European Journal of Cardiovascular Medicine

Lung cancer accounts for 11.6% of all new cancer cases identified each year and is quickly becoming Lung cancer is one of the most frequent cancers and a major cause of cancer death worldwide. the most prevalent fatal neoplastic disorder in the world, accounting for 18.4% of all cancer-related fatalities worldwide¹. Every year, lung cancer kills about 1.6 million people, more than breast, colon, and prostate cancers combined. Tobacco smoking remains the leading cause of lung cancer².

However, roughly 25% of all lung malignancies diagnosed worldwide are in people who have never smoked³.Approximately 10% of lung cancer patients are asymptomatic upon diagnosis. However, the majority are symptomatic and may appear with non-specific symptoms such as weight loss or exhaustion, as well as direct signs and symptoms produced by the initial tumor or its intrathoracic or extrathoracic dissemination. However, in India, lung cancer is frequently misdiagnosed or delayed due to the non-specific character of symptoms and the high prevalence of tuberculosis. Many patients appear with a variety of co-morbidities, which can have a negative impact on diagnosis and outcome. The majority of patients are detected at an advanced stage of the disease, making curative treatment impractical⁴.

The most prevalent histological forms are adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell undifferentiated carcinoma, which account for more than 90% of all lung cancers⁵. This study aimed to investigate the clinical profile of lung cancer cases reported to our tertiary care hospital.

1. To study the clinical profile of newly diagnosed bronchogenic carcinoma patients.
2. To study the clinicopathological correlation among various histological types of bronchogenic carcinoma in the above patients.
3. To study the extrapulmonary manifestations and the prevalence of identifiable paraneoplastic syndromes (if present) in patients with bronchogenic carcinoma.

Study Design: Prospective hospital-based observational study.

Study area:  The study was conducted in the Department of Pulmonary Medicine, Government Medical College, Kadapa. 

Study Period:  June 2023 – December 2023.

Sample size: The study consisted of 52 subjects.

Minimum Sample Size = 4pq/d2 = (4*88.4*11.6/8.8*8.8) = 52 4= square of [Z value of alpha error at 5% = 1.96 approx.2]

p = Prevalence of bronchogenic carcinoma from previous study q = 100-p

d = Absolute Precision (here 10 % of p = 8.4)

(Since the incidence of bronchogenic carcinoma in India was found to be 0.01% in males and 0.0025% among females with which it is difficult to obtain an adequate sample size, p was taken as 50 so that the maximum sample size could be obtained.)

Sampling method: Simple random Sampling Technique.

Inclusion criteria: Patients attending hospital, diagnosed with bronchogenic carcinoma in the specified period.

Exclusion criteria:

• Patients with primary malignancy elsewhere and presenting with secondary lung malignancy.
• Patients were not willing to participate in the study.

Ethical consideration: Institutional Ethical committee permission was taken prior to the commencement of the study.

Study tools and Data collection procedure:

Patients included in the study were selected according to the inclusion and exclusion criteria. After obtaining informed consent, data was gathered from history, objective examination of the patients and lab investigations using a semi-structured questionnaire. The localisation of the tumors was done by chest x-ray, fibre optic bronchoscopy and/or CT scan as required. Tissue diagnosis was obtained by FNAC/ biopsy or other cytology and histopathological examination of the specimen was carried out. The type pattern of paraneoplastic syndromes was noted.

Statistical analysis:

For statistical calculations, data is spread in an Excel sheet descriptive and inferential statistical analysis has been carried out in the present study. Results on continuous measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in   Number (%).  Significance is assessed at a 5% level of significance. The Chi-square/Fisher Exact test has been used to find the significance of study parameters on a categorical scale between two or more groups. A p-value < 0.05 was considered statistically significant. The Statistical software namely SPSS 21.0 was used for the analysis of the data.

Table no.1: DISTRIBUTION OF AGE

38.46% of the study population was between 60 and 75 years and 34.62% were between 45-60 years of age. 96.16% of the study population was above 45 years of age.

63.5% of the study population was males while 36.5% were females. 77% of the study population was from rural areas and 23% were from urban areas. Male urban to rural ratio is 1:3.125 while the female urban-to-rural ratio is 1:3.75.

Most of the study population was manual laborers followed by others, farmers, office workers and housewives.

Table no.2: CLINICAL PRESENTATION

Cough (78.8%) was the most predominant symptom followed by constitutional symptoms (59.6%) and dyspnea (57.6%), chest pain (44.2%), hemoptysis (23%) and fever (15.3%). 55.7% of patients had symptoms due to local spread and 11.5% of patients presented with metastatic symptoms.

COPD (65.38%) and Diabetes (23%) were the common co-morbidities affecting the study population followed by HTN (19.2%). H/O old PTB was noted in 11.5% of the patients and 1 patient (1.9%) had h/o ILD. 2(3.8%) patients had past h/o malignancy. One patient had h/o squamous cell carcinoma of the right ear another patient had cervical cancer and 1 (3.8%) patient had a family history of malignancy (first-degree relative).

Out of 52 patients,46 patients (88.4%) were smokers while 6(11.5%) were non-smokers. 71.1% of the study population were heavy smokers, 13.4% were moderate smokers and 3.8% were light smokers. 11.5% of the population was non-smokers. 65.3% of the study population was underweight while 32.7% had normal BMI. We noticed pallor among 34.6%, clubbing in 38.4%, supraclavicular lymphadenopathy in 25%, axillary lymphadenopathy in 9.6% and both supraclavicular and axillary lymphadenopathy in 5.7% of the study population. 13.4%             of the study population had thrombocytosis, followed by peripheral neuropathy (3.8%), gynaecomastia, hypercalcemia and hyponatremia 1.9% each.

Table no.3: CHEST X RAY FINDINGS

Table no.4: CT FINDINGS

Peripherally located malignancies (53.8%) were more common than centrally located malignancies (44.2%). In total, the upper lobe was the most common lobe affected (51.8%) under which the right (49.9%) was more affected than the left (28.8%) while the lower lobe contributed only (19.2%). Pleura was the most common site for local metastasis In patients with distant metastasis, the liver was the most common site of distant metastasis followed by bone (5.76%), adrenal (3.8%), brain (1.9%) and contralateral lung (1.9%).

Table no.5: FIBREOPTIC BRONCHOSCOPY FINDINGS

Lung FNAC was the most common method used for histological diagnosis (44.2%) followed by lymph node FNAC (34.6%) followed by FOB brush cytology (32.6%) and FOB wash (23%). FOB biopsy helped in diagnosis in 15.4%.

Table no.6: HISTOLOGICAL TYPE

adenocarcinoma (51.9%) is the most common histological type of malignancy observed in this study followed by squamous cell carcinoma (40.3%). small cell carcinoma (3.8%) and undifferentiated Carcinoma 3.8% were other histological diagnoses.

In males, squamous cell carcinoma predominated in 48.5% and adenocarcinoma predominated in 39.4%. Small cell carcinoma and undifferentiated carcinoma predominated in 6% each. In females, adenocarcinoma predominated in 73.6 % followed by squamous in 26.3 %.

Table no. 7: ASSOCIATION OF HEMOPTYSIS AND HISTOLOGICAL TYPE

Chi-Square = 8.40            p Value = 0.003

In patients presenting with hemoptysis, squamous cell carcinoma was more predominant (75%) while adenocarcinoma comprised (16.7%). In patients with no hemoptysis as their presenting symptom, adenocarcinoma was the predominant histological type (62.5%) but squamous cell carcinoma comprised only 30%. Here we note that the proportion of squamous cell carcinoma is higher in patients presenting with hemoptysis which may be due to the more common central location of the tumor.

On the whole, COPD was present in 65.3% of the study population. This may be due to the predominantly old-age population and the presence of common risk factors. 55.8% of the patients with squamous cell carcinoma had COPD while 44% of adenocarcinoma had COPD. The more common association of squamous cell carcinoma with smoking may be a reason for this.

Table no.8: Association of Clubbing and Histological Type

Chi-Square value = 10.942            p value = 0.0009

In patients presenting with clubbing, 75% were adenocarcinoma while 10% were squamous. In 5% the histology was undifferentiated and small cells in 10%. Most of the paraneoplastic syndromes were noted in adenocarcinoma followed by small-cell lung carcinoma.

Table no. 9: Association of location of malignancy and histological type

Chi-Square value = 15.404            p-value = 0.00008

Peripherally located malignancies (53.8%) were more common than centrally located malignancies (44.2%). 75% of adenocarcinomas were peripheral in location while 14.2% of squamous cell carcinoma were peripheral. 69.5% of squamous cell carcinomas were central in location while 26.08% of adenocarcinoma were central in location. Among small cell carcinomas, 4.35% were central and 3.5% peripheral. All undifferentiated carcinomas in this study were peripheral. (71.4%).

3.84% of small cell carcinoma, 63.4% of adenocarcinomas, 44.2% of patients with squamous cell carcinoma and 3.84% of undifferentiated carcinoma had distant metastasis at the time of presentation. At the time of the initial clinicopathological evaluation, 11 out of 52 patients presented with metastasis. The liver was the most common site of distant metastasis observed followed by bone (5.76%), adrenal (3.8%), brain (1.9%) and contralateral lung (1.9%). In the study conducted, liver metastasis was the most common in adenocarcinoma (3.8%).

The most frequent type of carcinoma is lung carcinoma, which causes a variety of clinical signs. The symptoms of lung cancer might be nonspecific, which delays diagnosis for people who present with this disease.⁶ Although the majority are generic, certain signals can be acquired from history, enhancing the clinician's suspicion of the presence of lung cancer.⁷

The majority of cases (38.46%) were in the age group of 60-74 years in our study. The mean age of patients with lung carcinoma has remained relatively constant over the years. The mean age in this study was 67 years which is similar to that reported by Sundaram V et al.⁷ 63.5% of the study population were males whereas 36.5% were females. The male-to-female ratio of patients with lung carcinoma has varied in different studies. The present study observed a male-to-female ratio of 1.73:1. A study by Pandhi N et al.⁹ showed a male-to-female ratio of 2.7:1.

Cough was the commonest presenting symptom in the present study, being present in 78.8% of cases in our study. It was not related to any particular time or posture. The result was similar to that reported by Jindal et al.¹⁰ Arora et al.¹¹ This may be because even early mucosal changes induced by the tumor can result in a cough. Another explanation is that most patients are smokers and have associated chronic bronchitis. The second most common presentation was constitutional symptoms (59.6%) followed by dyspnea (57.6%). Haemoptysis in this series was seen in 12 (23%) patients. The presentation was with blood-streaked sputum, but massive haemoptysis was not encountered. Haemoptysis was found in patients with squamous cell carcinoma. This could be explained by the frequent occurrence of squamous cell carcinoma in central locations, and its tendency to cavitate or form lung abscesses. The frequency of haemoptysis found in other studies was 61% in Le Roux et al (1968)68 24 % in P.N. Chhajed et al.¹² 57.6% of patients had symptoms due to local spread and 11.5% of patients presented with metastatic symptoms.

Smoking was the most common predisposing factor seen in our study. Out of the 52 patients included in the study, 46 (88.4%) subjects were smokers and only 6 (11.5%) were non-smokers. Similar results were seen in a study by Notani P et al.13 and Jindal SK et al.10 on lung carcinoma patients. In the study by Jagdish Rawat et al.¹⁴, smoking was found to be a risk factor in 81.77%. In this study population, patients had the following paraneoplastic syndromes – 13.4% of the study population had thrombocytosis, followed by peripheral neuropathy (3.8%), gynaecomastia, hypercalcemia and hyponatremia 1.9% each. In a study by Vurgese et al.¹⁵, the following was noted - hyponatremia (1.3%), hypercalcemia (0.6%), gynecomastia (1.9%), HPOA (0.6%), acanthosis (0.6%), peripheral neuropathy (1.9%), ichthyosis (0.6%), fever (16%), anaemia (35.9%), leucocytosis (27.6%) and thrombocytosis -5 (9.6%), limbic encephalitis -3, (5.8%), SIADH-3 (5.8%), peripheral neuropathy- 2 (3.8%), GBS-1(1.9%), pancytopenia-3 (5.8%).¹⁵

The most common chest X-ray finding was mass lesion (73%) followed by pleural effusion (44.2%) and hilar prominence (11.5%). The most common finding in CT was mass lesion which was present in 100% of the study population. Pleural effusion was seen in 51.9%. 17.3% were found to have cavities while 23% had consolidation. 11.5% of the study population had fibrosis and calcification was noted in 3.8%. 32.6% had mediastinal lymphadenopathy and 1.9% had invasion to heart/pericardium. 1.9% of the study population had an invasion into the oesophagus. 75% of adenocarcinomas were peripheral in location while 14.2% of squamous cell carcinoma was peripheral. 69.5% of squamous cell carcinomas were central in location while 26.08% of adenocarcinoma were central in location. Among small cell carcinomas, 4.35% were central and 3.5% peripheral. All undifferentiated carcinomas in this study were peripheral. (71.4%) The study by Bhadke B¹⁶. on patients with lung carcinoma also denoted that squamous cell carcinoma commonly presents as central tumours, whereas adenocarcinoma is a peripheral tumour.

In the total study population, fibre optic bronchoscopy was done in 46 patients (88.4%). Narrowing of bronchus was noted in 45.6% followed by intra-bronchial mass in 19.5%. Vocal cord palsy and external compression were noted in 10.8% each. 6.5% had mucosal irregularity and 6.5% had normal findings. Fibre-optic bronchoscopy was done in 46 (88.4%). 45.6% of those had intraluminal Lesions with narrowing of the bronchus, 19.5% had mucosal irregularity, another 10.8% had external compression, and 6.5% had vocal Cord palsy. In a study by Navin Pandhi et al.⁹, fibreoptic bronchoscopy with endobronchial biopsy or brushing was the most useful investigation which yielded results in 64 out of 150 cases (42%). Adenocarcinoma was the most common histological type (51.9%) followed by squamous cell (40.3%). small cell carcinoma (3.8%) and undifferentiated carcinoma 3.8% were other histological diagnoses. The shift in the incidence of squamous cell carcinoma to adenocarcinoma may be associated with the switch from non-filtered to filtered cigarettes and the depth of inhalation had been altered.^10,17 Another reason can be due to increasing urbanisation, which exposes individuals to different carcinogens other than cigarette/beedi smoke.¹⁸ Historical trends indicate that cigarette smoking prevalence peaked about two decades earlier in men than in women; thus, the epidemic of lung cancer started later in women.¹⁹

In the young (<45) 50% were diagnosed as adenocarcinoma and another 50% as undifferentiated carcinoma.

In patients between 45-59 years, adenocarcinoma was predominant involving 55.5% followed by squamous cell carcinoma in 44.4 %. Of patients in the age group of 60-74 years, 55% were diagnosed with adenocarcinoma, 44% with squamous cell carcinoma and 5% were observed with small cell carcinoma. In the age bracket of >75 years, adenocarcinoma and squamous cell carcinoma showed the same result - 47.6% each whereas squamous cell carcinoma and undifferentiated carcinoma. In males, squamous cell carcinoma predominated in 48.5% and adenocarcinoma predominated in 39.4%, small cell carcinoma and undifferentiated carcinoma predominated in 6% each. In females, adenocarcinoma predominated in 73.6 % followed by squamous in 26.3%. In a study by Jinyu Kong, FangxiuXu²⁰, the most common histological types of lung cancer were squamous cell carcinoma (SQCC) in men and adenocarcinoma (ADC) in women.

On the whole, COPD was present in 65.3% of the study population. This may be due to the predominantly old-age population and the presence of common risk factors. 55.8% of the patients with squamous cell carcinoma had COPD while 44% of adenocarcinoma had COPD as seen in table no 35 and graph no 28. The more common association of squamous cell carcinoma with smoking may be a reason for this. A study by A Papi, G Casoni, and G Caramori found that the presence of COPD increased the risk for the squamous cell histological subtype by more than four times.²¹ In a study conducted by Wieslaw Jedrychowski, and Heiko Becher it was confirmed that cigarette smoking is associated with all histological types of lung cancer and the overall relative risk for smoking in small-cell and squamous cell carcinoma was 15.4 and 13.5 respectively, whereas that for adenocarcinoma was weaker (relative risk=3.1). The attributable risks for smoking in squamous and small-cell carcinoma were much higher (90% and 88% respectively) than for adenocarcinoma (64%).²² Claire H. Kim et al.²³ noted that the association with secondhand smoke is stronger for small-cell lung cancer than for the other histological types.

In a study conducted by S Taneja, V Talwar. among the SCLC group, 34% metastasis which included bone (14), SCLN (6), liver (14), lung (5), adrenal (20), pancreas (2), pericardium (1), and kidney (1). 12 patients (24%) were detected to have brain metastasis at initial presentation. Among NSCLC large number of patients (n = 103, 63.9%) harboured stage IV disease at presentation with sites of metastasis elsewhere in the body which included bone (58), liver (22), lung (27), adrenal (8), synovium (1), pericardium (1), and kidney (1). Brain was the second most common site of metastasis after bone and was present in 49/161 (30.4%) patients of NSCLC.²⁴

Lung cancer is a rapidly progressive disease with a very high mortality rate but treatment in the early stage may give a good prognosis. High-risk patients with a smoking history should be evaluated clinicoradiologically with high suspicion so that early diagnosis can be made and the quality of life of patients can be improved. Primary lung cancer should always be suspected in a person presenting with unexplained cough for several weeks with other symptoms such as weight loss, and fever with non-resolving collapse-consolidation on chest radiograph.

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