MMP-9的高表达和术前选择性减黄对肝门部胆管癌预后影响的相关研究

发布时间：2018-08-22 10:44

【摘要】：目的：研究基质金属蛋白酶(MMP-9)的高表达与肝门部胆管癌患者的预后有无相关性,判断其是否可以作为预后的指标。方法：回顾性调查山东大学齐鲁医院肝胆外科从2005年1月到2011年12月期间住院治疗的70例肝门部胆管癌患者,所有70位患者均接受了根治性的切除,其术后的病理诊断也证实为肝门部胆管癌。术后90天内死亡及因其他非肿瘤因素死亡的病例被排除。最终,有58例符合标准的患者,而且患者无胆石症及硬化性胆管炎等其他相关疾病。对这些患者进行定期随访,日期从手术当天开始计算,并于2013年1月份结束。在患者接受胆管癌根治术后的最初两年中,我们对每位患者每隔3个月进行一次随访,搜集总结患者的各项辅助检查结果。两年之后,每6个月对患者进行一次回访。必要时行CT等影像学检查。同时收集这58位患者的组织病理样本,通过免疫组化方法进行MMP-9检测,判断其在癌组织中的表达程度,进而通过统计学方法判断二者之间的相关性。另外,统计患者的性别、年龄、肿瘤分型、组织分化的程度、淋巴结是否转移等因素,并研究其对肝门部胆管癌患者预后情况的影响。结果：所有58例患者中,共41名男性及17名女性,最年轻者年龄为36岁,最大者为77岁,中位年龄为58岁。肝门部胆管癌组织中MMP-9的表达与胆管癌患者的年龄、性别、肿瘤大小、分化程度、Bismuth分型、TNM分期、淋巴结转移等没有明显的相关性(P0.05)。而在时序检验中,MMP-9及淋巴结的转移情况与患者的生存期有明显相关性(P0.05)。结论：相比低表达或者不表MMP-9的患者,MMP-9高表达的患者总体生存率明显较差。多变量分析证实,MMP-9是肝门部胆管癌预后的独立危险因素(P=0.007)。因此, MMP-9的表达情况有希望成为判定肝门部胆管癌预后好坏的指标。目的：研究需要联合肝切除的肝门部胆管癌患者(也称Klatskin瘤),术前选择性肝内胆道引流是否能够降低术后的总体并发症以及死亡率。方法：回顾收集山东大学齐鲁医院2007年1月至2012年1月共计116例患者,其均为血清总胆红素(TB)在85μmol/L以上(正常17.1μmol/L)且需联合肝部分切除的肝门部胆管癌手术切除病人的病历资料,分析评价术前选择性肝内胆道引流对于肝功能及其术后总体并发症、病死率的影响。结果：所收集病例中,无术前引流直接手术组共54例(46.6%),术前引流组共62例(53.4%),平均引流9天,引流组术前总胆红素较引流前下降至(214±115) u mol/L,与引流前的总胆红素水平(290±100)μmol/L相比有显著性差异(p=0.010)。术前选择性肝内胆道引流可有效降低谷草转氨酶(AST)、Y-谷氨酰转肽酶(GGT)、谷丙转氨酶(ALP)、总胆红素(TB)、结合胆红素(DB)水平。术后总体并发症的发生率为55.2%(64/116)；术前肝内胆管引流组为58.1%(36/62),未引流直接手术组为51.9%(28/54),两组之间无显著性差异。两组之间单个并发症(如胆漏、腹腔感染等)的总发生率亦无显著性差异。术前胆道引流组死亡6例(9.7%),未引流直接手术组死亡6例(11.1%),两组病死率之间比较无显著性差异(P=0.859)。结论：术前选择性肝内胆道引流能够有效降低肝门部胆管癌患者血清胆红素水平及改善需行根治性手术治疗患者的肝功能；但术后相关并发症以及死亡率并不会明显减少。
[Abstract]:Objective: To study the correlation between the high expression of matrix metalloproteinase (MMP-9) and the prognosis of patients with hilar cholangiocarcinoma, and to determine whether it can be used as a prognostic indicator. All patients underwent radical resection, and the postoperative pathological diagnosis confirmed hilar cholangiocarcinoma. Patients who died within 90 days after surgery and died due to other non-neoplastic factors were excluded. In the end, 58 patients met the criteria and were free of cholelithiasis and other related diseases such as sclerosing cholangitis. During the first two years after radical resection of cholangiocarcinoma, each patient was followed up every three months to collect and summarize the results of various auxiliary examinations. Two years later, the patient was followed up every six months. If necessary, CT and other imaging studies were performed. At the same time, the histopathological samples of 58 patients were collected, and the expression of MMP-9 in cancer tissues was detected by immunohistochemical method, then the correlation between them was judged by statistical method. Results: Among the 58 patients, 41 were male and 17 were female, the youngest was 36 years old, the oldest was 77 years old, and the median age was 58 years old. There was no significant correlation between MMP-9 and lymph node metastasis (P 0.05). However, there was a significant correlation between MMP-9 and lymph node metastasis and survival time (P 0.05). Conclusion: The overall survival rate of patients with high expression of MMP-9 was significantly worse than those with low expression or no expression of MMP-9. Objective: To investigate whether preoperative selective intrahepatic biliary drainage can reduce the overall postoperative complications in patients with hilar cholangiocarcinoma requiring combined hepatectomy. Methods: Retrospectively collected 116 cases of hilar cholangiocarcinoma in Qilu Hospital of Shandong University from January 2007 to January 2012. All of them were patients with serum total bilirubin (TB) above 85 micromol/L (normal 17.1 micromol/L) who needed combined partial hepatectomy. The effect of drainage on liver function, postoperative complications and mortality was studied. Results: Among all the cases, 54 (46.6%) were operated without preoperative drainage, 62 (53.4%) were operated with preoperative drainage. The average drainage time was 9 days. Preoperative selective intrahepatic biliary drainage could effectively reduce the levels of glutamic oxaloacetic aminotransferase (AST), Y-glutamyl transpeptidase (GGT), alanine aminotransferase (ALP), total bilirubin (TB), and bilirubin (DB). The overall incidence of postoperative complications was 55.2% (64/116) and 58.1% (36/62) in the preoperative intrahepatic biliary drainage group. There was no significant difference in the total incidence of single complications (such as bile leakage, abdominal infection, etc.) between the two groups. Conclusion: Preoperative selective intrahepatic biliary drainage can effectively reduce serum bilirubin levels and improve liver function in patients with hilar cholangiocarcinoma requiring radical surgery, but postoperative complications and mortality are not significantly reduced.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.8

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