多层螺旋CT灌注成像在肾肿瘤中的应用及与分子病理学的相关性

[目的]探讨多层螺旋CT（MSCT）灌注成像在肾肿瘤诊断中的价值。[方法]59例肾肿瘤行MSCT灌注扫描．应用perfusion2软件包计算血流量（BF）、血容量（BV）、表面通透性fPS）及平均通过时间（MTT）．同时检测肾肿瘤及肿瘤旁正常组织中血管内皮生长因子（VEGF）的表达及微血管密度（MVD）,[结果]59例肾肿瘤术后病理证实为。肾癌48例,肾盂癌6例,肾血管平滑肌脂肪瘤5例。在不同级别的肾细胞癌中．其灌注参数BF、BV和PS均明显低于正常肾皮质（P〈0．01）,且高级别的肾癌灌注参数BF、BV和PS均明显高于低级别的肾癌（P〈0．01）。肾血管平滑肌脂肪瘤和肾盂癌的灌注值均明显低于肾癌,有显著性差异（P〈0．01）。肾癌的BF、BV、PS值与肿瘤的VEGF表达呈显著正相关（P〈0．01）,MTT、值与VEGF表达呈显著负相关（P〈0．01）。[结论]MSCT灌注成像能定量评价肿瘤血管生成,血管灌注及血管通透性改变,有助于肾细胞癌的术前分级．并在肾肿瘤的鉴别诊断方面具有一定的临床应用价值。     

重组人血管内皮抑制素联合TACE对兔VX-2肝癌模型微血管密度及Notch通路的影响

目的:探讨重组人血管内皮抑制素（rhES）联合经导管动脉内化疗栓塞术（TACE）对果蝇双翅边缘缺刻同源基因（Notch）通路的调控作用,及对兔VX-2肝癌模型微血管密度（MVD）的影响。方法:取新西兰大白兔60只,随机取50只用肿瘤种植法建立兔VX-2肝癌模型,分为模型组、TACE组、TACE+rhES组（TACE术+rhES溶液0.75 mg/kg）、Notch激活剂jagged1组（TACE术+jagged1溶液13 ng/kg）、TACE+rhES+jagged1组（TACE术+rhES溶液0.75 mg/kg+jagged1溶液13 ng/kg）,每组10只,未造模的10只兔作为正常对照组。治疗2周后,行CT成像,获取兔肿瘤周边血流量（BF）、血容量（BV）、毛细血管表面渗透面积（PS）值;称取兔体重并处死取肝脏,计算肝脏指数、肿瘤体积;免疫组化法检测肝脏MVD;蛋白免疫印迹法（Western blot）检测癌灶周边非坏死肝脏组织Notch、Notch配体（jagged1）、血管内皮生长因子（VEGF）、活化蛋白1（AP-1）蛋白相对表达水平。结果:与正常对照组相比,模型组兔出现饮食、活动减少及精神萎靡现象,肿瘤结节为暗红色且出现坏死、液化及囊性改变等病理损伤,肝脏指数、肿瘤体积、肝组织MVD、Notch、jagged1、VEGF、AP-1蛋白表达升高（P＜0.05）,体质量、BF、BV及PS水平下降（P＜0.05）。与模型组相比,TACE组肿瘤结节为乳白色,肿瘤体积显著下降（P＜0.05）,其余指标差异无统计学意义（P＞0.05）;jagged1组兔精神萎靡及肿瘤组织坏死程度加重,肝脏指数、肿瘤体积、MVD、Notch、jagged1、VEGF、AP-1蛋白表达升高（P＜0.05）,体质量、BF、BV及PS水平下降（P＜0.05）;TACE+rhES组兔饮食、精神等好转,肿瘤组织坏死程度减轻,肝脏指数、肿瘤体积、Notch、jagged1、VEGF、AP-1蛋白表达降低（P＜0.05）,体质量、BF、BV及PS水平升高（P＜0.05）。与TACE+rhES组相比,TACE+rhES+jagged1组上述指标变化趋势相反且有统计学差异（P＜0.05）。结论:TACE+rhES联合治疗可通过抑制Notch/jagged1信号通路激活,抵抗肝癌模型兔肿瘤血管生成。     

CTX小剂量化疗在抗肺癌血管生成中的作用

目的：研究小剂量环磷酰胺（CTX）对肺癌血管生成的影响及其机制。方法：培养人肺腺癌A549细胞，建立裸鼠移植瘤模型，随机分为小剂量CTX组、大剂量CTX组和对照组进行化疗，观察裸鼠体重变化和抑瘤效果，免疫组化检测肿瘤微血管密度（MVD）、缺氧诱导因子-1α（hypoxia-inducible factor 1 alpha，HIF-1α）和VEGF的表达。结果：小剂量组肿瘤生长缓慢，体重减轻等副作用明显小于大剂量组和对照组（P〈0．01或P〈0．05）；与大剂量组、对照组比较，小剂量组MVD、HIF-1α和VEGF表达均明显减少（P〈0．01），且小剂量组移植瘤中HIF-1α和VEGF、HIF-1α和MVD、VEGF和MVD之间均有相关性。结论：与大剂量组和对照组相比，小剂量CTX化疗组能更显著地抑制肺癌血管生成，抑瘤效果更明显，其机制可能与下调HIF-1α蛋白表达有关。     

动脉内内皮抑制素联合化疗栓塞治疗原发性肝癌后血浆VEGF水平的动态观察

目的：探讨动脉内重组入血管内皮抑制素（recombinant human endostatin，rh-endostatin）及化疗栓塞（transarterial chemoembolization，TACE）治疗原发性肝癌（hepatocellular carcinoma，HCC）对血浆血管内皮生长因子（vascular endothelial growthfactor，VEGF）表达的动态变化。方法：40例临床诊断为HCC的患者，随机分成2组，各20例，分别用rh-endostatin加TACE术或单纯TACE术治疗，所有病例均于TACE术前、术后3、7d及1个月时抽血，用ELISA法定量检测血浆中VEGF的表达水平。结果：rh-endostatin加TACE术组HCC患者血浆中VEGF表达水平术后3d明显升高，与术前比较差异有统计学意义（P=0．019），术后7d、1个月血浆中VEGF表达水平下降至与术前比较差异无统计学意义（P=0．577及P=0．740）；单纯TACE术组HCC患者血浆VEGF表达水平在术后3d、术后7d逐渐升高，与术前比较差异有统计学意义（P=0．014及P=0．002），术后1个月血浆VEGF表达水平逐渐下降，与术前比较差异无统计学意义（P=0．710）。结论：通过动态检测2组HCC患者血浆VEGF的表达水平，反映了rh-endostatin对血浆VEGF表达的影响，间接说明rh-endostatin对肿瘤血管生成有一定的抑制作用。     

兔VX2脑瘤血管生成的灌注CT研究

Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.     

尿纤溶酶原激活物及血管内皮生长因子在食管癌中的表达及对肿瘤血管形成的影响

目的探讨尿纤溶酶原激活物（uPA）、血管内皮生长因子（VEGF）在食管癌中的表达及对肿瘤血管生成的影响。方法采用免疫组织化学sP法检测正常食管黏膜上皮组织（18例）及食管癌组织（68例）中uPA、VEGF的表达,检测CD。用以标记肿瘤微血管密度（MVD）,根据MVD均值分为高、低MVD组,分析食管癌uPA、VEGF的表达和临床病理特征的关系及对肿瘤血管形成的影响。结果uPA蛋白在正常食管黏膜上皮组织、食管癌组织中的阳性率分别为27．8％（5／18）和70．6％（48／68）,差异有统计学意义（X^2=11．63,P〈0．05）;VEGF蛋白在正常食管黏膜上皮组织、食管癌组织中的阳性率分别为22．2％（4／18）和63．2％（43／68）,差异有统计学意义（X^2=9．78,P〈0．05）。食管癌组织中uPA与VEGF表达有一致性（X^2=9．72,P〈0．05）。MVD平均为42．38±11．62,高MVD组uPA、VEGF蛋白表达显著高于低MVD组（X^2值分别为6．13和10．12,均P〈0．05）。uPA、VEGF蛋白表达与年龄、性别、病理类型无关（均P〉0．05）,均与临床病理分期、分化程度和淋巴结转移相关（P〈0．05）。结论食管癌组织中uPA、VEGF蛋白高表达,可能促进肿瘤血管形成,提示预后不良。     

肿瘤相关巨噬细胞与胃癌血管生成及转移关系

[目的]探讨肿瘤相关巨噬细胞（TAMs）浸润与胃癌血管生成及转移的关系。[方法]采用免疫组织化学法检测51例胃癌组织微血管密度（MVD）、TAMs和血管内皮生长因子（VEGF）的表达。[结果]TAMs的表达在高分化癌组织中明显低于中-低分化组（P〈0．05）；淋巴结转移组高于无淋巴结转移组（P〈0．05）；TAMs与VEGF及MVD均呈正相关（r=0．74，P〈0．01：r=0．58，P〈0．05）。[结论]胃癌组织中TAMs在血管生成及肿瘤转移中可能起重要作用。     

多层螺旋CT灌注成像对肺肿瘤的临床诊断价值

目的探讨多层螺旋CT（MSCT）灌注成像对肺部肿瘤的临床诊断价值。方法回顾性分析肺内有肿瘤的患者38例,其中良性肿瘤14例,恶性肿瘤24例。对所有患者进行多层螺旋CT灌注成像扫描,采用CTperfusion3软件对数据进行处理分析。计算患者肿瘤的表面通透性（PS）,平均通过时间（MTF）,血容量（BV）以及血流量（BF）。结果在MTT与BF方面恶性肿瘤与良性肿瘤间差异无统计学意义（P〉0．05）,而在PS与BV方面恶性肿瘤与良性肿瘤间差异有统计学意义（P〈0．05）。结论多层螺旋CT灌注成像可以为良、恶性的肿瘤提供功能信息,有利于提高肺内肿瘤的临床诊断准确率。     

原发陛肾细胞癌螺旋CT多期增强扫描征象与肿瘤血管的相关性研究

目的探讨原发性肾细胞癌（RCC）螺旋CT（SCT）征象与病理、肿瘤微血管密度（MVD）、血管内皮生长因子（VEGF）表达之间的关系。方法收集经手术及病理证实的RCC30例,术前行SCT平扫及三期增强扫描,标本用免疫组织化学生物素－过氧化物酶复合法（SABC法）染色,检测肿瘤MVD及VEGF的表达。结果SCT多期增强扫描对30例RCC检出率100％,定性诊断正确率100％,术前分期正确率83．33％。MVD平均为（36±12．40）条／视野,VEGF阳性表达率73．33％。MVD与VEGF的表达无相关性（r=0．057,P〉0．05）。SCT征象：直径〉3．0cm组、瘤内有出血坏死组、无假包膜组、有静脉癌栓组,病理核分级、VEGF阳性表达及MVD均高于相对应组（P均〈0．05）。有淋巴结转移组的病理核分级及MVD均高于相对应组（P〈0．05）。CMP期RCC强化的CT值、强化程度分别与MVD呈正相关（r=0．784、P〈0．05,r=0．789,P〈0．05）。结论SCT多期增强扫描是RCC可靠的检查方法,能准确反映其病理学基础;RCC的部分征象与MVD及VEGF的表达有关,可预测RCC的侵袭和转移。     

血管内皮抑素对小鼠体内Lewis肺癌血管生成及转移影响的研究

目的：观察血管内皮抑素（Endostatin）对C57小鼠体内Lewis肺癌生长、血管生成及转移的影响。方法：将荷Lewis肺癌的C57鼠进行不同剂量组的内皮抑素和顺铂干预，观察肿瘤生长、移植瘤及转移瘤体内的血管内皮生长因子（VEGF）和微血管密度（MVD）的表达及转移发生率，并作统计学分析。结果：内皮抑素对鼠Lewis肺癌的生长有明显的抑制作用。内皮抑素处理组（内含400μg、300μg、200μg和200μg＋DDP组）和模型组转移率间的差异有统计学意义（P=0．0303）。内皮抑素能显著下调移植瘤及转移瘤内的VEGF。移植瘤中模型组与其余各组之间均存在显著差异（P〈0．01）；400μg组与200μg组、DDP组、联合用药组之间均存在统计学差异（P〈0．05）；300μg组与200组之间存在统计学差异（P〈0．05）；转移瘤中模型组与其余各组之间均存在统计学差异（P〈0．05）。300μg与200μg之间有统计学差异（P〈0．05），200μg与DDP组和200μg＋DDP组之间有统计学差异（P〈0．05）。原位移植瘤与肺转移肿瘤组织中VEGF表达呈正相关（r=0．977，P=0．001）。内皮抑素能显著下调移植瘤及转移瘤内和MVD。在移植瘤中400μg和300μg组肿瘤微血管密度最小，彼此无差异；200μg加DDP组肿瘤微血管密度次之，200μg组肿瘤微血管密度再次，DDP组肿瘤微血管密度在各实验组中最多，模型组肿瘤微血管密度最大。在转移瘤中400μg、300μg和200μg组微血管密度最小，这三组彼此无差异。200μg加DDP组肺转移瘤组织微血管密度次之，DDP组肺转移瘤组织微血管密度在各实验组中最多；模型组肿瘤微血管密度最大。内皮抑素可以减少肿瘤肺转移，作用程度在一定范围内与内皮抑素剂量呈正相关。结论：血管内皮抑素可以通过下调瘤组织中的VEGF和MVD抑制肿瘤生长及转移。     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

Second-line chemotherapy with cisplatin-ifosfamide in patients with ovarian cancer previously treated with carboplatin-cyclophosphamide.

In an effort to use antineoplastic drug combinations which are active in platinum resistant ovarian cancer or which can induce a second response after a platinum first-line treatment, we conducted a study on 30 ovarian cancer patients previously treated with carboplatin plus cyclophosphamide who were given ifosfamide 5 g/m2 i.v. divided over days 1 to 3 plus mesma combined with cisplatin 100 mg/m2 i.v. divided over days 1 to 3 every 4 weeks as second-line treatment. Eight patients had never entered remission with first-line chemotherapy while 22 patients had tumor recurrence within 6 to 18 months after the end of chemotherapy and their tumors were considered potentially platinum sensitive. Responding patients received 6 courses while palliative treatment for nonresponders was provided. Of the 22 patients with tumor recurrence, 8 patients responded with one partial response (PR) and 7 complete clinical responses (CCR). Two out of the 8 patients with platinum resistant disease demonstrated short lasting PR. Seven patients with CCR underwent second-look operation and in two a pathological CR was documented. Median time to progression was 6 mo (4-12). The median overall survival was 12 mo (4-20). Myelotoxicity despite G-CSF administration was significant with grade 4 leukopenia in 40% and grade 3 thrombocytopenia in 20% of patients. Central nervous system (CNS) toxicity was significant with 30% somnolence, 20% disorientation and an episode of grand-mal epilepsy ascribed to ifosfamide. With a 33% response rate the combination is as effective as new agents employed in relapsed ovarian cancer. Platinum-refractory disease may respond to a lesser degree. The most important determinant of response was the progression-free interval from first-line chemotherapy. Whether patients recurring after carboplatin plus cyclophosphamide have a greater chance to respond to cisplatin plus ifosfamide or vice-versa cannot be supported by the current data and therefore randomized studies should be performed to this end.     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs