Letters to Editor
Lung cancer epidemiology and clinical profile in North India: Similarities and differences with other geographical regions of India Sir, This is in reference to the mini‑symposium on lung cancer epidemiology that was published in a recent issue of your journal. The three articles published therein provided a contemporary view of lung cancer epidemiology from tertiary care centers in West, South, and East India. [1‑3] In this context, we would like to share our recent assessment of the clinico‑epidemiological profile of lung cancer in North India. One of our most important observations has been the lack of change in the distribution of different histologic types with time. At our center, squamous cell carcinoma continues to remain the most common histologic type overall as well as amongst smokers (approximately 38%).[4] Frequency of other histologic types has also remained similar to what was witnessed at our center three decades ago. [5] In addition to histology, the other clinico‑epidemiological variables namely gender, disease stage, and smoking profile have also not changed substantially with time.[4] The second important observation has been the presence of significant differences in the key clinico‑epidemiological characteristics between current/former smokers and non‑smokers. Current/former smokers had higher mean age, higher percentage of males, higher frequency of squamous and small cell histologies as well as lower percentage of advanced non‑small cell lung cancer (NSCLC). [4] Furthermore, when we assessed for presence of these differences in relation to quantified smoking status (using the smoking index) [6] amongst NSCLC patients, we observed a strong and inverse association between heavy smoking and presence of advanced stage as well as of extra‑thoracic disease (ETD) at diagnosis. [7] On multivariate analysis, heavy smoking had significantly lower odds as compared to never‑smokers for presence of advanced NSCLC (odds ratio [OR] = 0.25; 95% confidence interval [CI] = 0.11‑0.61) and for ETD (OR = 0.29; 95% CI = 0.16‑0.53). Even on subgroup analyses by histology and gender, the Indian Journal of Cancer | October–December 2013 | Volume 50 | Issue 4
inverse and independent association of heavy smoking with advanced disease and ETD was consistently observed amongst NSCLC patients. Interestingly, non‑squamous histology had significantly higher odds as compared to squamous histology for presence of ETD (OR = 2.31; 95% CI = 1.50‑3.57). The third important association that we have noted has been the high incidence (approximately 45%) of low body mass index (BMI) among newly diagnosed lung cancer patients. [8] Here again, heavy smoking was found to have an independent association with presence of low BMI (OR = 3.74; 95% CI = 1.59‑8.80). Bidi smoking is the most common type of smoking product in India overall, and the same has been observed by us amongst lung cancer patients presenting to our center. [7,9] It is possible that some or all of the above mentioned observations are in part linked to the continued predominance of bidi smoking in North India. These data also suggest that India has geographical diversity not just for its population profile, but even for a disease like lung cancer. Longitudinal studies can help to assess whether temporal trends that have been witnessed globally and perhaps in some geographical regions of India are observed in other areas as well. Singh N, Behera D Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India Correspondence to: Dr. Navneet Singh, E‑mail: [email protected]
References 1.
2.
3.
4. 5. 6. 7.
Noronha V, Dikshit R, Raut N, Joshi A, Pramesh CS, George K, et al. Epidemiology of lung cancer in India: Focus on the differences between non‑smokers and smokers: A single‑centre experience. Indian J Cancer 2012;49:74‑81. Krishnamurthy A, Vijayalakshmi R, Gadigi V, Ranganathan R, Sagar TG. The relevance of "Nonsmoking‑associated lung cancer" in India: A single‑centre experience. Indian J Cancer 2012;49:82‑8. Dey A, Biswas D, Saha SK, Kundu S, Kundu S, Sengupta A. Comparison study of clinicoradiological profile of primary lung cancer cases: An Eastern India experience. Indian J Cancer 2012;49:89‑95. Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Unchanging clinico‑epidemiological profile of lung cancer in north India over three decades. Cancer Epidemiol 2010;34:101‑4. Jindal SK, Behera D. Clinical spectrum of primary lung cancer: Review of Chandigarh experience of 10 years. Lung India 1990;8:94‑8. Jindal SK, Malik SK, Dhand R, Gujral JS, Malik AK, Datta BN. Bronchogenic carcinoma in Northern India. Thorax1982;37:343‑7. Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Quantified smoking status and non‑small cell lung cancer stage at presentation: Analysis of a North Indian cohort and a systematic 367
Letters to Editor
8.
9.
review of literature. J Thorac Dis 2012;4:474‑84. Singh N, Aggarwal AN, Gupta D, Behera D. Prevalence of low body mass index among newly diagnosed lung cancer patients in North India and its association with smoking status. Thoracic Cancer 2011;2:27‑31. Jindal SK, Aggarwal AN, Chaudhry K, Chhabra SK, D’Souza GA, Gupta D, et al. Tobacco smoking in India: Prevalence, quit‑rates and respiratory morbidity. Indian J Chest Dis Allied Sci 2006;48:37‑42.
Cryptosporidial diarrhea in a patient of all-transretinoic-acid syndrome treated successfully with azithromycin Sir, All‑trans‑retinoic‑acid (ATRA) syndrome, a recognized serious toxicity of ATRA therapy for acute promyelocytic leukemia, occurs within 2‑20 days of treatment.[1,2] Though, clinical manifestations of ATRA syndrome are multisystemic, diarrhea is not reported along with its course.[1] We are reporting one case of cryptosporidial diarrhea in patient recovering from ATRA syndrome. Possible relation of cryptosporidial diarrhea with the treatment of ATRA syndrome has been explored in this report. A 21‑year‑old female was admitted to our hematology department with bone marrow biopsy finding of promyelocytic leukemia (M3) with Auer rods with normal baseline chest radiograph. ATRA therapy was initiated dose at 40 mg/m 2 /day. Twelve days after beginning of ATRA, she developed fever (38.9°C), skin ecchymosis, hemoptysis, and breathlessness. Bilateral diffuse ronchi, crepitations were heard on chest auscultation. Her chest radiograph showed bilateral alveolar infiltrates [Figure 1] and arterial blood gas showed hypoxia. ATRA syndrome was suspected, and the patient was treated with invasive lung protective mechanical ventilation with closed suction, along with broad spectrum antibiotics, enteral nutrition, and dexamethasone (10 mg twice daily). Her blood, endotracheal, and urine cultures were negative. ATRA therapy was continued because of some clinical and laboratory parameters are suggesting a component of hospital acquired pneumonia component (leukocyte count 24,000/cmm, procalcitonin 7.8 units). 7 days after, though, symptoms of her ATRA syndrome were settling, she developed profuse watery diarrhea (volume loss around 1 l/day). We changed feed formulation but diarrhea persisted. So, we sent for stool microscopy and culture. Microbiologist found oocyst of Cryptosporidium parvum in stool 368
Access this article online Quick Response Code:
Website: www.indianjcancer.com DOI: 10.4103/0019-509X.123581 PMID: *******
samples [Figure 2]. Clostridium dificile antigen test was found negative. However, she was HIV seronegative with normal CD4+ T cell count (608 cells/µl). We started azithromycin as a treatment (500 mg/day for 7 days). Follow‑up stool samples (after 10 days of antibiotics) were negative for the oocyst. Later, she was extubated and discharged from the hospital. The patient completed a full 6 weeks course of ATRA. C. parvum is an opportunistic protozoa that can cause life‑threatening diarrhea in immunosuppressed patients. [3,4] It is indeed, a world‑wide threat due to its poorly understood pathogenesis and unavailability of treatment protocol.[4] Even, host immune responses controlling C. parvum infection are poorly understood, but cellular immunity, i.e., Th‑1 response with the help of interferon (IFN)‑γ and interleukin (IL)‑12 is playing a major role.[5] Thus patient’s CD4+ T cell number and function are important in host response against it.[3,4] For treating intestinal cryptosporidiosis, utmost care to be taken to eradicate oocyst for prevention of subclinical infection and carrier state.[2] Azithromycin, a macrolide, with its dose‑dependent efficacy, prolonged terminal half‑life, excellent intracellular penetration is now more and more used in the treatment of cryptosporidial infection even in immunosuppressed patients.[3] It is thought that after starting ATRA therapy, acute promyelocytic cells release mediators which cause hemostatic abnormalities that lead to ATRA syndrome.[1] ATRA syndrome is managed according to recent recommendations with administration of glucocorticoids (intravenous dexamethasone 10 mg twice daily until symptoms improve) and sometimes interruption of ATRA therapy (in severe cases).[1] When glucocorticoids act on naïve CD4+ T lymphocytes, there is suppression in secretion of Th‑1 type cytokines, such as IFN‑γ and TNF‑α, with an increased secretion of Th‑2 type cytokines.[6] When glucocorticoids act on monocytes they reduce secretion of IL‑12. [6] Glucocorticoids also decrease IL‑12 responsiveness through inhibition of Stat‑4 phosphorylation. [6] These mechanisms contribute to the less formation of Th‑1 cell from naïve CD4+ T cells. Thus, cellular immunity decreased while using glucocorticoids during treatment of ATRA syndrome led to cryptosporidial diarrhea. To our knowledge, it is the first case of cryptosporidial diarrhea with normal CD4+ T cell count, occurred Indian Journal of Cancer | October–December 2013 | Volume 50 | Issue 4
Copyright of Indian Journal of Cancer is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Lung cancer epidemiology and clinical profile in North India: Similarities and differences with other geographical regions of India Sir, This is in reference to the mini‑symposium on lung cancer epidemiology that was published in a recent issue of your journal. The three articles published therein provided a contemporary view of lung cancer epidemiology from tertiary care centers in West, South, and East India. [1‑3] In this context, we would like to share our recent assessment of the clinico‑epidemiological profile of lung cancer in North India. One of our most important observations has been the lack of change in the distribution of different histologic types with time. At our center, squamous cell carcinoma continues to remain the most common histologic type overall as well as amongst smokers (approximately 38%).[4] Frequency of other histologic types has also remained similar to what was witnessed at our center three decades ago. [5] In addition to histology, the other clinico‑epidemiological variables namely gender, disease stage, and smoking profile have also not changed substantially with time.[4] The second important observation has been the presence of significant differences in the key clinico‑epidemiological characteristics between current/former smokers and non‑smokers. Current/former smokers had higher mean age, higher percentage of males, higher frequency of squamous and small cell histologies as well as lower percentage of advanced non‑small cell lung cancer (NSCLC). [4] Furthermore, when we assessed for presence of these differences in relation to quantified smoking status (using the smoking index) [6] amongst NSCLC patients, we observed a strong and inverse association between heavy smoking and presence of advanced stage as well as of extra‑thoracic disease (ETD) at diagnosis. [7] On multivariate analysis, heavy smoking had significantly lower odds as compared to never‑smokers for presence of advanced NSCLC (odds ratio [OR] = 0.25; 95% confidence interval [CI] = 0.11‑0.61) and for ETD (OR = 0.29; 95% CI = 0.16‑0.53). Even on subgroup analyses by histology and gender, the Indian Journal of Cancer | October–December 2013 | Volume 50 | Issue 4
inverse and independent association of heavy smoking with advanced disease and ETD was consistently observed amongst NSCLC patients. Interestingly, non‑squamous histology had significantly higher odds as compared to squamous histology for presence of ETD (OR = 2.31; 95% CI = 1.50‑3.57). The third important association that we have noted has been the high incidence (approximately 45%) of low body mass index (BMI) among newly diagnosed lung cancer patients. [8] Here again, heavy smoking was found to have an independent association with presence of low BMI (OR = 3.74; 95% CI = 1.59‑8.80). Bidi smoking is the most common type of smoking product in India overall, and the same has been observed by us amongst lung cancer patients presenting to our center. [7,9] It is possible that some or all of the above mentioned observations are in part linked to the continued predominance of bidi smoking in North India. These data also suggest that India has geographical diversity not just for its population profile, but even for a disease like lung cancer. Longitudinal studies can help to assess whether temporal trends that have been witnessed globally and perhaps in some geographical regions of India are observed in other areas as well. Singh N, Behera D Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India Correspondence to: Dr. Navneet Singh, E‑mail: [email protected]
References 1.
2.
3.
4. 5. 6. 7.
Noronha V, Dikshit R, Raut N, Joshi A, Pramesh CS, George K, et al. Epidemiology of lung cancer in India: Focus on the differences between non‑smokers and smokers: A single‑centre experience. Indian J Cancer 2012;49:74‑81. Krishnamurthy A, Vijayalakshmi R, Gadigi V, Ranganathan R, Sagar TG. The relevance of "Nonsmoking‑associated lung cancer" in India: A single‑centre experience. Indian J Cancer 2012;49:82‑8. Dey A, Biswas D, Saha SK, Kundu S, Kundu S, Sengupta A. Comparison study of clinicoradiological profile of primary lung cancer cases: An Eastern India experience. Indian J Cancer 2012;49:89‑95. Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Unchanging clinico‑epidemiological profile of lung cancer in north India over three decades. Cancer Epidemiol 2010;34:101‑4. Jindal SK, Behera D. Clinical spectrum of primary lung cancer: Review of Chandigarh experience of 10 years. Lung India 1990;8:94‑8. Jindal SK, Malik SK, Dhand R, Gujral JS, Malik AK, Datta BN. Bronchogenic carcinoma in Northern India. Thorax1982;37:343‑7. Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Quantified smoking status and non‑small cell lung cancer stage at presentation: Analysis of a North Indian cohort and a systematic 367
Letters to Editor
8.
9.
review of literature. J Thorac Dis 2012;4:474‑84. Singh N, Aggarwal AN, Gupta D, Behera D. Prevalence of low body mass index among newly diagnosed lung cancer patients in North India and its association with smoking status. Thoracic Cancer 2011;2:27‑31. Jindal SK, Aggarwal AN, Chaudhry K, Chhabra SK, D’Souza GA, Gupta D, et al. Tobacco smoking in India: Prevalence, quit‑rates and respiratory morbidity. Indian J Chest Dis Allied Sci 2006;48:37‑42.
Cryptosporidial diarrhea in a patient of all-transretinoic-acid syndrome treated successfully with azithromycin Sir, All‑trans‑retinoic‑acid (ATRA) syndrome, a recognized serious toxicity of ATRA therapy for acute promyelocytic leukemia, occurs within 2‑20 days of treatment.[1,2] Though, clinical manifestations of ATRA syndrome are multisystemic, diarrhea is not reported along with its course.[1] We are reporting one case of cryptosporidial diarrhea in patient recovering from ATRA syndrome. Possible relation of cryptosporidial diarrhea with the treatment of ATRA syndrome has been explored in this report. A 21‑year‑old female was admitted to our hematology department with bone marrow biopsy finding of promyelocytic leukemia (M3) with Auer rods with normal baseline chest radiograph. ATRA therapy was initiated dose at 40 mg/m 2 /day. Twelve days after beginning of ATRA, she developed fever (38.9°C), skin ecchymosis, hemoptysis, and breathlessness. Bilateral diffuse ronchi, crepitations were heard on chest auscultation. Her chest radiograph showed bilateral alveolar infiltrates [Figure 1] and arterial blood gas showed hypoxia. ATRA syndrome was suspected, and the patient was treated with invasive lung protective mechanical ventilation with closed suction, along with broad spectrum antibiotics, enteral nutrition, and dexamethasone (10 mg twice daily). Her blood, endotracheal, and urine cultures were negative. ATRA therapy was continued because of some clinical and laboratory parameters are suggesting a component of hospital acquired pneumonia component (leukocyte count 24,000/cmm, procalcitonin 7.8 units). 7 days after, though, symptoms of her ATRA syndrome were settling, she developed profuse watery diarrhea (volume loss around 1 l/day). We changed feed formulation but diarrhea persisted. So, we sent for stool microscopy and culture. Microbiologist found oocyst of Cryptosporidium parvum in stool 368
Access this article online Quick Response Code:
Website: www.indianjcancer.com DOI: 10.4103/0019-509X.123581 PMID: *******
samples [Figure 2]. Clostridium dificile antigen test was found negative. However, she was HIV seronegative with normal CD4+ T cell count (608 cells/µl). We started azithromycin as a treatment (500 mg/day for 7 days). Follow‑up stool samples (after 10 days of antibiotics) were negative for the oocyst. Later, she was extubated and discharged from the hospital. The patient completed a full 6 weeks course of ATRA. C. parvum is an opportunistic protozoa that can cause life‑threatening diarrhea in immunosuppressed patients. [3,4] It is indeed, a world‑wide threat due to its poorly understood pathogenesis and unavailability of treatment protocol.[4] Even, host immune responses controlling C. parvum infection are poorly understood, but cellular immunity, i.e., Th‑1 response with the help of interferon (IFN)‑γ and interleukin (IL)‑12 is playing a major role.[5] Thus patient’s CD4+ T cell number and function are important in host response against it.[3,4] For treating intestinal cryptosporidiosis, utmost care to be taken to eradicate oocyst for prevention of subclinical infection and carrier state.[2] Azithromycin, a macrolide, with its dose‑dependent efficacy, prolonged terminal half‑life, excellent intracellular penetration is now more and more used in the treatment of cryptosporidial infection even in immunosuppressed patients.[3] It is thought that after starting ATRA therapy, acute promyelocytic cells release mediators which cause hemostatic abnormalities that lead to ATRA syndrome.[1] ATRA syndrome is managed according to recent recommendations with administration of glucocorticoids (intravenous dexamethasone 10 mg twice daily until symptoms improve) and sometimes interruption of ATRA therapy (in severe cases).[1] When glucocorticoids act on naïve CD4+ T lymphocytes, there is suppression in secretion of Th‑1 type cytokines, such as IFN‑γ and TNF‑α, with an increased secretion of Th‑2 type cytokines.[6] When glucocorticoids act on monocytes they reduce secretion of IL‑12. [6] Glucocorticoids also decrease IL‑12 responsiveness through inhibition of Stat‑4 phosphorylation. [6] These mechanisms contribute to the less formation of Th‑1 cell from naïve CD4+ T cells. Thus, cellular immunity decreased while using glucocorticoids during treatment of ATRA syndrome led to cryptosporidial diarrhea. To our knowledge, it is the first case of cryptosporidial diarrhea with normal CD4+ T cell count, occurred Indian Journal of Cancer | October–December 2013 | Volume 50 | Issue 4
Copyright of Indian Journal of Cancer is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
