Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans

Background and aims-The mechanism of gastrointestinal damage (mucositis) in duced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage followi ng chemotherapy in humans. Methods-Patients receiving chemotherapy underwent upper gastrointestinal en doscopy (a maximum of two per patient) with duodenal biopsy prior to chemot herapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was tak en for morphometry, disaccharidase assays, electron microscopy, and for ass essment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. Results-Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height d ecreased at three days after chemotherapy. Disaccharidase activities remain ed unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices impr oved by 16 days. Conclusion-Small intestinal mucositis is associated with apoptosis in crypt s that precedes hypoplastic villous atrophy and loss of enterocyte height.