Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Chenodeoxycholic acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Fatty liver is an independent risk factor for gallbladder polyps

BACKGROUND Gallbladder polyps(GBPs)are known to be associated with obesity and metabolic diseases.However,to date,the relationship between GBPs and abnormal body fat distribution,such as fatty liver,visceral obesity,or sarcopenia,has not yet been established.AIM To evaluate whether GBPs are associated with fatty liver,visceral obesity,or sarcopenia.METHODS We retrospectively reviewed the medical records of subjects who underwent various laboratory tests,body composition measurement with a non-invasive body composition analyzer,and abdominal ultrasonography during health checkups.A total of 1405 subjects with GBPs were compared with 2810 age-and sex-matched controls.RESULTS The mean age of the subjects was 46.8±11.7 years,and 63.8%were male.According to multiple logistic regression analysis,the presence of fatty liver[odds ratio(OR)1.413;95%confidence interval(CI)1.218-1.638;P<0.001]was an independent risk factor for GBP,together with low levels of alanine aminotransferase(OR 0.993;95%CI 0.989-0.996;P<0.001).Additionally,fatty liver showed both independent(OR 1.629;95%CI,1.335-1.988;P<0.001)and dosedependent(moderate to severe fatty liver;OR 2.137;95%CI,1.662-2.749;P<0.001)relationship with large GBPs(≥5 mm).The presence of sarcopenia and high visceral fat area were not significantly associated with GBPs.CONCLUSION Fatty liver was found to be closely associated with GBPs irrespective of sarcopenia and visceral obesity.

Confocal laser endomicroscopy distinguishing benign and malignant gallbladder polyps during choledochoscopic gallbladderpreserving polypectomy:A case report

BACKGROUND In the last decade, confocal laser endomicroscopy (CLE) has emerged as a newendoscopic imaging modality for real-time in vivo histological examination at themicroscopic level. CLE has been shown to be useful for distinguishing benign andmalignant lesions and has been widely used in many digestive diseases. In ourstudy, we used CLE for the first time to examine the morphology of cholesterolpolyps as well as the different parts of normal gallbladder mucosa.CASE SUMMARY A 57-year-old woman was diagnosed by ultrasound with a polyp of 21 mm in thegallbladder wall. She consented to polyp removal by laparoscopic choledochoscopy.During laparoscopic cholecystectomy combined with choledochoscopicpolyp resection, CLE was used to observe the morphology of the polyp surfacecells. The appearance of the mucosa and microvessels in various parts of thegallbladder were also observed under CLE. Through comparison betweenpostoperative pathology and intraoperative CLE diagnosis, the reliability ofintraoperative CLE diagnosis was confirmed. CLE is a reliable method to examineliving cell pathology during cholecystectomy. Based on our practice, CLE shouldbe prioritized in the diagnosis of gallbladder polyps.CONCLUSION Compared with traditional histological examination, CLE has several advantages.We believe that CLE has great potential in this field.

A Nomogram-based Model to Predict Neoplastic Risk for Patients with Gallbladder Polyps

Background and Aims:Gallbladder polyp(GBP)assessment aims to identify the early stages of gallbladder carcinoma.Many studies have analyzed the risk factors for malignant GBPs.In this retrospective study,we aimed to establish a more accurate predictive model for potential neoplastic polyps in patients with GBPs.Methods:We devel-oped a nomogram-based model in a training cohort of 233 GBP patients.Clinical information,ultrasonographic find-ings,and blood test findings were analyzed.Mann-Whitney U test and multivariate logistic regression analyses were used to identify independent predictors and establish the nomogram model.An internal validation was conducted in 225 consecutive patients.Performance and clinical bene-fit of the model were evaluated using receiver operating characteristic curves and decision curve analysis(DCA),re-spectively.Results:Age,cholelithiasis,carcinoembryonic antigen,polyp size,and sessile shape were confirmed as independent predictors of GBP neoplastic potential in the training group.Compared with five other proposed predic-tion methods,the established nomogram model presented better discrimination of neoplastic GBPs in the training co-hort(area under the curve[AUC]:0.846)and the validation cohort(AUC:0.835).DCA demonstrated that the greatest clinical benefit was provided by the nomogram compared with the other five methods.Conclusions:Our developed preoperative nomogram model can successfully be used to evaluate the neoplastic potential of GBPs based on simple clinical variables that maybe useful for clinical decision-making.

Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor prognosis of gallbladder adenocarcinoma

BACKGROUND: Gallbladder cancer (GBC) is one of the most aggressive malignant neoplasms with an extremely poor prognosis. Early diagnosis significantly increases the survival rate. The present study was undertaken to evaluate the diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder lesions and to develop a possible alternative treatment for GBC. METHODS: A total of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15 gallbladder polyp and 35 chronic cholecystitis tissues were included. S1P1 and ERp29 expressions were evaluated by immunohistochemistry The correlation between S1P1 and ERp29 expression and tumor pathological features and prognosis was analyzed. RESULTS: S1P1 positive rate was significantly higher in gallbladder adenocarcinomas than that in peritumoral adenomatous, polyp, and chronic cholecystitis tissues. On the contrary, ERp29 positive rate was significantly lower in adenocarcinomas than that in peritumoral, adenomatous polyp, and chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative ERp29 expression showed moderate or severe atypical hyperplasia in the gallbladder epithelium The overexpression of S1P1 or non-expression of ERp29 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis, and adenocarcinoma invasion Univariate Kaplan-Meier analysis showed that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely associated with decreased survival rate. Multivariate Cox regression analysis showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an independent predictor of poor prognosis in gallbladder adenocarcinoma.CONCLUSION: S1P1 overexpression or ERp29 absence is related to the carcinogenesis and progression, and may be potential biomarkers for early detection of gallbladder adenocarcinoma.

Perfect pair,scopes unite—laparoscopic-assisted transumbilical gastroscopy for gallbladder-preserving polypectomy:A case report

BACKGROUND Gallbladder polyps are one indication for cholecystectomy,but this procedure carries some disadvantages,including the potential for severe injury and high risk of post-operative complications.Laparoscopy combined with endoscopic surgery is a minimally invasive treatment option.We herein report a young patient with a gallbladder polyp who was successfully discharged from the hospital after laparoscopic-assisted endoscopy.This procedure may offer an alternative in the management of such lesions.CASE SUMMARY A 24-year-old female patient was hospitalized primarily for a gallbladder polyp.Due to the surgical risk associated with cholecystectomy and the low postoperative quality of life,the woman underwent laparoscopic-assisted transumbilical gastroscopy for gallbladder-preserving polypectomy under endotracheal intubation and general anaesthesia.The operation went smoothly.CONCLUSION We conclude laparoscopic-assisted transumbilical gastroscopy for gallbladderpreserving polypectomy is a safe and effective technique for the treatment of gallbladder polyps.