ABSTRACT: ANTIOXIDANT THERAPY IN CHRONIC PANCREATITISChronic pancreatitis (CP) is characterised by chronic, frequent, disabling abdominal pain. It often leads to exocrine and endocrine insufficiency resulting in malabsorption and diabetes mellitus respectively. The incidence of CP is 5-10 per 100,000 population worldwide and is on the rise in UK.Alcohol (70%) is the commonest aetiologic cause, idiopathic (20%) and others (10%) being second and third respectively. There are various medical and surgical treatment options available depending on clinical characteristics and the stage of disease. In spite of wide spectrum of therapeutic options, pain control still remains a challenging problem to the clinicians. Surgical treatments for chronic pancreatitis, broadly classified into resectional and drainage procedures, may offer relief of symptoms. These surgeries are associated with severe morbidity and high mortality. In addition, our comprehensive review of surgery in chronic pancreatitis demonstrated lack of criteria for baseline assessment of patients with CP; resulting in lack of standardization, variation in indication and comparability in published literature on surgical treatment of chronic pancreatitis. These factors have collectively forced the medical fraternity to look for other non or minimally invasive options. Oxidative stress and deficiency of anti-oxidants have long been implicated in pathogenesis of CP. Our review of literature on oxidative stress and antioxidants has highlighted the shortcomings and inadequacies from the previously published reports. These reports were underpowered and not all included patients had chronic pancreatitis. This in turn led us to propose a well designed randomised, double blind, placebo controlled trial of antioxidant therapy in CP. Considering the loss of time and productivity, it is necessary to undertake Qol as an outcome measure in any intervention related to CP. Our study assessed the suitability and feasibility of validated quality of life indices in patients with painful chronic pancreatitis. After correction for disease duration, the outcome of contemporary quality of life assessments showed that patients with CP taking Antox had better scores than controls. Cytokines, a group of proteins and glycoproteins that act in regulation of immunity, inflammation and haematopoiesis are implicated in oxidative stress related pathogenesis of chronic pancreatitis. They are broadly classed as pro-inflammatory and anti-inflammatory. There have been few experimental studies suggesting that antioxidants ameliorate cytokine response in chronic pancreatitis. However our study has failed to demonstrate a significant effect on cytokine levels after six months of antioxidant therapy.Similarly, on the clinical front, a randomised, double blind placebo controlled study (referred to as ANTICIPATE TRIAL) has shown no benefit of antioxidant therapy in painful chronic pancreatitis, irrespective of age, gender, aetiology or operative intervention. So we are afraid to say that until we discover any novel treatment in management of intractable painful chronic pancreatitis, surgery and interventional endoscopy might be the only viable options.
|Date of Award||1 Aug 2017|
- The University of Manchester
|Supervisor||Ajith Siriwardena (Supervisor)|
- Antioxidant therapy, Antioxidants, Antox.
- Chronic, Pancreatitis, Quality of life.