Chronic pancreatic insufficiency

Flour 13 Postprandial duodenal pH in 6 healthy controls (solid line) and 6 patients with chronic pancreatic Insufficiency (broken line). Ban show mean SEM , p< 0.05. (From Ref. 61.)... 

The major application of the assays that measure CHY activity in stool is in the investigation of chronic pancreatic insufficiency. CHY in feces is often reduced below the lower reference limit in such subjects in whom steatorrhea has developed, but it is not usefid in identifying subjects with early pancreatic insufficiency. (See Table 48-15.) CHY measurement in patients with chronic pancreatic insufficiency treated with oral pancreatic enzyme supplements may indicate whether the therapy is adequate or whether increased supplementation is necessary. 

El measurement in stool is the most reliable and sensitive noninvasive procedure for the diagnosis of chronic pancreatic insufficiency. However, such a test does not consistently separate mild to moderate insufficiency cases from healthy controls (see Table 48-15). Unlike fecal CHY, El provides no information helpful to the therapeutic management of the patient. 

PPL Therapeutics reported positive results of its Phase II clinical trial using transgenic BSSL to treat patients with pancreatic insufficiency [63]. The milk-derived product was equally as effective as Creon , the current market leader used to improve digestion and restore fat absorption to normal levels. Creon capsules are administered orally and contain delayed-re-lease microencapsulated porcine pancreatic pancrelipase. Six patients with chronic pancreatic insufficiency were successfully treated, four patients having chronic pancreatitis and one suffering from cystic fibrosis. The larger commercial opportunity for this product is for premature infants... 

These drug are prescribed as replacement therapy for those with pancreatic enzyme insufficiency. Conditions or diseases that may cause a decrease in or absence of pancreatic digestive enzymes include cystic fibrosis, chronic pancreatitis, cancer of the pancreas,... 

The incidence of chronic pancreatitis is approximately 1 in 10,000 people. O The most common cause of chronic pancreatitis in adults in Western countries is ethanol abuse. The most common cause in children is cystic fibrosis, due to preexisting pancreatic insufficiency inherent in the disease. Gallstones can occur at the same time as chronic pancreatitis but are not often implicated as the cause. Unlike acute pancreatitis, chronic pancreatitis has an unknown etiology in a significant number of cases (30%).29,3°... 

Exocrine pancreatic insufficiency is most commonly caused by cystic fibrosis, chronic pancreatitis, or pancreatic resection. When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss. Pancreatic enzyme supplements, which contain a mixture of amylase, lipase, and proteases, are the mainstay of treatment for pancreatic enzyme insufficiency. Two major types of preparations in use are pancreatin and pancrelipase. Pancreatin is an alcohol-derived extract of hog pancreas with relatively low concentrations of lipase and proteolytic enzymes, whereas pancrelipase is an enriched preparation. On a per-weight basis, pancrelipase has approximately 12 times the lipolytic activity and more than 4 times the proteolytic activity of pancreatin. Consequently, pancreatin is no longer in common clinical use. Only pancrelipase is discussed here. 

Tissue reserves of retinoids in the healthy adult are sufficiently large to require long-term dietary deprivation to induce deficiency. Vitamin A deficiency occurs more commonly in chronic diseases affecting fat absorption, such as biliary tract or pancreatic insufficiency, sprue, Crohn s disease involving the terminal ileum, and portal cirrhosis deficiency may also occur following partial gastrectomy or during extreme, chronic dietary inadequacy. 

Pancreatic exocrine insufficiency with nutrient maldigestion as described in the case report is both a classical complication and a defining leading symptom of chronic pancreatitis. Therefore, taking a careful history provides the key for the diagnosis. 

It is important to keep in mind, however, that not all patients with chronic pancreatitis develop clinical pancreatic exocrine insufficiency approximately 25% of patients still have sufficient exocrine function after 25 years of disease. On the other hand, it is also important to note that 10%-15% of patients with chronic pancreatitis have primary painless disease in these patients, pancreatic exocrine insufficiency may be the first (and possibly only) clinical manifestation. Thus, the absence of pain or a history of pancreatitis does not exclude the diagnosis (DiMagno et al., 1993). 

Pancreatic function tests are therefore indicated if and when one or more of the following aspects need be clarified Is a symptom or sign caused by pancreatic exocrine insufficiency Has pancreatic exocrine insufficiency developed in the course of chronic pancreatitis Does a patient require enzyme supplementation treatment ... 

Pancreatic exocrine insufficiency Decreased intraluminal fat digestion Chronic pancreatitis Cystic fibrosis... 

Nutrient maldigestion due to pancreatic exocrine insufficiency is a classical complication of chronic pancreatitis. In most cases, it occurs... 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

In addition to steatorrhea and nutritional deficiencies, patients with pancreatic exocrine insufficiency also develop symptoms such as postprandial pain, cramps, bloating, and distention. These are caused by profound alterations of upper gastrointestinal secretory and motor functions in response to increased nutrient delivery to the distal small intestine, particularly the ileum. In the first 5-10 years of chronic pancreatitis, overt malabsorption is usually neither detected nor a major clinical problem, although enzyme output may decrease by 60%-90%. Still, there is evidence that, even in the early stages of chronic pancreatitis, the site of maximal nutrient digestion and absorption is shifted from the duodenum to the more distal small intestine. 

Direct tests of secretory function such as fecal chymotrypsin and elastase 1 are the tests of first choice if the main diagnostic goal consists of noninvasive confirmation of chronic pancreatitis. Indirect tests may be preferred, however, if the main goal is to verify maldigestion (which needs not be due to loss of pancreatic secretory capacity) or to optimize enzyme treatment. For patients for whom noninvasive direct or indirect tests are negative or equivocal and diagnosis or exclusion of pancreatic exocrine insufficiency appears relevant, the invasive secretin-cerulein (SC) test should be considered. 

Why is steatorrhea the most important digestive malfunction in pancreatic exocrine insufficiency in chronic pancreatitis ... 

Enzyme replacement therapy (ERT) is a therapeutic approach in which the specific enzyme that is absent or inactive in affected individuals is replaced with a functional enzyme molecule. Pancreatic enzyme preparations of porcine or bovine origin have been available in the United States for treatment of exocrine pancreatic insufficiency (EPI) in children and adults with cystic fibrosis and chronic pancreatitis since before the enactment of the Federal Food, Drug and Cosmetic Act of 1938 (ref FDA guidance on EIP April 2004). A... 

Insufficient digestive agents Biliary obstruction Chronic liver failure Chronic pancreatitis Cystic fibrosis Lactase deficiency Pancreatic cancer Pancreatic resection Sucrase-isomaltase deficiency... 

A palindromic arthropathy with effusion and pancreatitis occurred in association with stibogluconate treatment for kala-azar in a 30-year-old man on hemodialysis for chronic renal insufficiency (SEDA-16, 311). 

A 42-year-old woman with insuhn-dependent diabetes and chronic renal insufficiency developed pancreatitis 5 days after taking enalapril 2.5 mg and recovered after drug withdrawal. The pancreatitis relapsed one week after her general practitioner had prescribed losartan 50 mg/day, with full recovery after withdrawal. A rechallenge test with losartan was fully positive. 

A number of laboratory tests are available to measure exocrine function in the investigation of pancreatic insufficiency (most commonly caused by cystic fibrosis in children and chronic pancreatitis in adults). Tests fall into two categories, invasive and noninvasive. Invasive tests require GI, intubation to collect pancreatic samples noninvasive tests (or tubeless tests ) were developed to avoid intubation, which is uncomfortable for the patient, time-consuming, and therefore expensive. Noninvasive tests are simpler and cheaper to perform, but in general they lack the sensitivity and specificity of the invasive tests, particularly for the diagnosis of mild pancreatic insufficiency. It is important to recognize that biochemical tests have a limited clinical application in the diagnosis of pancreatic disease because of either the complexity of the invasive tests or the inadequate... 

Lankisch PG, Schmidt I, Konig H, Lehnick D, Knoll-man R, Lohr M, et al. Faecal elastase 1 not helpftd in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency. Gut 1998 42 551-4. 

Gregory, P.C., Tabeling, R., Fassmann, C. and Kamphues, J. (2002) Therapy of pancreatic exocrine insufficiency new experimental data. In Chronic pancreatitis Novel concepts in biology and therapy (Buckler,... 

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