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Background: The most common indication for cholecystectomy in children is cholelithiasis, and routine histopathological examination is performed on all gallbladder specimens. Currently, selective histopathological examination is suggested instead of routine examination due to the low frequency of gallbladder cancer in adults. The purpose of this study was to evaluate the indications, clinical, laboratory and histopathological findings of the cholecystectomy in children. We also questioned the contribution and cost-effectiveness of routine histopathological evaluation in diagnosis and treatment., Methods: A total of 114 children underwent cholecystectomy between the years 2008 and 2022. The clinical findings, laboratory, and imaging results of the patients and histopathological findings of the gallbladder specimens were evaluated retrospectively., Results: Cholelithiasis were diagnosed in 71%, choledochal malformation in 15.8%, hydrops of gallbladder and/or biliary sludge in 12.3%, and hypoplasia of gallbladder in 0.9% of the patients. Histopathologically significant findings were observed in only 3 patients (2.6%); adenomyomatosis in 2 and angiodysplasia and pyloric metaplasia in 1. While the cost of a cholecystectomy and histopathologic examination combined amounted to 27.77% of the minimum wage in Türkiye in 2024, the histopathologic examination alone constitutes just 0.67% of the minimum wage and 2.4% of the operation fee., Conclusion: In children undergoing cholecystectomy, histopathological examination does not provide any significant contribution to the patient's diagnosis and follow-up management. In children, selective gallbladder histopathological examination might reduce health costs and save time for pathologists., Competing Interests: The authors declare that there is no conflict of interest.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation., (© 2024. The Author(s).)

Cholelithiasis, commonly known as gallstones, represents a prevalent hepatobiliary disorder. This study aimed to elucidate the therapeutic role and mechanism of Danyankang capsulein treating cholelithiasis induced by a high-fat diet in C57BL/6 mice. The therapeutical potential of Danyankang was assessed through biochemical analyses, histopathological examinations, protein detection, and 16S rDNA sequencing. A high-fat diet resulted in cholelithiasis manifestation in mice, with discernable abnormal serum biochemical indices and disrupted biliary cholesterol homeostasis. Danyankang treatment notably ameliorated liver inflammation symptoms and rectified serum and liver biochemical abnormalities. Concurrently, it addressed biliary imbalances. Elevated expressions of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB)/pNF-κB, HMGCR, CYP7A1, and CYP8B1 observed at the inception of cholelithiasis, were notably reduced upon Danyankang administration. Furthermore, 16S rDNA analysis revealed a decline in species number and diversity of the intestinal flora in cholelithiasis-treated mice, while the decline was reversed with Danyankang treatment. Danyankang capsules reduced the abundance of Verrucomicrobiota and increased the abundance of Actinobacteriota and Proteobacteria. In conclusion, the present study demonstrates that Danyankang exerts potent therapeutic efficacy against high-fat diet-induced cholelithiasis. This beneficial outcome is potentially linked to the inhibition of the TLR4/pNF-κB and SHP/CYP7A1/CYP8B1 signaling pathways, as well as the enhancement of intestinal flora species abundance.

Background: Cholecystectomy is routinely performed during living donor hepatectomy both to see the structure of the biliary tract and to determine the demarcation line based on the biliary tract junction. This study aims to present the general histopathological features of the gallbladder specimen obtained from living liver donors (LLD)., Methods: Data from 2577 LLDs who underwent living donor hepatectomy (n = 2511) or aborted living donor hepatectomy (n = 66) in our Liver Transplantation Institute between September 2005 and June 2021 were analyzed retrospectively. Age, gender, macroscopic (length, diameter, and wall thickness), and microscopic (histopathological) features of the gallbladder of the LLDs were recorded for use in this study., Results: A total of 2493 LLDs (men: 1486, women: 1007) with a median age of 29 years (interquartile range [IQR]: 13) met the inclusion criteria in this study. The median length, width and wall thickness of the gallbladder specimens were measured as 70 mm (IQR: 20), 50 mm (IQR: 20), and 2 mm (IQR: 1), respectively. The most common histopathological findings are normal structure (2026; 81.3%), chronic cholecystitis (n = 446; 17.9%), adenomyomatosis (n = 9), and papillary hyperplasia (n = 6), respectively. The most common pathologic findings in the gallbladder lumen are cholesterolosis (n = 207; 0.4%), cholelithiasis (n = 53), cholesterol polyp (n = 31), and noncholesterol polyp (n = 19), respectively. Significant differences were detected between the male and female genders in terms of age (P < .001), height (P < .001), weight (P < .001), body mass index (P < .001), gallbladder width (P = .001), gallbladder length (P < .001), histopathological finding (content) (P < .001), and lymph node around the gallbladder (P = .015)., Conclusions: The results we obtained in this study are true gallbladder pathologies that can be detected in healthy people. In this study, it was shown that the diameter and size of the gallbladder were larger in men, whereas the incidence of cholesterolosis and cholelithiasis was higher in women., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To identify any concomitant complications other than bleeding (COTB) before and after endoscopic treatment of esophagogastric variceal bleeding (EGVB) in liver cirrhosis patients and explore the underlying risk factors., Materials and Methods: Cirrhotic patients complicated with EGVB, who underwent interventional endoscopic treatments in our hospital from November 2017 to August 2020, were enrolled in this study. Clinical data were retrospectively analyzed for COTB at admission and within 2 years of the first endoscopic treatment. Patients were screened for potential risk factors of COTB before and after the treatment. Univariate analysis was performed to identify clinical factors of secondary complications, and statistically significant factors were included in the multivariate Cox and logistic regression analyses., Results: Of the 547 patients with cirrhosis, 361 individuals had COTB in the first endoscopic treatment. In this cohort, the top 3 prevalent incidences were portal vein thrombosis (PVT) or spongiosis, cholelithiasis, and pathogenic infections. The COTB did not occur at admission in 171 liver cirrhosis patients but happened at the follow-up. Higher Child-Pugh scores indicated potential risks of multiple concurrent complications, including bleeding. Risk factors for concomitant PVT or cavernous changes after endoscopic treatment of EGVB, pathogenic infections, and cholelithiasis could prolong the cirrhosis symptoms, while noncholestatic cirrhosis patients might have a lower risk than posthepatitis B cirrhosis patients, in the context of a higher degree of EGV and serum level of D-D and a lower blood calcium level., Conclusions: Clinical treatment and interventions can be tailored to avoid other complications during and after EGVB treatment, which can affect the outcome and prognosis of bleeding symptoms., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Xiaowei Duan et al.)

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Sickle cell anaemia affects about 4 million people across the globe, making it an inherited disorder of public health importance. Red cell lysis consequent upon haemoglobin crystallization and repeated sickling leads to anaemia and a baseline strain on haemopoiesis. Vaso-occlusion and haemolysis underlies majority of the chronic complications of sickle cell. We evaluated the clinical and laboratory features observed across the various clinical phenotypes in adult sickle cell disease patients., Methods: Steady state data collected prospectively in a cohort of adult sickle cell disease patients as out-patients between July 2010 and July 2020. The information included epidemiological, clinical and laboratory data., Results: About 270 patients were captured in this study (165 males and 105 females). Their ages ranged from 16 to 55 years, with a median age of 25 years. Sixty-eight had leg ulcers, 43 of the males had priapism (erectile dysfunction in 8), 42 had AVN, 31 had nephropathy, 23 had osteomyelitis, 15 had osteoarthritis, 12 had cholelithiasis, 10 had stroke or other neurological impairment, 5 had pulmonary hypertension, while 23 had other complications. Frequency of crisis ranged from 0 to >10/year median of 2. Of the 219 recorded, 148 of the patients had been transfused in the past, while 71 had not., Conclusion: The prevalence of SLU, AVN, priapism, nephropathy and the other complications of SCD show some variations from other studies. This variation in the clinical parameters across different clinical phenotypes indicates an interplay between age, genetic and environmental factors.

Background: Thyroid hormone (TH) deficiency has been associated with increased cholesterol gallstone prevalence. Hypothyroidism impacts hepatic lipid homeostasis, biliary secretion, gallbladder motility, and gallstone (LITH) gene expression, all potential factors contributing to cholesterol gallstone disease (CGD). However, how TH deficiency may lead to gallstone formation is still poorly understood. Therefore, we performed molecular studies in a CGD mouse model under lithogenic conditions and modulation of TH status. Methods: Male, three-month-old C57BL/6 mice were randomly divided into a control (euthyroid) group, a hypothyroid (hypo) group, a gallstone (litho) group, and a gallstone+hypothyroid (litho+hypo) group and were treated for 2, 4, and 6 weeks ( n  = 8/treatment period). Gallstone prevalence, biliary composition and cholesterol crystals, hepatic expression of genes participating in cholesterol, bile acid (BA), and phosphatidylcholine synthesis ( Hmgcr , Cyp7a1 , Pcyt1a ), and canalicular transport ( Abcg5 , Bsep , Abcb4 ) were investigated. Results: Increased cholesterol gallstone prevalence was observed in hypothyroid mice under lithogenic diet after 4 and 6 weeks of treatment (4 weeks: 25% vs. 0%; 6 weeks: 75% vs. 37.5%). Interestingly, neither the composition of the three main biliary components, cholesterol, BAs, and phosphatidylcholine, nor the hepatic expression of genes involved in synthesis and transport could explain the differences in cholesterol gallstone formation in the mice. However, TH deficiency resulted in significantly increased hydrophobicity of primary BAs in bile. Furthermore, downregulation of hepatic sulfonation enzymes Papss2 and Sult2a8 as well as diminished biliary BA sulfate concentrations in mice were observed under hypothyroid conditions all contributing to a lithogenic biliary milieu as evidenced by microscopic cholesterol crystals and macroscopic gallstone formation. Conclusions: We describe a novel pathogenic link between TH deficiency and CGD and suggest that the increased hydrophobic character of biliary BAs due to the diminished expression of hepatic detoxification enzymes promotes cholesterol crystal precipitation and enhances cholesterol gallstone formation in the bile of hypothyroid mice.

Background: Rapid weight loss is associated with a high incidence of cholelithiasis., Objectives: To identify the incidence of gallstone formation after weight loss surgery and to detect the efficacy of 6 months regimen of prophylactic Ursodeoxycholic acid (UDCA)., Methods: RCT included a total of 1530 morbid obese patients who were subjected to either laparoscopic one anastomosis gastric bypass (OAGB), sleeve gastrectomy (SG), or greater curve plication (GCP). Patients with previous or concomitant cholecystectomy and missed follow-up were excluded, leaving 1432 patients to analyze. They were randomly allocated into two groups receiving either UDCA or placebo with a minimum follow-up of one year for assessment of cholelithiasis and weight loss., Results: The overall incidence of cholelithiasis after surgery was 9.7%. There was a significant decrease in the incidence of gallstone formation from 22% in placebo to 6.5% in treated group with UDCA. The mean percentage of excess weight loss (%EWL) was significantly higher in those who develop gallstones than others. Of those developing gallstones, there was 64.7 % with SG versus 28.1% and 7.2% in OAGB and GCP, respectively, which is statistically significant. NNT to prevent cholelithiasis is six, AR% is 70.4%, and RR is 3.4%., Conclusions: Cholelithiasis after SG and OAGB was higher than GCP. %EWL was rapid and higher in OAGB and SG contributing to the higher rate of symptomatic cholelithiasis and could be predictive for post-bariatric cholelithiasis. A 6-month use of UDCA is an effective prophylaxis decreasing gallstone formation after bariatric surgery at short-term follow-up.

Cholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10-20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.

Objective: to describe the histological findings of the gallbladders of patients undergoing cholecystectomy and to evaluate the presence of factors associated with gallbladder incidental cancer., Methods: we conducted a descriptive, cross-sectional, observational study with 1,278 histopathological exams of gallbladders coming from cholecystectomy for cholelithiasis and of their reports, held from January 2008 to December 2017., Results: the most common pathological finding was chronic cholecystitis, present in 1,251 patients (97.8%), followed by gallbladder cholesterolosis, in 131 (10.2%). Gallbladder cancer was identified in six patients, with a prevalence of 0.5% in this sample. There was a significant association between the presence of cancer and age ≥60 years and wall thickness ≥0.3cm., Conclusion: there was low prevalence of gallbladder cancer in this population, higher occurrence in the elderly and association of the tumor with gallbladder wall thickness.

Background: Carcinogen metabolism pathway and tumor suppressor gene polymorphisms have been reported to be associated with increased gallbladder cancer risk. However, the association of genetic variants and gallbladder cancer risk in Indians are not well studied. We examined whether genetic polymorphisms of metabolic enzymes cytochrome P450 1A1 and glutathione S-transferase and tumor suppressor gene p53 (TP53) are associated with an increased risk of gallbladder cancer in North Indians., Methods: This hospital-based case-control study was conducted in 96 gallbladder cancer patients with gallstones (cases) and 93 cholelithiasis patients (controls) at the Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India from July 2014 through May 2017. Genomic DNA was extracted from white blood cells of each patient using a simple salting-out procedure. The genotypic frequencies of CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 polymorphisms were investigated using TaqMan SNP Genotyping Assay and GSTM1 and GSTT1 polymorphisms were analyzed using the multiplex PCR assay., Results: The frequency of CC genotype of TP53 rs1042522 polymorphism was 27.1% (26/96) in cases and 12.9% (12/93) in controls. The CC genotype was associated with an increased risk of gallbladder cancer in North Indians (age- and sex-adjusted odds ratio, 2.81; 95% confidence interval, 1.19-6.61; P = 0.02). No significant differences in genotypic and allelic frequencies of the metabolic pathway gene polymorphisms were found between cases and controls., Conclusions: Our data provide preliminary evidence that the CC genotype of the TP53 rs1042522 polymorphism may be associated with an increased risk of gallbladder cancer in North Indians.

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., Competing Interests: The authors have declared that no competing interests exist.

Follicular cholecystitis (FC) is a relatively rare entity with uncertain causal associations. In this study, we aimed to explore different clinicopathologic associations of FC, and to better characterize the entity. A retrospective review of archival hematoxylin and eosin slides and pertinent clinical information was undertaken for all cholecystectomy cases with a rendered diagnosis of "follicular cholecystitis," from 1991 to 2017. Concurrent conventional chronic cholecystitis (CC) and lymphocytic cholecystitis (LC) were documented. Forty-three consecutive patients were confirmed to have FC. The majority of the patients (88.4%) had at least one other histologic association in the gallbladder (LC, CC, or both). Remarkably, functional distal biliary obstruction (from choledocholithiasis, sclerosing cholangitis, distal biliary strictures, or malignancies of the pancreatic head or ampulla) was found in 76.7% of the patients, irrespective of the presence of other concurrent histologic findings. FC associated with CC was relatively more common in females (61%) and strongly associated with cholelithiasis (70%). However, those without CC were predominantly males (70%) and had a significant association with LC (75%). All four cases of FC without any other histologic associations who had clinical information available showed some form of distal biliary obstruction. FC cases without concurrent LC were often associated with CC (74%). FC is strongly associated with extrahepatic biliary obstruction distal to the gallbladder. Therefore, this finding at routine cholecystectomy may warrant further evaluation to rule out a cause for distal biliary tract obstruction. Additionally, it is commonly associated with other concomitant histologic abnormalities in the gallbladder such as CC and/or LC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Gallbladder cancer (GBC) is a fatal condition with dismal prognosis and aggressive local invasiveness; and with uncharacterised molecular pathology relating to non-specific therapeutic modalities. Given the importance of oxidative stress in chronic diseases and carcinogenesis, and the lacunae in literature regarding its role in gallbladder diseases, this study aimed to study the involvement of oxidative stress and deregulation in the base excision repair (BER) pathway in the pathogenesis of gallbladder diseases including GBC. This study involved patients from the North-East Indian population, where the numbers of reported cases are increasing rapidly and alarmingly. Oxidative stress, based on 8-OH-dG levels, was found to be significantly higher in gallbladder anomalies (cholelithiasis [CL] and cholecystitis [CS]) and GBC at the plasma and DNA level, and was associated with GBC severity. The expressions of key BER pathway genes were downregulated in gallbladder anomalies and GBC compared to controls, and in GBC compared to both non-neoplastic controls and gallbladder anomalies. Expression of XRCC1 and hOGG1 was significantly associated with both susceptibility and severity of GBC. The XRCC1 codon280 polymorphism was associated with disease susceptibility; and significantly higher oxidative stress was observed in hOGG1 genotypic variants. The genomes of GBC patients were found to be more hypermethylated compared to controls, with the promoters of XRCC1 and hOGG1 being hypermethylated and, therefore, being silenced. This study underlined the prognostic significance of the oxidative stress marker 8-OH-dG and BER pathway genes, especially hOGG1 and XRCC1, in gallbladder anomalies and GBC, as well as stated their potential for therapeutic targeting.

Objective: Ultrasound (US) evaluation of biliary pathology can be influenced by a variety of factors. This study examines the effect of patient specific factors on the accuracy of sonographic evaluation of gallbladder wall thickness (GBW)., Methods: We performed a retrospective review of all patients who underwent cholecystectomy at a single institution from November 2012 to October 2015. GBW measured on US was compared with pathology results. Results were analyzed in relation to patient specific factors to include BMI, age, presence of diabetes, sex, and urgent versus elective cases., Results: In total 601 patients underwent cholecystectomy, 484 of which had paired preoperative US GBW measurement and postoperative pathologic specimen measurement. No significant difference in accuracy or precision of US measurement of the GBW based on BMI was found. Accuracy was not related to age, sex, urgency, or diabetes. Precision decreased with pathologic thickening, age, male sex, and urgent case performance., Conclusions: US is accurate in measuring GB wall thickness regardless of patient specific factors. A nonsignificant trend exists with decreased precision with pathologic thickening, age, male sex, and urgently performed cases.

Interstitial cells of Cajal (ICC) were first described by Santiago Ramon y Cajal over 100 years ago. They are thought to play an important role in the regulation of gastrointestinal motility. There is increasing evidence that the decline in their number in the gallbladder wall contributes to the formation of concrements. The aim of the study was to determine the exact location of interstitial cells of Cajal in the gallbladder wall in patients with calculous and non-calculous cholecystitis. Sixty-eight patients were examined, of whom 50 were cases of cholelithiasis and 18 were of non-calculous cholecystitis. The technique of immunohistochemistry with the CD117 antibody was used to determine the cells of Cajal, while to distinguish them from mast cells the technique with mast cell tryptase (MCT) was applied. Redistribution of the interstitial cells of Cajal from the muscle membrane to lamina propria of mucous tissue was observed in the cases of cholelithiasis, while in the group of non-calculous cholecystitis most of the ICC was located within the muscle tissue.

Introduction: A reduced number of interstitial Cajal-like cells (ICLCs) in the gallbladder have been proposed to play a role in the pathogenesis of cholelithiasis. Therefore, this prospective study was conducted to investigate the relationship between gallbladder contractility and the number of gallbladder ICLCs in patients with cholelithiasis., Material and Methods: Patients admitted to the Department of Hepatobiliary Surgery for cholecystectomy were divided into the cholelithiasis (n = 18) and non-cholelithiasis (n = 8) groups based on their clinical data. Patients' clinical data were collected on admission, and B-mode ultrasonography was performed to assess their gallbladder contractility. The resected gallbladder specimens were fixed, paraffin sections mounted on slides, and the immunofluorescence staining with the anti-human CD-117 and anti-human tryptase antibodies was performed to identify ICLSs and mast cells, respectively. The number of ICLCs was counted in 10 high-power fields (HPFs) randomly., Results: Independent sample t-tests revealed differences between the cholelithiasis and non-cholelithiasis groups in the number of ICLCs (mean ± standard deviation: 88.61 ± 28.22 vs. 115.89 ± 27.87 per HPFs, P = 0.032) and gallbladder contractility (43.94% ± 18.50% vs. 61.00% ± 20.50%, P = 0.046). Pearson and Spearman cor-relation analyses revealed no significant correlation between the number of ICLCs and gallbladder contractility., Conclusion: The results suggest that the number of gallbladder ICLCs in the wall of the gallbladder of patients with or without cholelithiasis is not a decisive factor affecting gallbladder contractility.

Purpose: Gallbladder cancer is a highly mortal disease with poor prognosis because of late presentation of disease. Survivin and X-linked inhibitor of apoptosis (XIAP) are one of the two important members of inhibitors of apoptosis. Thus, this study aimed to look at the expression of Survivin and XIAP in gallbladder cancer patients., Methods: Survivin and XIAP expression were investigated in tissues of gallbladder cancer patients (40 cases) and compared with cholelithiasis as control (40 cases) by using immunohistochemistry. Their expression was correlated with clinicopathological parameters., Results: Significantly higher (p < 0.05), Survivin protein was expressed in gallbladder cancer (n = 67.5%) than control (n = 35%). But it did not show any significant association with any of the clinicopathological parameter while XIAP was not expressed in the GBC patients (p > 0.05)., Conclusion: Overexpression of Survivin in gallbladder cancer suggests its possible role and association with poor prognosis. But XIAP has not been found to be associated with gallbladder carcinogenesis.

Introduction: The incidence of gallstone disease is increasing and represents a strain on healthcare systems worldwide. Following cholecystectomy, gallbladder specimens are generally submitted for histopathologic examination and the diagnostic yield of this strategy remains questionable. This study aimed to evaluate the usefulness of routine pathologic examination of the gallbladder specimens and investigate the results of routine postoperative follow-up visits., Methods: All cholecystectomies performed between January 2011 and July 2017 at a single center were evaluated. All gallbladder specimens were routinely pathologically examined. The outcome parameters were the macro- and microscopic gallbladder anomalies at pathology and the reported symptoms during routine follow-up visits 2-6 weeks after surgery., Results: In the study period a total of 2763 patients underwent cholecystectomy, of which 2615 had a postoperative visit in the outpatient clinic. Seventy-three patients (3%) complained of persistent abdominal pain, and 29 of these patients were referred for further treatment, resulting in a resolution of symptoms in 97%. Of all gallbladder specimens, 199 (7%) displayed macroscopic anomalies and in four (2%) of these, gallbladder carcinoma was diagnosed., Discussion: Selective pathologic examination of gallbladder specimens in case of macroscopic anomalies appears justified. Also routine follow-up after cholecystectomy appears not useful since 97% of patients do not report any symptoms at follow-up. A selective pathology and follow-up strategy could save significant healthcare costs.

BACKGROUND In patients with end-stage renal disease, cholelithiasis is observed with an increased frequency. In transplant recipients, symptoms might be obscured, which may delay the diagnosis and lead to complications. The aim of our study was to evaluate the frequency of gallbladder pathologies in kidney transplant recipients (KTRs) in the Caucasian population, and to discuss the potential benefits of prophylactic cholecystectomy before kidney transplantation (KT). MATERIAL AND METHODS Data from 434 patients who underwent KT was analyzed. Demographic data along with gallbladder status were collected from the pre-transplantation charts. We compared our results to data from the general Polish population. RESULTS In our analyzed group of KTRs, there were 284 men and 150 women. Complete data, including abdominal ultrasound description, were available in 412 cases. In this group, 36 patients (8.74%) underwent cholecystectomy before KT. Other gallbladder pathologies (gallstones and polyps) were found in 41 patients (9.95%) at pre-transplantation evaluation. The incidence of gallbladder pathologies in KTRs, being mostly cholelithiasis, was higher than in the general Polish population. CONCLUSIONS In specific age subgroups of KTRs, the frequency of gallbladder pathologies was higher than in the general population. Prophylactic cholecystectomy may potentially offer benefits in these subgroups of patients.

A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal-like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles in physiological and pathophysiological processes., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Purpose: To compare anthropometric data (body mass index [BMI]) in patients without lithiasis to patients with symptomatic simple cholelithiasis or choledocholithiasis., Methods: We retrospectively reviewed data from 147 patients undergoing laparoscopic cholecystectomy between 2001-2015. Complete growth data from 98 patients was compared with anthropometric data from the population of the Czech Republic and a control group (BMI of 100 consecutive patients without biliary stones in abdominal ultrasound who were admitted to a surgical department for suspected appendicitis)., Results: The BMI of 75 children with simple cholelithiasis and 23 with choledocholithiasis was compared to the standard Czech pediatric population and to the control group. The median age (simple cholelithiasis and choledocholithiasis) was 16 years, and 35 patients (24%) had a family history of gallstones. Types of lithiasis included multiple (n = 120), solitary (n = 11), and sludge (n = 10). Five cases had polyps and one had gallbladder dysplasia. Patients with simple cholelithiasis had significantly higher BMI compared to the control group without cholelithiasis (p<0.0001) and the standard Czech population (p = 0.03). Patients with choledocholithiasis had a mean BMI significantly higher than that of the general population (p = 0.001) and the control group (p = 0.0001). Patients with choledocholithiasis had significantly higher BMI than those with simple cholelithiasis (p = 0.03)., Conclusion: Patients with cholelithiasis had significantly higher BMI than the general population, and patients with choledocholithiasis had significantly higher BMI than patients with simple lithiasis. Elevated BMI is a risk factor for developing choledocholithiasis. ERCP and early laparoscopic cholecystectomy in patients with choledocholithiasis offer equivalent outcomes in patients with simple cholelithiasis.

Salmonella typhi and Helicobacter infections have been shown to increase risk of gallbladder cancer (GBC), but findings have been inconsistent. Other bacterial infections may also be associated with GBC. However, information on microbial pathogens in gallbladder bile of GBC patients is scarce. We aimed to investigate the microbial communities in gallbladder bile of patients with GBC and cholelithiasis (CL). Seven GBC patients and 30 CL patients were enrolled in this study. Genomic DNA was extracted from bile and the V3-V4 region of 16S rRNA was amplified. The sequencing results were compared with the 16S database, and the bacteria were identified by homology searches and phylogenetic analysis. DNA was detected in the bile of three GBC (42.9%; Bolivia, 1; Chile, 2) and four CL patients (13.3%; Bolivia, 1; Chile, 3). Of the 37 patients, 30 (81.1%) were negative and unable to analyze. Salmonella typhi and Helicobacter sp. were not detected in bile from any GBC patients. As the predominant species, Fusobacterium nucleatum, Escherichia coli, and Enetrobacter sp. were detected in bile from GBC patients. Those in bile from CL patients were Escherichia coli, Salmonella sp., and Enerococcus gallinarum. Escherichia coli was detected in bile samples from both GBC and CL patients. Whether the bacteria detected in bile from GBC patients would associated with the development of GBC warrant further investigation., (Creative Commons Attribution License)

Bile acids or bile salts, belong to a large family of biological steroid derivatives found predominantly in the bile of mammals and other vertebrates. These amphipathic molecules possess numerous functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate catabolites, emulsifying fat-soluble vitamins to enable their absorption, aiding in motility and in reducing the bacteria flora found in the small intestine and biliary tract. In this review, we investigate progress towards synthetic bile acid derivatives, with special emphasis on how they might be used for various biological applications and the challenges that remain in developing these compounds as potent drugs of the future especially in the field of microbiology (antimicrobial activities) and cancer (anticancer agents). We will emphasize the fact that even few researches are devoted around these peculiar structures. All the researches pointed out the important potential of such derivatives for the design of new classes of drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

There is a well-established link between biliary tract cancers (BTC) and chronic inflammatory conditions such as primary sclerosing cholangitis, chronic cholecystitis, chronic cholelithiasis, liver fluke-associated infestations, and chronic viral hepatic infections. These associated risk factors highlight the potential for development of immune-modulatory agents in this poor-prognostic disease group with limited treatment options. Clinical trials have evaluated the role of immune cells, inflammatory biomarkers, vaccines, cytokines, adoptive cell therapy, and immune checkpoint inhibitors in patients with BTC. Although these have demonstrated the importance of the immune environment in BTC, currently none of the immune-based therapies have been approved for use in this disease group. The role of immunomodulatory agents is a developing field and has yet to find its way 'from bench to bedside' in BTC., (© 2018 S. Karger GmbH, Freiburg.)

Background: Multiport laparoscopic cholecystectomy is the standard surgical procedure for symptomatic gallbladder diseases. The latest evolution is single incision laparoscopic cholecystectomy (SILC). Single-site robotic cholecystectomy (SSRC) overcomes several limitations of manual SILC. The aim of this study is to present our initial experiences in SSRC and to compare its clinical outcomes with those of SILC., Methods: This study retrospectively reviewed data for patients who received SSRC or SILC from February 2014 to September 2015. The following variables were analyzed: age, sex, body mass index, indications, pain scale, length of stay, and complications. The data were analyzed with Student t test or by Fisher exact test., Results: The analysis included 51 SSRC (33 women, 18 men) and 63 SILC patients (40 women, 23 men). Patients in both groups had similar demographic features and indications for surgery. The SSRC group required no conversions to conventional laparoscopy and no additional trocars, whereas the SILC group had two (3.17%) cases. Length of stay did not significantly differ between the SSRC and SILC groups (4.29 ± 0.72 vs. 4.13 ± 0.93 days, respectively; p = 0.823). However, the SSRC group had shorter operative time (71.30 ± 48.88 vs. 74.70 ± 30.16 minutes; p = 0.772), less perioperative bile spillage (9.81% vs. 19.05%; p = 0.189), and less postoperative bile leakage (0% vs. 3.17%; p = 0.501). However, the parameters mentioned above were not statistically significant, whereas pain scale scores were significantly lower in the SSRC group (2.11 ± 0.76 vs. 3.98 ± 0.84; p < 0.01)., Conclusions: Both SSRC and SILC are safe and feasible procedures for performing single incision cholecystectomy. SSRC, however, has the advantage of significantly decreased postoperative pain., (Copyright © 2016. Published by Elsevier Taiwan.)

Despite the overwhelming prevalence of cholelithiasis, many health care professionals are not familiar with the basic pathophysiology of gallstone formation. This article provides an overview of the biochemical pathways related to bile, with a focus on the physical chemistry of bile. We describe the important factors in bile synthesis and secretion that affect the composition of bile and consequently its liquid state. Within this biochemical background lies the foundation for understanding the clinical and sonographic manifestation of cholelithiasis, including the pathophysiology of cholesterol crystallization, gallbladder sludge, and gallstones. There is a brief discussion of the clinical manifestations of inflammatory and obstructive cholestasis and the impact on bile metabolism and subsequently on liver function tests. Despite being the key modality in diagnosing cholelithiasis, ultrasound has a limited role in the characterization of stone composition.

An 18-year-old man presented with spontaneous severe epigastric pain, progressing and radiating to back since 3 days. It was associated with epigastric tenderness, bilious vomiting and jaundice. He had been intermittently experiencing these symptoms for the last 1 year. No known comorbid. Ultrasound showed a poorly visualised heterogeneous focus at porta hepatis; considering poor visualisation, this might represent an enlarged calcified lymph node or cystic duct calculus causing extrinsic compression or a large sludge ball within the common bile duct (CBD), leading to dilatation of common hepatic duct and intrahepatic biliary system. Subsequent magnetic resonance cholangiopancreatography revealed a focal saccular dilatation of middle part of CBD, a type I-B choledochal cyst, large heterogeneous focus seen within it representing choledochocystolithiasis. Later, CT was performed for further characterisation of surrounding anatomy and pathology, which confused the appearance of choledochocystolithiasis for Mirizzi syndrome. Later, surgery and histopathology confirmed type I-B choledochocystolithiasis and chronic cholecystitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

High-grade dysplasia (HGD) of the cystic duct margin without evidence of concurrent malignancy is a rare occurrence. We present a case of a 36-year-old woman who developed gallstone pancreatitis and subsequently underwent a laparoscopic cholecystectomy. On histopathology, she was found to have HGD at the cystic duct margin. Following evaluation, she underwent excision of the cystic duct remnant with no malignancy being present on final pathology. We present this case to discuss the management of cystic duct dysplasia in the absence of gallbladder malignancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

With an increased number of pet reptiles, many diseases occur due to nutritional disorders. Between 2013 and 2015, irregular gallbladder contents (sludge/choleliths) in adult bearded dragons (Pogona vitticeps) were recorded in many of the routinely conducted necropsies at the reptile rescue station in Munich (Auffangstation für Reptilien, München e.V., Munich, Germany). Nine animals, six from the rescue station and three from an associated veterinary practice (Tierärztliche Praxis für Exoten, Augsburg, Germany), were studied. Gallbladder contents from all animals were analysed at the Institute for Clinical Chemistry in Zurich, Switzerland. In three of nine animals, one cholelith composed of 100% calcium carbonate (CaCO 3 ) was detected and it precipitated either as pure calcite or as a calcite:vaterite combination. In the remaining six animals, analyses suggested a protein-based material. The detection of choleliths/sludge was not anticipated at necropsy or surgery in eight of nine animals. The diet of the six animals from the rescue station was retrospectively described as mainly insects, whereas the diet of the three animals from the veterinary practice also contained little plant matter. Fed insect species were mealworm larva (Tenebrio molitor), house cricket (Acheta domestica), migratory locust (Locusta migratoria) and zophobas larva (Zophobas morio), all high in protein and fat. In other species, a nidus must be present for CaCO 3 to precipitate. As a protein-based sludge was detected in six gallbladders, it is possible that a high-protein diet could lead to such a nidus and subsequently to cholelith formation. Cholelithiasis seems to be a rising problem in adult bearded dragons and is likely underdiagnosed, as many choleliths were found at necropsy. This rise in cholelithiasis may correlate with an unnatural high-protein, high-fat insect-based diet instead of a balanced plant-based diet., (Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.)

Background: Gallbladder cancer has high incidence in northeastern India; mortality too is high as the disease is often diagnosed late. Numerous studies have shown the role of sonic hedgehog (shh) in different cancers, an important ligand of the hedgehog signaling pathway., Aim: This study was carried out to evaluate the shh gene mutations in gallbladder cancer patients., Methods: PCR-SSCP was performed for shh gene in 50 samples each of gallbladder cancer, cholelithiasis, and control. The samples showing aberration in banding pattern were sequenced., Results: Variation in banding pattern was observed in 20% gallbladder cancer cases, 10% in cholelithiasis, and none of the control (χ 2  = 11.111; p < 0.05). Sequencing results revealed seven novel point mutations in GBC cases. These novel mutations were found to be associated with histopathology (p < 0.05) and stage (p < 0.05) of gallbladder cancer., Conclusion: This study reveals several novel individual and repetitive mutations of shh gene in GBC and cholelithiasis samples that may be used as diagnostic markers for gallbladder carcinogenesis.

Background: Cholecystectomy alters bile release dynamics from pulsatile meal-stimulated to continuous, and results in retrograde duodeno-gastric bile reflux (DGR). Bile is implicated in mucosal injury after gastric surgery, but whether cholecystectomy causes esophagogastric mucosal inflammation, therefore increasing the risk of metaplasia, is unclear., Study Design: This study examined whether cholecystectomy-induced DGR promotes chronic inflammatory mucosal changes of the stomach and/or the esophagogastric junction (EGJ). Four groups of patients were studied and compared with controls. A group of patients was studied before and 1 year after cholecystectomy; 2 further groups were studied long-term post-cholecystectomy (LTPC) at 5 to 10 years and 10 to 20 years. All underwent abdominal ultrasound and upper gastrointestinal endoscopy with gastric antral and EGJ biopsies, noting the presence of gastric bile pooling. Biopsy specimens were stained for Ki67 and p53 overexpression, and the bile reflux index (BRI) was calculated., Results: At endoscopy, bile pooling was observed in 9 of 26 (34.6%) controls, in 8 of 25 (32%) patients pre-cholecystectomy, in 15 of 25 (60%) 1 year post-cholecystectomy patients (p = 0.047), and 23 of 29 (79.3%) LTPC patients (p = 0.001). Bile reflux index positivity at the EGJ increased from 19% of controls through 41% of LTPC patients (p = 0.032). Ki67 was overexpressed at the EGJ in 19% of controls, but in 62% of LTPC patients (p = 0.044); p53 was overexpressed at the EGJ in 19% of controls compared with 66% of LTPC patients (p = 0.001)., Conclusions: Duodeno-gastric bile reflux was more common in patients with gallstones than in controls, and its incidence doubled after cholecystectomy. This was associated with inflammatory changes in the gastric antrum and the EGJ, evident in most LTPC patients. Ki67 and p53 overexpression at the EGJ suggests cellular damage attributable to chronic bile exposure post-cholecystectomy, increasing the likelihood of dysplasia. Further studies are required to determine whether DGR-mediated esophageal mucosal injury is reversible or avoidable, and whether surveillance endoscopy is indicated after cholecystectomy., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cholecystectomy is one of the most commonly performed general surgery procedures in the USA. It is most frequently performed for benign biliary disease such as biliary colic or cholecystitis; however, resected specimens are frequently sent for histopathological analysis due to the perceived risk of incidental gallbladder carcinoma (iGBC). The principle aim of this study is to review the pathology results from gallbladder specimens sent for routine pathology, determine the incidence of iGBC in our population, and determine whether surgeons need to send specimens for further analysis if no preoperative or intraoperative suspicion for malignancy is present., Methods: We performed a large single-center case-controlled retrospective study of all gallbladder specimens sent for routine histopathological analysis between 2009 and 2014. The results were tabulated, including both common and rare findings. We then analyzed patient outcomes and survival for the case group of iGBC patients and determined value in life years (LY) gained per dollar spent on pathological screening., Results: A total of 2153 pathology reports were reviewed. After exclusion criteria, a total of 1984 were included in data analysis. The incidence of iGBC was 0.25 % (95 % CI 0.08, 0.59), and dysplasia was 0.70 % (0.39, 1.20). The most common pathological findings included chronic cholecystitis in 89 % (87.4, 90.3) and cholelithiasis in 81 % (79.1, 82.6) of specimens. Total charges for pathological screening were $65,404 per LY to date; however, two patients have ongoing disease-free survival and this figure is expected to decrease., Conclusions: The incidence of significant pathology necessitating change in clinical management is extremely low in our population. Despite this, the cost per LY gained from routine pathological analysis appears to be of sufficient value to continue with current practice. Alternatively, selective screening based on risk factors, intraoperative findings, and on-table examination of specimen may be a more cost-effective approach.

It has been reported that intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risk of coronary heart disease. It also influences bile composition, decreasing biliary cholesterol saturation in the bile of patients with gallstones. In addition to bile composition disturbances, gallbladder hypomotility must be a cofactor in the pathogenesis of cholelithiasis, as it leads to the prolonged nucleation phase. Our current knowledge about gallbladder motility has been enhanced by the study of a population of newly described interstitial (stromal) cells-telocytes (TCs). The purpose of this study was to determine whether TC loss, reported by our team recently, might be related to bile lithogenicity, expressed as cholesterol saturation index or the difference in biliary PUFA profiles in patients who suffer from cholecystolithiasis and those not affected by this disease. We determined biliary lipid composition including the fatty acid composition of the phospholipid species in bile. Thus, we investigated whether differences in biliary fatty acid profiles (ω-3 PUFA and ω-6 PUFA) in gallbladder bile may influence its lithogenicity and the quantity of TCs within the gallbladder wall. We conclude that the altered PUFA concentrations in the gallbladder bile, with elevation of ω-6 PUFA, constitute important factors influencing TC density in the gallbladder wall, being one of the possible pathophysiological components for the gallstone disease development. This study established that altered bile composition in patients with cholelithiasis may influence TC quantity within the gallbladder muscle, and we concluded that reduction in TC number may be a consequence of the supersaturated bile toxicity, while some other bile components (ω-3 PUFA, glycocholic, and taurocholic acids) may exert protective effects on TC and thus possibly influence the mechanisms regulating gallbladder and extrahepatic bile duct motility. Thus, ω-3 PUFA may represent a possible option to prevent formation of cholesterol gallstones.

Background: Gallstones (GS) associated diseases are among the most recurrent and frequent diseases delineated in India and United Arab Emirates. Several reports suggest that the association of GS with gallbladder cancer (GBC) is very high in Northern part of India; however, its occurrence in UAE and Southern part of India is notably low. Therefore, in the present study, we aimed to perform compositional analysis of GS in three different geographical areas by Solid State Nuclear Magnetic Resonance and Fourier Transformed Infrared spectroscopy., Methods: Natural abundance 13C cross polarization magic angle spinning Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy is employed for the analysis of human gallstone., Results: Cholesterol, bilirubin and calcium carbonate were present in variant concentrations in GS obtained from three different geographical regions. Cholesterol was present predominantly in gallstones from North India. Bilirubin was found to be a main constituent in gallstones pertaining to South India. Whereas GS from UAE showed both cholesterol and bilirubin as their major constituents. Calcium carbonate was found in varying concentrations in gallstones acquired from different regions., Conclusion: Variation in environmental condition and dietary habits may contribute and affect the GS formation. Alterations in bile composition influence the GB and augment the crystallization of cholesterol. Analysis of different geographical regions GS could be an important stride to understand the etiology of GS diseases., Competing Interests: The authors have declared that no competing interests exists.

Background and Aims: Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with fiberoptic instruments. The role of a new, digital, single-operator cholangiopancreatoscopy (SOC) system for diagnosis and treatment of pancreatobiliary disorders in clinical practice is not known., Methods: We performed a multicenter, observational study of 105 consecutive patients with suspected pancreatobiliary disorders. The main outcome measures were (1) sensitivity and specificity of SOC visual appearance and biopsies in the diagnosis of indeterminate biliary strictures and (2) achieving complete duct clearance in patients with biliary or pancreatic duct stones., Results: A total of 98 cholangioscopy and 7 pancreatoscopy procedures were performed in 105 patients. Superior views of the ductal lumen and mucosa were obtained in all 44 patients with indeterminate biliary strictures. Among the 44 patients who underwent SOC-guided biopsies, the specimen was adequate for histologic evaluation in 43 patients (97.7%). The sensitivity and specificity of SOC visual impression for diagnosis of malignancy was 90% (95% confidence interval [CI], 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively. The sensitivity and specificity of SOC-guided biopsies for diagnosis of malignancy was 85% (95% CI, 64.0%-94.8%) and 100% (95% CI, 86.2%-100%). In patients with biliary or pancreatic duct stones (N = 36), complete duct clearance with stone removal in 1 session was accomplished in 86.1% of patients (31/36). Three patients (2.9%) experienced SOC-related adverse events that included cholangitis in 2 patients and postprocedure pancreatitis in 1 patient., Conclusions: SOC has become an integral part of the ERCP armamentarium and has high accuracy in the evaluation of indeterminate biliary strictures. Complete stone clearance was achieved in all but 1 patient with challenging biliary or pancreatic duct stones. (, Clinical Trial Registration Number: NCT01815619.)., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute pancreatitis (AP) is an uncommon disease with a wide clinical course varying from mild and self-limiting to severe with eventual death. However, death caused by AP is rare. Most cases of AP reported in the English-language literature are based on clinical data; few are medico-legal studies., Case Presentation: The author recently experienced a case of sudden unexpected death in a young man caused by extensive severe hemorrhagic AP secondary to cholelithiasis, not chronic alcoholism, which is a much more prominent etiology of AP in medico-legal perspectives. The deceased had complained of dizziness, nausea, and fatigue without significant abdominal pain for about 1 week and received some home medications for symptomatic treatment including an antibiotic drug from a clinic just 2 days prior to his death. He had complained of lower extremity weakness, intense thirst, and subsequently collapsed and was brought to a nearby hospital where he was pronounced dead shortly after his admission following unsuccessful advanced cardiopulmonary resuscitation attempts., Conclusion: This case is herein reported with an extensive review of the pertinent literature to highlight the findings of the case and raise awareness within the medico-legal profession and also the medical profession.

A mature female squirrel monkey was noted during routine semiannual examinations to have moderate progressive weight loss. Serum chemistry panels revealed marked increases in hepatic enzyme, bilirubin, and bile salt concentrations and hypoalbuminemia. Abdominal ultrasonography revealed echogenic, shadowing debris in the gallbladder, consistent with cholelithiasis. At necropsy, marked thickening and distension of the gallbladder, cystic duct, and common bile duct was noted, and more than 50 irregularly shaped, black gallstones were removed from the biliary tract. Gallbladder tissue, bile, and gallstones cultured positive for Escherichia coli and Proteus spp., suggesting a brown-pigment gallstone type secondary to a bacterial nidus. Histopathology revealed severe chronic-active diffuse cholecystitis and severe chronic-active hepatic degeneration and necrosis with severe cholestasis. To our knowledge, this report is the first description of spontaneous choleilthiasis in a squirrel monkey.

Background: The etiological factor for intrahepatic cholangiocarcinoma (ICC) is not clear. Although it has been widely accepted that intrahepatic biliary tree stone is associated with increased risk of ICC, the role of extrahepatic biliary tree stone in the incidence of ICC is controversial. In the present study we aim to evaluate the association between pre-existing choledocholithiasis and cholecystolithiasis and the risk of ICC., Methods: PubMed, Embase, and Web of Science were searched to identify cohort and case-control studies on the association between choledocholithiasis or cholecystolithiasis and the risk of ICC. Studies that met the inclusion criteria were subjected to a meta-analysis performed with Stata statistical software. Either a fixed or random effect model was used, depending on the heterogeneity within the studies. Egger's test was performed to assess publication bias., Results: Seven case-control studies met our inclusion criteria. Of the 123,771 participants, 4763 (3.85 %) were patients with ICC, and 119,008 were tumor-free controls. The presence of pre-existing bile duct stones (choledocholithiasis alone or choledocholithiasis accompanied by hepatolithiasis) was associated with the risk of ICC (odds ratio [OR] 17.64, 95 % confidence interval [CI] 11.14-27.95). Even the presence of choledocholithiasis alone (in the absence of hepatolithiasis) was associated with a high risk of ICC (OR 11.79, 95 % CI 4.17-33.35). Cholecystolithiasis may possibly contributed to the incidence of ICC (OR 2.00, 95 % CI 1.16-3.42), with large heterogeneity within studies (I (2) = 78.5 %)., Conclusions: Bile duct stones including choledocholithiasis are important risk factors for ICC. Careful surveillance of patients with extrahepatic biliary tree stone should be considered.

Background: Gallbladder (GB) cancer is rare. Most cases are incidentally found in specimens after a cholecystectomy. Cholelithiasis is almost always present when this diagnosis is made. Obesity is a known risk factor for gallstone formation and thus may be related to GB cancer., Objectives: To highlight the importance of evaluating the gallbladder before surgery, resecting the gallbladder whenever required, and screening the resected tissue for malignancy., Methods: We retrospectively searched a prospectively maintained database of all bariatric procedures during the last 8 years for cases of concomitant laparoscopic sleeve gastrectomy (LSG) and laparoscopic cholecystectomy (LC). Pathologic reports of the gallbladders were reviewed. Demographic data and perioperative parameters were documented., Results: Of 2708 patients reviewed, 1721 (63.55%) were females and 987 (36.45%) males. Excluded were 145 (5.35%) who had a previous cholecystectomy. Of the remaining 2563, 180 (7.02%) had symptomatic gallbladder disease and underwent LSG with LC. Of these, two females (BMI 53 kg/m2 and 47 kg/m2, both age 60) were found by histological examination to have adenocarcinoma in their GB specimens (1.11%). Both were reoperated, which included partial hepatectomy of the GB bed, resection of the cystic stump, lymph node dissection, and resection of the port sites. One patient is doing well, with no evidence of disease at a postoperative follow-up of 4 years. The second patient had recurrent disease with peritoneal spread and ascites 20 months post-surgery and died 18 months later., Conclusions: GB cancer is a rare finding in cholecystectomy specimens. The incidence of this entity might be higher in obese older females owing to the higher incidence of cholelithiasis in these patients.

Background: Hepatolithiasis is a calculus disease of the liver with no known cause that is relatively uncommon, and is characterized by a refractory nature and high frequency of recurrence. Hepatolithiasis is one of the diseases listed by the Ministry of Health, Labour and Welfare of Japan under Research on Intractable Diseases, and it requires further research on the pathogenesis as well as the therapeutic strategy. It is also included in the clinical guidelines for cholelithiasis of the Japanese Society of Gastroenterology, which suggest guiding principles for the treatment of hepatolithiasis., Methods: we performed questionnaire surveys of hepatolithiasis twice in 2010 and in 2012. Verification of the evidence-based clinical practice guidelines a questionnaire survey of 22 facilities in 2010 and 25 facilities in 2012 across Japan that provided cooperation, which enabled us to assess 210 new cases over a two-year period., Conclusions: Comparison with two surveys that have been carried out previously revealed the main factor associated with hepatolithiasis was a history of biliary tract surgery, which was noted in the majority of cases. In addition, there was an increase of patients in whom balloon endoscopy was performed using transduodenal approach. This method is not included in the treatment options of the current clinical guidelines for cholelithiasis, so there may be a need to take it into consideration when the guidelines are revised.

Background: No previous meta-analysis was to report the association between the apolipoprotein B (APOB) XbaI and EcoRI polymorphisms and serum lipids in Chinese. We performed the study to investigate their potentially association., Methods and Results: Studies in English and Chinese were found via a systematic search of Pubmed, Embase, CNKI and Wanfang databases. The dominant genetic model and random-effects model were used to pool data from individual studies. As a result, a total of 30 articles with 5611 subjects for XbaI and 2653 subjects for EcoRI were included in the current study. For the XbaI polymorphism, overall, subjects carrying X+ allele were significantly associated with higher TC,TG and LDL compared with X-X- genotype (Pvalue = 0.0006, OR (95 %) = -0.55 (-0.86,-0.23); Pvalue = 0.0004, OR (95 %) = -0.30 (-0.47,-0.14); (Pvalue = 0.05, OR (95 %) = -0.23(-0.46,-0.00), respectively). Similar results were observed in the subgroups of Han, healthy individuals (HT), coronary heart disease (CHD), cerebral infarction (CI), and cholelithiasis. For HDL, positive association between X+ allele with Lower lipid value was found in CHD and CI subgroups. For EcoRI polymorphism, overall, the E- allele carriers were found to be obviously linked with elevated LDL and lower HDL compared with E + E+ genotype (Pvalue = 0.02,OR (95 %) = -0.27 (-0.49,-0.05); Pvalue = 0.01, OR (95 %) = 0.17 (0.03, 0.30), respectively). TC was significantly high in subjects carrying E- allele in the subgroup of hyperlipidemia. No evidence of publication bias was observed., Conclusions: The two genetic variants of APOB may be associated with serum lipids in Chinese.

This Quasi-experimental study was done to assess the effectiveness of hydro-dissection in difficult laparoscopic cholecystectomies in Hamdard University Hospital, Karachi, Pakistan, from April 2012 to March 2014. All consecutive patients who presented with cholelithiasis and planned for laparoscopic cholecystectomy were enrolled in this study. Per-operatively the degree of difficulty of the operation was assessed by Cuschieri's scale after grading; Grade II, III and IV cholecystectomies were included in this study. Hydro dissection with saline jet through 5mm simple irrigation and suction probe was used, Operative findings and the total number of patients, in whom anatomy of calot's triangle was clearly displayed with hydro-dissection, was recorded. A total 55 patients were included in the study after assessing the degree of difficulty per operatively by Cuschieri Scale. Thirty one (31) patients were in Group II, 22 in Group III and 02 were included in group IV of Cuschieri scale in which hydro-dissection was used. This method cleared the obscure anatomy in all patients in Group II but in 3 patients of Group III, dense adhesions required sharp dissection to clear the operative field. Two patients, in whom conversion was required, were grouped in Cuschieri's scale IV. Methods of dissection in difficult cholecystectomies are of paramount importance to avoid iatrogenic injuries. Hydro-dissection using suction irrigation probe is a safe and effective technique to clear the difficult anatomy.

Objective: To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis., Methods: Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay., Results: A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1., Conclusions: Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)