Background: Patients with jejunoileal neuroendocrine tumors (JINETs) can live for many years despite liver metastases. Evidence suggests that tumor heterogeneity is prognostically important, hence the selection of Ki67 hotspots for tumor grading. According to the stepwise metastasis model, clonal hotspots should predominate in the metastases. However, an alternative view holds that the polyclonality of metastases is consistent with origin from genetically heterogeneous clusters of disseminated cells. The shortcomings of Ki67 grading are also being recognized, thus renewing the search for other prognostic parameters. Methods: A 20-year retrospective study that paired JINETs and hepatic metastases was conducted by analyzing them for various parameters. Results: There were 43 patients (mean follow-up of 7.234 years); 14 were dead due to the disease, 22 were alive with the disease, and 7 were alive with no evidence of the disease. Most JI NETs (22/30) were grade 1, eight were grade 2, and none were grade 3. Tumor grades for both the primaries and liver metastases were not prognostic (p-values = 0.1260 and 0.2566, respectively). Seventeen of the 41 JI NETs showed mesenteric fibrogenesis (MF), and 18 had EMVI, with a high level of agreement between these parameters (92.68%) (kappa value 0.85), and both were strongly associated with poor outcomes. Conclusions: JINETs and their liver metastases tend to have low proliferation rates. However, an important mechanism in the metastatic cascade appears to be mesenteric fibrogenesis. It encases vessels, which enhances extramural vascular invasion, thereby conveying clusters of tumor cells to the liver. This supports the polyclonal nature of tumor progression rather than origin from hotspot aberrant clones.
背景：空回肠神经内分泌肿瘤（JINETs）患者即使存在肝转移仍可存活多年。有证据表明肿瘤异质性对预后至关重要，因此选择Ki67热点区域进行肿瘤分级。根据逐步转移模型，克隆性热点应在转移灶中占主导地位。然而，另一种观点认为转移灶的多克隆性符合其源自遗传异质性播散细胞簇的理论。Ki67分级的局限性正逐渐被认识，这促使人们重新寻找其他预后参数。 方法：通过一项为期20年的回顾性研究，对配对的原发性JINETs与肝转移灶进行多参数分析。 结果：研究纳入43例患者（平均随访7.234年），其中14例死于该疾病，22例带病生存，7例无疾病证据存活。大多数JINETs（22/30）为1级，8例为2级，无3级病例。原发灶与肝转移灶的肿瘤分级均无预后意义（p值分别为0.1260和0.2566）。41例JINETs中17例出现肠系膜纤维化（MF），18例存在血管外侵犯（EMVI），这两项参数具有高度一致性（92.68%，kappa值0.85），且均与不良预后显著相关。 结论：JINETs及其肝转移灶通常具有较低的增殖率。然而，转移级联反应中的一个重要机制似乎是肠系膜纤维化。该过程包裹血管，增强血管外侵犯，从而将肿瘤细胞簇输送至肝脏。这支持了肿瘤进展的多克隆特性，而非源自热点异常克隆。
肿瘤(癌症)患者之家