Cholesterol Stones Research Articles

Percutaneous transhepatic papillary balloon dilation combined with dual-frequency double-pulse laser lithotripsy for large-diameter common bile duct stones

Objective: To evaluate the safety and efficacy of percutaneous transhepatic papillary balloon dilation (PTPBD) combined with flexible ureteroscopy-guided dual-frequency double-pulse ND:YAG (FREDDY) laser lithotripsy (PTPBD-FREDDY) for the treatment of giant (>1.5 cm diameter) common bile duct stones. Methods: A retrospective analysis was conducted on 26 patients with large-diameter difficult choledocholithiasis admitted to two medical centers from December 2017 to October 2021. Among these patients, four could not tolerate surgery or endoscopic treatment, six experienced failure of endoscopic treatment, and 16 refused to undergo endoscopic or surgical treatment. All patients underwent the PTPBD-FREDDY procedure. The FREDDY laser lithotripsy was performed under ureteroscopic guidance, followed by a balloon to push the stones into the duodenum. The primary endpoint was the technical success rate, and the secondary endpoints included the rate of stone recurrence and related complications. Results: All 26 patients successfully completed the operation, achieving a technical success rate of 100%. The average lithotripsy frequency and operation time for bilirubin stones were significantly higher than those of mixed stones and cholesterol stones (P<0.01). The main postoperative complications included mild fever (n=3), abdominal pain (n=3), nausea (n=2) and vomiting (n=1). One patient experienced biliary tract bleeding, which improved after conservative treatment. No serious complications such as pancreatitis, sepsis, or biliary perforation were observed. After 2 years of follow-up, no cases of stone recurrence were observed. Conclusions: PTPBD-FREDDY is a safe and effective treatment for patients with giant common bile duct stones. It provides a new therapeutic option for patients with giant choledocholithiasis who can not tolerate surgery or have failed endoscopic treatment, demonstrating promising prospects.

Follow-up study of gallbladder stones in 44 children.

Cholesterol stones affect a certain subpopulation of children. Concerns have been raised on the impact of gallbladder surgery on the growth of children and adolescents. To study the population characteristics, clinical features, treatment, and prognosis of gallstones in children. The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected, the children were followed up by telephone to monitor their prognoses. The follow-up ended in August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. The population characteristics, general clinical characteristics, and treatments were retrospectively analyzed. The children were divided according to whether they underwent surgical gallbladder removal into an operation group (n = 28) and a non-operation group (n = 16), The effects of surgical gallbladder resection on the growth and development of children were analyzed. The male-female ratio in the population was 6:5 and 84.09% of the children had onset in adolescence. Furthermore, 29.55% of the children were overweight or obese. The study identified 26 cases with metabolic abnormalities, 9 with hemolytic anemia, and 4 with choledochal cyst. Of the population, 68.18% had recurrent symptomatic cholecystolithiasis. Surgical treatment accounted for 63.64%, with laparoscopic cholecystectomy accounting for 71.43% of surgical treatment. No significant differences were observed in symptoms and complications between the surgery and non-surgery groups. Furthermore, no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during follow-up. The sex characteristics of gallstones in children were not observed. Most gallstones occurred in adolescents and rarely in young children. A considerable proportion of children have inborn causes, which are often concurrent with metabolic abnormalities and hemolytic anemia. Most children had recurrent symptomatic gallstones. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. Surgical treatment did not affect the growth and development of children who underwent gallstone removal.

Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis.

Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.

Hif-1α expression targets the TMA/Fmo3/TMAO axis to participate in gallbladder cholesterol stone formation in individuals living in plateau regions

The incidence of gallbladder cholesterol stones (GCS) increases rapidly among people living in high-altitude hypoxic environments compared to those in normoxic areas. Upregulation of hepatic hypoxia inducible factor 1α (Hif-1α) plays a key role in the formation of GCS. High plasma trimethylamine-N-oxide (TMAO) levels are positively correlated with the occurrence of GCS. We hypothesized that HIF-1α may upregulate TMAO levels by promoting the transcription of flavin-containing monooxygenase 3 (Fmo3), which eventually leads to GCS formation. Our study shows that in women, high plasma total cholesterol and apolipoprotein B were positively correlated with cholecystolithiasis and hypoxia. Hif-1α binds to the Fmo3 promoter and promotes Fmo3 expression. Hypoxia and lithogenic diet induce the expression of Hif-1α, Fmo3, TMAO and cholesterol tube transporters in the livers of mice, disturb the proportion of bile and plasma components, and induce the formation of GCS. In cell experiments, silencing Hif-1α downregulates the expression of Fmo3, TMAO and cholesterol tube transporters. In a mouse model of hypoxic cholecystolithiasis, silencing Hif-1α downregulates the expression of related genes, restores the proportion of bile and plasma lipid components, and reduces the formation of GCS. Our study shows that Hif-1α binds to the promoter region of Fmo3 and promotes Fmo3 transcription. Thus, it mediates the transcriptional activation of the TMA/Fmo3/TMAO pathway, upregulates the expression of ATP-binding cassettes (Abc) g5 and g8, and participates in the regulation of the occurrence of GCS in the plateau region.

The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study.

Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls. We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics. Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness. Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.

Gallbladder microbial species and host bile acids biosynthesis linked to cholesterol gallstone comparing to pigment individuals.

Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment, or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate, and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

Periapical Lesions Associated with Demographic Variables, Dental Conditions, Systemic Diseases, and Habits.

The aim of this study was to analyze the prevalence of periapical lesions and possible associations with demographic, dental conditions, systemic diseases, and habit variables in patients from a private Brazilian university. Data from 452 patients of both sexes, aged 18-78 years, from a Brazilian university were evaluated. Panoramic radiographs were analyzed, and the presence of periapical lesions was recorded. In these cases, the dental condition was assessed for the presence or absence of endodontic treatment. Medical records provide information related to general health (diabetes, cardiovascular diseases, altered cholesterol, autoimmune diseases, gallstones, or kidney stones) and habits (smoking or alcoholism). The data were descriptively analyzed, and then logistic regression and the Wald test were performed in Stata/SE v.14.1. A rate of 58.4% of participants were women, and the mean age was 36.4 (±14.6) years. Periapical lesions prevailed in 193 (42.7%) patients, and 281 (72.4%) teeth were not previously endodontically treated. Mandibular first molars (19%) and men (48.9%) were the most affected. The adjusted model showed that the age group of 26-45 years was 5 times more likely [odds ratio (OR) = 5.01; 95% confidence interval (CI): 2.85-8.82] to have lesions than those aged ≤25 years. Participants aged above 46 years were 19.1 times more prone (OR = 19.1; 95% CI: 10.2-36.0) to morbidity than younger ones (≤25 years). The studied sample showed that periapical lesions were more prevalent in males, in mandibular molars, and without prior endodontic treatment. There was no observed association between periapical lesions and comorbidities or habits; however, a significant correlation occurred with advancing age. Comorbidities and habits were not associated with the presence of periapical lesions. However, aging has been identified as a significant risk factor for the development of periapical lesions. This finding is clinically relevant as it highlights the importance of monitoring and maintaining oral health in patients with advanced age. How to cite this article: dos Santos VC, de Oliveira Kublitski PM, Marques da Silva B, et al. Periapical Lesions Associated with Demographic Variables, Dental Conditions, Systemic Diseases, and Habits. J Contemp Dent Pract 2023;24(11):864-870.

Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

Sphincter of Oddi Dysfunction Induces Gallstone by Inhibiting the Expression of ABCB11 via PKC-α.

The abnormal increase of Oddi sphincter pressure and total bile duct pressure may play an important role in the formation of cholesterol stones, but the specific molecular mechanism is still unclear. This study aims to investigate it through in vitro and in vivo experiments. A mouse model of Oddi sphincter dysfunction was constructed by stone-inducing diet. We compared the two groups with PKC-α inhibitor GÖ6976 and PKC-α agonist thymeleatoxin. Oddi sphincter pressure and total bile duct pressure were measured. Biochemical analysis of total cholesterol, bile acid and bilirubin was then conducted. The histopathologic changes of bile duct were observed by HE staining and the ultrastructure of liver cells and surrounding tissues was observed by transmission electron microscopy. Through the above experiments, we found that the change of PKC-α expression may affect the formation process of gallstones. The relationship between PKC-α and ABCB11 was further verified by in vitro and in vivo experiments. Our results suggest that ABCB11 and PKC-α are co-expressed in the tubule membrane of hepatocytes and interact with each other in hepatocytes. The high cholesterol diet further enhances the activation of PKC-α and thus reduces the expression of ABCB11. The formation of cholesterol stones is associated with the down-regulation of ABCB11 expression in the tubule membrane of hepatocytes due to kinase signaling. This is the first study to demonstrate that sphincter of Oddi dysfunction induces gallstones through PKC-α inhibition of ABCB11 expression.

Microbial Association with Gallstone Disease in Maysan Province, Iraq

Good health and well-being are among the UN Sustainable Development Goals. Based on this, the present study aimed to investigate a prevalent disease in Iraq, namely gallstone disease, along with the microbial infections associated with cholelithiasis and their antibiotic sensitivity patterns. The study was conducted at Teaching al-Sadr Hospital and Al-Zahrawi Surgical Hospital in Maysan, Iraq, from November 2021 to December 2022. Sixty cases of cholelithiasis in men and women between the ages of 20 and 50, who underwent cholecystectomy, were selected. The most common organism identified was Escherichia coli, found in 20 patients (33%). This was followed by Pseudomonas fluorescens in 7 patients (11.6%), Klebsiella pneumoniae in 6 patients (10%), Serratia marcescens in 6 patients (10%), Pseudomonas aeruginosa in 5 patients (8.3%), Kluyvera cryocrescens in 5 patients (8.3%), Proteus vulgaris in 5 patients (8.3%), Raoultella orithinolytica in 3 patients (5%), Klebsiella oxytoca in 2 patients (3.3%), and Enterobacter cloacae in 1 patient (1.6%). The biliary organisms showed various antibiotic sensitivity patterns. The highest sensitivity was observed with Cefotaxime (71%). The other antibiotics arranged as following; Amikacin (56%), Gentamicin (50%), Ciprofloxacin (46%), Meropenem (40%), Ceftazidime (35%), Imipenem (35%), Ertapenem (10%), Ampicillin (10%), Amoxicillin clavulanate (10%), and Cefepime (8%). In addition, female gender and advanced age were noted as contributing factors to gallstones. Cholesterol stones were found to be more common than other kinds of gallstones.

Correlation of serum biochemical characteristics and ABCG8 genetic variant (rs 11887534) with gall stone compositions and risk of gallstone disease in a group of Egyptian patients.

The overexpression of the cholesterol transporter: ATP-binding cassette transporter (ABCG8) due to the effect of ABCG8 genetic variant (rs11887534) leads to the precipitation of cholesterol crystals and gallstone disease (GSD). To evaluate the chemical composition of gallstones and the role of ABCG8 (rs11887534) in the susceptibility to GSD. We enrolled 77 patients with GSD treated with standard laparoscopic or open cholecystectomy and 75 age and sex-matched healthy controls. Chemical analysis of the extracted gallstones was performed. Analysis of the rs11887534 was performed by real-time PCR TaqMan technique for both cases and controls. Pure cholesterol stones were the main type of stones in GSD patients. The CC genotype carriers of rs11887534 were more prone to gallstone formation than other genotypes. The CC genotype carriers were 100 folds at increased risk to develop pure cholesterol stones. The most prevalent type of gallbladder stones is pure cholesterol stone. ABCG8 (rs11887534) could be associated with increased risk for cholesterol gallstones formation, this risk was more pronounced in female patients.

A case of gallstone pancreatitis due to cholesterol stones in which magnetic resonance cholangiopancreatography was useful

A case of gallstone pancreatitis due to cholesterol stones in which magnetic resonance cholangiopancreatography was useful

Study the predicators and risk factors for formation of gallstones in a sample of asymptomatic Iraqi patients in Baghdad

Background: A gallbladder stone (GBS) is a foremost reason of morbidity worldwide. Majority of the cases are asymptomatic (&gt;80%). Gallstones can be divided into three main types: cholesterol, pigment and mixed stones. The documented risk factors for GBS mostly are the advanced age, female gender, obesity, high-caloric diets and oral contraceptive, all of these can increase the lithogenicity of bile. Methods: This is a cross-sectional study was conducted at general surgical consultation departments in two major multispecialty hospitals in Baghdad (Al-Yarmook and Al Karama Teaching Hospitals) and in different health centers in Baghdad and through an online survey between February 2022 and February 2023. The study sample included 225 participants of both genders. The study questionnaires were sent through electronic format to the participants and the questions were asked to the others directly with enough time to respond well. The target population was all segments of society in the city of Baghdad. Results: The 225 patients were collected which their age range from 18 to 80 years of age. According to the collected data which showed that the percentage of GBS higher in female than male in value (54.2%) while for male (45.8%). Additionally, also it was found that the residence place has an important impact for this study and it presented that residency in urban places was (96.9%) which is higher than rural places which was only (3.1%). Also, most of patients were with: collage education (73.8%), non-employed (52.9%), middle-income class (72.4%). The results showed significant result (p&lt;0.05) and good association between age, and type of stones present (solitary or multiple); but for the gender, education level, occupation status, residence, socioeconomic class the results was non-significant (p&gt;0.05). Conclusions: The prevalence of asymptomatic gallstone was relatively high in this region. Female gender, age, high cholesterol level, family history of gallstones, and increased BMI independent risk factors for gallstones formation.

Cholelithiasis Associated to Acute Pancreatitis and Chronic Cholecystitis; A Case Report

Background: Cholelithiasis is a condition in which rare in children but in recent years has been increasing due to ultrasound used. This problem associated to inflammation, infection, obesity, children who received long total parenteral nutrition, resection of bowel, chronic liver disease or genetic. Most of cholelithiasis in children are asymptomatic. Gallstones are divided into cholesterol stones and pigment stones, could be on lucent or opaque description in abdominal x-ray. There are no special guidelines defined indications for medical or surgical treatment in children with cholelithiasis. Case Presentation: A 7 years 2 months old boy complaint of abdominal pain getting worse since 6 hours before admission; colicky pain, does not spread to other region of abdominal, and especially after eating. Vomit was frequently after eating. Symptoms are repeated for 3 times hospitalization and established as acute pancreatitis in second hospitalization but confirmed as cholelithiasis in recent admission. Conclusion: cholelithiasis in children could be related to inflammation and/ or infection of organs around the gallbladder. Keywords: Cholelithiasis, acute pancreatitis, chronic cholecystitis, case report.

Evaluation of Different Types of Gallstones Extracted by Endoscopic Retrograde Cholangiopancreatography

Objective: To study frequency of various types of gall stones extracted from bile duct using ERCP Study design: This is a cross sectional study Study place and duration: Study was conducted in the department of Gastroenterology Sir Ganga Ram Hospital Lahore. Study was completed in six months duration from January 2022 to June 2022. Materials and methods: Diagnosed cases of bile duct stones were underwent ERCP and extracted stones were analyzed to determine their composition. Ages of the patients were 20-70 years. Cases of either gender irrespective of residential area were included in this study. Patients with ischemic heart disease, asthma, liver cirrhosis, malignancy, tuberculosis, chronic obstructive pulmonary disease, interstitial lung disease and pregnancy were excluded from the study. During ERCP gross findings of the stones were noted. Results: Total 140 cases were studied having bile duct stones including 55(39.3%) male and 85(60.7%) females. There were 80(57%) cases with the age ≤50 years and 60(42.9%) cases above 50 years. Mean age of the patients was 46 ± 4.72 years. 58(41.4%) cases were from rural area and 82(58.6%) from urban area. Diabetes, hypertension and obesity was found in 38(27%), 47(33.6%) and 49(35%) cases respectively. Cholesterol stones were found in 51(36.4%), mixed stones in 70(50%) and brown pigmented stones in 19(13.6%) cases. Conclusion: Mixed cholesterol gall stones were most commonly found followed by pure cholesterol and brown pigmented stones. Keywords: Gallstones, Bile duct stones, ERCP, Endocscopy, Cholesterol stones,

A Review of Synchronous Findings of Hypothyroidism and Cholelithiasis.

Cholelithiasis is considered to bethe most common biliary pathology. They have been categorized into three types, which are pigment stones, cholesterol stones, and mixed types of stones with varying incidence. The condition may be asymptomatic for significantly long durations and in most cases, the presence of gall stones is an incidental finding. The patients may present with pain in the abdomen in stages of cholecystitis or advanced stages or cases of gall stones causing the obstruction. Gallbladder stones are formed through a very complex procedure with the contribution of numerous factors, where the main initiating step is supposed to be the development of a state wherein there is supersaturation of the bile, which in turn gives rise to accumulation and stasis of the bile and the development of gall stones. One of the factors is said to be the hypothyroid state. Hypothyroidism itself is a significantly common endocrine disorder that affects almost every nucleated cell in the body. There is decreased efficacy of the thyroid gland. The serum T3 and T4 levels might be found on the lower side whereas thyroid-stimulating hormone (TSH) values are found to be high. In some of the cases, though the T3 and T4 levels are maintained within the normal limits, the TSH shows raised values, which are labeled as subclinical hypothyroidism. The state of hypothyroidism may act upon the amount of bile secretion, the flow of bile into the intestines, cholesterol metabolism, and the action of the sphincter of Oddi. Studies have shown results pointing towards the correlation between these two factors. The basicmechanism behind the correlation between cholelithiasis and hypothyroidism is supposed to be due to the action of the hypothyroid state on the functioning of the sphincter of Oddi. The hypothyroid state is supposed to be decreasing the tendency of the sphincter of Oddi to relax, thus causing stasis of the bile, which over time leads to initiation of supersaturation of the bile and formation of gall stones. Both subclinical hypothyroidism and clinical hypothyroidism are found to be significantly common in patients having cholelithiasis. We, in this review article, have taken into consideration various studies which have been performed regarding this topic worldwide. The studies have been performed on individuals who are already diagnosed with either of these diseases and are then screened for the presence of the other disease included in this study. The degree of correlation varies according to the location of the stones and their sizes. Though various studies show varying results to some extent, overall almost all the studies show significant pieces of evidence of the correlation between cholelithiasis and hypothyroidism.

S3198 Was It Always in the Genes? ABCB4 and Its Variable Presentations

Introduction: Progressive familial intrahepatic cholestasis (PFIC), low phospholipid-associated cholestasis (LPAC), and autosomal dominant intrahepatic cholestasis of pregnancy (ICP) are rare genetic disorders that should be considered in patients with elevated alkaline phosphatase and unrevealing primary work ups. We present a case of a 36-year-old female with a history of ICP who presented with elevated ALP, eventually found to have a nonspecific variant in the ABCB4 gene, concerning for Type 3 PFIC. Case Description/Methods: A 36-year-old female with a history of ICP treated with Ursodiol, current oral contraceptive use (OCP), and remote cholecystectomy presented to a gastroenterologist for asymptomatic ALP elevation. Initial labs revealed ALP 279 U/L, bile acids 9.9 μmol/L, and gamma-glutamyl transferase (GGT) 283U/L. Magnetic resonance cholangiopancreatography (MRCP) was unrevealing. Given no signs of hepatic dysfunction, portal hypertension, or steatosis on fibroscan, liver biopsy was obtained, which was unremarkable. Due to persistent elevation in ALP without a clear etiology and history of ICP, genetic testing was pursued. Genetic testing revealed a heterozygous variant of uncertain significance in the ABCB4 gene that is associated with PFIC type 3. OCPs were discontinued due to an association of ICP and OCP induced cholestasis. Ursodiol was restarted given high rates of recurrent cholelithiasis in patients with PFIC. Discussion: Type 3 PFIC, LPAC, and ICP are rare genetic disorders linked to unique mutations in the ABCB4 gene responsible for ALP elevation. The ABCB4 gene may manifest later in life as cholestasis, jaundice, or pruritus. Mutations in the ABCB4 gene can cause a reduction in biliary phospholipid concentration, leading to sludge, cholesterol stones, and microlithiasis. Type 3 PFIC has a unique presentation associated with elevated GGT, unseen in type 1 or 2. LPAC should be considered in patients presenting with cholelithiasis before the age of 40, recurrent cholithialsis after cholecystectomy, ICP, and family history of cholelithiasis. The variant of uncertain significance in our patient’s ABCB4 gene appeared to be a unifying diagnostic factor given her history of ICP, cholelithaisis at age 18 years requiring cholecystectomy, and persistent new elevation in ALP. She ultimately met criteria for Type 3 PFIC, LPAC and ICP. Given the rapidly evolving nature of medical genetics, reclassification and evaluation of genetic mutations requires follow up.

S2995 Gallstone Ileus: An Unusual Cause of Small Bowel Obstruction After Liver Transplantation

Introduction: Liver transplantation is the only curative treatment for patients with decompensated liver disease. The prevalence of biliary complications after a deceased donor liver transplant is estimated between 10 to 15%. Biliary leaks and strictures are the most common biliary complications. We are presenting a rare case of gallstone ileus at the biliary limb in a patient with a complicated post-liver transplant course. Case Description/Methods: A 78-year-old female with a history of NASH cirrhosis for which she underwent a deceased donor liver transplant ten years before presentation. Post-transplant course was complicated by anastomotic biliary strictures, recurrent choledocholithiasis, and recurrent cholangitis requiring multiple ERCPs with placement of multiple biliary stents. She underwent Roux-en-Y hepaticojejunostomy three years before presentation with marked improvement in the number of cholangitis episodes. She presented with intractable nausea and vomiting. Physical exam showed abdominal distention and periumbilical tenderness but no rebound tenderness or rigidity. Labs were significant for a mild rise in serum creatinine but no leukocytosis and liver chemistries were normal. CT abdomen revealed small bowel obstruction with a transition point at the right lower quadrant anastomosis suspecting phytobezoar at the jejuno-jejunal anastomosis. The patient underwent push enteroscopy to decompress the obstructed limb and remove the suspected food material. The scope was advanced to the jejuno-jejunal anastomosis. About 15 cm beyond the afferent limb, the lumen was entirely occluded by a giant stone measuring (3.5 cm x 2.5 cm). The stone had sequential rings and appeared as a cholesterol stone. The stone was fragmented using grasping forceps, snares, and dilating balloons. It was successfully fragmented into 15-20 smaller stones over three hours duration. The scope was advanced beyond the fragmented stones. A nasogastric tube was inserted for decompression. Patient symptoms resolved following the procedure, and she was discharged home with no recurrence. (Figure) Discussion: Biliary leaks and strictures are the most common biliary complications following liver transplant. Gallstone ileus should be considered in liver transplant patients presenting with small bowel obstruction, especially if they have a history of recurrent biliary complications. Prompt recognition of this complication is key, endoscopic lithotripsy should be attempted first in these patients as they are usually high risk surgical candidates.Figure 1.: Panel A: CT abdomen and pelvis showing dense luminal material at the transition point. Panel B: Endoscopic image of the cholesterol stone occluding the lumen before lithotripsy. Panel C: Endoscopic image of the cholesterol stone after the lithotripsy.

Clinical and pathological profile of Gallbladder Cancer (GBC) and Gallstone disease GSD) among the patients admitted in tertiary care institute in Kolkata

Background: Gallstone disease (GSD) is one of the most common surgical problems throughout the world. The rise in gallstone disease burden and its wide spectrum of non-specific presentation makes the disease more challenging. Gall bladder cancer (GBC) is a common cancer in the northern and North-eastern States of India. The six cancer registries of the Indian Council of Medical Research (ICMR) (1990-1996) show a 10 times lower incidence of GBC per 1 00 000 in South India compared with the North. The objective of present study was to assess the epidemiological and pathological profile of GSD and GBC patients of Eastern India visiting tertiary care hospital of Kolkata.Method: This cross-sectional observational study was conducted, over a period of 18 months, at a tertiary referral hospital of Kolkata. In this study, 66 gallstone disease patients and 24 gallbladder cancer patients who undergone surgery were included in the study after their written informed consent. Data on their demographic and pathological profile, type of gallstones, their number and staging and type gallbladder cancer were collected. Results: GSD GBC were found to afflict females, Male to female ratio was 1:2 1:3 for GSD and GBC respectively. We found that nearly half (45.4%) GSD patients were in the age group of 21-40 years and more than half (58.6%) GBC patients were in age group of 41-60 years. Majority of GSD patients had multiple stones (57.6%) and cholesterol stones were most common (59.1%). Out of 24 GBC patients, nearly one-third (33.3%) had stage II cancer and only 12.5% patients had stage IV cancer. More than one-fourth (29.2%) GBC patients had poorly differentiated carcinoma.Conclusion: The results of this study reaffirm that female gender is a strong predisposing factor for GSD and GBC and patients in their fourth decade, are more at risk. Large population based multicentric analytical study is necessary to strengthen this study findings.