Early Cholecystectomy Questioned for More Severe Acute Biliary Pancreatitis

Early — rather than delayed — cholecystectomy for adults hospitalized with more severe cases of acute biliary pancreatitis (ABP) was associated with worse postoperative outcomes, an international study found.

Among 378 patients with moderately severe and severe ABP consecutively treated with cholecystectomy, higher postoperative rates of mortality, morbidity, and infection were observed in those who received early versus delayed cholecystectomy (P<0.001 for all):

• Mortality: 15.6% vs 1.2%, respectively
• Morbidity: 30.3% vs 10.3%
• Infection: 14.6% vs 1.3%

As described in JAMA Surgery, higher mortality or morbidity after early cholecystectomy in this more severe subset of patients was linked with patient age, American Society of Anesthesiologists score, absence of preoperative bile duct clearance by endoscopic retrograde cholangiopancreatographies (ERCPs), and severe ABP-related complications requiring surgical interventions.

The findings provide “real-life data on a gray area of the literature, namely, the treatment of patients with moderately severe and severe ABP,” according to researchers led by Marcello Di Martino, MD, PhD, of the A.O.R.N. Cardarelli in Naples, Italy.

In their study, patients with this more-advanced presentation of ABP tended to be more frail and, not surprisingly, had significantly worse postoperative outcomes compared to those with mild ABP.

“Consequently, these patients should be treated carefully,” the study authors concluded. “Based on the current evidence, it is recommended that older and more fragile patients with severe complications of moderately severe and severe ABP or those without bile duct clearance should not be considered for [early cholecystectomy].”

The goal of cholecystectomy in ABP is to thwart recurrent attacks of the disease. Without it, ABP carries up to a 33% risk of recurrence, and current guidelines recommend early cholecystectomy (within the first 2 weeks of admission) for patients hospitalized with mild ABP.

But the timing of the procedure in moderately severe and severe ABP “remains controversial and unclear,” noted Panu Mentula, MD, PhD, and Pauli Puolakkainen, MD, PhD, both of Helsinki University Hospital, writing in an accompanying editorial.

Despite the study findings, cholecystectomy as a prophylactic measure could potentially be indicated for moderately severe ABP cases, they suggested, but not for critically ill patients with severe disease and multiple organ failure.

“In these patients, cholecystectomy should probably be postponed until the patients have recovered from organ dysfunctions, which usually takes more than 2 weeks,” they said. “However, cholecystectomy could be performed simultaneously with surgical procedures that are performed to treat severe ABP.”

Mentula and Puolakkainen said the findings should be interpreted with caution given the study’s various limitations, including the extensive statistical testing without P-value adjustment and the likelihood of selection bias when it came to the timing of cholecystectomy.

“The mortality risk in severe ABP is high during the first 2 weeks, whereas the risk is considerably lower after 4 weeks from the disease onset,” the editorialists wrote. “Therefore, increased mortality and morbidity might be related to the ABP and not to cholecystectomy.”

The duo pointed out that a quarter of the moderately severe and severe ABP patients in the study also underwent surgical necrosectomy, though the timing of the procedure was not detailed.

“If necrosectomies are performed simultaneously with cholecystectomies, it is more likely that morbidity and mortality are associated with early necrosectomy,” wrote Mentula and Puolakkainen.

To conduct their analysis, Di Martino and colleagues used data from the MANCTRA-1 (Compliance With Evidence-Based Clinical Guidelines in the Management of Acute Biliary Pancreatitis) study, which included more than 5,000 patients hospitalized for ABP at centers across 42 countries in Europe, Asia, Africa, South America, and Oceania from January 2019 to December 2020.

Of the 3,696 patients in the current study (all of those who ultimately underwent cholecystectomy), the vast majority had mild disease (90%) per revised Atlanta classification, while 7% had moderately severe disease and 3% had severe disease. A little less than a third underwent early cholecystectomy while the remaining received delayed cholecystectomy. Median patient age was 58.5 years, and 51.5% were women.

Across all patients, early versus delayed cholecystectomy was associated with higher postoperative mortality (1.4% vs 0.1%, respectively) and morbidity (7.7% vs 3.7%; P<0.001 for both). Patients undergoing early cholecystectomy for mild ABP had significantly lower rates of mortality (0%), morbidity (5.5%), and infection (0.4%) when compared with those with more severe cases.

Regardless of ABP severity, patients undergoing early cholecystectomy tended to be younger (57 vs 60 years) and were more likely to have ischemic heart disease (11.9% vs 8.4%) than those receiving delayed cholecystectomy. Those in the early group were also more likely to undergo ERCPs (27.3% vs 20.7%) or surgical necrosectomy (2.2% vs 0.8%), and to have severe ABP complications requiring surgical intervention (1.9% vs 0.6%).

In adjusted analyses, factors associated with increased mortality after early cholecystectomy included moderately severe and severe ABP (OR 361.46 vs mild disease, 95% CI 2.28-57,212.31) and severe complications of ABP requiring surgical intervention, such as abdominal compartment syndrome, bowel ischemia, and bowel fistula (OR 646.44, 95% CI 5.55-75,261.08). Factors associated with increased morbidity after early cholecystectomy included moderately severe and severe ABP (OR 2.64, 95% CI 1.35-5.19) and severe ABP-related complications requiring surgical intervention (OR 6.77, 95% CI 1.74-26.36).

Limitations cited by Di Martino and his fellow study authors included the retrospective nature of the analysis, the different levels of expertise across centers, and possible underrepresentation of patients with early cholecystectomy.

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