Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.

P-P10 The survival benefit of pancreatic enzyme replacement therapy in adult patients undergoing treatment of pancreatic neuroendocrine tumours

Background Patients with pancreatic neuroendocrine tumours (pNETs), treated with somatostatin analogues (SSAs) or pancreaticoduodenectomy, are at risk of exocrine pancreatic insufficiency. This is frequently undiagnosed but can be treated with pancreatic enzyme replacement therapy (PERT). PERT improves survival and nutritional status in other exocrine pancreatic insufficiency-associated conditions such as pancreatic adenocarcinoma. This single-centre retrospective cohort study aimed to establish whether PERT increases survival or weight maintenance in SSA or pancreaticoduodenectomy-treated patients with pNETs. Methods Departmental databases identified patients (n = 82) diagnosed with pNETs between 2009 and 2019 and managed with SSAs and/or pancreaticoduodenectomy. Their baseline characteristics, treatments and outcomes were established from clinical records. Cases (n = 47) received PERT 3 months after either pancreaticoduodenectomy or commencement of SSAs, controls (n = 35) did not. Overall survival was analysed using the Kaplan-Meier method, the log-rank test and multivariable Cox regression. Percentage monthly weight changes were compared using the Mann-Witney U test. The cohort was investigated as a whole and stratified by intervention (pancreaticoduodenectomy or SSAs) as more cases having undergone pancreaticoduodenectomy was a potential confounder. Results Median survival was not reached in either group. Cases experienced significantly greater 5-year overall survival (81% vs 53%, p = 0.010), however, PERT was not independently associated with survival (Hazard ratio 0.47, 95% CI 0.17-1.30, p = 0.143). Cases showed superior median weight maintenance (+0.04% vs -0.10% per month, p = 0.013), but had lower mean baseline weights (70.0kg vs 81.9kg, p = 0.003). Considering SSA-treated patients (n = 55) only, cases (n = 27) showed greater median weight maintenance (+0.04% vs -0.21% per month, p = 0.025) and a trend towards improved median overall survival (55.5, 95% CI 10.3-100.7 vs 47.7, 95% CI 19.1-76.4 months, p = 0.054). Conclusions PERT may improve the maintenance of weight and therefore nutrition in patients with pNETs, treated with SSAs or pancreaticoduodenectomy. PERT may also convey a survival benefit in this same population, however, due to the numerous factors which affect survival, this study appears underpowered to reliably explore this outcome. Further studies are required to accurately define the use and benefits of PERT in this population.

P-O18 Pancreatic Enzyme Replacement Therapy in Upper GI Surgery- A Retrospective Audit

Background Pancreatic enzyme insufficiency (PEI) appears to be under recognised and under treated in upper GI surgery due to limited clinical data regarding the prevalence of PEI after gastric surgery, therefore potentially leading to malnutrition in an already vulnerable patient group. This retrospective audit looked at a total of 197 resections in a two year time period and aimed to determine what type of upper GI surgery pancreatic enzyme replacement therapy (PERT) was used in, if use of PERT improved malabsorption symptoms and/or nutritional markers (weight and grip strength) and finally if there was a consistent PERT dosage that was prescribed with good effect. Methods Retrospective audit recorded all patients that had undergone a total gastrectomy, subtotal gastrectomy, oesophagectomy, colonic interposition, palliative bypass and GIST resections between 2018-2019 that were undertaken in a regional centre for upper GI cancer surgery. Through means of patient electronic records it was recorded which of these patients started on PERT and if there was any improvement in their symptoms. Nutritional markers were recorded at specific intervals and the final dosage of PERT used with good effect. Results 66.6% of total gastrectomies were commenced on PERT with 68.1% reporting an improvement in symptoms and 27.2% reporting some improvement. 34.7% of subtotal gastrectomies were commenced on PERT and 100% of these patients experienced symptomatic relief. 22.4% of oesophagectomies were commenced on PERT with 68% reporting an improvement in symptoms and 9% some improvement. 33% of the colonic interpositions were commenced on PERT with 100% of patients reporting an improvement with symptoms. PEI was not identified in palliative bypass or GIST surgery. No significant improvement in weight was seen 9-12 months post-operatively in patients who began Creon 0-3 months after their operation, with a p-value of 0.19. Not enough grip strength data was available to analyse. The average final PERT dosage in patients that reported some improvement to improvement in symptoms was 50,000 – 75,000 units with every meal and snack. Conclusions More prevalent usage of PERT seen in total gastrectomy resections with good effect. This finding would benefit from further higher quality research to determine the mechanism behind this to support wider PERT usage in this patient group. In view of the overall positive outcomes in regards to symptom control across gastrectomies and oesophagectomies, albeit in small numbers, it should be a considered treatment and regularly screened for. In order to get a statistically significant result in regards to weight improvement when commenced on PERT a bigger sample size would be needed

Case report: Proton pump inhibitor drug-related problem in pancreatic cancer patient unmasks pancreatic enzyme insufficiency

Introduction Palliative care aims to improve the quality of life of patients with a life-limiting or life-threatening illness and is multifaceted involving comprehensive interdisciplinary assessments and interventions. Interdisciplinary palliative care in the setting of untreatable cancer diagnoses is of particular importance due to additional considerations that must be taken as patients are often undergoing palliative chemotherapy and/or radiation therapy. These patients' complexity warrants special considerations and attentiveness to drug-related problems. Case report The purpose of this case report is to highlight the importance of both complete and comprehensive medication histories in cancer care and the impact of proton pump inhibitors on pancreatic enzyme insufficiencies secondary to pancreatic cancers. This case involves a drug-related problem involving three medications that are commonly used in pancreatic cancer patients: pancreatic enzyme replacement therapy, a proton pump inhibitor, and a fluoroquinolone antibiotic. The patient presented in this case report is an 80-year-old man diagnosed with unresectable pancreatic cancer with a history of symptomatic gastroesophageal reflux disease managed with a proton pump inhibitor, specifically tablets of the 40 mg strength of pantoprazole magnesium taken orally once daily. During the patient's first of five 28-day cycles of palliative-intent chemotherapy with gemcitabine and nab-paclitaxel, the patient presented to the emergency department due to fever and, although not severely neutropenic, was prescribed amoxicillin/clavulanate and ciprofloxacin due to his advanced age. After reading a patient advisory on a ciprofloxacin patient information sheet that advised avoidance of concomitant administration of ciprofloxacin and magnesium, the patient self-discontinued his pantoprazole as it was a magnesium salt formulation. This discontinuation was followed by two weeks of persistent foul-smelling diarrhea, flatulence, and abdominal pain. Management and outcome The patient's healthcare team symptomatically managed the patient with oral and intravenous rehydration unaware of the cause of the symptoms. A trial of pancreatic enzyme replacement therapy was initiated; however, it was unsuccessful in resolving his symptoms. After further investigation and a more in-depth patient interview, it was discovered that the discontinued proton pump inhibitor was likely the cause of the patient's new symptoms and was subsequently re-initiated. Pancreatic enzyme replacement therapy in combination with re-initiation of pantoprazole therapy essentially resolved all symptoms. Discussion Before his diagnosis of unresectable pancreatic cancer, the patient had been on proton pump inhibitor therapy for nearly a decade. He had significant atrophy of the pancreas and an undoubtedly decreased pancreatic enzyme and bicarbonate production; however, he did not experience foul-smelling diarrhea indicative of pancreatic enzyme insufficiency while he was on his proton pump inhibitor. We believe that with his proton pump inhibitor therapy, he was unknowingly being partially treated for his worsening pancreatic enzyme insufficiency, specifically the component related to his lack of bicarbonate production and secretion. His discontinuation of his proton pump inhibitor led to a decrease in gastric acid, small bowel, and normal intraduodenal pH, which resulted in any remaining pancreatic enzyme reserve to become non-functional, unmasking his pancreatic enzyme insufficiency. An initial empiric trial of pancreatic enzyme replacement therapy failed in the absence of a proton pump inhibitor; however, within days of restarting his proton pump inhibitor along with pancreatic enzyme replacement therapy, his gastrointestinal symptoms completely resolved. This is due to the decrease of gastric and intraduodenal acidity, which better enabled the function of pancreatic enzymes present in pancreatic enzyme replacement therapy.

Pancreatic Enzyme Replacement Therapy in Patients Undergoing First-Line Gemcitabine Plus nab-paclitaxel for Advanced Pancreatic Adenocarcinoma

BackgroundThe clinical consequences of pancreatic exocrine insufficiency and its treatment in advanced pancreatic ductal adenocarcinoma (PDAC) are poorly investigated. This retrospective study aims at investigating the pancreatic enzyme replacement therapy (PERT) use and its impact on survival and maldigestion-related symptoms in advanced PDAC patients undergoing chemotherapy.MethodsA retrospective analysis was conducted on advanced PDAC patients, treated with first-line gemcitabine plus nab-paclitaxel at two academic institutions (March 2015-October 2018). Data were correlated with overall survival (OS) using Cox regression model. Kaplan-Meier curves were compared using Log-Rank test.ResultsData from 110 patients were gathered. PERT was administered in 55 patients (50%). No significant differences in baseline characteristics with those who did not receive PERT were found. Median OS for the entire group was 12 months (95% CI 9-15). At multivariate analysis, previous surgical resection of the primary tumor, (HR 2.67, p=0.11), weight gain after 3 months (HR 1.68, p=0.07) and PERT (HR 2.85, p ≤ 0.001) were independent predictors of OS. Patients who received PERT reported an improvement of maldigestion-related symptoms at 3 months more frequently than patients who did not (85.2% vs 14.8%, p ≤ 0.0001).ConclusionPERT is associated with significantly prolonged survival and maldigestion-related symptoms alleviation in advanced PDAC patients.