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Peribiliary glands are complex lobular structures containing mucus and serous glands, distributed along the extrahepatic and intrahepatic bile ducts. In this report, we describe a case of intraductal papillary neoplasm of the bile duct suspected to be of peribiliary glands origin. The patient was an 80-year-old man who was referred to our hospital for a hepatic mass. On further examination, a 38 × 34 mm cystic lesion with papillary growth was found in S1/4. Because the lesion was extensively bordered by both hepatic ducts and the connection was unclear, it was difficult to determine the extent of hepatic resection. To confirm the location, a peroral cholangioscopy was performed. The connection with the cyst was detected in the right hepatic duct and a villous tumor mucosa protruded through the conduit lumen. Since we found that the lesion communicated with the right hepatic duct, a right hepatectomy was subsequently performed. The postoperative pathological diagnosis was an intraductal papillary neoplasm of the blie duct with associated invasive carcinoma. The postoperative course was good, and the patient experienced no recurrence.

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ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS), a traditional Chinese medicinal formula derived from Treatise on Febrile Diseases, is considered effective in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice. However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. AIM OF THE STUDY: This study aimed to evaluate the effect, explore the bioactive ingredients and the underlying mechanisms of SNS in ameliorating ulcerative colitis (UC) and associated liver injury in dextran sodium sulphate (DSS)-induced mouse colitis models. MATERIALS AND METHODS: The effect of SNS (1.5, 3, 6 g/kg) on 3% DSS-induced acute murine colitis was evaluated by disease activity index (DAI), colon length, inflammatory cytokines, hematoxylin-eosin (H&E) staining, tight junction proteins expression, ALT, AST, and oxidative stress indicators. HPLC-ESI-IT/TOF MS was used to analyze the chemical components of SNS and the main xenobiotics in the colon of UC mice after oral administration of SNS. Network pharmacological study was then conducted based on the main xenobiotics. Flow cytometry and immunohistochemistry techniques were used to demonstrate the inhibitory effect of SNS on Th17 cells differentiation and the amelioration of Th17/Treg cell imbalance. LC-MS/MS, Real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting techniques were performed to investigate the oxysterol-Liver X receptor (LXRs) signaling activity in colon. Targeted bile acids metabolomics was conducted to reveal the change of the two major pathways of bile acid synthesis in the liver, and the expression of key metabolic enzymes of bile acids synthesis was characterized by RT-qPCR and western blotting techniques. RESULTS: SNS (1.5, 3, 6 g/kg) decreased the DAI scores, protected intestinal mucosa barrier, suppressed the production of pro-inflammatory cytokines, improved hepatic and splenic enlargement and alleviated liver injury in a dose-dependent manner. A total of 22 components were identified in the colon of SNS (6 g/kg) treated colitis mice, and the top 10 components ranked by relative content were regarded as the potential effective chemical components of SNS, and used to conduct network pharmacology research. The efficacy of SNS was mediated by a reduction of Th17 cell differentiation, restoration of Th17/Treg cell homeostasis in the colon and spleen, and the experimental results were consistent with our hypothesis and the biological mechanism predicted by network pharmacology. Mechanistically, SNS regulated the concentration of 25-OHC and 27-OHC by up-regulated CH25H, CYP27A1 protein expression in colon, thus affected the expression and activity of LXR, ultimately impacted Th17 differentiation and Th17/Treg balance. It was also found that SNS repressed the increase of hepatic cholesterol and reversed the shift of BA synthesis to the acidic pathway in UC mice, which decreased the proportion of non-12-OH BAs in total bile acids (TBAs) and further ameliorated colitis and concomitant liver injury. CONCLUSIONS: This study set the stage for considering SNS as a multi-organ benefited anti-colitis prescription based on the significant effect of ameliorating intestinal and liver damage, and revealed that derivatives of cholesterol, namely oxysterols and bile acids, were closely involved in the mechanism of SNS anti-colitis effect.

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Bile acids are byproducts of cholesterol metabolism in the liver and constitute the primary components of bile. Disruption of bile flow leads to cholestasis, characterized by the accumulation of hydrophobic bile acids in the liver and bloodstream. Such accumulation can exacerbate liver impairment. This review discussed recent developments in understanding how bile acids contribute to liver damage, including disturbances in mitochondrial function, endoplasmic reticulum stress, inflammation, and autophagy dysfunction. Mitochondria play a pivotal role in cholestatic liver injury by influencing hepatocyte apoptosis and inflammation. Recent findings linking bile acids to liver damage highlight new potential treatment targets for cholestatic liver injury.

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Objective: To assess the potential value of fibroblast growth factor 19 (FGF19) as a predictor of gastrointestinal (GI) dysfunction in patients with sepsis. Methods: A prospective study was conducted, and 209 patients who were diagnosed with sepsis and admitted to the intensive care unit (ICU) at teaching hospitals in China were enrolled from June 2023 to December 2023. The serum FGF19 level was determined at ICU admission. The differences in serum FGF19 levels between the two groups were compared via the Mann-Whitney U test, and Spearman's correlation coefficient was used to identify the correlations of the FGF19 concentration with other clinical variables and biomarkers. Receiver operating characteristic (ROC) analysis was used to determine the value of FGF19 in predicting GI dysfunction in patients with sepsis. Results: The total ICU mortality rate was 13.3% (24/180). There was a tendency toward increased ICU mortality in patients with sepsis-associated GI dysfunction compared with patients without GI dysfunction with statistical significance (21.9% vs. 8.6%, p = 0.031). Serum FGF19 levels were significantly higher in patients with sepsis-associated GI dysfunction than in patients without GI dysfunction [355.1 (37.2, 2315.4) µg/mL vs. 127.4 (5.7, 944.2) µg/mL, p = 0.003]. The results of receiver operating characteristic (ROC) curve analysis revealed that the area under the ROC curve (AUC) for the ability of FGF19 to predict GI dysfunction in patients with sepsis was 0.773 (95% CI 0.712 ~ 0.827), which was greater than the predictive capacity of PCT [AUC = 0.632 (95% CI 0.562 ~ 0.804)]. Conclusion: Serum FGF19 could be considered as a novel predictor or biomarker of GI dysfunction in patients with sepsis.

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ETHNOPHARMACOLOGICAL RELEVANCE: Current treatment options for cholestatic liver diseases are limited, and addressing impaired intestinal barrier has emerged as a promising therapeutic approach. Si-Ni-San (SNS) is a Traditional Chinese Medicine (TCM) formula commonly utilized in the management of chronic liver diseases. Our previous studies have indicated that SNS effectively enhanced intestinal barrier function through the modulation of gut microbiota. AIM OF THE STUDY: This study aims to verify the therapeutic effects of SNS on cholestatic liver injury, focusing on elucidating the underlying mechanism involving the gut-liver axis. MATERIALS AND METHODS: The 16s RNA gene sequencing, non-targeted metabolomics were used to investigate the effects of SNS on the gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) was conducted to identify potential beneficial probiotics underlying the therapeutic effects of SNS. RESULTS: Our results demonstrated that SNS significantly ameliorated cholestatic liver injury induced by partial bile duct ligation (pBDL). Additionally, SNS effectively suppressed cholestasis-induced inflammation and barrier dysfunction in both the small intestine and colon. While SNS did not impact the intestinal FXR-FGF15-hepatic CYP7A1 axis, it notably improved gut microbiota dysbiosis and modulated the profile of microbial metabolites, including beneficial secondary bile acids and tryptophan derivatives. Furthermore, gut microbiota depletion experiments and FMT confirmed that the therapeutic benefits of SNS in cholestatic liver disease are dependent on gut microbiota modulation, particularly through the promotion of the growth of potential probiotic P. goldsteinii. Moreover, a synergistic improvement in cholestatic liver injury was observed with the co-administration of P. goldsteinii and SNS. CONCLUSION: Our study underscores that SNS effectively alleviates cholestatic liver injury by addressing gut microbiota dysbiosis and enhancing intestinal barrier function, supporting its rational clinical utilization. Furthermore, we highlight P. goldsteinii as a promising probiotic candidate for the management of cholestatic liver diseases.

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The involvement of the inflammatory response has been linked to the development of liver illnesses. As medications with the potential to prevent and cure liver illness, probiotics have garnered an increasing amount of interest in recent years. The present study used a piglet model with acute liver injury (ALI) induced by lipopolysaccharides (LPS) to investigate the regulatory mechanisms of Bacillus amyloliquefaciens SC06. Our findings indicated that SC06 mitigated the liver structural damage caused by LPS, as shown by the decreased infiltration of inflammatory cells and the enhanced structural integrity. In addition, After the administration of SC06, there was a reduction in the increased levels of the liver damage markers. In the LPS group, there was an increase in the mRNA expression of inflammatory cytokines, apoptosis cell rate, and genes associated with apoptosis, while these alterations were mitigated by SC06 administration. Furthermore, SC06 prevented pigs from suffering liver damage by preventing the activation of the NLRP3 inflammasome, which was normally triggered by LPS. The examination of serum metabolic pathways found that ALI was related to several metabolic processes, including primary bile acid biosynthesis, pentose and glucuronate interconversions and the metabolism of phenylalanine. Significantly, our research revealed that the administration of SC06 effectively controlled the concentrations of bile acids in the serum. The correlation results also revealed clear relationships between bile acids and liver characteristics and NLRP3 inflammasome-related genes. However, in vitro experiments revealed that SC06 could not directly inhibit NLRP3 activation under ATP, monosodium urate, and nigericin stimulation, while taurochenodeoxycholic acid (TCDCA) activated NLRP3 inflammasome related genes. In conclusion, our study proved that the hepaprotective effect of SC06 on liver injury, which was closely associated with the restoration of bile acids homeostasis and NLRP3 inflammasome inhibition.

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BACKGROUND: Miscarriage has the characteristics of recurrent attacks and complex etiology, so it is gradually attracted the wide attention of scholars in the fields of reproduction. Potential association between gut microbiome (GM) and pregnancy disorders has been investigated. Jianwei Shoutai pills (JWP), as a representative formula, have been proven to have protective effect in both clinical and experimental research in miscarriage. However, the specific mechanism of JWP in miscarriage through GM remains unclear. PURPOSE: To investigate the underlying mechanism of JWP against miscarriage through the gut-uterus axis. METHODS: The effects of JWP on an RU486-induced rat model of miscarriage were evaluated by embryo resorption rate, vaginal bleeding rate, and appearance of the uterus and embryo. We used 16S rRNA sequencing to measure the extent of the effect of JWP on GM of rats with miscarriage. Bile acid (BA) content of the feces of rats treated with JWP was evaluated by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The activation of bile acid-associated receptor, Farnesoid X receptor (FXR), was evaluated by immunofluorescence. The expression level of NLRP3 inflammasome-associated protein was detected by Western blot or Elisa. Fecal microbiota transplantation (FMT) was used to confirm that GM was essential for the therapeutic effect of JWP in miscarriage. RESULTS: JWP significantly ameliorated miscarriage symptoms and embryo resorption rate caused by RU486-induced miscarriage as well as restored the abnormal activation of NLRP3-inflammasome at the maternal-fetal interface. Furthermore, JWP can significantly regulated GM dysbiosis and closely associated with BA metabolism by KEGG pathway prediction analysis. Several BA content were significantly restored by HPLC-MS. The expression of NLRP3 inflammasome-associated protein at maternal-fetal interface was reversed by JWP. Combined with FMT, JWP could regulate activation of NLRP3 at the maternal-fetal interface by BAs produced by GM. CONCLUSION: JWP restored abnormal activation of the NLRP3-inflammasome in an RU486-induced miscarriage rat model, and corrected the BA disorder by regulating imbalance of the GM.

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Background: The most common therapy for gallstones is laparoscopic cholecystectomy (LC). How to help young residents avoid bile duct injuries (BDI) during surgery and grasp LC seems to be a paradox. Methods: We retrospectively reviewed 145 cases of LC operated by two residents under indocyanine green (ICG)-guided mode or normal LC procedures to illustrate the role of ICG mode in boosting the LC learning curve. The clinic data were analyzed by logistic regression, receiver operator curve tests, Cumulative Sum (CUSUM), and Risk-Adjusted Cumulative Sum (RA-CUSUM) analysis. Results: The operation failure rate is similar. However, operation time under ICG mode is shorter than that under normal mode. The peak at the 49th case represented the normal resident's complete mastery of the surgery, while the peak point of ICG mode appeared at the 36th case in the fitting curve. The most significant cumulative risk (peak point) of operation failure of LC was at the 35th case in ICG LC mode, while it appeared in the 49th in normal LC mode. Conclusions: Owing to the advantage of real-time imaging and the stable success rate of cholangiography, ICG-guided LC helps residents shorten the operation time, boost the learning curve, and manage to control the operation failure rate.

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Patients with hepatic failure are often accompanied by hepatic retinopathy, but the cellular and molecular mechanisms underlying the hepatic retinopathy remain unclear. In this study, we investigated how liver failure leads to hepatic retinopathy using bile duct ligation (BDL) rats as a cholestasis animal model. Light-dark box test was used to assess sensitivity to light, indexed as visual acuity. On D28 post-BDL, rats were subjected to light-dark box test and blood samples were collected for biochemical analyses. The rats then were euthanized. Liver, spleen and both side of eye were quickly harvested. We showed that BDL impaired rat sensitivity to light, significantly decreased the thickness of inner nuclear layer (INL), outer nuclear layer (ONL) and total retina, as well as the retinal cell numbers in ONL and ganglion cell layer (GCL). The expression of rhodopsin (RHO), brn-3a and GPX4 was significantly decreased in retina of BDL rats, whereas the expression of cleaved caspase 3, 8, 9, bax/bcl-2, RIP1, GFAP, and iba-1, as well as TUNEL-positive cells were significantly increased. In cultured retinal explant, we found that NH4Cl (0.2, 1, 5 mM) concentration-dependently impaired activity of retinal explant, decreased thickness of INL and ONL, downregulated expression of brn-3a, RHO and GFAP, increased expression of cl-caspase 3 and TUNEL-positive cell numbers, with NH4Cl (5 mM) almost completely disrupting the structure of the cultured retina; bilirubin (1 µM) significantly upregulated GFAP expression, whereas high level (10 µM) of bilirubin downregulated expression of GFAP. We further demonstrated in vivo that hyperammonemia impaired rat sensitivity to light, decreased thickness of INL and ONL, downregulated expression of RHO, brn-3a, GFAP and increased expression of cl-caspase 3; hyperbilirubinemia impaired rat sensitivity to light, upregulated expression of GFAP and iba-1. In conclusion, BDL impaired rat visual acuity due to the elevated levels of ammonia and bilirubin. Ammonia induced loss of retinal ganglion cells and rod photoreceptor cells via apoptosis-mediated cell death. Bilirubin impaired retinal function via activating microglia and Müller cells.

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Background & Aims: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis (PSC) are lacking. We evaluated the predictive value of serum and biliary biochemistry for the progression of bile duct disease in PSC using repeated endoscopic retrograde cholangiopancreatography (ERCP) examinations to identify surrogate markers for more personalized surveillance. Methods: We conducted a prospective analysis including patients with PSC who underwent ERCP for confirmation of diagnosis, monitoring of disease progression, or dysplasia surveillance. ERCP findings were scored, and dilatation was performed if a dominant stricture was diagnosed or if a cytology brush could not be passed. Bile samples were aspirated for biliary IL8 and calprotectin. We analysed optimal cut-off values and AUCs for 20 laboratory markers and evaluated their association with the time to an ERCP score increase of ≥2 points or first dilatation, whichever came first. Of the 1,002 patients, 653 had ≥2 ERCP examinations and ≥3 years of follow-up. After excluding patients with PSC-overlap syndrome or initial dilatation, 398 patients were included. Results: Of the patients included, 62% had mild or moderate and 38% had advanced bile duct disease. During follow-up, 41% of patients demonstrated progression of disease. Biliary calprotectin (AUC 0.76; 95% CI 0.69 to 0.82) and IL8 (AUC 0.76; 95% CI 0.69 to 0.84) were the only variables that demonstrated predictive value for disease progression and/or need for dilatation. Conclusions: Biliary calprotectin and IL8 are promising surrogate markers for identifying patients with PSC at risk of progression and determining the timing for subsequent imaging. Conventional liver function tests may not be sensitive or specific enough to monitor PSC progression, particularly in the short term. Impact and implications: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis are lacking. In this prospective study, based on sequential endoscopic retrograde cholangiopancreatography examinations, biliary calprotectin and IL8 levels turned out to be more sensitive for predicting bile duct progression than traditional liver function tests, such as alkaline phosphatase, in the short term. These findings could lead to more personalized patient surveillance and improve clinical practice by providing a more accurate method for monitoring disease progression and treatment responses. Additionally, these markers have potential as surrogate endpoints in clinical drug trials. The limitation is that measurement of biliary IL8 and calprotectin requires endoscopic retrograde cholangiopancreatography with bile sampling.

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Depression is a psychological disorder associated with prolonged stress, which involves abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of glucocorticoids (GC). Excessive GC can cause damage to the structure and function of the hippocampus, thereby triggering depressive symptoms. Studies suggest that the bile acid receptor farnesoid X receptor (FXR) may play a role in adrenal GC synthesis. This study aimed to explore the potential therapeutic effects of dried bear bile (DBB) on depression and its mechanism. We used the chronic unpredictable mild stress (CUMS) mouse model and FXR agonist GW4064 stimulated mice, as well as H295R human adrenal cortical carcinoma cells, employing behavioral tests, biochemical analysis, and gene expression analysis to assess the effects of DBB treatment on depressive behavior, serum corticosterone (CORT) levels, and adrenal FXR and steroid biosynthesis-related gene expression. The results showed that in both CUMS and GW4064-stimulated mice, DBB treatment significantly improved depressive-like behaviors and reversed serum CORT levels. Additionally, DBB suppressed the expression of steroidogenic regulatory genes in the adrenal glands of CUMS mice. In H295R cells, DBB treatment effectively reduced cortisol secretion induced by Forskolin, inhibited the expression of steroid biosynthesis-related genes, and suppressed cortisol production and HSD3B2 expression under conditions of FXR overexpression and FXR activation. Our findings suggest that DBB regulates adrenal FXR to modulate glucocorticoid synthesis and exerts antidepressant effects. DBB may serve as a potential therapeutic agent for depression by regulating GC levels and steroidogenesis pathway. Further research is underway to test the antidepressant effects of each DBB component to understand their specific contribution.

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BACKGROUND: In adults, upfront intraoperative cholangiogram with laparoscopic common bile duct exploration (LCBDE) is well accepted for management of choledocholithiasis. Despite recent evidence supporting LCBDE utility in children, there has been hesitation to adopt this surgery first (SF) approach over ERCP first (EF) due to perceived technical challenges. We compared rates of successful stone clearance during LCBDE between adult and pediatric patients to evaluate if pediatric surgeons could anticipate similar rates of successful clearance. METHODS: A multicenter, retrospective review of pediatric (<18 years) and adult patients with choledocholithiasis managed from 2018 to 2024 was performed. Demographic and clinical data were obtained. Rate of successful duct clearance with LCBDE was compared. Surgical and endoscopic complications (infections, bleeding, pancreatitis, bile leak) were also compared. RESULTS: 724 patients, 333 (45.9%) pediatric and 391 (54.0%) adults, were included. The median age of pediatric vs adult patients was 15.2 years [13.1, 16.6] vs 55.5 years [34.1, 70.5], respectively. Of these, 201 (60.4%) pediatric vs 169 (43.2%) adult patients underwent SF, p < 0.001. LCBDE was attempted in 84 (41.7%) pediatric vs 140 (82.8%) adults, p = 0.002. LCBDE success was higher in pediatric vs adult patients (82.1% vs 71.4%, p = 0.004). Complications rates were similar however, pediatric patients who underwent EF had higher endoscopic complications (9.1% vs 3.6%, p = 0.03). CONCLUSION: LCBDE is highly successful in children vs adults with no increased surgical complications. This data, coupled with the limited ERCP access for children, supports that LCBDE is an equally effective tool for managing choledocholithiasis in children as is accepted in adults. LEVEL OF EVIDENCE: Level III.

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INTRODUCTION: Given the increasing interest for surgeons to reclaim the common bile duct in managing choledocholithiasis, there is a growing movement to perform common bile duct exploration (CBDE). Advantages of concomitant CBDE with cholecystectomy include fewer anesthetic events and decreased length of stay. As there is a paucity of literature evaluating the use of the robotic platform for CBDE, our study aims to compare intraoperative and post-operative outcomes between robotic-assisted one-stage and two-stage management of choledocholithiasis. METHODS: A retrospective chart review was performed from May 1, 2022 to December 31, 2023, identifying patients with choledocholithiasis who underwent robot-assisted laparoscopic cholecystectomy and transcystic CBDE with choledochoscopy (one-stage management). Preoperative, intraoperative, and post-operative variables were compared to a control group of subjects with choledocholithiasis who underwent laparoscopic cholecystectomy with pre- or post-operative ERCP (two-stage management). Statistical analysis was performed using Chi-squared, Fisher's exact, Student's T, or Mann-Whitney test. RESULTS: Fifty-three subjects who underwent one-stage management and 101 subjects who underwent two-stage management met inclusion criteria. Groups had similar demographics and medical history. Time to CBD clearance (45.2 h vs 47.0 h, p = .036), total length of stay (3.9 days vs 5.1 days, p = .007), fluoroscopy time (70.3 s vs 151.4 s, p < .001), and estimated radiation dose (23.0 mSv vs 40.3 mSv, p = .002) were significantly lower in the one-stage group compared to two-stage. Clearance rates, complication rates, and 30-day readmission rates were similar for both groups. Total length of stay and radiation exposure remained significantly lower on subanalysis comparing one-stage management to two-stage management with ERCP either before or after cholecystectomy. CONCLUSION: Robotic-assisted laparoscopic cholecystectomy with transcystic common bile duct exploration via choledochoscopy is a safe and feasible option in the management of choledocholithiasis. It offers a shorter time to duct clearance, shorter length of stay, and less radiation exposure when compared to two-stage management.

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Introduction Surgeons-in-training (SIT) perform laparoscopic cholecystectomy (LC); however, it is challenging to complete the procedure safely in difficult cases. We present a surgical technique during difficult LC, which we named the hanging strap method. Methods We retrospectively compared the perioperative outcomes between patients undergoing difficult LC with the hanging strap method (HANGS, n = 34), and patients undergoing difficult LC without the hanging strap method (non-HANGS, n = 56) from 2022 and 2024. Difficult LC was defined as cases classified as more than grade II cholecystitis by the Tokyo Guidelines 18 and cases when LC was undergoing over five days after the onset of cholecystitis. Results The proportion of SIT with post-graduate year (PGY) ≤ 7 was significantly higher in the HANGS group than in the non-HANGS group (82.4% vs. 33.9%, P < 0.001). The overall rate of bile duct injury (BDI), postoperative bile leakage and operative mortality were zero in the whole cohort. There were no significant differences between the HANGS and non-HANGS groups in background characteristics, operative time (122 min vs. 132 min, P = 0.830) and surgical blood loss (14 mL vs. 24 mL, P = 0.533). Conclusions Our findings suggested that the hanging strap method is safe and easy to use for difficult LC. We recommend that the current method be selected as one of the surgical techniques for SIT when performing difficult LC.

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We present the case of an 82-year-old female with obstructive jaundice secondary to a malignant distal biliary stricture. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) was performed. The presence of a giant hiatal hernia induced dynamic liver movement during respiration, leading to unstable scope positioning. Despite the successful placement of a long, partially covered metal stent from the left intrahepatic bile duct to the intra-abdominal stomach, computed tomography performed three days later revealed free air and an increased distance between the liver and stomach. A subsequent endoscopy confirmed impending stent migration into the abdominal cavity, necessitating the insertion of an additional metal stent through the existing stent's mesh. The presence of a giant hiatal hernia may be considered a relative contraindication for EUS-HGS due to dynamic movements of the stomach and liver during respiration, which can cause stent migration, increased air leakage, and difficulty in establishing a stable fistula between these organs.

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The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P < 0.05). According to the results of gut microbial function prediction, the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig. Sixty-five bile acids were further screened by metabolomics, of which 4 were upregulated (P < 0.05) and 2 were downregulated (P < 0.05) in obese pigs compared to lean pigs. The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-ß-D-glucuronide (CDCA-3Gln) and ω-muricholic acid (ω-MCA) had a negative correlation with abdominal fat weight and abdominal fat rate, while isoallolithocholic acid (IALCA) was positively associated with crude fat in the liver and abdominal fat rate. There was a positive correlation between loin muscle area and CDCA-3Gln and ω-MCA (P < 0.05), however, IALCA and 3-oxodeoxycholic acid (3-oxo-DCA) were negatively associated with loin eye muscle area (P < 0.05). Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma (PPARG) and the number of lipid droplets (P < 0.05), promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro. In conclusion, the concentration of bile acids, especially gut microbiota related-secondary bile acids, in obese pigs was different from that in lean pigs, which may contribute to lipid accumulation within obese pigs.

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Background: At present, some common bile duct stones (CBDSs) cannot be removed by conventional endoscopic treatment. Percutaneous transhepatic papillary ballooning and extraction (PTPBE) is a promising treatment for CBDSs. This study aimed to evaluate the feasibility and efficacy of PTPBE for removing CBDSs. Methods: From April 2013 to April 2021, 29 patients with CBDSs underwent PTPBE at The First Affiliated Hospital of Zhengzhou University; their clinical data were retrospectively analyzed. The technical success, clinical success, procedure time, radiation dose, 1-year CBDSs recurrence rate, and incidence of early/late complications were recorded, and white blood cell (WBC) counts and alanine aminotransferase (ALT), C-reactive protein (CRP), total bilirubin (TBIL), and carbohydrate antigen-199 (CA-199) levels were compared before the interventional procedure and 1 month later. Results: The CBDSs were successfully removed in 29 patients (the CBDSs in 20 patients were resolved once, and in 9 patients, they were resolved twice). The mean procedure time and radiation dose were 56.38±13.56 minutes and 732.07±262.23 miligray (mGy), respectively. The technical and clinical success rates were both 100%. The incidence of early complications (including pancreatitis and bile duct bleeding) and late complications (reflux cholangitis) was 10.34% and 3.45%, respectively. The WBC (both P<0.01), ALT (both P<0.01), CRP (both P<0.01), CA-199 (both P<0.01), and TBIL (both P<0.01) significantly decreased before PTPBE and 1 month later. Conclusions: PTPBE is a safe and effective alternative solution for elderly patients who cannot undergo or refuse traditional surgical and endoscopic treatments.

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Background: Bile duct resection and reconstruction for bile duct cancer (BDC) is a complex surgical and oncologic procedure that requires extensive resection and reconstruction of the biliary tract. Hepaticojejunostomy is commonly performed for biliary reconstruction after extrahepatic mid-bile duct resection, while hepaticoduodenostomy (HD) is performed only rarely due to the risk of ascending cholangitis. However, the efficacy of HD has not been well-established in extrahepatic mid-BDC surgery. In this study, we aimed to analyze the outcomes of HD in patients who underwent bile duct resection for extrahepatic mid-BDC. Methods: We retrospectively analyzed 38 extrahepatic mid-BDC patients who underwent bile duct resection in our center between January 2018 and June 2023. We compared postoperative outcomes, cancer recurrence, and patient survival between hepaticojejunostomy (n=20) and HD (n=18) groups. Results: Operation time for the HD group was significantly shorter than that of the hepaticojejunostomy group (188 vs. 206 min, P=0.044) with no significant differences in postoperative outcomes. Regression analysis showed that a HD was not associated with a significantly high risk of cancer recurrence or decrease in patient survival. Conclusions: HD appears to have comparable operative benefits, postoperative complications, and oncologic outcomes to hepaticojejunostomy in extrahepatic mid-BDC patients.

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Pathogen infections remain a significant public health problem worldwide. Accumulating evidence regarding the crosstalk between bile acid (BA) metabolism and immune response reveals that BA metabolism regulates host immunity and microbial pathogenesis, making it an attractive target for disease prevention and infection control. However, the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors remains to be depicted. Here, we investigated the effect of viral (vesicular stomatitis virus, VSV) and bacterial (lipopolysaccharide, LPS) infections on BA metabolism and signaling. Infection models were successfully established by intraperitoneally injecting VSV and LPS, respectively. VSV and LPS injection significantly changed the circulating BA profiles, with highly increased levels of taurine-conjugated BAs and significant decreases in unconjugated BAs. Consistent with the decreased levels of circulating cholic acid (CA) and chenodeoxycholic acid (CDCA), the expression of BA biosynthesis-related rate-limiting enzymes (Cyp7a1, Cyp27a1, Cyp8b1, and Hsd3b7) were significantly reduced. Furthermore, hepatic and pulmonary BA receptors (BARs) expression varied in different infection models. LPS treatment had an extensive impact on tested hepatic and pulmonary BARs, resulting in the upregulation of TGR5, S1PR2, and VDR, while VSV infection only promoted VDR expression. Our study provides insights into the involvement of BA metabolism in the pathophysiology of infection, which may provide potential clues for targeting BA metabolism and BAR signaling to boost innate immunity and control infection. IMPORTANCE: This study focuses on the crosstalk between bile acid (BA) metabolism and immune response in VSV infection and LPS treatment models and depicts the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors. These findings provide insights into the effect of infection on BA metabolism and signaling, adding a more comprehensive understanding to the relationship between infection, BA metabolism and immune responses.

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PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.

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