Pancreas and Digestion

Editor’s note: More than half of people with VHL will have one or more cysts or tumors of the pancreas.  Most frequently these are cysts, which in themselves are considered harmless.  Hard tumors of the pancreas need to be monitored closely, as described in the VHL Handbook and in more recent research from Dr. Steven Libutti in the U.S. and Dr. Pascal Hammel in France.

Those “harmless” cysts in the pancreas, however, can often cause issues simply by blocking the pancreatic duct, preventing enzymes from reaching the gut, and causing disruption of normal digestion.   This new article in the Journal of Supportive Oncology(see Note 1) provides a strategy for helping get the digestion back on track by prescribing some pills to provide more pancreatic enzymes.

When the amount of pancreatic enzymes being delivered to the digestive tract is insufficient to do the job, there may be vague abdominal discomfort, pain, abdominal distention, excessive foul-smelling flatus (wind), belching, diarrhea, steatorrhea (excess fat in the stool)), and weight loss. This is a condition called pancreatic exocrine insufficiency.  It is common in people with pancreatic tumors, most commonly after surgery. However, most people with pancreatic cysts and tumors will have a blocked or partially blocked pancreatic duct and are also likely to have some need of Enzyme Substitution Therapy (EST).

These distressing symptoms have a negative impact on both the physical and psychological health of patients. It is important to maintain a healthy weight in order to maintain stamina for life and for treatment of any other issues.

Even though EST is simple and inexpensive, doctors are not always aware to check these levels and prescribe the pills.  Recognizing the importance of this issue, the latest version of the National Comprehensive Cancer Network guidelines (http://www.nccn.org/pancreaticcancer) lists pancreatic enzyme replacement as one of the key factors in the supportive care of patients with pancreatic tumors.  The article reviews the rationale, indications, diet, and future directions relevant to EST.

Pancreatic enzymes are essential for proper digestion and absorption of nutrients.  The key enzymes are amylase, lipase, trypsin, and chymotrypsin.  The pancreas secretes these enzymes in a rhythm coordinated with the cycles of the gastric system.  Following the emptying of the stomach, the pancreas gets to work secreting enzymes to process the food. The exocrine secretion rate rises by three to six times within an hour, and is back to the base rate about 3-4 hours after eating.

The quantity and duration of secretion is coordinated with the caloric value of food eaten, the free fatty acid content, the presence of certain amino acids, the solidity of a meal, and the readiness of the food for absorption by the body.  After a standard meal, the output of lipase rises by 3 to 6 times, and the output of amylase and trypsin rises by 10 to 20 times.  To prevent rapid degradation of lipase, the acid balance in the duodenum has to be within the right range, and the amount of bicarbonate secreted into the duodenum is critical for fat digestion. (See Note 2)

Nutritional care of patients with pancreatic cysts and tumors presents numerous challenges, as patients often suffer from a myriad of gastro-intestinal (GI) symptoms, and people who have had pancreatic surgery have additional considerations.  The goals of nutrition in such patients are to prevent or correct malnutrition; prevent wasting of muscle, bone, and lean body mass; and reduce nutrition-related side effects.

Fats are a concentrated source of calories, providing more than double the calories per gram provided by carbohydrate and fat.  The digestion of long-chain fatty acids occurs in the small intestine and requires both bile and lipase. A diet containing 30%–35% of calories from fat is normally the starting recommendation.

Before restricting fats, the doctor should investigate other potential causes of diarrhea, such as lactose intolerance, bacterial overgrowth, bile acid insufficiency, and infection with Clostridium difficile. In cases of fat restriction, short-chain and medium-chain triglycerides (MCTs) can be used as a calorie source and do not require the aid of bile acids and lipase to be shuttled to the liver. MCT oils (such as coconut oil) can be purchased over the counter in many pharmacies and supermarkets. They can be used as a fat replacement in cold foods but should not be used in cooking due to a low boiling point.

Carbohydrate digestion begins in the mouth with saliva, and is further broken down in the small intestine with the help of pancreatic juices.  Incomplete carbohydrate digestion due to insufficient amylase can result in diarrhea from undigested starches reaching the colon. Patients who have had a non–pylorus-preserving pancreaticoduodenectomy (as in a Whipple procedure) should avoid simple sugars, which can cause dumping syndrome and can make diarrhea worse. Recommendations for carbohydrate intake range from 45%–60% of calories depending how well the pancreatic enzymes are balanced.

Protease is required for protein digestion. Poor protein digestion and absorption can lead to production of toxic substances in the intestine and an increased risk of intestinal infections. Protein needs in patients with pancreatic tumors are not well known.  Initially, protein can constitute 15%–20% of caloric intake. A 24-hour urea nitrogen test may be helpful to determine nitrogen balance and to offer a better estimation of protein needs.

Alcohol inhibits gastric lipase secretion, and therefore should be avoided.

If pancreatic imbalance goes on for a long time, making it hard for the body to absorb the nutrients in the food, it can result in vitamin and mineral deficiencies. Absorption of Vitamins A, D, E, and K depends on absorption of fats. Vitamin B12 deficiency may also be present, because protease is required for cleavage of vitamin B12 from protein.  Iron deficiency can occur when proton pump inhibitors (antacids) are prescribed. (See Note 3) Post Whipple patients have an increased propensity toward calcium, zinc, and iron deficiencies.   (See Note 4) When a patient presents with anemia, testing for serum B12, red blood cell folate, and iron can help identify the cause of anemia. No current data exist on vitamin supplementation in pancreas patients.

Trace element deficiencies have been documented in patients with chronic pancreatitis and may occur in people with pancreatic cysts and tumors. In our experience, patients often limit food variety, so we believe it is good to prescribe a multivitamin with minerals. If symptoms of malabsorption persist, it can help to take a form of fat-soluble vitamins that can be mixed with water (“watermiscible” vitamins). Vitamin B12 is indicated for those found to have a deficiency; the sublingual (under-the-tongue) variety avoids some other balancing issues. Additional micronutrient supplementation can be provided as indicated by blood testing.

In our experience, oleic acid breath test, assessment of stool elastase, and estimation of fecal fat content are the main methods of estimating the degree of fat malabsorption.  We advocate EST to all patients with pancreatic cancer, and would therefore assume it would be helpful also to people with VHL.  EST has been shown to help patients with a greater than 15% loss of fat in feces, but its application in patients with less than a 15% loss is debatable. However, Dominguez-Munoz demonstrated a role of EST in patients with pancreas issues who do not have digestive symptoms and who have less than a 15% loss of fat in feces, as these patients are likely to have low levels of vitamins A, D, E, and K; ferritin; and prealbumin. (See Note 5)

The article cites a number of studies showing the effectiveness of EST.

Practice Guidelines for Physicians

The main principle of EST is simulation of the normal complement of pancreatic enzymes by taking supplements during or just after meals.  EST can often relieve many of the symptoms associated with pancreatic enzyme deficiency, and can allow patients to increase food intake and to improve their nutritional status. Patients should be instructed on the signs and symptoms of malabsorption (Table 1) as well as the rationale for starting EST. Table 2 offers patient information that can be provided when patients start EST.

Replacement pancreatic enzymes are available in different formulations and dosages, at varying costs. EST preparations are dosed by lipase content but also contain amylase and protease. Enzymes can be dosed by fat intake or by weight.

In our practice, we prefer calculating the dosage by fat intake.  Our usual starting dose is 50,000 IU per meal; we escalate the dose depending on how well it relieves symptoms, and by monitoring for appropriate weight gain. A patient-generated diary documenting food intake, EST compliance, and the incidence of diarrhea can help identify a need for changes to the dosages.

If steatorrhea persists despite enzyme changes, a lower fat diet may be warranted. The amount of pancreatic enzymes required will vary with the amount of food eaten and may need to be increased with larger meals (eg, two with a meal and one with a snack).

The effectiveness of EST depends on how well the patient manages these calculations and the timing of food and pills.

In the opinion of the authors, EST has a unique role in the management of pancreatic insufficiency and should be considered for most patients with pancreatic cysts and tumors to provide supportive care.  Newer, “enteric” pills, coated to protect the stomach lining, are usually tolerated better than older preparations which are not enteric coated as only 1% of these preparations actually reach the duodenum, as shown by Dimagno et al. (See Note 2) The use of antacid medications with EST may make the enzymes more effective.

Control of symptoms such as fat malabsorption and diarrhea may have a major impact on an individual’s quality of life.

Notes:  

The full article, Venugopal Damerla, MD, Vladimir Gotlieb, MD, Heidi Larson, RD, and M. Wasif Saif, MD. “Pancreatic Enzyme Supplementation in Pancreatic Cancer” J Support Oncol 2008;6:393-396, is available on the internet at
http://www.supportiveoncology.net/journal/articles/0608393.pdf

2. DiMagno EP, Malagelada JR, Go VL. The relationships between pancreatic ductal obstruction and pancreatic secretion in man. Mayo Clin Proc 1979;54:157–162 PMID 7032685

3. Examples of proton pump inhibitors.  Read the active ingredients on the label.  Brand names vary by country.

- Omeprazole (some brands: Losec, Prilosec, Zegerid, ocid)
- Lansoprazole (brands: Prevacid, Zoton, Inhibitol)
- Esomeprazole (brands: Nexium)
- Pantoprazole (brands: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan)
- Rabeprazole (brands: Rabecid, Aciphex, Pariet, Rabeloc)

4. Anderson JJB. Minerals. In: Mahan LK, Escott- Stump S, eds. Krauses’s Food Nutrition and Diet Therapy. 11th ed. Philadelphia: WB Saunders; 2003:120–163.

5. Munoz JE. Management of maldigestion in chronic pancreatitis: a practical protocol. In: Dominguez-Munoz JE, ed. Clinical Pancreatology for Practicing Gastroenterologists and Surgeons. London: Blackwell Publishing; 2005:288–295.

As printed in the VHL Family Forum 17:1, January/February 2009. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.