Dear Editor,
We read with interest the expert opinion from Panzuto and colleagues [Citation1] on the development of pancreatic exocrine insufficiency (PEI) secondary to somatostatin analogue (SSA) therapy in patients with gastroenteropancreatic neuroendocrine neoplasia (GEP-NENs).
We concur with the suggestion that efficient and effective diagnosis of PEI in GEP-NENs is important but complicated due to overlap in symptoms of PEI, and other gastrointestinal pathologies associated with NENs [Citation2]. The impact of treatment for PEI can be highly effective as reported in both studies from Saif et al and Rinzivillo et al [Citation3,Citation4]. Pancreatic enzyme replacement therapy (PERT) has been shown to be associated with improved survival among patients with pancreatic adenocarcinoma [Citation5], though evidence for PERT in the setting of NENs is scarce.
We challenge the authors’ suggestion that diagnosis of PEI is ‘easy’. The widespread use of the Faecal elastase-1 (FE-1) stool test relates to its acceptable sensitivity and lack of invasiveness. However, with experience from our own practice, FE-1 is a cumbersome test for both patients and laboratory staff. Additionally, evidence for its accuracy is scarce and conflicting [Citation6–9].
Our center is currently conducting a prospective, observational, cohort study to determine the incidence of PEI in this patient cohort, before and after they receive treatment with SSA. Within the study, we are comparing two diagnostic tests for PEI: FE-1 and 13C-labeled mixed triglyceride (13CMTG) breath test. The latter boasts superior accuracy and reliability to the FE-1 test in the literature. It is a potential alternative to FE-1 for PEI diagnosis, though it is not in widespread use due to expense, requirement of strict control measures and a 6-hour testing timeframe [Citation10,Citation11]. We look forward to reporting our results in due course.
We agree with the authors’ recommendation for a large prospective study to enhance current understanding of this condition, whilst encouraging exploration of alternative diagnostic strategy for PEI.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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References
- Panzuto F, Magi L, Rinzivillo M, et al. Expert Opinion on Drug Safety Exocrine pancreatic insufficiency and somatostatin analogs in patients with neuroendocrine neoplasia. Expert Opin Drug Saf [Internet]. 2021;1–4. DOI:https://doi.org/10.1080/14740338.2021.1881478
- Khan MS, Walter T, Buchanan-Hughes A, et al. Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: a systematic review. World J Gastroenterol. 2020 Aug;26(30):4537–4556.
- Saif MW, Larson H, Kaley K, et al. Chronic octreotide therapy can induce pancreatic insufficiency: a common but under-recognized adverse effect. Expert Opin Drug Saf. England. 2010;9:867–873.
- Rinzivillo M, De Felice I, Magi L, et al. Occurrence of exocrine pancreatic insufficiency in patients with advanced neuroendocrine tumors treated with somatostatin analogs. Pancreatol Off J Int Assoc Pancreatol. [et al]. 2020 Jul;20(5):875–879.
- Roberts KJ, Schrem H, Hodson J, et al. Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy. Hpb [Internet]. 2017;19(10):859–867.
- Symersky T, Van Der Zon A, Biemond I, et al. Faecal elastae-I: helpful in analysing steatorrhoea? Neth J Med. 2004;62(8):286–289.
- Halloran CM, Cox TF, Chauhan S, et al. Partial pancreatic resection for pancreatic malignancy is associated with sustained pancreatic exocrine failure and reduced quality of life: a prospective study. Pancreatology [Internet]. 2011;11(6):535–545.
- Benini L, Amodio A, Campagnola P, et al. Fecal elastase-1 is useful in the detection of steatorrhea in patients with pancreatic diseases but not after pancreatic resection. Pancreatology [Internet]. 2013;13(1):38–42.
- Lindkvist B, Phillips ME, Domínguez-Muñoz JE. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: prevalence and diagnostic use. Pancreatology. 2015;15(6):589–597.
- Domínguez-Muñoz JE, Nieto L, Vilariño M, et al. Development and diagnostic accuracy of a breath test for pancreatic exocrine insufficiency in chronic pancreatitis. Pancreas. 2016;45(2):241–247.
- Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol. 2007;5(4):484–488.