Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.

BACKGROUND: The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. METHODS: Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). RESULTS: Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. CONCLUSIONS: We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Litholytic agents as an alternative treatment modality in patients with biliary dyspepsia.

Biliary dyspepsia presents as biliary colic in the absence of explanatory structural abnormalities. Causes include gallbladder dyskinesia, sphincter of Oddi dysfunction, biliary tract sensitivity, microscopic sludges, and duodenal hypersensitivity. However, no consensus treatment guideline exists for biliary dyspepsia. We investigated the effects of medical treatments on biliary dyspepsia.We retrospectively reviewed the electronic medical records of 414 patients who had biliary pain and underwent cholescintigraphy from 2008 to 2018. We enrolled patients who received litholytic agents and underwent follow-up scans after medical treatment. We divided the patients into the GD group (biliary dyspepsia with reduced gallbladder ejection fraction [GBEF]) and the NGD group (biliary dyspepsia with normal GBEF). We compared pre- and post-treatment GBEF and symptoms.Among 57 patients enrolled, 40 (70.2%) patients had significant GBEF improvement post-treatment, ranging from 34.4 ±â€Š22.6% to 53.8 ±â€Š26.8% (P < .001). In GD group (n = 35), 28 patients had GBEF improvement after medical treatment, and value of GBEF significantly improved from 19.5 ±â€Š11.0 to 47.9 ±â€Š27.3% (P < .001). In NGD group (n = 22), 12 patients had GBEF improvement after medical treatment, but value of GBEF did not have significant change. Most patients (97.1% in GD group and 81.8% in NGD group) had improved symptoms after medical treatment. No severe complication was reported during treatment period.Litholytic agents improved biliary colic in patients with biliary dyspepsia. Therefore, these agents present an alternative treatment modality for biliary dyspepsia with or without gallbladder dyskinesia. Notably, biliary colic in patients with gallbladder dyskinesia resolved after normalization of the GBEF. Further prospective and large-scale mechanistic studies are warranted.

Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.

Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and consistent inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. CFTR was expressed apically in non-CF pig gallbladder epithelium but was absent in CF. CF pig gallbladders lacked cAMP-stimulated anion transport. Using a novel gallbladder epithelial organoid model, we found that Cl- or HCO3- was sufficient for non-CF organoid swelling. This response was absent for non-CF organoids in Cl-/HCO3--free conditions and in CF. Single-cell RNA-sequencing revealed a single epithelial cell type in non-CF gallbladders that coexpressed CFTR, MUC5AC, and MUC5B. Despite CF gallbladders having increased luminal MUC5AC and MUC5B accumulation, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. In conclusion, these data suggest that loss of CFTR-mediated anion transport and fluid secretion contribute to microgallbladder development and luminal mucus accumulation in CF.

A Whole-Food-Based Health Product (A-F Betafood®) Improves Gallbladder Function in Humans at Risk of Gallbladder Insufficiency: A Randomized, Placebo-Controlled Clinical Trial.

A-F Betafood® is a whole food-based health product. The product contains phytonutrients and bioactives with antioxidant properties that may support gallbladder and liver function. Herein, we investigated the efficacy of A-F Betafood® on gallbladder and liver function. In this randomized, placebo-controlled, parallel study fifty overweight but otherwise healthy adults received A-F Betafood® or placebo for 12 weeks. Gallbladder function as assessed by gallbladder volume, ejection fraction (GBEF), ejection rate, wall thickness and liver function determined via aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase, and high-sensitivity c-reactive protein analysis at baseline and week 12 were the primary outcomes. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and oxidative stress markers including oxidized low-density lipoprotein, tumor necrosis factor-α, adiponectin and malonyldialdehyde (MDA) were assessed as secondary outcomes. A-F Betafood®-supplementation significantly reduced gallbladder wall thickness (p = 0.049) by 9% compared to placebo from baseline to week 12. The A-F Betafood® group alone had significant improvements in gallbladder volume (32%; p = 0.044) and GBEF (19%; p = 0.047) at week 12. There were no changes in liver function, oxidative stress markers or blood lipid concentrations, though MDA concentrations decreased in both groups. Our findings demonstrate A-F Betafood®-supplementation significantly improves measures of gallbladder function and support healthy gallbladder function in the individuals with gall bladder condition.

Pathophysiological connections between gallstone disease, insulin resistance, and obesity.

Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.

Self-reported Outcomes After Cholecystectomy for Pediatric Hyperkinetic Biliary Dyskinesia.

BACKGROUND: Biliary dyskinesia (BD) is a common indication for cholecystectomy in children. Current literature demonstrates an improvement in symptoms after cholecystectomy in most pediatric patients with an EF <35%; however, data supporting the efficacy of cholecystectomy for hyperkinetic BD (EF >65%) is sparse. We sought to determine whether children with hyperkinetic BD (HBD) had resolution of their symptoms after laparoscopic cholecystectomy at our institution. MATERIALS AND METHODS: We conducted a retrospective chart review of children who had undergone laparoscopic cholecystectomy for HBD at our institution between September 2010 and July 2015. Patients completed a phone survey about symptom resolution, whether they were happy to have undergone cholecystectomy, overall satisfaction on a 1-10 scale, and additional workup for those with ongoing pain. Analysis was performed using STATA statistical software with a P-value < 0.05 as statistically significant. RESULTS: Thirteen patients met inclusion criteria. Median gallbladder ejection fraction was 93% [IQR: 90, 97]. Median postoperative follow-up was 59 d [IQR: 25, 151] at which time 50% reported resolution of symptoms. Eight patients participated in the survey at a median follow-up of 45 mo [IQR: 40, 66]. Fifty percent reported ongoing abdominal pain. Frequency of pain varied among patients with pain, occurring from <1 time per week to a few times per day. Five patients (63%), including one patient with ongoing pain, were happy that their gallbladder had been removed and overall satisfaction rating was 5 on a scale of 1-10. CONCLUSIONS: Only half of children with HBD were asymptomatic at long-term follow-up. Cholecystectomy for HBD may or may not improve symptoms.

GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrum.

The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty-eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

The association between eating difficulties and biliary sludge in the gallbladder in older adults with advanced dementia, at end of life.

OBJECTIVES: In clinical settings, untreatable biliary sludge in the gallbladder can be observed in older adults with advanced dementia. The underlying cause of biliary sludge existence in patients with dementia is currently unknown. Therefore, we aimed to investigate the prevalence, risk factors, and related outcomes of biliary sludge formation in the gallbladder of older adults with dementia. DESIGN: Cross-sectional study. SETTING: Geriatric ward of University Hospital in Japan. PARTICIPANTS: Inpatients aged 80 and older living with dementia. MEASUREMENTS: We evaluated the presence of biliary sludge by diagnostic ultrasonography and collected data regarding patient demographic information, cognition (mini-mental state examination [MMSE]), physical activity (Barthel Index), oral food intake (food intake level scale [FILS]), clinical stage of dementia (functional assessment staging [FAST] of dementia), and patient performance status (Zubrod/ Karnofsky score). RESULTS: Male sex, larger gallbladder volume and calories from oral intake were significantly associated with the presence of biliary sludge (P = .02, .02, .002, respectively). There was a significant negative correlation between the FAST stage and the FILS level in all patients (P < .001). More advanced dementia and dysphagia was more likely to be found in patients with Alzheimer disease (AD) with biliary sludge, compared to patients with AD without biliary sludge (FAST 7a, FILS II and FAST 6c, FILS V, respectively, P = .06, 04). A logistic regression analysis revealed that the eating status of FILS I and II, generally called "fasting or anorexia", was a significant risk factor for forming biliary sludge in older adults with dementia (P = .031, odds ratio: 5.25, 95% confidence interval: 1.16-23.72). CONCLUSIONS: Fasting status may be associated with the existence of biliary sludge in older adults with dementia. Therefore, supportive care for eating might be an important solution to comfortable end-of-life care for older adults with advanced dementia.

A novel YOLOv3-arch model for identifying cholelithiasis and classifying gallstones on CT images.

Locating diseases precisely from medical images, like ultrasonic and CT images, have been one of the most challenging problems in medical image analysis. In recent years, the vigorous development of deep learning models have greatly improved the accuracy in disease location on medical images. However, there are few artificial intelligent methods for identifying cholelithiasis and classifying gallstones on CT images, since no open source CT images dataset of cholelithiasis and gallstones is available for training the models and verifying their performance. In this paper, we build up the first medical image dataset of cholelithiasis by collecting 223846 CT images with gallstone of 1369 patients. With these CT images, a neural network is trained to "pick up" CT images of high quality as training set, and then a novel Yolo neural network, named Yolov3-arch neural network, is proposed to identify cholelithiasis and classify gallstones on CT images. Identification and classification accuracies are obtained by 10-fold cross-validations. It is obtained that our Yolov3-arch model is with average accuracy 92.7% in identifying granular gallstones and average accuracy 80.3% in identifying muddy gallstones. This achieves 3.5% and 8% improvements in identifying granular and muddy gallstones to general Yolo v3 model, respectively. Also, the average cholelithiasis identifying accuracy is improved to 86.50% from 80.75%. Meanwhile, our method can reduce the misdiagnosis rate of negative samples by the object detection model.

Can surgical treatment be justified for neuroendocrine carcinoma of the gallbladder?

Clinical features and treatment of GB neuroendocrine carcinoma (GB-NEC) are not well understood. This study aimed to analyze clinical outcomes of GB-NEC and verify the oncologic benefit of surgical treatment.From October 1994 to December 2014, the medical records of 31 patients with GB-NEC at a single center were retrospectively reviewed. There were 18 inoperable cases due to distant metastasis, including 7 of best supportive care (Tx.1) and 11 of non-operative palliative treatment (Tx.2). 4 patients received non-curative, palliative resection (Tx.3). Only 9 patients were able to undergo curative-intent resection (Tx.4).Among the 31 patients with GB-NEC, preoperative mean value of carbohydrate antigen 19-9 (CA 19-9) was 74.8 ±â€Š156.1 U/mL and the median overall survival time was 10 months (range 7.0-12.0 months). Of these, 21 (67.7%) patients received systemic treatment. Among 9 patients who underwent curative-intent resection (Tx.4), 9 patients had poorly differentiated cancer cells and 7 patients received radical cholecystectomy. 6 patients had adjuvant treatment including concurrent chemoradiation therapy (CCRT) or chemotherapy alone. The recurrence rate was 88.9%. The median overall survival between 4 groups was as follows: 4.0 (3.0-18.0) months in Tx.1 (n = 7) versus 9.0 (3.0-21.0) months in Tx.2 (n = 11) versus 11.0 (3.0-15.0) months in Tx.3 (n = 4) versus 23.0 (8.0-34.0) months in Tx.4 (n = 9), respectively. Significant differences in median overall survival time existed between Tx.2 and Tx.4; 9 (3.0-21.0) months versus 23.0 (8.0-34.0) months (P = .017).Most GB-NECs show poor biologic behavior. Nonetheless, curative-intent resection could possibly promote longer survival than other treatment modalities for GB-NEC. Efforts to undergo curative resection through early detection and development of adjuvant treatment are needed.

Ultrasound Evaluation of Biliary Atresia Based on Gallbladder Classification: Is 4 Hours of Fasting Necessary?

OBJECTIVES: The aim of this study was to evaluate the influence of fasting time on the ultrasound identification and exclusion of biliary atresia in jaundiced infants through the use of the gallbladder classification scheme and to test the value of the gallbladder classification scheme in the diagnosis of biliary atresia in inexperienced individuals. METHODS: A total of 188 jaundiced infants were enrolled in this study. All patients received detailed abdominal sonograms. Diagnoses were confirmed via liver biopsy, surgical findings, or follow-up. Infants were grouped into either the fasting group (fasting time ≥ 4 h) or the nonfasting group (fasting time < 4 h). According to the gallbladder classification scheme, the gallbladders were classified into 4 types. The accuracy of diagnosing biliary atresia based on the gallbladder classification scheme was compared between the 2 groups. The gallbladders of 177 infants that were detectable by ultrasonography were used to compare the diagnostic performances between a junior radiologist and an experienced radiologist. RESULTS: The accuracies in the diagnosis of biliary atresia with the gallbladder classification scheme were 86.3% (82 of 95 patients) for the fasting group and 93.5% (87 of 93 patients) for the nonfasting group (P = .100). The diagnostic accuracies of biliary atresia were 88.7% (157 of 177 patients) for the junior radiologist and 90.4% (160 of 177 patients) for the experienced radiologist (P = .250). The κ value for the agreement between the 2 radiologists was 0.859. CONCLUSIONS: The performance of gallbladder diagnoses was not influenced by the fasting time with the use of the gallbladder classification scheme. Additionally, the gallbladder classification scheme may help junior radiologists to more effectively identify biliary atresia and nonbiliary atresia.

Gallbladder GIST: A review of literature.

Mesenchymal tumors of the gallbladder are rarely encountered in clinical practice. The Gastrointestinal Stromal Tumor (GIST) of the gallbladder is rarely encountered. These tumors most commonly arise from the interstitial cells of Cajal (ICC), the pacemakers of the intestinal system. There can be benign as well as malignant forms of GIST. The literature on GIST arising from the gallbladder wall is limited to a few case reports only. In extensive search of the indexed literature, only 9 cases of gallbladder GIST were retrieved. Based on the available literature these tumors are commonly found in females. They usually present with hypochondrial pain with or without other features of cholangitis. These tumors are usually malignant and warrant a radical surgical excision. The data on postoperative adjuvant therapy and survival is limited. The authors presented a review of the available literature on this rare pathology.

Ultrasound Assessment of Hepatobiliary and Splenic Changes in Patients With Dengue and Warning Signs During the Acute and Recovery Phases.

OBJECTIVES: To evaluate whether abdominal ultrasound (US) with a gallbladder (GB) contractility study or motor function test can be used as a diagnostic tool in patients with dengue and warning signs in acute and recovery phases. METHODS: Fifty-one individuals in the acute phase of dengue presenting with warning signs (dengue group) and 49 healthy individuals without a history of dengue or hepatobiliary disease (control group) were studied with abdominal US and a GB contractility study. RESULTS: Statistical differences in US measurements of the liver (right lobe, P = .012; left lobe, P = .001) and spleen (P = .008) dimensions, GB wall thickness (P < .001), and the GB emptying fraction (P < .001) were observed in dengue during the acute phase compared with the control group. After 60 days, abdominal US of the dengue group showed a statistical difference in liver (right lobe, P < .001; left lobe, P = .078) and spleen (P < .001) dimensions, GB wall thickness, and the GB emptying fraction (P < .001) compared with the results obtained during the acute phase. Furthermore, a statistical difference in the spleen volume and GB emptying fraction (P < .001) was observed when comparing dengue after clinical recovery and the control group. Abdominal pain in patients with dengue was positively associated with hepatomegaly (P = .031), splenomegaly (P = .008), increased GB wall thickness (P = .016), and a reduced GB emptying fraction (P = .038) during the acute phase and with splenomegaly (P = .001) and a reduced GB emptying fraction (P = .003) after clinical recovery. CONCLUSIONS: Abdominal US with a GB motor function test can be used as a diagnostic tool in patients with dengue during acute and recovery phases.

New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.

CONTEXT: Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility. EVIDENCE ACQUISITION: The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility. EVIDENCE SYNTHESIS: Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder. CONCLUSIONS: GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials.

Neutrophils injure gallbladder interstitial Cajal-like cells in a guinea pig model of acute cholecystitis.

Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.

Choledocholithiasis in elderly patients with gallbladder in situ - is ERCP sufficient?

INTRODUCTION: Along with increased life expectancy, the proportion of elderly patients with choledocholithiasis will increase and with this, the need for endoscopic cholangiopancreatography (ERCP). Current recommendations suggest laparoscopic cholecystectomy in all patients with choledocholithiasis to prevent biliary events. However, adherence to these recommendations is low, especially in older patients. METHODS: Retrospective study that included non-cholecystectomized patients aged > =75 years who underwent ERCP for choledocholithiasis from 2013-2016 (n = 131). A new biliary event was defined as the need for a new ERCP, cholecystitis, cholangitis or gallstone pancreatitis. AIM: The aim of this study was to compare the outcomes of new biliary events and mortality in cholecystectomized vs non-cholecystectomized patients after ERCP. RESULTS: Cholecystectomy was performed in 22% of the patients (92% laparoscopic). The post-cholecystectomy complication rate was 13% and the mortality rate was 7%. During the follow-up period (669 ± 487 days) a new biliary event occurred in 20% of patients - 10% new ERCP, 9% cholecystitis, 9% cholangitis and 2% pancreatitis. Cholecystectomized patients had fewer events (7% vs 24%, p = .048) and longer time to event (p = .016). There was no statistically significant difference in all-cause mortality (14% vs 27%, p = .13), mortality related to lithiasis (0% vs 9%, p = .11) or time to mortality from all causes (p = .07) and related to biliary events (p = .07). CONCLUSIONS: In this group of elderly patients, cholecystectomy after ERCP prevented the occurrence of new biliary events but resulted in a non-statistically significant difference in mortality.

Pediatric Biliary Dyskinesia: Evaluating Predictive Factors for Successful Treatment of Biliary Dyskinesia with Laparoscopic Cholecystectomy.

Biliary dyskinesia (BD) is a motility disorder of the gallbladder that can result in right upper quadrant (RUQ) pain, nausea, vomiting, and diarrhea. Cholecystectomy is considered the standard of care for BD. Up to 23 per cent of pediatric patients who undergo surgery for BD have persistent symptoms postoperatively. We performed a retrospective review to identify preoperative factors significantly associated with symptom resolution after cholecystectomy. We retrospectively reviewed pediatric patients aged 10-17 years diagnosed with BD who underwent cholecystectomy between 2006 and 2016. Patients were divided into two groups based on postoperative symptom resolution. Chi-squared and student t tests were used to compare patient groups. Two hundred and thirty-six patients were included in the study. The most common preoperative symptoms included RUQ pain (80.1%), nausea (54.2%), postprandial pain (44.5%), vomiting (32.6%), and epigastric pain (19.9%). The rate of postoperative symptom resolution was 68.6 per cent. Comparative analysis showed patients who presented with RUQ pain, nausea, postprandial pain, or constipation experienced significantly higher rates of symptom resolution postoperatively. In addition, patients with ejection fraction <35 per cent or pain reproducible with cholecystokinin were found to have significantly higher rates of symptom resolution as well. To date, it remains difficult to predict successful outcomes for pediatric patients undergoing cholecystectomy for BD. In our study, patient demographics and duration of symptoms did not affect postoperative outcomes. Pediatric patients who presented with RUQ pain, nausea, postprandial pain, constipation, an ejection fraction of <35 per cent on hepatobiliary iminodiacetic acid, or pain reproducible with cholecystokinin injection, were found to have significantly higher rates of symptom resolution.

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.

Advanced gallbladder inflammation is a risk factor for gallbladder perforation in patients with acute cholecystitis.

Background: Acute perforated cholecystitis (APC) is probably the most severe benign gallbladder pathology with high rates of morbidity and mortality. The cause of APC has not been fully understood. We postulated that APC is a complication of advanced gallbladder inflammation. The aim of this study was to investigate the extent of gallbladder inflammation in patients with APC. Methods: Patients with intraoperative and histopathologic diagnosis of APC were compared with cases with acute cholecystitis without perforation with respect to the extent of inflammation on histopathology as well as surgical outcomes. Results: Fifty patients with APC were compared to 150 cases without perforation. Advanced age > 65 years and elevated CRP were confirmed on multivariate analysis as independent risk factors for APC. Advanced gallbladder inflammation was seen significantly more often in patients with APC (84.0 vs. 18.7%). Surgery lasted significantly longer 131.3 ± 55.2 min vs. 100.4 ± 47.9 min; the rates of conversion (22 vs. 4%), morbidity (24 vs. 7%), and mortality (8 vs. 1%) were significantly higher in patients with APC. ICU management following surgery was needed significantly more often in the APC group (56 vs. 15%), and the overall length of stay (11.2 ± 12.0 days vs. 5.8 ± 6.5 days) was significantly longer compared to the group without perforation. Conclusion: Acute gallbladder perforation in patients with acute cholecystitis represents the most severe complication of cholecystitis. Acute perforated cholecystitis is a sequela of advanced gallbladder inflammation like empyematous and gangrenous cholecystitis and is associated with poor outcome compared to non-perforated cases.