Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease
Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease
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DOI：
10.1007/s00262-005-0101-y
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
van Egmond, M.
中科院分区：
文献类型：
--
作者：
Oosterling, S. J.;van der Bij, G. J.;van Egmond, M.
背景：大网膜常累及胃肠道和卵巢肿瘤。因此，在手术治疗中，尤其是胃癌和卵巢癌的常见做法包括切除大网膜。矛盾的是，许多免疫细胞，如积聚在所谓的乳状斑点中的巨噬细胞，驻留在大网膜内，在体外对肿瘤细胞具有细胞毒性。因此，大网膜巨噬细胞可能在杀死肿瘤细胞中发挥重要作用，并可能因此阻止肿瘤发展为局部腹膜复发。因此，在本研究中，我们评估了网膜的作用和网膜切除术在微小残留疾病（MRD）中的临床意义。方法：采用dii标记的cc531肿瘤细胞检测大鼠大网膜上肿瘤细胞的播散规律。此外，在第21天进行网膜切除术或假手术后腹腔注射cc531细胞的大鼠腹膜内（i.p.）肿瘤负荷进行了研究，这代表MRD。结果：注射后4 h，肿瘤细胞以乳白色斑点为主黏附。此后，细胞数量迅速下降，表明这些特异性免疫聚集体具有最初的肿瘤杀伤功能。尽管最初在乳状斑点中观察到肿瘤细胞减少，但在网膜边缘的脂肪组织条纹中肿瘤细胞数量增加。这表明在这些位置有增殖，这与肿瘤细胞注射后第21天大网膜的宏观观察相一致。网膜切除术导致腹腔内肿瘤负荷减少，这完全归因于网膜的缺失，因为其他部位的肿瘤发展没有差异。即使在MRD组中，位于网膜的肿瘤细胞的微观集群最终也发展成宏观结节。结论：由于大网膜乳白色斑点即使在MRD上也不足以阻止腹腔内肿瘤的生长，对于腹腔内易扩散的腹腔内肿瘤，手术治疗建议采用大网膜切除术，减少肿瘤负荷。
Background: The greater omentum is frequently involved in the course of gastrointestinal and ovarian tumors. Therefore, common practice in surgical treatment for especially gastric and ovarian cancer includes removal of the greater omentum. Paradoxically, many immune cells, such as macrophages that accumulate in so-called milky spots, reside within the omentum and are cytotoxic against tumor cells ex vivo. Consequently, omental macrophages might play an important role in killing tumor cells, and may hereby prevent development into local peritoneal recurrences. In the present study, we therefore evaluated the role of the omentum and the clinical relevance of omentectomy in minimal residual disease (MRD). Methods: Tumor cell dissemination patterns on the omentum in a rat model were examined using DiI-labelled CC531s tumor cells. Additionally, intra peritoneal (i.p.) tumor load was investigated in rats that underwent omentectomy or sham laparotomy followed by i.p. injection of CC531s cells on day 21, which represented MRD. Results: At 4 h post injection, tumor cells predominantly adhered on milky spots. Number of cells thereafter declined rapidly suggesting initial tumor killing functions in these specific immune aggregates. Despite initial reduction observed in milky spots, numbers of tumor cells however increased at fatty tissue stripes that border the omentum. This indicated proliferation at these locations, which corresponded to macroscopic observations of the omenta on day 21 after tumor cell injection. Omentectomy resulted in reduced intra-abdominal tumor load, which was completely attributable to the absence of the omentum, as tumor development did not differ on other sites. Even in the MRD group microscopic clusters of tumor cells located in the omentum eventually developed into macroscopic nodules.Conclusion: Since the ability of omental milky spots is, even in MRD, insufficient to prevent intra abdominal tumor outgrowth, omentectomy, which reduces tumor load, is recommended in surgical treatment of intra abdominal tumors that are prone to disseminate intraperitoneally.