Preventing recurrent *idiopathic* acute pancreatitis through laparoscopic cholecystectomy (PICUS-2):
a multicenter randomized trial

Acute pancreatitis occurs in 6,500 patients annually in the Netherlands. In 25%
of these cases no definitive cause can be determined after routine medical
check-up. These cases are deemed to be idiopathic acute pancreatitis (IAP). IAP
has a high recurrence rate due to the unknown cause of the disease. It is
hypothesized that microlithiasis and biliary sludge are the most common causes
of IAP. Laparoscopic cholecystectomy (LC) is highly effective in treating
microlithiasis and biliary sludge as a cause of acute pancreatitis. Currently
no trial has been done comparing LC with conventional treatment for IAP in
patients with *true* idiopathic acute pancreatitis, where an EUS (endoscopic
ultrasound) has been performed.

The goal of this trial is to determine the efficacy of LC in patients with IAP
in the prevention of recurrent acute pancreatitis and biliary events. The
secondary goal of this trial is to assess the occurrence of biliary events,
complications of LC, number and severity of recurrent episodes of pancreatitis,
quality of life (QALY), costs (hospital and societal) and cost-effectiveness.

Only *true* idiopathic acute pancreatitis will be included, excluding all
patients with biliary acute pancreatitis. To accomplish this goal EUS will be
performed in all included patient and solely EUS negative patients will be
included.

This study was designed to be a multicenter randomized controlled superiority
trial. Patients with a first episode of idiopathic will be screened for
eligibility. These patients have undergone the routine work-up for acute
pancreatitis as described in appendix A. In this work-up an EUS after repeat
transabdominal ultrasound will also be performed. When this work-up does not
reveal a definitive aetiology of the acute pancreatitis, idiopathic acute
pancreatitis as a diagnosis is assumed. Informed consent to participate in the
PICUS-2 trial will be obtained from these patients. In total 262 patients will
be included in this trial. Patients will be randomized in two groups. Patients
in one group will receive conventional treatment for idiopathic acute
pancreatitis, while the other group receives laparoscopic cholecystectomy.
Follow-up will start after the randomization of the patients and will take up
one year.

Laparoscopic cholecystectomy will be performed by a surgeon in routine
practice. The GI-surgeon will report possible complications of LC, such as bile
duct injury and bleeding, requiring the need for additional surgical,
endoscopic, or radiological intervention, infection and other complications
such as pneumonia, bacteraemia, and new-onset organ failure.

Conventional treatment for idiopathic acute pancreatitis consists of fluid
resuscitation, pain treatment and no oral intake (in case of severe
pancreatitis). Possible complications following acute pancreatitis must be
conservatively treated. If indications for intensive care treatment are present
(eg. Shock or respiratory insufficiency) intensive care treatment will be
initiated.

Should the patient be readmitted for a recurrence of acute pancreatitis after
the routine work-up could not find a cause for this recurrent episode,
performing an additional MRCP is recommended in order to rule out structural
anomalies such as pancreas divisum, as is in accordance with current guidelines.

All included patients will be asked to fill out five questionnaires over a
period of 12 months. The questionnaire contains questions concerning the
quality of life of the patient in a validated Dutch translation. The patient
will also be asked to grant permission to the investigators regarding access to
their medical records to collect data on medical history, readmissions,
recurrence and complications.

The intervention of this study is a laparoscopic cholecystectomy performed
within four weeks of the first episode of idiopathic acute pancreatitis or
during initial admission.

The risks of a cholecystectomy are small and include a 0.5% risk of bile duct
injury and 5% risk of (wound) infection. A further burden for the patient is
the recovery period ranging from one to max four weeks until full recovery.

As a result of this study it is expected/ estimated that a relative reduction
of 60% of recurrent pancreatitis can be achieved by performing laparoscopic
cholecystectomy. Pancreatitis causes severe pain to the patient in combination
with a 3 to 5% risk of mortality, therefore a reduction in recurrent acute
pancreatitis cases significantly reduces these burdens for the patient.