Reproducibility of perfusion CT derived CBV and rCBV measurements with different slice thickness in patients with brain neoplasms

Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.

Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients

AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.

Brain metastasis of hepatocellular carcinoma:A case report and review of the literature

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy it accounts for only 1-2% of malignant rumors, The disease is usually manifested in the the 6^th and 7^th decade of life. HCC is one of the highly malignant neoplasms, Extrahepatic metastases are seen in 64% of patients with HCC. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of HCC metastasis^[1-3], But, metastasis to brain and skull is extremely rare. Table I shows some of the reported cases of HCC with brain metastasis. These case reports reaffirms the complex and multidisciplinary care of these patients^[4-5].

Occludin and connexin 43 expression contribute to the pathogenesis of traumatic brain edema

The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney＇s free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Changes in brain water content were determined using the wet and dry weights. Our results showed that water content of tissue significantly increased after traumatic brain injury, and reached minimum at 24 hours. Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury, particularly at 3 days, with nerve cell edema, degenera- tion, and necrosis observed, and the apoptotic rate significantly increased. Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually de- creased as injury time advanced and reached a minimum at 3 days after injury; the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after in-jury. The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema, and may reflect the pathogenesis of brain injury.

Studies on Parkinson’s-Disease-Linked Genes, Brain Urea Levels and Histopathology in Rotenone Induced Parkinson’s Disease Rat Model

Parkinson’s disease (PD) is a debilitating neurological disorder that affects the aged population globally. This study aimed to explore how oral- and intraperitoneal-rotenone-induced PD alters brain urea levels, histopathology, and key Parkinsonism-related genes in the striatum. Hematoxylin and eosin staining was performed for histopathology assessment and real-time polymerase chain reaction was performed for gene expression. Rotenone 3 mg/kg body weight (Rot-3-ip) for 21 days and rotenone 50 mg/kg body weight (Rot-50-po) for 28 days significantly (p < 0.05) altered alpha-synuclein and tyrosine hydroxylase protein expression and Snca, Becn1 and Prkaa1 gene expression in the striatum. Lewy bodies were visible in both Rot-3-ip and Rot-50-po rat brains. There were contrasting features in brain and liver histopathology between the oral and intraperitoneal rotenone treatment groups. However, there was no significant (p < 0.05) difference in the brain urea levels between intraperitoneal and oral rotenone treatment groups. The propagation of PD through oral and intraperitoneal rotenone can have different impacts on the pathological sequence of events based on the molecular approach.

Parent’s Perceived Provision of Information Regarding Diagnosis to Children with Brain Tumors

Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2 - 4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5 - 11 years were provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12 - 18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety, Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.

^(99)mTc-DTPA断层显像在全脑放疗血脑屏障通透性研究中的应用

目的研究脑转移瘤全脑放疗中血脑屏障变化规律,为全脑放疗过程中化疗的介入时机提供影像学依据。方法对接受6MVX射线全脑外照射的20例脑转移瘤患者,在放射治疗前、放射治疗20Gy、40Gy及放射治疗结束后2周采用99mTc-DTPA核素进行脑断层显像,选择一帧显示肿瘤最好的横断层像,于肿瘤区(T)、对侧正常脑组织区(N)以及颅骨周围软组织外本底区(B)设置相同的感兴趣区,采集各区的放射性计数,分别计算放疗前、放疗20Gy、40Gy及放疗结束后2周时病灶、受到照射的正常脑组织部位的计数与本底区域计数的比值。结果放疗前20例患者其30个脑转移瘤的比值T/B和N/B分别为(142.2±51.1),(82.6±42.3);放疗20Gy时其比值分别为(260.3±121.5),(150.7±72.5);放疗40Gy时其比值分别为(251.6±118.3),(161.8±68.4);放疗结束后2周其比值分别为(250.3±117.2),(158.6±73.5)。20Gy组、40Gy组及放疗结束后2周组分别与放疗前组比较差异均有统计学意义(P<0.05),但20Gy组、40Gy组及放疗结束后2周组两两比较差异无统计学意义(P>0.05)。结论放射线具有降低血脑屏障功能的作用,照射20～40Gy及放疗结束后2周内其通透性明显增加,故20～40Gy及放疗结束后2周内均可成为化疗介入时机。

COX-2、u-PA和TSP-1在胃癌及周围淋巴结中的表达及意义

目的:研究COX-2、u-PA和TSP-1在胃癌及周围淋巴结中的表达状况,探讨它们在胃癌浸润和淋巴结转移中的作用和意义。方法:用组织芯片技术和免疫组化法检测COX-2、u-PA和TSP-1的表达。结果:COX-2、u-PA和TSP-1在胃癌组阳性表达率分别为67.7%、78.1%和78.6%,均显著高于对照组(40.0%、6.7%和40.0%,P<0.05)。COX-2表达与浸润深度有关(P<0.05)。u-PA表达与浸润深度和淋巴结转移均有关(P<0.05)。TSP-1表达与浸润深度和淋巴结转移均无关(P>0.05)。COX-2、u-PA和TSP-1在转移淋巴结和对应癌组织间的表达差异无显著性(P>0.05)。COX-2和u-PA、TSP-1的表达呈正相关,u-PA和TSP-1的表达无相关关系。结论:胃癌中COX-2、u-PA和TSP-1高表达;COX-2表达与胃癌的浸润深度有关,u-PA表达与浸润深度和淋巴结转移有关。

EPAS1、VEGF在胰腺癌中表达及其相关性

目的研究胰腺癌组织中缺氧诱导因子2(EPAS1/HIF-2α)、血管内皮生长因子(VEGF)和微血管密度(MVD)的表达及与临床病理特征之间的关系。方法应用逆转录聚合酶链反应(RT-PCR)、免疫印迹Western blot、免疫组化SP法检测60例胰腺癌及相应正常胰腺组织中EPAS1、VEGF mRNA和蛋白的表达和分布,同时检测MVD作为判断血管生成的指标,分析其间的相关性以及与肿瘤临床病理特征之间的关系。结果EPAS1、VEGF和MVD在胰腺癌组织中的表达明显高于正常胰腺组织,VEGF在mRNA和蛋白水平均增高(P<0.01),但EPAS1只在蛋白水平增高(P<0.01)。此外,三者之间的表达具有显著相关性(P<0.01)。EPAS1和VEGF的阳性表达与胰腺癌的TNM分期、肿瘤大小有关。结论胰腺癌组织中EPAS1和VEGF呈过量表达,且EPAS1的表达与VEGF及MVD呈显著正相关。EPAS1可通过上调VEGF表达来促进胰腺癌血管生成从而在胰腺癌的发生、发展中起重要作用。

Gd-DTPA对脑肿瘤扩散张量成像观测指标的影响

目的评价钆喷替酸葡甲胺(Gd-DTPA)对脑肿瘤扩散张量成像(DTI)观测指标表观扩散系数(ADC)值和部分各向异性分数(FA)值的影响。方法对27例经手术病理或临床证实的脑肿瘤患者术前行常规MRI及DTI检查,DTI分别于Gd-DTPA注入前、注入后即刻和7min进行。分别测量肿瘤强化区、瘤周水肿区、对侧正常脑组织及正常胼胝体的ADC值和FA值,并进行统计学分析。结果肿瘤强化区ADC值、FA值在增强前与增强后即刻及增强前与增强后7min间比较,差异均有统计学意义(P均<0.01),但增强后即刻与增后7min比较,差异无统计学意义(P>0.05);瘤周水肿区、对侧正常脑组织和胼胝体压部ADC值、FA值在增强前、增强后即刻及增强后7min间两两比较,差异均无统计学意义(P均>0.05)。结论静脉注入Gd-DTPA后可致肿瘤强化部分ADC值明显降低和FA值明显升高。如需进行DTI,应尽量在增强扫描前完成。

盐酸右美托咪定联合酒石酸布托啡诺对老年创伤性颅脑患者应激状态及NPAS4、NSE的影响

目的探讨盐酸右美托咪定(DHI)联合酒石酸布托啡诺(BTI)对老年创伤性颅脑患者应激状态及血清神经元PAS结构域蛋白4(NPAS4)、神经元特异性烯醇化酶(NSE)的影响。方法回顾性选取上海市浦东新区人民医院2017年1月至2019年1月收治的老年创伤性颅脑患者101例作为研究对象,按治疗方法不同分成A、B、C组,各35例、34例、32例,其中A组单纯予以DHI治疗,B组单纯予以BTI治疗,C组联合(DHI联合BTI)治疗。分析给药前、给药后1d、给药后3d时3组患者平均动脉压(MAP)、心率、C反应蛋白(CRP)水平、白细胞介素-6(IL-6)水平以及NPAS4和NSE蛋白表达的变化。结果①给药前3组患者MAP、心率、CPR水平、IL-6水平、NPAS4和NSE蛋白表达量比较,差异均无统计学意义(P>0.05);给药后1、3d时的MAP、心率、CPR水平、IL-6水平及NPAS4和NSE蛋白表达量均较给药前明显下降,差异有统计学意义(P<0.05);A组与B组给药后1、3d时上述指标比较,差异无统计学意义(P>0.05);C组上述指标均显著低于A、B组,差异有统计学意义(P<0.05)。②Logistic回归分析发现,MAP、心率、CPR、IL-6与创伤性颅脑损伤呈正相关(OR=0.351、0.671、0.642、0.637,P<0.05),NPAS4、NSE与创伤性颅脑损伤呈负相关(OR=-0.692、-0.475,P<0.05)。结论在老年创伤性颅脑损伤患者的临床治疗中,科学、合理地予以DHI联合BTI治疗能有效地改善患者的应激状态及NPAS4、NSE蛋白表达量,有较好的临床应用与推广价值。

基质降解酶u-PA、PAI-1与人口腔鳞状细胞癌细胞侵袭转移的相关性研究

目的 探讨体外培养细胞系TSCCa和GNM细胞的u -PA及PAI - 1活性和表达与口腔鳞状细胞癌侵袭转移的关系。方法 采用酶联免疫反应法和免疫组化法测定了两细胞系中u -PA及PAI - 1的活性和表达 ,同时对GNM细胞在BALB/CA裸鼠皮下种植瘤组织的u -PA及PAI - 1抗原表达进行了测定。结果 两细胞系均能产生u -PA及PAI- 1,但u -PA在两细胞系中的表达不同 ,在GNM细胞u -PA为高表达 ,在TSCCa细胞中u -PA为低表达 ,PAI- 1在两细胞系中均为高表达 ;种植瘤组织中u -PA呈阳性～强阳性表达 ,PAI- 1为阴性表达。结论 u

PAX8、ASAH1、Cullin7在脑胶质瘤患者癌组织与癌旁组织中的蛋白表达及与生存状况的相关性分析

【目的】探究配对盒基因8(PAX8)、酸性神经酰胺酶(ASAH1)、Cullin7在脑胶质瘤(GC)患者癌组织与癌旁组织中的蛋白表达情况及与生存状况的相关性。【方法】选取2014年1月至2017年7月本院收治的75例GC患者,均行手术切除,比较癌组织与癌旁组织中PAX8、ASAH1、Cullin7蛋白表达情况,分析三者表达之间相关性,并分析三者与临床病理特征的相关性。分析PAX8、ASAH1、Cullin7蛋白表达与患者3年生存率的相关性。【结果】癌组织中PAX8、ASAH1、Cullin7蛋白阳性表达率高于癌旁组织,差异有统计学意义(P<0.05);PAX8蛋白与ASAH1蛋白呈正相关,ASAH1蛋白与Cullin7蛋白呈正相关,Cullin7蛋白与PAX8蛋白呈正相关(P<0.05);PAX8、ASAH1、Cullin7蛋白与GC患者病理类型、病理分级、分化程度、浸润深度、瘤周水肿显著相关(P<0.05);PAX8、ASAH1、Cullin7蛋白阳性表达与3年生存率呈负相关(P<0.05)。【结论】GC患者癌组织PAX8蛋白、ASAH1蛋白、Cullin7蛋白均呈阳性表达,并与生存状况存在负相关性。

脑泰方提取物干预大鼠脑缺血后MMP-9-mRNA及PA-mRNA表达研究

目的研究大鼠脑缺血后益气活血中药脑泰方提取物(黄芪、川芎、地龙、僵蚕)干预对缺血区脑水肿及MMP-9-mRNA、PA-mRNA表达的影响。方法随机将SD大鼠分为假手术组、模型组、脑泰方提取物(NTE)低、中、高剂量组(3,9,27g/kg)。各组大鼠预处理ig给药连续3d,每日1次,MCAO模型制备术后ig给药1d。术后1d取材检测各组脑组织含水量,RT-PCR检测MMP-9-mRNA及PA-mRNA表达。结果实验表明高、中NTE组与模型组比较,脑含水量均有明显降低(P<0.05)。NTE高剂量组脑缺血区MMP-9-mRNA、PA-mRNA表达明显降低(P<0.05)。结论脑泰方提取物干预可减轻脑水肿的发生,可能是通过降低MMP-9-mRNA及PA-mRNA的表达,减少MMP-9、PA的生成,发挥保护急性脑缺血血脑屏障的作用。

凋亡相关蛋白Livin及Caspase-3在膀胱移行细胞癌中的表达及临床意义

【目的】探讨凋亡相关蛋白Livin及Caspase-3在膀胱移形细胞癌(BTCC)中的表达及其临床意义。【方法】应用SP免疫组织化学法检测55例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Livin和Caspase-3表达的情况,结合临床资料进行分析,并探讨两者相关性。【结果】Livin在膀胱移形细胞癌标本中的表达阳性率为76.4%(42/55),而正常对照组中无一例呈阳性表达;Caspase-3在膀胱移行细胞癌标本中的表达阳性率为32.7%(18/55),与对照组阳性率90%(9/10)相比差异有统计学意义(P<0.05)。Livin的表达与膀胱移行细胞癌的初发和复发显著相关(P<0.05),但与组织学分级、临床病理分期、转移与否、肿瘤数目无关;Caspase-3的表达与膀胱移行细胞癌的初发复发、组织学分级、临床病理分期、转移与否、肿瘤数目均无关。相关性分析表明,膀胱移行细胞癌中的Livin表达与Caspase-3表达呈负相关。【结论】Livin蛋白与膀胱癌的发生和复发有关,可作为BTCC早期诊断和评判术后高复发风险的一项重要指标,且Livin的高表达和Caspase-3蛋白的低表达在膀胱移行细胞癌的发生发展起着重要作用。

膀胱移行细胞癌组织中HPA、VEGF基因的表达及其意义

【目的】研究膀胱移行细胞癌（BTCC）组织中乙酰肝素酶（HPA）及血管内皮细胞生长因子（VEGFmRNA）的表达及其临床意义。【方法】应用RT—PCR技术检测62例BTCC组织中HPAmRNA及VEGF mRNA表达，并以12例正常膀胱组织作对照，分析HPAmRNA表达与肿瘤部分临床、病理学特征的关系，并分析HPA与VEGF表达的相关性。【结果】12例正常膀胱组织未发现HPAmRNA阳性表达，BTCC组织中HPAmRNA阳性表达率为58．06％（36／62）。其表达与肿瘤的病理分级、临床分期、淋巴结转移及复发明显相关。而且，HPA与VEGF二者的表达具有明显相关性（r=0．501，P〈0．01）。【结论]HPAmRNA阳性表达与BTCC侵袭转移密切相关，HPA在BTCC组织中过度表达可能通过释放VEGF促进肿瘤血管生成。

急性脑梗死rt-PA溶栓治疗后血浆BNP的变化及临床意义

目的探讨rt-PA溶栓后脑梗死患者血浆脑钠肽(BNP)水平变化及对复发预测的临床意义。方法对36例急性脑梗死行rt-PA溶栓治疗后观察不同时间血浆BNP水平,比较溶栓再通组和溶栓未通组之间及复发组和未复发组之间的BNP水平的差异。结果溶栓再通组和溶栓未通组之间血浆BNP水平在24h、3d及14d有显著差异,溶栓未通组患者BNP水平较溶栓再通组高,差异有统计学意义(P<0.01);死亡组患者血浆BNP水平较存活组高,差异有统计学意义(P<0.05);复发组与未复发组之间血浆BNP水平差异无统计学意义(P>0.05)。结论溶栓治疗再通后能显著降低急性脑梗死患者血浆BNP水平,血浆BNP可作为脑梗死溶栓治疗再通和死亡风险的预测指标之一;同时对于预测该类患者复发尚无明确预测意义。

颅内肿瘤大剂量Gd-DTPA MR灌注成像的临床应用及安全性

目的探讨颅内肿瘤大剂量Gd-DTPA MR灌注成像的应用价值及安全性。方法收集经病理证实的颅内肿瘤36例,其中低级别胶质瘤（Ⅰ-Ⅱ级）15例,高级别胶质瘤（Ⅲ-Ⅳ级）12例,脑膜瘤7例,胆脂瘤1例,脉络丛乳头状瘤1例,使用FID-EPI序列行Gd-DTPA灌注成像。在脑血流容积的伪彩色图像上测得肿瘤的rCBV值,并对各组肿瘤的rCBV值进行统计学t检验;记录注药后患者的表现及不良反应,评价大剂量Gd-DTPA灌注的安全性。结果低级别胶质瘤与高级别胶质瘤的rCBV值,低级别胶质瘤与脑膜瘤的rCBV值比较有统计学意义（P〈0.05）,而高级别胶质瘤与脑膜瘤的rCBV值比较没有统计学意义（P〉0.05）。1例脉络丛乳头状瘤的rCBV值为9.15,表现为高灌注;1例胆脂瘤的rCBV值为0.09,表现为低灌注;36例灌注患者未见药物过敏反应。结论大剂量Gd-DTPA的MR灌注成像有助于脑胶质瘤的分级及与其他颅内肿瘤的鉴别诊断,临床应用的安全性良好。