of mediastinal lymph nodes has become a clinically useful minimally invasive method for detecting malignant lymph node invasion, as shown in this issue of CHEST (see page 339) by Fritscher-Ravens and colleagues. The accuracy of EUS-guided mediastinal lymph node FNA in this series was 97%, which is comparable to the accuracy in studies from other centers.12–15 In addition, this procedure appears to be safe in expert hands, with no significant complications occurring in the current series. This procedure is performed under conscious sedation, similar to any other endoscopy, and the patient can be discharged from the hospital after observation in the recovery room for 45 to 60 min. Following is a summarization of the advantages and limitations of this technique, so that EUS-guided FNA of mediastinal lymph nodes could be used in the appropriate clinical setting. (1) In patients with known non-small cell lung cancer who have mediastinal lymph nodes on CT scan and who have a negative transbronchial FNA, EUS-guided FNA can be used as an accurate,
minimally invasive method to stage the mediastinum. The accuracy of EUS-guided FNA in this setting is about 96%.12 A positive result by FNA for cancer would then obviate the need for more invasive staging modalities such as mediastinoscopy. (2) EUS-guided FNA also appears to have a cost advantage over mediastinal lymph node staging in lung cancer. Cost data in a study12 on EUS-guided FNA for staging lung cancer revealed that the total cost for EUS was $1,975, with mediastinoscopy and thoracotomy significantly more expensive at $7,759 and $26,028, respectively. As mentioned before, if a EUS-guided FNA result is positive for cancer, it would obviate the need for more expensive and invasive procedures, such as mediastinoscopy and thoracotomy. A decision model analysis has also been performed to calculate the average cost per year of survival in patients with lung carcinoma. This model resulted in an average cost per year of survival of EUS-guided FNA to be $3,810 and $9,757 for mediastinoscopy.16 (3) When a primary lung mass is suspected on CT and mediastinal lymph nodes are seen, if bronchoscopic and transbronchial methods fail to acquire a primary diagnosis, EUS-guided mediastinal FNA in these patients could potentially provide a primary diagnosis (as well as staging information). These were the inclusion criteria for the current study by Fritscher-Ravens et al, and a final diagnosis of malignancy was achieved in 25 of 35 patients. Furthermore, EUS can also play a significant role in evaluating mediastinal lymphadenopathy of unknown origin with no primary lung mass on CT. If transbronchial FNA results are negative in these patients, EUS-guided FNA can provide a diagnosis of malignancy.13 (4) Lymph nodes that are located in the subcarina, aortopulmonary window, and the paraesophageal area are difficult to approach during procedures such as mediastinoscopy.12,14 However, these locations are best suited and the most accessible for puncture during transesophageal EUS.12,14 (5) Previous studies on the utility of EUS-guided FNA have only included patients who have enlarged mediastinal lymph nodes by CT scan. Generally by CT scan criteria, lymph nodes that are ⱖ 1 cm in size are considered to be enlarged. However, using size alone as a criteria for malignant invasion of lymph nodes by CT may not be ideal, since lymph nodes ⬍ 1 cm can potentially have malignant invasion. In a series of patients who underwent CT scan and EUS, we found a significant number of patients with thoracic malignancies who had posterior mediastinal lymphadenopathy by EUS with negative CT criteria for enlarged lymph nodes. Only 50% of patients in this series who underwent EUS-guided transesophCHEST / 117 / 2 / FEBRUARY, 2000
299
ageal FNA had enlarged nodes by CT scan.17 Early data from another group also suggest that EUSguided FNA can diagnose malignant invasion in small mediastinal lymph nodes that are negative by CT criteria.18 This concept is further strengthened by FritscherRavens and colleagues. It is noteworthy that seven patients who underwent EUS-guided mediastinal lymph node FNA had lymph nodes that were ⬍ 1 cm in diameter and would not have been classified as enlarged by CT scan. Four of these aspirates revealed malignant cells. Thus, in suspected or known pulmonary malignancies, even if small (⬍ 1 cm) lymph nodes are seen in the posterior mediastinum, it might be worthwhile to perform EUS imaging and possible FNA of these lymph nodes. However, further studies in this area are needed to establish the utility of EUS in patients who do not have enlarged nodes by CT criteria. EUS with FNA also has some limitations. Endosonography is the newest advance in GI endoscopy, with a long learning curve. Currently, this technique is generally performed by experts at some (but not all) tertiary referral centers, and the procedure is not uniformly available throughout the United States as well as around the world (although the number of centers offering EUS with FNA is steadily increasing). In contrast, transbronchial FNA and other invasive methods such as mediastinoscopy are more established modalities and more uniformly available worldwide. EUS is unable to image and sample lymph nodes that are anterior and lateral to the trachea. Early data on endobronchial ultrasound have been reported19 and may be a prelude to endobronchial real-time ultrasound-guided transbronchial FNA of lymph nodes, and further development in this area may significantly improve the yield of transbronchial mediastinal sampling techniques, and potentially decrease the indications for a transesophageal approach. In conclusion, in patients with known or suspected lung cancer with mediastinal lymph nodes or in patients with mediastinal lymphadenopathy of unknown etiology, EUS-guided transesophageal FNA is a safe and minimally invasive method with high accuracy. When EUS is available, it should be used as the next logical step for mediastinal lymph node sampling if transbronchial methods are nondiagnostic, provided the lymph nodes are not located anterior and lateral to the trachea. Locations such as subcarina, aortopulmonary window, and paraesophageal area are especially suited for EUS-guided FNA, as these locations are hard to access during mediastinoscopy. Physicians performing EUS-guided transesophageal FNA can play an important role in helping pulmonary and thoracic surgery colleagues in the workup 300
of mediastinal lymphadenopathy. Even with the development of endobronchial ultrasound-guided FNA, certain lymph node locations may be best approached transesophageally. Future research in this area should focus on the cost, complications, and technical feasibility based on the location of the lymph nodes and accuracy of current and evolving techniques for mediastinal lymph node sampling. This will allow physicians to select the most appropriate sequential application of technology on a case-to-case basis. Manoop S. Bhutani, MD Gainesville, FL Dr. Bhutani is Director, Center for Endoscopic Ultrasound; Director, Center for Experimental Endoscopy; and Associate Professor of Medicine, University of Florida, Gainesville, FL. Correspondence to: Manoop S. Bhutani, MD, Director, Center for Endoscopic Ultrasound, PO Box 100214, University of Florida, Gainesville, FL 32610-0214; e-mail: [email protected]
References 1 Bhutani MS, ed. Interventional endoscopic ultrasonography. Amsterdam, Holland: Harwood Academic Publishers, 1999 2 Wiersema MJ, Vilmann P Giovannini M, et al. Endosonography guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997; 112:1087–1095 3 Chang K J, Nguyen P, Erickson RA, et al. The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma. Gastrointest Endosc 1997; 45:387–393 4 Giovannini M, Seitz J-F, Monges G, et al. Fine needle aspiration cytology guided by endoscopic ultrasonography: results in 141 patients. Endoscopy 1995; 27:171–177 5 Vilmann P, Hancke S, Henriksen FW, et al. Endoscopic ultrasonography with guided fine needle aspiration biopsy of malignant lesions in the upper gastrointestinal tract. Endoscopy 1993; 25:523–527 6 Bhutani MS, Hawes RH, Baron PL, et al. Endoscopic ultrasound guided fine needle aspiration of malignant pancreatic lesions. Endoscopy 1997; 29:854 – 858 7 Hoffman BJ, Knapple W, Bhutani MS, et al. Treatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidance. Gastrointest Endosc 1997; 45:77–79 8 Wiersema MJ, Wiersema LM. Endosonography-guided celiac plenus neurolysis. Gastrointest Endosc 1996; 44:656 – 662 9 Gress F, Ciaccia D, Kiel J, et al. Endoscopic ultrasound guided celiac plexus block for management of pain due to chronic pancreatitis: a large single center experience [abstract]. Gastrointest Endosc 1997; 45:594 10 Chang KJ, Nguyen PT, Thompson JA, et al. Phase I clinical trial of local immunotherapy (Cytoimplant) delivered by endoscopic ultrasound (EUS) guided fine needle injection (FNI) in patients with advanced pancreatic carcinoma [abstract]. Gastrointest Endosc 1998; 47:AB144 11 Catalano MF, Sivak MV Jr, Rice T, et al. Endosonographic features predictive of lymph node metastases. Gastrointest Endosc 1994; 40:442– 446 12 Gress F, Savides TJ, Sandler A, et al. Endoscopic ultrasonography, fine needle aspiration guided by endoscopic ultrasonography, and computed tomography in the preoperative Editorials
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staging of non-small cell lung cancer: a comparison study. Ann Intern Med 1997; 127:604 – 616 Bhutani MS, Hawes RH, Hoffman BJ. A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion. Gastrointest Endosc 1997; 45:474 – 479 Silvestri GA, Hoffman BJ, Bhutani MS, et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61:1441–1446 Huhnerbein M, Ghadimi BM, Haensch W, et al. Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance. J Thorac Cardiovasc Surg 1998; 116:554 –559 Aabaken L, Silvestri G, Hawes R, et al. Cost effectiveness of endoscopic ultrasonography with fine needle aspiration vs mediastinoscopy in the staging of patients with lung cancer [abstract]. Gastrointest Endosc 1996; 43:414 Bhutani MS, Nadella P. Comparison of endoscopic ultrasound (EUS) and EUS-guided FNA with computed tomography for detection of mediastinal lymphadenopathy [abstract]. Gastrointest Endosc 1998; 93:1664 Ciaccia D, Imperiale T, Kim J, et al. Operating characteristics and clinical utility of endoscopic ultrasound (EUS) guided FNA in the preoperative staging of non-small cell lung cancer (NSCLCA) in computerized tomographic patients preliminary results [abstract]. Gastrointest Endosc 1999; 49:AB155 Kurimoto N, Murayama M, Yoshioka S, et al. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest 1999; 115:1500 –1506
Disorders of Ventilation Weakness, Stiffness, and Mobilization article by Misuri et al, “Mechanism of CO T heRetention in Patients With Neuromuscular Dis2
ease,” in this issue of CHEST (see page 447) points out something concerning the lungs of patients with neuromuscular disorders that has long been recognized concerning their limbs: the loss of function results from a combination of weakness and increases in soft tissue elastance. The latter is caused by the failure to fully mobilize the soft tissues and joints because of muscle weakness.1 Muscle strength also diminishes as soft tissues adaptively shorten over time. As muscle loses its normal flexibility and weaker muscles are stretched by their stronger antagonists, changes in their length-tension relationships result in decreased peak tensions, strength, and endurance.2,3 When a foreshortened position of a muscle is maintained for ⬎ 5 to 7 days, the loose connective tissue in the muscle belly shortens and then gradually changes into dense connective tissue.1 These tissues lose their normal elasticity and plasticity, resulting in the loss of range of motion (ROM) and joint contractures.2 A joint is contracted when it lacks full passive ROM. The muscle and other soft
tissue limitations that result in joint contractures can also cause bony deformities, particularly in young, growing patients.1 Upper limb contractures cause discomfort and diminish the ability to perform activities of daily living.4 Lower limb contractures cause the premature loss of the ability to walk.5 For example, contractures of hip flexors reduce hip extension, thereby shortening stride and requiring the patient to walk on the balls of the feet with increased lumbar lordosis and a consequent increase in energy consumption.1 Knee flexion contractures of 30° increase the work of the calf muscles and the knee extensors by 50%. It has been demonstrated that while the combination of moderate leg weakness and contractures can result in frequent falls and wheelchair dependence, when leg contractures are prevented by ROM mobilization or surgery, the same patients can walk longer without assistance and without falls despite worsening weakness.5 Flexibility exercises performed three times a week for 10 to 15 min in healthy but inactive subjects are sufficient to maintain the optimal resting lengths of the long muscles that would otherwise not be put through full ROM during normal daily activities. However, the independent performance of flexibility exercises requires that the subjects have normal strength. When strength is diminished, passive ROM with a sustained terminal stretch can be effective in preventing contractures if applied for 20 to 30 min bid.1 Normally, people take deep breaths or sigh regularly. These actions stretch the respiratory structures. Patients with chronic respiratory muscle weakness have reductions in lung volumes and vital capacity (VC) and can develop hypercapnia that greatly exceeds what might be anticipated from the loss of muscle force; and they may have decreases in lung distensibility that contribute to the disproportionate hypercapnia from lung volume restriction.6,7 As shown by Mizuri et al, failure to fully expand the lungs causes increases in lung tissue and chest wall elastance and decreases in compliance. The total mechanical work of breathing (WOB) is the sum of the work of overcoming both the elastic and frictional forces opposing inflation. In healthy adults, about two thirds of the WOB can be attributed to elastic forces opposing ventilation. The remaining third is due to frictional resistance to gas and tissue movement. In diseased states, the WOB can dramatically increase. In patients with restrictive lung disease, work is the integration of the volumepressure breathing curve. The increase in the WOB is a function of tissue elastance and an inverse function of pulmonary compliance.8,9 Failure to take periodic deep breaths can change CHEST / 117 / 2 / FEBRUARY, 2000
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