Comparative incidence of incidental gallbladder cancer in emergency cholecystectomies versus in elective cholecystectomies.

analyse the incidence of incidental gallbladder cancer in emergency cholecystectomies versus in elective cholecystectomies performed in public hospitals in Teresina city, Piaui state (PI). Methods: descriptive, quantitative, observational, cross-sectional study, whose scenarios were two public hospitals in Teresina-PI. We analysed 6,329 medical records of patients undergoing cholecystectomy between January 2011 and December 2017. The collected data were divided into two groups and statistically compared using Z-test for difference between proportions. Results: incidental gallbladder cancer was detected in 6.53% of emergency cholecystectomies and in 0.38% of elective ones. Regarding gender, it was observed that in emergency surgeries 69% of patients were women and 31% men, while in elective procedures 78% were women and 22% men. Regarding age, most patients were over 60 years old, and, among these, 69.3% underwent emergency cholecystectomies and 82.6% underwent elective cholecystectomies. The histopathological type “adenocarcinoma” was found in 84.6% of patients who underwent emergency surgeries and in 100% of patients who underwent elective surgeries. Conclusion: incidental gallbladder cancer was more frequent in urgent cholecystectomies compared to elective cholecystectomies. The profile of patients with this malignant disease in both types of procedure was female, older than 60 years, and with histopathological diagnosis of adenocarcinoma.


INTRODUCTION
G allbladder cancer is a rare tumor with high mortality rates. It is the cancer that occurs in the bile ducts with the lowest median survival at the time of diagnosis, the most common bile duct cancer, and the fifth most common among gastrointestinal cancers 1,2 .
In the vast majority, patients are asymptomatic or have nonspecific symptoms, such as nausea, abdominal pain, or weight loss, which are similar signs to those presented by patients with benign gallbladder disease, which makes early diagnosis difficult. Only 30% of gallbladder carcinomas are suspected preoperatively, while the others are discovered incidentally during or after cholecystectomy 3 . The incidence of incidental gallbladder cancer has significantly increased and is currently the most frequent presentation of this entity, with diagnosis established by histopathological examination of the surgical specimen 4 .
Among the factors related to the etiopathogenesis of gallbladder cancer, lithiasis, mainly in coexistence with gallbladder mud, is present in 96% of patients, being the main risk factor 5 . Obesity, chronic inflammation, female gender, age greater than 65 years, Asian or African-American ethnicity, and high preoperative alkaline phosphatase values are also related to a higher incidence of gallbladder cancer 6  were female and five (22%) male (p=0.00013).     although there was a sample difference between moderately differentiated adenocarcinoma and welldifferentiated adenocarcinoma, which were the two most commonly found, both were equally considered the most prevalent (p=0.3595). When comparing these two histopathological types with the others, there was a statistically significant difference (p=0.0012), confirming that they were the most common.
The most common histopathological type, both in cancers diagnosed after emergency cholecystectomies (p<0.05) and in those evidenced after elective surgeries, was adenocarcinoma, and, when comparing the most prevalent data of emergency cholecystectomy versus the ones of elective cholecystectomy, it could be stated that there was a statistically significant difference (p=0.049), so that elective surgery had a higher incidence of adenocarcinoma when compared to emergency surgery (Figure 3).

DISCUSSION
Although rare, gallbladder cancer is responsible for 80% to 95% of cases of malignant diseases involving the biliary tract, being the most common cancer in this region 8 . Nevertheless, few studies have been reported on gallbladder cancerrelated aspects, as it is still relatively rare in western countries 9 . In this context, the histopathological examination of gallbladder specimens is an important step to confirm the diagnosis 1 .  Evidence that this disease is more common after emergency cholecystectomy has also been shown in other studies, such as the one by Torres et al. 12 , which has suggested that prolonged chronic gallbladder stress, which occurs in symptomatic patients who are submitted to emergency surgery, increases the exposure time to oncogenes and the degree of epithelial dysplasia.
Regarding the most affected gender, it is possible to observe in a statistically significant manner that females have higher incidence in both surgical procedures, as shown in the study by Ishak et al. 13 14 has also demonstrated that there is higher incidence and higher mortality coefficient in females.
The increased risk of gallbladder cancer in women is explained by the higher incidence of cholelithiasis in women when compared to men. In addition, longer exposure to female sex hormones may also be a predisposing factor. Therefore, younger menarche age, early first pregnancy, multiple pregnancies, and prolonged reproductive period, as these are situations of prolonged exposure to hormonal agents, may also increase the risk of biliary tract cancer 11 . In addition, women seek care more often than men and this may justify the higher incidence in females.

Regarding age range, most of literature is
in agreement with what is evidenced here, as the study by Tian et al. 15 , which has concluded that the average of incidental gallbladder cancer patients' age has been 61 years, and the research by Pais-Costa et al. 9 , which has evidenced that the average of incidental gallbladder cancer patients' age has been 71 years.
The study by Meirelles-Costa et al. 11 has also demonstrated that the incidence of precancerous lesions, as well as of cancer, should increase with age, due to longer exposure time to mutations and oncogen production, with the highest incidence occurring among patients over 60 years, confirming what is shown in this research.
Aging is also associated with a longer exposure to risk factors, such as infections, adenoma-carcinoma sequence, obesity, and activation of genetic factors, which increase the probability of incidental cancer diagnosis.
Finally, this study shows that the most common histopathological type is the adenocarcinoma, which is in agreement with what is evidenced in most of literature, as in the studies by Kalita et al. 16 , which have shown that, of the 18 incidental gallbladder cancers found, 15 have been adenocarcinomas, and in the study by Apodaca-Rueda et al. 17 , which has revealed adenocarcinoma in 90% of incidental gallbladder cancer cases.
Therefore, we conclude that incidental gallbladder cancer has higher incidence in emergency surgery when compared to elective surgery, and that, in both surgical analysed modalities, cancer is more frequent in females and in patients over 60 years, being the adenocarcinoma the most common histopathological type. Occasional