Endoscopic ultrasound guided central versus bilateral celiac plexus neurolysis for pain management in advanced pancreatobiliary cancer: An Assessor blinded randomised controlled trial

Patients with Pancreatico-biliary malignancies have disabling abdominal pain which is a frequent symptom in patients due to the perineural invasion of tumor cells, and present in 70%–90% of the patients at diagnosis and has very complex medical management. It markedly reduces the quality of life and is considered a prognostic factor for survival. Medical management for pain is often challenging and usually begins with the administration of nonopioid analgesics followed by opioids in refractory cases. High dosage of analgesics often cause reduction in patient’s survival & hamper Quality of Living. Opioids often provide suboptimal pain relief but have many adverse effects, such as nausea, constipation, urinary retention, drowsiness, and can lead to patient tolerance.

The Celiac plexus (CP) is responsible for transmitting pain sensations originating from the upper abdominal organs, including the pancreas, liver, gallbladder, stomach, and ascending and transverse colons. When a neurolytic agent is injected into the celiac plexus, it disrupts the transmission of pain signals from afferent nerves to the spinal cord.

Traditionally, access to the celiac plexus has been done under fluoroscopic, computed tomography (CT) guided, ultrasound (USG) guided. These guided procedures were technically difficult and it was necessary to avoid the different structures while performing access to celiac plexus.However, endosonographic (EUS) approach is advantageous in multiple ways. Firstly, it allows CPN to be performed close enough to the celiac plexus through the gastric wall, which is much safer and has more effective access. Secondly, Better control of the needle above or lateral to the celiac trunk, real-time guidance, short puncture distance, use of the anterior pathway, avoiding puncture through the posterior diaphragm space and use of Doppler to visualize vessel interposition.

Endosonography-guided celiac plexus neurolysis (EUS-CPN) was first introduced by Faigel et al. and Wiersema in 1996. It is an alternative in patients who have refractory pain or cannot tolerate increas­ing amounts of opioid medications or analgesic ceiling is achieved because of neurotoxicity. EUS-CPN is performed to ameliorate pain and reduce the dosage of analgesics.   Furthermore, a recent study suggested that early EUS-CPN provides better pain-relief and greater reduction in morphine consumption than conventional management. EUS-CPN achieve chemical ablation of the nerve tissue by injection of Absolute ethanol (usual neurolytic agent) and local anaesthetic (mainly bupivacaine) into the celiac plexus.  It induces a local inflammatory reaction which is followed by fibrosis during the healing process.

The timing of the celiac intervention relative to pain onset appears to be an important predictor of pain response in patients with pancreatic cancer. Early pancreatic cancer pain appears to derive mainly from the celiac plexus involvement, while pain during the terminal stages of the disease may also involve other visceral, bone metastasis and somatic nerves involvement. Thus, CPN performed soon after the onset of pain from pancreatic cancer may increase the rate of response.

EUS-CPN is performed by 2 Approaches. Firstly, is the central technique which involves injection of a neurolytic agent at the base of the celiac axis. In the bilateral technique, the neurolytic agent is injected on both sides of the celiac axis. This study aims to assess and compare the pain response rate & efficacy in patients undergoing EUS-CPN for refractory pain via both techniques i.e. Unilateral and Bilateral approach.