Alcoholic Chronic Pancreatitis avid hitco b, M

Alcoholic Chronic Pancreatitis
David Whitcomb, MD, PhD*
Roland H . Pfützer, MD
Adam Slivka MD , PhD
Division of Gastroenterology and Hepatology, 571 Scaife Hall,
3550 Terrace St., Pittsburgh, PA 15261.
Current Treatment Options in Gastroenterology 1999, 2:273–282
Current Science Inc., ISSN 1092–8472
Copyright © 1999 by Current Science Inc.
Opinion statement
The most important intervention in the treatment of alcoholic chronic pancreatitis is
alcohol cessation, and therefore, it should be a primary treatment goal. This measure
alters the natural course of the disease and may improve long-term survival. Smoking
cessation should also be encouraged, since the risk of pancreatic cancer increases with
prolonged chronic pancreatitis, and is again doubled by smoking. Maldigestion is
treated in a way similar to other types of chronic pancreatitis. Treatment of pain
should begin with an effort to identify reversible causes, including pseudocysts and
duct obstruction. Chronic pain management should follow a multi-step treatment
regimen that reserves narcotics for only the most severe cases. Since pain tends to
diminish during the natural history of pancreatitis, treatment of pain needs to be
continually reevaluated. Endoscopic or surgical interventions are indicated only for the
management of complications, but have no significant effect on the natural
history of alcoholic chronic pancreatitis. In the future, diagnosis of patients within
the earliest stages of alcoholic chronic pancreatitis, and intervention with effective
strategies to prevent progression of fibrosis and other complications, may offer the
best solution for eliminating this disease. Thus, the focus of management should be
early identification of patients at risk, and institution of effective new therapies.
Alcohol-associated pancreatitis is usually recognized
in the late chronic phase, which is characterized structurally by pancreatic sclerosis with ectatic pancreatic
ducts and calcifications, and functionally by steatorrhea, diabetes mellitus, and intractable pain. Current
opinion on the pathogenesis of acute and/or chronic
pancreatitis in the alcoholic differs widely, and this
reflects relative ignorance about the disease. Three
principles are generally accepted. First, individuals
who stop drinking alcohol do better than those who
continue drinking. Second, endoscopic and surgical
interventions offer temporary pain relief for wellselected patients with specific complications. Third,
endoscopic or surgical interventions fail to change the
natural history of the disease.
Alcoholic chronic pancreatitis is often heralded by
acute pancreatitis [1••]. Some experts theorize that
underlying chronic pancreatitis leads to episodes of
acute pancreatitis [2•], while others believe that acute
pancreatitis initiates the process leading to chronic pancreatitis either by a necrosis-fibrosis sequence [1••,3•],
or by causing infiltration and differentiation of the
inflammatory cells necessary to cause fibrosis [4]. The
natural history of chronic pancreatitis is illustrated in
Figure 1. Once alcoholic chronic pancreatitis is established, it usually progresses along an unrelenting
course, regardless of current surgical or medical interventions. The figure also illustrates the clinical observation that loss of pancreatic exocrine function and
development of malabsorption (eg, fecal chymotrypsin
value of >120 µg/g) usually occurs 10 to 15 years before
pancreatic endocrine dysfunction and diabetes mellitus.
The primary treatments for end-stage alcoholic
chronic pancreatitis center on replacement of the previous functions of the pancreas with pancreatic enzymes
supplementation and insulin for diabetes, management
of pseudocysts and other structural complications, and
management of pain.
Figure 1. Probability of remaining free of
exocrine insufficiency (---) or diabetes
mellitus (—) after the onset of alcoholic
chronic pancreatitis. Note that the onset
of diabetes occurs about 10 to 15 years
after exocrine insufficiency. (Adapted from
Ammann et al. [6••], Figures 4 and 5.)
The authors wish to thank Kenneth K. W. Lee, MD, for a critical review and suggestions for
the manuscript. This work was supported by a VA Merit Review (DCW) and a grant from
the NIH DK50236 (DCW)
Diet and lifestyle
• Excessive alcohol intake by any patients suggests underlying social and/or
emotional dysfunction, and leads to numerous health related problems.
• Cessation of alcohol intake is the single most important intervention
known. Some studies have shown that cessation of alcohol use delays the
progression of pancreatic dysfunction in alcoholic pancreatitis [5•], and
that the rate of marked physical impairment, unemployment and death
rate is three times higher in those who continue to drink [6••].
• Specific supporting psychotherapy (eg, Alcoholics Anonymous) should be
considered in patients with alcoholism. Failure of a previous therapy
should not preclude attempts at future therapy, since the long-term costs of
alcohol addiction and its role on the outcome of chronic pancreatitis justify
further therapy attempts.
• Smoking increases the risk of alcoholic chronic pancreatitis [7] and
pancreatic cancer [8]. Therefore, smoking should also be discontinued.
Dietary modifications
• Although some recommend specific dietary modifications (eg, a low-fat
diet), no clear consensus has been reached. Fats remain an important
source for calories and vitamins in malnourished patients, and additional
restrictions must be considered in the diabetic. With progressive pancreatic
dysfunction, fat absorption is most severely affected because functional loss
of lipase occurs early. This differs from carbohydrate digestion because
Alcoholic Chronic Pancreatitis Whitcomb et. al.
there are no brush border lipases, lipase is pH sensitive and pancreatic
bicarbonate secretion is limited, and lipase is rapidly destroyed by
proteases in the small intestine [9].
Fat malabsorption is recognized clinically as steatorrhea. Pancreatic
enzyme supplementation is the primary therapy for this condition
([9] and below). A partial substitution of dietary long-chain triglycerides
with medium-chain triglycerides (MCT) has the theoretic advantage of
being absorbed without requiring pancreatic lipase digestion. However,
a recent study failed to show improved fat absorption with MCT [10].
Because of malnutrition and maldigestion, alcoholic patients may
require supplementation of the fat-soluble vitamins A, D, E and K,
and vitamin B12.
Several smaller meals during the day are usually tolerated better than large
meals because of limited meal-stimulated enzyme secretion.
Diabetes mellitus is a major complication of alcoholic chronic pancreatitis.
The most important therapeutic intervention in patients with alcoholic
chronic pancreatitis and diabetes mellitus is the adequate dietary education
and training of the patient and the person who prepares his or her meals.
If possible, patients should be trained to monitor their own diet and blood
glucose levels.
Pharmacologic treatment
• The treatment of alcoholic pancreatitis is geared toward relief
of symptoms.
• Maldigestion occurs with loss of more than 90% of pancreatic
exocrine function [11] and is treated most effectively with enteric or nonenteric-coated pancreatic enzymes when >20,000 IU of lipase are delivered
to the duodenum with every meal. Although this amount of lipase only
represents about 10% of the secretory capacity of the normal pancreas [11],
it is sufficient to treat steatorrhea in most cases.
• Dietary fibers may alter pancreatic enzyme activity, so patients should avoid
fiber-enriched diets [12].
• Gastric acid suppression may improve the effectiveness of enzyme
• Overt diabetes with the need for oral hypoglycemic agents or insulin
develops within 20% of patients within 6 years of the onset of alcoholic
chronic pancreatitis, and 50% at 10 years [6••].
• Narcotics should be avoided in the alcoholic when possible, but prescribed
when necessary. Since the natural history of pain in alcoholic pancreatitis
leads to its eventual disappearance, the use of narcotics should be considered a temporary measure.
• When using NSAIDs in the required doses, the risk of gastrointestinal side
effects always has to be considered. (For a recent review on gastrointestinal
toxicity of NSAIDs see [13].)
• Pain from duct obstruction or pseudocysts should be recognized, and
endoscopic or surgical treatment considered (see below).
Treatment of maldigestion
Pharmacologic therapy
Non-enteric coated pancreatic enzymes
Standard dosage
Main drug interactions
Main side effects
Special points
Viokase 6-8 capsules per meal; Cotazym 6-8 capsules per meal.
Hypersensitivity to pork digestive enzymes, acute pancreatitis (controversial).
May bind to dietary fiber.
Nausea, cramping, diarrhea; hyperuricosuria, hyperuricemia (in high doses).
Must be given in high doses or with adequate meal-stimulated acid suppression to
overcome destruction in the stomach.
Cost effectiveness May be more expensive than enteric coated preparations if gastric acid suppression
is included.
Enteric coated pancreatic enzymes
Standard dosage Creon 20, 2 capsules per meal; Pancrease MT20, 2 capsules per meal; Ultrase MT20,
2 capsules per meal; Zymase 3 capsules with each meal.
Contraindications Hypersensitivity to pork digestive enzymes; acute pancreatitis.
Main drug interactions May bind to dietary fibers.
Main side effects Nausea, cramping, diarrhea; hyperuricosuria, hyperuricemia (in high doses);
colonic strictures in children with cystic fibrosis.
Special points Usually does not require additional acid suppression.
Cost effectiveness Overall cost may be less than the cost of non-enteric coated preparations when the
number of capsules per meal, the need for acid suppression, and compliance issues
are considered.
G astric acid suppression by H2 receptor antagonists
Standard dosage Cimetidine, 400 mg b.i.d. (before meals); Ranitidine, 150 mg b.i.d. (before meals);
Famotidine, 20 mg b.i.d.; Nizatidine, 150 mg b.i.d.
Contraindications None.
Main drug interactions May potentiate effect of drugs metabolized by liver microsomal enzymes,
particularly Cimetidine.
Main side effects Headache, dizziness, constipation, diarrhea, somnolence, seizures, palpitations,
depression. May cause arrhythmia, gynecomastia, increased serum
transaminases, particularly Cimetidine.
Special points Must suppress meal-stimulated acid secretion. If used with a non-enteric coated
pancreatic enzyme supplement and symptoms of maldigestion persist, the dosage
should be increased or a proton pump inhibitor (PPI) employed.
Cost effectiveness Less expensive than PPIs.
G astric acid suppression by a proton pump inhibitor (PPI)
Standard dosage Omeprazole, 20 mg daily; Lansoprazole,15–30 mg daily
Contraindications Drug hypersensitivity.
Main drug interactions May potentiate diazepam, phenytoin, warfarin (omeprazole); may alter absorption
of pH-dependent drugs; clearance of lansoprazole may be altered in liver disease.
Main side effects Diarrhea, abdominal pain, nausea, headache, dizziness, constipation.
Special points May improve enzyme treatment of steatorrhea better than H2 receptor blockers.
Cost effectiveness More expensive but more effective than H 2 receptor blockers.
Alcoholic Chronic Pancreatitis Whitcomb et. al.
Treatment of pain
• See recent reviews by Conwell (this issue), Warshaw [14••], and
Mõssner [15••].
Standard dosage
Main drug interactions
Main side effects
Special points
Acetaminophen 500 mg up to q.i.d.
Active consumption of alcohol; poor nutrition [16].
Hepatotoxicity risk increased by chronic, heavy, alcohol use.
Hepatotoxicity, nephrotoxicity.
Dose should be limited to a maximum of 2 g per day if the patient is suspected
of drinking more than two alcoholic beverages per day.
Cost effectiveness Least expensive pain medication.
Nonsteroidal antiinflammatory drugs ( NSAI Ds)
Standard dosage Aspirin, 250–500 mg po q 4–6 hr up to 4 g per day; diclofenac, 50 mg po q 8–12
hr; ibuprofen 200–400 mg po q 4h up to 1.2 g per day; indomethacin
25–50 mg po q 6–8 hr; ketoprofen 12.5–25 mg po q 4h up to 75 mg per day;
nabumetone 500–1000 mg po q 12 h; naproxen 200–400 mg po q 8–12 h.
Contraindications History of GI bleed, drug hypersensitivity.
Main drug interactions Lithium serum levels increase; many drug-specific considerations.
Main side effects GI bleeding [13], hepatotoxicity.
Special points Misoprostol may reduce the risk of GI bleed but complicate the assessment
of diarrhea. Duration of therapy should be limited if possible. NSAIDs should not
be used in combination.
Cost effectiveness Variable.
Tramadol ( Ultram )
Standard dosage
Main drug interactions
Main side effects
Special points
Cost effectiveness
Tramadol 50 mg po q 4–6 h.
Alcohol or hypnotic intoxication.
MAO inhibitors.
Seizures, dizziness, nausea, vomiting, constipation.
Narcotic-like effects.
Relatively expensive.
Standard dosage Codeine, 30–60 mg po q 6 h; fentanyl patches, 25–100 µg/h; hydrocodone, 5–10
mg po q 4–6 h; hydromorphone, 2–4 mg po q 4–6 h; methadone, 2.5–10 mg po q
4–6 h; morphine sulfate (extended release), 30–60 mg po q 8–12 h;
oxycodone, 5–10 mg po q 6 h; pentazocine, 25–50 mg po q 4–6 h; propoxyphene,
65 mg po q 4–6 hours up to 390 mg per day.
Contraindications Impaired respiration, drug hypersensitivity.
Main drug interaction Potentiation with alcohol. May increase serum levels of antidepressants, anticonvulsants, and coumarin anticoagulants.
Main side effects Euphoria, dysphoria, constipation, nausea, vomiting, respiratory depression,
and hypotension.
Special points The timing of narcotic dosing in practice remains empiric, and the authors use
different approaches. Some use narcotics before meals based on the rationale that
pain is often worse during meals and therefore limits nutritional intake; that the
narcotics inhibit pancreatic exocrine secretion and thereby reduce secretory
pressure within the pancreas; and that narcotics slow intestinal transit, thereby
prolonging the time for digestion and absorption. Others use narcotics after the
meal based on the rationale that narcotics cause sphincter of Oddi spasm through
inhibition of inhibitory neurotransmitter release, thereby causing functional
pancreatic duct outlet obstruction. Morphine, for example, is a potent inhibitor of
sphincter of Oddi relaxation. Dosing based on providing continuous pain
relief is also used. Dependence is common. Narcotic abuse is always a
concern in alcoholics. In their case, the physician should consider involving
a multidisciplinary pain management team. Tolerance to narcotics may develop
in patients receiving them. Narcotics are available in combination with acetanophen and NSAIDs.
Cost effectiveness For a week’s dosage equivalent of oxycodone 5 mg q6 hours, methadone is the least
expensive (~$7 per week), followed by codeine. Progressively more expensive are
hydrocodone, oxycodone, and hydrocodone ($10–$20 per week), and fentanyl
patches are the most expensive (~$45 per week).
Endoscopic therapy
• Endoscopic retrograde cholangiopancreatography (ERCP) is indicated
for the diagnosis of chronic pancreatitis by evaluating the pancreatic duct
for strictures or stones (Cambridge classification [17]). May be effective
in the treatment of pancreatic duct obstruction, stones, disruption, or
symptomatic pseudocysts. ERCP is the gold standard for evaluating the
pancreatic duct.
Endoscopic ultrasound
Standard procedure An endoscope with an ultrasound transducer at its tip (usually 5–12 MHz)
is passed into the stomach and duodenum for evaluation of the pancreas.
Contraindications General contraindications for upper endoscopy.
Complications Perforation, with fine needle aspiration (FNA); bleeding, infection, pancreatitis.
Special points May be the most sensitive imaging modality to diagnose chronic pancreatitis based
on heterogeneous echogenicity of the parenchyma and ectasia of the ducts. Cannot
differentiate focal inflammation from malignancy. May be used to guide FNA.
Cost effectiveness More expense compared to test of maldigestion or CT, which must be balanced
against a greater sensitivity in identifying pancreatitis at an earlier stage.
Endoscopic retrograde cholangiopancreatography (ERCP)
Standard procedure A side view duodenoscope is moved into the duodenum and the papilla of Vater
identified. A catheter is placed in the bile or pancreatic duct, followed by injection
of a radio-opaque contrast to obtain a ductogram under fluoroscopic visualization.
Contraindications General contraindications for upper endoscopy.
Complications Acute pancreatitis, perforation, bleeding, and infection. Chronic pancreatitis may
have a protective role in preventing post-ERCP pancreatitis.
Special points Important therapeutic options are available: Pancreatic stricture dilation and
short-term stent therapy for symptomatic obstruction or duct disruption; transpapillary pseudocyst drainage; endoscopic stone removal; transluminal pseudocyst
drainage. Symptomatic biliary strictures from chronic pancreatitis respond poorly
to chronic endoscopic therapy.
Cost effectiveness More expensive and invasive than CT or MRCP in diagnosing chronic pancreatitis,
but less expensive than surgery for therapeutic interventions.
Alcoholic Chronic Pancreatitis Whitcomb et. al.
• Surgery may not be effective in decelerating the natural history of
chronic pancreatitis with respect to exocrine or endocrine insufficiency
or calcifications [6••]. Lasting pain relief occurs in 70% of patients with
cyst drainage, 66% with lateral pancreaticojejunal drainage, and 60% of
patients with a partial resection [6••].
• Surgical procedures can be divided into drainage procedures and resection
procedures, or combinations of both. Drainage procedures may be more
effective than partial or complete resections for pain relief in patients
with a dilated duct system, whereas surgery for pain relief in patients without ductal dilatation generally has a less satisfactory outcome.
• Drainage and limited resection procedures provide comparable benefit in
pain relief in appropriately selected patients. Some have claimed that
resection procedures have shown superiority to pure drainage procedures
in regard to long-lasting pain relief, and reoperation rates. Morbidity and
mortality are higher than in pure drainage procedures, but may reflect more
complicated pancreatic pathology. (For an overview about current surgical
procedures see Buchler et al. [18•].)
• In the United States, most surgeons require that the patient remain
abstinent from alcohol for three to six months or more before any surgery
is considered.
Procedure Partington-Rochelle (or Rochelle-Partington)—Lateral pancreaticojejunostomy
(sometimes incorrectly called a Puestow—see below).
Contraindications Inflammatory masses in the pancreas, acute pancreatitis, Non-dilated pancreatic
duct (<6–7 mm).
Complications Recurrence of symptoms in up to 50% after five years, as the cause for
the obstruction (often an inflammatory process in the head of the pancreas)
remains untouched. Pain relief may be 80% after five years or higher in highly
selected patients.
Special points Since no functional tissue is resected, exocrine and endocrine functions remain
unchanged or even improve slightly over a limited time.
Combined surgical procedures
Procedures Puestow: end and lateral pancreaticojejunostomy combined with a pancreatic
resection; Frey: lateral pancreaticojejunostomy in combination with limited
resection of inflamed tissue of the head of the pancreas
Contraindications Acute pancreatitis, non-dilated pancreatic duct (<6–7 mm)
Complications Higher percentage of iatrogenic diabetes with a drastically worsened long-time
prognosis compared to pure drainage procedures.
Special points The Puestow is mostly of historical importance since a resection of the tail of the
pancreas is now used only in patients with an inflammatory process in that area.
The Frey procedure is used for treatment of a dilated pancreatic duct and enlarged
pancreatic head.
Resection procedures
Procedures Traverso-Longmire (pylorus-preserving Whipple): pancreatoduodenectomy; Beger:
duodenum-preserving pancreatic head resection [19]; total pancreatectomy.
Contraindications Acute pancreatitis.
Complications Possible occurrence of ulcers at the anastomosis, diabetes, exocrine insufficiency.
Special points The resection procedures are usually reserved for patients with a large inflammatory mass in the head of the pancreas. The reported success in relieving pain
varies greatly among various centers. Total pancreatectomies are associated with
brittle diabetes and exocrine insufficiency. Recurrence of pain in many patients.
Management of pseudocysts
• Pseudocysts develop in 15%–30% of patients with alcoholic chronic
pancreatitis, but usually early in the disease process. Only symptomatic
pseudocysts require therapy.
• Common complications include pain, infection, compression of
surrounding organs, rupture, and bleeding.
• Different treatment options are available and should be considered. The
main options are CT or ultrasound-guided transcutaneous needle or
pigtail catheter drainage, endoscopic cystenterostomy, cystgastrostomy or
transpapillary drainage, and surgical drainage procedures.
Transcutaneous drainage
Procedure The pseudocyst is drained with a needle or percutaneous catheter placed under
CT or ultrasound guidance.
Indication Pseudocysts must be easily accessible.
Complications Pancreatocutaneous fistula, infections, pseudocyst recurrence.
Special points Simple and safe procedure. Should not be used if a pancreatic duct disruption
has been demonstrated or suspected. May be temporizing or definitive therapy for
infected pseudocysts.
Endoscopic drainage
Procedure The pseudocyst is localized by visualization of the pseudocyst bulging into
the gastric or duodenal lumen. Endoscopic ultrasound may be used to assist
localization. A small window into the pseudocyst is made with needle puncture
with or without cautery, and the entry point is enlarged by balloon dilation.
A stent or multiple stents are temporarily left in the window to facilitate drainage.
In other cases, a transpapillary stent is may be placed.
Indication Pseudocysts located <1 cm from lumen wall by CT.
Complications Infection, bleeding, stent occlusion, dislocation, or free perforation.
Special points EUS may be useful in identifying puncture site and avoiding blood vessels.
Surgical management
Procedure Cystogastro-, cystoduodeno- or cystojejunostomy. Occasionally,
external drainage may be used depending on the location of the pseudocyst,
and other factors.
Indications Operative candidate without active pancreatic inflammation, failure of nonsurgical drainage, complicated pseudocysts (bleeding, rupture, infection).
Complications Pancreatic abscess and gastric ulceration with cystogastrostomy.
Special points Internal drainage requires a durable wall of the pseudocyst that is usually reached
within six weeks. In case of recurrence, a resection should be considered.
Additional treatments (pain)
• Celiac plexus blockade—Usually provides pain relief for three to
six months.
• Somatostatin analogues—May reduce the severity of pain in a subset of
patients. The treatment is very expensive.
Alcoholic Chronic Pancreatitis Whitcomb et. al.
• Pancreatic enzymes—Non-enteric coated enzymes may be useful for pain
control in mild to moderated idiopathic chronic pancreatitis, but do not
appear to play a role in pain management of alcoholic chronic pancreatitis.
• Antioxidants—Various vitamins and antioxidants may have a theoretical
role in limiting the progression of alcoholic pancreatitis, but convincing
controlled trials are lacking.
• Extracoporal shock wave lithotripsy (ESWL)—May be used as an adjunct to
endoscopic pancreatic stone extraction. Fluoroscopic targeting is superior
to ultrasound-guided targeting.
Emerging technologies
Magnetic Resonance Cholangiopancreatography (MRCP) with or without the use of secretin
MRCP is a less invasive alternative to diagnostic ERCP, and is particularly attractive
in children. Stimulation with secretin provides non-invasive imaging
of the pancreatic duct. The absence of duct dilation following the intravenous
administration of secretin may suggest pancreatic insufficiency, but further
validating studies are needed. Supplies of secretin are currently quite limited.
Persistent duct dilation after secretin may suggest pancreatic duct obstruction.
MRCP may be useful for distinguishing primary pancreatic insufficiency and
duct obstruction.
Modified bacterial lipases for enzyme supplemental therapy
Since porcine lipase is very susceptible to acid degradation and proteases, various
attempts have been made to find another source of supplemental enzymes.
A recently published study in dogs showed that steatorrhea could be abolished
with bacterial lipase, and that the total mass of lipase (in mg) required was 75
times lower than with porcine lipase [20].
Gene therapy for exocrine insufficiency
In 1994, the in-vitro infection of a human gallbladder epithelial cell line with
a vector containing pancreatic lipase cDNA was reported. The infected cells
showed lipase activity for about two weeks [21]. Clinical applications are possible
in the future.
References and Recommended Reading
Papers of particular interest have been highlighted as:
Of special interest
•• Of outstanding interest
1.•• Ammann RW, Heitz PU, Kloppel G: Course of
alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study. Gastroenterology 1996,
This paper correlates the clinical and histopathologic
findings of 73 patients with alcoholic chronic pancreatitis.
Progressive pancreatic dysfunction was found to correlate
with histologic deterioration.
2.• Freedman SD: New concepts in understanding the
pathophysiology of chronic pancreatitis. Int
J Pancreatol 1998, 24(1):1–8.
An important review of the traditional views on the
pathophysiology of chronic pancreatitis.
3.• Kloppel G, Maillet B: Pathology of acute and chronic
pancreatitis. Pancreas 1993, 8(6):659–670.
A clear presentation on the necrosis-fibrosis sequence hypothesis.
4. Whitcomb DC: Hereditary panceatitis: new insights
into acute and chronic pancreatitis. Gut 1999, in press.
5.• Gullo L, Barbara L, Labo G: Effect of cessation of
alcohol use on the course of pancreatic dysfunction
in alcoholic pancreatitis. Gastroenterology 1988,
This article demonstrates that pancreatic damage continues
even after cessation of alcohol intake, but the rate of damage
slows compared to what occurs with continued drinking.
6.•• Ammann RW, Muellhaupt B, Group SPS: The natural
history of pain in alcoholic chronic pancreatitis.
Gastroenterology 1999, 116:1132–1140.
The clinical course of 290 patients with alcoholic chronic
pancreatitis is documented with respect to pain. Two pain
patterns are recognized. Comparison of surgical and medical
interventions for pain could not be assessed, but the probability of pain relief, probability of loss of exocrine function
and probability of the development of diabetes was identical
between interventions.
7. Talamini G, Bassi C, Falconi M, et al.: Cigarette
smoking: an independent risk factor in alcoholic
pancreatitis. Pancreas 1996, 12(2):131–137.
8. Lowenfels AB, Maisonneuve P, Cavallini G, et al.:
Pancreatitis and the risk of pancreatic cancer.
N Engl J MedInternational Pancreatitis Study Group.
9. Layer P, Keller J: Pancreatic enzymes: secretion and
luminal nutrient digestion in health and disease.
J Clin Gastroenterol 1999, 28(1):3–10.
10. Caliari S, Benini L, Sembenini C, et al.: Medium-chain
triglyceride absorption in patients with pancreatic
insufficiency. Scand J Gastroenterol 1996, 31(1):90–94.
11. DiMagno EP, Go VL, Summerskill WH: Relations
between pancreatic enzyme ouputs and malabsorption in severe pancreatic insufficiency. N Engl J Med
1973, 288(16):813–815.
12. Dutta SK, Hlasko J: Dietary fiber in pancreatic disease:
effect of high fiber diet on fat malabsorption in
pancreatic insufficiency and in vitro study of the interaction of dietary fiber with pancreatic enzymes. Am J
Clin Nutr 1985, 41(3):517–255.
13. Wolfe M, Lichtenstein D, Singh G: Gastrointestinal
toxicity of nonsteroidal antiinflammatory drugs.
N Engl J Med 1999, 340(24):1888–1899.
14.••Warshaw A, Banks PA, Femandez-del Castillo C:
AGA technical review: treatment of pain in chronic
pancreatitis. Gastroenterology 1998, 115:765–776.
A critical review of the current literature on pain management
in chronic pancreatitis.
15.••Mossner J, Keim V, Niederau C, et al.: Guidelines for
therapy of chronic pancreatitis. Consensus Conference
of the German Society of Digestive and Metabolic Diseases [German]. Z Gastroenterol 1998, 36(5):359–367.
An organized and rational step-wise guide to management of
chronic pancreatitis.
16. Whitcomb DC, Block GD: Association of acetaminophen hepatotoxicity with fasting and ethanol
use. JAMA 1994, 272(23):1845.
17. Sarner M, Cotton PB: Classification of pancreatitis.
Gut 1984, 25:756–759.
18.• Büchler MW, Friess H, Baer H-U, et al.: Surgical
treatment of chronic pancreatitis: new standards.
Digest Surg 1996, 13(2): 1–96.
An excellent journal issue dedicated to a review of the major
surgeries used in treating chronic pancreatic diseases.
19. Beger HG, Schlosser W, Siech M, et al.: The surgical
management of chronic pancreatitis: duodenumpreserving pancreatectomy. Adv Surg 1999, 32:87–104.
20. Suzuki A, Mizumoto A, Rerknimitr R, et al.: Effect of
bacterial or porcine lipase with low- or high-fat diets
on nutrient absorption in pancreatic-insufficient
dogs. Gastroenterology 1999, 116(2):431–437.
21. Maeda H, Danel C, Crystal RG: Adenovirus-mediated
transfer of human lipase complementary DNA to the
gallbladder [see comments]. Gastroenterology 1994,