PTBS has been used in patients with malignant obstructive jaundice who are not suitable for surgery. Compared with endoscopic retrograde cholangiopancreatography (ERCP) (3%-10%), the morbidity of pancreatitis after PTBS is lower (0.8%-5.1%) [1, 9, 16]. In this research, the morbidity of postoperative pancreatitis was 20%, which is higher than that in previous studies. That’s probably because this research only selected patients with distal malignant biliary tract obstruction. Some scholars believe that postoperative pancreatitis is more likely to occur in patients with relatively low obstruction, which probably owing to a higher incidence of stimulation of the pancreas during the procedure.
To the best of our knowledge, studies on risk factors of acute pancreatitis after PTBS are scarce. In a previous meta-analysis, female gender, difficult cannulation, previous pancreatitis, previous post-ERCP pancreatitis (PEP), intraductal papillary mucinous neoplasm (IPMN), sphincter of Oddi dysfunction (SOD), endoscopic sphincterotomy (EST), precut sphincterotomy and main pancreatic duct injection are risk factors for post-ERCP pancreatitis [17, 18]. Combined with previous reports and clinical experience, 20 variables were included in our study to analyze their influence on pancreatitis after PTBS (Table 1). In previous studies, main pancreatic duct injection was a risk factor of postoperative pancreatitis, while the morbidity of postoperative pancreatitis in patients who had atrophy of pancreas and dilation of main pancreatic duct significantly decreased [19]. In present study, main pancreatic duct injection and main pancreatic duct expansion were not significant risk factors (P = 0.857, P = 0.296, respectively).
Univariate analysis showed that stent type, stent implantation across the duodenal papilla, preoperative white blood cell count > 10 × 10 9 /L, preoperative alkaline phosphatase level and preoperative (within 3 days) administration of PPIs were significant influence factors for postoperative pancreatitis. Our results show that the OR of preoperative white blood cell count > 10 × 10 9 /L was 0.107, which suggested this variable has a protective effect. One explanation of this condition may be that clinicians usually treat patients who have leukocytosis with antibiotics. Meanwhile, some scholars believe that prophylactic use of antibiotics before surgery may reduce the risk of postoperative infection. Therefore, preoperative administration (within 3 days) of antibiotics was enrolled in the multivariate analysis instead of white blood cell count. Multivariate analysis showed that stent type, stent implantation across the duodenal papilla, preoperative administration of PPIs and preoperative administration of antibiotics have statistically significant difference, stent implantation across the duodenal papilla and preoperative administration of PPIs were risk factors for developing pancreatitis, while preoperative administration of antibiotics was a protective factor. The OR of alkaline phosphatase is close to 1, which reveals that it has little influence on the occurrence of pancreatitis. In this study, the postoperative pancreatitis rate with different stent was statistically significant. However, bias such as the capacity for medical payment by patients in the choice of stents should not be ignored. Thus, our study could not properly assess whether pancreatitis rate is significantly related to stent types, and a large sample multicenter trial is necessary.
If biliary tumors involve the lower part of the common bile duct or the ampulla, it is inevitable that the stent will cross the duodenal papilla. However, stents placed across the duodenal papilla can block the discharge of pancreatic fluid, leading to acute pancreatitis [20]. Generally speaking, the length of the stent to enter the intestinal tract should be controlled within 1 cm to avoid the stimulation and injury of the distal end of the stent to the contralateral duodenal wall of the ampulla. If biliary tumors are located in the middle part or above of the common bile duct, the stent should not cross the duodenal papilla as far as possible, so as to retain the important function of the duodenal papilla. At this time, the lower edge of the bracket should not be too close to the duodenal papilla. If the distance between them is < 2 cm, there may be a possibility of papilla spasm. Shunsuke Sugawara et al. [19] found that biliary stent implantation across the papilla for MBO would increase the morbidity of pancreatitis, which was consistent with the present study. Some scholars also believe that no matter whether the tumor involves the lower segment of the common bile duct and the ampulla, the stent should be placed across the duodenal papilla in order to facilitate drainage and reduce the incidence of cholangitis after stent implantation, which is still controversial and needs more clinical evidence to support [21]. When it comes to the fact that the disease indicates the need to stent across the papilla, clinicians can take preventive measures preoperatively in order to reduce the risk of pancreatitis.
PPIs combined with somatostatin are commonly used in the treatment of acute pancreatitis [22–24]. However, the prophylactic effect of using PPIs alone on the risk of acute pancreatitis is controversial since some studies suggest that its efficacy is limited to patients at high risk of postoperative pancreatitis. PPIs work on gastric wall cells and block acid production by inhibiting H+-K+-ATPase. However, a previous study revealed that PPIs therapy did not show benefit on alleviating systemic inflammatory response and clinical scores in severe pancreatitis patients [25]. In addition, gastric acid is an important barrier for the body to prevent abnormal colonization of bacteria in the upper digestive tract. Theoretically, inhibition of gastric acid secretion by PPIs may lead to abnormal composition and higher temporal instability of their intestinal microbiota, which may be an initiating factor for associated infections of pancreas.
The effect of PPIs consumption on the risk of pancreatitis after PTBS has not been investigated. According to a previous study reported by Carmelo Scarpignato et al. [26], PPIs did not affect the clinical course of acute pancreatitis, so they are not recommended routinely in this clinical setting [27, 28]. In the present study, multivariate analysis showed an increased risk of postoperative pancreatitis was associated with preoperative administration of PPIs, and the difference was statistically significant. As a consequence, the management of PPIs abuse before surgery should be emphasized.
Several studies have shown that strategies such as the administration of periprocedural antibiotic could decrease the incidence of postoperative complications. Rty S et al. [29] found that antibiotic prophylaxis effectively decreases the risk of pancreatitis. Multivariate analysis in the present study revealed that preoperative administration of antibiotics has been linked to lower incidence and severity of postoperative pancreatitis, which is an independent protective factor.
There are several limitations in our study. First, this was a single-center retrospective study, in all patients with pancreatitis, the increase of amylase and lipase was detected in emergency laboratory only after presenting symptoms such as abdominal pain, nausea and vomiting. It cannot be excluded that some patients without clinical symptoms also have the increase of amylase and lipase. Thus, the authenticity of the assessed data was relatively low to some extent. Second, clinical treatment strategies, such as stent implantation position and the selection of stent, were decided by the physician. As a result, selection bias may have inflated the results. Additionally, the uneven surgical ability of different surgeons may also cause different prognosis.
In conclusion, biliary stent implantation across the duodenal papilla may significantly increase the risk of postoperative pancreatitis. Preoperative (within 3 days) administration of PPIs was another independent risk factor. Consequently, PPIs should be used with great caution before operation. Moreover, prophylactic administration of antibiotics before PTBS may reduce the risk of pancreatitis.