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Somatostatin in pancreatic disease
A single agent that treats acute and chronic pancreatitis, controls pancreatic fistula, reduces operative morbidity and mortality rates, and even helps in the management of some pancreatic tumours would seem to be the alchemist's dream. Is somatostatin the fulfilment of this dream for the pancreatic surgeon? The answer is not easy, except to say that the therapy does not produce dramatic results and, despite many trials (often of low validity), definitive statements cannot be made about the use of somatostatin in clinical practice. Somatostatin is a cyclic peptide consisting of 14 amino acids and is best regarded as a phylogenetically ancient multigene family of peptides with two important bioactive products: somatostatin 14 and somatostatin 28. It modulates neurotransmission in the central nervous system and regulates the secretion of growth hormone and thyrotropin. It has a regulatory role in the gastrointestinal tract, as well as in the exocrine and endocrine pancreas. When synthesized and released by endocrine and nerve cells in the gastrointestinal tract and pancreas, somatostatin acts in an autocrine, paracrine or neuronal regulatory manner to inhibit glandular secretion, neurotransmission, smooth muscle contractility and absorption of nutrients. It also inhibits the function of activated immune cells'.
It is hardly surprising that a transmitter with such wide-ranging actions has more than a single specific effect on the pancreas of use to the pancreatic surgeon. There are four properties of somatostatin that may influence the course of pancreatic disease: (1) inhibition of pancreatic secretion; ( 2 ) haemodynamic effect, reducing pancreatic blood flow; ( 3 ) cytoprotection; and (4) stimulation of the reticuloendothelial system2. Clinical use of somatostatin was initially hampered by its short duration of action and postinfusion rebound hypersecretion of hormones. Octreotide, the first somatostatin analogue introduced for clinical purposes, has a longer half-life and so is of practical use in the management of pancreatic disease.
One of the most effective uses of octreotide is probably in the management of pancreatic islet cell tumours. Some 7 per cent of all pancreatic tumours are of neuroendocrine origin. Most are non-secretory and do not express somatostatin receptors; nevertheless some do, are slowly growing and often secrete substances that cause considerable clinical disturbance, depending on the dominant hormone produced. Clinical improvement occurs in 50-85 per cent of affected patients during treatment with octreotide 150-8OOpg per day, given as a subcuticular injection at intervals of 8 h. Patients learn to inject themselves and often are able to regulate their dosage according to the degree of symptom control. Such therapy may be combined with a proton pump inhibitor if there is excess secretion of gastrointestinal fluid. These patients are often neglected and mistreated as having inoperable pancreatic cancer for which there is no palliation; their good response can be gratifying.
The second indication for octreotide relates to pancreatic surgery. There are now four clinical trials suggesting that octreotide can substantially reduce the risk of complications after surgery for both benign and malignant disease, but none is conclusive because the current low mortality rate from pancreatic operations has meant that the studies have had insufficient power to show a decrease in mortality ~v e r a l l ~, ~.
Nevertheless, the reduction in complications and length of stay suggest that after operation subcutaneous octreotide 100-200 pg at intervals of 8 h for 5-7 days is an appropriate adjunct.
The third indication is in the management of pancreatic fistula. Patients treated with a regimen of nil by mouth, total parenteral nutrition plus somatostatin had fistulas close within a significantly shorter time, with a reduction in the length of hospital stay5. Some studies, however, are confused by the type of underlying fistula. It is pointless administering octreotide to patients whose fistula arises from the body or tail of the pancreas, separated from the head of the gland, or to those who have a stricture in the head of the pancreas, unless the stricture is relieved, for instance by a stent. The ideal patient is fit and has an intact main duct with a side-