Abstract
Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study. Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group. Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.
Highlights
While a variety of techniques are available to restore biliary-enteric continuity, the biliary tree is most commonly anastomosed to the jejunum; choledochojejunostomy (CJS) has been widely adopted to biliary surgeries and represents a routine method of biliary reconstruction after surgical resection of pancreatic head carcinoma, cholangiocarcinoma, ampullary carcinoma, duodenal papillary carcinoma, and other tumors (Hirano et al, 2012; Singh and Arora, 2014)
Our study aims to figure out the potential effect of combining anisodamine with neostigmine on local scar formation at anastomotic stoma in the novel rat model following Roux-en-Y choledochojejunostomy (RCJS)
Since the procedure inevitably brings destruction to the function of Oddi’s sphincter, intestinal content and bile reflux have always been a huge problem in spite of the great progress we have made in medical techniques, and recurring cholangitis caused by intestinal fluid reflux will cause scar hyperplasia, eventually resulting in CJS stenosis and even canceration (Asano et al, 2016; Dimou et al, 2016)
Summary
While a variety of techniques are available to restore biliary-enteric continuity, the biliary tree is most commonly anastomosed to the jejunum; choledochojejunostomy (CJS) has been widely adopted to biliary surgeries and represents a routine method of biliary reconstruction after surgical resection of pancreatic head carcinoma, cholangiocarcinoma, ampullary carcinoma, duodenal papillary carcinoma, and other tumors (Hirano et al, 2012; Singh and Arora, 2014). As the morbidity of cancer and radical resection rate increased in recent years, CJS is gaining more and more popularity in clinical settings, among which Roux-en-Y choledochojejunostomy (RCJS) is the most commonly used surgical procedure in clinical practice. Continuous stimulation of refluxing fluid can lead to cholangitis and local scar tissue hyperplasia, eventually causing CJS stenosis and even cancer (Kadaba et al, 2017; Bettschart et al, 2002). Our previous research studies concluded that the root cause of anastomotic scar formation is the early inflammatory stimulation caused by intestinal content reflux which leads to the activation of fibroblasts and the proliferation of collagen and smooth muscle fibers, forming a scar (Lyu et al, 2021). The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model
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