Reply to Dr. Hall and coworkers

We would like to thank Mr. Hall and coworkers for their interesting comments on our brief editorial review [1]. Owing to the emerging role of potential exocrine pancreatic insufficiency (EPI) in patients with neuroendocrine neoplasia (NENs) receiving somatostatin analogs (SSAs), any effort to increase the chance for an early diagnosis of this condition is advised to reduce the risk of malnutrition and deterioration of patients’ quality of life. We take up the challenge proposed by the authors, EPI diagnosis (and treatment) may not be easy in the clinical practice mostly if a complete patient’s assessment from clinical and biochemical point of view is not done. In this diagnostic work-up, which must include a combination of clinical features and biochemical laboratory parameters (with particular focus on glycemia, glycated hemoglobin, cholesterol, triglycerides, and D and K vitamins), the fecal elastase 1 (FE-1) test plays a significant role, being recognized as a quick and relatively cheap indirect assessment of residual pancreatic function. As mentioned by Varga et al. in a systematic review and meta-analysis, the FE-1 usefulness relies on the underlying prevalence of EPI in the evaluated population [2]. Although it might not be accurate in a low prevalence population (i.e. irritable bowel syndrome), the FE-1 diagnostic accuracy significantly rises in those setting of patients with high prevalence of pancreatic dysfunction, including pancreatic cancer, chronic pancreatitis, and NEN patients treated with SSAs [3,4]. Its overall sensitivity and specificity to diagnose severe EPI was equally high compared with both direct (97% and 91%, respectively) and indirect tests (96% and 88%, respectively), a figure which is similar to available data on ¹³C-labeled mixed triglyceride (¹³CMTG) breath test (sensitivity 90–100% and specificity 90–92%, respectively) [2,5]. However, assuming a similar diagnostic accuracy for both tests, it is undoubted that ¹³CMTG has some limitations compared with FE-1: i. It is more costly and time-consuming; ii. It is not yet widely available; iii. The amount of available literature supporting the role of ¹³CMTG is clearly scarce compared with FE-1 (few decades of records vs hundreds of articles are retrieved in Pubmed for those two tests, respectively – search performed on 31 March 2021). Translating this ‘evidence’ in the clinical setting of NENs is particularly hard, owing to the rarity of these tumors and the risk of overlap between tumor related specific symptoms (in patients with carcinoid syndrome), previous history of pancreatic or intestinal surgery, comorbidities, and the possible impact of SSAs therapy on exocrine pancreatic function. In this challenging clinical scenario, the clinical trial proposed by Mr. Hall and coworkers might give its contribution to fill the gap in the knowledge on the potential role of SSAs on pancreatic dysfunction in patients with NENs. We look forward to reading the results of that study, in the meantime we suggest physicians dealing with NEN patients receiving SSAs to carefully seek for EPI by checking clinical status, routinely assessing laboratory nutritional parameters, and performing pancreatic function tests (whatever available in their hospital) to improve the care of their patients.

Declaration of interest

F Panzuto received honoraria as speaker from Mylan Italia. The authors have no other 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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Funding

This paper was not funded.