Live birth and maternity outcome in childhood and adolescent cancer survivors under 18 years at diagnosis: a 40-year population-based cohort study.

BACKGROUND: Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced. METHODS: We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis. FINDINGS: The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. INTERPRETATION: We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses.

The association between diabetes medication and weight change in a non-surgical weight management intervention: an intervention cohort study.

AIM: To compare weight change in a lifestyle-based weight management programme between participants taking weight-gaining, weight-neutral/loss and mixed diabetes medications. METHODS: Electronic health records for individuals (≥ 18 years) with Type 2 diabetes who had been referred to a non-surgical weight management programme between February 2008 and May 2014 were studied. Diabetes medications were classified into three categories based on their effect on body weight. In this intervention cohort study, weight change was calculated for participants attending two or more sessions. RESULTS: All 998 individuals who took oral diabetes medications and attended two or more sessions of weight management were included. Some 59.5% of participants were women, and participants had a mean BMI of 41.1 kg/m2 (women) and 40.2 kg/m2 (men). Of the diabetes medication combinations prescribed, 46.0% were weight-neutral/loss, 41.3% mixed and 12.7% weight-gaining. The mean weight change for participants on weight-gaining and weight-neutral/loss diabetes medications respectively was -2.5 kg [95% confidence interval (CI) -3.2 to -1.8) and -3.3 kg (95% CI -3.8 to -2.9) (P = 0.05) for those attending two or more sessions (n = 998). Compared with those prescribed weight-neutral medications, participants prescribed weight-gaining medication lost 0.86 kg less (95% CI 0.02 to 1.7; P = 0.045) in a model adjusted for age, sex, BMI and socio-economic status. CONCLUSIONS: Participants on weight-neutral/loss diabetes medications had a greater absolute weight loss within a weight management intervention compared with those on weight-gaining medications. Diabetes medications should be reviewed ahead of planned weight-loss interventions to help ensure maximal effectiveness of the intervention.

High-resolution profiles of the Streptococcus mitis CSP signaling pathway reveal core and strain-specific regulated genes.

BACKGROUND: In streptococci of the mitis group, competence for natural transformation is a transient physiological state triggered by competence stimulating peptides (CSPs). Although low transformation yields and the absence of a widespread functional competence system have been reported for Streptococcus mitis, recent studies revealed that, at least for some strains, high efficiencies can be achieved following optimization protocols. To gain a deeper insight into competence in this species, we used RNA-seq, to map the global CSP response of two transformable strains: the type strain NCTC12261T and SK321. RESULTS: All known genes induced by ComE in Streptococcus pneumoniae, including sigX, were upregulated in the two strains. Likewise, all sets of streptococcal SigX core genes involved in extracellular DNA uptake, recombination, and fratricide were upregulated. No significant differences in the set of induced genes were observed when the type strain was grown in rich or semi-defined media. Five upregulated operons unique to S. mitis with a SigX-box in the promoter region were identified, including two specific to SK321, and one specific to NCTC12261T. Two of the strain-specific operons coded for different bacteriocins. Deletion of the unique S. mitis sigX regulated genes had no effect on transformation. CONCLUSIONS: Overall, comparison of the global transcriptome in response to CSP shows the conservation of the ComE and SigX-core regulons in competent S. mitis isolates, as well as species and strain-specific genes. Although some S. mitis exhibit truncations in key competence genes, this study shows that in transformable strains, competence seems to depend on the same core genes previously identified in S. pneumoniae.

Socio-economic inequalities in the incidence of four common cancers: a population-based registry study.

OBJECTIVES: To investigate the relationship between socio-economic circumstances and cancer incidence in Scotland in recent years. STUDY DESIGN: Population-based study using cancer registry data. METHODS: Data on incident cases of colorectal, lung, female breast, and prostate cancer diagnosed between 2001 and 2012 were obtained from a population-based cancer registry covering a population of approximately 2.5 million people in the West of Scotland. Socio-economic circumstances were assessed based on postcode of residence at diagnosis, using the Scottish Index of Multiple Deprivation (SIMD). For each cancer, crude and age-standardised incidence rates were calculated by quintile of SIMD score, and the number of excess cases associated with socio-economic deprivation was estimated. RESULTS: 93,866 cases met inclusion criteria, comprising 21,114 colorectal, 31,761 lung, 23,757 female breast, and 15,314 prostate cancers. Between 2001 and 2006, there was no consistent association between socio-economic circumstances and colorectal cancer incidence, but 2006-2012 saw an emerging deprivation gradient in both sexes. The incidence rate ratio (IRR) for colorectal cancer between most deprived and least deprived increased from 1.03 (95% confidence interval [CI] 0.91-1.16) to 1.24 (95% CI 1.11-1.39) during the study period. The incidence of lung cancer showed the strongest relationship with socio-economic circumstances, with inequalities widening across the study period among women from IRR 2.66 (95% CI 2.33-3.05) to 2.91 (95% CI 2.54-3.33) in 2001-03 and 2010-12, respectively. Breast and prostate cancer showed an inverse relationship with socio-economic circumstances, with lower incidence among people living in more deprived areas. CONCLUSION: Significant socio-economic inequalities remain in cancer incidence in the West of Scotland, and in some cases are increasing. In particular, this study has identified an emerging, previously unreported, socio-economic gradient in colorectal cancer incidence among women as well as men. Actions to prevent, mitigate, and undo health inequalities should be a public health priority.

A retrospective cohort study of the influence of lifestyle factors on the survival of patients undergoing surgery for colorectal cancer.

AIM: Several modifiable and nonmodifiable health-related behaviours are associated with the incidence of colorectal cancer (CRC), but there is little research on their association with survival. This work aimed to investigate possible relationships between modifiable behavioural factors and outcomes on a study cohort of CRC patients undergoing potentially curative surgery. METHOD: A retrospective cohort study was carried out of patients diagnosed with nonmetastatic CRC residing in the NHS Greater Glasgow and Clyde area, UK and undergoing elective curative surgery (January 2011 to December 2012). Data were obtained from the Scottish Cancer Registry, National Scottish Death Records. Preoperative assessment of smoking, alcohol consumption, nurse-measured body mass index (BMI) and exercise levels were recorded, and patients were followed until death or censorship. Survival analysis was carried out and proportional hazards assumptions were assessed graphically using plots and were then formally tested using the PHTEST procedure in stata. RESULT: Of the initial 527 patients, 181 (34%) satisfied the inclusion criteria. The total duration of follow-up was 480 person-years. At the preoperative assessment, 75% of patients were overweight or obese, 10.6% were current smokers, 13.1% recorded excess alcohol consumption and 8.5% had physical difficulty climbing stairs. Age, BMI, histopathological stage and physical capacity all independently affected survival (P < 0.05). Overweight patients [hazard ratio (HR) 2.81] and those who had difficulty climbing stairs (HR 3.31) had a significantly poorer survival. CONCLUSION: This study found evidence that preoperative exercise capacity and BMI are important independent prognostic factors of survival in patients undergoing curative surgery for CRC.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

A comparison of tumour and host prognostic factors in screen-detected vs nonscreen-detected colorectal cancer: a contemporaneous study.

AIM: In addition to TNM stage there are adverse tumour and host factors, such as venous invasion and the presence of an elevated systemic inflammatory response (SIR), that influence the outcome in colorectal cancer. The present study aimed to examine how these factors varied in screen-detected (SD) and nonscreen-detected (NSD) tumours. METHOD: Prospectively maintained databases of the prevalence round of a biennial population faecal occult blood test screening programme and a regional cancer audit database were analysed. Interval cancers (INT) were defined as cancers identified within 2 years of a negative screening test. RESULTS: Of the 395 097 people invited, 204 535 (52%) responded, 6159 (3%) tested positive and 421 (9%) had cancer detected. A further 708 NSD patients were identified [468 (65%) nonresponders, 182 (25%) INT cancers and 58 (10%) who did not attend or did not have cancer diagnosed at colonoscopy]. Comparing SD and NSD patients, SD patients were more likely to be male, and have a tumour with a lower TNM stage (both P < 0.05). On stage-by-stage analysis, SD patients had less evidence of an elevated SIR (P < 0.05). Both the presence of venous invasion (P = 0.761) and an elevated SIR (P = 0.059) were similar in those with INT cancers and in those that arose in nonresponders. CONCLUSION: Independent of TNM stage, SD tumours have more favourable host prognostic factors than NSD tumours. There is no evidence that INT cancers are biologically more aggressive than those that develop in the rest of the population and are hence likely to be due to limitations of screening in its current format.

Critical care provision after colorectal cancer surgery.

BACKGROUND: Colorectal cancer (CRC) is the 2nd largest cause of cancer related mortality in the UK with 40 000 new patients being diagnosed each year. Complications of CRC surgery can occur in the perioperative period that leads to the requirement of organ support. The aim of this study was to identify pre-operative risk factors that increased the likelihood of this occurring. METHODS: This is a retrospective observational study of all 6441 patients who underwent colorectal cancer surgery within the West of Scotland Region between 2005 and 2011. Logistic regression was employed to determine factors associated with receiving postoperative organ support. RESULTS: A total of 610 (9 %) patients received organ support. Multivariate analysis identified age ≥65, male gender, emergency surgery, social deprivation, heart failure and type II diabetes as being independently associated with organ support postoperatively. After adjusting for demographic and clinical factors, patients with metastatic disease appeared less likely to receive organ support (p = 0.012). CONCLUSIONS: Nearly one in ten patients undergoing CRC surgery receive organ support in the post operative period. We identified several risk factors which increase the likelihood of receiving organ support post operatively. This is relevant when consenting patients about the risks of CRC surgery.

Long-term epidemiological survey of Kudoa thyrsites (Myxozoa) in Atlantic salmon (Salmo salar L.) from commercial aquaculture farms.

Kudoa thyrsites (Myxozoa) encysts within myocytes of a variety of fishes. While infected fish appear unharmed, parasite-derived enzymes degrade the flesh post-mortem. In regions of British Columbia (BC), Canada, up to 4-7% of fillets can be affected, thus having economic consequences and impacting the competitiveness of BC's farms. K. thyrsites was monitored in two farms having high (HP) or low (LP) historical infection prevalence. At each farm, 30 fish were sampled monthly for blood and muscle during the first year followed by nine samplings during year two. Prevalence and intensity were measured by PCR and histology of muscle samples. In parallel, fillet tests were used to quantify myoliquefaction. Infections were detected by PCR after 355 and 509 degree days at LP and HP farms, respectively. Prevalence reached 100% at the HP farm by 2265 degree days and declined during the second year, whereas it plateaued near 50% at the LP farm. Infection intensities decreased after 1 year at both farms. Blood was PCR-positive at both farms between 778 and 1113 degree days and again after 2000 degree days. This is the first monitoring project in a production environment and compares data between farms with different prevalence.

Diet, exercise, obesity, smoking and alcohol consumption in cancer survivors and the general population: a comparative study of 16 282 individuals.

BACKGROUND: Cancer survivors may be particularly motivated to improve their health behaviours. METHODS: We compared health behaviours and obesity in cancer survivors with the general population, using household survey and cancer registry data. RESULTS: Cancer survivors were more likely than those with no history of cancer to eat fruit and vegetables (ORadj 1.41, 95% CI 1.19-1.66), less likely to engage in physical activity (ORadj 0.79, 95% CI 0.67-0.93) and more likely to have stopped smoking (ORadj 1.25, 95% CI 1.09-1.44). CONCLUSIONS: Most health-related behaviours were better in cancer survivors than the general population, but low physical activity levels may be amenable to health promotion interventions.

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland.

BACKGROUND: Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. METHODS: Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. RESULTS: In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P⩽0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P⩽0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P⩽0.001). CONCLUSIONS: Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer.

The role of short chain fatty acids in appetite regulation and energy homeostasis.

Over the last 20 years there has been an increasing interest in the influence of the gastrointestinal tract on appetite regulation. Much of the focus has been on the neuronal and hormonal relationship between the gastrointestinal tract and the brain. There is now mounting evidence that the colonic microbiota and their metabolic activity have a significant role in energy homeostasis. The supply of substrate to the colonic microbiota has a major impact on the microbial population and the metabolites they produce, particularly short chain fatty acids (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary fibres and resistant starch, undergo fermentation by the colonic microbiota. Both the consumption of fermentable carbohydrates and the administration of SCFAs have been reported to result in a wide range of health benefits including improvements in body composition, glucose homeostasis, blood lipid profiles and reduced body weight and colon cancer risk. However, published studies tend to report the effects that fermentable carbohydrates and SCFAs have on specific tissues and metabolic processes, and fail to explain how these local effects translate into systemic effects and the mitigation of disease risk. Moreover, studies tend to investigate SCFAs collectively and neglect to report the effects associated with individual SCFAs. Here, we bring together the recent evidence and suggest an overarching model for the effects of SCFAs on one of their beneficial aspects: appetite regulation and energy homeostasis.

Optimising gut colonisation resistance against Clostridium difficile infection.

Clostridium difficile is the dominant cause of pseudomembranous colitis in nosocomial environments. C. difficile infection (CDI) generally affects elderly (≥65 years of age) hospital inpatients who have received broad-spectrum antimicrobial treatment. CDI has a 30 % risk of re-infection and a subsequent 60 % risk of relapse thereafter, leading to a high economic burden of over 7 billion pounds sterling and over 900,000 cases in the USA and Europe per annum. With the long-term consequences of faecal transplantation currently unknown, and limited spectrum of effective antibiotics, there is an urgent requirement for alternative means of preventing and treating CDI in high-risk individuals. Metagenomics has recently improved our understanding of the colonisation resistance barrier and how this could be optimised. pH, oxidation-reduction potentials and short-chain fatty acids have been suggested to inhibit C. difficile growth and toxin production in in vitro and in vivo studies. This review aims to pull together the evidence in support of a colonisation resistance barrier against CDI.

1000 Port-A-Cath ® placements by subclavian vein approach: single surgeon experience.

INTRODUCTION: Totally implantable venous access ports are widely used for the administration of chemotherapy in patients with cancer. Although there are several approaches to implantation, here we describe Port-A-Cath(®) (PAC) placement by percutaneous puncture of the subclavian vein with ultrasonographic guidance. PATIENTS AND METHODS: Data on our vascular access service were collected prospectively from June 2004. This service included port-a-caths and Hickman lines. Once 1000 consecutive port-a-caths(®) had been reached the study was closed and data analysed for the port-a-caths(®) alone. The left subclavian vein was the preferred site for venous access, with the right subclavian and jugular veins being the alternative choices if the initial approach failed. Patients were followed up in the short-term, and all the procedures were carried out by a single surgeon at each one of two institutions. RESULTS: Venous access by PAC was established in 100 % of the 1,000 cases. Of the 952 patients where the left subclavian vein was chosen for the first attempt of puncture, the success rate of PAC placement was 95 % (n = 904). Pneumothorax occurred in 12 patients (1.2 %), and a wound haematoma occurred in 4 (0.4 %) out of the total 1,000 patients. No infections were recorded during the immediate post-operative period but only in the long-term post-operative use with 8 patients requiring removal of the PAC due to infection following administration of chemotherapy. CONCLUSION: This is a very large series of PAC placement with an ultrasound-guided approach for left subclavian vein and X-ray confirmation, performed by a single surgeon, demonstrating both the safety and effectiveness of the procedure.

Piscine reovirus in wild and farmed salmonids in British Columbia, Canada: 1974-2013.

Piscine reovirus (PRV) was common among wild and farmed salmonids in British Columbia, western Canada, from 1987 to 2013. Salmonid tissues tested for PRV by real-time rRT-PCR included sections from archived paraffin blocks from 1974 to 2008 (n = 363) and fresh-frozen hearts from 2013 (n = 916). The earliest PRV-positive sample was from a wild-source steelhead trout, Oncorhynchus mykiss (Walbaum), from 1977. By histopathology (n = 404), no fish had lesions diagnostic for heart and skeletal muscle inflammation (HSMI). In some groups, lymphohistiocytic endocarditis affected a greater proportion of fish with PRV than fish without PRV, but the range of Ct values among affected fish was within the range of Ct values among unaffected fish. Also, fish with the lowest PRV Ct values (18.4-21.7) lacked endocarditis or any other consistent lesion. From 1987 to 1994, the proportion of PRV positives was not significantly different between farmed Atlantic salmon, Salmo salar L. (44% of 48), and wild-source salmonids (31% of 45). In 2013, the proportion of PRV positives was not significantly different between wild coho salmon, Oncorhynchus kisutch (Walbaum), sampled from British Columbia (5.0% of 60) or the reference region, Alaska, USA (10% of 58).

Changes in BMI and waist circumference in Scottish adults: use of repeated cross-sectional surveys to explore multiple age groups and birth-cohorts.

OBJECTIVE: To document changes in body mass index (BMI) and waist circumference (WC) over a 10-year period 1998-2008, in representative surveys of adults. SUBJECTS: Adults aged 18-72 in the Scottish Health Surveys conducted in 1998, 2003 and 2008 were divided, separately for men and women, into eleven 5-year age bands. 'Synthetic birth-cohorts' were created by dividing participants into thirteen 5-years-of-birth bands (n=20 423). Weight, height and WC were objectively measured by trained observers. RESULTS: SUBJECTS with data available on BMI/WC were 7743/6894 in 1998, 5838/4437 in 2003 and 4688/925 in 2008 with approximately equal gender distributions. Mean BMI and waist were both greater in successive surveys in both men and women. At most specific ages, people were consistently heavier in 2008 than in 1998 by about 1-1.5 BMI units, and WCs were greater by about 2-6 cm in men and 5-7 cm in women. Greater increases were seen at younger ages between 1998 and 2003 than between 2003 and 2008, however increases continued at older ages, particularly in waist. All birth-cohorts observed over the 10 years 1998-2008 showed increases in both BMI and waist, most marked in the younger groups. The 10-year increases in waist within birth-cohorts (mean 7.4 cm (8.1%) in men and 8.6 cm (10.9%) in women) were more striking than in BMI (mean 1.8 kg m(-2) (6.6%) in men and 1.5 kg m(-2) (6.4%) in women) were particularly steep in older women. CONCLUSION: People were heavier and fatter in 2003 than those of the same age in 1998, with less marked increases in WC between 2003 and 2008 than between 1998 and 2003. There were proportionally greater increases in WC than in BMI, especially in older women. This suggests a disproportionate increase in body fat, compared with muscle, particularly among older women.

Contribution of surgical specialization to improved colorectal cancer survival.

BACKGROUND: Reorganization of colorectal cancer services has led to surgery being increasingly, but not exclusively, delivered by specialist surgeons. Outcomes from colorectal cancer surgery have improved, but the exact determinants remain unclear. This study explored the determinants of outcome after colorectal cancer surgery over time. METHODS: Postoperative mortality (within 30 days of surgery) and 5-year relative survival rates for patients in the West of Scotland undergoing surgery for colorectal cancer between 1991 and 1994 were compared with rates for those having surgery between 2001 and 2004. RESULTS: The 1823 patients who had surgery in 2001-2004 were more likely to have had stage I or III tumours, and to have undergone surgery with curative intent than the 1715 patients operated on in 1991-1994. The proportion of patients presenting electively who received surgery by a specialist surgeon increased over time (from 14·9 to 72·8 per cent; P < 0·001). Postoperative mortality increased among patients treated by non-specialists over time (from 7·4 to 10·3 per cent; P = 0·026). Non-specialist surgery was associated with an increased risk of postoperative death (adjusted odds ratio 1·72, 95 per cent confidence interval (c.i.) 1·17 to 2·55; P = 0·006) compared with specialist surgery. The 5-year relative survival rate increased over time and was higher among those treated by specialist compared with non-specialist surgeons (62·1 versus 53·0 per cent; P < 0·001). Compared with the earlier period, the adjusted relative excess risk ratio for the later period was 0·69 (95 per cent c.i. 0·61 to 0·79; P < 0·001). Increased surgical specialization accounted for 18·9 per cent of the observed survival improvement. CONCLUSION: Increased surgical specialization contributed significantly to the observed improvement in longer-term survival following colorectal cancer surgery.

The impact of socio-economic circumstances on overall and grade-specific prostate cancer incidence: a population-based study.

BACKGROUND: If the observed increasing incidence of prostate cancer and higher incidence in more affluent men are due to differences in diagnostic sensitivity, an excess of asymptomatic low-grade tumours might be expected. METHODS: We conducted a descriptive population-based study of incident cases of prostate cancer (International Classification of Diseases version 10 codes for prostate cancer) in the West of Scotland, using the Scottish Cancer Registry data from 1991 to 2007. Socio-economic circumstances were measured using the Carstairs score, and disease grade measured using the Gleason score. Deprivation-specific European age-standardised incidence rates were calculated, and joinpoint regression analysis were used to identify significant changes in trends over time. RESULTS: A total of 15 519 incident cases of prostate cancer were diagnosed. Incidence increased by 70% from 44 to 75 per 100 000 cases between 1991 and 2007, an average annual growth of 3.6%. Men aged <65 years experienced the largest increase in incidence. A widening socio-economic deprivation gap in incidence appeared from 1998 onwards in low-grade disease only. From 2003 to 2007, the deprivation gap (affluent to deprived) was 40.3 per 100 000 cases (P<0.001; trend), with rates 37% lower among the most deprived compared with the most affluent. This deprivation gap represents an estimated 1764 cases of prostate cancer over a 5-year period. CONCLUSION: Prostate cancer incidence continues to increase; an increase in low-grade disease in affluent men may suggest that prostate-specific antigen testing is responsible, but it does not explain the overall increases in all grades of disease.

Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer.

BACKGROUND: Quantitative differences in biomarker expression relative to age and molecular subtypes have not been well documented in invasive breast cancer (IBCA). METHODS: Oestrogen receptor (ER), progesterone receptor (PR), HER2, ki67, p53 and DNA ploidy was performed by image analysis in 162 consecutive IBCAs in women (≤ 40 years) and compared with women ≥ 50 years (100 cases). Molecular subtypes were defined by immunohistochemistry (IHC). RESULTS: Among young women, tumours were frequently ER negative (P=0.01) with lower ER (P<0.00), PR (P=0.03), higher ki67 index (KI) (P=0.01) and p53 (P=0.00) compared with older women. Triple negative was more frequent among young women with frequent lymph node involvement compared with older women. Luminal B among young vs old women showed lower ER (67% vs 88%), PR (32% vs 52%), higher KI (48% vs 34%) and p53 (19% vs 7%). Linear regression model showed increasing KI (P<0.0001) and p53 (P=0.0003) according to the molecular subtypes. Survival difference among subtypes was demonstrated by multivariate analysis (P=0.0092) after adjusting for age, race, tumour size, grade and stage. CONCLUSION: We demonstrated significant differences in biomarker expression relative to age and molecular subtypes. Molecular subtype defined by IHC was an independent prognostic factor.

A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer.

BACKGROUND: The neutrophil lymphocyte ratio (NLR) has prognostic value in patients with a variety of cancers. Many chemotherapeutic trial databases hold information on white cell and neutrophil counts only. The aim of the present study was to compare the prognostic value of the NLR with a derived score (dNLR), composed of white cell and neutrophil counts. METHODS: Patients (n=27,031) who were sampled incidentally between 2000 and 2007 for neutrophil, lymphocyte and white cell counts, and also had a diagnosis of cancer (Scottish Cancer Registry), were identified. Of this group, 12,118 patients who had been sampled within 2 years of their cancer diagnosis were studied. RESULTS: On follow-up, there were 7366 deaths, of which 6198 (84%) were cancer deaths. The median time from blood sampling to diagnosis was 2.1 months. The area under the receiver-operating characteristic (ROC) curve for cancer-specific survival was 0.650 for the NLR and 0.640 for the dNLR. The NLR and dNLR were independently associated with survival in all cancers studied (all P<0.001). The optimal thresholds, on the basis of hazard ratios and area under the curve, were 4 : 1 for the NLR and 2 : 1 for the dNLR. CONCLUSION: The results of the present study show that the dNLR has similar prognostic value to the NLR. Therefore, the universally available dNLR is to be commended for use in the risk stratification of patients undergoing chemotherapy.