Pancreatic insufficiency after gastrectomy: an underdiagnosed condition?

As survival rates post-gastrectomy improve,1 there is increased focus on postoperative outcomes and quality of life. Exocrine pancreatic insufficiency has emerged as a leading cause of gastrointestinal symptoms, with an incidence ranging from 47% to 100%.2-4 Pancreatic insufficiency results in fat malabsorption which in turn may cause steatorrhea, bloating, abdominal pain, and weight loss. Unfortunately, the consequences of fat malabsorption extend beyond just troublesome symptoms. Pancreatic insufficiency has been associated with cardiovascular disease,5 micronutrient deficiencies, and an inability to regain a healthy weight with associated frailty. This collectively contributes to higher morbidity and mortality rates in patients with untreated pancreatic insufficiency.6, 7 It is therefore of paramount importance to recognize and treat pancreatic insufficiency promptly. Why does pancreatic insufficiency occur after gastrectomy? In patients who are missing most or all of their stomach, several problems occur. First, the loss of a gastric reservoir equates to a lack of mechanical digestion of food into chyme and, instead, quick transit of food particles into the small intestine.8 Larger food particles are less potent stimulators of cholecystokinin, an important secretagogue for pancreatic enzymes.9, 10 Second, a Roux-en-Y reconstruction with bypass of the duodenum also results in less cholecystokinin secretion.11 Third, postcibal asynchrony occurs where the release of pancreatic enzymes is not coordinated with the intestinal transit of food. This may result in pancreatic maldigestion.12 And finally, truncal vagotomy has been shown to reduce the secretion of pancreatic trypsin and lipase by 50 to 60%.13 Surgeons must have a high index of suspicion! Pancreatic insufficiency can be difficult to diagnose in the early stages because compensatory mechanisms exist. In fact, clinical symptoms may not manifest until exocrine pancreatic function is less than 10% of normal.14 In addition, some symptoms of pancreatic insufficiency are very similar to dumping syndrome which may occur following gastrectomy. We recently tested 12 consecutive gastrectomy patients at our centre at 3 months postoperatively, and found a 30% incidence of pancreatic insufficiency. Of interest, only one patient was symptomatic (unpublished data). In patients with no or minimal symptoms, dietitians may be instrumental in identifying pancreatic insufficiency by quantifying oral intake with weight loss to evaluate the likelihood of malabsorption. A multitude of tests for exocrine pancreatic function have been developed over the years. However, many of these are cumbersome (e.g., 72-h faecal fat test) and/or available at only limited centres (e.g., the 13C-mixed triglyceride breath test).15 The faecal elastase-1 test is one of the most available, as well as sensitive and specific, test for severe pancreatic insufficiency. Faecal elastase levels of 100–200 μg/g indicate moderate, and <100 μg/g severe, pancreatic enzyme insufficiency.16 However, given steatorrhea may only occur when pancreatic enzyme secretion falls below 10% of normal levels, with a corresponding decrease in enteral absorption rate to less than 93%,14 it is not good at picking up early or mild pancreatic insufficiency.17 The need for formed stools for the analysis of faecal elastase to minimize a dilutional effect should also be noted, which may be problematic in chronic diarrhoea.16 Once a diagnosis of pancreatic insufficiency is made, and/or whilst awaiting confirmation, what are next steps? With careful history-taking and clinical suspicion for pancreatic insufficiency, empiric treatment with pancreatic enzyme replacement therapy (PERT) may be commenced.18 It is important to note that PERT will not affect faecal elastase-1 testing as this measures human elastase levels only. Recommended starting doses are 50,000 units of lipase with meals and 25,000 units with snacks or nutritional supplements, and to escalate doses up to 100,000 units per meal if initial dosing is ineffective with ongoing symptoms of fat malabsorption. Beyond this dose other comorbidities (such as inflammatory bowel disease, lactose intolerance etc.) warrant exclusion. Patients should be instructed to take the capsules over the course of a meal for optimal absorption and to best mimic pancreatic function. In addition, it may benefit post-gastrectomy patients to open the capsules and sprinkle the granules on an acidic purée (e.g., apple sauce, jam, and fruit yoghurt), as the gelatin capsule may not breakdown in the absence of sufficient gastric acid. PERT efficacy has been somewhat inconsistent17 with some studies demonstrating marginal improvements of steatorrhea or other functional gastrointestinal symptoms,19, 20 whilst others report overwhelmingly positive outcomes.21 Can the surgeon do better to prevent the occurrence of pancreatic insufficiency? Probably not. Certainly, the incidence was less prior to the widespread adoption of Roux-en-Y reconstructions. A comparative study of 31 patients who underwent Roux-en-Y versus Bilroth I reconstruction after subtotal gastrectomy showed a greater reduction of fat digestion and absorption in the Roux-en-Y group.22 However, surgeons had good reason to move to bypass the duodenum in order to prevent bile reflux, and to attain a more oncological resection. In summary, pancreatic insufficiency is an underdiagnosed condition post gastrectomy and an important cause of malabsorption associated with increased morbidity. Pancreatic insufficiency stems from a complex interplay of factors including decreased endogenous stimulation, postcibal asynchrony, vagal denervation, loss of gastric reservoir and duodenal transit. Understanding these mechanisms is critical for effective management to mitigate the effects of malnutrition, and ultimately, to improve patient outcomes. Open access publishing facilitated by Flinders University, as part of the Wiley - Flinders University agreement via the Council of Australian University Librarians. Christina McVeay: Data curation; investigation; project administration; writing – original draft; writing – review and editing. Caitlin A. Davis: Supervision; writing – review and editing. Dr. Thompson is an Editorial Board member of ANS Journal and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication.