Bile Acids: Major Regulator of the Gut Microbiome.

Bile acids are synthesized from cholesterol and play an important role in regulating intestinal microflora. The different degrees of hydrophobicity and acidity of individual bile acids may affect their antimicrobial properties. We examined the antimicrobial effects of different bile acids on various microorganisms in vitro and confirmed whether these remain consistent in vivo. Using human bile acids, including ursodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, a disc diffusion test was performed, and a rodent model was created to determine the antimicrobial effects of each bile acid. The fecal bacterial population was analyzed using a real-time polymerase chain reaction. Each bile acid showed different microbial inhibitory properties. The inhibitory activity of bile acids against microbiota which normally resides in the gastrointestinal tract and biliary system, was low; however, normal flora of other organs was significantly inhibited. Changes in microbial counts after bile acid administration in a rodent model differed in the colon and cecum. The in vivo and in vitro results show that the antimicrobial effects of bile acids against intestinal microbiota were similar. In conclusion, bile acids could be a novel treatment strategy to regulate gut microbiota.

Comparison of Oncologic Outcomes between Transduodenal Ampullectomy and Pancreatoduodenectomy in Ampulla of Vater Cancer: Korean Multicenter Study.

This study used multicenter data to compare the oncological safety of transduodenal ampullectomy (TDA) with that of pylorus-preserving pancreatoduodenectomy (PPPD) in early ampulla of Vater (AoV) cancer. Data for patients who underwent surgical resection for AoV cancer (pTis-T2 stage) from January 2000 to September 2019 were collected from 15 institutions. The clinicopathologic characteristics and survival outcomes were compared between the PPPD and TDA groups. A total of 486 patients were enrolled (PPPD, 418; TDA, 68). The oncologic behavior in the PPPD group was more aggressive than that in the TDA group at all T stages: larger tumor size (p = 0.034), advanced T stage (p < 0.001), aggressive cell differentiation (p < 0.001), and more lymphovascular invasion (p = 0.002). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the two groups when considering all T stages or only the Tis+T1 group. Among T1 patients, PPPD produced significantly better DFS (PPPD vs. TDA, 84.8% vs. 66.6%, p = 0.040) and superior OS (PPPD vs. TDA, 89.1% vs. 68.0%, p = 0.056) than TDA. Lymph node dissection (LND) in the TDA group did not affect DFS or OS (TDA + LND vs. TDA-only, DFS, p = 0.784; OS, p = 0.870). In conclusion, PPPD should be the standard procedure for early AoV cancer.

Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice.

BACKGROUND AND AIMS: Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. APPROACH AND RESULTS: Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor-suppressing T cells within the tumor microenvironment. CONCLUSIONS: ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

Laparoscopic appendectomy under spinal anesthesia with dexmedetomidine infusion.

BACKGROUND: Laparoscopic appendectomy (LA) is rarely performed under regional anesthesia because of pneumoperitoneum-related problems. We expected that dexmedetomidine would compensate for the problems arising from spinal anesthesia alone. Thus, we performed a feasibility study of spinal anesthesia with intravenous dexmedetomidine infusion. METHODS: Twenty-six patients undergoing LA received spinal anesthesia with intravenous dexmedetomidine infusion. During surgery, the patient's pain or discomfort was controlled by supplemental fentanyl or ketamine injection, and all adverse effects were evaluated. RESULTS: No patient required conversion to general anesthesia, and all operations were completed laparoscopically without conversion to open surgery. Seventeen (65.4%) patients required supplemental injection of fentanyl or ketamine. Bradycardia occurred in seven (26.9%) patients. CONCLUSIONS: Spinal anesthesia with dexmedetomidine infusion may be feasible for LA. However, additional analgesia, sedation, and careful attention to the potential development of bradycardia are needed for a successful anesthetic outcome.

Graft rotation and late portal vein complications in pediatric living donor liver transplantation using left-sided grafts: long-term computed tomography observations.

Right-side rotation of the graft is an uncommon event after pediatric living donor liver transplantation (LDLT) with a left-sided graft. However, graft rotation might lead to gradual portal vein (PV) stretching and late portal vein complications (PVCs). The goal of this study was to quantify the degree of graft rotation (R) by computed tomography (CT) and to determine the effect of graft rotation on the development of late PVCs. One hundred ten patients underwent LDLT with left-sided grafts between 1996 and 2009; CT images were available and were reviewed for 66 of these patients. To quantify R, the following variables were measured with CT: the longest distance between the midline and the extrahepatic PV at the level of the hepatic hilum (A), the distance between the midline and the center of the superior mesenteric vein at the level of the confluence of the splenic vein and superior mesenteric vein (B), and the inner transverse diameter of the body cavity at the level at which A was measured (C). R was calculated as (A - B)/C. In patients with a patent PV (n = 59) and in patients with late PVCs (n = 7), the median R values were 0.16 (range = 0.03-0.38) and 0.25 (range = 0.13-0.39), respectively; there was a significant difference between the 2 groups (P = 0.003). Multivariate analysis showed that R ≥ 0.2 was the only independent risk factor for the development of late PVCs (P = 0.021). In conclusion, the gradual stretching of the PV after right-side rotation of left-sided grafts might play an important role in the development of late PVCs. PV patency should be closely monitored when graft rotation is noted during clinical follow-up.