Pancreatic Exocrine Insufficiency Years After Bariatric Surgery: Clinical Insights From 2 Cases

Introduction

Obesity is a global health pandemic, and bariatric surgery has been established as an effective intervention for significant and sustained weight loss in morbidly obese individuals [1–3]. Among various surgical options, RYGB is a widely performed procedure that alters the gastrointestinal anatomy to promote weight loss and improve metabolic conditions. However, this anatomical alteration can lead to adverse events. A common symptom after bariatric surgery is diarrhea, which can be caused by dumping syndrome, bile acid malabsorption, short-bowel syndrome, and disruption of the gut microbiota, but can also be the result of PEI, which if unrecognized can cause prolonged malnutrition and unnecessary surgeries in post-bariatric patients [4–6]. Incidence rates of PEI after RYGB have been reported at 9–37% [5–10].

PEI results from insufficient delivery of pancreatic enzymes to the small intestine, impairing the digestion and absorption of nutrients. Symptoms include diarrhea, steatorrhea, abdominal pain, and unintended weight loss. The diagnosis is primarily based on clinical presentation and confirmed by low fecal elastase-1 levels, a marker of exocrine pancreatic function. Although PEI is a recognized complication of bariatric surgery, due to limited awareness it is challenging to diagnose and treat. The pathophysiology involves exclusion of the duodenum and proximal jejunum, reducing cholecystokinin and other hormones that stimulate pancreatic secretion [5–8]. This report aims to raise awareness of delayed-onset PEI as a potential cause of chronic gastrointestinal symptoms in long-term RYGB patients and to highlight the clinical implications of its underdiagnosis, including prolonged malnutrition and unnecessary surgical interventions.

This case report presents 2 female patients who had undergone RYGB surgery and developed delayed-onset PEI at 7 and 10 years after their initial RYGB operation, emphasizing the importance of considering PEI in the differential diagnosis when post-bariatric patients present with gastrointestinal symptoms. This report aims to raise awareness of delayed-onset PEI as a potential cause of chronic gastrointestinal symptoms such as diarrhea in long-term RYGB patients.

Case Reports

CASE 1:

A woman in her 40s with type-2 diabetes mellitus and Ehler-Danlos syndrome underwent sleeve gastrectomy 2015 for morbid obesity, with an initial BMI of 43 kg/m². Because of severe vomiting and abdominal pain, she was converted to RYGB in 2017. She was then reoperated because of anastomotic leakage and stenosis of the jejuno-jejunostomy. Her BMI eventually stabilized at 24–26 kg/m² after the RYGB operation. Seven years after the conversion to RYGB, she presented with unexplained severe diarrhea and progressive weight loss from 75 kg to 42 kg (BMI 15.8 kg/m²) in a few months, as well as amenorrhea. At presentation, she appeared severely cachectic, had severe hair loss, hypoalbuminemia 18 g/L (35–55 g/L), anemia, and low iron level, and her BMI eventually fell to 15.8. Her micronutrient evaluation revealed low vitamin D and zinc levels. She was referred to a gastroenterologist and an oncologist due to unexplained progressive weight loss and severe diarrhea, especially to rule out malignancies and inflammatory bowel disease, and repeated examinations were performed, with normal results from upper-GI endoscopies, colonoscopy, and chest, abdominal, and pelvic CT scans, as well as gastrointestinal passage X-ray. Her blood test revealed normal transglutaminase IgA and normal tumor markers. Her fecal elastase level was 77 μg/g (reference range>200 μg/g) and her pancreatic amylase level was 0.11 (ref range 0.38–1.42 microkatals/L). Despite the possibility of false low fecal elastase due to diarrhea, the therapeutic response to PERT supported PEI after RYGB as the main diagnosis.

She was put on total parenteral nutrition because of severe malnutrition. She was also started on pancreatic enzyme replacement treatment (PERT) with daily dose of 50 000 units distributed over the 3 main daily meals, with good effect, but the most effective dose was found to be a daily dose of 75 000 units distributed across the 3 daily main meals. After introduction of the replacement therapy, her diarrhea stopped and she was discharged home with PERT. At the 3-month follow-up review she had gained weight up to 62 kg (BMI 23 kg/m²), her quality of life had improved, her blood parameters were back to normal, her hair loss stopped, and her menstrual cycle returned to normal.

CASE 2:

This was a woman in her 50s with a history of RYGB 10 years prior for morbid obesity, with an initial BMI of 46 kg/m². She had an uneventful postoperative course. Her postoperative BMI fell to 28 kg/m². She was eventually evaluated at our clinic for sudden-onset persistent diarrhea and left-sided abdominal pain, which had been ongoing for 6 months (10 years after RYGB), which negatively impacted her quality of life. Her BMI was 36 kg/m² before symptoms started. She had also at this stage experienced an unintended additional weight loss of 15 kg and her BMI declined from 36 to 29 kg/m². An abdominal CT scan suggested adhesions around the jejuno-jejunostomy, and laparoscopic adhesiolysis was performed, but her symptoms persisted unchanged. Postoperatively, fecal elastase-1 testing showed a level of 53 μg/g, confirming the suspicion of PEI. She was referred to a gastroenterologist to rule out any other cause of diarrhea such as SIBO, bile acid malabsorption, and inflammatory bowel diseases. Examinations were performed with upper-GI endoscopies, colonoscopy, and chest, abdominal, and pelvic CT scans, which were normal except for a suspicion of adhesions around the jejunojejunostomy. She was started on PERT (75 000 units per meal), which resulted in significant symptom relief, especially regarding the diarrhea, as well as weight stabilization. The left-sided abdominal pain decreased but was not completely relieved. She was discharged home on PERT. At the 3-month follow-up, her BMI had increased to 31 kg/m² and her quality of life had improved significantly.

Discussion

Gastrointestinal complications after bariatric surgery are common. PEI is one of the possible complications after bariatric surgery but it remains an underrecognized and underreported diagnosis. PEI is often overlooked after RYGB, as its symptoms can overlap with other gastrointestinal disorders such as small-intestine bacterial overgrowth, bile acid malabsorption, dumping syndrome, and short-bowel syndrome [8]. The incidence of PEI after bariatric surgery varies depending on the type of procedure performed. A meta-analysis found that 23% of patients developed PEI after bariatric metabolic surgery, underscoring the need for awareness and timely intervention [11]. Studies have reported that PEI is more prevalent following malabsorptive procedures such as RYGB and biliopancreatic diversion with duodenal switch (BPD-DS) compared to restrictive procedures like sleeve gastrectomy (SG). A recent prospective study by Uribarri-Gonzalez et al found that malabsorptive procedures like RYGB are associated with higher PEI prevalence compared to restrictive procedures [12]. Moore et al found that 47.9% of patients who underwent RYGB and 70.0% of those who had BPD-DS developed PEI, whereas only 17.4% of SG patients were affected [9]. Diagnosing PEI in post-bariatric patients can be tricky due to symptoms overlapping with those of other postoperative conditions. Although there is no specific method for the diagnosis of PEI, suspecting the diagnosis based on clinical findings and excluding other possible diagnoses plays a critical role. Although the fecal elastase test is not specific for PEI, it is frequently used to support the diagnosis. Fecal elastase-1 testing is a non-invasive test measuring elastase levels in stool. Levels below 200 μg/g suggest PEI. Another test is the fecal fat test, with increased levels indicating malabsorption. Fecal elastase can yield false positives in patients with diarrhea or colitis, but the clear therapeutic response to PERT strengthens the PEI diagnosis despite these limitations. While not diagnostic, imaging can rule out other causes of symptoms [13,14].

There are recently reported cases of delayed-onset PEI manifesting several years after RYGB. Bhatia et al presented a case of a 53-year-old man who developed PEI 7 years after RYGB, presenting with chronic diarrhea and weight loss. Revisional surgery and PERT led to symptom resolution [15]. A similar case was reported by Freedman, in which a 50-year-old woman was diagnosed with PEI and treated with PERT [16].

The exact mechanism of PEI after bariatric surgery is not known, but the literature suggests that the duodenum plays a crucial role in triggering pancreatic enzyme secretion through hormonal signaling. The exclusion of the duodenum and proximal jejunum from the alimentary tract can reduce release of hormones such as cholecystokinin, which plays a crucial role in stimulating pancreatic exocrine function. Procedures like RYGB and BPD-DS significantly alter the anatomy of the gastrointestinal tract, bypassing portions of the stomach and small intestine. This anatomical modification can lead to reduced stimulation, altered levels of pancreatic polypeptide, and secretion of incretin enzymes due to decreased exposure of the proximal GI tract to ingested nutrients, leading to gut hormone and peptide level changes. Gastrin levels decrease and postprandial cholecystokinin level increase after RYGB. Furthermore, surgical resection can disrupt the neural pathways that regulate pancreatic secretion, further contributing to pancreatic insufficiency [5–8]. However, the mechanism of delayed-onset PEI is unclear. The symptoms of PEI often overlap with common postoperative concerns, making diagnosis challenging. Typical manifestations include steatorrhea, diarrhea, weight loss, abdominal pain, and bloating [8,9,14]. Management typically involves PERT, which has been shown to alleviate symptoms and improve nutritional status [6,13,14,17,18]. The International Study Group on Pancreatic Surgery recommends starting with 40 000–50 000 units with main meals, whereas another study suggests that higher doses of up to 75 000 units with meals may be necessary [19,20].

Our 2 cases demonstrate delayed-onset PEI at 7 years and 10 years after gastric bypass surgery, which dramatically improved with PERT, and aid in raising awareness of the condition.

Conclusions

PEI is a significant but often overlooked complication following bariatric surgery, particularly after procedures like RYGB and BPD-DS. Due to the nonspecific nature of its symptoms, their overlap with typical postoperative concerns and lack of a specific diagnostic method, a high index of suspicion is necessary for timely diagnosis. PEI may be considered in the differential diagnosis of patients presenting with symptoms of malabsorption after RYGB, even years after surgery. Implementing appropriate diagnostic measures and initiating PERT can lead to substantial improvements in these patients’ symptoms. These cases raise awareness of delayed-onset PEI as a rare but important cause of chronic diarrhea and malnutrition after RYGB. While the therapeutic response to PERT was compelling, causality cannot be definitively established from case reports alone. Further research is needed to define standardized diagnostic and management pathways for post-RYGB PEI.