The PONCHO trial is designed to answer the question of whether early cholecystectomy leads to a reduction of re-admissions for biliary events in patients with a first episode of mild biliary pancreatitis.
Several treatment guidelines state that cholecystectomy should be performed in the first weeks after recovery of mild biliary pancreatitis in order to minimize re-admissions for biliary events [4, 6, 7, 10, 11, 16]. In a systematic review we demonstrated that cholecystectomy should probably be performed during index admission because an early procedure was not associated with an increased risk of complications whereas interval cholecystectomy (after median 40 days) was associated with a biliary event recurrence rate of 18% . In contrast to this finding, several nationwide audits from the UK, the USA, Germany and Italy have shown that most patients undergo cholecystectomy weeks or even months after discharge from the hospital for mild biliary pancreatitis [12–15]. As long as the gallbladder is in situ, these patients are at increased risk for re-admissions for biliary events including a potentially fatal episode of acute pancreatitis or other biliary events.
Why are surgeons not routinely performing early laparoscopic cholecystectomy after biliary pancreatitis? Early cholecystectomy may have three potential downsides: a technically more difficult and demanding procedure potentially resulting in more complications; poorer patient condition; and logistical hurdles.
Traditionally, early cholecystectomy has been suggested to be technically more demanding than interval cholecystectomy but data to support this statement are lacking. Notably, a recent study found that early cholecystectomy was technically less demanding, which is in keeping with the nature of peritoneal healing and adhesion formation . This concept is supported by a recent retrospective study from India that focused on difficult dissection during laparoscopic cholecystectomy after mild biliary pancreatitis .
Traditionally, it is felt that patients should recover fully from pancreatitis prior to cholecystectomy being performed. However, the current study will only include patients with mild pancreatitis who are fit to undergo surgery. In contrast to severe pancreatitis, patients with mild pancreatitis recover quickly, and are discharged within 5 to 10 days after admission.
Problems with operating room capacity could arise due to the need for semi-urgent (<72 hours) cholecystectomy. In the participating centers, however, dedicated operating room programs for semi-urgent surgery are present, and hence no major problems with protocol compliance are envisaged [41.
The only way to provide convincing, level I evidence that early cholecystectomy is indeed superior to interval cholecystectomy is to perform a randomized controlled trial. A double-blinded controlled trial would be the optimal design. However, due to the difference in timing of cholecystectomy, blinding is not possible. To compensate for this fact there will be a blinded outcome assessment.
A time interval of 72 hours was chosen for the early cholecystectomy group to provide a feasible time frame for semi-urgent cholecystectomy by an experienced surgeon. The 25-day to 30-day interval (4 weeks) was chosen as a trade-off between: the Dutch guideline that advices cholecystectomy within 3 weeks after discharge, and the data from our retrospective multicenter study demonstrating that cholecystectomy is delayed for 6 weeks in current Dutch clinical practice .
The rationale for including ASA I and II older people/octogenarians is because several series have demonstrated that cholecystectomy is safe, even after ES, in older patients [42, 43]. Patients with severe pancreatitis are excluded because this is considered an indication for delayed cholecystectomy .
For the proper timing of randomization we have chosen five discharge criteria that all have to be fulfilled in order to only include patients who are fit to undergo surgery and are without signs of severe pancreatitis. In contrast to severe pancreatitis, patients with mild pancreatitis recover quickly and are typically discharged within 5 to 10 days. There will be a variation in time since the onset of pancreatitis and hospital admission and between admission and discharge. This variation is mainly caused by co-morbidity. Owing to the randomization, there should be no relevant differences between both study arms.
The primary endpoint is a composite endpoint of mortality and re-admissions for biliary events. This composite endpoint was chosen because a study aimed at demonstrating a reduction in mortality only would require an unrealistic large sample size. In addition, other studies have shown that re-admissions for biliary events have much impact on the prognosis of patients .
The PONCHO trial is a randomized controlled multicenter trial designed to show a reduction in the composite primary endpoint of re-admissions for biliary events and mortality following an early cholecystectomy compared with an interval cholecystectomy in patients with a first episode of mild biliary pancreatitis.
The trial was registered in the ISRCTN register on 29 June 2010. The first patient was randomized on 22 December 2010. As of 21 October 2012, 172 patients have been randomized and inclusion is on schedule.