胃癌患者血清细胞因子水平变化及与肿瘤分化程度的关系

目的探讨胃癌患者机体细胞免疫状态变化,为肿瘤免疫治疗提供依据。方法研究对象为山东大学附属省立医院2001年5月-2009年1月住院手术的胃癌患者78例（胃癌组）及同期健康体检者80例（对照组）,两组均抽取空腹外周静脉血3ml（胃癌组术前）,分离血清,-20℃冻存。采用ELISA法检测血清细胞因子IL-2、IFN-γ,IL4、IL-6、IL-10、IL-12水平。结果与对照组比较,胃癌组血清IL-2、IFN-γ及IL-12均显著降低,IL-4、IL-6和IL-10均显著升高（P〈0．05、0．001）;胃癌分化程度越低IL-2、IFN-γIL-γ2降低幅度及IL-4、IL-6、IL-10升高幅度越明显。结论胃癌患者处于Th2型细胞占优势的Th1／Th2细胞漂移状态,并与肿瘤分化程度相关;纠正Th1／Th2细胞漂移、诱导Th0细胞向Th1细胞增殖分化,有望促进机体免疫功能恢复、激活抗肿瘤免疫应答,进而提高肿瘤综合治疗效果。     

FACL4 mRNA在PHC中的表达及与肿瘤临床病理特征的相关性

目的 探讨脂肪酸辅酶A连接酶长链4 (FACL4)在原发性肝癌(PHC)发生中的作用.方法 收集40例PHC患者手术切除的癌组织及相应癌旁组织,采用半定量RT-PCR方法检测FACL4 mRNA表达,并分析其与PHC临床病理特征的关系.结果 FACL4 mRNA在癌组织中的表达显著高于癌旁组织(P＜0.01);FACL4 mRNA表达水平与肿瘤大小、病理分级、肝硬变类型等未见明显相关性(P均>0.05).结论 FACL4 mRNA过表达可能在PHC发生中具有一定作用,此为PHC的临床诊断及治疗提供了新的思路.     

Survivin在胃肠道间质瘤中的表达及其与VEGF表达的相关性

目的 探讨凋亡抑制蛋白Survivin在胃肠道问质瘤(GISTs)组织中的表达情况及其与VEGF表达的相关性.方法 采用免疫组化S-P法检测57例胃肠道间质瘤组织中Survivin蛋白和VEGF蛋白的表达情况.结果 57例GISTs中,Survivin阳性率为66.7%,VEGF阳性率为73.7%.Survivin和VEGF蛋白的阳性表达与GISTs的恶性潜能相关(P<0.01,P<0.05),两者的表达均与GISTs浸润转移、肿瘤直径及坏死相关(P<0.01,P<0.05),而与年龄、性别及发病部位无关(P>0.05).Survivin表达与VEGF表达成正相关(P<0.05).结论 Survivin、VEGF可作为反映GISTs生物学特性的标志物,检测Survivin、VEGF的表达有助于GISTs恶性潜能的评估.Survivin与GISTs组织中VEGF的表达成正相关,两者可能协同促进GISTs的血管生成,参与GISTs的发生发展.     

Morphometric study of salivary glands in primary Sj?gren's syndrome

The relationship between structural changes of the minor salivary glands with age was evaluated by morphometric analysis in twenty patients with primary Sj?gren's syndrome (prim. SS) (Group I) and in twenty sex and age-matched normal subjects (Group II). No statistically significant differences were found in the acinar tissue, intralobular ducts (ILD) and fibrous tissue between the two Groups. In contrast, there was a 5-fold increase in the volume fraction of inflammatory cells in Group 1. In both Groups the percentage of fibrous tissue and ILD increases and the percentage of acinar tissue decreases linearly with age. In Group I the increase in the volume percentage of fibrous tissue and the decrease in the volume fraction of the acinar tissue were not related to the volume percentage of inflammatory cells. These results demonstrate that in prim. SS the acinar atrophy is not related to the inflammatory process but is an age-dependent phenomenon.     

Single-level dynamic spiral CT of hepatocellular carcinoma：Correlation between imaging features and density of tumor microvessels

AIM: To investigate the correlation of enhancement features of hepatocellular carcinoma (HCC) revealed by single-level dynamic spiral CT scanning (DSCT) with tumor microvessel density (MVD), and to determine the validity of DSCT in assessing in vivo tumor angiogenic activity of HCC. METHODS: Twenty six HCC patients were diagnosed histopathologically. DSCT was performed for all patients according to standard scanning protocol. Time-density curves were generated, relevant curve parameters were measured, and gross enhancement morphology was analyzed. Operation was performed to remove HCC lesions 1 to 2 weeks following CT scan. Histopathological slides were carefully prepared for the standard F(8)RA immunohistochemical staining and tumor microvessel counting. Enhancement imaging features of HCC lesions were correlatively studied with tumor MVD and its intra-tumor distribution characteristics. RESULTS: On DSCT images of HCC lesions, three patterns of time-density curve and three types of gross enhancement morphology were recognized. Histomorphologically, the distribution of positively stained tumor endothelial cells within tumor was categorized into 3 types. Curve parameters such as peak enhancement value and contrast enhancement ratio were significantly correlated with tumor tissue MVD (r=0.508 and r=0.423, P<0.01 and P<0.05 respectively). Both the pattern of time-density curve and the gross enhancement morphology of HCC lesions were also correlated with tumor MVD, and reflected the distributive features of tumor microvessels within HCC lesions. Correlation between the likelihood of intrahepatic metastasis of HCC lesions with densely enhanced pseudocapsules and rich pseudocapsular tumor MVD was found. CONCLUSION: Enhancement imaging features of HCC lesions on DSCT scanning are correlated with tumor MVD, and reflect the intra-tumor distribution characteristics of tumor microvessels. DSCT is valuable in assessing the angiogenic activity and tumor neovascularity of HCC patients in vivo.     

原发性干燥综合征肾脏损害病理及其临床相关性分析

目的分析原发性干燥综合征（pSS）合并肾脏损害的病理特点及其与临床的关系。方法采用半定量分析方法对比研究16例有肾脏损害pSS患者的肾活检病理，分析肾小管、间质、肾小球病理变化间相互关系及肾脏病理变化与临床特征、唇腺病理相关性。结果16例患者肾脏组织病理分类：间质性肾炎（IN）8例（50％），其中单纯IN5例，合并IN3例；弥漫系膜增殖性肾小球肾炎（MePGN）3例；轻度系膜增殖性肾小球肾炎3例；局灶节段硬化性肾小球肾炎（FSGS）2例；膜增殖性肾炎（MPGN）1例；膜型肾病（MN）2例。免疫荧光检查发现系膜区、肾小球、肾小管基底膜、间质可有IgG、IsA、IgM、C3、C1q沉积。85％以上病例存在间质局灶炎症且有弥漫分布的细胞浸润。临床存在肾小管酸中毒（RTA）患者11例（68．8％），其中8例有IN，肾功能不全2例患者中，1例为MN，1例同时有IN、FSGS。肾小球硬化率与血管壁增厚有关（r=0．77，P=0．001），与肾小管萎缩、间质纤维化无关。肌酐清除率与调整后慢性肾小管间质肾炎（CTIN）值有关（r=-o．52，P=0．04），肌酐清除率与肾小球硬化率有关（r=-0．53，P=0．04）。唇腺活检淋巴细胞灶数，与肾脏炎细胞灶数无相关（r=0．28，P=0．30）。结论pSS合并肾脏损害并非单一间质性肾炎，肾小球病变也不少见，且不完全继发于间质性肾炎，部分病例较重，及时活检有助合理治疗和判断预后。     

原发性肝细胞癌患者索拉菲尼服药依从性及与家庭关怀度的相关性

目的探讨原发性肝细胞癌(hepatocellular carcinoma,HCC)患者索拉菲尼服药依从性现状,分析服药依从性与家庭关怀度的相关性。方法应用Morisky服药依从性量表、家庭关怀度量表对我中心收治的218例HCC患者进行问卷调查,并对回收的215份有效问卷进行分析。结果HCC患者索拉菲尼服药依从性平均得分为(6.67±2.51)分,家庭关怀度总平均分为(7.21±2.84)分;相关性分析显示服药时间、情感度、合作度、适应度等家庭关怀度指标对患者服药依从性均有影响。结论HCC患者索拉菲尼服药依从性有待提高,医护人员可以通过鼓励延长服药时间、帮助改善家庭关怀度来提高患者服药依从性。     

Cancer biology for individualized therapy: correlation of growth fraction index in native-state histoculture with tumor grade and stage.

There is a need for individualization of all aspects of cancer therapy. Because of significant heterogeneity within a tumor class, there is a need to develop an in vitro test to accurately gauge tumor aggressiveness. Such a measurement would greatly aid treatment decision making. Current methodologies such as flow cytometry, which lacks unambiguous interpretation of cell-proliferative data, and determination of the thymidine-labeling index, which measures nucleotide uptake in a nonphysiological state, have not reproducibly attained this goal. We have developed an in vitro native-state three-dimensional gel-supported histoculture system that allows the growth of all human solid tumor types for relatively long time periods. The native-state system was used to identify the percent of cells capable of incorporating [3H]thymidine over a 4-day period, which we term the growth fraction index (GFI). We have compared the ability of cancer tissue to proliferate in native-state culture to the stage and histological grade of four major types of human carcinomas: breast, ovarian, colon, and lung. Eighty percent of tumor explants could be evaluated, even when sent from across the country. We have determined that the GFI correlates with tumor stage and grade for breast and ovarian carcinoma. In colon carcinoma, there is a trend toward higher GFIs in tumors of more advanced stage and grade. In non-small cell lung carcinomas, GFI, stage, and grade do not correlate. These results suggest the applicability of gel-supported three-dimensional native-state histoculture for prognostic purposes in patients with breast and ovarian cancers and demonstrate the clinical relevance of the native-state histoculture system.     

Esophagitis in infants. Morphometric histological diagnosis and correlation with measures of gastroesophageal reflux

To assess the incidence of histological esophagitis in infants less than 2 yr old with symptoms of gastroesophageal reflux, 35 infants were studied with esophageal suction biopsy and pH probe monitoring. Intraepithelial and lamina propria inflammatory cells, basal cell layer thickness, and papillary height were quantitated. Distal esophageal sections from infant sudden death trauma victims were used to provide normal morphometric control values. The upper limit of normal for each of the four histological parameters of esophagitis was defined as the mean plus three standard deviations. The values thus derived were similar to established adult normal values. Seventy-seven percent of the patients had at least one abnormal histological parameter (intraepithelial eosinophils or neutrophils, thickened basal cell layer, or increased papillary height) and were thus considered to have esophagitis. These measures of esophagitis all correlated well with each other, providing an internal consistency to the histological interpretation. Lamina propria eosinophilia correlated highly with intraepithelial eosinophils (r = 0.98) and was found to have a sensitivity of 41% and specificity of 89% for diagnosing histological esophagitis, defined as abnormality of any of the four histological parameters. Ninety-three percent of the patients with histological esophagitis had significant reflux as determined by pH probe monitoring. However, there was generally poor correlation between the severity of the esophagitis as quantitated by morphometric parameters and severity of the reflux as measured by pH monitoring. Esophageal suction biopsies, which provide adequate specimens for morphometric interpretation, are appropriate for diagnosing reflux esophagitis in infants.     

miR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome

We previously showed that microRNA-429 (miR-429) played an important role in epithelial–mesenchymal transition (EMT) of urothelial cell carcinoma of the bladder. We herein evaluated the expression of miR-429 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival. Relative expression levels of miR-429 in surgical bladder cancer tissue specimens obtained from 76 patients with bladder cancer were measured by chromogenic in situ hybridization. miR-429 expression was significantly higher in specimens from alive patients than expired patients in both of 5-year overall survival (OS) (0.59 ± 0.09 vs. 0.27 ± 0.12; p < 0.05) and 5-year recurrence-free survival (RFS) (0.63 ± 0.10 vs. 0.33 ± 0.10; p < 0.05). The univariate Cox proportional hazards analysis revealed that tumor grade, stage, and miR-429 expression were significantly associated with patient survival. In multivariate analysis, tumor stage and miR-429 expression were significantly associated with 5-year OS (hazard ratio [HR] 4.70, p < 0.001) and 5-year-RFS (HR 2.20, p < 0.05). The Kaplan–Meier analysis showed that patients with miR-429 expression had significantly better 5-year OS and 5-year RFS rates than those without miR-429 expression (84.4% vs. 61.4%, p < 0.05 and 71.9% vs. 45.5%, p < 0.05, respectively). miR-429 may be considered as an adjunctive prognostic marker in addition to tumor grade and stage in bladder cancer.     

原发性肝癌组织P16蛋白的缺失与HBV感染

目的研究Ｐ１６蛋白缺失与原发性肝癌发生发展的关系以及ＨＢＶ感染与Ｐ１６蛋白缺失的相关性．方法用免疫组化技术（ＬＳＡＢ法）检测７０例原发性肝癌组织标本中的Ｐ１６蛋白和ＨＢｓＡｇ．结果有６０６％（４０／６６）的肝细胞癌（ＨＣＣ）和７５０％（１／４）的胆管细胞癌（ＣＣＣ）Ｐ１６蛋白缺失；Ⅰ，Ⅱ，Ⅲ和Ⅳ级（按Ｅｄｍｏｎｄｓｏｎ标准）ＨＣＣＰ１６蛋白缺失率分别为００％（０／１），４４１％（１５／３４），８２１％（２３／２８）和６６７％（３／４），组间差异显著（Ｐ＜００５）．在有癌旁肝组织的４８例标本中，癌组织Ｐ１６蛋白阴性率（７２６％）明显高于癌旁肝组织（４１２％，Ｐ＜００５）．有６２５％（３０／４８）的ＨＣＣ癌旁肝组织ＨＢｓＡｇ阳性．ＨＢｓＡｇ阳性病例与阴性病例的Ｐ１６阴性率分别为７３３％（２２／３０）和６６７％（１２／１８），差异无显著性（Ｐ＞００５）．结论Ｐ１６蛋白缺失与原发性肝癌相关，与肝癌的恶性发展关系密切，可能对预后有重要影响．ＨＢＶ感染与Ｐ１６蛋白缺失无明显相关性．     

肿瘤退缩分级标准的对比及其在直肠癌诊治中的应用进展

随着新辅助治疗在直肠癌中的规范化推广,肿瘤退缩分级（TRG）标准逐渐引起广泛关注和重视。多项研究证实TRG与直肠癌患者新辅助治疗反应、生存预后有一定相关性,在患者生存预测、随访和临床诊疗策略等方面均有应用前景,甚至也有报道考虑将其纳入临床试验替代终点。但是目前TRG标准各异,尚未统一化、规范化,故本文旨在对目前常见TRG标准进行汇总对比,并进一步探讨其在直肠癌诊治中的临床应用。     

The prognostic impact of primary tumor resection in pancreatic neuroendocrine tumors with synchronous multifocal liver metastases

Background

Whether primary tumor resection benefits patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors remains controversial. We investigated whether primary tumor resection significantly affects survival in this study.

Evaluation of microvessels in colorectal tumors by narrow band imaging magnification

BACKGROUND: Narrow band imaging (NBI) uses optical filters for sequential green and blue illumination and narrows the bandwidth of spectral transmittance. OBJECTIVE: We determined the clinical usefulness of NBI magnification for evaluation of microvascular architecture and qualitative diagnosis of colorectal tumors. DESIGN: This study was a retrospective study. SETTING: Department of Endoscopy, Hiroshima University, Hiroshima, Japan. PATIENTS AND MAIN OUTCOME MEASUREMENTS: A total of 189 colorectal lesions were analyzed. Each lesion was observed by NBI magnifying endoscopy and classified according to microvascular features (ie, thickness and irregularity). Microvessel thickness was classified as invisible, thin, or thick, and microvessel irregularity was classified as invisible, regular, mildly irregular, or severely irregular. NBI endoscopic images were compared with histologic findings. RESULTS: With respect to microvessel thickness, invisible microvessels were found significantly more often in hyperplasia lesions, and thick microvessels were found significantly more often in carcinoma with submucosal massive invasion (sm-m) (P < .01). With respect to microvessel irregularity, invisible microvessels were found significantly often in hyperplasia lesions, and severely irregular microvessels were found significantly often in sm-m lesions (P < .01). Accuracy of diagnosis of sm-m on the basis of thick and severely irregular lesions was 100%. CONCLUSION: Microvascular features determined by NBI magnification are associated with histologic grade and depth of submucosal invasion. These results indicate that NBI magnification is useful for the prediction of histologic diagnosis and selection of therapeutic strategies of colorectal tumors.     

肝癌组织IFITM3蛋白表达水平及其与肝细胞癌患者手术切除术后肝内肿瘤复发的相关性分析*

目的 探讨肝细胞癌（HCC）组织干扰素诱导跨膜蛋白 3（IFITM3）表达水平及其临床意义。方法 在我院接受根治性手术切除治疗的43例HCC患者,术中取癌组织和癌旁肝组织,分别采用Western blot法和免疫组化法检测组织IFITM3蛋白表达情况,比较肝内肿瘤复发与未复发患者癌组织IFITM3表达的差异。结果 经Western blot法检测肝癌组织IFITM3表达水平为（1.2386±0.1901）,显著高于癌旁组织的（0.9496±0.0995,t=8.832,P=0.000）;免疫组化法检测显示肝癌组织IFITM3蛋白阳性率为72.1%（31/43）,明显高于癌旁组织的14.0%（6/43,x²=29.647,P=0.000）;中分化肝癌组织IFITM3蛋白阳性率为90.9%（10/11）,低分化肝癌组织为95.2%（20/21）,均明显高于高分化组的9.1%（1/11）（x²=14.727, P=0.000;x²=23.748,P=0.000）;术后复发组癌组织IFITM3蛋白阳性率为81.0%（17/21）,未复发组为22.7%（5/22）,两者比较差异具有统计学意义（x²=14.578,P=0.000）。结论 HCC组织IFITM3蛋白呈高表达,且肝癌分化越差,IFITM3表达也越强,并可能与术后肿瘤复发有关。     

A primary solitary tumor of the lesser omentum with immunohistochemical features of gastrointestinal stromal tumors

We here present a primary solitary tumor of the lesser omentum that was found in a 71-yr-old woman. Differential diagnosis could not be made preoperatively; therefore, histopathological examination including immunohistochemical studies were performed to determine the nature of the tumor.
The resected specimen, measuring 17 cm at the largest point, consisted of the outer solid part and the inner multiloculated cysts. Microscopically, the tumor was characterized by interlacing bundles of elongated spindle cells, with the nuclei focally showing a palisading pattern. However, skeinoid fibers were not observed anywhere. One to three mitoses per 50 high power fields were observed. Immunohistochemically, the tumor was negative for S-100 protein and smooth muscle–specific actin, but stained positive for CD34. The microscopic features were consistent with those of potentially malignant gastrointestinal stromal tumors.
Stromal tumors that represent the differentiation toward neither typical leiomyomas or schwannomas rarely occur in the lesser omentum with only one such instance having been reported to date. Due to this rarity, it is difficult to make the differential diagnosis preoperatively, even with existing imaging techniques, and predicting the clinical behavior of such omental tumors is also often difficult. Therefore, complete resection should be performed when such tumors are encountered in daily practice.     

Gene expression and angiotropism in primary CNS lymphoma

Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth is restricted to the central nervous system. We used cDNA microarray analysis to compare the gene expression signature of primary CNS lymphomas with nodal large B-cell lymphomas. Here, we show that while individual cases of primary CNS lymphomas may be classified as germinal center B-cell, activated B-cell, or type 3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B-cell lymphomas by high expression of regulators of the unfolded protein response (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct regulators of apoptosis. We demonstrate that interleukin-4 (IL-4) is expressed by tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify high expression in CNS lymphomas of several IL-4-induced genes, including X-box binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6 in tumors was associated with short survival in an independent set of patients with primary CNS lymphoma who were treated with high-dose intravenous methotrexate therapy.     

Survivin、COX-2及VEGF在大肠癌中的表达及与肿瘤微血管密度的关系

目的:研究Survivin, COX-2, VEGF和肿瘤微血管密度(MVD)在大肠癌组织中的表达, 探讨其与大肠癌肿瘤血管生成的关系.方法:2007-09/2008-05哈尔滨医科大学附属第二临床医学院内镜下取材的大肠癌、肠息肉及肠炎标本. 所有标本均经病理检查证实诊断. 试验对象共分3组, 分别为大肠癌组织26例, 大肠息肉组织10例, 大肠黏膜慢性炎症组织7例. 采用免疫组织化学方法检测Survivin,COX-2, VEGF和CD34在大肠组织中的表达.结果:Survivin, COX-2与VEGF蛋白在大肠癌组织中阳性表达率分别为76.9%, 80.8%和69.28%, 明显高于大肠息肉组与肠炎组的表达( P<0.01或0.05). 大肠癌组织中MVD(CD34)明显高于大肠息肉组与肠炎组(23.69±9.96 vs13.10±7.05, 10.43±4.24, 均P<0.01). Survivin,COX-2和VEGF蛋白在大肠癌组中的表达与MVD相关(均P<0.05), Survivin和促血管形成因子COX-2, VEGF在大肠癌组织中的表达密切相关(χ2 = 11.18, 4.72, 均P<0.005).结论:Survivin可能通过COX-2, VEGF促进大肠癌肿瘤血管的形成.