Effect of Proton Pump Inhibitor in patients undergoing Endoscopic Ultrasound guided transluminal drainage of Walled Off Necrosis : A randomised controlled trial

Acute Pancreatitis(AP) is one of the most common gastrointestinal cause for hospital admissions. The spectrum of AP ranges from interstitial pancreatitis to necrotising pancreatitis. The severity of AP is classified into mild, moderately severe and severe based on  local complications and organ failure. The organ failure is classified based on the modified Marshall Scoring system. Necrotising pancreatitis is seen in around 10-15% of patients with AP, the necrosis can involve the pancreatic parenchyma(<5%), the peripancreatic tissue(20%) or both (75-80%).  The revised Atlanta classification has classified the pancreatic fluid collection into four categories based on the duration after onset of pancreatitis, the content of collection (liquid vs presence of solid debris) and presence or absence of encapsulating wall. The four categories are -Acute peripancreatic fluid collection, Acute necrotic collection, pseudocyst and Walled Off Necrosis(WON) . It is important to differentiate necrotic collection from other fluid collections. Magnetic resonance imaging(MRI) or Ultrasound is better modality than contrast enhanced computed tomography (CECT) to differentiate the same. WON (walled-off necrosis) is defined as a mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well-defined inflammatory wall. It is estimated that approximately 10%-15% patients with AP develop WON and majority of patients with WON requires interventions either due to infection, persistent SIRS, persistent organ failure or presence of pressure symptoms like abdominal pain, early satiety, weight loss or biliary duct compression. Management of WON in recent years is mainly done by step-up approach. Depending on the location of WON, it is drained by either endoscopic ultrasound (EUS) guided transluminal drainage or by percutaneous catheter drainage. If WON is predominantly located near the lesser sac or peripancreatic area, EUS guided drainage is feasible, however, if WON is predominantly mesenteric, or paracolic in location, percutaneous approach is used. After initial successful drainage, still 40-55% of patients still require step-up therapies in form of Direct Endoscopic Necrosectomy (DEN) or percutaneous catheter upgradation or Video Assisted Retroperitoneal Debridement (VARD) due to presence of large solid material or larger size of the collection. DEN involves passing the endoscope directly into the cavity and removing the necrosis mechanically(5). In a retrospective study,  47 % patients with WON required DEN in the course of illness and 27 % of these patients required at-least 4 sessions of DEN. In a recent study by L Yan et al, it was showed that around 74 % patients with WON required on demand necrosectomy. It was also shown that Pancreatic Fluid collections(PFCs) >10 cm in size, paracolic extension, or >30% solid necrosis are more likely to require step-up therapy and should be considered for early and aggressive endoscopic reintervention. In the last decade, the technical success and dissemination of knowledge regarding technique of EUS guided drainage of WON has improved drastically with availability of plethora of stents and cautery enhanced stents. However, despite that need for necrosectomy and instruments of necrosectomy still remains the same. Hence, even after achieving technical success in patients with WON, an optimum endoscopic necrosectomy remains an ‘Achilles Hill’ for the clinical success. Frequent requirement of necrosectomy results in repeated hospitalization, prolonged hospitalization, increases morbidity and over healthcare related costs. To circumvent this problem, in recent times, multiple novel devices like EndoRotor or H2O2 guided necrosectomy have been attempted.(15,16) However, availability of special device remains an issue. Moreover, effect of H2O2 guided necrosectomy is modest at best. Gao L et al., did a ex-vivo study on effect of normal saline, 5% sodium bicarbonate, 3% H2O2 and artificial gastric juice. In that study, they found that exposure of artificial gastric juice for 2 hours had highest efficacy in causing liquefaction of pancreatic necrosum compared to other materials. Based on this observation, Powers PC et al., did a multicentric retrospective study on effect of PPI on need for necrosectomy and risk of stent occlusion. In that study, they found that patients on PPI required higher number of necrosectomies compared to patients who were not on PPI (4.6 vs 3.2 respectively,P<0.01) and had higher risk of stent occlusion (20.1% vs 9.5%;p=0.012). Hamm J et al., also did a multicentric retrospective study comparing patients who were on continuous PPI vs not on PPI. In that study as well, patients who were on continuous PPI had higher rate of stent occlusion compared to patients who were not on PPI (29.8% vs 22.5%; p=0.039). However, in absence of any prospective study, role of usage of stoppage of PPI is still not clear. Hence, we decided to conduct a randomized trial to compare role of PPI in patients with WON who are undergoing EUS guided transluminal drainage.