Page 8 - Acute Pancreatitis (Viêm tụy cấp)

CHAPTER 58 Acute Pancreatitis 899

(both side branch and main duct) was the cause for AP anywhere is thought that a stepwise progression occurs to fibrosis from
from 12% to 67%. Metastases to the pancreas from other can- recurrent episodes of AP. Support for this theory is seen in a 58
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cers (lung, breast) have also caused pancreatitis. Large adeno- clinical study by Ammann and colleagues. In their study, 254
mas of the major papilla can likewise occasionally be the cause of patients were prospectively followed after the first episode of
obstructive pancreatitis (see Chapter 69). alcoholic pancreatitis. There was a direct correlation between
the frequency and severity of attacks to the rate of progression
Other Causes to chronic pancreatitis.
2. Direct metabolic-toxic effect of alcohol on acinar cells.
Other obstructive conditions that are rarely associated with AP 3. Oxidative stress due to free radicals.
are discussed elsewhere in other chapters and include choled- 4. The Sentinel Acute Pancreatitis Event (SAPE) hypothesis
ochoceles, duodenal diverticula, annular pancreas, and para- states that most causes of chronic pancreatitis are due to a
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sitic diseases that obstruct the pancreaticobiliary system, such as 2-hit model, where a single episode of AP causes infiltration
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ascariasis or clonorchiasis. Ascariasis obstructing the PD rep- of inflammatory cells and activation of pancreatic stellate cells
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resents the leading cause of AP in children (60%) and accounts and in susceptible individuals with risk factors, further leads
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for 23% of all causes of AP in the Kashmir region of India, the to fibrosis. If the inciting factors are removed (e.g., a drug),
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second most common cause of AP in Kashmir. then the pancreas returns to normal. If the inciting factor (e.g.,
alcohol) is not removed, the acinar cells continue to secrete cy-
tokines in response to the oxidative stress and the stellate cells
Ethyl Alcohol and Other Toxins continue to be activated to lay down matrix and collagen. This
Ethyl Alcohol model, using a sentinel event, also represents a time for disease
modifying therapy, when such therapy becomes available.
Alcohol is the second most common cause of AP after gall-
stones and causes at least 30% of the cases. Alcohol is the The above theories and animal models do not completely
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most common etiology of chronic pancreatitis in developed explain the development of alcoholic pancreatitis in humans.
countries. Prolonged alcohol consumption (more than 4 to 5 It is quite possible that a proportion of patients will progress
drinks per day for at least 5 years) is required, and the lifetime from acute alcoholic pancreatitis to chronic pancreatitis through
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risk of AP in such drinkers is only 2% to 5%. The relation- mechanisms like Sentinel Acute Pancreatitis Event, but the rest
ship between acute and chronic pancreatitis is very complex, might develop an unknown indolent fibro-inflammatory response
particularly in alcoholic chronic pancreatitis. The classic teach- that eventually presents clinically as AP. More importantly, the
ing is that alcohol causes chronic pancreatitis, and that alcoholic development of AP in an alcoholic individual without obvious
patients who present clinically with AP already have underlying structural damage suggests the possibility that a patient with idio-
chronic disease. This hypothesis was questioned in the 1990s pathic pancreatitis, found to have a history of alcohol use, may be
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when Ammann et al. followed a group of acute alcoholic pancre- inappropriately labeled as having alcoholic AP. It is important for
atitis over a time and by way of surgical pathology demonstrated clinicians to recognize that alcohol has been better established as
progression from acute to chronic stages. This line of evi- a cause of chronic pancreatitis than AP. Some level of skepticism
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dence suggested that alcohol causes AP in early stages without is likely to be helpful in the evaluation of a patient suspected as
underlying chronic pancreatitis, but leads to chronic pancreatitis having acute alcohol-induced pancreatitis in the absence of obvi-
through the “necrosis-fibrosis hypothesis.” Some autopsy stud- ous structural damage to the pancreas.
ies also have demonstrated the occurrence of alcoholic AP with-
out underlying chronic pancreatitis in a significant proportion Other Toxins
of such patients. However, a surgical series of 21 patients with
alcoholic AP showed that all 6 patients with first attack already Methyl alcohol, organophosphorus insecticides, and the venom
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had chronic pancreatitis at the time of first attack. Thus the of the Trinidad scorpion have been reported to induce AP. The
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debate as to whether alcoholic AP only occurs in a gland that mechanism of the latter 2 toxins is thought to be by hyperstimula-
already has changes of chronic pancreatitis continues. Several tion of the pancreas. Cigarette smoking has been shown to be an
recent studies (including population-based studies and studies independent risk factor for AP. 99-101 Although a population study
in pediatric patients) and meta-analysis clearly demonstrated the from the USA showed smoking to be a risk factor for nongallstone
progression of AP in some patients to recurrent AP and then AP, 102 surprisingly a study from Taiwan reported that smoking
to chronic pancreatitis. 89-91 A meta-analysis reported that 10% was not associated with an increased risk. 102 In another study,
of patients with a first attack of AP (from all causes) and 36% smoking was found to be associated with a lower age at the time of
of patients with recurrent AP progress to chronic pancreatitis diagnosis of AP and with a higher rate of recurrence. 103
and that alcohol, smoking and male sex are risk factors for such
progression. However, these observations do not address the Drugs
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controversy as to whether chronic pancreatitis was present at the
time of first attack of AP but only about the clinical detection of Medications are an infrequent but important cause of AP. Although
chronic pancreatitis subsequently. there are reports that drug-induced AP accounts for 1% to 4% of
all cases, these studies are largely unconvincing; drug-induced AP
The various mechanisms for chronic pancreatitis include: probably accounts for less than 1% of cases. 104 Although more than
120 drugs have been implicated, mostly from anecdotal case reports,
1. The necrosis-fibrosis sequence, suggested by Comfort clinicians must be careful not to blame a drug when a patient with
et al., 93,94 envisions the development of fibrosis from recur- AP does not have an obvious underlying cause. Many of the pub-
rent, perhaps subclinical, bouts of AP. Inflammation and ne- lished case reports suffer from a combination of inadequate criteria
crosis from the initial episodes of AP produce scarring in the for the diagnosis of AP, failure to rule out more common causes, or
periductular areas, and scarring causes obstruction of the duct- a lack of a rechallenge with the medication. In addition, many case
ules, leading to stasis within the duct and subsequent stone reports inappropriately implicate drugs when the latter have been
formation. Support for this theory comes from histopathologic administered for very long periods (>6 months) before the onset of
studies that revealed mild perilobular fibrosis in resolving AP, AP. Drug-induced pancreatitis tends to occur within 4 to 8 weeks
with marked fibrosis with ductal distortion occurring later. It of beginning a drug. In the absence of well-designed clinical trials,