A Phase II Multicentre Trial of Endoscopic Ultrasound Guided Radiofrequency Ablation of Cystic Tumours of the Pancreas (RADIOCYST01)

Pancreatic cystic tumours are an emerging and growing diagnostic challenge for the clinician. Due to the widespread use of high quality crosssectional imaging techniques, between 1.2 to 2.6% of patients that undergo a CT for a nonpancreatic indication are found to have an incidental pancreatic cystic tumour. Pancreatic cysts encompass a range of pathologies from benign to malignant. Premalignant pancreatic cysts are known to be indolent for a number of years before transforming into an invasive cancer, creating a window of opportunity for intervention and cure. There is a strong correlation between pancreatic cysts and age. In a recent series of patients with incidental pancreatic cystic tumours, no cases were found in patients less than 40 years of age, while 8.7 percent of the patients aged 80 to 89 years had a pancreatic cyst. The natural history of pancreatic cystic tumours remains poorly understood, so significant uncertainty exists regarding the appropriate diagnostic workup, how to differentiate between benign and malignant lesions and choice of therapy.

Characterisation of pancreatic cystic lesions is usually made by a combination of noninvasive cross sectional imaging and where necessary, endoscopic ultrasound guided fine needle aspiration (EUSFNA) of tissue and/or cyst fluid. In those undergoing EUSFNA, fluid aspirates for cytology are obtained in up to 80% of cases but samples frequently have a low cellularity so sensitivity for diagnostic cytology ranges between 31% and 85%. Pancreatic EUSFNA is a safe test, with complication rates (mainly pancreatitis, rarely infection and bleeding) occurring in approximately 12.4%. Our own published complication rates demonstrated a 0% mortality and 0.6% morbidity (mild acute pancreatitis).

To guide treatment a consensus document was published by the International Association of Pancreatology in 2006 and updated in 2012. The guidelines recommend the surgical resection of all pancreatic cysts that cause symptoms or are larger than 3 cm, contain a mural nodule or are associated with dilatation of the main pancreatic duct. If the cyst is less than 3cm and does not have any of these features the guidelines recommend that the lesions can be safely followed up with serial imaging. They recommended annual imaging for lesions <10mm, 6 monthly imaging for lesions 1020mm and 3 monthly imaging for lesions >20mm. How long patients should be followed up for or when they should be referred for surgical resection is unclear and is associated with a growing surveillance cost to the NHS.

Surgical resection of the pancreas is a considerable undertaking and is associated with a significant morbidity (21 to 59%) and mortality (07%). In addition, many elderly patients have significant comorbidity and will not be fit enough to undergo pancreatic surgery. To date, there have been only a few small studies using ablative techniques as an alternative to surgical resection. EUSguided injection of alcohol has been associated with cyst ablation rates of 35 to 62%, on short term follow up. However, this technique did not achieve total cyst ablation in cysts with septations and was associated with complication rates (pain and pancreatitis) of 4 to 20%. A major potential advantage of EUS guided RFA is that ablation of septated cystic tumours is feasible and that treatment effects can be monitored under realtime EUS control.

Radiofrequency ablation: