Ann Otol 84: 1975
EARLY LUNG CANCER DETECTION AND LOCALIZATION DAVID
R.
SANDElI.SON, M.D.
ROBERT S. FONTANA, M.D. ROCHESTER, MINNESOTA
SUMMARY - The Mayo Lung Project was established to develop and evaluate a screening program for early lung cancer in high-risk subjects. Men who are more than 45 years of age and who smoke one package of cigarettes or more daily are screened by the use of thoracic roentgenograms, three-day pooled sputum cytology, and lung health questionnaires at fourmonth intervals. These data are compared with data from similar subjects screened only on entry into the project. During the past three years, 34 patients who had no roentgenographic evidence of lung cancer were identified and examined because of carcinoma cells in sputum. Of these 34 patients, 27 have had bronchoscopic localization of their tumors and definitive treatment, and 3 had upper respiratory tract neoplasms and also have been treated. Of the remaining four, one patient died suddenly after myocardial infarction and three patients have not had localization or treatment because of other severe complicating medical problems. Localization of roentgenographically occult lung cancer is reliable by the use of bronchofiberoscopy and meticulous, thorough sampling from the tracheobronchial tree. A search must be made for upper airway cancers in the same high-risk population, and the possibility of second primary bronchogenic tumors also must be considered. Although follow-up is short, 22 of the 27 treated lung cancer patients were found with stage I disease. The outlook for 19 of these 27 is encouraging an average of 16 months after surgical resection.
Bronchogenic carcinoma continues to increase as a major public health problem. The American Cancer Society estimates that 91,000 new cases will be diagnosed in 1975 and that there will be 81,000 deaths. °1 Some observers have expressed doubt whether curable lung cancer can be detected effectively by any means." However, data from the American Joint Committee for Cancer Staging and End Results Reporting (AJC) show definite differences in long-term survival, depending on the histologic classification of the lesion and its stage when treatment is accomplished," The National Cancer Institute has established a Cooperative Early Lung Cancer Group to develop and evaluate
a program for screening high-risk subjects." Multidisciplinary groups at Johns Hopkins Hospital, Memorial SloanKettering Cancer Center, and Mayo Clinic were assigned the task of determining whether screening will make it possible to lower the mortality rate due to bronchogenic carcinoma from that in a matched population not screened regularly. The Mayo Lung Project (MLP) was established to screen men who are more than 45 years of age and who smoke one package of cigarettes or more daily (or who have done so within the previous year) from a population that presents for routine health examinations. 5 •6 Persons are excluded who already have respiratory cancer, who
"Incidence estimates are based on rates from the National Cancer Institute's Third National Cancer Survey. From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota. This investigation was supported in part by Research Grant CB-53886 from the National Institutes of Health, Public Health Service. Presented at the meeting of the American Broncho-Esophagological Association Atlanta Georgia, April 7-8, 1975. ' , 583
Downloaded from aor.sagepub.com at CARLETON UNIV on June 16, 2015
584
SANDERSON-FONTANA
have other serious illnesses that make five-year survival unlikely, or who have a respiratory reserve so severely diminished that surgical resection of at least one lobe of the lung is impossible. With these criteria for exclusion, the population is randomized into two groups. One group is followed regularly at four-month intervals, at which time a three-day pooled sputum cytology examination, 14- by 17-inch thoracic roentgenogram, and lung health questionnaire are completed. Every effort is made by mail or telephone to ensure completion of each screening procedure. The other group is advised, at the initial enrollment, of the desirability of getting regular annual sputum tests and chest roentgenograms, but the person must initiate such action. All persons in either group are to be followed for at least five years. Any patient in whom carcinoma of the lung develops will be treated as promptly as possible, depending on type of tumor, its localization, and other medical considerations. All patients treated for lung cancer will continue to receive frequent follow-up indefinitely. When the thoracic roentgenogram demonstrates a persistent new lesion compared with the previous normal film, the likelihood of malignancy is high and early resection nrobablv will follow. However, when the roentgenogram of the chest is normal but sputum cytology examination indicates suspicion or conclusive evidence of malignancy, the task of localizing the source of the exfoliated cancer cells presents a major challenge. A specific protocol for investigating patients with this problem has been evolved by the Coooerative Early Lung Cancer Group (CELC Croup)." Earlier reports from Johns Hopkins" and Mayo Clinic" have outlined the procedures to be followed. PRE-ENDOSCOPY EXAMINATION
After a patient with positive sputum cytology and normal routine chest
roentgenography is identified, a series of prebronchoscopy tests is completed. A complete physical examination, routine laborary studies (including hemogram, blood chemistry profile, and urinalysis), and electrocardiography are carried out. Roentgenographic studies include stereoscopic paired posteroanterior views at 140 kvp and lateral chest roentgenograms, whole lung tomograms, and a 14- by 17-inch posteroanterior projection made at 350 kvp. Pulmonary function is assessed by standard spirometry to measure VC. FEV" MBC, and MMF O (before and after nebulized isoproterenol is given). If doubt exists regarding respiratory reserve, arterial blood gas measurements are also obtained. Special attention is given to examination of the larynx and oropharynx in search of lesions of the upper respiratory tract. The patient is asked to discontinue smoking for one to two weeks before the examination. Oral bronchodilators and antibiotics may be given in an effort to improve the underlying chronic bronchitis. The patient is then hospitalized and bronchoseeped while under general anesthesia, as described by Perry and Sanderson." Care is taken to ensure the maintainence of optimal levels for arterial blood gases during and after the prolonzed examination of the tracheobronchial tree. PROTOCOL FOR BRONCHOSCOPIC EXAMINATION
The methods employed are modified after the description of Marsh and colleagues? and subsequently standardized by the CELC Croup." After induction of anesthesia, an open rigid ventilating bronchoscope with inflatable cuff placed distally is inserted. One hundred percent oxygen is insufflated, and the bronchoscope is positioned in the left main bronchus. Lavage is repeated on the left side two or three times before the cuff is deflated. After another one- to two-minute interval with the patient breathing 1000;
---;-Vc - Vital capacity. FEV - Forced expiratory volume. MBC - Maximum breathing capacity. MMF - Maximal midflow.
Downloaded from aor.sagepub.com at CARLETON UNIV on June 16, 2015
LUNG CANCER DETECTION
oxygen, the bronchoscope is positioned in the right main bronchus just proximal to the right upper lobe orifice and the cuff is reinflated. The right side is again lavaged two or three times, and washings are submitted separately for examination. The cuff is deflated, and ventilation is resumed before withdrawal of the open bronchoscope. A cuffer endotracheal tube of 9 or 10 mm internal diameter is inserted in order to complete the procedure. A specially fitted T-adapter permits access with the bronchofiberscope while controlled ventilation and general anesthesia are maintained. Both sides of the tracheobronchial tree are inspected completely, and the entire accessible bronchial mucosa area is recorded on video-tape using color television. Any locally suspicious areas are also documented with still photography using a 35 mm halfframe camera. Brush, curette, and forcep biopsy specimens are obtained when an obviODS bronchogenic carcinoma is seen. However, if no grossly abnormal lesion is seen, samples are taken from all accessible segmental and subsegmental branches, and each sample is labeled and submitted separately for examination. Generally, all brush and curette samples are taken before the multiple biopsy collections are begun because the latter is more likely to cause bleeding, which may obscure subtle mucosal changes. After bronchoscopic sampling has been completed, the patient is allowed tel waken and is transferred to the postoperative recovery room for further observation. Arterial blood gases are monitored during and after the procedure to ensure adequate, safe oxygenation and alveolar ventilation. RESULTS
Since Jan. 1, 1972, 34 patients with no roentgenographic evidence for cancer localization have been evaluated by the MLP because of sputum cytology positive for carcinoma cells. Fifteen of these patients were included in an earlier report on roentgenographically
585
occult lung cancer, and the others have been seen since that time. These 34 patients represent three categories of presentation. Ten had sputum positive on initial screening of an ambulatory outpatient population of male smokers more than 45 years of age ("prevalence"). Five had sputum that became positive after initial negative screening (
EARLY LUNG CANCER DETECTION AND LOCALIZATION DAVID
R.
SANDElI.SON, M.D.
ROBERT S. FONTANA, M.D. ROCHESTER, MINNESOTA
SUMMARY - The Mayo Lung Project was established to develop and evaluate a screening program for early lung cancer in high-risk subjects. Men who are more than 45 years of age and who smoke one package of cigarettes or more daily are screened by the use of thoracic roentgenograms, three-day pooled sputum cytology, and lung health questionnaires at fourmonth intervals. These data are compared with data from similar subjects screened only on entry into the project. During the past three years, 34 patients who had no roentgenographic evidence of lung cancer were identified and examined because of carcinoma cells in sputum. Of these 34 patients, 27 have had bronchoscopic localization of their tumors and definitive treatment, and 3 had upper respiratory tract neoplasms and also have been treated. Of the remaining four, one patient died suddenly after myocardial infarction and three patients have not had localization or treatment because of other severe complicating medical problems. Localization of roentgenographically occult lung cancer is reliable by the use of bronchofiberoscopy and meticulous, thorough sampling from the tracheobronchial tree. A search must be made for upper airway cancers in the same high-risk population, and the possibility of second primary bronchogenic tumors also must be considered. Although follow-up is short, 22 of the 27 treated lung cancer patients were found with stage I disease. The outlook for 19 of these 27 is encouraging an average of 16 months after surgical resection.
Bronchogenic carcinoma continues to increase as a major public health problem. The American Cancer Society estimates that 91,000 new cases will be diagnosed in 1975 and that there will be 81,000 deaths. °1 Some observers have expressed doubt whether curable lung cancer can be detected effectively by any means." However, data from the American Joint Committee for Cancer Staging and End Results Reporting (AJC) show definite differences in long-term survival, depending on the histologic classification of the lesion and its stage when treatment is accomplished," The National Cancer Institute has established a Cooperative Early Lung Cancer Group to develop and evaluate
a program for screening high-risk subjects." Multidisciplinary groups at Johns Hopkins Hospital, Memorial SloanKettering Cancer Center, and Mayo Clinic were assigned the task of determining whether screening will make it possible to lower the mortality rate due to bronchogenic carcinoma from that in a matched population not screened regularly. The Mayo Lung Project (MLP) was established to screen men who are more than 45 years of age and who smoke one package of cigarettes or more daily (or who have done so within the previous year) from a population that presents for routine health examinations. 5 •6 Persons are excluded who already have respiratory cancer, who
"Incidence estimates are based on rates from the National Cancer Institute's Third National Cancer Survey. From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota. This investigation was supported in part by Research Grant CB-53886 from the National Institutes of Health, Public Health Service. Presented at the meeting of the American Broncho-Esophagological Association Atlanta Georgia, April 7-8, 1975. ' , 583
Downloaded from aor.sagepub.com at CARLETON UNIV on June 16, 2015
584
SANDERSON-FONTANA
have other serious illnesses that make five-year survival unlikely, or who have a respiratory reserve so severely diminished that surgical resection of at least one lobe of the lung is impossible. With these criteria for exclusion, the population is randomized into two groups. One group is followed regularly at four-month intervals, at which time a three-day pooled sputum cytology examination, 14- by 17-inch thoracic roentgenogram, and lung health questionnaire are completed. Every effort is made by mail or telephone to ensure completion of each screening procedure. The other group is advised, at the initial enrollment, of the desirability of getting regular annual sputum tests and chest roentgenograms, but the person must initiate such action. All persons in either group are to be followed for at least five years. Any patient in whom carcinoma of the lung develops will be treated as promptly as possible, depending on type of tumor, its localization, and other medical considerations. All patients treated for lung cancer will continue to receive frequent follow-up indefinitely. When the thoracic roentgenogram demonstrates a persistent new lesion compared with the previous normal film, the likelihood of malignancy is high and early resection nrobablv will follow. However, when the roentgenogram of the chest is normal but sputum cytology examination indicates suspicion or conclusive evidence of malignancy, the task of localizing the source of the exfoliated cancer cells presents a major challenge. A specific protocol for investigating patients with this problem has been evolved by the Coooerative Early Lung Cancer Group (CELC Croup)." Earlier reports from Johns Hopkins" and Mayo Clinic" have outlined the procedures to be followed. PRE-ENDOSCOPY EXAMINATION
After a patient with positive sputum cytology and normal routine chest
roentgenography is identified, a series of prebronchoscopy tests is completed. A complete physical examination, routine laborary studies (including hemogram, blood chemistry profile, and urinalysis), and electrocardiography are carried out. Roentgenographic studies include stereoscopic paired posteroanterior views at 140 kvp and lateral chest roentgenograms, whole lung tomograms, and a 14- by 17-inch posteroanterior projection made at 350 kvp. Pulmonary function is assessed by standard spirometry to measure VC. FEV" MBC, and MMF O (before and after nebulized isoproterenol is given). If doubt exists regarding respiratory reserve, arterial blood gas measurements are also obtained. Special attention is given to examination of the larynx and oropharynx in search of lesions of the upper respiratory tract. The patient is asked to discontinue smoking for one to two weeks before the examination. Oral bronchodilators and antibiotics may be given in an effort to improve the underlying chronic bronchitis. The patient is then hospitalized and bronchoseeped while under general anesthesia, as described by Perry and Sanderson." Care is taken to ensure the maintainence of optimal levels for arterial blood gases during and after the prolonzed examination of the tracheobronchial tree. PROTOCOL FOR BRONCHOSCOPIC EXAMINATION
The methods employed are modified after the description of Marsh and colleagues? and subsequently standardized by the CELC Croup." After induction of anesthesia, an open rigid ventilating bronchoscope with inflatable cuff placed distally is inserted. One hundred percent oxygen is insufflated, and the bronchoscope is positioned in the left main bronchus. Lavage is repeated on the left side two or three times before the cuff is deflated. After another one- to two-minute interval with the patient breathing 1000;
---;-Vc - Vital capacity. FEV - Forced expiratory volume. MBC - Maximum breathing capacity. MMF - Maximal midflow.
Downloaded from aor.sagepub.com at CARLETON UNIV on June 16, 2015
LUNG CANCER DETECTION
oxygen, the bronchoscope is positioned in the right main bronchus just proximal to the right upper lobe orifice and the cuff is reinflated. The right side is again lavaged two or three times, and washings are submitted separately for examination. The cuff is deflated, and ventilation is resumed before withdrawal of the open bronchoscope. A cuffer endotracheal tube of 9 or 10 mm internal diameter is inserted in order to complete the procedure. A specially fitted T-adapter permits access with the bronchofiberscope while controlled ventilation and general anesthesia are maintained. Both sides of the tracheobronchial tree are inspected completely, and the entire accessible bronchial mucosa area is recorded on video-tape using color television. Any locally suspicious areas are also documented with still photography using a 35 mm halfframe camera. Brush, curette, and forcep biopsy specimens are obtained when an obviODS bronchogenic carcinoma is seen. However, if no grossly abnormal lesion is seen, samples are taken from all accessible segmental and subsegmental branches, and each sample is labeled and submitted separately for examination. Generally, all brush and curette samples are taken before the multiple biopsy collections are begun because the latter is more likely to cause bleeding, which may obscure subtle mucosal changes. After bronchoscopic sampling has been completed, the patient is allowed tel waken and is transferred to the postoperative recovery room for further observation. Arterial blood gases are monitored during and after the procedure to ensure adequate, safe oxygenation and alveolar ventilation. RESULTS
Since Jan. 1, 1972, 34 patients with no roentgenographic evidence for cancer localization have been evaluated by the MLP because of sputum cytology positive for carcinoma cells. Fifteen of these patients were included in an earlier report on roentgenographically
585
occult lung cancer, and the others have been seen since that time. These 34 patients represent three categories of presentation. Ten had sputum positive on initial screening of an ambulatory outpatient population of male smokers more than 45 years of age ("prevalence"). Five had sputum that became positive after initial negative screening (
