L ung cancers can be divided into two major types

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1 Bronchofiberscopy With Curette Biopsy and Bronchography in the Evaluation of Peripheral Lung Lesions" Ryosuke 000, M.D.;t Jacob Loke, M.D.;* and Shigeto Ikeda, M.D., F.C.C.P. Flexible broncbo&berscopy using a double-hinged curette biopsy and onder ftuoroscopic guidance was performed on 46 patients with peripbenl lung carcinomas smaller than 2 em, PrIor mapping of the location of the lung lesion was achieved with selective periphenl broilebograpby. With these diagnostic tools, a positive cyto- logic diagnosis for lung carcinomas was made in 45 of 46 patients, a yield of 97.8 percent. CompUcatioDS ass0 ciated with the curette biopsy included minor bleedidg In three cases and pneumothorax requiridg a chest tube In one case. L ung cancers can be divided into two major types based on anatomiclocation: the "hilar" ( or "central") type and the "peripheral" type. I 2 Benfield and associates" observed that at least 60 percent of all carcinomas of the lung originate in the periphery of the lung and subsequently spread centrally. It is the peripheral lung lesion, detected early, that offers a relatively good prognosis.t" In peripheral lung cancers the diagnostic yield of bronchofiberscopy with forceps biopsies, brushings, and washings ranges from 48 percent to 80 percent. 5-8 This variable diagnostic accuracy for a positive cytologic answer in peripheral lung carcinomas may be due to different diagnostic techniques and size of lesions. However, Tsuboi et al 9 at the National Cancer Center Hospital in Japan reported a diagnostic yield of 92.8 percent for peripheral lung tumors ( smaller than 2 cm) after using a specially designed, single-hinged curette through a modified Metras bronchial catheter with Huoroscopic guidance. This study reviews our experience in diagnosing peripherallung carcinomas with a double-hinged curette! for obtaining biopsies through the flexible bronchofiberscope under fluoroscopic guidance. Before the bronchoscopic procedure, mapping of the location of the peripheral lung lesion was done with a selective peripheral bronchogram. From the Deparbnent of Chest Diagnosis, National Cancer Center Hospital, Tokyo, Japan. Presented in part at the World Congress on Bronchoscopy, Tokyo, July 10-12, tattending physician, Department of Chest Diagnosis, National Cancer Center Hospital, Tokyo, Japan. :Visiting Assistant Professor, National Cancer Center Hospital, Tokyo, Japan; Assistant Professor in Medicine, Yale University School of Medicine, New Haven, Connecticut. Chairman, Department of Enaoscopy and Chest Diagnosis, National Cancer Center Hospital, Tokyo, Japan. Manuscript received November 7, 1979; revision accepted March 3. Reprint request8: D". Loke, Pulmona"" Section, PO Box 3333, 333 Cedar Street, New Haven ONO, LOKE, IKEDA MATERIALS AND METHODS From January 1969 to December 1977,400 peripheral lung cancer cases were resected at the National Cancer Center Hospital. In the routine workup of these patients before thoracotomy was a chest roentgenogram, lung tomograms, sputum cytology, and bronchography, including the use of selective peripheral bronchogram and the Machida flexible bronchofiberscope ( Model FBS-5, FBS-6TII, FBS-6TLII, Machida Endoscope Co Ltd). Of these 400 lung cancer cases, 52 fulfilled the criteria of "early" lung cancer, te, the resected tumor was less than 2.0 cm in diameter and without metastases.! These 52 cases form the basis of this review. There were 33 males (all cigarette smokers) and 19 females (all nonsmokers), with a mean age of 54 years (range, 31 to 76). The majority of patients (35 of 52) were between the fifth and seventh decade of life. To evaluate the peripheral solitary nodule or infiltrate, bronchography was performed initially to determine the site of the lesion. Bronchography was performed with a flexible broncho-catheter FBC-6 (Machida Endoscope Co Ltd, Fig 1). The patient's pharynx and larynx were sprayed with 2 percent xylocaine solution, and then the flexible bronchocatheter was inserted transorally into the trachea. A 2 percent xylocaine solution was injected into the bronchi of the affected left or right lung through the open channel tube of the flexiblebroncho-catheterwith the aid of x-ray fluoroscopy. The tip of the broncho-catheter was wedged into the respective distal bronchi, and aqueous Dionosil contrast material was gradually injected into the different segmental orifices and surrounding bronchi with the guidance of fluoroscopy. Standard spot exposure roentgenograms were obtained in addition to magnification spot roentgenograms, the latter with a 50-", focal spot x-ray tube (Toshiba Co, Fig 2). Bronchofiberscopy was performed approximately seven to ten days after bronchography. The bronchography procedure takes about 30 minutes. Under local anesthesia with xylocaine spray, bronchofiberscopy was performed through a transorally inserted endotracheal tube.! The information obtained from the selective peripheral bronchography regarding the site of the tumor was used to guide the insertion of the double-hinged curette catheter through the biopsy channel of the bronchofiberscope. The curette catheter was advanced and directed to the lung lesion with the aid of fluoroscopy. The curette could be CHEST, 79: 2, FEBRUARY, 1981

2 FIGURE 1. Instruments used for bronchography consisting of flexible broncho-catheters (foteground) with head mirror,laryngeal mirror, xylocaine solutions for anesthetizing oralpharyngeal and laryngeal area and aqueous Dionosil contrast material. Hexed to 40 and rotated with the distal handle of the catheter. The curette scraped the lesion several times, then the bronchobberscope was withdrawn together with the curette at the distal end of the bronchoscope. A second bronchofiberscope was inserted through the endotracheal tube to evaluate any bleeding and to suction any blood present from the curette biopsy. The curette specimen was put immediately onto a slide, and the slide was immersed in a 95 percent alcohol solution for cytologic evaluation. Two or three curette biopsies were performed at each procedure, and biopsy forceps were not used. REsuLTS The chest roentgenographic pattern of the peripheral lung lesions of the 52 patients was divided into the three types shown in Table 1. Almost all of the lesions were distinct solitary nodules-or indistinct infiltrates. The location of the peripheral lung lesion is shown in Figure3. Both upper lobe bronchi were involved in 33 cases (63 percent)., -,.... ~ - ~. ".. ) FIGURE 2. Bronchography with standard and special magnification spot roentgenographic machine. Left panel shows patient with flexible broncho-catheter under x-ray machine. Right panel, standard x-ray equipment and special magnification 50 II- focal spot x-ray tube (center). CHEST, 79: 2, FEBRUARY, 1981 BRONCHOFIBERSCOPY WITH CURmE BIOPSY AND BRONCHOGRAPHY 163

3 Tablel-C...X-ray Fiadi...iraPeripl&eral Typeof,.".Caneer Radiologic Patterns Dense coin lesion with distinct border Faint indistinct solitary shadow with unclear border Linear or feathery shadow with indistinct border No.of Cases Using the curette biopsy to obtain the specimen for cytologic examination, a positive diagnosis for lung carcinoma was achieved in 45 of 46 patients, a yield of 97.8 percent. The remaining six patients refused bronchofiberscopy. Of this group, one had a diagnosis of malignancy made by needle biopsy, and the other five patients had the diagnosis of lung carcinoma obtained by thoracotomy. In five of 46 patients (11 percent) a second bronchofiberscopy with curette biopsy was required before a positive cytologic diagnosis could be made. The average time for a bronchofiberscopy procedure, excluding the topical anesthesia to the oral pharynx and the insertion of the endotracheal tube, was about 30 minutes, Complications associated with the curette biopsy included minor bleeding in three cases, which were self-limited and did not require blood transfusions, and pneumothorax requiring a chest tube in one case. Broken curettes retained in the lungs were not observed. Selective peripheral bronchograms were valuable in the localization of the tumor in the 46 cases in which bronchofiberscopy and curette biopsy were done. The following case illustrates the usefulness of selective peripheral bronchograms. The patient was a 65-year-old male smoker who had no respiratory symptoms, but a rcutine chest roentgenogram during a community-wide chest roentgenographic survey for lung cancer among high-risk patients who FIc:mm 3. Location of peripheral lung lesions in bronchial tree are smokers showeda peripheralsolitarylunglesion. Multiple sputum cytologies were negative for tumor cells. Chest roentgenograms, routine bronchography, and a selective peripheral bronchogram were performed (Fig 4A to 4C). Mter identifying the tumor site in the B6 subsegmental 0" bronchus (Fig 4B), a double-hinged curette was directed to that area via the bronchofiberscope under Huoroscopic guidance (Fig 4C). A diagnosis of adenocarcinoma was obtained from the curettage material. The cell types of the surgically resected specimens were adenocarcinoma in 41 patients (79 percent) and squamous cell carcinoma in eight patients (15 percent); one patient had a small-cell carcinoma, one a large-cell carcinoma, and one an adenosquamous cell carcinoma. The resected tumors were smaller than 1 cm in diameter in 12 patients and 1 em to 2 em in 40 patients. These cases had diagnosis and treatment during a period from January 1969 to June 1979; 33 of the patients (64 percent) have survived for five years or more. DISCUSSION In cases of peripheral lung carcinoma, the diagnostic accuracy for peripheral lung carcinoma with the flexible bronchofiberscope, using either the biopsy forceps or bronchial brushes, varies between48 percent and 80 percent.v'' Using a 1.7-mm nylon brush mounted on a steel guide wire, Richardson et al? made a diagnosis of lung carcinoma in 41 of 52 patients (79 percent) with mid or peripheral mass on a chest roentgenogram. Shoenbaum et al" used biopsy forceps in ten peripheral lung carcinomas ranging from 1.3 em to 6 em in diameter and obtained a positive diagnosis for malignancy in eight (80 percent); the positive yield with the biopsy forceps was in lesions 3 em or wider. It is the small peripheral lesion, 2 cm or smaller, that may be difficult to diagnose with forceps biopsy or bronchial brushings. In an earlier study at this institution, Tsuboi et al" used a specially designed single-hinged curette through a Metras' bronchial catheter for peripheral lung carcinomas smaller than 2 cm and had a positive cytologic diagnosis in 13 of 14 patients (92.8 percent). With the development of the Hexible bronchofiberscope by Ikeda,' the bronchofiberscope was used together with a doublehinged curette. The proximal part of the doublehinged curette used in this study can be Hexed to 40 0, leading to a 95 0 Hexion of the distal curette cup. In addition, this curette has greater flexibility, mobility, and directional guide than the routine biopsy forceps and bronchial brushes. Although the double-hinged curette is a delicate instrument, it is able to scrape or curettage in or around a lung lesion , LUKE, IKEDA CHEST, 79: 2, FEBRUARY, 1981

4 FIGURES 4A. B. C. Chestx-ray (a, left) selective peripheral bronchograms. (b, center) and curette biopsy (c. right) was performed in patient with peripheral lung lesion in left B6 subsegmental "b" bronchus. in a vigorous fashion. Mter curettage, it is withdrawn together with the bronchofiberscope from the endotracheal tube. The double-hinged curette is to be used for peripheral lung lesions and not for central lesions in which the biopsy forceps and bronchial brushes are preferred. Most bronchoscopists in the United States do not use the curette biopsy instruments.to However, Zavala demonstrated a diagnostic yield of 76 percent with the single-hinged curette in 13 of 17 patients with peripheral bronchogenic carcinoma in which the tumor was not visible endoscopically, In contrast, there was a positive cytologic diagnosis of 69 and 70 percent, respectively, when the biopsy forceps and bronchial brushes were used.'! Although the bronchofiberscope is a valuable diagnostic tool for the evaluation of lung cancer, 1 the positive diagnostic yield for peripheral lung lesion has been about 70 percent5-8 l1 using biopsy forceps and bronchial brushes but without bronchography or curette biopsy. Even with a selective peripheral bronchogram and the double-hinged curette, a small proportion of our patients required a second bronchoscopic procedure before a cytologic diagnosis was achieved. This further emphasizes the occasional difficulty of obtaining a diagnostic yield in peripheral lung lesion. Bronchography has been used by various investigators for the evaluation of lung caneer.p'" but it has not been used widely in the evaluation of suspected lung carcinoma in patients in U.S. medical centers." Fraser and Pare 16 do not recommend bronchography in the radiologic evaluation of suspected bronchogenic carcinoma, since the branchofiberscope can visualize the airways down to the subsegmental bronchi. However, in a small peripheral lung lesion, there is usually no endobronchial lesion, no stenosis of the bronchial orifice, and no abnormal mucosa pattern suggestive of carcinoma. Thus, the endoscopist has no guide to help direct the biopsy forceps or curette biopsy catheter, as is the case in most central types of carcinoma. Stitik and Proctor used tantalum bronchography" for the evaluation of radiologically occult bronchogenic carcinoma. IS They observed that if tantalum bronchography was done before bronchoscopy, the time spent in bronchoscopy to look for an occult lung cancer would be significantly decreased It should be noted that tantalum is an experimental contrast agent that has not been approved for routine use in the United States. At the National Cancer Center in Japan, selective bronchography's is used routinely in evaluating a peripheral lung lesion. In patients with positive sputum cytology for malignant cells but with a normal chest roentgenogram, bronchography may help in localizing the abnormal bronchus. We agree with Fraser and Pare l6that bronchography may not be necessary for the central type of bronchogenic carcinoma, but the selective peripheral bronchograms are valuable in identifying the exact location of a peripheral solitary lung lesion in the subsegmental bronchus of the bronchial tree. One can guide the curette directly to the affected subsegmental orifices without exploring other subsegmental bronchi. In addition, fluoroscopy is indispensable during the procedure and complements the bronchogram in directing the curette biopsy catheter to the site of the tumor. The time spent in performing bronehofiberscopic exainination is reduced. CHEST, 79: 2, FEBRUARY, 1981 BRONCHOFIBERSCOPY WITH CURmE BIOPSY AND BRONCHOGRAPHY 165

5 We were able to achieve a high diagnostic yield (97.8 percent) in the detection of peripheral lung carcinoma by using a combination of diagnostic tools-selective bronchography followed by broncho 6berscopy with curette biopsy under fluoroscopic visualization. The double-hinged curette catheter should only be used by bronchoscopists experienced with this technique. REFERENCES 1 Ikeda S. Atlas of flexible bronchofiberscopy. Tokyo; Igaku Shoin Ltd; Baltimore; University Park Press, Ikeda S, Tsuboi E, Ono R, et ale Flexible bronchofiberscope. Jap J Clin Onco11971; 1: Benfield JR, Juillard GJF, Pilch YH, et ale Current and future concepts of lung cancer. Ann Intern Moo 1975; 83: Weiss W, Boucot KR. The Philadelphia pulmonary neoplasm research project: early roentgenographic appearance of bronchogenic carcinoma. Arch Intern Med 1974; 134: Springfleld JT ill, Markowitz D], Bentz RR. The effect of tumor size and location on diagnosis by fiberoptic bronchoscopy. Chest 1977; 72: Schoenbaum SW, Koerner SK, Ramakrishna B, et ale Transbronchial biopsy of peripheral lesions with fluoroscopic guidance: use of the fiberoptic bronchoscope. J Can Assoc Radioll974; 25: Richardson RH, Zavala oc, Mukerjee PK, et at The use of fiberoptic bronchoscopy and brush biopsy in the diagnosis of suspected pulmonary malignancy. Am Rev Respir Dis 1974; 109: Kovnat DM, Rath GS, Anderson WM, et al. Bronchial brushing through the flexible 6beroptic bronchoscope in the diagnosis of peripheral pulmonary lesions. Chest 1975; 67: Tsuboi E, Ikeda S, Tajima M, Shimosato Y, et ale Transbronchial biopsy smear for diagnosis of peripheral pulmonary carcinoma. Cancer 1967; 20: Sackner MA. Bronchofiberscopy. Am Rev Respir Dis 1975; Ill: Zavala DC. Diagnostic 6beroptic bronchoscopy: techniques and results of biopsy in 600 patients. Chest 1975; 68: Mason WE, Templeton AW. Bronchographic signs useful in the diagnosis of lung cancer. Dis Chest 1966; 49: Rinker CT, Garrotto LJ, Lee KR, et ale Bronchography: diagnostic signs and accuracy in pulmonary carcinoma. Am J Roentgenoll968; 104: Bachynski JE. Selective bronchography of solitary mass lesions in the lung. J Can Assoc Radio11971; 22: Ono R, Ikeda S. Diagnosis of early lung cancer by applying the bronchography. Lung Cancer 1975; 15: Fraser RG, Pare JAP. Diagnosis of diseases of the chest. Philadelphia: WB Saunders Co, 1978, Vol 2, pp Stitik FP, Proctor DF. Delayed clearance of tantalum by radiologically occult cancer. Ann Oto11975; 84: Baker RR, Marsh BR, Frost JK, et ale The detection and treatment of early lung cancer. Ann Surg 1974; 179: rd Annual Environmental Health Conference The Third Annual Park City Environmental Health Conference: Legal and Ethical Dilemmas in Occupational Health, will be held at the Prospector Square Lodge, Park City, Utah, April For information, contact the Rocky Mountain Center for Occupational and Environmental Health, Attn: K. Blosch, Building 112, University of Utah, Salt Lake City, ONO, LOKE, IKEDA CHEST, 79: 2, FEBRUARY, 1981

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