Thread by @DeMadaria

Pancreatic exocrine insufficiency: causes, consequences, diagnosis and treatment.

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Pancreatic juice is composed by
- Acinar secretion, rich in enzymes
- Ductal secretion: A) Water that will help to flush the acinar secretion B) Bicarbonate that will neutralize gastric acid in the duodenum; some enzymes like lipase do not work in an acid environment

The arrival of acid and protein products to the duodenum induce S-cells to produce secretin which stimulates ductal secretion. Fatty acids, amino-acids and vagus nerve induce I-cells to produce cholecystokinin (CCK) which stimulates acinar secretion

According to @my_ueg evidence-based guidelines for chronic pancreatitis, pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes (acinar function) and/or sodium bicarbonate (ductal function) @UEGJournal @maloehr1 ncbi.nlm.nih.gov/pmc/articles/P…

According to the classic Eugene P. DiMagno study published in @NEJM 1973, steatorrhea (>7 grams of fat in stools/24h in a diet containing 100g of fat/day) only develops when pancreatic secretion of lipase is ≤10% of normal @MayoClinic nejm.org/doi/full/10.10…

PEI may be due to A) Insufficient secretion: acute/chronic pancreatitis, cystic fibrosis, Shwachman–Diamond and other rare congenital syndromes, B) Obstruction of the Wirsung duct: acute/chronic pancreatitis, cystic fibrosis, pancreatic/periampullary cancer

C) Surgery: altered gastro-intestinal-biliopancreatic anatomy which is associated to some/all of the following problems:
- poor coordination between food, enzymes and bile
- denervation
- low secretin/CCK secretion
D) Insufficient secretin/CCK secretion due to celiac disease

On the long term, 50-70% patients with chronic pancreatitis (CP) will develop a PEI dx.doi.org/10.1007/s11938… Alcoholic CP develops PEI sooner than idiopathic CP (mean 13 vs 26 years) @AGA_Gastro ncbi.nlm.nih.gov/pubmed/7926511

A third of patients with acute pancreatitis (AP) will have PEI (steatorrhea) in long-term follow-up sciencedirect.com/science/articl…
Risk factors for this complication are to have a severe AP, necrotizing AP and alcohol etiology doi.org/10.1007/s10620…

Many patients with pancreatic surgery develop PEI, for more details read our systematic review insights.ovid.com/pubmed?pmid=27…

If a patient with a PEI-predisposing disease complaints of fatty diarrhea that responds to oral pancreatic enzymes, no pancreatic function test is needed @AmCollegeGastro insights.ovid.com/pubmed?pmid=15…

In the past PEI was determined by measuring pancreatic juice with a Dreiling tube, a double-lumen tube to remove gastric juice (acid inactivates both lipase and bicarbonate) and to collect pancreatic juice after stimulation with secret/CCK or a fatty meal ncbi.nlm.nih.gov/pubmed/18107439

Tests measuring pancreatic juice (volume, bicarbonate, enzyme activity...) are called direct tests. Nowadays the Dreiling tube is almost abandoned, it can be performed by endoscopy but it seems inaccurate, so direct tests are only performed for research insights.ovid.com/pubmed?pmid=28…

Other tests are called indirect tests: fecal fat excretion, fecal elastase-1 and triglyceride breath test. Acid steatocrit, another indirect test is seldom used, probably it needs to be standardized

Determination of fecal fat may be considered as a gold standard to select patients who must receive pancreatic enzyme replacement therapy (PERT, oral enzymes to help digesting food) This can be done by means of the classic Van de Kamer test or a technique called NIRA

The problem with fecal fat determination is that the patient should receive a diet containing 100 g of fat for several days and get stools from 3 consecutive days, which is disgusting and cumbersome for both the patient and the lab staff ncbi.nlm.nih.gov/pubmed/18107439

Pancreatic elastase is a pancreatic enzyme, it hydrolyzes amides and esters amongst many proteins in addition to elastin, a type of connective tissue (that´s from the wikipedia) en.wikipedia.org/wiki/Pancreati…

Elastase-1 is delivered to the duodenum and it can be measured in stools. This is much more simple than fecal fat determination: only a small sample of stool is needed, no diet is necessary, and it´s a stable protein that can be sent to a reference lab. It is also quite cheap

The problem is that fecal elastase-1 (FE-1) has no lineal relationship with fecal fat excretion. When normal, it rules out PEI (high negative predictive value), when low, some patients have steatorrhea but not others (low positive predictive value) sciencedirect.com/science/articl…

Triglyceride breath test is another indirect test. It is more expensive than FE-1, it requires a special diet the day before, the test lasts for 6 hours and accuracy seems similar to FE-1, so it´s probably better to use FE-1 sciencedirect.com/science/articl…

Nutritional markers used in patients with diseases that are frequently associated to PEI may be enough evidence to start PERT if no other tests are available, follow-up after PERT should be done sciencedirect.com/science/articl…

So if fatty diarrhea, proceed to PERT. If FE-1 is normal, the patient has no PEI. If FE-1 is low, look for fecal fat excretion or nutritional markers and proceed to PERT if any of them is abnormal. If FE-1/fecal fat is not available, look for symptoms/nutritional markers

Regarding PERT, according to the @my_ueg guidelines @UEGJournal, a minimum lipase dose of 40,000–50,000 PhU is recommended with main meals, and half that dose with snacks, remember to verify that nutritional markers or fecal fat excretion improves! ncbi.nlm.nih.gov/pmc/articles/P…