|Year : 2018 | Volume
| Issue : 6 | Page : 199-202
Association of pulmonary tuberculosis with lung carcinoma: An epidemiological study
Partha Dasgupta, Kakali Choudhury, Nishana Paul, Krishnangshu Bhanja Choudhury, Bodhisatta Roy, Shampa Maity
Department of Radiotherapy, R. G. Kar Medical College, Kolkata, West Bengal, India
|Date of Web Publication||18-Jan-2019|
Dr. Kakali Choudhury
Department of Radiotherapy, R. G. Kar Medical College, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Introduction: Tuberculosis (TB) is a serious public health problem in developing countries, with India bearing highest burden. Lung cancer (LC), especially adenocarcinoma, is also increasing all over the world, with India having highest mortality in males due to lung cancer. Both diseases do co-exists producing diagnostic dilemma and treatment controversies. We intended to explore the incidence of both diseases at a tertiary cancer centre. Materials and Methods: This longitudinal study was conducted between 2014 to 2017. Diagnosis and treatment of TB were according to DOTS protocol. For lung cancer biopsy was mandatory for diagnosis. Results: Our study was conducted on 42 patients at the Department of Radiotherapy, R.G. Kar Medical College. In 19 of the 42 patients, the diagnosis of TB and LC occurred simultaneously, whereas, in 23, the occurrence was sequential. Fifteen (35.7%) patients reported having had TB twice. TB treatment was given as Category 1 of DOTS in 21 patients (50%) and Category 2 in 15 (35.7%). In 6 (14.3%) patients, the data on treatment regimen were either not provided or unavailable. Regarding carcinoma lung management, 50% of patients were purely treated as palliative intent. Twenty percent of patients received chemotherapy with platinum doublet. Thirty percent of patients were given best supportive care. Conclusion: The symptoms of TB and lung carcinoma overlap with each other. If we get any patient with lung cancer not much improving after anticancer treatment, diagnosis of TB should be kept in mind. Similarly, in any diagnosed case of pulmonary TB, development of lung cancer should be considered if not improved with anti-tubercular treatment.
Keywords: Lung carcinoma, pulmonary tuberculosis, simultaneous and sequential
|How to cite this article:|
Dasgupta P, Choudhury K, Paul N, Choudhury KB, Roy B, Maity S. Association of pulmonary tuberculosis with lung carcinoma: An epidemiological study. Clin Cancer Investig J 2018;7:199-202
|How to cite this URL:|
Dasgupta P, Choudhury K, Paul N, Choudhury KB, Roy B, Maity S. Association of pulmonary tuberculosis with lung carcinoma: An epidemiological study. Clin Cancer Investig J [serial online] 2018 [cited 2019 Jul 19];7:199-202. Available from: http://www.ccij-online.org/text.asp?2018/7/6/199/250401
| Introduction|| |
Tuberculosis (TB) is a serious public health problem in developing countries. Medical science is getting improved day by day, and still, the odds of treatment against TB are also developing, for example, emergence of multidrug resistant. India is the highest TB burden country, with the World Health Organization statistics for 2011 giving an estimated incidence figure of 2.2 million cases of TB for India out of a global incidence of 9.6 million cases.
Lung cancer is a deadly type of cancer seen worldwide and in India. There were 1.8 million new lung cancer cases estimated to occur in 2012. In India, lung cancer constitutes 6.9% of all new cancer cases and 9.3% of all cancer-related deaths in both sex; it is the most common cancer and cause of cancer-related mortality in men. Risk of developing lung cancer increases in the presence of a chronic inflammation, pulmonary fibrosis due to TB, and TB scar tissue., Lung cancer and its treatments result in immunosuppression which attracts the bacillus to infect the victim.
Simultaneous or sequential occurrence of TB in lung cancer patients affects the prognosis.,, In addition, one study demonstrated that the association between TB and lung cancer varies in different ethnic groups and in different regions; it is important to know the characteristics of these cases in India. Therefore, the objective of this study was to describe the clinical characteristics of patients with pulmonary TB and lung cancer.
Aims and objective
The study was performed to reveal epidemiology and treatment outcome in pulmonary TB with lung cancer and how are these two mutually affected. The study period was from November 2014 to October 2017. The study was conducted at the Department of Radiotherapy, R.G. Kar Medical College, Kolkata.
| Materials and Methods|| |
This was a longitudinal study, involving prospective data collection, conducted to determine the characteristics of patients with TB and lung cancer who were treated in R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India. The study involved patients diagnosed with TB and lung cancer, either simultaneously or sequentially.
For each and every patient, a standardized protocol was followed:
- We searched for the demographic data of the patients, and all relevant data for pulmonary TB and lung carcinoma were collected, e.g., occupation, residence, and history of prolonged exposure to polluted air or not
- We took a detailed history of each and every patient, including family history and smoking history
- Thorough examination was done for assessing performing status of the patients, and any other significant findings were noted
- We also reviewed the reports, and what was the treatment done for diagnosed pulmonary tuberculosis (PTB) cases, i.e., according to Directly Observed Treatment Short Course (DOTS).
- The diagnosis of pulmonary TB was based on consensus criteria:
- Positive Ziehl–Neelsen staining for acid fast baccilus (AFB) (two positive smears)
- A positive smear and a positive culture for Mycobacterium tuberculosis
- Positive Ziehl–Neelsen staining for AFB and radiological findings consistent with pulmonary TB
- A single positive culture for M. tuberculosis
- Epidemiological, clinical, and radiological findings consistent with pulmonary TB, associated with a favorable response to treatment with antitubercular drugs.
The diagnosis of lung cancer was based on the histopathological findings.
The data were entered into Microsoft Excel spreadsheets, after which they were processed and analyzed with the Statistical Package for the Social Sciences, version 18.0 (SPSS Inc., Chicago, IL, USA). We carried out a descriptive analysis of the study variables. Quantitative data are presented as mean ± standard deviation and qualitative data are expressed as n.
| Results|| |
The diagnosis of lung cancer and TB was classified by timing as follows:
- Group 1: Pulmonary TB occurred before 2 months of diagnosis of lung carcinoma, and during our study, the TB was in active phase, possibility of scar cancer,
- Group 2: Pulmonary TB and lung cancer occurred simultaneously within 2 months of diagnosis of any of the disease
- Group 3: Pulmonary TB occurred after 2 months of diagnosis of lung cancer.
We took two groups, i.e., Group 1 and Group 3 both in one arm as sequential.
Group 2 was considered as simultaneous occurring of both diseases in concern.
The study involved 42 patients diagnosed with TB and lung cancer and registered in our outpatient department between November 2015 and October 2017. The epidemiological characteristics of the patients are shown in [Table 1]. In 19 of the 42 patients, the diagnosis of TB and lung cancer occurred simultaneously, whereas, in 23 patients, the occurrence was sequential as stated in our criteria. Fifteen (35.7%) patients reported having had TB twice. The diagnosis of TB was established by the following methods: smear microscopy of spontaneous sputum, in 10 patients; culture of spontaneous sputum, in 6; smear microscopy of induced sputum, in 7; bronchoalveolar lavage (BAL) culture, in 5; PCR positivity for M. tuberculosis in BAL samples, in 9; and clinical and radiological findings consistent with TB, in 5. TB treatment was as follows: Category 1 of DOTS in 21 patients (50%) and Category 2 of DOTS in 15 (35.7%). In 6 (14.3%) patients, the data on treatment regimen were either not provided or unavailable.
Only 2 (4.7%) patients reported noncompliance with TB treatment, 5 (11.9%) patients died, and 24 (57.1%) patients were discharged as cured. No treatment outcome data were available for 11 (26.2%) patients. The mean age of lung cancer diagnosis was 65 ± 10 years. Of the 42 patients, 35 (83.33%) patients presented with distant metastases at diagnosis; of them, 71% were diagnosed with LC and TB simultaneously.
The following LC treatments were performed:
- Twenty-one patients, i.e., 50% of patients, were purely treated as palliative intent. Of them, 20% received palliative RT (30 Gy in 10#). The rest 30% of patients received palliative chemotherapy containing 4–6 cycles of platinum doublet combination with injection cisplatin 100 mg/m2, intravenous (IV) D1, and injection etoposide 100 mg/m2 IV D1–D3
- Twenty percent of patients received chemotherapy with platinum doublet combination with injection cisplatin 100 mg/m2, IV D1, and injection etoposide 100 mg/m2 IV D1–D3, followed by concomitant chemoradiation with a radiation dose 50 Gy in 25# over 5 weeks along with weekly cisplatin injection 40 mg/m2.
- Thirty percent of patients were kept in best supportive care, considering the performance status, tolerance, age, etc.
The epidemiological characteristics of our study population is shown in [Table 1] (n = 42).
| Discussion|| |
In this study, we described the characteristics of 42 patients developing TB and lung cancer, either simultaneously or sequentially. TB was diagnosed before lung cancer in most of the patients (23), and in none of the cases, lung cancer was diagnosed before TB. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type. The relation of pulmonary TB and LC was first described in 1810, and it was demonstrated histologically a few years later. Several studies on this association have been published, most of which are case series and case–control studies.,,,,,,, However, the cause of development of lung cancer in TB patients is still not clear, whether it can be explained with some biologically plausible theory. One hypothesis would be that inflammation associated with infections can contribute to carcinogenesis. Reactive oxygen or nitrogen species produced by activated neutrophils can bind to the DNA, inducing genetic damage and neoplastic transformation., Alterations of the fragile histidine triad gene in patients with chronic pulmonary TB may result in lung carcinogenesis., During the development of bacillary nidus, carcinogens tend to act more on the hyperactive area. Even metaplastic changes occur in the epithelium of the hyperactive area. The cases described here are similar to those reported in previous studies.,,,,,,, Adenocarcinoma was the most common histological type followed by squamous cell carcinoma in our study.
TB may present before lung cancer in most of the cases due to reversible causality bias, i.e., due to the development of cancer immunity decreases, so the latent TB infection perhaps which was present before may get activated., Around 81% of the cases in our study were smokers, so it may look like a confounding factor. Although, after cessation of smoking, TB itself stands as a risk factor for lung carcinoma, it increases the risk around 2.5 times. A meta-analysis supported this evidence, showing that the association between TB and lung cancer was not due to the effects of smoking, because, when considering only nonsmoking patients, there was a 1.78-fold increase in lung cancer risk among patients with TB. That same meta-analysis demonstrated that the association between TB and lung cancer was not due to the time since the diagnosis of TB. Because the initial symptoms of these two diseases are similar, it should be considered that there can be a delay in the diagnosis of either condition, and consequently, patients can present with either LC or TB at a more advanced stage., In a recent, retrospective case–control study involving 36 patients with lung cancer, 10 (27.8%) were diagnosed with TB and cancer concomitantly, whereas 26 (72.2%) were diagnosed with TB after being diagnosed with cancer. In a case series conducted in Japan, the diagnoses were concomitant in six patients, TB was diagnosed before lung cancer in five cases, and lung cancer was diagnosed before TB in the remaining five. It is also possible that TB was diagnosed before lung cancer more frequently because of a reverse causality bias, i.e., an occult cancer can reduce immunity and lead to reactivation of latent TB. Therefore, TB can present clinically before lung cancer.,
- In Berksonian bias for hospital based studies, patients with an index diagnosis are more likely to be diagnosed with another disease than those who are without an index diagnosis. For instance in our study, patients with TB, at follow-up chest X-ray, are more prone to be diagnosed with cancer than those who are not diagnosed with TB.
- Some cases were lost to follow-up.
| Conclusion|| |
We should advise the TB-diagnosed patients to avoid lung carcinogens, such as tobacco smoking, as much as possible, because these agents contribute to a substantial increase in lung cancer risk. In conclusion, the present study demonstrated that most of the patients with TB and lung cancer were smokers, and that TB was diagnosed either before or simultaneously with lung cancer. Family history of TB is also an important epidemiological factor. Association of lung cancer, especially adenocarcinoma, is increasing in female gender. The presence of indoor air pollution or residence (urban area) also affects the development of lung cancer. Hence, we can warn those patients or their relatives beforehand. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type we got in our study.
Hence, if we get any patient with lung cancer not much improving after anticancer treatment, diagnosis of TB should be kept in mind. Similarly, in any diagnosed case of pulmonary TB, development of lung cancer should be considered if not improved with antitubercular treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al
. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. [Last accessed on 2018 Jan 21].
Indian Council of Medical Research. National Cancer Registry Programme. Three Year Report of Population Based Cancer Registries: 2009-2011; 2013. Available from: http://www.ncrpindia.org
. [Last accessed on 2018 Jan 21].
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.
Engels EA. Inflammation in the development of lung cancer: Epidemiological evidence. Expert Rev Anticancer Ther 2008;8:605-15.
Kim HR, Hwang SS, Ro YK, Jeon CH, Ha DY, Park SJ, et al.
Solid-organ malignancy as a risk factor for tuberculosis. Respirology 2008;13:413-9.
Brenner AV, Wang Z, Kleinerman RA, Wang L, Zhang S, Metayer C, et al.
Previous pulmonary diseases and risk of lung cancer in Gansu province, China. Int J Epidemiol 2001;30:118-24.
Liang HY, Li XL, Yu XS, Guan P, Yin ZH, He QC, et al.
Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: A systematic review. Int J Cancer 2009;125:2936-44.
Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, Muo CH, et al.
Increased lung cancer risk among patients with pulmonary tuberculosis: A population cohort study. J Thorac Oncol 2011;6:32-7.
Conde MB, Melo FA, Marques AM, Cardoso NC, Pinheiro VG, Dalcin Pde T, et al.
III Brazilian thoracic association guidelines on tuberculosis. J Bras Pneumol 2009;35:1018-48.
Cha SI, Shin KM, Lee JW, Lee SY, Kim CH, Park JY, et al.
The clinical course of respiratory tuberculosis in lung cancer patients. Int J Tuberc Lung Dis 2009;13:1002-7.
Libshitz HI, Pannu HK, Elting LS, Cooksley CD. Tuberculosis in cancer patients: An update. J Thorac Imaging 1997;12:41-6.
Dacosta NA, Kinare SG. Association of lung carcinoma and tuberculosis. J Postgrad Med 1991;37:185-9.
] [Full text]
Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007;117:1175-83.
Rosin MP, Anwar WA, Ward AJ. Inflammation, chromosomal instability, and cancer: The schistosomiasis model. Cancer Res 1994;54:1929s-33s.
Song L, Yan W, Deng M, Song S, Zhang J, Zhao T, et al.
Aberrations in the fragile histidine triad(FHIT) gene may be involved in lung carcinogenesis in patients with chronic pulmonary tuberculosis. Tumour Biol 2004;25:270-5.
Song L, Yan W, Zhao T, Deng M, Song S, Zhang J, et al. Mycobacterium tuberculosis
infection and FHIT gene alterations in lung cancer. Cancer Lett 2005;219:155-62.
Dheda K, Booth H, Huggett JF, Johnson MA, Zumla A, Rook GA, et al.
Lung remodeling in pulmonary tuberculosis. J Infect Dis 2005;192:1201-9.
Nalbandian A, Yan BS, Pichugin A, Bronson RT, Kramnik I. Lung carcinogenesis induced by chronic tuberculosis infection: The experimental model and genetic control. Oncogene 2009;28:1928-38.
Le CH, Ko YC, Cheng LS, Lin YC, Lin HJ, Huang MS, et al.
The heterogeneity in risk factors of lung cancer and the difference of histologic distribution between genders in Taiwan. Cancer Causes Control 2001;12:289-300.
Singh VK, Chandra S, Kumar S, Pangtey G, Mohan A, Guleria R, et al.
A common medical error: Lung cancer misdiagnosed as sputum negative tuberculosis. Asian Pac J Cancer Prev 2009;10:335-8.
Dasgupta P, Chakrabarti A, Halder D, Acharyya S, Gangopadhyay S. Results of diagnostic dilemma between lung cancer and sputum negative pulmonary tuberculosis: A retrospective study. J Indian Med Assoc 2012;110:898-900.
Watanabe A, Tokue Y, Takahashi H, Sato K, Nukiwa T, Honda Y, et al.
Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. Clinical study on pulmonary tuberculosis associated with lung cancer patients. Kekkaku 1999;74:157-62.
Fontham ET, Correa P, Reynolds P, Wu-Williams A, Buffler PA, Greenberg RS, et al.
Environmental tobacco smoke and lung cancer in nonsmoking women. A multicenter study. JAMA 1994;271:1752-9.