Application of 3-Step Laparoscopic Cholecystectomy in Acute Difficult Cholecystitis.

BACKGROUND: With the aging of the global population, the incidence rate of acute cholecystitis is increasing. Laparoscopic cholecystectomy is considered as the first choice to treat acute cholecystitis. How to effectively avoid serious intraoperative complications such as bile duct and blood vessel injury is still a difficult problem that puzzles surgeons. This paper introduces the application of laparoscopic cholecystectomy, a new surgical concept, in acute difficult cholecystitis. METHODS: This retrospective analysis was carried out from January 2019 to January 2021. A total of 36 patients with acute difficult cholecystitis underwent 3-step laparoscopic cholecystectomy. The general information, clinical features, surgical methods, surgical results, and postoperative complications of the patients were analyzed. RESULTS: All patients successfully completed the surgery, one of them was converted to laparotomy, and the other 35 cases were treated with 3-step laparoscopic cholecystectomy. Postoperative bile leakage occurred in 2 cases (5.56%), secondary choledocholithiasis in 1 case (2.78%), and hepatic effusion in 1 case (2.78%). No postoperative bleeding, septal infection, and other complications occurred, and no postoperative colon injury, gastroduodenal injury, liver injury, bile duct injury, vascular injury, and other surgery-related complications occurred. All 36 patients were discharged from hospital after successful recovery. No one died 30 days after surgery, and there was no abnormality in outpatient follow-up for 3 months after surgery. CONCLUSIONS: Three-step laparoscopic cholecystectomy seems to be safer and more feasible for acute difficult cholecystitis patients. Compared with traditional laparoscopic cholecystectomy or partial cholecystectomy, 3-step laparoscopic cholecystectomy has the advantages of safe surgery and less complications, which is worth trying by clinicians.

Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

The ciliary protein Spef2 stimulates acinar Ampkα/Sirt1 signaling and ameliorates acute pancreatitis and associated lung injury.

Background: Pancreatic acinar cells are susceptible to nuclear factor kappa B (NF-κB)-mediated inflammation and resulting cell necrosis during early acute pancreatitis. As adenosine monophosphate-activated protein kinase alpha (Ampkα)/sirtuin 1 (Sirt1) pathway activity attenuates NF-κB activity, we examined whether the Ampkα/Sirt1 axis affects the progression of acute pancreatitis and associated lung injury in vivo. Furthermore, we explored the role of the ciliary protein sperm flagellar 2 (Spef2, Kpl2) in regulating Ampkα/Sirt1 activity in vitro and in vivo. Methods: Pancreatic injury, oxidative stress, acinar cell necrosis and apoptosis, acinar levels of Ampkα/Sirt1/NF-κB signaling activity, NF-kB-mediated inflammatory markers, and markers of associated lung injury were measured in rat models of acute pancreatitis following pharmacological Ampkα activation with A769662 or self-complementary recombinant adeno-associated virus serotype 6 (scAAV6)-mediated Spef2 overexpression. Additional in vivo rescue studies involving Ampkα silencing and/or constitutively active (CA)-Sirt1 overexpression were performed in acute pancreatitis rats. In vitro immunoblotting and Ampkα activity assays were conducted in the pancreatic acinar cell line AR42J. Results: Pharmacological Ampkα activation or Spef2 overexpression reduced acute pancreatitis severity, oxidative stress, necrosis, apoptosis, NF-kB-mediated inflammatory markers, and the degree of associated lung injury. Spef2 overexpression in AR42J cells in vitro promoted AmpkαThr172 phosphorylation and Ampkα activity. In vivo rescue studies revealed that Spef2's suppressive effect on acute pancreatitis and associated lung injury is mediated via the Ampkα/Sirt1 axis. Conclusions: This study established the existence of a Spef2/Ampkα/Sirt1 axis in pancreatic acinar cells that is involved in the regulation of NF-κB-mediated acinar cell inflammation and resulting cell necrosis during acute pancreatitis.