In patients with chronic pancreatitis (CP), the most important clinical problem is the management of pain, which often occurs daily and is disabling [1, 2]. CP is also associated with pancreatic insufficiency, both endocrine and exocrine [3, 4], which develops in 50% and 80% of patients within 5 years, respectively. CP is related to several causative factors, most notably alcohol toxicity. Other factors such as genetics, anatomic abnormalities and autoimmunity also play a role .
In current practice, patients with CP are managed by a conservative step-up practice. The first step is medical management, ranging from pancreatic enzymes and mild analgesics to opioids. When medical management fails, the next step is usually endoscopic intervention. Surgical intervention is kept as an option of last resort when other treatments have failed and the severity of disease has increased substantially and pain becomes unmanageable [6, 7]. This approach is based on the so called ‘burnout hypothesis’, assuming that CP is a ‘self-limiting’ disease in which pain will ultimately resolve spontaneously due to progressive parenchymal destruction of the pancreas . Many reports have questioned the validity of this hypothesis, including the group that first introduced it [4, 8]. The main argument against the burnout hypothesis is the long time it takes for pain to subside; e.g. after 5 years of the onset of the disease about 60% of the patients will still experience substantial pain, and that in many reports complete insufficiency (‘burnout’) of the gland does not guarantee pain relief [4, 8].
As an alternative to the current conservative step-up practice, there is emerging evidence to suggest that surgery early in the clinical course of CP is beneficial in terms of pain control and pancreatic function. First, pathophysiological studies of pain in CP have shown that prolonged periods of pain are associated with peripheral and central nerve sensitization. Consequently, a self-perpetuating pain state develops, which is very difficult to reverse and manage . Secondly, experimental and clinical studies suggest that early surgical intervention can mitigate disease progression. In an experimental model of early versus late surgical drainage for CP in piglets, we have previously demonstrated that early surgery resulted in less histological cell damage and better exocrine pancreatic function . Clinically, two observational cohort studies have shown that surgical interventions, especially drainage procedures, have the potential to delay the progressive loss of pancreatic function in CP patients [11–13]. We recently also performed an observational study that supports the hypothesis that longstanding disease is associated with poor pain control after surgical intervention. In 266 consecutive patients undergoing an operation for CP we observed that surgery after 3 years of onset of symptoms was independently associated with worsened pain outcome and increased rates of endocrine pancreatic insufficiency. Additionally, preoperative use of opioids (indicative of severity of disease and time-delay to surgery) were significantly associated with bad outcome of surgery in terms of pain control .
Finally, in a small pilot randomized trial, 32 patients with early stage CP and dilated pancreatic duct were randomized between early surgical drainage and a conservative approach [13, 15]. Substantial pain relief was observed in 16/17 (94%) patients in the surgical group compared to 2/15 (13%) patients in the conservative group. New onset endocrine and exocrine pancreatic insufficiency were respectively observed in 2/13 (15%) and 1/15 (7%) in the early surgical group compared to 10/12 (83%) and 11/14 (79%) in the conservative group .
Despite the evidence suggesting a benefit of early surgery, most patients with chronic pancreatitis are not managed by this approach in current practice. Therefore, the Dutch Pancreatitis Study Group designed a randomized controlled multicenter trial to evaluate the benefits, risks and costs of early surgical intervention: the Early Surgery versus Optimal Current Step-up Practice for Chronic Pancreatitis (ESCAPE) – trial.