Milstein Dan M J, te Boome Liane C J, Cheung Yuk Wah, Lindeboom Jérôme A H, van den Akker Hans P, Biemond Bart J, Ince Can
Departments of Translational Physiology and Oral and Maxillofacial Surgery, Academic Medical Center and Academic Center for Dentistry, Amsterdam, The Netherlands.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Jan;109(1):91-7. doi: 10.1016/j.tripleo.2009.08.041.
Oral mucositis (OM) is a common toxic side effect among patients receiving high-dose chemotherapy (CT) with autologous stem cell transplantation (ASCT) for hematologic malignancies. The aim of this study was to investigate changes in submucosal microcirculation in myeloma patients receiving high-dose CT with ASCT by assessing capillary density and microvascular structural integrity.
Ten consecutive patients with multiple myeloma who underwent first-time CT treatment with high-dose melphalan (200 mg/m(2)) and ASCT were included in this study. Baseline buccal mucosa capillary density, expressed as the mean number of capillaries +/- SD per mm(2) (cpll/mm(2)), was measured with sidestream dark-field imaging after treatment was performed, after 30 and 60 minutes, and then on days 2, 4, 6, 8, and 14. A linear mixed model was used to examine capillary density over time and a P value of <.05 was considered to be statistically significant.
Baseline mucosal capillary density was 19 +/- 2.4 cpll/mm(2). Mucosal capillary density after melphalan infusion after 30 and 60 minutes and on days 2 and 4 showed no statistically significant differences. A decrease in capillary density with statistical significance was observed on days 6 (10 +/- 3.0 cpll/mm(2); P < .01) and 8 (12 +/- 4.9 cpll/mm(2); P < .01). On day 14, capillary density returned to near baseline value.
High-dose CT alters microvascular structural integrity and dysregulates tissue perfusion in the oral mucosa by decreasing the number of perfused submucosal capillaries in the oral mucosa. The findings of this investigation suggest that acute CT toxicity alters oral microcirculation and may be an important mechanism responsible for driving early mucosal barrier disturbances associated with CT-induced OM.
口腔黏膜炎（OM）是接受大剂量化疗（CT）联合自体干细胞移植（ASCT）治疗血液系统恶性肿瘤患者中常见的毒性副作用。本研究旨在通过评估毛细血管密度和微血管结构完整性，研究接受大剂量CT联合ASCT的骨髓瘤患者黏膜下微循环的变化。
本研究纳入了10例连续接受首次大剂量美法仑（200 mg/m²）CT治疗及ASCT的多发性骨髓瘤患者。在治疗后、30分钟和60分钟后，以及第2、4、6、8和14天，采用侧流暗视野成像测量基线颊黏膜毛细血管密度，以每平方毫米毛细血管平均数量±标准差（cpll/mm²）表示。使用线性混合模型检查随时间变化的毛细血管密度，P值<.05被认为具有统计学意义。
基线黏膜毛细血管密度为19±2.4 cpll/mm²。美法仑输注后30分钟、60分钟以及第2天和第4天的黏膜毛细血管密度无统计学显著差异。在第6天（10±3.0 cpll/mm²；P<.01）和第8天（12±4.9 cpll/mm²；P<.01）观察到毛细血管密度有统计学显著下降。在第14天，毛细血管密度恢复至接近基线值。
大剂量CT通过减少口腔黏膜灌注的黏膜下毛细血管数量，改变微血管结构完整性并使口腔黏膜组织灌注失调。本研究结果表明，急性CT毒性改变口腔微循环，可能是导致与CT诱导的OM相关早期黏膜屏障紊乱的重要机制。
