直肠腺癌和黏液腺癌腔内超声图像分析

目的探讨直肠腺癌和黏液腺癌的腔内超声图像的不同特点。方法回顾分析30例直肠进展期腺癌和28例直肠进展期黏液腺癌腔内超声特征,并与病理结果进行对比。结果进展期直肠腺癌28例腔内表面凹凸不平,肿瘤浸润肠壁回声19例无层次感,10例部分区域有模糊层次感,1例有清晰层次感。癌浸润最深处的边界17例有毛刺、呈角或呈结节样突起,5例呈波浪状起伏,8例光整平直。直肠黏液腺癌20例腔内表面平坦,肿瘤浸润肠壁回声6例有清晰层次感,13例部分区域有层次感,6例无层次感。癌浸润最深处的边界8例光滑平直,10例呈波浪状起伏,7例局部有少许毛刺、呈角或呈结节样突起。超声诊断癌浸润肠壁深度与病理诊断对比,直肠腺癌有25例诊断正确,2例诊断过浅,3例诊断过深;直肠黏液腺癌有10例诊断正确,14例诊断过浅,1例诊断过深。黏液腺癌浸润深度超声诊断符合率明显低于腺癌,且大部分为过浅诊断。结论直肠腺癌和黏液腺癌各有一定的声像图特点,对其特征的分析有助于两种癌的分型诊断。腺癌与黏液腺癌的鉴别有助于减少过浅诊断。     

结肠黏液腺癌临床病理特征分析

目的：探讨结肠黏液腺癌的临床病理特征及预后特点。方法回顾性分析672例初治的接受根治性手术的结肠癌患者,其中黏液腺癌为41例,非黏液腺癌为631例,比较两者临床病理特征和复发方式。结果黏液腺癌患者比非黏液腺癌患者更年轻（<50岁比例：48.8豫 vs 31.4豫,P <0.05）,肿瘤直径更大（6.0 cm vs 4.5 cm,P <0.05）,更多位于右半结肠（右半结肠比例：44.0豫 vs 17.3豫,P <0.05）和病理 T 分期更高（T3、T4比例：90.2豫 vs 72.7豫,P <0.05）,3 a 生存率更短（39.2豫 vs 68.5豫,P <0.05）。复发情况中,黏液腺癌腹膜转移率比非黏液腺癌更高（57.1豫 vs 1.5豫,P <0.05）。结论与非黏液腺癌比较,结肠黏液腺癌发病年龄更年轻,更多处于晚期和右半结肠,腹膜转移可能性更大,治疗预后更差,提示结肠黏液腺癌患者需要特异的治疗方案。     

FOLFOX和FOLFIRI方案用于大肠黏液癌辅助化疗的比较

目的:探讨FOLFOX及FOLFIRI方案在大肠黏液腺癌术后辅助化疗中的疗效差异。方法:将40例术后病理证实为大肠黏液腺癌患者随机分为2组,实验组应用FOLFIRI方案化疗,对照组应用FOLFOX方案化疗。比较两组的无病生存时间（DFS）和不良反应,并应用Kaplan-Meier法进行生存率统计分析。结果:FOLFOX组的中位DFS为13个月,FOLFIRI组的中位DFS为18个月。FOLFIRI方案组DFS比FOLFOX方案组DFS长5个月,差异有统计学意义（P=0.038）。结论:对于大肠黏液腺癌,术后应用FOLFIRI方案化疗比FOLFOX方案可延长DFS。     

LDH-A乙酰化在结直肠腺癌组织中的表达及意义

目的 探讨乳酸脱氢酶A(LDH-A)的乙酰化在结直肠腺癌组织中的表达及其与结直肠腺癌患者临床特征的关系.方法 应用免疫组织化学染色法检测40例结直肠腺癌患者的结直肠腺癌组织及其相应的40例癌旁正常组织中乙酰化LDH-A的表达情况.结果 结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率为22.5％(9/40),低于癌旁正常组织的47.5％(19/40),差异有统计学意义(P﹤0.05).Ⅰ～Ⅱ期结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率高于Ⅲ～Ⅳ期的结直肠腺癌组织,差异有统计学意义(P﹤0.05).不同年龄、性别、分化程度结直肠腺癌患者的结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05).结论 LDH-A乙酰化水平在结直肠癌组织中呈低表达,提示其与结直肠癌的发生可能具有一定的关系,在结直肠癌发展中,LDH-A乙酰化可能起到负性调节的重要作用.     

原发性肺黏液腺癌的研究进展

原发性肺黏液腺癌多发生于成年男性,是发病率低的肺腺癌的一种亚型,因其无明显临床特异性,容易造成误诊,给患者造成不良的预后,因此我们需要进一步了解该种疾病并通过多种手段早期确诊.手术治疗仍然是该病的首选方式,不仅可以切除病灶还可以进一步病理确诊、基因检测、肿瘤分期及预后判定,以及为后续化疗做准备.最近几年,随着基因技术的不断发展与创新,发现该疾病的发生与KRAS基因突变、ALK基因重排以及其相关信号通路有关.相关基因突变和信号通路可成为治疗该病的靶点,这为新的靶向药物的研制提供了多种思路.但是仍然有许多问题需要进一步研究,包括原发性肺黏液腺癌的标准化疗方案、靶向药物的耐药问题以及新的KRAS抑制剂的研制.本文从原发性肺黏液腺癌的定义和发病机制、诊断以及最新的一些治疗手段研究进行综述.     

细丝蛋白A 在结直肠腺癌中的特异性表达*

目的:研究细丝蛋白A（FLNa）在结直肠腺癌组织中的表达情况,探讨FLNa在结直肠腺癌发生发展中的作用。方法:选择2009年1 月～9 月河北医科大学第四医院外二科60例患者手术切除的结直肠腺癌组织和正常结直肠组织。癌组织取自肿瘤中心处,正常组织取自距肿瘤边缘至少10cm处。采用RT-PCR 法和Western blot法检测60例结直肠腺癌患者癌组织和结直肠正常组织中FLNa的mRNA 和蛋白质的表达情况。同时采用免疫组化法检测FLNa在结直肠癌组织和结直肠正常组织中的分布,并分析组间的FLNa阳性率表达差异。所有病例均经病理诊断确诊,均无其他部位原发肿瘤,术前无化疗、放疗和免疫治疗史。结果:结直肠癌组织中FLNa mRNA的表达水平（0.22± 0.02）较结直肠正常组织低（0.94± 0.04）（P=0.018）;Western blot法检测显示:FLNa蛋白在结直肠癌组织中的表达水平（0.34± 0.03）也较结直肠正常组织低（0.85± 0.02）（P=0.028）;Pearson相关分析显示:FLNamRNA 和蛋白水平呈正相关（r=0.654,P<0.05）。 FLNa免疫组化阳性染色产物位于细胞质。FLNa在结直肠癌组织组和结直肠正常组织组的阳性表达率分别为50.00% 、91.67% ,癌组织组明显低于正常组织组（χ2=50.037,P=0.000）。 结论:FLNa的特异性低表达与结直肠腺癌的发生、发展具有高度相关性,有望成为新的肿瘤标志物,为临床诊治提供的新靶点。      

乳腺黏液腺癌的超声表现及其与病理特征的关系

目的探讨乳腺黏液腺癌超声表现与病理特征的关系。方法于彩超下观察乳腺黏液腺癌患者的超声表现,根据其病理特征分为单纯型、混合型2组,分析超声表现与病理特征的关系。结果混合型乳腺黏液腺癌患者中检测到动脉血流频谱占88.6%,高于单纯型乳腺黏液腺癌患者,差异有统计学意义(P<0.05);2组患者的峰值血流速度、阻力指数无明显差异(P>0.05);混合型乳腺黏液腺癌患者血流信号达2级、3级者分别为37.1%、20.0%,明显高于单纯型乳腺黏液腺癌患者,差异有统计学意义(P<0.05)。2组患者的肿瘤边界、肿瘤边缘、肿瘤后方回声分型、瘤内钙化有显著差异(P<0.05);在回声类型、肿瘤形态无明显差异(P>0.05)。结论与单纯型乳腺黏液腺癌相比,混合型黏液腺癌在超声下具有动脉血流频谱、血流信号分级升高,肿瘤边界不清、边缘模糊、肿瘤后方回声增强、瘤内出现钙化的特点。     

19例肺炎型黏液腺癌的临床分析

目的 分析肺炎型黏液腺癌的影像表现及对应病理基础,探讨其形成及播散的机制。方法 回顾首都医科大学附属 北京世纪坛医院2015年11月至2019年12月收治的肺癌患者。影像初筛表现为磨玻璃渗出、片状不规则实变等影像学符合肺 炎,通过病理最终确诊为肺黏液腺癌的 19例患者,并整理出对应的临床资料及病理资料。结果 17例患者出现咳嗽、咳痰症 状,1例无明显症状,1例表现为咳嗽。影像学表现为片状分布实变（100%）、磨玻璃渗出（78.9%）、空洞（15.8%）、支气管充气征 （26.3%）,52.6%双侧肺部受累,15.8%左肺下叶受累,15.8%右肺下叶受累。73.7%的患者经过评估后给予药物化疗,3例行肺 叶切除,1例靶向治疗。中位生存时间6个月。肺炎型黏液腺癌可累及多叶多段肺叶,抗感染治疗效果不佳,磨玻璃渗出、实变 从病理上判断为肺泡腔内黏液填充及部分肿瘤细胞的播散。同时对患者排出的黏液痰涂片行迪夫染色,可见肿瘤细胞。结 论 影像表现为磨玻璃影、实变,同时有结节、空洞、枯树枝征等表现,需要考虑肺炎型黏液癌的可能。影像上磨玻璃改变警惕 肺黏液腺癌通过黏液中腺癌细胞播散进而导致的支气管‐肺内转移。     

结直肠癌微卫星不稳定（MSI）与其发病及预后的关系

抑癌基因及癌基因之间的相互作用是结直肠癌发病主要发病原因,近年研究发现微卫星不稳定成为结直肠癌发病另一重要机制,尤其是遗传性非息肉病性结直肠癌（hereditary non-polyposis colorectal cancer,HNPCC）及部分散发性结直肠癌发生的重要原因。微卫星不稳定的结直肠患者具有独特的临床病理特征,如低分化、黏液腺癌、多位于右半结肠、淋巴细胞浸润明显等。化疗是结直肠癌患者手术后重要治疗手段,氟尿嘧啶类药物为结直肠癌患者化疗的基本药物,因此结直肠癌患者对于氟尿嘧啶类药物敏感性成为患者能否从化疗中获益的重要因素,也成为各位学者的研究热点。近年来有学者提出微卫星不稳定及其他分子标记物可预测结直肠癌患者化疗敏感性,同时也可成为判断预后的指标。微卫星不稳定将来可成为结直肠癌患者的预后及化疗敏感性的判断因素,也可为个体化治疗提供理论依据,但目前尚需大样本的前瞻性临床试验进一步证实。结直肠癌目前在国内外发病率均逐渐升高,成为危害人类生命的重要疾病,且遗传倾向明显,是目前人类恶性肿瘤中遗传变化最明显的肿瘤。对于结直肠癌的发病研究表明,染色体不稳定（chromosome instability）为结直肠癌发病的主要原因,其机制仍未完全阐明。近年的研究发现微卫星不稳定（microsatelite instability）为结直肠癌发病的另一重要机制,是遗传性非息肉病性结直肠癌（heredi? tary non-polyposis colorectal cancer,HNPCC）及部分散发性结直肠癌发生的重要原因。目前关于微卫星不稳定的研究不仅于发病机制上,与结直肠癌预后的关系也成为目前研究的热点。      

肺肠型腺癌研究进展

肺肠型腺癌是原发性肺腺癌的罕见病理亚型, 指肺腺癌中肠型分化成分超过50%者, 因其与结直肠腺癌在形态学及免疫组化特征方面有某些共同点而得名, 二者间的共同特征也造成肺肠型腺癌与转移性结直肠癌的鉴别诊断具有困难。肺肠型腺癌可能起源于吸烟等危险因素刺激所致的呼吸道基底细胞肠化生, KRAS是其相对高频突变基因, 其他驱动基因突变罕见。结合PubMed收录涉及肺肠型腺癌文献分析, 肺肠型腺癌CK7阳性率为88.2%(149/169), CDX2阳性率为78.1%(132/169), CK20阳性率为48.2%(82/170), TTF1阳性率为38.8%(66/170);临床特征方面, 肺肠型腺癌平均发病年龄为62岁, 男性患者占56.5%(35/62), 吸烟者占78.8%(41/52), 41.4%(24/58)原发病灶位于右肺上叶;治疗方面, 现多推荐采用传统非小细胞肺癌治疗方案而非结直肠癌治疗方案对其进行治疗。目前仍亟待更多基础及临床研究, 从组学等水平对其分子图谱及发病机制等方面进行深入探索, 寻找最优的化疗方案及可能有效的靶向或免疫治疗方案。     

Genome-wide molecular characterization of mucinous colorectal adenocarcinoma using cDNA microarray analysis

Mucinous colorectal carcinoma exhibits distinct clinicopathological features compared to non-mucinous colorectal carcinoma. Previous studies have discovered several molecular genetic features in mucinous colorectal carcinomas, but have limitations as they are confined to a small number of molecules. To understand the mucinous colorectal carcinoma system, this study was designed to identify genes that are differentially expressed in mucinous colorectal carcinoma compared to non-mucinous colorectal carcinoma using cDNA microarrays. cDNA microarray experiments were performed using human cDNA 17k chips with 25 mucinous and 27 non-mucinous cancer tissues. Differentially expressed genes (DEGs) were determined by Welch's t-test and more accurate classifiers were selected from the DEGs using the prediction analysis for microarrays (PAM) software package. Array results were validated using quantitative real-time RT-PCR. The identified gene set was functionally investigated through in silico analysis. Sixty-two DEGs were identified and the 50 highest ranking genes could be used to accurately classify mucinous and non-mucinous colorectal carcinomas. The identified gene set included up-regulated TFF1 (4-fold), AGR2 (3.3-fold), FSCN1 (2.2-fold), CD44 (1.5-fold) and down-regulated SLC26A3 (0.2-fold) in MC. TFF1, AGR2 and SLC26A3 were validated by quantitative real-time RT-PCR. The functions of these DEGs were related to tumorigenesis (14 genes), cell cycle progression (6 genes), invasion (2 genes), anti-apoptosis (7 genes), cell adhesion and proliferation (5 genes) and carbohydrate metabolism (3 genes). We suggest that MC has distinct molecular characteristics from NMC and therefore, that the expression signatures of DEGs may improve the understanding of molecular pathogenesis and clinical behaviors in MC.     

Mucinous differentiation in colonic adenocarcinoma is associated with a reduction in tumour-infiltrating lymphocytes.

AIMS: The aim of this study was to examine the density of tumour-infiltrating lymphocytes (TILs) in colorectal carcinomas showing mucinous differentiation. METHODS: We examined 33 adenocarcinomas showing variable mucinous differentiation and compared the density of TILs with that of 65 adenocarcinomas of no special type (NOS) showing no mucinous differentiation. RESULTS: Mucinous differentiation is associated with a significantly lower density of TILs compared to adenocarcinoma NOS (P=0.0016; chi-squared test with continuity correction). This reduction in TILs is present also in adjacent foci of adenocarcinoma NOS within mucinous tumours. CONCLUSIONS: There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show mucinous differentiation, which may help explain the increased biological aggressiveness associated with this pattern of differentiation. Copyright Harcourt Publishers Limited.     

TNM Stages and Prognostic Features of Colorectal and Mucinous Adenocarcinoma Patients: a Meta Analysis

Aim: The significance of the mucinous adenocarcinoma in TNM staging and prognosis for colorectal tumorpatients is still controversial. The aim was to provide a meta-analysis for TNM staging and prognostic featuresof colorectal tumors. Methods: 30 individual case-control studies were finally included into this meta-analysis,involving a total of 444,489 cancer cases and 45,050 mucinous adenocarcinomas, of relations with TNM stagingand prognostic features. Results: Compared to non-mucinous adenocarcinoma patients, the TNM IV stageaccounted for a larger percentage of mucinous adenocarcinomas (OR=1.48, 95%CI 1.28-1.71, POR<0.001) andthe prognosis was significantly poor (HR=1.06, 95%CI 1.04-1.08, P<0.001). After heterogeneity testing, the resultswas similar to the holistic approach outcome (HR=1.48, 95%CI 1.35-1.62, P<0.001). Conclusion: Compared topatients with non-mucinous adenocarcinomas, mucinous adenocarcinoma patients with later TNM staging makeup a big percentage, and mucinous adenocarcinoma is an independent risk factor for poor prognosis.     

乳腺黏液癌7例临床病理分析

目的：探讨乳腺黏液癌的临床及病理特征,对其诊断、病理分型和鉴别诊断进行讨论。方法：对7例乳腺黏液癌患者进行回顾性分析,同时复习相关文献。结果：本组黏液腺癌占同期乳腺癌的4.73%,中位年龄42岁,绝经前患者占71.43%,病灶大小1.0-6.5cm。单纯型黏液癌均无腋窝淋巴结转移,混合型转移率为33.33%。结论：国内30-50岁女性,临床诊断为良性纤维瘤的乳房肿块,需警惕为乳腺黏液癌。乳腺黏液癌生长缓慢,预后较好。     

Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer.

BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.     

Mucinous carcinoma of the colon and rectum.

The clinicopathologic significance of mucus production by adenocarcinoma of the colon and rectum was analyzed in retrospective study with stage matched non-mucus producing control carcinomas. Mucinous carcinoma of the colon and rectum comprised 132 (15%) of 893 cases of colorectal carcinoma. The rectum was the most common site (33% of cases).While 120 mucinous cancers had a poorer five-year survival than non-mucinous tumors (34% vs. 53%, p less than .005), these had a particularly bad prognosis in the rectum (18% 5 year survival vs. 49% for the non-mucinous tumor controls, p less than .00k). The theoretical basis for this location-dependent behavior is considered. From this study, distinctive clinico-pathologic features emerge. There were seven documented cases of ulcerative colitis and 8 additional patients gave a history of "colitis". An additional five patients had received prior pelvic irradiation. Of particular note was the fact that 31% of mucinous carcinomas were associated with villous adenomas, implying a histogenetic relationship. Moreover, this finding again emphasizes the neoplastic potential of the villous adenoma, especially in the rectum where the development of mucinous carcinoma is particularly ominous.     

BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer

Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non-mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non-mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non-mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non-mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes.     

Clinicopathological studies and patterns of recurrence of mucinous colorectal carcinoma with curative resection

In 771 cases of Stage II and III colorectal carcinoma with curative resection, clinicopathological characteristics, recurrent rate, patterns of recurrence, and prognosis of 24 cases (3%) of mucinous carcinoma were compared with those of 725 cases (94%) of well-moderately differentiated adenocarcinoma. Compared with well-moderately differentiated adenocarcinoma, mucinous carcinoma was found to be larger in tumor size, more severe lymphatic invasion, and a greater likelihood of Stage IIIb. Mucinous carcinoma had a highly recurrent rate and poorer prognosis than well-moderately differentiated adenocarcinoma. About the patterns of recurrence, mucinous carcinoma was found to be more significantly often as lymph node recurrences, but there was no liver metastasis in mucinous carcinoma. As for mucinous colorectal carcinoma, we should consider other different therapeutic strategies and surveillance.