title: Endoscopy in patients with diarrhea during treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors: Is the cause in the mucosa?
abstract: BACKGROUND
  Diarrhea is a frequently occurring adverse event during treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and is mostly accompanied by abdominal cramps, flatulence and pyrosis. These complaints impair quality of life and lead to dose reductions and treatment interruptions. It is hypothesized that the diarrhea might be due to ischemia in bowel mucosa or inflammation, but the exact underlying pathophysiological mechanism of the diarrhea is still unknown. We aimed at exploring the mechanism for diarrhea in these patients by thorough endoscopic and histological assessment.
  
  
  METHODS
  Endoscopies of the upper and lower gastrointestinal (GI) tract in 10 patients with metastatic renal cell carcinoma (mRCC) who developed diarrhea during treatment with VEGFR TKIs were performed.
  
  
  RESULTS
  Ten patients were included. The results showed endoscopically normal mucosa in the lower GI tract in seven patients without signs of ischemic colitis or inflammation. Gastroduodenoscopy revealed gastro-esophageal reflux disease, bulbitis and/or duodenitis with ulcers in eight patients. In three selected patients with bulbitis/duodenitis additional video capsule endoscopy was performed but revealed no additional intestinal abnormalities.
  
  
  CONCLUSIONS
  We observed frequent mucosal abnormalities in the upper GI tract in VEGFR TKI-treated mRCC patients with diarrhea. Although these abnormalities provide insufficient explanation for the occurrence of diarrhea, we suggest to perform routine upper GI endoscopy in VEGFR TKI-treated patients with GI complaints.
authors.affiliation: a Department of Medical Oncology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Marye J
authors.initials: MJ
authors.lastname: Boers-Sonderen
authors.affiliation: a Department of Medical Oncology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Sasja F
authors.initials: SF
authors.lastname: Mulder
authors.affiliation: b Department of Pathology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
authors.affiliation: c Department of Gastroenterology and Hepatology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Lauranne A A P
authors.initials: LA
authors.lastname: Derikx
authors.affiliation: c Department of Gastroenterology and Hepatology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Geert J A
authors.initials: GJ
authors.lastname: Wanten
authors.affiliation: d Department of Urology , Radboud University Medical Centre , Nijmegen , The Netherlands.
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.affiliation: a Department of Medical Oncology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.affiliation: c Department of Gastroenterology and Hepatology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Frank
authors.initials: F
authors.lastname: Hoentjen
authors.affiliation: a Department of Medical Oncology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D053704:Capsule Endoscopy / Q000379:methods; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced* / Q000473:pathology; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib