Trend Analysis of Gallbladder Cancer for Dibrugarh District, Assam, During the Period of 2003–2016

Abstract

The incidence of gallbladder cancer (GBC) is very high in India and it increases day by day due to population aging and changing of life style. The current study scrutinized the trend analysis of gallbladder cancer of Dibrugarh district. The registered gallbladder cancer data for the period of 14 years, i.e., 2003–2016, is collected from Population-Based Cancer Registry (PBCR), Upper Assam. The Mann Kendall and Sen’s Slop test is performed to analyze the gallbladder cancer data. A total of 716 number of patients with gallbladder cancer were included and overall gallbladder cancer was found highest among patients of age 50–70 years, accounting for 56.84% (n = 407). The disease was most common in females (69.13%) in comparison to males (30.87%) and most of the patients were from urban areas (66.89%). Majority (29.19%) of the patients had completed their primary education whereas 22.07% were illiterate. Mean of age at the time of diagnosis was 54.51 ± 12.29 years which was 57.43 ± 12.19 for male and 53.21 ± 12.13 for female. The time trends and patterns of gallbladder cancer have striking differences within the country as well as in the state of Assam. Large, focussed, inclusive studies are required in India to assess early detection and diagnosis of gallbladder cancer in the country.

Introduction

In developing countries like India, the burden of cancer increases day by day due to population aging and changing life styles. Among the different types of cancers, the incidence of gallbladder cancer is quite low [1]; however, it is the most common type of cancer of biliary tract. During 2001, the estimated number of gallbladder cancer is recorded as 14,986 which likely increase to 23,750 by 2016 [2]. The incidence of gallbladder cancer is 2–6 times more common in females as compare to males [3]. The world's highest incidence rates for females have been reported in Delhi, India (21.5/100000) [3–7].

Gallbladder cancer has marked geographical variations all over the world including the Indian subcontinent. The highest risk was observed in the North and North-east region [8]; the state like Assam showed highest incidence rates as compared to the southern part of India [9]. Among the districts of Assam, age-adjusted incidence rates were highest in Kamrup Urban district for both males (4.4%) and females (8.1%), followed by Cachar and Dibrugarh district [10]. Moreover, significant increase in cancer incidence rate was seen for gallbladder among males (10.8%) for Dibrugarh district [10].

Many risk factors may be allied with gallbladder cancer; among them, cholelithiasis in presence of chronic inflammation is the most prevalent [3] where risk increases with the increasing stone size. Besides, gallbladder polyp, porcelain gallbladder, mucocoele, adenomyomatosis of the gallbladder, and the certain dietary and environmental factors are also associated as risk factors for gallbladder cancer [4, 6, 7]. Close association of gallstone and gallbladder cancer has been found, whereas other risk factors for gallbladder cancer described in various studies were old age, female-sex, obesity, dietary pattern, environmental factors, genetic, female reproductive factors, and chronic inflammation [11, 12]. People having family history of gallstone disease (GSD) and gallbladder cancer has been associated with high risk of forming gallbladder cancer (95% CI 1.5–18.9) [13].

However, the lack of literature from this region revealed that Assam has not been exposed to serious scientific and statistical studies on gallbladder cancer till date. Therefore, the present analysis was carried out to scrutinize the trends of gallbladder cancer in the recent years in Dibrugarh district of Assam.

Materials and Methods

Study Area and Data Used

The study area of the current study is Dibrugarh district of Assam, India. It has approximately 1.3 million people residing in an area of 3381km². About 81.62% of the population resides in rural areas, and the remaining 18.38% lives in urban areas along with 51% males and 49% females [14]. The registered gallbladder cancer data of Dibrugarh district for the period of 14 years, i.e., 2003–2016, is collected from Population-Based Cancer Registry (PBCR), Dibrugarh. The registry was established in 2003 at Assam Medical College and Hospital, Dibrugarh, under the supervision of Indian Council of Medical Research (ICMR), Government of India. Data are analyzed for determining if the trend is going upward or downward. During the study period, the survey team actively collected and completed the data from hospitals, pathological clinics, CT scan centers and nursing homes, and outpatient’s private and public clinics. The entire pathological clinics located in Dibrugarh district along with the health care centers of rural and urban area were included and their data are collected by the survey team.

The PBCR collected cancer cases disaggregated by age and sex along with the geographical information of the respective patients. The registry also collected information on educational qualification (no education, primary, middle, secondary, and higher), marital status, mother tongue, religion, and cultural group of the target population.

Methods

We have used descriptive statistics, the Mann Kendall, and Sen’s Slop test in the analysis. A descriptive analysis was done to measure the overall prevalence of gallbladder cancer of Dibrugarh district. The results were presented in terms of percentage. The percentage of gallbladder cancer was defined as the total number of gallbladder cancer divided by the total number of all the cancer cases registered in the registry at a particular factor/reference point. The Mann–Kendall test is perhaps the most widely used nonparametric test to detect a monotonic upward or downward trend. Unlike the parametric regression analysis, the Mann Kendall test does not require the assumption that the data are normally distributed or linear.

Results

A total of 716 number of patients with gallbladder cancer were included in this analysis. The overall gallbladder cancer was highest among patients aged 50–70 years, accounting for 56.84% (n = 407). The disease was more common (69.13%) in females in comparison to males, i.e., 30.87%, and most (66.89%) of the patients were from urban areas. The majority (29.19%) of the patients had completed their primary level of education; 17.74% had completed their higher education; 16.62% had completed their middle level of education; 14.39% had completed their secondary education while 22.07% of the patients did not have any formal education (Table 1).

Table 1.

General characteristics of the study population of gallbladder cancer

Patients characteristics	Percentage	Number of cases
Age
Less than 50	33.80	242
50–70	56.84	407
Above 70	9.36	67
Sex
Male	30.87	221
Female	69.13	495
Education qualification
No education	22.07	158
Primary	29.19	209
Middle	16.62	119
Secondary	14.39	103
Higher	17.74	127
Place of residence
Urban	60.89	436
Rural	39.11	280
Total	100	716

The mean of age at the time of diagnosis was 54.51 ± 12.29 years, and patients’ age ranged between 20 and 90 years which was 57.43 ± 12.19 for males and 53.21 ± 12.13 for females (Fig. 1).

Fig. 1.

Error bar of mean age of diagnosis of gallbladder cancer by sex of the patients

The trend lines indicate the pattern of change in the percentage of registered gallbladder cancer patients of Dibrugarh districts over 14 years. The percentage of gallbladder cancer for males and females show increasingly similar fluctuating pattern (Fig. 2). This figure shows that the percentage of gallbladder cancer was higher for males than the females during the period 2003–2013 and declined slightly from 2013 to 2016 (Fig. 2).

Fig. 2.

The percentage distribution of registered gallbladder cancer cases by sex of the patients during the period of 2003–2016

The finding (Fig. 3) shows the number of registered cancer cases in Dibrugarh district along with the yearly percentage distribution of gallbladder cancer over the period of 14 years. The trend in number of cancer case registration was gradually increased from 557 in 2003 to 866 in 2007 and from 809 in 2010 to 985 in 2016. Additionally, the percentage of gallbladder cancer incidences increased slightly and significantly over the period of study. It went from 5.21% in 2003 to 6.40% in 2008 and from 5.96% in 2011 to 7.81% in 2016.

Fig. 3.

Number of notified gallbladder cancer cases in Dibrugarh district during the period of 2003–2016

The highest percentages of gallbladder cancer cases were observed in the age group of 20–29 years for females and in the age group 70–79 years for male patients. It was noted that the percentage of gallbladder cancer was increasing with the age group of males and decreasing with the age group of the females during this study period. Additionally, for all the age groups, the higher percentage of gallbladder cancer was observed among females as compared to males (Fig. 4).

Fig. 4.

Percentage of registered gallbladder cases for both sexes among different age group

Figure 5 show the percentage of gallbladder cases with their respective diagnostic status of Dibrugarh district. The majority of patients were diagnosed microscopically (56.01%) whereas a small percentage of patients were radiologically suspected (3.77%). Others (26.68%) included those cases which were clinically (surgically) diagnosed.

Fig. 5.

Percentage of registered gallbladder cases by their diagnostic status

Table 2 show the change in gallbladder cancer cases in Dibrugarh district for 2003 to 2016, using Mann Kendall and Sen’s slope. The test examined the statistical significance change (increase/decrease) in gallbladder cancer during the study period. Very similar to the results obtained from the Mann–Kendall test, Sen’s slope estimator test values are also negative for the patients with higher education, thereby representing a statistically significant downward trend throughout 2003 to 2016 at a 5% level of significance. However, there lies no increasing or decreasing trend for rural patients. In contrast, all other remaining categories of gallbladder patients show a remarkable upward trend for the same level of significance. Additionally, total gallbladder cancer cases show a high level of significance in the upward trend. This implies an increase in the total gallbladder cancer cases for the study area. This may lead to an alarming health issue for this area of Assam (Table 2).

Table 2.

Mann Kendall and Sen’s Slop result for gallbladder cancer from 2003 to 2016

Patients characteristics	Mann Kendall Z	Mann Kendall tau	P-value	Sen’s slope
Age
Less than 50	3.129	0.664	0.001	1.4
50–70	3.075	0.663	0.002	2
Above 70	1.931	0.407	0.053	0.455
Sex
Male	3.087	0.641	0.002	1.176
Female	3.016	0.619	0.002	2
Education
No education	2.652	0.557	0.008	1
Primary	2.264	0.475	0.023	1
Middle	3.745	0.775	0	2
Secondary	3.125	0.641	0.002	0.8
Higher	–1.511	–0.328	0.131	–0.3
Place of residence
Rural	–0.055	–0.023	0.955	0
Urban	3.235	0.663	0.001	3.5
Total	3.514	0.722	0.004	3.5

Discussion

The time trend analysis revealed a significant increase in gallbladder cancer over 14 years of time in Dibrugarh district for both the gender. Other population-based cancer registries of India have also shown the similar increasing trends of gallbladder cancer across the different regions of India [1].

Former study by Phadke et al. [9] made known that trend of gallbladder cancer was statistically non-significant among the males in Dibrugarh and Kamrup district of Assam. Whereas in the current study, we observed that it was significantly higher for both the sexes for the period of 2013–2016.

The incidence rate of gallbladder cancer increased in both the genders in Delhi Metropolitan areas [15]. Barbhuiya et al. [16] recorded that in Guwalior, females consisted of 69.5% and males constituted 30.5% of total gallbladder cancer cases which was considerably quite similar with our findings as we found that the disease was common among females (69.13%) in comparison to males (30.87%).

In terms of literacy, Lazcano‐Ponce et al. [17] recorded that the highest incidence of gallbladder cancer (6.8/100,000) was in the midst of illiterates (51% of the total affected) of the study population; however, in the present analysis, it has been observed that the majority of the patients completed their primary level of education (29.19%).

Gallbladder cancer is considered to be a disease of old age; its high incidence was observed in persons above the age of 65 years in the world population [16] while in the present investigation, it was observed that the overall gallbladder cancer was highest among patients aged between 50 and 70 years, accounting for 56.84% (n = 407) of the study population. Specifically in females, we observed a shift in trend towards involvement of younger age groups in the region.

Bhagabaty et al. [18] in their study reported that 81.1% (679/837) patients were from rural areas and 18.8% (158/837) from urban areas which contradicted with this study, where most of the patients were from urban areas (66.89%) compared to rural areas (39.11%). Moreover, the study of Malhotra et al. [15] made known that the gallbladder cancer was higher in the urban areas than other rural areas of North-eastern India, supporting our statistical data.

Furthermore, the diagnostic status of gallbladder cancer for the present study revealed that 56.01% of the cases were diagnosed microscopically either by histology of primary or by FNAC which was somehow comparable with the study of Hamdani et al. [5].

However, several factors such as early diagnosis and peoples’ awareness towards gallbladder cancer may be responsible for the data contradiction of the reported incidence of gallbladder cancer in the current study. Nevertheless, we used the registry data available in the ICMR database. So, there may some limitations in the study; viz., there may be some lack of information of those patients which were treated at the centers outside Dibrugarh district, as several people traveled outside Assam for better treatment of gallbladder cancer. On the other hand, it is often difficult for population-based cancer registries to collect reliable data on clinical extent of disease and treatment for the reason that data are collected from many sources and there are qualitative differences in investigative capabilities and documentation among different sources [19].

Conclusion

The time trends and patterns of gallbladder cancer have striking differences within the country as well as in the state of Assam. Before the problem reaches epidemic proportion, we need to have coordinated and focussed wide-ranging, multicentre studies for early detection and better treatment for the typical presentation of advanced gallbladder cancer in the country.

Author Contribution

ChandopalSaikia: research idea, literature search, data collection, manuscript preparation, correspondence to editor for publication.

DimpalPathak: research idea, statistical analysis, manuscript preparation.

Dr.ProjnanSaikia: research idea, supervision.

Dr.UtpalDutta: research idea, supervision, data analysis.

Funding

Nil. 

Data Transparency

Yes.

Declarations

Ethics Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.

Consent for Publication

Taken from all authors.

Conflict of Interest

The authors declare no competing interest.