The Epidemiology of Abdominal Pain in Inoperable Pancreatic Cancer and the Potential Role of Early Endoscopic Ultrasound-Guided Ceoliac Plexus Neurolysis

Koulouris, Andreas (2021) The Epidemiology of Abdominal Pain in Inoperable Pancreatic Cancer and the Potential Role of Early Endoscopic Ultrasound-Guided Ceoliac Plexus Neurolysis. Doctoral thesis, University of East Anglia.

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Abdominal pain commonly affects patients with inoperable pancreatic cancer. Its management relies mainly on strong opioid analgesia which is often ineffective, requires dose escalation and risks significant side-effects. Endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN) involves injecting a neurolytic agent into and/or around the coeliac plexus. It is often reserved for the latter stages of the patient’s treatment pathway when opioids have failed to control pain or their side-effects are unacceptable. It is unclear whether early EUS-CPN could prevent severe pain and reduce opiate burden in this patient group.
This research aims to explore the rationale, feasibility and design considerations of a clinical trial of early versus on demand EUS-CPN in patients with advanced pancreatic cancer. The first chapter reviews the anatomy and physiology of the normal pancreas, the clinical aspects of pancreatic cancer, the aetiopathogenesis of pain and its management.
The second chapter presents the results of a systematic review and meta-analysis of the efficacy of EUS-CPN in patients with pancreatic cancer-related abdominal pain. In addition, it estimates the individual efficacy of the three main technique variations of EUS-CPN: the central injection, the bilateral injection and the ganglia injection and provides a rationale for its use in clinical practice and in a future trial. The safety profile of EUS-CPN is also explored.
The third chapter reports a prospective observational study (The BAC-PAC study) where patients with newly diagnosed inoperable pancreatic cancer were followed up monthly with questionnaires on their pain levels, morphine use, quality of life and use of medical resources. This study provided data on pain-related and health economic parameters which would be assessed in a future trial. It also provides information on the methods of identification, recruitment and follow-up of patients in a future trial. Recruitment was hindered in part due to the COVID19 pandemic, and a separate study was developed to address this (chapter 5).
The fourth chapter presents the views of patients, their carers and pancreato-biliary endoscopists towards pain and endoscopic analgesia. Thematic analysis of interviews with an inductive and deductive approach was adopted. The experience of pain was found to be diverse among the patients and the intensity of pain is often under-reported. Low dose opioids are well-tolerated. The role of opioids is multi-dimensional: hypnotic, anxiolytic and soothing of the chemotherapy constitutional side-effects, such as generalised aches and myalgia. These properties may not be alleviated by EUSCPN. Patients were sceptical towards pain-preventative endoscopies because their emphasis is placed on imminent concerns, such as managing emotional distress or chemotherapy side-effects, rather than the potential for poorly-controlled pain in the future. The conduct and design of a future trial of early EUS-CPN requires effective communication with patients and their families, and strong Patient and Public Involvement (PPI) from the outset.
The fifth chapter details a longitudinal retrospective cohort study of 383 patients on the epidemiology of pain in patients with pancreatic cancer (PREDICT-PANC). This study was developed to meet key objectives of the BAC-PAC study given poor recruitment due to the COVID-19 pandemic. Pancreatic pain is prevalent in approximately 40% of patients in the first year of diagnosis. In 77% of the patients with pain, medical performance status was between 0 and 2, and should not be prohibitive of an endoscopic intervention, such as EUS-CPN. The median survival of those on opioids is 5.9 months. Clinical and radiological parameters at diagnosis are associated with the use of opioids at three months. A clinical model predictive of opioid use was constructed with good discrimination and calibration.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Kitty Laine
Date Deposited: 15 Jun 2022 15:17
Last Modified: 15 Jun 2022 15:17


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