食管癌多药耐药基因和多药耐药相关蛋白基因的研究

目的：探讨食管癌组织中多药耐药基因（ｍｄｒ－１）和多药耐药相关蛋白基因（ｍｒｐ）表达的意义。方法：运用逆转录－多聚酶链反应（ＰＴ－ＰＣＲ）技术检测了３２全 管癌患者的癌组织标本及癌旁组织中ｍｄｒ－１、ｍｒｐ表达,分析其与肿瘤分化程度,浸润深度及淋巴结转移的关系。结果：３２例食管癌组织中ｍｄｒ－１、ｍｒｐ表达的阳性率均高于癌旁组织（Ｐ〈０．０１,Ｐ〈０．０２５）,两基因的表达水平也显著高于癌旁组织（     

Connexin43在肝门部胆管癌中的表达及其意义

目的 探讨肝门部胆管癌组织中Connexin43的表达及其意义。方法 应用免疫组化法检测Connexin43蛋白在49例肝门部胆管癌组织及癌旁组织中的表达情况,并分析其与肝门部胆管癌临床病理特征及总生存期（OS）和无病生存期（DFS）的关系。结果 Connexin43蛋白在49例胆管癌组织中的阳性表达率为57.1％（28／49）,而在癌旁黏膜组织中不表达或微弱表达。Connexin43蛋白表达与性别、年龄、淋巴结转移、术式和神经侵犯无关,而与TNM分期、组织分化和肿瘤大小相关。肝门部胆管癌组织中Connexin43阳性表达者的中位DFS和OS分别为11.5个月和20.7个月,阴性者分别为21.4个月和38.4个月,两者差异均有统计学意义（P＜0.05）。Cox多因素回归分析显示,Connexin43蛋白表达是预测肝门部胆管癌复发和生存的独立因素。结论 Connexin43蛋白与肝门部胆管癌的发生、发展密切相关,是判断胆管癌预后的重要指标。     

贲门癌组织中多药耐药基因和多药而药相关蛋白基因表达的临床

目的 了解多药耐药基因（ＭＤＲＩ）和多药耐药相关蛋白基因（ＭＲＰ）在贲门癌组织中的表达及其临床意义。方法 采用反转录聚合酶链反应（ＲＴ－ＰＣＲ）技术,检测了５６例贲门癌及癌旁组织中ＭＤＲＩ和ＭＲＰ的表达。结果 癌组织 ＭＤＲＩ和ＭＲＰ表达的阳性率分别６３％和５０％,均高于癌旁组织（Ｐ〈０．０５）有化疗的ＭＤＲ１ ｍＲＮＡ和ＭＤＲ１和ＭＲＰ表达的水平高于未化疗者（Ｐ〈０．０５）;中低分化肿瘤的的ＭＤ     

荧光定量RT-PCR检测mdr-1基因表达

建立荧光定量ＲＴ－ＰＣＲ检测肿瘤细胞ｍｄｒ－１基因表达的方法,了解肺癌组织中ｍｄｒ的表达水平。方法：建立荧光定量ＲＴ－ＰＣＲ方法,在ＰＥ７７００型检测仪上定量检测Ｋ５６２／ＡＤＭ耐药株和Ｋ５６２不耐药株细胞ｍｄｒ－１有达水平,同时检测４５例初治肺部肿瘤病人组织标本。     

RT-PCR定量检测急性白血病多药耐药基因(MDR1)的表达

 用定量RT一PCR方法检测了急性白血病在初治、复发时MDRI的表达水平,并探讨其临床意义。     

MDRI基因在卵巢癌组织中的表达及其临床意义

目的 检测多药耐药基因MDR1 mRNA在卵巢癌组织中的表达及其临床应用价值。方法 选择卵巢癌组织30例、卵巢良性肿瘤组织30例、正常卵巢组织30例。采用RP－PCR复合定量技术检测卵巢癌组织中的耐药相关基因MDR1 mRNA的表达水平及分析其表达与临床化疗的相关性。结果 正常卵巢组织不表达MDR1基因;卵巢良性肿瘤组织MDR1基因表达率为10．0％;卵巢癌组织表达率为73．3％,其中高表达率占77．3％。卵巢癌组织中MDR1基因表达与卵巢良性肿瘤的比较,有非常显著性差异（P＜0．01）。卵巢癌术前化疗组MDR1基因表达率为83．3％;术前末化疗组MDR1基因表达率为58．3％,2组比较无显著性差异（P＞0．05）。定量分析表明化疗可以诱导MDR1基因表达水平增高,与非化疗组比较有非常显著性差异（P＜0．01）。结论 MDR1基因表达与卵巢癌有关。MDR1表达与卵巢癌化疗与否无关,但化疗可诱导MDR1基因表达水平增高。因此检测MDR1基因表达水平的变化可以预测继发耐药性。在判断卵巢癌临床用药时,检测MDR1耐药相关基因的表达情况可得到一定的耐药信息,对临床化疗方案的制定有较大的应用价值。     

用RT—PCR法检测新鲜癌组织中多药耐药基因（mdr—1）表达的体会

目的：恶性肿瘤细胞的多药耐药性（ＭＤＲ）已普遍受到关注，其分了学基础之一是ｍｄｒ－１基因的过表达，检测ｍｄｒ－１基因的方法较多。本研究旨在介绍反转录多聚酶链反应（ＲＴ－ＰＣＲ）检测ｍｄｒ－１基因表达的经验。方法：选取安阳市肿瘤医院１９９４年１１月～１９９５年９月术前未作治疗的恶性肿瘤切除标本１５１份。以ＲＴ－ＰＣＲ检测其ｍｄｒ－１基因的表达情况，评价ＲＴ－ＰＣＲ检测ｍｄｒ－１基因中的注意事项及优点     

生长激素受体在肝门部胆管癌中的表达及意义

肝门胆管癌指发生于左肝管、右肝管、左右肝管汇合部和肝总管上1／3段的黏膜上皮癌,又称近端胆管癌或高位胆管癌。手术切除率低,预后差,不易早期诊断。在围手术期改善患者营养状态、纠正低蛋白血症、提高机体免疫能力具有重要的意义。重组人生长激素（rhGH）在调节三大物质代谢、促进蛋白质合成和细胞的增殖以及降低外科患者术后死亡率等方面疗效明显,但需要依赖生长激素受体（GHR）才能发挥作用,本研究检测GHR在肝门胆管癌组织中的表达情况,探讨rhGH在肝门胆管癌患者中是否适用。     

肝门部胆管癌的放射治疗

随着肝门部胆管癌手术技术方法的改善,放射治疗设备更新及技术方法的提高,放射治疗在肝门部胆管癌治疗中的应用亦增多.全文综述近年来的相关文献,以阐述放射治疗在肝门部胆管癌治疗中的价值.     

线粒体三功能蛋白亚基A、B在肝门部胆管癌中的临床意义

目的 检测线粒体三功能蛋白亚基HADHA及HADHB在肝门部胆管癌中的表达情况,探讨其与肿瘤发展及患者预后的关系。方法 构建含91例肝门部胆管癌病例的组织芯片,应用免疫组织化学方法检测HADHA及HADHB在肝门部胆管癌中的表达,并分析其与临床病理参数及预后之间的关系。结果 HADHA及HADHB在肝门部胆管癌中的高表达率分别为71.4％（65／91）、59.3％（54／91）,均显著高于癌旁组织的10.4％（5／48）、20.8％（10／48）,差异有统计学意义（P＜0.05）。HADHA表达与肿瘤浸润深度及手术切缘有关（P＜0.05）,HADHB表达与手术切缘及淋巴结转移有关（P＜0.05）。HADHA、HADHB高表达患者的中位生存期和无进展生存期分别短于HADHA、HADHB低表达患者,差异均有统计学意义（P＜0.05）。Cox风险比例回归模型显示,肿瘤浸润深度、淋巴结转移情况、分化程度及HADHB表达均是影响患者预后的独立因素（P＜0.05）。结论 HADHA及HADHB在肝门部胆管癌的发生发展过程中发挥了癌基因的作用,可能与肿瘤细胞的侵袭性生物学行为有关,并且HADHB可作为判断患者预后的独立指标。     

Surgery for hilar cholangiocarcinoma: The Leeds experience

Aim

To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre.

Methods

A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration.

Results

Tumours were staged as follows (UICC 6th edition): stage IB, n = 10 IIA, n = 9; IIB, n = 20; III, n = 8; IV, n = 14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n = 3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p = 0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p = 0.0034, 95% confidence interval 0.1007–6.342).

Conclusions

Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.     

抗肿瘤药物体外诱导新鲜癌组织及其外周血淋巴细胞mdr-1基因表达的相关性研究

目的: 通过对恶性肿瘤患者的癌组织细胞及其外周血淋巴细胞进行抗肿瘤药物的体外诱导,用RT-PCR法检测其mdr-1基因表达状况,从而找出两者之间的相关性,从基因水平解决非手术癌患者化疗用药个体化.方法:在采集手术标本的同时抽取该患者外周血,用8种抗肿瘤药物进行体外诱导,RT-PCR法检测32例恶性肿瘤患者癌组织细胞及其外周血淋巴细胞的mdr-1基因表达状况.利用SAS软件计算两者之间的相关关系.结果:32例恶性肿瘤患者的新鲜癌组织细胞与其外周血淋巴细胞的抗肿瘤药物体外诱导mdr-1基因表达呈正相关关系.结论:对于失去手术机会或病灶很小不能取材的患者可以用外周血淋巴细胞替代癌细胞做RT-PCR体外药敏检测.这将从基因水平为肿瘤患者个体化用药提供一个新的途径.     

影像学检查对肝门部胆管癌可切除性评估的价值

目的 探讨影像学检查对肝门部胆管癌可切除性的评估价值。方法 对43例经术后病理组织学证实的肝门部胆管癌患者的CT及MRI资料进行回顾性分析,包括肿瘤的大小、胆管受侵犯的长度、肿瘤侵犯门静脉及肝动脉的程度、淋巴结转移及远处转移的情况、胆管受侵犯的范围及改良建议性T分期与可切除性的关系。结果 浸润型肝门部胆管癌的可切除率为8.3％,肿块型的可切除率为51.6％（P=0.017）。不同肿块大小和肿瘤浸润胆管的长度组别间可切除率的差异无统计学意义（P＞0.05）。Bismuth分型各型可切除率的差异无统计学意义（P＞0.05）。改良建议性T分期各期的可切除率的差异有统计学意义（P＜0.01）,且可切除率随T分期的增加而下降（P＜0.01）。结论 浸润型肝门部胆管癌的可切除率低于肿块型;肿块的大小和肿瘤浸润胆管的长度与肿瘤的可切除性均无关;改良建议性T分期较Bismuth分型在指导肝门部胆管癌的可切除性上更有价值。     

肝门部胆管癌组织中VEGF和血管生成相关性的研究

目的：探讨肝门部胆管癌组织中血管内皮细胞生长因子（ＶＥＧＦ）和血管生成的相关性。方法：应用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）和免疫组化技术对２６例肝门部胆管癌、癌周组织及１２例正常组织中ＶＥＧＦｍＲＮＡ和蛋白及微血管密度（ＭＶＤ）进行了检测。结果：２６例肝门部胆管癌组织中ＶＥＧＦｍＲＮＡ阳性表达率为７６．９％（２０／２６）;癌周组织阳性表达率为２８．９％（７／２６）;正常组织表达率为８．３％（１／１２）,三者差异有显著性（Ｐ＜０．０１）。ＶＥＧＦｍＲＮＡ阳性表达与ＶＥＧＦ蛋白表达具有一致性;ＶＥＧＦｍＲＮＡ阳性者ＭＶＤ值显著高于阴性者（Ｐ＜０．０１）;ＶＥＧＦｍＲＮＡ表达和ＭＶＤ与肝门部胆管癌的分化程度、浸润转移密切相关（Ｐ＜０．０５）;而与发生部位、病理类型、肿瘤大小、临床分型无关（Ｐ＞０．０５）。结论：ＶＥＧＦ在肝门部胆管癌发生和浸润转移过程中发挥重要作用,肿瘤血管生成与肝门部胆管癌浸润转移密切相关。     

外科治疗肝门部胆管癌68例临床分析

目的：探讨提高肝门部胆管癌尤其是肝门部血管受肿瘤侵犯病例的外科治疗方法。方法：回顾性分析我院1986年1月～2004年12月收治手术的肝门部胆管癌68例。结果：按Bismuth-Corlette分型法：Ⅰ型7例,Ⅱ型15例,ⅢA型19例,ⅢB型12例,Ⅳ型15例（包括不能分型3例）。26例（38.24%）确诊前曾有胆囊结石和/或肝内外胆管结石手术史,或同时合并有胆石症。B超、CT和MRCP的确诊率分别为71.43%、84.00%和91.43%。手术方式：根治性切除24例,姑息性切除14例,胆道引流30例。术后1、2、3年生存率：根治性切除组分别为85.0%（17/20）、60.0%（12/20）和25.0%（5/20）,其中3例生存时间超过5年;姑息性切除组分别为58.3%（7/12）、25.0%（3/12）和0,两组之间的3年生存率比较有显著性差异（P〈0.05）;胆道引流组1、2、3年生存率分别为21.4%（6/28）、10.7%（3/28）和0。结论：积极提高手术切除率是改善肝门部胆管癌预后的惟一有效方法;肝十二指肠韧带骨髂化、肝部分切除可提高根治性切除率。姑息性切除、胆道引流有助于改善患者生活质量,延长生存。     

Clinical outcome after resection of early-stage hilar cholangiocarcinoma

BackgroundLiver transplantation in patients with unresectable early-stage (<3 cm, node negative) hilar cholangiocarcinoma has been recently reported to be associated with longer survival compared to liver resection and therefore suggested as potential treatment option also in resectable disease. Here, we investigated the outcome of resection in early-stage tumours as the standard of care in an experienced European centre.MethodsPatients with de novo resectable hilar cholangiocarcinomas who underwent liver resection between mid-2009 and December 2017 were classified as early-stage (<3 cm and node negative) or later-stage tumours (≥3 cm and/or node positive), and were investigated with respect to clinical outcome.ResultsFifty-six patients were analyzed of whom 17 had early-stage tumours and 39 had later-stage tumours. The sex ratio (m:f) was 30:26. The median age was 65 years (range 33–80). The median follow-up was 17.0 months (range 0.7–92.4). 5-year overall survival (OS) rates were 82% in patients with early-stage tumours and 23% in patients with later-stage tumours, respectively. Median OS was 89.9 months and 27.6 months, respectively (HR 0.25 (95% CI 0.08–0.84), P = 0.024).ConclusionsIn an experienced European centre, 5-year survival rates after liver resection for early-stage hilar cholangiocarcinoma are comparable with reported outcomes after transplantation. The results of this study question the value of liver transplantation in this setting, especially with respect to the shortage of transplantable organs worldwide.