Residential dissonance and mode choice

Residential dissonance refers to the mismatch in land-use patterns between individuals’ preferred residential neighbourhood type and the type of neighbourhood in which they currently reside. Current knowledge regarding the impact of residential dissonance is limited to short-term travel behaviours in urban vs. suburban, and rural vs. urban areas. Although the prevailing view is that dissonants adjust their orientation and lifestyle around their surrounding land use over time, empirical evidence is lacking to support this proposition. This research identifies both short-term mode choice behaviour and medium-term mode shift behaviour of dissonants in transit oriented development (TODs) vs. non-TOD areas in Brisbane, Australia. Natural groupings of neighbourhood profiles (e.g. residential density, land use diversity, intersection density, cul-de-sac density, and public transport accessibility levels) of 3957 individuals were identified as living either in a TOD (510 individuals) or non-TOD (3447 individuals) areas in Brisbane using the TwoStep cluster analysis technique. Levels of dissonance were measured based on a factor analysis of 16 items representing the travel attitudes/preferences of individuals. Two multinomial logistic (MNL) regression models were estimated to understand mode choice behaviour of (1) TOD dissonants, and (2) non-TOD dissonants in 2009, controlling for socio-demographics and environmental characteristics. Two additional MNL regression models were estimated to investigate mode shift behaviour of (3) TOD dissonants, and (4) non-TOD dissonants between 2009 and 2011, also controlling for socio-demographic, changes in socio-demographic, and built environmental factors. The findings suggest that travel preference is relatively more influential in transport mode choice decisions compared with built environment features. Little behavioural evidence was found to support the adjustment of a dissonant orientation toward a particular land use feature and mode accessibility they represent (e.g. a modal shift to greater use of the car for non-TOD dissonants). TOD policies should focus on reducing the level of dissonance in TODs in order to enhance transit ridership.

Optical and biomechanical factors, associated with near work and myopia

Near work may play an important role in the development of myopia in the younger population. The prevalence of myopia has also been found to be higher in occupations that involve substantial near work tasks, for example in microscopists and textile workers. When nearwork is performed, it typically involves accommodation, convergence and downward gaze. A number of previous studies have examined the effects of accommodation and convergence on changes in the optics and biometrics of the eye in primary gaze. However, little is known about the influence of accommodation on the eye in downward gaze. This thesis is primarily concerned with investigating the changes in the eye during near work in downward gaze under natural viewing conditions. To measure wavefront aberrations in downward gaze under natural viewing conditions, we modified a commercial Shack-Hartmann wavefront sensor by adding a relay lens system to allow on-axis ocular aberration measurements in primary gaze and downward gaze, with binocular fixation. Measurements with the modified wavefront sensor in primary and downward gaze were validated against a conventional aberrometer using both a model eye and in 9 human subjects. We then conducted an experiment to investigate changes in ocular aberrations associated with accommodation in downward gaze over 10 mins in groups of both myopes (n = 14) and emmetropes (n =12) using the modified Shack-Hartmann wavefront sensor. During the distance accommodation task, small but significant changes in refractive power (myopic shift) and higher order aberrations were observed in downward gaze compared to primary gaze. Accommodation caused greater changes in higher order aberrations (in particular coma and spherical aberration) in downward gaze than primary gaze, and there was evidence that the changes in certain aberrations with accommodation over time were different in downward gaze compared to primary gaze. There were no obvious systematic differences in higher order aberrations between refractive error groups during accommodation or downward gaze for fixed pupils. However, myopes exhibited a significantly greater change in higher order aberrations (in particular spherical aberration) than emmetropes for natural pupils after 10 mins of a near task (5 D accommodation) in downward gaze. These findings indicated that ocular aberrations change from primary to downward gaze, particularly with accommodation. To understand the mechanism underlying these changes in greater detail, we then extended this work to examine the characteristics of the corneal optics, internal optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 mins. Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure corneal topography and ocular biometrics in downward gaze, a rotating Scheimpflug camera and an optical biometer were inclined on a custom built, height and tilt adjustable table. We found that both corneal optics and internal optics change with downward gaze, resulting in a myopic shift (~0.10 D) in the spherical power of the eye. The changes in corneal optics appear to be due to eyelid pressure on the anterior surface of the cornea, whereas the changes in the internal optics (an increase in axial length and a decrease in anterior chamber depth) may be associated with movement of the crystalline lens, under the action of gravity, and the influence of altered biomechanical forces from the extraocular muscles on the globe with downward gaze. Changes in axial length with accommodation were significantly greater in downward gaze than primary gaze (p < 0.05), indicating an increased effect of the mechanical forces from the ciliary muscle and extraocular muscles. A subsequent study was conducted to investigate the changes in anterior biometrics, axial length and choroidal thickness in nine cardinal gaze directions under the actions of the extraocular muscles. Ocular biometry measurements were obtained from 30 young adults (10 emmetropes, 10 low myopes and 10 moderate myopes) through a rotating prism with 15° deviation, along the foveal axis, using a non-contact optical biometer in each of nine different cardinal directions of gaze, over 5 mins. There was a significant influence of gaze angle and time on axial length (both p < 0.001), with the greatest axial elongation (+18 ± 8 μm) occurring with infero-nasal gaze (p < 0.001) and a slight decrease in axial length in superior gaze (−12 ± 17 μm) compared with primary gaze (p < 0.001). There was a significant correlation between refractive error (spherical equivalent refraction) and the mean change in axial length in the infero-nasal gaze direction (Pearson's R2 = 0.71, p < 0.001). To further investigate the relative effect of gravity and extraocular muscle force on the axial length, we measured axial length in 15° and 25° downward gaze with the biometer inclined on a tilting table that allowed gaze shifts to occur with either full head turn but no eye turn (reflects the effect of gravity), or full eye turn with no head turn (reflects the effect of extraocular muscle forces). We observed a significant axial elongation in 15° and 25° downward gaze in the full eye turn condition. However, axial length did not change significantly in downward gaze over 5 mins (p > 0.05) in the full head turn condition. The elongation of the axial length in downward gaze appears to be due to the influence of the extraocular muscles, since the effect was not present when head turn was used instead of eye turn. The findings of these experiments collectively show the dynamic characteristics of the optics and biometrics of the eye in downward gaze during a near task, over time. These were small but significant differences between myopic and emmetropic eyes in both the optical and biomechanical changes associated with shifts of gaze direction. These differences between myopes and emmetropes could arise as a consequence of excessive eye growth associated with myopia. However the potentially additive effects of repeated or long lasting near work activities employing infero-nasal gaze could also act to promote elongation of the eye due to optical and/or biomechanical stimuli.

Incidence of hypotony and sympathetic ophthalmia following trans scleral cyclophotocoagulation for glaucoma and a report of risk factors

Background: To report the incidence and risk factors for hypotony and estimate the risk of sympathetic ophthalmia following diode laser trans-scleral cyclophotocoagulation (TSCPC). Design: Retrospective study using data from a private tertiary glaucoma clinic and review of the literature. Participants: Seventy eyes of 70 patients with refractory glaucoma who received TSCPC treatment. Methods: Review of the records of consecutive patients who underwent TSCPC by a single ophthalmic surgeon and review of the literature. Main Outcome Measures: Hypotony (including phthisis bulbi), sympathetic ophthalmia. Results: Seven eyes (10%; CI 5-19%) developed hypotony and included 4 eyes that developed phthisis. Higher total energy delivered during TSCPC treatment was associated with an increased risk of hypotony: eyes that developed hypotony received a mean total energy of 192.5 ± 73.2 joules, compared to a mean of 152.9 ± 83.2 joules in hypotony-free cases. The difference in mean energy delivered between the hypotony and non-hypotony group was 38.53 (95% CI: -27.57 to 104.63). The risk of sympathetic ophthalmia estimated from a review of the published literature and current series was one in 1512, or 0.07% (CI 0.03% - 0.17%). Conclusions: Total laser energy is one of several risk factors that act in a sufficient component cause-model to produce hypotony in an individual patient. The small sample size precluded inference for other individual putative risk factors but titrating laser energy may help decrease the occurrence of hypotony. The risk of sympathetic ophthalmia calculated from the literature is likely an overestimate caused by publication bias.

Prevalence, trends and associated socio-economic factors of obesity in South Asia

Aim Worldwide obesity levels have increased unprecedentedly over the past couple of decades. Although the prevalence, trends and associated socio-economic factors of the condition have been extensively reported in Western populations, less is known regarding South Asian populations. Methods A review of articles using Medline with combinations of the MeSH terms: 'Obesity', 'Overweight' and 'Abdominal Obesity' limiting to epidemiology and South Asian countries. Results Despite methodological heterogeneity and variation according to country, area of residence and gender , the most recent nationally representative and large regional data demonstrates that without any doubt there is a epidemic of obesity, overweight and abdominal obesity in South Asian countries. Prevalence estimates of overweight and obesity (based on Asian cut-offs: overweight ≥ 23 kg/m(2), obesity ≥ 25 kg/m(2)) ranged from 3.5% in rural Bangladesh to over 65% in the Maldives. Abdominal obesity was more prevalent than general obesity in both sexes in this ethnic group. Countries with the lowest prevalence had the highest upward trend of obesity. Socio-economic factors associated with greater obesity in the region included female gender, middle age, urban residence, higher educational and economic status. Conclusion South Asia is significantly affected by the obesity epidemic. Collaborative public health interventions to reverse these trends need to be mindful of many socio-economic constraints in order to provide long-term solutions.

Validity of dietary questionnaires in Sri Lankan adults and the association of dietary intake with obesity

Traditionally, infectious diseases and under-nutrition have been considered major health problems in Sri Lanka with little attention paid to obesity and associated non-communicable diseases (NCDs). However, the recent Sri Lanka Diabetes and Cardiovascular Study (SLDCS) reported the epidemic level of obesity, diabetes and metabolic syndrome. Moreover, obesity-associated NCDs is the leading cause of death in Sri Lanka and there is an exponential increase in hospitalization due to NCDs adversely affecting the development of the country. Despite Sri Lanka having a very high prevalence of NCDs and associated mortality, little is known about the causative factors for this burden. It is widely believed that the global NCD epidemic is associated with recent lifestyle changes, especially dietary factors. In the absence of sufficient data on dietary habits in Sri Lanka, successful interventions to manage these serious health issues would not be possible. In view of the current situation the dietary survey was undertaken to assess the intakes of energy, macro-nutrients and selected other nutrients with respect to socio demographic characteristics and the nutritional status of Sri Lankan adults especially focusing on obesity. Another aim of this study was to develop and validate a culturally specific food frequency questionnaire (FFQ) to assess dietary risk factors of NCDs in Sri Lankan adults. Data were collected from a subset of the national SLDCS using a multi-stage, stratified, random sampling procedure (n=500). However, data collection in the SLDCS was affected by the prevailing civil war which resulted in no data being collected from Northern and Eastern provinces. To obtain a nationally representative sample, additional subjects (n=100) were later recruited from the two provinces using similar selection criteria. Ethical Approval for this study was obtained from the Ethical Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka and informed consent was obtained from the subjects before data were collected. Dietary data were obtained using the 24-h Dietary Recall (24HDR) method. Subjects were asked to recall all foods and beverages, consumed over the previous 24-hour period. Respondents were probed for the types of foods and food preparation methods. For the FFQ validation study, a 7-day weight diet record (7-d WDR) was used as the reference method. All foods recorded in the 24 HDR were converted into grams and then intake of energy and nutrients were analysed using NutriSurvey 2007 (EBISpro, Germany) which was modified for Sri Lankan food recipes. Socio-demographic details and body weight perception were collected from interviewer-administrated questionnaire. BMI was calculated and overweight (BMI ≥23 kg.m-2), obesity (BMI ≥25 kg.m-2) and abdominal obesity (Men: WC ≥ 90 cm; Women: WC ≥ 80 cm) were categorized according to Asia-pacific anthropometric cut-offs. The SPSS v. 16 for Windows and Minitab v10 were used for statistical analysis purposes. From a total of 600 eligible subjects, 491 (81.8%) participated of whom 34.5% (n=169) were males. Subjects were well distributed among different socio-economic parameters. A total of 312 different food items were recorded and nutritionists grouped similar food items which resulted in a total of 178 items. After performing step-wise multiple regression, 93 foods explained 90% of the variance for total energy intake, carbohydrates, protein, total fat and dietary fibre. Finally, 90 food items and 12 photographs were selected. Seventy-seven subjects completed (response rate = 65%) the FFQ and 7-day WDR. Estimated mean energy intake (SD) from FFQ (1794±398 kcal) and 7DWR (1698±333 kcal, P<0.001) was significantly different due to a significant overestimation of carbohydrate (~10 g/d, P<0.001) and to some extent fat (~5 g/d, NS). Significant positive correlations were found between the FFQ and 7DWR for energy (r = 0.39), carbohydrate (r = 0.47), protein (r = 0.26), fat (r =0.17) and dietary fiber (r = 0.32). Bland-Altman graphs indicated fairly good agreement between methods with no relationship between bias and average intake of each nutrient examined. The findings from the nutrition survey showed on average, Sri Lankan adults consumed over 14 portions of starch/d; moreover, males consumed 5 more portions of cereal than females. Sri Lankan adults consumed on average 3.56 portions of added sugars/d. Moreover, mean daily intake of fruit (0.43) and vegetable (1.73) portions was well below minimum dietary recommendations (fruits 2 portions/d; vegetables 3 portions/d). The total fruit and vegetable intake was 2.16 portions/d. Daily consumption of meat or alternatives was 1.75 portions and the sum of meat and pulses was 2.78 portions/d. Starchy foods were consumed by all participants and over 88% met the minimum daily recommendations. Importantly, nearly 70% of adults exceeded the maximum daily recommendation for starch (11portions/d) and a considerable proportion consumed larger numbers of starch servings daily, particularly men. More than 12% of men consumed over 25 starch servings/d. In contrast to their starch consumption, participants reported very low intakes of other food groups. Only 11.6%, 2.1% and 3.5% of adults consumed the minimum daily recommended servings of vegetables, fruits, and fruits and vegetables combined, respectively. Six out of ten adult Sri Lankans sampled did not consume any fruits. Milk and dairy consumption was extremely low; over a third of the population did not consume any dairy products and less than 1% of adults consumed 2 portions of dairy/d. A quarter of Sri Lankans did not report consumption of meat and pulses. Regarding protein consumption, 36.2% attained the minimum Sri Lankan recommendation for protein; and significantly more men than women achieved the recommendation of ≥3 servings of meat or alternatives daily (men 42.6%, women 32.8%; P<0.05). Over 70% of energy was derived from carbohydrates (Male:72.8±6.4%, Female:73.9±6.7%), followed by fat (Male:19.9±6.1%, Female:18.5±5.7%) and proteins (Male:10.6±2.1%, Female:10.9±5.6%). The average intake of dietary fiber was 21.3 g/day and 16.3 g/day for males and females, respectively. There was a significant difference in nutritional intake related to ethnicities, areas of residence, education levels and BMI categories. Similarly, dietary diversity was significantly associated with several socio-economic parameters among Sri Lankan adults. Adults with BMI ≥25 kg.m-2 and abdominally obese Sri Lankan adults had the highest diet diversity values. Age-adjusted prevalence (95% confidence interval) of overweight, obesity, and abdominal obesity among Sri Lankan adults were 17.1% (13.8-20.7), 28.8% (24.8-33.1), and 30.8% (26.8-35.2), respectively. Men, compared with women, were less overweight, 14.2% (9.4-20.5) versus 18.5% (14.4-23.3), P = 0.03, less obese, 21.0% (14.9-27.7) versus 32.7% (27.6-38.2), P < .05; and less abdominally obese, 11.9% (7.4-17.8) versus 40.6% (35.1-46.2), P < .05. Although, prevalence of obesity has reached to epidemic level body weight misperception was common among Sri Lankan adults. Two-thirds of overweight males and 44.7% of females considered themselves as in "about right weight". Over one third of both male and female obese subjects perceived themselves as "about right weight" or "underweight". Nearly 32% of centrally obese men and women perceived that their waist circumference is about right. People who perceived overweight or very overweight (n = 154) only 63.6% tried to lose their body weight (n = 98), and quarter of adults seek advices from professionals (n = 39). A number of important conclusions can be drawn from this research project. Firstly, the newly developed FFQ is an acceptable tool for assessing the nutrient intake of Sri Lankans and will assist proper categorization of individuals by dietary exposure. Secondly, a substantial proportion of the Sri Lankan population does not consume a varied and balanced diet, which is suggestive of a close association between the nutrition-related NCDs in the country and unhealthy eating habits. Moreover, dietary diversity is positively associated with several socio-demographic characteristics and obesity among Sri Lankan adults. Lastly, although obesity is a major health issue among Sri Lankan adults, body weight misperception was common among underweight, healthy weight, overweight, and obese adults in Sri Lanka. Over 2/3 of overweight and 1/3 of obese Sri Lankan adults believe that they are in "right weight" or "under-weight" categories.

Risk factors for ocular surface squamous neoplasia recurrence after treatment with topical mitomycin C and interferon alpha-2b

Purpose To determine the rate of recurrence and associated risk factors following the use of mitomycin C (MMC) and/or interferon alpha-2b (IFN) for management of non-invasive ocular surface squamous neoplasia (OSSN). Design Retrospective non-comparative interventional case series. Methods Clinical practice setting of 135 patients treated consecutively with topical MMC (0.4 mg/mL) and/or IFN (1 million units/mL) for OSSN observed for clinical recurrence. Results Clinical recurrences were diagnosed in 19 of 135 (14.1%) eyes following topical treatment. The mean time to recurrence was 17.2 months (range 4 - 61) with 14 (73.7%) recurring within a two year period. There was no greater risk of recurrence identified for variables including lesion size, lesion location, gender, age, treatment type or duration. Post-hoc log-Rank pairwise comparisons revealed that lesions initially treated using surgery alone had significantly reduced time to recurrence (21.1 ± 5.6 months) compared to previous topical treatment with MMC (with or without surgery) (29.6 ± 4.7 months) (p = 0.04) and primary OSSN (23.2 ± 1.8 months) (p = 0.09). Conclusions Topical MMC and IFN are an effective treatment modality for a wide range of non-invasive OSSN. Topical therapy avoids the morbidity of excisional surgery with equivalent or reduced recurrence rates and should be considered as primary therapy.

Surgical resection for non-small cell lung cancer : clinical features and outcomes for a consecutive series at an Irish tertiary referral centre

Background: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. Methods: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. Results: A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. Conclusion: We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres. © 2012 Royal Academy of Medicine in Ireland.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

A biological staging model for operable non-small cell lung cancer

Background Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system. Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets. Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC. Methods A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken. Immunohistochemical analysis was performed on paraffin embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers. Results Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)), and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74)) were independent prognostic factors. Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73)) or neither (HR 4.43 (2.29-8.57)) of these markers. EGFR expression correlated with tumour cell MMP-9 expression (p<0.001). Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)). Conclusion Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient. The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.

Angiogenesis and non-small cell lung cancer

Lung cancer is the commonest cause of cancer death in the western world. Recent evidence suggests that angiogenesis is related to poor prognosis in many solid tumours including non-small cell lung cancer. Angiogenesis is controlled by a complex interaction between growth and apoptotic factors, proteases and adhesion molecules. The angiogenic process may prove a target for novel therapies such as matrix metalloproteinase inhibitors, growth factor antisense RNA, growth factor receptor antagonists and naturally occurring antiangiogenic peptides. These agents may be used alone or in combination with traditional chemotherapy, radiotherapy and surgery. (C) 2000 Elsevier Science Ireland Ltd.

Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer

Background: Microvessel density, an indirect measure of angiogenesis, has been shown to be an independent prognostic marker in many solid tumours including non-small cell lung cancer (NSCLC). Platelets transport and release angiogenic growth factors. Platelets are increasingly likely to adhere to tumour microvessels due to raised expression of platelet-binding proteins and stasis in blood-flow. Increased vascular permeability in tumour microvessels facilitates platelet extravasation into the extracellular matrix. Adherence and extravasation both lead to platelet activation and release of growth factors capable of instigating the angiogenic process. Methods: A total of 181 patients were identified who underwent resection of stage I-IIIa NSCLC with a post-operative survival >60 days. Patients were followed-up for a minimum of 24 months. Sections from the tumour periphery were stained for the endothelial marker CD34 (Novocastra NCL-END) using standard ABC immunohistochemistry. Chalkley counting was used to assess microvessel density. Results: A pre-operative platelet count greater than the median and above the normal range (>400) was associated with a poor outcome (P = 0.01 and P = 0.04, respectively). Tumours with an above median and high Chalkley count (upper tertile) had a worse prognosis (P = 0.007 and P = 0.0006, respectively). There was no association between platelet count and Chalkley count. Conclusions: Platelet and microvessel counts are both potential prognostic markers for NSCLC. The role of platelets in the angiogenic process needs to be further investigated. (C) 2000 Elsevier Science Ireland Ltd.

Prognostic factors for malignant mesothelioma in 142 patients : validation of CALGB and EORTC prognostic scoring systems

Background The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. Methods Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. Results Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3.5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. Conclusions This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively). Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Prognostic value of angiogenesis in operable non-small cell lung cancer

Tumour angiogenesis is an important factor for tumour growth and metastasis. Although some recent reports suggest that microvessel counts in non-small cell lung cancer are related to a poor disease outcome, the results were not conclusive and were not compared with other molecular prognostic markers. In the present study, the vascular grade was assessed in 107 (T1,2-N0,1) operable non-small cell lung carcinomas, using the JC70 monoclonal antibody to CD31. Three vascular grades were defined with appraisal by eye and by Chalkley counting: high (Chalkley score 7-12), medium (5-6), and low (2-4). There was a significant correlation between eye appraisal and Chalkley counting (P < 0.0001). Vascular grade was not related to histology, grade, proliferation index (Ki67), or EGFR or p53 expression. Tumours from younger patients had a higher grade of angiogenesis (P = 0.05). Apart from the vascular grade, none of the other factors examined was statistically related to lymph node metastasis (P < 0.0001). A univariate analysis of survival showed that vascular grade was the most significant prognostic factor (P = 0.0004), followed by N-stage (P = 0.001). In a multivariate analysis, N-stage and vascular grade were not found to be independent prognostic factors, since they were strongly related to each other. Excluding N-stage, vascular grade was the only independent prognostic factor (P = 0.007). Kaplan-Meier survival curves showed a statistically significant worse prognosis for patients with high vascular grade, but no difference was observed between low and medium vascular grade. These data suggest that angiogenesis in operable non-small cell lung cancer is a major prognostic factor for survival and, among the parameters tested, is the only factor related to cancer cell migration to lymph nodes. The integration of vascular grading in clinical trials on adjuvant chemotherapy and/or radiotherapy could substantially contribute in defining groups of operable patients who might benefit from cytotoxic treatment.

bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.