Symposium on Surgery of the Chest
Lung Biopsy: Transbronchoscopic, Percutaneous, Open
Howard A. Andersen, M.D., W. Eugene Miller, M.D., and Philip E. Bernatz, M.D.
A substantial number of diseases are manifested solely in the lungs, cause no diagnostic or characteristic secretions, and may present no detectable extrapulmonary clues of their nature. A definitive histologic or bacteriologic diagnosis of diffuse or nodular pulmonary disease must be a goal in every such case. Empiric therapy has a place in the practice as well as the art of medicine, but the potential harmfulness of therapeutic agents makes it imperative they be used only with specific and adequate indications. Of equal importance is the solution of occupational or ecologic pulmonary problems so that prevention may be achieved and medicolegal disputes settled. Several methods of obtaining tissue have been used by others and by us, but our more recent experience has been confined largely to three: (1) transbronchoscopic, (2) percutaneous aspiration, and (3) open lung biopsy.
TRANSBRONCHOSCOPIC LUNG BIOPSY In 1965 we reported a technique of lung biopsy using forceps inserted into the periphery of the lung via a rigid bronchoscope. 3 Our continuing experience with this method was reported in 19704 and again in 1972.2 Results have been sufficiently satisfactory so that, to June 1,1972, transbronchoscopic lung biopsy had been done in 525 cases at our institution. Indications Candidates for this procedure have been patients with roentgenologic evidence of non suppurative pulmonary parenchymal disease that defied diagnosis by other means. Most commonly the disease was bilaterally diffuse (Fig. 1), but in some cases it was limited to one lung or even to a segment of one lung (Fig. 2). Usually the process has been
Surgical Clinics of North America- Vol. 53, No.4, August 1973
EUGENE MILLER AND PHILIP
Figure 1. Diffu e bilateral pulmonary process. Transbronchoscopic lung biop y di cIo ed Pneumocy ti carinii.
Figure 2. Al eolar-cell carcinoma in left lower lobe. Diagno i wa e tabli hed by tran broncho copic lung biop y. (From Ander en HA , Fontana RS , Sander on DR, et aI.: Transbroncho copic lung biop yin diffu e pulmonary di ease : re ult in 300 ca e . Med Clin orth Am 54:951 - 959 , 1970.)
present several weeks or months. It has not been our policy to biopsy acute pneumonitis; but there were exceptions, as in the case of suspected pneumonitis caused by Pneumocystis carinii. Pulmonary suppurative disease has been a deterrent, though not an absolute contraindication to the performance of transbronchoscopic lung biopsy by this method. We have believed that the possibility of creating,,! bronchopleural fistula and empyema if pneumothorax occurs is too great. No such instance has occurred in our series, however; and a lower incidence of pneumothorax in recent cases may cause us to reconsider. We have not been very successful in obtaining satisfactory specimens from lungs with diffuse nodular disease, especially if the nodules are 4 to 5 mm in diameter. Many of our failures to obtain satisfactory tissue have occurred in this group.
Technique The method of transbronchoscopic lung biopsy using forceps through a rigid bronchoscope was described in 19653 and more fully in 1972.2 Bronchoscopy is done in the usual fashion, most commonly with topical anesthetic. It is desirable to have the patient awake and able to cooperate, but this is not essential. General anesthesia has been used for all children and a few adults, and there have been no complications from it thus far. In the past 2 years, intramuscular premedication has been supplemented by intravenous administration of diazepam (Valium) in most cases. During examination of the bronchial tree, secretions and washings are aspirated for cultures and other indicated laboratory procedures. For performance of the lung biopsy we favor a small, blunt flexible forceps made by American Cystoscope Makers, Inc., which is approximately 7 F in circumference and approximately 60 cm long (Fig. 3). It has a cup ap-
Figure 3. Small flexible forceps used for transbronchoscopic lung biopsy. (From Andersen HA, Fontana RS, Sanderson DR, et al.: Transbronchoscopic lung biopsy in diffuse pulmonary disease: results in 300 cases. Med Clin North Am 54:951-959, 1970.)
HOWARD A. ANDERSEN,
EUGENE MILLER AND PHILIP
Table 1. Transbronchoscopic Biopsy and Diagnosis of Diffuse Pulmonary Disease DIAGNOSIS
None No lung tissue Insufficient tissue Interstitial pneumonitis and fibrosis Metastatic cancer Granulomatous disease Collagen disease Vasculitis and pulmonary purpura Pneumoconiosis Abnormal lung with systemic disease Normal lung Desquamative interstitial pneumonitis Alveolar-cell carcinoma Pneumocystis carinii infection Lymphoma Lipoid pneumonitis His tiocytosis X Alveolar proteinosis, busulfan fibrosis, cryptococcal pneumonitis (1 each) TOTAL
52 32 236 22 69 23 12 13 8 25 5 10 6 4
3 2 3
proximately 2 by 4 mm, which seems large enough to obtain a satisfactory bite of tissue, yet small enough to reach the periphery of the lung. The forceps is inserted gently into a segmental bronchus beyond the point of endoscopic direct vision until it becomes engaged in a tiny bronchus. This point is detected by motion of the forceps with inspiration and expiration, no pressure being applied by the endoscopist. If the patient experiences no chest pain, the forceps is opened on inhalation and closed at the end of exhalation. Tissue usually pulls away easily. Pain experienced during insertion of the forceps probably means that pressure has been applied against parietal pleura. In this circumstance, the forceps should be withdrawn without taking a specimen and reinserted in a different bronchus. Usually we attempt to obtain a minimum of three specimens, and we have taken as many as five. We ordinarily obtain them from one lung only. Believing that tactile guidance is more helpful than fluoroscopic visualization, we prefer not to use roentgenologic guidance. After specimens of the lung have been obtained, random bronchial specimens should be taken. In some cases they have provided valuable information not available from pulmonary tissue. Results Table 1 summarizes our results in 525 cases. In 441 (84%), tissue was obtained that helped in establishing a diagnosis. Failure to obtain satisfactory tissue was more frequent if the disease was nodular or very fibrotic. Excessive coughing during bronchoscopy and bleeding after the first biopsy also caused the endoscopist to be so cautious that insufficient tissue frequently was obtained.
The taking of multiple biopsies when the procedure progresses satisfactorily enhances the likelihood of success. With experience we have learned that the gross specimen of lung tissue fluffs and floats when placed in liquid, whereas the more compact bronchial tissue sinks to the bottom. This immediate recognition of proper tissue is partially responsible for the gradual decrease in the percentage of cases with "insufficient tissue" from 20% in our first 3004 cases to 11 % in the latest 225. Failure to obtain satisfactory tissue averaged 16% in the current review of our total 525 cases. Results may be improved by exchange of information between the clinician and pathologist. For example, the history of occupational exposure to dust alerts the pathologist to the need for additional analytic studies.s As our experience has increased, we have been asked to perform transbronchoscopic lung biopsy on patients who are gravely ill-even preterminal-in hope that we might find a reversible disease. This has been especially true of patients receiving cytotoxic or immunosuppressive agents, who are especially likely to develop pneumonitis due to P. carinii. A review of these cases9 in which transbronchoscopic lung biopsy was done revealed no false negatives. Complications There has been one death among the 525 patients. This occurred in a man who was desperately ill from lymphosarcoma-cell leukemia with diffuse pulmonary infiltration and hypoxemia. Evidence of a small pneumothorax was noted on a roentgenogram made immediately after bronchoscopy. His condition appeared to be stable, but he died suddenly 70 minutes after the end of the procedure. When we began doing transbronchoscopic biopsy, we had thoracic roentgenography done immediately after bronchoscopy and again 12 to 24 hours later. Practically all pneumothoraces appeared on the initial roentgenogram, however; so we have discontinued the later roentgenography as a routine procedure. Pneumothorax, bleeding (estimated as 50 ml or more), and mediastinal emphysema are reported in Table 2. Pneumothorax was never a serious problem, except in the one fatal instance. Intrapleural suction was used for 24 to 48 hours in approximately 50% of the patients with this complication. Table 2.
Transbronchoscopic Biopsy of Lung Complications of Diffuse Pulmonary Disease FIRST
Pneumothorax (intrapleural suction) Mediastinal emphysema Bleeding
29 (17) 4 5
HOWARD A. ANDERSEN,
EUGENE MILLER AND PHILIP
Mediastinal emphysema has not caused difficulty to the few patients who developed it. Bleeding has nearly ceased to be a problem since we began using the small forceps almost exclusively. If bleeding is encountered, however, it can be controlled very simply by packing the appropriate segmental bronchus with narrow gauze tape while the bronchoscope is still inserted. The tape may be removed after 1 or 2 minutes, and reinserted if the bleeding continues. The bleeding has not become serious in any case where this method has been used. The opportunity for such satisfactory control of bleeding is a distinct advantage to the transbronchoscopic method of lung biopsy.
TRANSTHORACIC PERCUTANEOUS NEEDLE ASPIRATION BIOPSY Dahlgren and Nordenstrom developed the percutaneous technique now widely used for obtaining tissue for cytologic diagnosis of discrete pulmonary lesions (nodules 0.5 mm or larger in diameter).6, 17, 13 Needles 1.1 mm in diameter have proved large enough to aspirate enough tissue for cytologic diagnosis, especially if neoplasm is present, and small enough to minimize complications of serious pneumothorax and hemothorax in most cases.
Technique This procedure was described almost a century ago; but modern image-intensification fluoroscopy, which provides guidance for directing needles to even small lesions, has made it practical. Unless the patient shows much anxiety, only the skin and chest wall (down to and including the pleura) need to be anesthetized; and this is done with 1 % lidocaine (Xylocaine). The patient is positioned on the fluoroscopic table so as to provide the shortest distance for needle travel from the skin to the underlying pulmonary lesions. The skin is cleansed with alcohol solution. A small skin incision is made, to minimize needle friction and maximize ability to feel the needle entering the lesion as it is advanced under fluoroscopic control. A long-handled needle holder is used to minimize radiation exposure of the radiologist's hands. Many types of needles have been advocated for this procedureY' 14 We use a standard thin-walled 18gauge angiographic needle, usually 6 inches in length, with the bevel about its orifice sharpened to maximize cutting when the needle is rotated in the lesion. As the needle is advanced with the patient breathing quietly, the lesion if large can be palpated with the needle; or if it is small, the nodule is seen to move when pushed by the needle tip. With experience, singleplane fluoroscopy suffices-although biplane fluoroscopy, if available, would be helpful in a few difficult cases. With a needle in the periphery of the lesion, the stylet is withdrawn and a 30-ml Luer-Lok syringe is used to provide vigorous suction for aspirating material while the needle is rotated within the lesion. The specimen can be smeared upon slides and immediately immersed in 70% alcohol solution to prevent cell distortion from drying; or
material can be placed in a Millipore container with a Nucleopore filter. The Millipore container can be utilized to preserve all bits of material by rinsing the needle in the 7rtfo alcohol placed in the filter chamber. If the specimen is bloody (and it frequently is), most of the blood can be removed by the filter, leaving tissue behind for cytologic processing. Also, if sufficient material is obtained, slides can be smeared for microbiologic evaluation. The specimen can be divided and some of it placed on a vial of culture medium for microbiologic studies. Results Malignant neoplasm was diagnosed from tissue obtained by needle aspiration biopsy in 78% of the first 83 cases where lung cancer was proved, and this accuracy has been increased slightly with continued experience. We now have performed needle biopsy in 273 cases. The vast majority of patients were selected because of strong suspicion of neoplasia. In the cases reported as negative, either the disease was benign or not enough tumor tissue was obtained for diagnosis. In culturing organisms in the presence of inflammatory disease, we have not achieved so much success as others have reported;5.13 but inflammatory disease can be verified microbiologically by this technique.
Complications Pneumothoraces occur in about half of these needle-biopsy patients, but only about 20% are severe enough to require placement of intercostal drainage tubes. Many of these pneumothoraces were asymptomatic and would have gone undetected if follow-up chest roentgenograms had not been taken on the next morning after the procedure. Hemoptysis, though frequent, is usually minimal. However, we now have had three patients with rather extensive bleeding and alveolarization of blood throughout both lungs. These patients became cyanotic and were in respiratory distress until coughing relieved their symptoms. Although we have had no fatalities, hemoptysis has been reported as a cause of death. One case of severe hemothorax occurred which amounted to several hundred milliliters of blood in the pleural space. Biopsy should not be done bilaterally. Two of our patients developed serious symptomatic pneumothoraces from this practice before it was discontinued. Comment Since the introduction of fiberoptic bronchoscopy, we have performed fewer transthoracic needle biopsies, but many peripheral nodules beyond the reach of fiberoptic bronchoscopy can be biopsied by this technique. It should be emphasized that solitary pulmonary lesions are not biopsied when surgery is indicated. It is only when multiple lesions or inoperable tumor is thought to be present, or when the patient is a very poor operative risk, that this diagnostic procedure is considered. OPEN-LUNG BIOPSY With the increasing effectiveness of transbronchoscopic and percutaneous aspiration biopsy techniques, the need for open-lung biopsy has
HOWARD A. ANDERSEN,
EUGENE MILLER AND PHILIP
decreased. Surgeons welcome this trend but recognize there will continue to be some cases in which other methods fail and open-lung biopsy is a necessity. This procedure obtains biopsy tissue every time, and a definitive diagnosis can be made in 95% of cases. Morbidity is low and mortality 0.5 to 2%1.7.10 (though obviously the selection of cases can influence the latter percentage). We rarely can plan on using local anesthesia for open-lung biopsy, because the limitations it imposes are unacceptable. When other methods have failed to provide a basis for diagnosis, open-lung biopsy must; and this may require extending the incision to permit multiple biopsies of various portions of the lung and removal of a hilar or mediastinal lymph node. We cannot relate morbidity to the size of the incision. There should be nothing to prevent obtaining appropriate tissue. The surgical pathologist should guide the surgical effort with histologic interpretation of fresh-frozen sections. This enables the surgeon to be sure the microbiologist is being provided with tissue that will give him the best opportunity to establish an etiologic diagnosis. Experience has shown that it may be necessary in some cases to biopsy more centrally to get adequate tissue-for example, in alveolar proteinosis. Whenever possible we employ a stapling device, saving considerable anesthesia time. It is absolutely essential that diseased lungs be well expanded by the anesthesiologist prior to closure of the thoracic incision. A pleural catheter is used for several hours postoperatively or as long as an air leak may be evident. It is not sufficient that the surgeon only get a specimen of appropriate tissue. He must get adequate amounts and refer the specimens to laboratories that will make proper investigation - by histochemistry, virology, electron microscopy, and microbiology, in addition to light microscopy. These investigative methods require special handling of the tissue, knowledge of which the surgeon must not forego. Although the number of patients who require open-lung biopsy is diminishing, the responsibility of the surgeon for making definite diagnosis possible is increased by the progress of the laboratory disciplines. Only if the surgeon provides his laboratory colleagues with representative tissue, in adequate amount and appropriately preserved, can the full benefit of their capabilities be realized.
SUMMARY Transbronchoscopic lung biopsy is done by choice in our institution for nonsuppurative parenchymal disease, whether diffuse or limited in distribution. Pulmonary insufficiency is not a contraindication. In diffuse nodular disease, especially with isolated nodules, percutaneous aspiration biopsy is elected. Open-lung biopsy is reserved for patients in whom the other methods have failed.
REFERENCES 1. Aaron BL, Bellinger SB, Shepard BM, et al: Open lung biopsy: a strong stand. Chest
59:18-22,1971 2. Andersen HA, Fontana RS: Transbronchoscopic lung biopsy for diffuse pulmonary diseases: technique and results in 450 cases. Chest 62:125-128, 1972
3. Andersen HA, Fontana RS, Harrison EG Jr: Transbronchoscopic lung biopsy in diffuse pulmonary disease. Dis Chest 48:187-192, 1965 4. Andersen HA, Fontana RS, Sanderson DR, et al: Transbronchoscopic lung biopsy in diffuse pulmonary disease: results in 300 cases. Med Clin North Am 54:951-959, 1970 5. Dahlgren S, Nordenstriim B: Transthoracic Needle Biopsy. Chicago, Year Book Medical Publishers, Inc, 1966 6. Fontana RS, Miller WE, Beabout JW, et al: Transthoracic needle aspiration of discrete pulmonary lesions: experience in 100 cases. Med Clin North Am 54:961-971,1970 7. Gaensler EA, Moister MVB, Hamm J: Open-lung biopsy in diffuse pulmonary disease. N Engl J Med 270:1319-1331,1964 8. Harrison EG Jr, Koves G, Andersen HA: X-ray diffraction and spectrographic analysis in pneumoconiosis. Arch Environ Health 14:412-423, 1967 9. Hodgkin JE, Andersen HA, Rosenow EC III: Diagnosis of Pneumocystis carinii pneumonia by transbronchoscopic lung biopsy (submitted for publication) 10. Hughes RL, Bogdonoff ML, Faber LP: Lung biopsy in the acutely ill: when and how. Chest 62:484, 1972. 11. Kremp RE, Klatte EC, Collins RD: Technical considerations of percutaneous pulmonary biopsy. Radiology 100:285-291, 1971 12. Lalli AF, Naylor B, Whitehouse WM: Aspiration biopsy of thoracic lesions. Thorax 22: 404-407, 1967. 13. Stevens GM, Weigen JF, Lillington GA: Needle aspiration biopsy of localized pulmonary lesions with amplified fluoroscopic guidance. Am J Roentgenol Radium Ther Nuel Med 103:561-571, 1968 14. Turner AF, Sargent EN: Percutaneous pulmonary needle biopsy: an improved needle for a simple direct method of diagnosis. Am J Roen tgenol Radium Ther N uel Med 104: 846850, 1968