Vitamin insufficiency after surgery for oesophagogastric neoplasms: a prospective intervention study VITAMin Insufficiency in oesophagogastric Neoplasms or the VITAMIN study

Background: Oesophageal cancer (EC) and gastric cancer (GC) are among the top ten cancers worldwide. Both diseases have impact on the nutritional status of patients and their quality of life (QoL). Preoperative malnutrition is reported in 42-80%. However, studies investigating postoperative nutritional status are limited and postoperative identification and treatment of micro- and macro-nutritional deficiencies are currently lacking in (inter-)national guidelines. The aim of this study is to identify and target micronutrient deficiencies after surgery for oesophageal or gastric neoplasms. Methods: This is a single-centre prospective intervention trial performed in Zuyderland Medical Centre. A total of 248 patients who underwent oesophagectomy (n=124) or (sub)total gastrectomy (n=124) from 2011 until 2022 will be included (Cohens’d 0.4, power 80%, two-sided α 0.05, 20% dropout). Both groups will receive Calcium Soft Chew D3 and a tailormade multivitamin supplement (MVS); the oesophagectomy group will receive Multi-E and the gastrectomy group will receive Multi-G. The MVSs will be taken once daily and Calcium Soft Chew D3 twice daily. Supplementation will start after baseline measurements. At baseline (T=0), blood withdrawal for micronutrient analysis and faecal elastase-1 analysis for exocrine pancreas insufficiency (EPI) will be performed. Additionally, patients will receive questionnaires regarding QoL and dietary behaviour. After 180 days of supplementation (T=1), baseline measurements will be repeated, and the supplement tolerance questionnaire will be completed. Measurements will also be conducted after 360 days (T=2) and after 720 days (T=3) of supplementation. The main study parameter is micronutrient deficiency (yes/no) for all measurements. Secondary parameters include occurrence of EPI (n, %), occurrence of diarrhoea (n, %), steatorrhea (n, %) or bloating (n, %), time between surgery and start of supplementation (mean in months), QoL (questionnaires) at all time points. We hypothesize that vitamin B12, folic acid, vitamin D and ferritin are the most common deficiencies, and supplementation may resolve measured deficiencies. Discussion: If micronutrient deficiencies are present in this population and daily supplementation resolves these deficiencies, routine monitoring and supplementation of micronutrient deficiencies can be implemented in the standard postoperative care of oesophageal and gastric surgery. Trial registration: registered as NL9787 in the Netherlands Trial Registration, registered on October 18 th , 2021 on https://www.trialregister.nl/trial/9787