胃癌前哨淋巴结临床意义的研究

目的 观察胃癌前哨淋巴结的分布，探讨其临床意义。方法 回顾性分析288例胃癌前哨淋巴结术中染色后显影的范围及特征。术中向肿瘤边缘的正常胃壁浆膜下肌层、黏膜下层注射亚甲蓝，观察淋巴结显影的情况；切取各站淋巴结行病理检查。结果 288例胃癌术后病理诊断为T1期102例，T2期126例，T3期60例。术中成功显影270例，阳性率为93．8％。102例患者有淋巴结转移，其中前哨淋巴结（SNs）与非前哨淋巴结（non—SNs）均有转移者66例，仅前哨淋巴结有转移者18例，仅非前哨淋巴结有转移者18例。结论 通过前哨淋巴结，术中能准确预测胃癌淋巴结转移状况。在手术治疗淋巴结转移阴性的胃癌患者中，前哨淋巴结术中标识有望免除常规淋巴清扫。     

血管生成抑制剂YH-16联合氟尿嘧啶抑制结直肠癌肝转移的研究

目的探讨血管生成抑制剂YH-16和氟尿嘧啶（5-FU）联合应用对结直肠癌肝转移的抑制作用。方法用MTT方法测定血管生成抑制剂YH-16和5-FU对血管内皮细胞和结肠癌细胞的IC50；建立小鼠肝转移模型。随机分为对照组、YH-16组（又分为低、中、高剂量3组）和5-Fu组及联合治疗组（YH-16加5-FU），术后2周观察各组小鼠肝转移瘤数目、原发灶大小和毒性反应。并检测肝转移瘤血管内皮生长因子（VEGF）的表达和肿瘤微血管密度（MVD）。结果YH-16对结肠癌细胞的IC50是血管内皮细胞的3．38倍，而5-Fu对两种细胞的IC50差别不大。高剂量YH-16组、5-FU组和联合治疗组肝转移瘤数目明显低于对照组。而联合治疗组又低于高剂量YH-16组和5-FU组（均P〈0．05）。YH-16各剂量组的脾原发瘤体积与对照组比较均P〉0．05。差异无统计学意义；而5-FU组和联合治疗组则小于对照组（均P〈0．05）。YH-16的毒性明显低于5-FU（P〈0．05），且两者联合使用其毒性与单用5-FU比较，差异无统计学意义（P〉0．05）。5-FU组和联合治疗组肝转移瘤组织中VEGF的表达明显降低，中、高剂量YH-16组和5-FU组及联合治疗组肝转移瘤组织中的MVD计数明显降低（均P〈0．05）。结论血管生成抑制剂YH-16明显抑制结直肠癌肝转移，YH-16与5-FU联合应用对结直肠癌肝转移的抑制具有协同作用。     

人肝门部胆管癌转移动物模型的建立及生物学特性研究

目的利用人肝门部胆管癌细胞系（FRH-0201）接种裸鼠脾脏，建立肝、肺转移模型。方法将FRH-0201细胞系（120代）接种于7只Balb／c裸小鼠脾脏。出现转移时，将转移瘤行组织病理学及超微结构观察。将转移的肿瘤行细胞培养，再次接种裸鼠脾脏，观察转移成瘤情况。结果脾脏局部成瘤率为100％（7／7），转移瘤发生率14．3％（1／7）。转移瘤细胞再次接种于裸小鼠脾脏，转移发生率100％。转移瘤电镜显示典型恶性细胞特征。转移瘤细胞染色体众数19条，主流范围18～44条。结论该实验所建立的肝门部胆管癌转移瘤，符合恶性肿瘤的特点，与人肝门部胆管癌生物学特性一致。     

抑癌基因KLF-6和APC在结直肠癌组织中的表达及临床意义

目的 研究抑癌基因KLF-6和APC在结直肠癌中的表达规律及其临床意义。方法 应用RT-PCR和免疫组织化学法对32例结直肠癌组织和正常黏膜组织中KLF-6和APC基因mRNA及蛋白的表达进行检测和分析。结果 KLF-6与APC的mRNA阳性表达率在结直肠癌组织中分别为37、5％和34，3％，明显低于正常结直肠黏膜组织的96．9％和93．8％（P〈0．05）。KLF-6与APC的免疫组化染色阳性表达率在结直肠癌组织中分别为28．1％和25．0％，明显低于正常结直肠黏膜组织的81．3％和84．4％（P〈0．05）。KLF-6与APC在结直肠癌中的表达存在相关性（P〈0．05），并与肿瘤组织的分化程度、浸润深度、淋巴结转移及临床分期均有明显相关性（P〈0．05）。结论 抑癌基因KLF-6和APC的低表达可能与结直肠癌的发生、发展、转移及预后有关，且两者存在相关性。     

中原地区遗传性非息肉病性大肠癌表型特征的临床研究

目的探讨中原地区遗传性非息肉病性大肠癌(HNPCC)的表型特征,为制订适合我国国情的HNPCC遴选标准提供依据。方法对符合Am sterdam标准的8个家系37例患者的临床资料(A组),与随机抽调我院40例确切无家族史的大肠癌患者的临床资料(B组)进行对比分析。结果①发病年龄:A组平均46岁,B组62.6岁,平均提前16.6年;<50岁者:A组73%(27/37),B组30%(12/40),两组比较P<0.01;第1、2、3代平均发病年龄分别为69.2、46.9、34.6岁,逐代比较差异有统计学意义(P<0.05或P<0.01)。②发病部位:右半结肠A组73.2%(30/41),B组39.0%(16/41),两组比较P<0.05。③同时、异时多发大肠癌:A组8.1%(3/37),B组2.5%(1/40)。④大肠外癌:A组17.1%(7/41),B组0,两组比较P<0.05。⑤合并腺瘤:A组0,B组22.5%(9/40),两组比较P<0.05。⑥组织学类型:低分化腺癌A组69.7%(23/33),B组40%(16/40),两组比较P<0.05。结论中原地区HNPCC有其独特的临床特征,国际遴选标准不能完全适用于中国人,制定适合我国国情的HNPCC遴选标准确有必要。     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.     

凝血栓蛋白1基因异常甲基化与大肠腺癌关联

目的 探讨凝血栓蛋白l（THBS1）基因启动子CpG岛异常甲基化与大肠腺癌及其临床病理特征的关联。方法 THBS1基因甲基化状态用甲基化特异性PCR检测。结果 大肠腺癌、癌旁组织中，THBSI基因启动子cpG岛甲基化率的差异有显著性（X^2=5．93，P=0．025）；老年患者肿瘤组织中THBS1基因甲基化率明显商于非老年患者（X^2=5.68，P=0．017），直径≥3cm的肿瘤组织中THBSl基因甲基化率显著高于直径〈3cm的肿瘤（X^2=4．16，P=0．041），C期和D期肿瘤组织中THBS1基因甲基化率显著高于A期或B期肿瘤（X^2=8．04，u=2，P=0．018）。结论 THBS1基因甲基化与大肠腺癌的发生有关，肿瘤以老年、晚期和直径较大的肿瘤多见。     

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

应用荧光多重聚合酶链反应法检测结直肠癌微卫星不稳定

目的建立一种敏感、稳定、高通量的结直肠癌微卫星不稳定(MSI)检测技术。方法105例散发性结直肠癌患者取其新鲜癌组织及正常肠黏膜,DNA提取,荧光多重聚合酶链反应(PCR)扩增5个微卫星位点,应用GeneScan方法分析PCR产物。结果105例结直肠癌患者26例(24.7%)存在微卫星不稳定,其中MSI-H 14例(13.3%),MSI-L 12例(11.4%),MSS 79例(75.3%)。D5S346、BAT26、BAT25、D17S250、D2S123突变率分别为5.6%、8.6%、10.5%、8.6%、10.5%。结论应用荧光多重PCR可以高通量检测结直肠癌微卫星不稳定,敏感性高,结果可靠,适合临床应用。     

18F-氟脱氧葡萄糖PET和PET-CT在结直肠癌术后复发或转移中的应用价值

临床常规检查方法对结直肠癌术后复发转移的诊断及再分期有一定局限性，^18F-氟脱氧葡萄糖（^18F-FDG）PET作为一种功能代谢显像检查，能早期探测到肿瘤有无复发，准确鉴别术后瘢痕与复发，且能提供全面、准确的再分期信息，有助于制定合理的临床治疗方案，但仍存在假阳性及假阴性诊断。PET-CT融合显像有助于PET图像的正确解释，定位、定性准确度高，应用前景广阔。