**The Surgical Management of Chronic Pancreatitis**

S. Burmeister, P.C. Bornman, J.E.J. Krige and S.R. Thomson *University of Cape Town South Africa* 

#### **1. Introduction**

428 New Advances in the Basic and Clinical Gastroenterology

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Chronic pancreatitis (CP) has been defined as a continuing inflammatory disease of the pancreas characterized by irreversible morphological changes, often associated with pain and with the loss of exocrine and endocrine function which may be clinically relevant (Clain JE Surg Clin North Am 1999). Pain is the principal cause of intractability and together with pancreatic insufficiency may have a significantly deleterious effect on a patient's quality of life as well as their ability to work and contribute to society, often leading to loss of their' social support network (Lankisch PG Digestion 1993). Progressive disease may culminate in severe and disabling symptoms requiring narcotic analgesia and frequent hospital admission with a consequent impact on health resources (Bornman PC W J Surg 2003; Braganza JM The Lancet 2011). The incidence and prevalence of disease has not been well documented however it is considered uncommon in Europe and the USA. This is in contrast to data available from South India where a prevalence of 114-200/100 000 people has been documented. Alcohol is the leading cause in western developed countries and some developing countries such as Brazil, Mexico and South Africa while idiopathic disease predominates in Asia and the subcontinent (Braganza JM The Lancet 2011; Garg PK J Gastroenterol Hepatol 2004).

Despite extensive study, the pathogenesis of chronic pancreatitis and the mechanisms which result in the development of pain remain poorly understood. As a result, treatment strategies have been largely empirical and based on symptoms, management of clinically evident exocrine and endocrine dysfunction and gross morphological abnormalities. Modalities employed have included medical support (with analgesics, anti-diabetic medication, pancreatic enzyme replacement, nutrient support and steroids in autoimmune disease), interventional endoscopy and surgery. The role of surgery has been primarily to relieve pain refractory to medical therapy, to address complications and to resect suspected or confirmed neoplastic disease (Bornman PC S Afr Med J 2010). The causes of pain in CP are likely multifactorial and proposed factors include excessive oxygen-derived free radicals, tissue hypoxia and acidosis, inflammatory infiltration accompanied by an influx of pain transmitted substances into damaged nerve ends and the development of pancreatic ductal and tissue fluid hypertension (Bornman PC W J Surg 2003). Surgical intervention for the relief of pain focuses primarily on the latter two proposed mechanisms. Two distinct principles have been applied in the development of

The Surgical Management of Chronic Pancreatitis 431

scenario with consequent tissue ischaemia and acidosis. (Karanjia ND Br J Surg 1994). While PDSO with ductal and tissue hypertension have not been consistently demonstrated in CP, nor a definite correlation shown with the development of pain (Novis BH Dig Dis Sc 1985; Manes G Int J Pancreatol 1994; Ugljesic M Int J Pancreatol. 1996; Bornman PC W J Surg 2003), surgical drainage procedures have been documented to reduce pancreatic tissue pressures (PTP), while a significant association between recurrence of pain and subsequent elevation of PTP has been shown. (Ebbehøj N Scand J Gastroenterol. 1990). On the other hand, ductal dilatation has been observed in the absence of ductal obstruction giving rise to the suggestion that dilatation may also be related to parenchymal destruction; this is supported by the association between duct dilatation and pancreatic insufficiency (Jensen AR Scand J Gastroent 1984). Thus, while PDSO is likely an important factor in generating pain, there are likely factors other than main pancreatic duct abnormalities that can also be implicated (Bornman PC W J Surg 2003). Furthermore, the role of side duct obstruction in the genesis of pain has not yet been clearly defined; it may be that side branch disease contributes to the development of an inflammatory mass in the pancreatic head which is recognised as important in driving the disease process (the so called "pacemaker" of

**2.2 Interaction between the processes of inflammation and damaged neural** 

**2.3 Toxin metabolism and generation of excessive oxygen derived free radicals** 

Acinar cells and proliferated islets of Langerhans are known to express cytochrome P450 (CYP) mono-oxygenases which metabolise xenobiotics (substances foreign to a living organism), often utilizing glutathione & catalysed by glutathione transferases. (Foster JR J Pathol 1993). There may however be adverse consequences to these metabolic reactions with the generation of reactive oxygen species (ROS) and toxic xenobiotic metabolites. Prevention of cellular injury relies on defences against ROS and xenobiotic metabolites; these defences include: selenium dependant glutathione peroxidase, glutathione transferases, glutathione and ascorbic acid. These varied properties make the pancreas a versatile yet vulnerable xenobiotic metabolizing organ (Braganza JM JOP 2010; Foster JR. Toxicology of the exocrine pancreas. In: General and applied toxicology 2009). Inhaled xenobiotics (such as cigarette smoke, occupational volatile hydrocarbons and petrochemicals) that pass through the pulmonary circulation represent the biggest threat by striking the pancreas through its rich

**resulting in electrophilic stress and inflammation** 

Histological studies have shown that there is invasion of neural tissue by inflammatory cells associated with chronic pancreatitis. This is accompanied by disruptions in the perineural sheaths which expose the internal neural compartments to the inflammatory response (Bockman DE Gastroenterol 1988). In addition, there are increased amounts of pain transmitted substances, pain modulators and nerve growth factors and receptors in enlarged / damaged pancreatic nerve structures, which appear to correlate with the intensity and frequency of pain (Büchler M Pancreas 1992, Zhu ZW Dig Dis Sci 2001,McMahon SP Nat Med 1995,Friess H Ann Surg 1999). Surgical resection of a pancreatic inflammatory mass effectively removes the pain stimulus together with the altered / damaged neural

disease) (Beger HG World J Surg 1990).

**structures** 

structures.

procedures to address these mechanisms. Resection of diseased pancreatic tissue, in particular inflamed tissue within the head of the pancreas containing altered neural tissue and diseased ducts, considered the "pacemaker of disease" (Beger HG World J Surg 1990) and drainage of the pancreatic ductal system, in order to relieve ductal and parenchymal tissue hypertension. Removal of sufficient pancreatic tissue as to result in effective and durable relief of symptoms must however be balanced against the desire to avoid surgically related morbidity and mortality as well as to prevent post-operative pancreatic functional insufficiency. This has led to the development of less extensive resections and hybrid procedures which attempt to combine the advantages while avoiding the disadvantages of each approach.

This chapter will describe the theories around the pathophysiology of pain in chronic pancreatitis, discuss the rationale and indications for surgical intervention and detail the procedures currently available. It will also review the literature guiding the choice of these procedures for the relief of pain.
