新生淋巴管在胰腺导管腺癌周围神经丛微转移过程中的机制研究

Lymphangiogenesis in the perineural micrometastasis of pancreatic adenocarcinoma

目的研究新生淋巴管在胰腺导管腺癌周围神经丛微转移过程中的作用与机制。方法收集2005年9月至2006年10月长海医院行胰腺癌扩大根治术的30例胰腺导管腺癌患者的临床资料，术中采集胰腺肿瘤、癌旁、胆管下段、胰尾、肠系膜上动脉（SMA）旁组织（含胰周神经丛）以及区域淋巴结标本。常规病理检查，采用双重免疫组化方法检测毛细淋巴管，计算淋巴管密度（LVD）。结果胰内和（或）胰周神经丛浸润25例（83．3％），其中胰内合并胰周神经丛浸润20例，单纯胰内神经浸润5例，无单纯胰周神经丛浸润病例。神经浸润与患者年龄、性别、淋巴结转移、肿瘤大小、肿瘤部位无明显相关性（P〉0．05），但与JPS临床分期相关（P〈0．05）。癌组织内的平均LVD为每视野（4．2±3．4）个，显著少于癌旁的（11．3±6．9）个及正常胰腺组织的（10．8±4．4）个（P〈0．01），正常胰腺组织与癌旁组织平均LVD值差异无统计学意义。18例胰腺癌患者在非癌组织清晰可见肿瘤浸润淋巴管，而且胰周神经丛浸润与淋巴管肿瘤浸润间亦有明显相关性（P〈0．05）。结论胰腺导管腺癌周围神经丛浸润的发生率较高，神经浸润与JPS临床分期、淋巴管浸润有明显相关性，提示胰腺导管腺癌存在通过新生淋巴管途径扩散转移的可能性。

Objectives To investigate the role of lymphangiogenesis in the perineural micrometastasis of pancreatic adenocarcinoma. Methods The clinical data of 30 pancreatic adenocarcinoma patients who were admitted from Sep. 2005 to Oct. 2006 for extended radical surgery were collected. The samples including pancreatic cancer, adjacent tissue, lower bile duct, pancreatic tail, the structure surrounding the SMA （peripancreatic nerve plexus） and lymph nodes were collected during operation. They were subjected to conventional pathological examination. The lymphatic capillaries weredetected by double immunohistochemical staining and the lymphatic vessel density （LVD） was measured. Results Intra-pancreatic and/or peripancreatic neural invasion was observed in 25 patients （ 83.3% ）, of which 20 were found to have both the peri-pancreatic and intra-pancreatic neural invasion. The other 5 only had the intrapancreatic neural fiber invasion and there was no single patient with peri-pancreatie neural fiber invasion only. Peri-neural invasion was not significantly associated with patients＇ age, gender, lymph node metastasis, tumor size and the location （ P 〉 0.05 ）, but was obviously associated with JPS clinical staging （ P 〈 0.05 ）. The mean intratumoral LVD was （4.2 ± 3.4） per field, which was significantly lower than （ 11.3 ± 6.9 ） per field of adjacent tissue and （10.8 ±4.4）per field of normal pancreatic tissue（ P 〈0. 01 ）. The mean intratumoral LVD between adjacenttissue and normal pancreatic tissue was not statistically different. Lymphatic： vessel invasion was observed in non-malignant tissues in 18 patients, and there was a distribution correlation between lymphatic vessel invasion and extra-pancreatic neural plexus invasion （ P 〈 0.05 ）. Conclusions The incidence of peri-neural invasion was high, peri-neural invasion was associated with JPS clinical staging and lymphatic vessel invasion, which suggested the possibility of the cancer spreading by peritumoral lymphangiogenesis route into the peri-SMA neural plexuses.