Introduction
Cholelithiasis are hardened deposits (stones) of digestive fluid formed in the gallbladder, which are located within it or migrate to the main bile duct (MBD) and intrahepatic bile ducts. They are classified according to their composition and cholesterol stones are the most frequent with a prevalence of 10-15% in adults1,2.
Its prevalence reaches its peak between 60-70 years (30% in women and 20% in men). However, studies indicate that its global prevalence is 64.1% in women and 29.5% in men3. It is a common problem in developed countries, representing a significant health burden, in the United States (EU) between 20 and 25 million adults have it4, consuming up to $6.5 billion5,6. In Latin America, it occurs between 5 and 15%, and in Mexico 14.3% of adults present it (8.5% men and 20.5% women)7.
More than 80% of cases are asymptomatic, only 10-20% will present symptoms within 5-20 years after diagnosis. Biliary colic occurs in 1-2% per year8,9. Its complications (cholecystitis, choledocholithiasis, pancreatitis due to gallstones, and cholangitis) occur with an annual rate of 0.1-0.3%8. Among its main risk factors are obesity, a diet rich in fat and a sedentary lifestyle10,11.
Lipid profile abnormalities in patients with cholelithiasis
Altered serum lipids in cholelithiasis due to cholesterol stones suggest metabolic syndrome. More than half of patients with cholelithiasis could have a lipid disorder. It is accepted that the main event in the pathogenesis of cholesterol stones is altered lipid metabolism due to an increase in cholesterol levels compared to other lipids secreted by the liver into the bile12.
Dyslipidemia is characterized by elevated levels of total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL), and low levels of high-density lipoproteins (HDL). Studies have shown the association between dyslipidemia and stones, especially the increase in TG and LDL13.
Channa et al. analyzed the serum lipid profile in patients with cholelithiasis and patients without cholelithiasis. They showed that elevated levels of TC, free cholesterol, LDL, TG, and reduced levels of HDL played an important role in the pathogenesis of gallstones in 45-year-old women with more than three children14.
Acute/chronic cholecystitis is a chronic relapsing hepatobiliary disease, which can result from impaired metabolism of cholesterol, bilirubin, and bile acid. Many studies have shown an association between gallstones and abnormal lipids15,16. Due to cholelithiasis, various histopathological changes are produced in the mucosa of the gallbladder (acute, chronic and granulomatous inflammation, hyperplasia, cholesterolosis, dysplasia, and carcinoma). Being symptomatic, therapeutic intervention is necessary17.
The objective of this study was to investigate the association between the histopathological finding of gallbladder lithiasis (secondary to an inflammatory process, hyperplasia, metaplasia, or carcinoma) and the lipid profile of patients undergoing laparoscopic cholecystectomy.
Material and methods
An observational, cross-sectional, analytical, and retrospective study was carried out. Records of patients over 18 years of age from the “Eduardo Liceaga” General Hospital of Mexico, who underwent laparoscopic cholecystectomy for cholelithiasis were analyzed in the period of January 2015 to January 2020. The pre-operative lipid profile was considered. Cases of patients older than 18 years of both sexes who underwent laparoscopic cholecystectomy for cholelithiasis were included in the study. Patients with incomplete clinical records were excluded from the study. The study was submitted for review by the Research Bioethics Committee of the General Hospital of Mexico “Eduardo Liceaga”. Obtaining the following variables age, sex, BMI, comorbidities (diabetes, dyslipidemia, hypertension, cirrhosis, and other), LDL-c, HDL-c, TC, TG, cholesterolosis, polyps, xanthogranulomatosis, acute cholecystitis, chronic cholecystitis, and other finding histopathological. For the statistical analysis, the IBM SPSS version 24 software was used.
Results
Three hundred and two files were reviewed, of which 133 met the inclusion criteria. Twenty-five were men and 108 women, with an average age of 42.5 ± 13.86 years. The average weight in men was 77 ± 11.91 kg and 68.43 ± 12.03 kg for women. Height was 1.68 ± 0.08 m in men and 1.56 ± 0.06 m in women. The BMI in male patients was 27.86 ± 4.0 kg/m2 and 27.92 ± 4.34 kg/m2 in female patients.
Serum levels of LDL, HDL, cholesterol, and triglycerides of patients
TC levels were 172.5 ± 41.94 mg/dl, TG 165.1 ± 114.06 mg/dl, LDL-c 110 ± 42.67 mg/dl, and HDL-c 46.8 ± 12.82 mg/dl. In addition, the proportion of patients who presented abnormal values of these lipids was analyzed. It was found that 16.5% of the patients had hypercholesterolemia (values > 200 mg/dl), 39% hypertriglyceridemia (> 150 mg/dl), 16.5% high levels of c-LDL (> 130 mg/dl), and 57.8% low levels of c-HDL (< 50 mg/dl) (Fig. 1).
Frequency of cholesterolosis, polyps, xanthogranulomatosis, acute cholecystitis, chronic cholecystitis, and other histopathological findings
Chronic cholecystitis was found in 94 cases, cholesterolosis in 38, acute and chronic cholecystitis in 10, autolysis in 8, and adenocarcinoma in one case (Fig. 2).
Comparison between dyslipidemias and normal levels with reported pathologies
The Chi-square test was performed (CI 122-197) to evaluate the concordance between dyslipidemia with each reported pathology, without finding an association (Table 1). The four most common pathology reports were compared with dyslipidemia data, without finding an association (Table 2).
Discussion
In the sociodemographic characteristics of our patients, 33% presented obesity and 39% overweight, compared with the national characteristics where 39.1% presented obesity and 36.1% overweight. Regarding dyslipidemia, 17% had hypercholesterolemia, 40% hypertriglyceridemia, 16% high levels of LDL-c, and 61% low levels of HDL-c (hypoalphalipoproteinemia). In Mexico, 31% have hypercholesterolemia, 47% hypertriglyceridemia, and 55.2% hypoalphalipoproteinemia18. Histopathological reports coincide with the three phases of gallbladder inflammation from cystic duct obstruction (edema, hemorrhage, and gallbladder wall necrosis and leukocyte infiltration with subsequent wall necrosis and perforation)5.
Among the international studies with the largest number of patients is the one of Yaylak et al., who reported 429 cases. The most common report was cholesterolosis (18%), followed by acute cholecystitis (10.7%). Battha and Singh reported 287 cases demonstrating chronic cholecystitis in 73.3% of cases. In our study, the most common finding was chronic cholecystitis (70%), cholesterolosis (28%), and acute cholecystitis (7%). No significant correlation between dyslipidemia and histopathological findings was found in comparison with the study by Battha and Singh19,20. However, we highlight the findings of gastric metaplasia and adenomyomatous hyperplasia in patients with altered lipid profile.
Conclusions
Alterations in the lipid profile were not associated with the following histopathological findings: Chronic cholecystitis, cholesterolosis, and xanthogranulomatosis in patients after elective laparoscopic cholecystectomy. However, the association of dyslipidemia with gastric metaplasia and adenomyomatous hyperplasia can be studied in a larger population. It should be noted that there are few reports that list all the histopathological findings of the gallbladder in the Mexican population, despite the fact that it is a very common pathology in our country, as we have already described. This, together with the characteristics of our population (overweight, obesity, and dyslipidemia) represents an area of opportunity in studies with a greater number of cases.