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The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

During a 13-year period, multiple primary lung cancers were diagnosed in 80 consecutive patients. Forty-four patients had metachronous cancers. The initial pulmonary resection was lobectomy in 36 patients, bilobectomy in 3, pneumonectomy in 1, and wedge excision or segmentectomy in 4. The second pulmonary resection was lobectomy in 16 patients, bilobectomy in 2, completion pneumonectomy in 7, and wedge excision or segmentectomy in 19. There were two 30-day operative deaths (mortality rate, 4.5%). Actuarial 5- and 10-year survival rates after the first pulmonary resection for stage I disease were 55.2% and 27.0%, respectively. Five-year and 10-year survival rates for stage I disease after the second pulmonary resection were 41.0% and 31.5%, respectively. The remaining 36 patients had synchronous cancers. The pulmonary resection was lobectomy in 18 patients, bilobectomy in 3, pneumonectomy in 10, and wedge excision or segmentectomy in 8. There were two 30-day operative deaths (mortality rate, 5.6%). Actuarial overall 5- and 10-year survival rates after pulmonary resection were 15.7% and 13.8%, respectively. We conclude that an aggressive surgical approach is safe and warranted in most patients with multiple primary lung cancers and that the presence of synchronous primary cancers is ominous.

From 1958 through 1985, a total of 113 consecutive patients had completion pneumonectomy (CP). Indications for pulmonary resection resulting in CP were lung cancer (LC) in 64 patients, pulmonary metastases (PM) in 20, and benign lung disease (BLD) in 29. Operative mortality was 12.4% (14 deaths) but varied according to the indication for CP. Mortality was 9.4% for LC, 0% for PM, and 27.6% for BLD. Forty-three patients (38.1%) had major complications (26 of 64 with LC, 40.6%; 1 of 20 with PM, 5.0%; and 16 of 29 with BLD, 55.2%). Five-year actuarial survival for patients with LC was 26.4% but varied according to stage. Five-year survival for patients with PM was 40.8% and with BLD was 27.2%. We conclude that CP for BLD carries marked operative mortality and morbidity, usually due to intense reaction around hilar structures and concurrent active infection or fistula. In contrast, CP for LC and PM can be performed with low mortality, acceptable morbidity, and gratifying long-term survival.

Sixty-six patients (54 men and 12 women) with primary bronchogenic carcinoma and documented chest wall invasion underwent en bloc chest wall and pulmonary resection at the Mayo Clinic between January 1, 1960, and January 1, 1980. Ages ranged from 36 to 85 years, with a mean of 62.2. Forty-eight lobectomies, 16 pneumonectomies, and 2 wedge excisions were performed. After operation, 31 patients were classified as T3 N0 M0, 7 as T3 N1 M0, and 12 as T3 N2 M0. In 16 patients, the N classification could not be determined (T3 Nx M0). Operative mortality was 15.2%. Actuarial five-year survival (Kaplan-Meier method) of the 56 patients surviving operation was 32.9%. Five-year survival for patients with T3 N0 M0 neoplasms was 53.7%; five-year survival for patients with N1 and N2 neoplasms was only 7.4% (p = 0.001). The effect of various factors on survival, both singularly and in combination, was assessed by Cox's proportional hazards model. Only age had a significant association with survival. Among patients with T3 N0 M0 neoplasms, five-year survival was 84.6% for those 60 years of age or less and 27.7% for patients who were older than 60 years (p = 0.009). We conclude that en bloc resection for primary bronchogenic carcinoma with chest wall invasion, while associated with a significant mortality, can be performed with a strong likelihood of long-term survival if regional lymph nodes are not metastatically involved and there is no evidence of distant metastasis.

When the TNM staging system of the American Joint Committee (AJC) for Cancer Staging and End-Results Reporting was applied to 3,912 patients seen during a 6 year period at the Mayo Clinic, 624 (16%) fulfilled the criteria for postsurgical pathological Stage I non-small cell bronchogenic carcinoma. Of these 624 patients, 129 were excluded from further survival analysis for various reasons. The remaining 495 consisted of two groups: 350 patients who were enrolled within 30 days into a prospective postoperative 4 monthly follow-up program and 145 patients who were enrolled later or were followed less frequently. Because no significant difference was noted in survival rates between these groups, data were pooled. Of the combined group of 495 patients, 84% survived lung cancer for 2 years and 69% of 5 years (actuarial estimation). The survival of patients classified T1 N0 M0 (91% alive at 2 years and 80% at 5 years) is so good that it seems unlikely that adjuvant therapy in this group could demonstrate improved survival. In addition to TNM classification, age at operation, sex, and extent of operation were important determinants of survival.

Seventy-three patients (57 men and 16 women) underwent en bloc resection of lung and attached parietes between 1970 and 1982. All patients had documented malignant pleural invasion. Chest wall parietal pleura was invaded in 33 patients, pericardium in 14, phrenic or vagus nerve in nine, left atrium in five, superior vena cava in four, esophagus in two, diaphragm in one, and multiple structures in five. No patient underwent chest wall resection. Parietal pleurectomy was performed in all patients with involvement of the chest wall parietal pleura; 37 lobectomies and 36 pneumonectomies were performed. Operative mortality was 12.3%. The actuarial overall 5 year survival rate (Kaplan-Meier method) was 39.7%. We conclude that en bloc resection for primary bronchogenic carcinoma with invasion of adjacent intrathoracic structures, although associated with a significant mortality, can be performed with a reasonable likelihood of long-term survival.

The Mayo Lung Project (MLP) is a screening program designed to detect bronchogenic carcinoma at a curable stage. Screening tests include chest roentgenograms, three-day "pooled" sputum cytology studies, and lung-health questionnaires. These are being applied every four months to a study population of outpatients who have a high probability of developing lung cancer. Initial patient acceptance of the screening program has been excellent. Small asymptomatic lung cancers have been detected both roentgenographically and cytologically. The two procedures have complemented each other with little overlap. Chest roentgenography has proved most useful in diagnosing peripherally situated cancers, whereas sputum cytology studies have been most effective in identifying early squamous cancer involving major airways. At present, more cancers have been detected roentgenographically than cytologically, but the cytologically detected cases appear to have a better prognosis. Roentgenographically occult cancers have been localized with regularity, although the localization process is complicated. Theoretically, vigorous application of radiologic and cytologic screening, combined with optimum use of localizing procedures and treatment, could increase the five-year survival rate among lung cancer patients to nearly 50 percent. However, the actual survivorship attained will ultimately be determined by currently imponderable factors such as patient acceptance of longterm screening, frequency of multicentric respiratory cancers, and incidence of noncancerous smoking-related diseases, especially chronic obstructive pulmonary disease and ischemic heart disease.

Hematoporphyrin is preferentially concentrated by cancer tissue and therefore is a potentially useful chemical marker. This report demonstrates the effectiveness of a photoelectric hematoporphyrin fluorescence detector used simultaneously with flexible fiberoptic bronchoscopy as a means of detecting and localizing bronchogenic carcinoma. The detector generates an audio signal when fluorescence is within the visual field of the bronchoscope. Of interest is that an audio signal was generated which indicated hematoporphyrin fluorescence in areas where no mucosal abnormality had been seen. These areas proved to be carcinoma in situ.

Bronchogenic carcinoma complicated by ipsilateral cytologically positive effusion is considered unresectable. Bronchogenic carcinoma with cytologically negative effusion, even if bloody, has also been thought by many to be unresectable. Seventy-three patients with bronchogenic carcinoma and ipsilateral cytologically negative effusions were studied. Sixty-six underwent exploratory thoracotomy for staging or therapy; five had pleural biopsies and two had mediastinoscopies, all disclosing metastatic carcinoma. Four of the 73 patients (5.5 percent) had surgically resectable disease. They have remained free of disease for 3, 6, 7, and 14 years. Sixty-nine patients (94.5 percent) had unresectable carcinoma with metastases. Seventeen (94 percent) of 18 patients with bloody effusions had unresectable cancer. Carcinoma was resected in one patient with cytologically negative bloody effusion, and the patient remained free of disease during the 14-year follow-up period. Unresectability must be documented surgically in these patients to exclude those in whom curative resection can be performed.

The symptoms of progressive dyspnea, hemoptysis, spontaneous pneumothorax, chylous effusions, and cough in conjunction with ventilatory obstruction and abnormal gas exchange in a young woman should prompt the diagnosis of pulmonary lymphangiomyomatosis. Cytosol steroid-receptor assays and postmortem studies were conducted in an extensive investigation of a case of this disease. A biopsy specimen of the lung disclosed evidence of nuclear translocation of [3H]progesterone and the presence of a cytosolic receptor for progesterone, an indication that this disease could be treated effectively with progestin.

During the first 10 years of the Mayo Lung Project, 68 roentgenographically inapparent ("occult") lung cancers were localized and apparently completely resected. A pathologic classification was developed based on depth of tumor infiltration. The five categories were (1) in situ carcinoma confined to surface epithelium or ducts of mucous glands or acini (23 cancers), (2) intramucosal invasion not greater than 0.1 cm from mucosal surface (12 cancers), (3) invasion to bronchial cartilages (11 cancers), (4) invasion to full thickness of bronchial wall (10 cancers), and (5) extrabronchial invasion (12 cancers). Multicentricity of lung cancer was studied in 54 patients, none of whom had a history of cancer of the respiratory tract, and all of whom had had "complete" surgical resection of the initial occult lung cancer (or cancers). Neoplasms that were initially multicentric occurred in 4 patients, and a subsequent primary lung cancer developed in 11. The rate of detection of second primary lesions was 42 per 1,000 person-years of observation. A high incidence of unresectable cancers and a low survival rate were noted among patients who had a subsequent primary tumor. These findings were primarily attributable to invasiveness of the subsequent primary cancer or to respiratory insufficiency that resulted from obstructive lung disease or previous pulmonary resection. Because of the high risk of development of a second primary cancer after initial surgical resection, it is important to treat the initial occult cancer as conservatively as possible consistent with "cure."

Three hundred forty-six patients with post-surgical non-small cell Stage I bronchogenic carcinoma were followed from 5.0 to 10.8 years (median, 7.0 years). Recurrent cancer developed in 135 patients (39%). Seventy-five recurrences were nonregional metastases (55.6%); 35 (25.9%), a subsequent primary lung cancer; and 25 (18.5%), local recurrence only. The rate of recurrent lung cancer decreased from 15.0 patients per 100 patient-years the first postoperative year to 2.3 the seventh and subsequent years. The rate of recurrence varied among the three different types of recurrent cancer. Five years after pulmonary resection, 70.0% of patients with T1 N0 neoplasms had no evidence of recurrence compared with 58.2% of patients with T2 N0 tumors (p = 0.012) and only 31.8% of patients with T1 N1 neoplasms (p less than 0.001). There was no significant difference in overall rate of recurrence among the various cell types. Currently, 174 patients are alive. Lung cancer survival (Kaplan-Meier) was 69.1% at 5 years and 61.9% at 9 years. At 2 years following detection of subsequent lung cancer, 51.8% of patients with subsequent primary lung cancer had survived lung cancer compared with 23.4% for those with local recurrence and only 8.9% for those with nonregional metastases.

A cytologic examination of pleural fluid was performed on a pleural lavage specimen collected at the completion of operation after pulmonary resection in 135 of 599 patients undergoing curative pulmonary resection for a non-small cell carcinoma of the lung between 1977 and 1982. The cytologic results of lavage was positive for malignant cells in 12 of the 135 patients (8.9%). The incidence of positive results was correlated with lymph node status (N2 greater than N1 greater than N0), cell type (adenocarcinoma greater than other non-small cell lung cancers), stage (III greater than II greater than I), and visceral pleural status (invaded greater than not invaded). No positive cytologic results were noted in 39 patients having a diagnostic excisional pulmonary biopsy prior to more definitive resection. The disease has recurred in nine of the 12 patients with positive cytologic results (only two in the ipsilateral pleural space), and eight have died. The prognostic role of pleural lavage cytology needs more study.

En bloc resection of chest wall and lung for primary non-small cell bronchogenic carcinoma with chest wall invasion, although often associated with a significant operative mortality, can be performed with a reasonable expectation of long-term survival if lymph nodes are not metastatically involved. Older age appears to decrease long-term survival, but age alone should not abrogate surgical resection. Non-small cell carcinoma cell type, tumor size, depth of chest wall invasion, and extent of chest wall or lung resection do not significantly influence survival.

During a 6-yr period, 57 children and young adults less than 21 yr of age underwent 111 thoracotomies for pulmonary metastatic osteogenic sarcoma. Follow-up after the initial thoracotomy averaged 36.8 no and ranged from 1 to 78 mo. Twenty-eight patients (49%) underwent more than one thoracotomy--the number of multiple thoracotomies averaged 2.9 and ranged from two to eight. Twenty-six of the 57 patients are currently alive, and 25 of these are free of disease. Median survival was 36 mo. Actuarial survival curves demonstrated a 5-yr survival of approximately 40%. Seventy-one percent of patients who had a tumor-free interval of greater than 1 yr are currently alive, compared with 39% of patients who had a tumor-free interval of less than 1 yr. Patients with disease confined to one lobe at the initial thoracotomy had a better survival (64%) than patients with diffuse or bilateral disease (41%). An aggressive surgical approach toward osteogenic sarcoma with pulmonary metastasis thus appears to be justified.

A retrospective analysis of thirty patients who underwent pulmonary resection for metastatic osteosarcoma over a twenty-eight-year period revealed that most were young males with previous amputations for primary lesions of the lower extremity. In each, one to four thoracotomies had been performed, for a total of fifty-two chest operations with resection of 124 pulmonary metastatic lesions. At last follow-up, eleven of the thirty patients were alive and free of disease. At five years 28 per cent had survived: three of them were alive at more than nine years, and one was alive at nearly twenty years. Adverse survival factors identified were short tumor-free interval and multicentricity of pulmonary metastases. Long-term survival was associated with a tumor-free interval of more than two years and one to four thoracotomies at which few foci were present. As a group, patients selected for lung resection had significantly longer suvival than did patients whose pulmonary metastasis was untreated.

During the past 10 years, 54 patients, all men, were found to have roentgenographically occult lung cancer. The mean age was 61 years (range 45 to 76 years). All patients had abnormal findings on sputum cytologic study (carcinoma in 41 patients and squamous cell atypia in 13). The cancer was localized by bronchoscopy in all patients (range one to five examinations, mean 1.5). Seventy-five percent of the tumors were localized within 169 days of the abnormal sputum cytologic examination. Pulmonary resection for cure was performed in all patients: lobectomy in 38, pneumonectomy in nine, and bilobectomy in seven. Operative mortality was 5.6% (three patients). Fifty-eight cancers were resected, all squamous cell carcinomas (two had a component of large cell cancer). Tumor TNM classification (AJC) was TIS N0 M0 in 19 patients, T1 N0 M0 in 25, T1 N1 M0 in five, T2 N1 M0 in four, and T3 N0 M0 in one. Overall 5 year actuarial survival rate (lung cancer deaths only) was 90%. Five-year survival rate for the 44 patients with TIS N0 M0 and T1 N0 M0 neoplasms was 91%. Currently, 21 patients have died, but only 10 of lung cancer. Subsequent additional lung cancer developed in 12 patients (22%). Eleven of these patients had a second primary squamous lung cancer, six of which again were occult. We conclude that patients with occult lung cancer have a strong likelihood of long-term survival if treated early. Close surveillance is indicated because of the high incidence of a second primary lung cancer.