Therapeutic Potential of Danyankang Capsule in High-Fat Diet-Induced Cholelithiasis and Its Impact on Liver FXR Signaling and Gut Microbiota.

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.

Analysis of Complications and Risk Factors Other than Bleeding before and after Endoscopic Treatment of Esophagogastric Variceal Bleeding in Patients with Liver Cirrhosis.

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.

Histopathological Evaluation of Gallbladder Specimens Obtained From Living Liver Donors.

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.

Personal comorbidities and their subsequent risks for liver, gallbladder and bile duct cancers.

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.

Variations and characteristics of the various clinical phenotypes in a cohort of Nigerian sickle cell patients.

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.

Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids.

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.

Estado nutricional, actividad física y consumo de comida chatarra asociados a colelitiasis en huánuco: estudio de casos y controles / Nutritional status, physical activity and consumption of junk food were associating to colelitiasis in huánuco: a case-control study

Resumen Objetivos: Determinar la asociación entre el consumo de comida chatarra, actividad física y estado nutricional en pacientes con colelitiasis a la ecografía (casos), comparados con controles aparentemente sanos sin colelitiasis a la ecografía, en consulta externa del Hospital EsSalud II Huánuco. Materiales y Método: Estudio de casos y controles. Se incluyeron 107 casos y 107 controles. El consumo de comida "chatarra" se valoró con la encuesta validada por RSEQ (Red deportiva estudiantil de Québec), la frecuencia del consumo (días por semana); la actividad física por el cuestionario IPAQ (Cuestionario Internacional de Actividad Física) y el estado nutricional mediante el índice de masa corporal. En el análisis estadístico se empleó el χ2, U de Mann Whitney y Odds Ratio (p < 0,05). Resultados: La edad y la procedencia no fueron significativos. El consumo de comida "chatarra" estuvo asociado a la colecistitis (OR 10,30; IC 95% 5,48-19,37). La actividad física moderada-vigorosa (≥ 600 MET) promovió el diagnóstico de colecistitis (OR 8,38; IC 95% 4,54-15,48) y el estado nutricional (sobrepeso o mayor), en forma significativa, promovía la colecistitis (OR 11,38; IC 95% 6,01-21,55). Ser femenino estuvo asociado al desarrollo de colecistitis (OR 2,06; IC 95% 1,19-3,55). Conclusión: El consumo de comida "chatarra", la actividad física moderada-vigorosa (≥ 600 MET), el estado nutricional (sobrepeso o mayor) y el género (femenino) fueron asociados al desarrollo de colelitiasis diagnosticados mediante ecografía.

Aim: To determine the association between junk food consumption, physical activity and nutritional status in patients with cholelithiasis on ultrasound (cases), compared with apparently healthy controls without cholelithiasis on ultrasound, in an outpatient EsSalud II Hospital, Huánuco Hospital, 2017. Materials and Method: Case-control study. 107 cases and 107 controls were included. The consumption of junk food was assessed with the survey validated by RSEQ (Québec Student Sports Network), the frequency of consumption (days per week); Physical activity through the IPAQ questionnaire (International Physical Activity Questionnaire) and nutritional status through the Body Mass Index. The chi-square, Mann Whitney U and Odds Ratio (p < 0.05) were used in the statistical analysis. Results: Gender, age and origin were not significant. None or low consumption of "junk" food were associated with cholecystitis (OR 0.097; 95% CI 0.052-0.182). Low physical activity (< 600 MET) did not promote the diagnosis of cholecystitis (OR 0.119; 95% CI 0.064-0.22) and the nutritional status (normal weight), significantly, did not promote cholecystitis (OR 0.09; 95% CI 0.05-0.167). Being male was associated with the non-development of cholecystitis (OR 0.48; 95% CI 0.281-0.838). Conclusión: Low or no consumption of "junk" food, low physical activity (< 600 MET), nutritional status (normal) and gender (male) were associated for the non-development of cholelithiasis diagnosed by ultrasound.

Transcriptomic profiles reveal differences in zinc metabolism, inflammation, and tight junction proteins in duodenum from cholesterol gallstone subjects.

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.

Gallbladder histological alterations in patients undergoing cholecystectomy for cholelithiasis. / Alterações histológicas da vesícula biliar de doentes submetidos à colecistectomia por colelitíase.

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.

OBJETIVO: descrever os achados histológicos das vesículas biliares de pacientes submetidos à colecistectomia e avaliar a presença de fatores associados ao câncer incidental da vesícula. MÉTODOS: estudo descritivo, transversal e observacional de 1.278 exames anatomopatológicos de vesículas biliares oriundas de colecistectomias por colelitíase e de seus respectivos laudos, realizadas no período de janeiro de 2008 a dezembro de 2017. RESULTADOS: o achado anatomopatológico mais frequente foi a colecistite crônica, presente em 1.251 pacientes (97,8%), seguido pela colesterolose em 131 (10,2%). O câncer de vesícula foi identificado em seis pacientes, com prevalência de 0,5% nesta amostra. Houve associação significativa entre a presença de câncer e idade ≥60 anos e com a espessura da parede ≥0,3cm. CONCLUSÃO: houve baixa prevalência de câncer de vesícula na população avaliada, maior ocorrência na população idosa e associação de tumor com espessamento da parede vesicular.

Cholelithiasis after bariatric surgery, incidence, and prophylaxis: randomized controlled trial.

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.

Carcinogen Metabolism Pathway and Tumor Suppressor Gene Polymorphisms and Gallbladder Cancer Risk in North Indians: A Hospital-Based Case-Control Study.

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.

Comparison of the ICC location in the gallbladder wall in patients with cholelithiasis and patients with non-calculous changes.

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.

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.

Gallbladder interstitial Cajal-like cells and gallbladder contractility in patients with cholelithiasis: a prospective study.

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.

Oxidative stress and deregulations in base excision repair pathway as contributors to gallbladder anomalies and carcinoma - a study involving North-East Indian population.

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.

Follicular cholecystitis: clinicopathologic associations.

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.

Accuracy of Right Upper Quadrant Ultrasound in Estimating Gallbladder Wall Thickness.

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.

Alterações histológicas da vesícula biliar de doentes submetidos à colecistectomia por colelitíase / Gallbladder histological alterations in patients undergoing cholecystectomy for cholelithiasis

RESUMO Objetivo: descrever os achados histológicos das vesículas biliares de pacientes submetidos à colecistectomia e avaliar a presença de fatores associados ao câncer incidental da vesícula. Métodos: estudo descritivo, transversal e observacional de 1.278 exames anatomopatológicos de vesículas biliares oriundas de colecistectomias por colelitíase e de seus respectivos laudos, realizadas no período de janeiro de 2008 a dezembro de 2017. Resultados: o achado anatomopatológico mais frequente foi a colecistite crônica, presente em 1.251 pacientes (97,8%), seguido pela colesterolose em 131 (10,2%). O câncer de vesícula foi identificado em seis pacientes, com prevalência de 0,5% nesta amostra. Houve associação significativa entre a presença de câncer e idade ≥60 anos e com a espessura da parede ≥0,3cm. Conclusão: houve baixa prevalência de câncer de vesícula na população avaliada, maior ocorrência na população idosa e associação de tumor com espessamento da parede vesicular.

ABSTRACT 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.

Gallbladder Pathologies in Kidney Transplant Recipients: Single-Center Experience and a Review of the Literature.

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.

Cholelithiasis and choledocholithiasis in children; risk factors for development.

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.