Cholangiocarcinomas (CCAs) are tumours originating from canals of Hering of the main bile duct and comprising approximately 3% of gastrointestinal tumours(1). They are the second most common primary hepatic malignancies accounting for about 20% of the deaths from hepatobiliary cancers and 13% of the total cancer mortality worldwide(2). The overall incidence of CCA has increased progressively worldwide over the past four decades(3). 

 Due to the relatively asymptomatic nature in early stages, CCAs are usually diagnosed when the disease has already metastasized with 5-year overall survival rate as low as 10 %(4). The diagnosis of CCA remains a challenge due to difficult access to its location. Also a highly desmoplastic, paucicellular stroma, limits the sensitivity of cytological and pathological diagnostic approaches(5). Overall the prognosis of CCA is dismal due to the advanced stage of presentation and high chances of recurrence after resection. However, surgical resection still remains the only curative option due to relative chemoresistant nature of this disease(5). This study is done to present the basic demography of patient s of CCA attending a tertiary care cancer hospital of central India.

A retrospective analysis of a database of all the patients with CCAs registered at Chirayu cancer hospital, Bhopal, between January 2018 to December 2023 was performed. All patients diagnosed as CCA on imaging or cytology/biopsy were included. Evaluation included laboratory investigations with liver function tests, blood leucocyte count, coagulation profile, albumin, CA (Carbohydrate antigen) 19–9, CEA and viral markers (Hepatitis B and Hepatitis C). Radiological tests were performed for tumour evaluation including ultrasonography, triphasic contrast enhanced CT scan (CECT) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreaticography (MRCP). PET-CT was done for advanced and metastatic cases for proper disease mapping. Patients were categorized as localized (resectable), locally advanced (unresectable) and metastatic depending upon radiological and cholangiogram findings. All patients underwent evaluation in multidisciplinary tumour (MDT) board consisting of hepatobiliary surgeon, intervention radiologist, medical oncologist and radiation oncologist. The level of obstruction was ascertained using Bismuth-Corlette classification and decision was taken regarding resectability.  Patients who had obvious metastatic disease, Type IV involvement of bile ducts, bilateral or contralateral vascular involvement or multiple level obstructions indicative of underlying primary sclerosing cholangitis were considered unresectable.  Patients with locally advanced disease that were unresectable initially either due to tumour volume or proximity to vessels were given neoadjuvant chemotherapy after discussion in MDT. Patients deemed unfit for any tumour directed therapy were offered best supportive care and referred to palliative care services. Bile for cytology and bile duct brushings were collected for diagnosis of malignancy at the time of PTBD. For patients with mass within liver or hilum, image guided biopsy was performed for histological confirmation. A positive histology was not required for surgical resection if radiological findings were unequivocally suggestive of malignancy. However, attempt was made to obtain a positive cytology/biopsy prior to starting neo adjuvant treatment (NAT).

Out of the total cases, males were 42.26% and females were 57.74% (table1).

Table 1 gender distribution of the CCA patients

The age group most commonly affected was 51–60-year age group which accounted for 29.17% of total cases followed by 41–50-year age group which accounted for 23.8% of total case load (table2).

Table 2 Age group distribution of the CCA patients

Patients with localized, locally advanced and metastatic disease  were 9%, 19%, 72% respectively (table3). 

Table 3 Disease extent of the CCA patients

Bhopal district accounted for 19.34% of all cases while the districts with second highest number of case load were Satna and Sehore districts which accounted for 7.73% of total case load each (table4).

Table 4 Top four districts contributing to the case load of CCA

The mean age of presentation of CCA in India is younger than their counterparts in the USA and western European countries. The average age at diagnosis in India was 51±11 years in contrast to 71.2±12.5 years in the West (6). The mean/median age is usually 50–55 years. The age at presentation of CCA in India is a decade earlier than their western counterparts. Our study shows highest incidence in 51–60-year age group which is in sync with the other studies done on Indian population.

 Women are at 2–6 times higher risk for developing CCA (7). The observed risk is higher among women compared to men (OR 6.04; 95% CI: 4.52–8.07 versus OR 3.17; 95% CI: 2.23–4.50). Our study also has shown a higher incidence among women compared to men. Women are exposed to higher levels of estrogen and progesterone during their lifetime more so during pregnancies. The GB mucosa has been found to have estrogen and progesterone receptors which may promote GB stasis, stone formation, and this in turn increases exposure time of the GB mucosa to bacterial and chemical toxins (8). Women in India, also are less educated, have less access to economic resources, lesser access to nutrition and poorer access to medical care. These factors may further marginalize them in a socio-economically poor strata. Women in India also tend to be undernourished and thus are likely to have suboptimal immune status and micronutrient deficiencies both of which promote carcinogenesis.

In India, the incidence of CCA is 10 times higher in north India compared to the southern Indian states [8.9/100,000 population (Delhi) vs. 0.8/100,000 population (Chennai)] (9). The ICMR population-based registry (2009–2011) clearly divides India into high risk area and low risk area for CCA (10). The regions have been classified as high risk if the AAR is >5/100,000 population. The AAR varies from 0.2 to 17.1 per 100,000 population in different regions of the country. In a study by Tata Memorial Hospital Mumbai, residence in high-risk areas and period of residence in these regions was associated with increased risk for CCA.

The high-risk regions extend from the states of Jammu and Kashmir, Punjab, Haryana, Himachal Pradesh, Uttarakhand, UP, Bihar, Bengal, Assam and Manipur. Madhya Pradesh and Maharashtra are also considered high risk areas. A large part of these states is based along the major rivers of the country namely Sutlej, Ganges, Yamuna and Brahmaputra (Figure 1).

These rivers arise from the glaciers and flow from the northern Himalayas towards west and east and have become polluted due to human waste and industrial pollutants. As the Ganges flows towards east, the pollutants concentration as well as bacterial contamination have been found to steadily rise which may account partially for high incidence in this Gangetic region of the country. It is also an agricultural driven community. Untreated sewage, industrial waste and agricultural effluents unfortunately get added to the water along its course (11). The fecal coliform count steadily rises as the river flows towards the east (12). Salmonella typhi (S. typhi) and Helicobacter pylori (H. pylori) are feco-orally transmitted organisms which have been known to be associated with pathogenesis of CCA and are likely to be increased as the river flows downstream (13). Madhya Pradesh is also a region of multiple rivers and lakes which are also subjected to such industrial and biological pollutants. Most of our patient population consumes borewell water without treatment and thus this could explain the high incidence of this cancer in Madhya Pradesh and Bhopal region just like the Gangetic belt. In North, North east and eastern India, mustard oil is the staple cooking oil in contrast to coconut oil, sesame or groundnut oil in south and west India. Mustard oil has irritant property on the gut and is often adulterated with butter yellow which is known carcinogen (14). Individuals belonging to the poorer socioeconomic strata are unable to afford branded safe oils and thus consume loose mustard oils which may be contaminated/adulterated. Higher levels of sanguinarine and diethyl nitrosamine, carcinogenic adulterants in mustard oil, have been found in blood and tissue of CCA patients as compared to patients with cholelithiasis. Diethyl nitrosamine has been reported to induce hepatic carcinogenesis. Mustard oil has pro-inflammatory properties and induces tumors (15). High level of pesticides, heavy metals and nitrates both of which are carcinogenic have been identified as pollutants in Ganges (16). Also, patients with CCA have higher biliary concentration of these pesticides and nitrates compare to those with gallstones without CCA (17). Our patients too belong to the poor socio-economic strata and thus along with proximity to water bodies and rivers this could explain the higher incidence of this malignancy in madhya Pradesh,

In our study, majority of the patients presented with metastatic disease at the time of presentation. Patients with localized, locally advanced and metastatic disease  were 9%, 19%, 72% respectively. Our results are similar to that

reported in other series on cholangiocarcinoma (18). This finding could be attributed to the initially asymptomatic nature of the disease, poor socioeconomic background of our patients, lack of health awareness, poor health seeking behavior and unavailability of specialized centers within easy reach.

Cholangiocarcinoma is a serious contributor to the morbidity and mortality among cancer patients and is notorious to present in the later advanced stages. This calls for better patient education strategies and awareness among primary health care providers to have lower threshold for suspecting this disease. Females are more commonly affected by this malignancy and therefore special strategies should be devised and implemented across the female audience to create the necessary awareness. This disease is found to strike mostly in the fifth decade of life in india and the patients in this age group, therefore must be more diligently screened for this malignancy during health checkup drives. Madhya Pradesh comes under the high risk areas as per the ICMR data and since Bhopal and adjoining districts are found to be more commonly hit, an underground water analysis must be carried out taking the basis from the fact that this cancer is found to be mor prevalent in gangetic belt and similarly, madhyapradesh also is associated with various rivers and lakes which might be contributing towards the development of this disease owing to the industrial and biological pollutants in them. Importance of safe drinking water must be strongly stressed.

Compliance with ethical standards

The data of the present study were collected in the course of common clinical practice, and accordingly, the signed informed consent was obtained from each patient for any surgical and clinical procedure. The study protocol was in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments. Because this was a retrospective study, formal consent for this study is not required and no approval of the institutional research committee was needed.

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