叉头框M1在结直肠癌中的表达及临床意义

目的探讨叉头框M1(FOXM1)在结直肠癌中的表达及与临床病理特征、预后的关系。方法采用免疫组化SP法检测297例结直肠癌组织和80例对应癌旁正常组织中FOXM1的表达;Western blot法检测20例新鲜结直肠癌组织及对应癌旁组织中FOXM1的表达。结果 FOXM1在结直肠癌组织中的阳性率(70.97%)显著高于癌旁组织(17.50%,P0.01);FOXM1表达与结直肠癌浸润深度、淋巴结转移、脉管内癌栓转移、远处转移和TNM分期有关(P0.05);与患者年龄、性别、肿瘤部位、大小、分化程度、CEA、CA199等无关(P0.05)。结直肠癌组织中FOXM1蛋白相对表达量(0.855±0.063)明显高于相应癌旁组织(0.150±0.041,P0.01)。FOXM1阳性患者的3年生存率明显低于阴性患者(P0.01),且FOXM1为结直肠癌预后的独立性危险因素。结论 FOXM1蛋白在结直肠癌组织中过表达,且与患者临床病理特征、预后等因素有关,可能在结直肠癌的发生、转移等过程中起重要作用,有望成为结直肠癌新的肿瘤标志物和潜在的治疗靶点。     

结直肠癌肝转移预测及预后的影像组学综述

结直肠癌在国内外都是高发病率和高死亡率的肿瘤疾病，肝脏是结直肠癌血行转移最主要的靶器官，尽早准确地预测结直肠癌肝转移的发生以及监测患者治疗的预后反应，对患者的诊断和治疗尤为关键。新兴的影像组学为精准预测结直肠癌肝转移以及评估预后提供新的可能。对现有的结直肠癌肝转移影像组学研究进行综述，首先介绍结直肠癌肝转移研究的临床意义以及现有研究存在的缺陷，然后阐述结直肠癌肝转移影像组学的分析流程，接着对结直肠癌肝转移影像组学的4个研究方向展开综述，包括肝转移病理生长模式预测、隐匿性肝转移预测、肝转移疗效预后评估、肝转移患者生存期预后评估；阐明各个方向的最新研究进展及存在的缺陷性；最后对结直肠癌肝转移影像组学的未来发展趋势进行展望。     

结直肠癌淋巴管生成的特点及其临床病理意义

目的探讨结直肠癌中淋巴管的分布特点、增殖状态及其与转移和预后的关系。方法采用淋巴管特异标记podoplanin对96例结直肠癌及其相应正常组织进行免疫组织化学染色检测微淋巴管密度,以CD34标记血管检测微血管密度作为对比,并分别与Ki-67进行双标免疫组织化学染色检测淋巴管和血管增殖活性,结合结直肠癌临床病理参数和预后分析。结果结直肠癌中心及浅表部淋巴管多为闭锁的条索状,边缘区淋巴管多呈管样扩张状。结直肠癌边缘区淋巴管密度(51.2±25.5)及较正常结直肠组织(29.4±9.0)和肿瘤其他区域显著性增高(P<0.01),并且其淋巴管内皮Ki67指数(0.23±0.17)也较其他区域显著性增高(P<0.05)。结直肠癌边缘区微淋巴管密度与淋巴管受累、淋巴结转移、远处器官转移及预后密切相关(P<0.01或P<0.05)。结论结直肠癌组织中存在新生淋巴管,且主要分布于肿瘤边缘区,癌周围淋巴管密度增加与癌细胞转移相关,结直肠癌边缘区微淋巴管密度测定对评估其淋巴结转移和预后判断可能具有意义。     

术前血清CEA在结直肠癌患者预后判断上的作用

目的研究术前血清癌胚抗原(CEA)在判断结直肠癌患者预后中的价值。方法 426例结直肠癌患者按术前CEA水平分为两组:CEA正常组(﹤5ng/mL)和CEA升高组(≥5ng/mL)。跟踪随访上述病例并分析相关临床病理学指标同预后的关系。结果术前血清CEA水平与结直肠癌患者肿瘤大小、浸润深度、淋巴结转移及临床分期密切相关。血清CEA升高组患者的总生存期和无进展生存期明显低于CEA正常组(P<0.001,P<0.001)。单因素及多因素回归分析证明,术前血清CEA水平为判断结直肠癌患者预后的独立指标。结论血清CEA可为结直肠癌患者预后判断提供重要的临床参考依据。     

中性粒细胞与淋巴细胞比值联合检测纤维蛋白原对结直肠癌预后的判断价值

目的: 探讨中性粒细胞与淋巴细胞比值(NLR)和纤维蛋白原(Fibrinogen,FIB)联合形成指标FIB-NLR 在结直肠癌预后中的临床意义。方法:回顾性分析我院2010 年6 月至2011 年6 月接受手术治疗的250 例结直肠癌患者的临床资料,分别分析NLR 和FIB 与结直肠癌的病理特征的关系,将NLR 与FIB 进行联合形成一个指标(FIB-NLR)。将250 名结直肠癌患者分为3 组,患者NLR逸2.95 及FIB逸348 mg/ dl 定为FIB-NLR 2 分组,NLR逸2.95 及FIB<348 mg/ dl 或者NLR<2.95 及 FIB逸348 mg/ dl 定为1 分组,NLR<2.95 及FIB<348 mg/ dl 为0 分组,并分析3 组患者在结直肠癌的浸润深度、分期、淋巴结转移、神经浸润、远处转移、组织学分级中是否具有差异性。并将3 组患者按生存时间做生存分析,并对3 组患者的生存率进行比较。结果:中晚期及有淋巴结转移结直肠癌患者NLR 值明显高于分期较早及无淋巴结转移患者的NLR,差异具有统计学意义(P<0.001),肿瘤浸润深度较深、有神经浸润、有远处转移的患者其NLR 值明显高于浸润深度较浅、无神经浸润、无远处转移患者的NLR 值,差异具有统计学意义(P =0.006、P =0.002、P =0.007)。中晚期、有淋巴结转移、有远处转移的结直肠癌患者其FIB 值明显高于早期及无淋巴结转移、无远处转移的结直肠癌患者的FIB 值,差异具有统计学意义(P<0.001),浸润深度越深及有神经浸润的结直肠癌患者FIB 值明显高于浸润深度浅及无神经浸润患者的FIB 值,差异具有统计学意义(P =0.015、P=0.012)。NLR 与FIB 均在肿瘤的组织学分级、年龄大小、性别肿瘤部位无明显关联(P>0.05)。结直肠癌的临床分期越晚、浸润深度越深、有淋巴结转移、有远处转移、有神经浸润的患者其FIB-NLR 评分较早期、浸润深度浅、无淋巴结转移及无远处转移、无神经浸润患者高,差 异具有统计学意义(P<0.001)。生存分析发现,评分越高组其5 年生存率越低,差异具有统计学意义(P =0.001)。结论:FIB-NLR 可能是一个潜在的判断结直肠癌进展及预后的有效指标。     

糖尿病与结直肠癌患者预后相关研究进展

目前国内外大量研究证实糖尿病是诱发结直肠癌的独立危险因素,其机制与高血糖尧高胰岛素血症尧胰岛素样生长因 子尧胰岛素抵抗等密切相关遥为延长合并糖尿病的结直肠癌患者的生存期,改善患者的生存质量,关于糖尿病与结直肠癌预后 的研究越来越多遥本文就糖尿病与结直肠癌预后相关性的研究进展做一综述遥     

癌胚抗原阴性的结、直肠癌检测和结直肠癌预后相关生物标记

目的探讨结直肠癌的发生、发展过程中患者血清质谱多肽蛋白图谱的变化,筛选与结直肠癌预后及癌胚抗原(CEA)阴性检测相关的肿瘤标记分子。方法用蛋白指纹图谱技术检测结直肠癌,结直肠管状腺瘤患者和健康者血清质谱多肽蛋白图谱。结果初步筛选出对结直肠癌有代表性的7个差异蛋白;2个与其淋巴结转移相关的差异蛋白;4个与其远处转移相关的差异蛋白;3个在其根治性切除后表达下降的差异蛋白;而由3398·3u、5477·1u和8453·9u组成的诊断模型对CEA阴性表达结直肠癌的阳性检测率为100%。结论蛋白指纹图谱技术可筛选出有意义的生物标记差异蛋白,这对结直肠癌预后判断、CEA阴性的结直肠癌检测和改变结直肠癌的进程具有重要意义。     

微小RNA-143和微小RNA-145在结直肠癌中的研究进展

结直肠癌是严重威胁人类健康的恶性肿瘤之一,随着对微小RNA(miRNAs)研究的不断深入,越来越多的证据表明多种miRNAs参与了结直肠癌的发生、发展,并且可能作为其诊断、评估预后及复发转移的生物学标志。研究发现,miRNA-143/miRNA-145在多种肿瘤中的表达都发生了下调,能起到肿瘤抑制作用,其在结直肠癌中的研究也已较成熟。本文就miRNA-143/miRNA-145与结直肠癌的研究进展做一综述,为今后的结直肠癌机制和靶向治疗研究提供参考。     

人结直肠癌生物标记物概况

结直肠癌是全球最常见的肿瘤之一,其发病与社会环境、饮食习惯、遗传等多种因素有关。对结直肠癌患者,我们能做出较为准确的诊断,并进行相应的治疗,但目前我们缺少可以监测其治疗效果、预后水平等各方面的特异性指标。因此,研究者们对多种生物分子进行了大量实验,探究其作为结直肠癌特异性生物标记物的可行性。本文对目前各种结直肠癌生物标记物的研究进展进行综述。     

结直肠癌中5-氟尿嘧啶代谢酶的表达及临床意义

目的：分析5-氟尿嘧啶（5-F1uorouraci1,5-FU）代谢酶在结直肠癌中的表达及其与临床病理特征及预后的关系,为进一步探讨其在指导结直肠癌化疗中的潜在意义提供理论依据。方法构建含有72例结直肠癌、56例癌旁远端切缘的组织芯片,采用免疫组化EnVision两步法检测胸苷酸合成酶（ thymidy1ate synthetase,TS）、胸苷酸磷酸化酶（ thymidine phosphory1ase, TP）、二氢嘧啶脱氢酶（ dihydropyrimidine dehydrogenase,DPD）在两种组织芯片中的表达,并分析三者表达与结直肠癌临床病理特征及预后的关系。结果结直肠癌组织中的TS表达水平低于癌旁远端切缘组织（ P=0.876）;其表达与TNM分期有关（P=0.043）;与患者总生存期呈正相关（P=0.027）。结直肠癌组织中TP表达水平高于癌旁远端切缘组织（P=0.315）;其表达与淋巴结转移有关（ P=0.009）;与患者预后呈负相关（ P=0.040）。结直肠癌组织中DPD表达水平高于癌旁远端切缘组织（P=0.071）;其表达与组织学类型有关（P=0.029）;DPD高表达的患者总生存期显著缩短（P=0.011）。结论在以5-FU为基础化疗的结直肠癌患者中,TS、TP、DPD可以作为预后的重要指标。TS表达与临床分期密不可分,可作为结直肠癌进展的生物学标志。TP表达与淋巴结远处转移及复发密切相关,是影响患者术后复发转移的重要因素。     

循证护理在肝癌手术无瘤技术配合中的应用

目的 探讨循证护理在肝癌手术无瘤技术配合中的价值。方法 选择2014年6月~2018年6月我院80例接受肝癌切除术患者作为研究对象,按照随机数字表法分为对照组和观察组,每组40例。对照组给予常规肝癌手术护理配合,观察组循证护理基础上无瘤技术配合,比较两组肿瘤医源性腹腔内或创面种植转移发生率。结果 对照组术后出现3例肿瘤腹腔种植转移,占7.50%;1例肿瘤肝脏创面转移,占2.50%。观察组未发现医源性腹腔肿瘤种植和创面转移病例。两组肿瘤腹腔种植转移及肿瘤肝脏创面转移发生率比较,差异有统计学意义（P＜0.05）。结论 循证指导下严格实施系列化无瘤技术,能够有效防范医源性肿瘤细胞播散及种植,改善预后。     

结直肠癌原发灶中CXCR6的表达与临床意义

目的: 明确趋化因子受体CXCR6在结直肠癌原发灶中的表达特点及临床意义。方法: 收集2004年8月至2008年12月中山大学附属第一医院手术切除的143例结直肠癌标本及29例癌旁组织,应用免疫组化方法检测CXCR6的表达,采用Image-Pro Plus 6.0 软件分析图片的平均累积吸光度(mIA),分析CXCR6与同时性肝转移及预后的关系。结果: CXCR6在结直肠癌组织中呈不同程度的阳性表达,在癌旁正常组织中弱表达或不表达。结直肠癌原发灶中CXCR6的mIA在0.41~2.84之间,平均为1.54±0.04,其中同时性肝转移病例为1.63±0.05,无肝转移病例为1.41±0.08,两组比较差异有统计学意义(P<0.05)。以mIA值1.54为界,将病例划分为CXCR6低表达组(mIA<1.54)和CXCR6高表达组(mIA≥1.54)。CXCR6高表达患者的总生存率显著较低表达组差,两组差异有统计学意义(P<0.05)。多因素Cox回归分析发现年龄(P<0.05)、淋巴结转移(P<0.05)和同时性肝转移(P<0.01)为结直肠癌患者预后的独立危险因素,CXCR6为非独立危险因素。CXCR6表达与IV期肝转移患者预后无关(P>0.05),与I~III期结直肠癌患者预后呈负相关(P<0.01)。结论: CXCR6与结直肠癌肝转移的发生相关,它有望成为结直肠癌肝转移治疗的一个重要靶点。     

80岁以上结直肠癌患者手术治疗效果分析

目的：探讨80岁以上结直肠癌患者的临床特点及手术治疗效果。方法：回顾性分析我院2003年4月至2013年8月诊治的136例80岁以上结直肠癌患者临床资料,分析其临床及诊治特点、围手术期处理、手术治疗方法、术后并发症及预后。结果：术前合并症及并存病者84.6%(115/136)、术后出现并发症者54.4%(74/136),术后30 d内病死率为8.1%。根治性手术率72.1%,1、3、5年生存率分别为77%、43%、25%。结论：年龄并非高龄结直肠癌患者的手术禁忌,经过良好的围手术期处理,可取得较好的近期效果,但远期疗效并不理想。     

Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis

Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-Lewis^X (LEX-2), anti-sialyl Lewis^a (NS19-9), and anti-sialyl-dimeric Lewis^X (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.     

FAT10基因表达与结直肠癌患者临床病理因素及预后的关系

目的:探讨结直肠癌(CCT)组织中FAT10(Diubiquitin,双泛素)的基因表达与其病理因素及预后的关系。方法:收集我院2000～2003年73例有5年以上完整随访资料的结直肠癌术后患者,采用RT-PCR方法检测FAT10 mRNA在CCT、癌旁组织(TCT)和正常结直肠组织(NCT)中的表达情况,并分析临床病理因素对FAT10阳性表达率和相对表达量的影响,以及FAT10表达与预后的关系。结果:FAT10 mRNA在CCT阳性表达率为52.24%(35/67),且在CCT的相对表达量(0.735±0.034)明显高于TCT(0.561±0.044)和NCT(0.397±0.028)(P<0.05);FAT10 mRNA的阳性表达率及相对表达量受临床进展、淋巴结转移和TNM分级的影响较明显(P<0.05),而患者年龄、肿瘤大小、肿瘤分化程度等对其无明显影响(P>0.05);Log-Rank检验显示CCT患者中,FAT10表达阳性者生存率明显低于FAT10表达阴性者(P<0.01)。结论:FAT10在CCT的表达状况与CCT转移及预后关系密切,可以作为反映生物学行为和判断预后的有效指标。     

Prognostic significance of the molecular markers in human gastrointestinal cancer

Matrix metalloproteinases have been implicated in tumor progression. Matrilysin is one of the matrix metalloproteinases and is frequently overexpressed in gastrointestinal cancers. The aim of this study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47(42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage, and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor(T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.     

Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer.

Proteolytic activity of cancer cells is an important factor in metastasis. This study examined the relationship between MMP-1 expression of gastric cancer cells and peritoneal metastasis. MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a prognostic factor in case of advanced gastric cancer and might be useful in determining whether or not adjuvant therapy was indicated for patients at high risk of peritoneal recurrence.     

Immuno-PCI: A proposal for the implementation of “seed and soil” concept in the treatment of peritoneal carcinomatosis from colorectal cancer

The advent of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has revolutionized the approach to peritoneal carcinomatosis of colorectal cancer origin in appropriately selected cases. However, the high postoperative morbidity and mortality following the procedure underlines the need for optimizing the patient selection criteria, finally aiming to establish a patient-tailored approach. The introduction of tools enabling the quantification of the peritoneal spread of the metastatic deposits has been of paramount importance in the decision-making and the estimation of the prognosis. However, we believe that it is high time to attempt a further evolution of the current practice, by incorporating in the above mentioned quantification scores parameters indicative of the immune-response against the disease progression, fact which will probably reflect more accurately the dynamics of cancer progression and will sequentially be a crucial step towards individualized treatment of peritoneal carcinomatosis.     

Regulation of osmolality for cancer treatment

Disseminated metastasis is associated with a poor prognosis, and its management in the peritoneal or pleural cavity is crucial in the treatment of cancer. Recent studies show that ion and water transporters play important roles in fundamental cellular functions, including the regulation of cell volume that would be involved in the cancer process. Here, we review the evidence for hypotonic treatments of cancer and evaluate the potential of the cellular physiological approach in clinical management. The regulation of extracellular osmolality is a promising method, with several studies demonstrating the cytocidal effects of hypotonic solution on cancer cells. Peritoneal lavage with distilled water (DW) during surgery is reported to improve the survival rate of patients with spontaneously ruptured hepatocellular carcinoma. The in vitro studies included in this review also indicate the cytocidal effects of hypotonic shock on esophageal, gastric, colonic, pancreatic, and liver cancer cells with several unique methods and apparatuses, such as a differential interference contrast microscope connected to a digital video camera, a high-resolution flow cytometer and re-incubation analysis. The in vivo studies demonstrate the safeness of a peritoneal injection of DW into mice and indicate that the development of dissemination nodules can be prevented by the pre-incubation of cancer cells with DW or the peritoneal injection of DW. We also demonstrate that the blockade of Cl^? channels/transporters enhances the cytocidal effects of hypotonic shock by inhibiting regulatory volume decrease in various cancer cells. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for disseminated metastasis.