Clinico-Pathological Profile and Haematological Abnormalities Associated with Lung Cancer in Bangalore,India

Background: Lung cancer is one of the most common types of cancer causing high morbidity and mortality worldwide. An increasing incidence of lung cancer has been observed in India. Objectives:To evaluate the clinicpathological profile and haematological abnormalities associated with lung cancer in Bangalore, India. Materials and Methods: This prospective study was carried out over a period of 2 years. A total of 96 newly diagnosed and histopathologically confirmed cases of lung cancer were included in the study. Results: Our lung cancer cases had a male to female ratio of 3:1. Distribution of age varied from 40 to 90 years, with a major contribution in the age group between 61 and 80 years (55.2%). Smoking was the commonest risk factor found in 69.7% of patients. The most frequent symptom was cough (86.4%) followed by loss of weight and appetite (65.6%) and dyspnea (64.5%). The most common radiological presentation was a mass lesion (55%). The most common histopathological type was squamous cell carcinoma (47.9%), followed by adenocarcinoma (28.1%) and small cell carcinoma (12.5%). Distant metastasis at presentation was seen in 53.1% patients. Among the haematological abnormalities, anaemia was seen in 61.4% of patients, leucocytosis in 36.4%, thrombocytosis in 14.5% and eosinophilia in 19.7% of patients. Haematological abnormalities were more commonly seen in non small cell lung cancer. Conclusions: Squamous cell carcinoma was found to be the most common histopathological type and smoking still remains the major risk factor for lung cancer. Haematological abnormalities are frequently observed in lung cancer patients, anaemia being the commonest of all.     

Effects of melatonin on the oxidant/antioxidant status and lung histopathology in rabbits exposed to cigarette smoke

OBJECTIVES AND BACKGROUND: To evaluate the effects of cigarette smoking on the histopathology and the oxidant/antioxidant status of the lungs and to test the potential antioxidant benefits of melatonin on these induced changes. METHODOLOGY: Rabbits were exposed to cigarette smoke in a glass chamber for 1 h daily for 1 month with or without intraperitoneal melatonin injection. A melatonin control group was given intraperitoneal melatonin only. A control group was exposed to clean air only. At the end of 1 month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulphydryls, carbonyls, prostaglandin F2alpha (PGF2alpha), malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase (SOD) were measured. RESULTS: Intraparenchymal vascular congestion and thrombosis, intraparenchymal haemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar haemorrhage scores were significantly increased in rabbits exposed to cigarette smoke compared with the control group. Protein sulphydryls and SOD levels were significantly decreased; carbonyls, PGF2alpha and MDA levels were significantly increased in the smoke exposed rabbits. Administration of melatonin to rabbits exposed to cigarette smoke caused a reduction in the bronchoalveolar haemorrhage score and blood carbonyls levels. Other parameters were unaffected by melatonin. CONCLUSION: Exposure to cigarette smoke causes severe histopathological changes and negatively affects the oxidant/antioxidant status in the lungs of rabbits. A low daily dose of melatonin has some protective effects on histopathological changes and oxidant/antioxidant status of the lungs in smoke exposed rabbits.     

Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Variability and inequity in testing of somatic tissue for hereditary cancer: a survey of UK clinical practice

A growing body of literature demonstrates the benefits of molecular pathological investigations of tumour material in the identification of individuals with hereditary non-polyposis colorectal cancer and debates the best detection strategies. This testing is novel as it is the first widespread use of somatic tissue testing to inform genetic analysis and requires the co-ordination of both histopathology and molecular genetics laboratories. However, the clinical use and experience of microsatellite instability (MSI) testing and immunohistochemical analysis have not been reported. A respondent from every cancer genetics centre in the UK (n= 24, response rate 100%) and laboratory performing MSI testing (n= 5, response rate 100%) was interviewed by telephone to ascertain test availability, testing methods, eligibility criteria and post-test management. Twenty centres (83%) offer eligible clients at least one form of tumour testing, and all use tumour testing to determine who should have access to germ line genetic testing. However, no two laboratories used the same testing methods, seven different testing strategies were applied and there was considerable variation in eligibility criteria. The implications of these variations are considered, and recommendations for the development of a consistent service for testing of somatic tissue offered.     

Tissue reactions induced by different embolising agents in cerebral arteriovenous malformations: a histopathological follow-up

AIMS: Comparative histopathological analysis was performed in 47 incompletely embolised and resected cerebral arteriovenous malformations (AVMs). METHODS: Thirty-three AVMs were embolised with n-butyl-cyanoacrylate (NBCA), four with iso-butyl-cyanoacrylate (IBCA), seven with polyvinyl alcohol particles (PVA), one with a fibrin mixture, one with silicon pellets, and one with microcatheter balloons. Maximum exposure time (MET) of the embolising agent (interval between embolisation and surgery) ranged from <24 hours to 80 months. All AVMs were investigated regarding angionecrosis, angiofibrosis, acute inflammation, chronic inflammation, foreign-body reactions, vascular calcification, blood admixture to embolising cast, and capillary recanalisation within the AVMs. These parameters were correlated with MET, comparing different embolising agents, age, and sex. RESULTS: A typical sequence of events depending on MET is observed in all embolised AVMs: acute inflammation with mural angionecrosis is soon replaced by prominent chronic granulomatous vasculitis, which remains stable and is detectable for a very long time, even in AVMs with a MET of more than 6 years. CONCLUSION: Capillary recanalisation is always present in incompletely embolised AVMs, detectable after 3 months of MET, irrespective of the embolising agent used. Age and sex does not influence pattern and time course of tissue lesions and recanalisation in incompletely embolised AVMs.     

Dynamic diffusion tensor imaging of spinal cord contusion: A canine model

This study aimed to explore the dynamic diffusion tensor imaging (DTI) of changes in spinal cord contusion using a canine model of injury involving rostral and caudal levels. In this study, a spinal cord contusion model was established in female dogs using a custom‐made weight‐drop lesion device. DTI was performed on dogs with injured spinal cords (n=7) using a Siemens 3.0T MRI scanner at pre‐contusion and at 3 h, 24 h, 6 weeks and 12 weeks post‐injury. The tissue sections were stained for immunohistochemical analysis. Canine models of spinal cord contusion were created successfully using the weight‐drop lesion device. The fractional anisotropy (FA) value of lesion epicenter decreased, while the apparent diffusion coefficient (ADC), mean diffusivity (MD), and radial diffusivity (RD) values increased, and the extent of the curve was apparent gradually. The site and time affected the DTI parameters significantly in the whole spinal cord, ADC (site, P < 0.001 and time, P = 0.077, respectively); FA (site, P < 0.001 and time, P = 0.002, respectively). Immunohistological analysis of GFAP and NF revealed the pathologic changes of reactive astrocytes and axons, as well as the cavity and glial scars occurring during chronic SCI. DTI is a sensitive and noninvasive imaging tool useful to assess edema, hemorrhage, cavity formation, structural damage and reconstruction of axon, and myelin in dogs. The DTI parameters after contusion vary. However, the curves of ADC, MD, and RD were nearly similar and the FA curve was distinct. All the DTI parameters were affected by distance and time.     

慢性乙型肝炎患者临床和肝组织病理学特点及影响肝纤维化因素分析*

目的 分析HBeAg阴性与阳性慢性乙型肝炎（CHB）患者临床和肝组织病理学特点,探讨影响CHB患者发生明显肝纤维化的危险因素。方法 回顾性分析250例CHB患者血清HBV DNA水平、Fibroscan检测肝脏硬度（stiffness）值和肝穿刺组织病理学特点,应用多因素Logistic回归模型分析影响CHB患者发生明显肝纤维化的独立危险因素。结果 160例HBeAg阴性患者血清HBV DNA ≥1×10⁵ copies/ml者所占比例显著低于HBeAg阳性组（66.9%对99.4%,P<0.05）;HBeAg阴性组血清ALT和AST水平显著低于HBeAg阳性组（P<0.05）;血清HBeAg阴性组与阳性组肝组织炎症分级和纤维化分期总体分布差异无统计学意义（P>0.05）;多因素Logistic回归分析结果显示年龄≥40岁、HBV DNA水平高、PTA低和Stiffness水平高为CHB患者存在明显肝纤维化的独立危险因素。结论 血清HBeAg阴性与阳性CHB患者存在一些临床和肝组织病理学特征的差异,血清HBeAg阴性患者可能存在更为严重的临床和预后问题,需要给予特别的关注和管理。     

慢性乙型肝炎病毒携带者血清GP73水平与肝组织病理学变化的关系研究*

目的 探讨慢性乙型肝炎病毒携带者血清高尔基体蛋白73（GP73）水平与肝组织病理学变化的关系。方法 2014年1月~2016年12月我院诊治的慢性HBV携带者150例、慢性乙型肝炎患者150例和乙型肝炎肝硬化患者150例,另选同期健康人50例,采用ELISA法检测GP73水平,对150例慢性HBV携带者进行肝穿刺活检,采用Metavir评分对肝组织炎症和纤维化进行评价。结果 慢性HBV携带者血清GP73水平为（46.5±7.8） ng/ml,慢性乙型肝炎组为（90.2±10.9） ng/ml,乙型肝炎肝硬化组为（231.6±20.1） ng/ml,均显著高于健康人组的（36.7±6.6） ng/ml,差异有统计学意义（P<0.05）,肝硬化患者血清GP73水平也显著高于慢性乙型肝炎或HBV携带者（P<0.05）;经肝组织检查,150例慢性HBV携带者肝内炎症活动度分级和纤维化分期表现为G₀~G₁ 105例,G₂ 30例,G₃~G₄ 15例,其血清GP73水平分别为（45.2±12.8）ng/ml、（63.8±15.0）ng/ml和（83.7±20.1）ng/ml,S₀~S₁ 98例,S₂ 3₀例,S₃~S₄ 22例,其血清GP73水平分别为（45.1±16.8）ng/ml、（67.3±16.4）ng/ml和（72.0±18.4）ng/ml,肝组织炎症活动度分级和纤维化分期严重的患者血清GP73水平显著升高,与分级或分期轻的人群比,差异有统计学意义（F=16.8,F=19.2,P均<0.05）;Logistic回归分析发现血清GP73水平升高是慢性HBV携带者肝组织显著炎症（OR=1.1,95 % CI:1.0~1.1,P<0.05）和显著肝纤维化（OR=2.1,95% CI:0.8~1.2,P<0.05）的高危因素。结论 检测血清GP73水平可能有助于对慢性HBV携带者肝组织炎症分级和纤维化分期的判断,能否作为预测慢性HBV携带者肝组织炎症分级和纤维化分期的潜在标志物,还需要扩大验证。     

致病性小肠结肠炎耶尔森菌外膜蛋白A对SD大鼠免疫保护作用研究

目的 研究致病性小肠结肠炎耶尔森菌外膜蛋白A(OmpA)对大鼠的免疫保护作用,为研制疫苗提供技术基础。方法 将SD大鼠随机分为3组,通过腹股沟注射方式对大鼠进行免疫,包括OmpA免疫组(OmpA+弗氏不完全佐剂)、对照组(PBS+弗氏不完全佐剂)和空白对照组(未做任何处理)。经首次免疫(0.58 mg/只)和加强免疫(1 mg/只)后,用两个浓度的致病性小肠结肠炎耶尔森菌Ye92010(10⁶ CFU、10⁸ CFU)对OmpA免疫组和对照组进行攻毒,观察攻毒后各组大鼠的体征、排菌情况以及组织病理学改变。结果 攻毒后OmpA免疫组与对照组大鼠均出现厌食、被毛杂乱、粪便呈松软非颗粒状等症状。OmpA免疫组大鼠粪便排菌时间均为14 d,对照组大鼠粪便排菌时间分别为17 d(低剂量攻毒)和21 d(高剂量攻毒)。OmpA免疫组的肝、脾、肠组织病变程度相对较轻,组织变性及坏死灶情况明显优于对照组。结论 结合各组大鼠粪便排菌时间和大体观察结果,表明实验大鼠经OmpA免疫后可有效抵御致病性小肠结肠炎耶尔森菌的肠道定植,且组织病理学改变明显减轻,提示OmpA对SD大鼠具有良好的免疫保护作用。     

Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct

An 85-year-old woman diagnosed with amyotrophic lateral sclerosis died of pneumonia and was autopsied. Magnetic resonance imaging (MRI) performed 16 days before death revealed an intracortical high-intensity lesion in her right temporal cortex on three-dimensional (3D)-double inversion recovery (DIR) and 3D-fluid-attenuated inversion recovery (FLAIR) images. Histopathological examination indicated a cortical microinfarct (CMI) juxtaposed to cerebral amyloid angiopathy. Recently, in vivo detection of CMIs using 3D-DIR and 3D-FLAIR on 3-tesla MRI has been reported, and postmortem MRI study confirmed the presence of CMIs. This is the first case study to compare CMI findings detected upon premortem MRI to the CMI itself discovered upon postmortem neuropathological examination.