| Japanese Journal of Clinical Oncology | Pages |
Lung Cancer in Patients Who Had Received Thoracoplasty for Pulmonary Tuberculosis
Introduction
Patients
Results
Discussion
References
Lung Cancer in Patients Who Had Received Thoracoplasty for Pulmonary Tuberculosis
Background: In Japan in the 1950s, thoracoplasty was a powerful therapy for pulmonary tuberculosis. Now there are many aged people who have tuberculosis sequelae caused by thoracoplasty. We have encountered some cases of lung cancer among these people. Methods: To elucidate the features of lung cancer occurring after thoracoplasty for pulmonary tuberculosis, we reviewed for analysis 20 such cases. Results: There were 17 men and three women, aged 55 to 78 years (mean 65 years). All had respiratory dysfunction and most were cigarette smokers. Lung cancers were located in the upper lobes in nine cases, in the middle lobe in one and in the lower lobes in 10. Ten lung cancers were in the thoracoplastied lung and the remaining 10 in the opposite lung. Histologically, squamous cell carcinoma was predominant (11 cases). Eight lung cancers were detected in stages I and II and 12 in stages III and IV. Most cancer lesions were separate from tuberculosis lesions. Surgical resection was selected in only three of 11 stages I-IIIA cases in consideration of respiratory dysfunction and/or ventilatory impairment due to thoracoplasty. Chemotherapy and/or radiotherapy were performed in nine and supportive care alone was performed in eight. Fourteen patients died of lung cancer and four died of cor pulmonale due to tuberculosis sequelae. Five-year survival was achieved in only one surgical case. Eight of the nine patients who received chemotherapy or radiotherapy died within 1 year, and, further, seven of eight patients who received supportive care died within 6 months. Conclusion: Lung cancer in the patients who had received thoracoplasty occurred in each lung and every lobe, independent of thoracoplasty. In addition, delay of detection was such that stage III-IV cases were in the majority, there were some limitations in therapeutic benefits related to thoracoplasty and the prognosis was very poor. Physicians should avoid delay in the detection of lung cancer through careful follow-up of such patients.
Key words: lung cancer - pulmonary tuberculosis - thoracoplasty - tuberculosis sequelae - treatment - prognosis
INTRODUCTION
Previously, tuberculosis was extremely prevalent in Japan and in the 1950s 3,000,000 people had active tuberculosis. At this time no powerful agents against tuberculosis, such as rifampicin, were available and thoracoplasty was one of the effective treatments for pulmonary tuberculosis. Thoracoplasty resulted in a clinical cure of tuberculosis in many patients, but later these patients aged and in many there were tuberculosis sequelae caused by irreversible, anatomical changes of the lung (1).
We have encountered at our hospital some cases of lung cancer among these patients. Since the first report on the co-existence of lung cancer and pulmonary tuberculosis by Bayle (2) in 1810, the association between the two diseases has been reported and discussed by many workers. However, there have been few studies on lung cancer after thoracoplasty. We therefore assessed 20 lung cancer cases for analysis to clarify the clinical features of lung cancer in patients who had received thoracoplasty.
PATIENTS
Between 1982 and 1998, 1635 patients with lung cancer were admitted to the Tokyo National Chest Hospital. Of thesepatients, we encountered 20 who had previously undergone thoracoplasty for pulmonary tuberculosis. Through analysis of chest radiographs, pulmonary function tests and other medical records, we assessed the clinical details of these patients, such as sequelae due to tuberculosis, features of lung cancer, treatment and course.
RESULTS
Of the 20 patients, 17 were men and three were women. The ages at which lung cancer was detected at our hospital ranged from 55 to 78 years (mean 65 years), with the highest incidence in the sixth decade of life. The clinical background of these patients is summarized in Table 1. The occurrence of tuberculosis was mainly in the 1940s to 1950s and many of the patients underwent thoracoplasty in the 1950s to 1960s. In four of the 20 patients, lobectomy or segmentectomy was also performed in addition to thoracoplasty. In most patients, the interval between thoracoplasty and detection of lung cancer was over 20 years. Performance status was grades 1-2 in 14 patients and grades 3-4 in six patients. All had chronic symptoms such as cough, sputum and/or shortness of breath. Mild to severe pulmonary dysfunction was evident in all 17 patients who had had pulmonary function tests and four patients were under home oxygen therapy. Sixteen patients were past or current cigarette smokers and 13 of the 16 had smoked more than 20 cigarettes per day for at least 20 years.
Table 1. Clinical background of patients at the time of detection of lung cancer
| Gender | |
| Male | 17 |
| Female | 3 |
| Age | |
| <60 | 6 |
| 61-70 | 9 |
| [ge]71 | 5 |
| Period of thoracoplasty | |
| 1970 or before | 15 |
| 1971-1980 | 5 |
| Interval between thoracoplasty and lung cancer (years) | |
| <20 | 3 |
| [ge]21 | 17 |
| Performance status | |
| 1 | 8 |
| 2 | 6 |
| 3 | 4 |
| 4 | 2 |
| VC/FEV1.0 (ml) | |
| <1000 | 3/6 |
| 1001-2000 | 9/10 |
| [ge]2001 | 5/1 |
| NE | 3/3 |
Characteristics of the lung cancers are shown in Table 2. Twelve of the cancers were in the right lung and eight in the left; nine were in the upper lobes, one in the middle lobe and 10 in the lower lobes; and 10 were in the thoracoplastied lung and 10 in the opposite lung. Clinical stages of disease were stage IA in two patients, stage IB in three, stage IIB in three, stage IIIA in three, stage IIIB in three and stage IV in six. Histologically, 11 of the 20 lung cancers were squamous cell carcinoma, five adenocarcinoma, three small cell carcinoma and the remaining one a large cell carcinoma. Further, seven of the 11 squamous cell carcinomas, all five of the adenocarcinomas, one of the three small cell carcinomas and one large cell carcinoma originated in the peripheral lung fields. The localization of cancers did not differ between the histological types (Table 3).
Table 2. Characteristics of lung cancer
| Localization | |
| RUL | 3 |
| RML | 1 |
| RLL | 8 |
| LUL | 6 |
| LLL | 2 |
| Thoracoplastied lung | 10 |
| Opposite lung | 10 |
| Histological type | |
| Squamous cell carcinoma | 11 |
| Adenocarcinoma | 5 |
| Small cell carcinoma | 3 |
| Large cell carcinoma | 1 |
| Stage | |
| IA | 2 |
| IB | 3 |
| IIA | 0 |
| IIB | 3 |
| IIIA | 3 |
| IIIB | 3 |
| IV | 6 |
Table 3. Anatomical relationship between thoracoplasty and histological type of lung cancer
| Thoracoplastied lung | Opposite lung | |
| Squamous cell carcinoma | 5 | 6 |
| Peripheral | 4 | 3 |
| Central | 1 | 3 |
| Small cell carcinoma | 2 | 1 |
| Peripheral | 0 | 1 |
| Central | 2 | 0 |
| Adenocarcinoma (peripheral) | 2 | 3 |
| Large cell carcinoma (peripheral) | 1 | 0 |
| Total | 10 | 10 |
Full radiographic observations revealed that the cancer lesions appeared to be separate from inactive tuberculosis lesions, except for one cancer lesion originating from lung parenchyma near the site of thoracoplasty. All of the 12 patients who were shown to be in stage III-IV were referred to our hospital after enlargement of tumor shadows on chest X-rays, while all of the five patients whose cancers were detected in stage I had been in and out of our hospital because of deterioration of chronic respiratory distress.
Details of treatment for the lung cancer patients are summarized in Table 4. Curative resection was performed in only three cases (1/5 stage I, 1/3 stage II and 1/3 stage IIIA). In two of these three patients (stage I, stage II) the cancer lesion was located in the thoracoplastied lung. Although forced expiratory volume in 1 s (FEV1.0) was poor in these patients (990 and 1020 ml), pneumonectomy was performed without severe respiratory complications. In the third patient (stage IIIA) the lung cancer was located in the opposite lung. Despite an FEV1.0 value of 1390 ml, the patient experienced severe respiratory distress after lobectomy. In the remaining five patients with stage I-IIIA disease, four stage I patients were receiving home oxygen therapy and surgical resection was impossible. Further, two of the three stage II lung cancers and two of the three stage IIIA lung cancers were located in the opposite, relatively healthy lung and surgery was not considered because of the likelihood of severe respiratory distress as a result not only of the lobectomy but also of partial resection of the healthy lung.
Table 4. Relationship between localization of lung cancer and treatment
| Thoracoplastied lung | Opposite lung | |
| Surgical resection | 2 | 1 |
| Radiotherapy | 3 | 1 |
| Chemotherapy | 2 | 3 |
| Supportive care alone | 3 | 5 |
| Curative resection | 10 | 10 |
Palliative radiotherapy was performed in four (two stage IIIB, two stage IV) patients, with cancer in the thoracoplastied lung predominant (three cases) over that in the opposite lung (one case). Irradiation that ranged from 47 to 55 Gy was administered without adverse effects, but also without beneficial effect. Chemotherapy containing cisplatin was administered in five cases (one stage II, two stage IIIA, two stage IV) without beneficial effects. All five patients completed one cycle of administration. No anti-cancer therapy was performed in the remaining eight patients in consideration of factors such as age, performance status, extent of disease, respiratory function and location of lung cancers.
The outcome of treatment of the 20 patients is shown in Table 5. Surgical resection resulted in a good course in two cases in which lung cancer occurred in the thoracoplastied lung. One of these patients survived for 102 months after pneumonectomy without recurrence of tumor (Fig. 1) and the other is alive 20 months after pneumonectomy without recurrence.However, the third patient for whom surgery was performed and who had lung cancer in the opposite lung died 9 months after surgery due to recurrence of cancer.
Figure 1. Lung cancer found in the right lower lobe on chest X-ray (arrowhead). Pneumonectomy was performed and pathological examination revealed that the cancer was in stage IA. Recurrence of the tumor did not occur and the patients died of cor pulmonale 102 months later.
Table 5. Relationship between treatment and outcome
| Surgical resection | Radiotherapy | Chemotherapy | Supportive care | |
| Prognosis | ||||
| Alive | 1 | 0 | 0 | 1 |
| Died | 2 | 4 | 5 | 7 |
| [le]6 months | 0 | 2 | 3 | 7 |
| 7-12 months | 1 | 1 | 2 | 0 |
| [ge]13 months | 1 | 1 | 0 | 0 |
| Cause of death | ||||
| Cancer-related | 1 | 4 | 5 | 4 |
| Cor pulmonale | 1 | 0 | 0 | 3 |
The survival time of four patients who had received radiotherapy ranged from 2 to 16 months and all but one patient died within 1 year. The period of survival was poor, ranging from 3 to 8 months, in the five patients who received chemotherapy (Fig. 2). Further, seven of eight patients with only supportive care died within 6 months after diagnosis of lung cancer. As for the cause of death in patients who did not receive surgical resection, three patients, whose cancer was in stage I, died of cor pulmonale due to tuberculosis sequelae. The cause of death was thought to be cancer-related in the remaining 13 patients, but a poor respiratory condition appeared to shorten the period of survival.
Figure 2. Left upper lobe atelectasis caused by lung cancer found on chest X-ray. Although the cancer was clinically thought to be in stage IIB, surgical resection was impossible because of poor respiratory and systemic conditions. Bronchial arterial infusion of cisplatin was administered, but was not effective. The patient died of lung cancer 8 months later.
DISCUSSION
There have been many studies on lung cancer associated with pulmonary tuberculosis and the possible relationship between these two diseases has been discussed for many years from etiological and/or pathogenic aspects (3-8). In Japan, tuberculosis had been the most frequently occurring infectious diseaseand at present there are many people who have active or inactive tuberculosis. Therefore, many Japanese reports on co-existing lung cancer and pulmonary tuberculosis have been published and these have shown that lung cancer occurred in 1% of patients with active tuberculosis and that, conversely, active tuberculosis occurred in 4% of patients with lung cancer (9-11). In the present series, we did not evaluate the frequency of lung cancer in patients with inactive tuberculosis from the etiological aspect, because aged patients admitted to our hospital usually have some degree of inactive tuberculous shadows besides thoracoplasty on chest X-rays, with or without a history of medication for tuberculosis. The interest in this study was the pathogenic relationship between pulmonary tuberculosis and lung cancer, including the special environmental influences on carcinogenesis caused by thoracoplasty.
The histological type of lung cancer in patients with tuberculous lesions varied in previous reports. Many reports showed that squamous cell carcinoma predominated (9-14) and others showed that there were no significant differences between histological types of lung cancer that occurred with or without pulmonary tuberculosis (15,16). Also, some studies indicated that the histological type was apt to differ between patients with active and inactive tuberculosis. Mirany et al. (17) showed that squamous cell carcinoma predominated in inactive tuberculosis patients but adenocarcinoma predominated in activetuberculosis patients, whereas Yatsuka et al. (18) showed that squamous cell carcinoma predominated in the presence of active tuberculosis. In our series, squamous cell carcinoma was predominant. The higher rate of squamous cell carcinoma may be influenced by external factors, such as smoking, because in our series most patients were heavy, chronic cigarette smokers.
Localization of lung cancer and tuberculosis lesions has also been discussed from pathogenic aspects. In early reports, the anatomical changes due to tuberculosis such as metaplasia and chronic irritation of bronchi and lung parenchyma could be carcinogenic (7,19). The theory of `scar cancer' described by Friedrich (20) in 1939 was also noted and some reports showed that lung cancer arose in pulmonary scars that were the result of healed tuberculous infection (21,22). However, later pathological analyses (23,24) revealed that scarring is the result rather than the predecessor of tumor growth of peripheral lung cancer. In fact, many Japanese investigations indicated that cancer and tuberculosis lesions tended to be seen within the same lobe but were located independently; a mixture of the two lesions is rare(8-10,25,26). In this study, all but one lung cancer were detected on chest X-rays separately from tuberculosis lesions, including sites around thoracoplasty. We consider that scar cancer is rare in patients who had undergone thoracoplasty.
Another pathogenic factor for carcinogenesis in our cancers may be ventilatory impairment due to thoracoplasty. Yoneyama et al. (27) reported that in 46 patients with pre-existing unilateral lung disease, including eight patients who had received thoracoplasty, there was a much higher incidence of lung cancer in the better ventilated lung and that most of so-called Kreyberg's group I cancers (28), such as squamous cell carcinoma and small cell carcinoma, occurred in the better ventilated lung. They suggested that, as an environmental effect on cancer, the bronchial epithelium of the healthy lung is more exposed to exogenous carcinogens than is that of the diseased, unventilated lung, resulting in a high risk of development of Kreyberg's group I cancers. Later reports (18,29) similarly showed that lung cancer in patients who had undergone thoracoplasty was apt to occur in the opposite, relatively healthy lung. In our series, however, there was no difference in incidence between lung cancers in the thoracoplastied lung and those in the opposite lung and, further, we found no association between thoracoplasty and Kreyberg's group I cancer. We conclude that in patients who received thoracoplasty for tuberculosis, lung cancer may occur in each lung and every lobe, independent of thoracoplasty.
It has been indicated that pre-existing pulmonary conditions due to inactive tuberculosis cause some difficulties in detecting by chest X-ray small lung cancer shadows and in management of lung cancer patients (30). In this study we have elucidated the clinical problems of lung cancer in patients who had received thoracoplasty. First, lung cancers were apt to be found in far-advanced stages. However, in fact, the lung cancers were mostly apart from the tuberculosis and frequent X-ray examinations yielded early detection of lung cancers in patients who were frequently in and out of our hospital. Second, because of ventilatory impairment caused by thoracoplasty, benefits from local therapy such as surgical resection and, probably, radiotherapy were limited. Finally, prognosis of the patients was very poor, which may be associated with not only an advanced stage at detection but also an underlying poor respiratory condition.
In the present series, many of our patients were in an unsuitable state for cancer treatment, resulting in a poor prognosis.However, in a few of our patients whose cancer was detected at an early stage and located in the thoracoplastied lung and, further, whose systemic and respiratory conditions were relatively preserved, aggressive therapy such as pneumonectomy was possible, resulting in a good prognosis. Therefore, care should be taken by physicians not to delay in the diagnosis of lung cancer by careful follow-up of patients who had received thoracoplasty.
References
Received February 22, 1999; accepted July 16, 1999
For reprints and all correspondence: Atsuhisa Tamura, Department of Respiratory Diseases, Tokyo National Chest Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan
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Copyright© 1999 Foundation for the Promotion of Cancer Research.
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