Efficacy of Common Bile Duct Stenting on the Reduction in Gallstone Migration and Symptoms Recurrence in Patients with Biliary Pancreatitis Who Were Candidates for Delayed Cholecystectomy.

BACKGROUND: In patients with severe biliary pancreatitis, delayed cholecystectomy associated with a high risk of recurrence is recommended. The current study aimed to evaluate the effect of common bile duct (CBD) stenting on reducing gallstones migration and recurrence of symptoms in patients with pancreatitis and delayed cholecystectomy candidates. METHODS: To this purpose, the randomized, controlled clinical trial was performed on 40 patients with biliary pancreatitis who were candidates for delayed cholecystectomy. Patients were randomly divided into two groups of A and B that underwent CBD stenting after ERCP and received endoscopic treatment without stenting, respectively. A checklist recorded demographics and complications. Group A was followed up after four weeks to remove the stent and record the complications. Group B underwent MRCP to examine the migration of new gallstones as well as the complications. RESULTS: Of the 40 patients, 20 subjects (11 males and 9 females) were allocated to each group, matched for demographic variables. In the one-month follow-up, only one subject in group A manifested symptoms of gallstone migration and recurrence, while in group B, recurrence was observed in 6 patients (P = 0.037). There was no significant difference in the success rate of ERCP and the incidence of complications between the two groups. CONCLUSION: CBD stenting in patients with biliary pancreatitis and gallstone could reduce the risk of recurrence and remigration of gallstones in delayed cholecystectomy cases.

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Effect of Ageing on the Common Bile Duct Diameter.

INTRODUCTION: The aim of the study was to determine if the common bile duct (CBD) diameter increases physiologically with age and investigate whether gallstones lead to changes in CBD diameter. METHOD: Our study is composed of 721 patients in 2 groups: 517 asymptomatic patients and 204 gallstones patients who underwent MRCP. Their CBD diameter was measured at its widest visible portion on MRCP. Simple linear regression of the average of these measurements was used to investigate the relationship between age and CBD diameter in both populations. Subjects were further divided into 8 subgroups age-wise, respectively, and their means compared decade-wise using ANOVA. Furthermore, each subgroup mean from both populations was compared with each other using a t test. RESULTS: Among the 517 subjects, the mean CBD diameter was 5.3663 mm ± 1.43546 and correlated with age (p < 0.01), dilating at 0.07 mm/year. The mean diameter of our oldest group was 7.9 mm, resulting in a plausible upper limit of 8 mm for the asymptomatic population. The mean CBD diameter of the cholelithiasis population was 5.6738 mm ± 1.40986 and also correlated with age (p < 0.01). The mean CBD diameter of the age groups from the cholelithiasis population was larger than that from the asymptomatic population, but none were statistically significant. CONCLUSION: Although the CBD increases physiologically with age, there is no significant difference in CBD size between the general population and the cholelithiasis patients at any particular age. Gallstones do not independently dilate the CBD.

Liver function tests as predictors of common bile duct stones in acute cholecystitis patients with a chronic history: A retrospective cohort study on the ACS-NSQIP database.

ABSTRACT: Liver function tests (LFTs) use for common bile duct stone (CBDS) prediction in acute cholecystitis (AC) patients is challenging, especially in patients with chronic cholecystitis (CC) history.This study aims to describe characteristics of AC patients with CC history and assess LFTs' utility for CBDS prediction in these patients.A retrospective cohort study was conducted on adults with a diagnosis of AC and CC history included in the National Surgical Quality Improvement Program database from 2008 to 2016. Patients were categorized into CBDS- (without CBDS) and CBDS+ (with CBDS). Multivariate logistic regression was used to determine CBDS predictors.This study included 7458 patients, of which 40.2% were CBDS+. CBDS+ patients were more commonly females (64.4% vs 54.7%, P < .001). Mean levels of bilirubin (1.70 vs 0.90, P < .001), SGOT (105.9 vs 49.0, P < .001) and ALP (164.6 vs 103.8, P < .001) were significantly higher among CBDS+ patients.Significant positive predictors of CBDS were female gender, increased BMI, and abnormal bilirubin, ALP and SGOT. AC patients with CC history are more likely to have CBDS. Abnormal LFTs are significantly associated with CBDS in this patient population. Familiarity with these findings can help raise clinical suspicion of providers for earlier evaluation and management of CBDS.

Surgical treatment of acute cholecystitis in obese patients.

<b>Introduction:</b> In today's technological climate, science and medicine have entered a new era. At the level of technological progress, we have identified millennia of "new" problems and diseases. If earlier diseases had a certain individuality then, in the third millennium, we face compliance and synergistic influence of diseases. Obesity is a problem of the third millennium. It is known that obesity is the main factor in the development of various chronic diseases [1-3]. With excess weight and obesity, bile is oversaturated with cholesterol, resulting in an increase of its lipogenicity index. As a result, frequency of gallstone disease increases; findings from this study document an increase of disease frequency as high as 50% to 60% [4]. In 20% of patients, housing concerns are combined with obesity [5]. Thus, obesity is one of the factors in the development of cholelithiasis and cholecystitis [6]. The presence of acute cholecystitis represents the most difficult situation for patients with gallstones. When obesity is also present, the patient's risk of surgical complications increases due to altered homeostasis and reduced reserve capacity [7]. A retrospective study of this issue [8] posed a number of questions about the possibility of influencing the course of disease in the preoperative period as well as the improvement and impact of surgical technicalities in patients with acute cholecystitis and obesity. Addressing these and additional questions is the main goal of this study. <br><b>Aim: </b>The aim of the study was to study and select the optimal method of surgery in patients with acute cholecystitis and obesity. <br><b>Materials and methods:</b> In our study, a prospective analysis was used. We analyzed 67 cases with diagnosis of acute cholecystitis and obesity; all were treated at Kyiv Regional Clinical Hospital in the period from September 2018 to March 2020. Patients with acute cholecystitis and obesity received either traditional or modified laparoscopic cholecystectomy. <br><b>Results:</b> Retrospective analysis indicates traditional laparoscopic cholecystectomy is technically difficult and costly in patients with acute cholecystitis and obesity. A modified laparoscopic cholecystectomy has been proposed to improve and enhance surgery in patients with acute cholecystitis and obesity. Surgical duration was shortened by 9.01 ± 0.41 minutes (p = 0.001; αα= 0.05) when a modified laparoscopic cholecystectomy was performed. <br><b>Conclusions:</b> Performing a modified laparoscopic cholecystectomy reduced the duration of surgery by 9.01 ± 0.41 minutes (p = 0.001; α = 0.05), prevents development of metabolic acidosis pH 7.39 ± 0.03 vs 7.30 ± 0.005 = 0.001; αα= 0.05, pCO2 5.05 ± 0.36 vs 6.03 ± 0.38 (p = 0.02; αα= 0.05), reducing the risk of hypercoagulation. Modified laparoscopic cholecystectomy (LHE) is effective in II and III degrees of obesity (p = 0.001; α = 0.05).

The influence of periampullary diverticula on ERCP for treatment of common bile duct stones.

In order to evaluate the effectiveness of various methods we applied to decrease the influence of periampullary diverticula (PAD) on the success rate and complications of endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of common bile duct (CBD) stones, we enrolled patients with CBD stones who had been treated by ERCP in our hospital between January 2015 and December 2018. According to the presence of PAD, the patients were divided into a PAD group and a non-PAD group. The rate of complete stone removal in the first session, the rate of overall stone removal, the frequency of application of mechanical lithotripsy, and procedure-related complications, including bleeding, hyperamylasemia, pancreatitis, perforation, and infection of biliary tract were recorded. A total of 183 cases, including 72 cases in the PAD group and 111 cases in the non-PAD group were enrolled. There was no statistical difference between the two groups regarding gender (P = 0.354). However, regarding age, there was a statistical difference (P = 0.002), and the incidence of PAD increased with age. There were 5 (6.9%) cases in the PAD group and 14 (12.6%) cases in the non-PAD group where mechanical lithotripsy was applied. There were 59 (81.9%) cases in the PAD group and 102 (91.9%) cases in the non-PAD group where there was complete removal of CBD stones in the first session, and there were 68 (94.4%) cases in the PAD group and 107 (96.4%) cases in the non-PAD group where there was complete removal of all stones. In the PAD group, there were 0 cases (0%) with gastrointestinal bleeding, 0 cases (0%) with gastrointestinal perforation, 13 cases (18.1%) with post-ERCP hyperamylasemia, 3 cases (4.2%) with post-ERCP pancreatitis, and 4 cases (5.6%) with biliary tract infection. In the non-PAD group, 1 case (0.9%) had gastrointestinal bleeding, 0 cases had gastrointestinal perforation, 18 cases (16.2%) had post-ERCP hyperamylasemia, 5 cases (4.5%) had post-ERCP pancreatitis, and 11 cases (9.9%) had biliary tract infection. This retrospective study showed that there was a statistical difference between the two groups regarding complete removal of CBD stones in the first session and application of mechanical lithotripsy (both P < 0.05), but no statistical difference according to the rates of overall stone removal and the complications (P > 0.05), which means that we can reduce the influence of PAD on ERCP for treatment of common bile duct stones.

Altered Bile Transporter Expression and Cholesterol Metabolism in Children With Cholesterol and Pigment Gallstones.

OBJECTIVES: We elucidated pathophysiology of pediatric gallstone disease by assessing liver expression of bile transporters in relation to bile acids and surrogates of cholesterol absorption and synthesis in serum and gallstones. METHODS: RNA expression of canalicular bile transporters in liver biopsies from 32 pediatric gallstone patients and from 6 liver donors (controls) was measured by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Concentrations of cholesterol and precursors, plant sterols and bile acids in gallstones, and in serum of the patients and 82 healthy children were measured. Primary outcomes were the difference in RNA expressions and serum sterol profiles between patients and controls. RESULTS: Cholesterol stones (CS; n = 15) contained cholesterol >42% and pigment stones (PS; n = 17) <9% of weight. CS patients had markedly lower serum plant sterols (absorption) and higher cholesterol precursors (synthesis) than PS patients or healthy controls. CS contained several times more cholesterol precursors and less plant sterols relative to cholesterol than PS, which were enriched by primary bile acids (12-5.2-fold, P < 0.001). Liver RNA expression of ABCG5/G8 was similarly increased 2.5- to 1.8-fold (P < 0.002) in CS and PS patients, whereas PS patients had higher ABCB11 expression (P < 0.05). In PS bile acid concentration correlated with gallstone plant sterols (R = 0.83, P < 0.0001), and ABCG5 expression with ABCB11 expression (R = 0.27, P = 0.03). CONCLUSIONS: In CS, upregulation of ABCG5/G8 expression associates with low absorption and high gallstone content of cholesterol. In PS, activation of bile acid transport by ACBC11 interconnects with hepatic upregulation of ABCG5/G8 enriching PS with bile acids and plant sterols.

Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones.

Cholecystokinin (CCK) is an important neuro-intestinal peptide hormone produced by the enteroendocrine I-cells in the upper part of small intestine. Protein- and fat-enriched food plays an important role in triggering CCK secretion from the intestine. Carbohydrates stimulate only small amounts of CCK release. The CCK-1 receptor (CCK-1R) is largely localized in the gallbladder, sphincter of Oddi, pancreas, small intestine, gastric mucosa, and pyloric sphincter, where it is responsible for CCK to regulate multiple digestive processes including gallbladder contraction, pancreatic secretion, small intestinal transit, and gastric emptying. Accumulated evidence clearly demonstrates that CCK regulates gallbladder and small intestinal motility through CCK-1R signaling cascade and the effect of CCK-1R on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. Disruption of the Cck or the Cck-1r gene in mice significantly increases the formation of cholesterol gallstones by disrupting gallbladder emptying and biliary cholesterol metabolism, as well as promoting intestinal absorption of cholesterol. Abnormalities in gallbladder motility function in response to exogenously administered CCK are found primarily in patients with cholesterol gallstones. Patients with pigment gallstones display an intermediate degree of gallbladder motility defect without gallbladder inflammation and enlarged fasting gallbladder. Dysfunctional gallbladder contractility has been found under several conditions such as pregnancy, obesity, diabetes, celiac disease, and total parenteral nutrition although gallstones are not observed. The gallbladder-specific CCK-1R-selective agonist may lead to an efficacious novel way for preventing gallstone formation by promoting gallbladder emptying, particularly for pregnant women and subjects with dysfunctional gallbladder motility function such as celiac patients, as well as patients with total parenteral nutrition.

Gastrointestinal defects in gallstone and cholecystectomized patients.

BACKGROUND AND AIM: Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. MATERIALS AND METHODS: Forty-six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. RESULTS: Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. CONCLUSION: Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.

Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment?

BACKGROUND: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed. RESULTS: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication. CONCLUSIONS: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

"Post-cut": An endoscopic technique for managing impacted biliary stone within an entrapped extraction basket.

BACKGROUND AND STUDY AIMS: Ampullary impaction of an entrapped stone-basket complex is not an infrequent yet challenging event during endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study is to evaluate the feasibility, safety, and efficacy of "post-cut" for the management of such scenarios. PATIENTS AND METHODS: Patients with impacted biliary stone with an entrapped basket during ERCP at West China Hospital, Chengdu, China, from October 2004 to August 2014 were included in this retrospective study. Adequate biliary sphincterotomy was performed in all cases before attempted stone basket removal. Using free hand needle knife techniques, the authors extended the sphincterotomy along the long axis of the distal common bile duct to manage the biliary stone-basket impaction. In comparison with "pre-cut", the authors coined the term "post-cut" referring to this technique. The feasibility, safety, and potential complications of post-cut were analysed. RESULTS: "Post-cut" was performed in consecutive 10 cases of impacted biliary stone within an entrapped extraction basket. The size of the removed stone ranged from 6 mm to 13 mm. The length of post-cut is 2 mm to 4 mm. The impacted basket was easily retrieved in all patients without complications, including bleeding, perforation, and pancreatitis. CONCLUSION: "Post-cut" is a feasible, effective, and safe endoscopic technique when impaction of a biliary stone with an entrapped extraction basket develops.

A model of gallbladder motility.

Impaired gallbladder motility leads to some clinical manifestations associated with its muscle contraction and/or the rate of filling with bile. To gain a better understanding of the possible reasons for different filling/emptying patterns we developed a mathematical model of the gallbladder that takes into account the kinetics of its filling and emptying and changes in the concentration of the accumulated bile. The model is based on four parameters responsible for the maximum speed of bile evacuation (Mg), pulsation of contractions (ω), the kinetic filling rate (kg) and the maximum bile mass accumulated in the gallbladder (mtotal). The model results were fitted to different clinical results describing gallbladder motility depending on the meal composition, patient's age and health condition (obesity and gallstones). Compatibility of the model results with the experimental data allows us to draw physiological conclusions. We found that different gallbladder emptying patterns may result from differences in the amplitude of contraction of gallbladder muscles (e.g. for various meal composition), differences in the rate of bile inflow (e.g. for obese patients during filling), and differences in gallbladder muscle pulsations (e.g. for lean patients during early gallbladder emptying). The model of gallbladder motility can facilitate identification of causes of disorders, help to explore complicated physiological pathways, and can be applied in etiology analysis or studies of observable clinical indicators.

Nonalcoholic fatty liver disease, cholesterol gallstones, and cholecystectomy: new insights on a complex relationship.

PURPOSE OF REVIEW: Gallstone disease (GSD) and nonalcoholic fatty liver disease (NAFLD often coexist in a given patient and both conditions are associated to obesity and insulin resistance. The relationship between GSD and NAFLD is complex and bidirectional. In the present review, we summarize the existing information on the complex link between GSD and NAFLD and the potential implications for patient care. RECENT FINDINGS: Several clinical studies and systematic reviews have addressed the association between NAFLD and GSD underscoring that NAFLD is an independent risk factor for GSD. Conversely, GSD has been found also to be an independent risk factor for NAFLD with GSD potentially being linked to greater disease severity. In addition to the data showing association of NAFLD and GSD, recent evidence has also showed that cholecystectomy may itself be a risk factor for NAFLD development. The complex and bidirectional relationship between these diseases is partially explained by a number of common pathogenic links but the precise underlying mechanisms of the association of GSD and NAFLD need to be better delineated. Also, although the mechanisms of the promotional effect of cholecystectomy on NAFLD development are unknown, recent findings unveiling new aspects of gallbladder physiology and endocrine actions of bile acids provide a framework to advance research in this field. SUMMARY: In this review, we address the different aspects of the complex association between NAFLD and GSD. The potential underlying mechanisms and recent information on endocrine actions of bile acids and the gallbladder are reviewed.

Mouse models of gallstone disease.

PURPOSE OF REVIEW: The establishment of mouse models of gallstones, and the contribution of mouse models to genetic studies of gallstone disease, as well as the latest advances in the pathophysiology of gallstones from mouse experiments are summarized. RECENT FINDINGS: The combined uses of genomic strategies and phenotypic studies in mice have successfully led to the identification of many Lith genes, which pave the way for the discovery of human LITH genes. The physical-chemical, genetic, and molecular biological studies of gallstone disease in mice with knockout or transgene of specific target genes have provided many novel insights into the complex pathophysiological mechanisms of this very common hepatobiliary disease worldwide, showing that interactions of five primary defects play a critical role in the pathogenesis of cholesterol gallstones. Based on mouse studies, a new concept has been proposed that hepatic hypersecretion of biliary cholesterol is induced by multiple Lith genes, with insulin resistance as part of the metabolic syndrome interacting with cholelithogenic environmental factors to cause the phenotype. SUMMARY: The mouse model of gallstones is crucial for elucidating the physical-chemical and genetic mechanisms of cholesterol crystallization and gallstone formation, which greatly increase our understanding of the pathogenesis of this disease in humans.

Current clinical algorithms for predicting common bile duct stones have only moderate accuracy.

BACKGROUND AND AIM: A risk-stratified approach for selecting patients likely to harbor common bile duct (CBD) stones to proceed directly to endoscopic or surgical stone clearance, rather than undergo less invasive testing, has been proposed. We assessed the performance of three clinical algorithms used to predict CBD stones. METHODS: All patients undergoing first-time endoscopic retrograde cholangiopancreatography (ERCP) in 2011-2012 as a result of suspected CBD stones were enrolled prospectively in a clinical database. Data such as imaging test findings and liver function tests (LFTs) were collected 48 h prior to and on the day of ERCP. Patients were stratified into different risk groups for harboring CBD stones according to three clinical algorithms using imaging and laboratory data. Findings on ERCP were used as gold standard. Performance characteristics of each algorithm were separately calculated for each time point of LFT assessment. RESULTS: Overall, 186 patients were analyzed, 75% of whom presented CBD stones on ERCP. Proportion of patients categorized as high-risk for harboring CBD stones varied among the three algorithms (67% vs 73% vs 56%). Also, the algorithms showed only moderate, albeit comparable, accuracy for predicting the presence of CBD stones (0.65, 95% confidence interval [CI] 0.62-0.68 vs 0.68, 95% CI 0.63-0.67 vs 0.59, 95% CI 0.57-0.61). Similar results were obtained when performance characteristics were recalculated using LFT from 48 h prior to ERCP (data not shown). CONCLUSION: Three diagnostic algorithms commonly used for predicting CBD stones have comparable but only moderate accuracy. Further research is warranted to improve risk stratification of patients with suspected CBD stones.

Clinical and radiological diagnosis of gallstone ileus: a mini review.

Gallstone ileus is a rare cause of bowel obstruction, which mainly affects the elderly population. The associated mortality is estimated to be up to 30%. The presentation of gallstone ileus is notoriously non-specific, and this often contributes to the delay in diagnosis. The diagnosis of gallstone ileus relies on a radiological approach, and herein we discuss the benefits and drawbacks of the use of different modalities of radiological imaging: plain abdominal films, computed tomography, magnetic resonance imaging, and ultrasound scanning. Based on our case experience and review of the literature, the authors conclude that although an effective first-line tool, plain abdominal films are not adequate for diagnosing gallstone ileus. In fact, the gold standard in an acutely unwell patient is computed tomography.

An update on the pathogenesis of cholesterol gallstone disease.

PURPOSE OF REVIEW: Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease. RECENT FINDINGS: Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated. SUMMARY: Ongoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.

Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia.

The prevalence of gallstones is 10% to 15% in adults. Individuals with acute cholecystitis present with right upper quadrant pain, fever, and leukocytosis. Management includes supportive care and cholecystectomy. The prevalence of choledocholithiasis is 10% to 20%, and serious complications include cholangitis and gallstone pancreatitis. The goal of management in individuals with choledocholithiasis consists of clearing common bile duct stones. Acute ascending cholangitis is a life-threatening condition involving acute inflammation and infection of the common bile duct. Treatment includes intravenous fluids, analgesia, intravenous antibiotics, and biliary drainage and decompression. Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones.