Impact of body mass index on the incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis

Introduction

Acute pancreatitis is a major complication after endoscopic retrograde cholangiopancreatography (ERCP). The incidence of post-ERCP pancreatitis (PEP) ranges from 1-9% in average-risk patients [1] and from 11-40% in high-risk patients, with a 0.1% mortality risk related to pancreatitis and an annual healthcare expenditure totaling $199 million in the United States [2-9].

Risk factors for PEP have been studied extensively and are classified into patient- and procedure-related factors. Procedure-related risk factors include difficult or failed biliary cannulation, biliary sphincter balloon dilatation, pancreatic sphincterotomy and pancreatic duct injection. Patient-related factors such as young age, female sex, suspected sphincter of Oddi dysfunction, history of recurrent pancreatitis, history of prior PEP, and absence of chronic pancreatitis have all been shown to increase the likelihood of PEP [10-13]. Identification of these risk factors has allowed clinicians to risk-stratify patients and determine if PEP prophylaxis is necessary.

Studies have shown that obesity may contribute to the incidence, severity and mortality of acute pancreatitis [14-17]. This is presumably due to the chronic low-grade inflammatory state that has been observed in obese patients [18]. Obesity is also associated with decreased levels of adiponectin, an anti-inflammatory adipokine that may be a protective factor for acute pancreatitis [19]. Additionally, peripancreatic and retroperitoneal fat deposits could be susceptible to fat necrosis and increase the risk of additional local complications of acute pancreatitis, such as abscesses and pseudocysts [15].

The correlation between obesity and the incidence and severity of PEP has not yet been elucidated. A larger retrospective study of 964 patients by Deenadayalu et al showed that rates of PEP did not differ between patients with a body mass index (BMI)≥30 kg/m2 and those with BMI<30 kg/m2 (12.5% vs. 16.4%, respectively, P=0.14).

In contrast, Cotton et al showed that obesity is associated with post-ERCP complications, including PEP [20]. To complicate things further, a recent retrospective study of 583 patients by Fujisawa et al demonstrated that obese patients (BMI≥30 kg/m2) had a significantly higher rate of PEP compared to overweight (BMI 25-30 kg/m2), normal-weight (BMI 18.5-25 kg/m2), and underweight (BMI<18.5 kg/m2) patients. However, one of the limitation of the Fujisawa et al study that only 20 patients were obese [21]. Furthermore, Kumar et al performed a national database analysis that was suggestive of a positive correlation between obesity and PEP (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.25-1.92) [24].

While numerous studies have examined the relationship between obesity and acute pancreatitis, far less is known about low BMI and acute pancreatitis, let alone PEP. Fujisawa et al reported that underweight patients (BMI<18.5) had higher rates of PEP compared to normal-weight individuals (BMI 18.5-25). There was no difference in the severity of PEP between normal- and underweight patients [19]. In comparison, a study by Deenadayalu et al examined the incidence of PEP in patients with BMI<20 and found no increase in PEP [21]. In this study, we aimed to better clarify the relationship between BMI and the incidence and severity of PEP.

Patients and methods

After approval by the University and Medical Center Institutional Review Board at East Carolina University/Vidant Medical Center, we conducted a retrospective study of all ERCPs performed at the Center from January 2009 to October 2016. The study included all patients who underwent diagnostic or therapeutic ERCP within the study period.

The procedures were performed by 4 experienced endoscopists. All patients underwent ERCP with a standard duodenoscope (JF 260 or 260V; Olympus Optical Co., Ltd., Tokyo, Japan). Patient characteristics and procedural details were collected. Patients noted to have had acute pancreatitis within 72 h before the procedure were excluded from the study.

We reviewed patient demographic information, relevant medical history and home medications. All available laboratory blood work, pre- and post-procedure imaging studies, and follow-up documentation were also reviewed. Procedure details, including sphincterotomy, biopsy, stent placement/removal, cannulation of the common bile duct, cannulation of the main pancreatic duct, cholangiogram, and pancreatogram were noted. Type and size of any endobiliary stent were noted, along with information on other interventions performed during the ERCP.

Follow up

All the documented complications of ERCP in the electronic health record from subsequent admissions, emergency room or follow-up clinic visits, nurse’s post-procedure phone calls and notifications of admission to another hospital or emergency room were reviewed. Complications were collected, including post-ERCP pancreatitis, end-organ damage, pancreatic necrosis, and death.

Results

A total of 2236 patients whose BMI was recorded and who had adequate follow up were included in the final analysis. The average patient age was 60±18 years; 1247 (56%) patients were female, and 991 (44%) were male. The average BMI was 29±8 (kg/m2). Procedure risk factors did not differ between the 2 groups.

Study outcome

Overall, 17% of the patients who underwent ERCP were high-risk for PEP. PEP was diagnosed in 107 (4.8%) patients. In total, 921 patients had BMI≥30 kg/m2 while 1315 patients had BMI<30 kg/m2. There was no statistically significant difference in the procedure or patients’ risk factors between the patients in the low- (<30 kg/m2) and high-BMI (≥30 kg/m2) groups. Of the 921 patients with BMI≥30, 49 were diagnosed with PEP (5.3%). In comparison, 58 patients (4.4%) were diagnosed with PEP of the 1317 patients with BMI<30 kg/m2 (odds ratio [OR] 1.2, 95%CI 0.82-1.8; P=0.32). There was no difference in the incidence of PEP in BMI subgroups (Fig. 1).

Figure 1 The number of PEP in each of the BMI subgroups PEP, post-endoscopic retrograde cholangiopancreatography pancreatitis; BMI, body mass index

In the univariate analysis, the following factors were associated with PEP: female aged <40 years, biliary sphincterotomy, pancreatic sphincterotomy, cannulation of the main pancreatic duct, contrast injection into the pancreatic duct (limited and complete pancreatogram), difficult cannulation, failed pancreatic duct stent placement, and a history of recurrent acute pancreatitis (Table 1).

Table 1 Incidence of PEP according to risk factors

In the multivariate model, female sex and <40 years of age, biliary sphincterotomy, pancreatic sphincterotomy, contrast injection into the pancreatic duct (limited and complete pancreatogram), difficult cannulation, and failed pancreatic duct stent placement were associated with PEP. However, BMI≥30 did not impact the incidence of PEP (OR 1.1, 95%CI 0.75-1.8; P=0.48) (Table 2). Likewise, there was no difference in the incidence of PEP in the subgroup analysis of different BMI categories (Table 3).

Table 2 Factors associated with PEP, multivariate analysis

Table 3 Incidence of PEP by BMI groups

Discussion

Results from our study indicated that increased BMI (≥30 kg/m2) does not increase the risk of PEP. Furthermore, different subcategories of BMI, including underweight, overweight, obese and morbidly obese, are not associated with a different incidence of PEP compared to normal-weight patients. Our results were consistent with those of Deenadayalu et al [21].

Likewise, our study clearly demonstrates that an increase or decrease in BMI does not impact the severity of PEP. We used the revised Atlanta classification to categorize the severity of PEP [22]. Persistent organ failure and necrosis were distributed equally between the obese and non-obese patients. Our results differ from observational studies that suggest obesity increases the incidence, severity, and mortality of acute pancreatitis [14-17]. This may be explained by differences in the etiology and mechanism of acute pancreatitis (such as alcohol or hypertrygliceridemia) and PEP. It has been suggested that local injury to the papilla from instrumentation, sphincterotomy or forceful and repetitive injection of contrast causes papillary edema or spasm. This is thought to result in ductal hypertension followed by reduced pancreatic duct drainage. The poor drainage initiates an inflammatory cascade, promoting intraluminal activation of proteolytic enzymes and autodigestion of the pancreas. Significant release of cytokines (interleukin -1, -6, and -8) results in a systemic inflammatory response with multiorgan involvement [8,23].

There are several strengths to our study, including the large sample size. Given the relatively low incidence of PEP, a large sample size is imperative for the study to have enough power to detect differences in PEP between various BMI groups. To date, this is the largest retrospective study to investigate the relationship between PEP and BMI. Another strength of our study is the comprehensive dataset, which includes all possible confounders and the use of univariate and multivariate analyses to accurately define the impact of BMI on PEP.

The study has a few notable limitations. First, BMI was used as a surrogate for obesity. BMI is imperfect, as it uses weight rather than body composition and therefore cannot distinguish between adiposity and increased muscle mass. Second, while our study had a large sample size, it was retrospective in design and was thus susceptible to confounding. We attempted to adjust for this using univariate and multivariate analysis to detect any confounding variables.