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Acute Pancreatitis

This is a brief history of a typical patient with pancreatitis. 80% of patients with acute pancreatitis, that in fact have self-limiting pancreatitis, pancretitis, pancreitis disease. It resolves in a few days and it has really a minimal morbidity and mortality. What we worry about is that 20% of patients who have a very substantial morbidity and mortality, 15-30%. In a few days that pancreas may well go on to look like this with edema, areas of necrosis. It may be even worse with a broadly edematous gland.

Clearly this can be a horrible problem and one that needs great help. The challenge in this disease is to identify the patients who will develop this severe disease early enough so that it can make a difference. We are also challenged to develop appropriate, safe and efficacious therapeutic options for these patients. Fortunately, in the last few years, there have been new insights that.

Well, our experience with pancreatitis in the literature goes back into the 1700ís. Reginald Phipps in 1889 gave a beautiful description. It was a systematic description of a very large series of patients and in fact there is little missing in that, in terms of what we know today. He describes the patterns of pain, fever and jaundice in this syndrome.

Pathologic classification is listed here, and thatís not to suggest that you should biopsy the pancreas to make this diagnosis. But I think that when we do look at histology, when we have the opportunity to, seeing what the morphology shows gives insight into whatís going on and the pathogenesis. Indeed, about 80% of cases of pancreatitis just have what we will call interstitial.

Certainly early on in the course of pancreatitis, the only imaging that is important is to rule out gallstones. CT scan, we use for a patient with a high APACHE score or organ failure, usually beyond about three days of disease. Itís useful in that setting to differentiate interstitial versus necrotizing pancreatitis. Iím going to give you the Balthazarís quantitative index for CT scan. John has shown you examples of other modalities to detect duct stones, so Iíll just pass through that and just talk about urgent ERCP in terms of Ö the only clear indication is in a patient that has biliary pancreatitis and cholangitis. We know that the studies support removing the stone in that setting, and that improves the patient. Otherwise the data are much less clear. This is the Balthazar criteria where values from 0-4 for the evidence of focal changes or fluid collections are added to values that go up to 6, depending on the degree of necrosis in the gland. Basically patients with fluid collection and necrosis involving more than one third of the gland are at substantial risk for severe complications.

Antibiotic use is something that Iíd like to make an argument against the literature for. We believe that in patients with necrosis and organ failure it is reasonable to initiate antibiotics that cover both anaerobes and aerobic organisms and that the literature has failed to show benefit in randomized studies in this setting has done that because the patients didnít really have severe pancreatitis or that they used the wrong antibiotics, that didnít reach the pancreatic bed.

This is a CT scan just showing the appearance of gas in the pancreatic bed, and once we get infective necrosis I think that itís time to get the surgeon involved. Certainly, when you get necrotizing pancreatitis without clinical improvement, itís important to distinguish whether it is infected necrosis or sterile necroses. Infected necrosis does require surgical debridement. Sterile necrosis however can be treated medically, at least in the initial period of 4-6 weeks.

The last few slides have to do with the anti-cytokine therapy that I mentioned. Unfortunately at this time there are no drugs available that block the effects of TNF or IL-1. However, there are drugs that are coming close to market for inhibition of platelet activating factor inhibition. Again, I showed you the therapeutic window. That is the critical thinking. Iíll pass through the experimental data for this and go right to this slide, which I think is very important. Here on the X axis is the