Oesophageal cancer survival in Europe:A EUROCARE-4 study

Oesophageal cancer survival is poor with variation across Europe. No pan-European studies of survival differences by oesophageal cancer subtype exist. This study investigates rates and trends in oesophageal cancer survival across Europe. Data for primary malignant oesophageal cancer diagnosed in 1995-1999 and followed up to the end of 2003 was obtained from 66 cancer registries in 24 European countries. Relative survival was calculated using the Hakulinen approach. Staging data were available from 19 registries. Survival by region, gender, age, morphology and stage was investigated. Cohort analysis and the period approach were applied to investigate survival trends from 1988 to 2002 for 31 registries in 17 countries. In total 51,499 cases of oesophageal cancer diagnosed 1995-1999 were analysed. Overall, European 1- and 5-year survival rates were 33.4% (95% CI 32.9-33.9%) and 9.8% (95% CI 9.4-10.1%), respectively. Males, older patients and patients with late stage disease had poorer 1- and 5-year relative survival. Patients with squamous cell carcinoma had poorer 1-year relative survival. Regional variation in survival was observed with Central Europe above and Eastern Europe below the European pool. Survival for distant stage disease was similar across Europe while survival rates for localised disease were below the European pool in Eastern and Southern Europe. Improvement in European 1-year relative survival was reported (p=0.016). Oesophageal cancer survival was poor across Europe. Persistent regional variations in 1-year survival point to a need for a high resolution study of diagnostic and treatment practices of oesophageal cancer.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent. © 2013 John Wiley & Sons Ltd.

Change in psychological distress in longer-term oesophageal cancer carers: are clusters of illness perception change a useful determinant?

Objective: This study provides a longitudinal assessment of distress in longer-term oesophageal cancer carers, while examining illness perception schema as a possible determinant of change in distress over time.
Methods: Oesophageal cancer carers (n=171), 48-months post-diagnosis, were assessed at baseline and 12-months later with the Illness Perception Questionnaire-Revised, Cancer Coping Questionnaire, Hospital Anxiety and Depression Scale and Concerns About Recurrence Scale.
Results: Findings report deterioration from normal to probable anxiety in 35.7% of carers and probable depression in 28.7% carers over time. Fear of recurrence remained stable. Changes in control, consequence and cause beliefs were identified as key determinants of a change in psychological morbidity.
Conclusions: Illness beliefs appear to be valuable targets for psychological intervention to improve wellbeing among carers of people with oesophageal cancer.

Markers of vitamin D exposure and oesophageal cancer risk: a systematic review and meta-analysis.

Vitamin D has been associated with reduced risk of many cancers, but evidence for oesophageal cancer is mixed. To clarify the role of Vitamin D, we performed a systematic review and meta-analysis to evaluate the association of Vitamin D exposures and oesophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's oesophagus and squamous dysplasia. Ovid MEDLINE, EMBASE and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D (n=3), Vitamin D intake (n=4), UVB exposure (n=1), and genetic factors (n=7) were retrieved. Higher 25-OHD was associated with increased risk of cancer (adenocarcinoma or SCC, OR=1.39;95%CI:1.04-1.74), with the majority of participants coming from China. No association was observed between Vitamin D intake and risk of cancer overall (OR=1.03;0.65-1.42); however, a non-significantly increased risk for adenocarcinoma (OR=1.45;0.65-2.24) and non-significantly decreased risk for SCC (OR=0.80;0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers, OR=0.45;0.00-0.91, and a suggestive association was observed for rs2107301. No consistent associations were observed between Vitamin D exposures and occurrence of oesophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made.

Does pre-operative estimation of oesophageal tumour metabolic length using F-18-fluorodeoxyglucose PET/CT images compare with surgical pathology length?

PURPOSE:
The aim of the study was to compare the pre-operative metabolic tumour length on FDG PET/CT with the resected pathological specimen in patients with oesophageal cancer.

METHODS:
All patients diagnosed with oesophageal carcinoma who had undergone staging PET/CT imaging between the period of June 2002 and May 2008 who were then suitable for curative surgery, either with or without neo-adjuvant chemotherapy, were included in this study. Metabolic tumour length was assessed using both visual analysis and a maximum standardised uptake value (SUV(max)) cutoff of 2.5.

RESULTS:
Thirty-nine patients proceeded directly to curative surgical resection, whereas 48 patients received neo-adjuvant chemotherapy, followed by curative surgery. The 95% limits of agreement in the surgical arm were more accurate when the metabolic tumour length was visually assessed with a mean difference of -0.05 cm (SD 2.16 cm) compared to a mean difference of +2.42 cm (SD 3.46 cm) when assessed with an SUV(max) cutoff of 2.5. In the neo-adjuvant group, the 95% limits of agreement were once again more accurate when assessed visually with a mean difference of -0.6 cm (SD 1.84 cm) compared to a mean difference of +1.58 cm (SD 3.1 cm) when assessed with an SUV(max) cutoff of 2.5.

CONCLUSION:
This study confirms the high accuracy of PET/CT in measuring gross target volume (GTV) length. A visual method for GTV length measurement was demonstrated to be superior and more accurate than when using an SUV(max) cutoff of 2.5. This has the potential of reducing the planning target volume with dose escalation to the tumour with a corresponding reduction in normal tissue complication probability.

Survival for oesophageal, stomach and small intestine cancers in Europe 1999-2007: Results from EUROCARE-5

Background: European regional variation in cancer survival was reported in the EUROCARE-4 study for patients diagnosed in 1995-1999. Relative survival (RS) estimates are here updated for patients diagnosed with cancer of the oesophagus, stomach and small intestine from 2000 to 2007. Trends in RS from 1999-2001 to 2005-2007 are presented to monitor and discuss improvements in patient survival in Europe. Materials and methods: EUROCARE-5 data from 29 countries (87 cancer registries) were used to investigate 1- and 5-year RS. Using registry-specific life-tables stratified by age, gender and calendar year, age-standardised 'complete analysis' RS estimates by country and region were calculated for Northern, Southern, Eastern and Central Europe, and for Ireland and United Kingdom (UK). Survival trends of patients in periods 1999-2001, 2002-2004 and 2005-2007 were investigated using the 'period' RS approach. We computed the 5-year RS conditional on surviving the first year (5-year conditional survival), as the ratio of age-standardised 5-year RS to 1-year RS. Results Oesophageal cancer 1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%). Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by 2005-2007, with Ireland and the UK (3%), and Central Europe (4%) showing large improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%) and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe had the best 5-year survival (30%), though only showing an improvement of 2% by 2005-2007. Small intestine cancer 5-year RS for Europe was 48%, with Central Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year patient survival improvement for Europe was 8% by 2005-2007, with Central, Southern and Eastern Europe showing the greatest increases (≥9%). Conclusions Survival for these cancer sites, particularly oesophageal cancer, remains poor in Europe with wide variation. Further investigation into the wide variation, including analysis by histology and anatomical sub-site, will yield insights to better monitor and explain the improvements in survival observed over time.

Fumonisin B-1 as a Urinary Biomarker of Exposure in a Maize Intervention Study Among South African Subsistence Farmers

Background: The consumption of maize highly contaminated with carcinogenic fumonisins has been linked to high oesophageal cancer rates. The aim of this study was to validate a urinary fumonisin B-1 (UFB1) biomarker as a measure of fumonisin exposure and to investigate the reduction in exposure following a simple and culturally acceptable intervention.

Methods: At baseline home-grown maize, maize-based porridge, and first-void urine samples were collected from female participants (n = 22), following their traditional food practices in Centane, South Africa. During intervention the participants were trained to recognize and remove visibly infected kernels, and to wash the remaining kernels. Participants consumed the porridge prepared from the sorted and washed maize on each day of the two-day intervention. Porridge, maize, and urine samples were collected for FB1 analyses.

Results: The geometric mean (95% confidence interval) for FB1 exposure based on porridge (dry weight) consumption at baseline and following intervention was 4.84 (2.87-8.14) and 1.87 (1.40-2.51) mg FB1/kg body weight/day, respectively, (62% reduction, P < 0.05). UFB1C, UFB1 normalized for creatinine, was reduced from 470 (295-750) at baseline to 279 (202-386) pg/mg creatinine following intervention (41% reduction, P = 0.06). The UFB1C biomarker was positively correlated with FB1 intake at the individual level (r - 0.4972, P < 0.01). Urinary excretion of FB1 was estimated to be 0.075% (0.054%-0.104%) of the FB1 intake.

Conclusion: UFB1 reflects individual FB1 exposure and thus represents a valuable biomarker for future fumonisin risk assessment.

Impact: The simple intervention method, hand sorting and washing, could positively impact on food safety and health in communities exposed to fumonisins. Cancer Epidemiol Biomarkers Prev; 20(3); 483-9. (C)2011 AACR.

Simple intervention method to reduce fumonisin exposure in a subsistence maize-farming community in South Africa

In the Centane magisterial area of South Africa, high rates of oesophageal cancer have been associated with home-grown maize contaminated with fumonisins. The aim of this study was to implement a simple intervention method to reduce fumonisin exposure in a subsistence-farming community. The hand-sorting and washing procedures, based on traditional maize-based food preparation practices, were previously customised under laboratory-controlled conditions. Home-grown maize and maize-based porridge collected at baseline were analysed for fumonisin B1, B2 and B3. The geometric mean (95% confidence interval) of fumonisin contamination in the home-grown maize at baseline was 1.67 (1.21-2.32) mg kg-1 and 1.24 (0.75-2.04) mg kg -1 (dry weight) in the porridge. Fumonisin exposure was based on individual stiff porridge consumption and the specific fumonisin levels in the porridge (dry weight) consumed. Porridge (dry weight) consumption at baseline was 0.34 kg day-1 and fumonisin exposure was 6.73 (3.90-11.6) mu g kg-1 body weight day-1. Female participants (n = 22) were trained to recognise and remove visibly infected/damaged kernels and to wash the remaining maize kernels. The discarded kernels represented 3.9% by weight and the fumonisins varied from 17.1 to 76.9 mg kg-1. The customised hand-sorting and washing procedures reduced fumonisin contamination in the maize and porridge by 84 and 65%, respectively. The intervention reduced fumonisin exposure by 62% to 2.55 (1.94-3.35) mu g kg-1 body weight day-1. This simple intervention method has the potential to improve food safety and health in subsistence-farming communities consuming fumonisin-contaminated maize as their staple diet.

Mycotoxins and human disease: a largely ignored global health issue

Aflatoxins and fumonisins (FB) are mycotoxins contaminating a large fraction of the world's food, including maize, cereals, groundnuts and tree nuts. The toxins frequently co-occur in maize. Where these commodities are dietary staples, for example, in parts of Africa, Asia and Latin America, the contamination translates to high-level chronic exposure. This is particularly true in subsistence farming communities where regulations to control exposure are either non-existent or practically unenforceable. Aflatoxins are hepatocarcinogenic in humans, particularly in conjunction with chronic hepatitis B virus infection, and cause aflatoxicosis in episodic poisoning outbreaks. In animals, these toxins also impair growth and are immunosuppressive; the latter effects are of increasing interest in human populations. FB have been reported to induce liver and kidney tumours in rodents and are classified as Group 2B 'possibly carcinogenic to humans', with ecological studies implying a possible link to increased oesophageal cancer. Recent studies also suggest that the FB may cause neural tube defects in some maize-consuming populations. There is a plausible mechanism for this effect via a disruption of ceramide synthase and sphingolipid biosynthesis. Notwithstanding the need for a better evidence-base on mycotoxins and human health, supported by better biomarkers of exposure and effect in epidemiological studies, the existing data are sufficient to prioritize exposure reduction in vulnerable populations. For both toxins, there are a number of practical primary and secondary prevention strategies which could be beneficial if the political will and financial investment can be applied to what remains a largely and rather shamefully ignored global health issue.

Mortality in Barrett's oesophagus:Results from a population based study

Background: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. Methods: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. Results: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231 )) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. Conclusions: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.

Achalasia: A review of clinical diagnosis, epidemiology, treatment and outcomes

Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function. Historically, annual achalasia incidence rates were believed to be low, approximately 0.5-1.2 per 100000. More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations. The aetiology of achalasia is still unclear but is likely to be multi-factorial. Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus, which elicits an autoimmune response. Risk of achalasia may be elevated in a sub-group of genetically susceptible people. Improvement in the diagnosis of achalasia, through the introduction of high resolution manometry with pressure topography plotting, has resulted in the development of a novel classification system for achalasia. This classification system can evaluate patient prognosis and predict responsiveness to treatment. There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller's myotomy procedure in the treatment of achalasia. A recent comparative study found equal efficacy, suggesting that patient preference and local expertise should guide the choice. Although achalasia is a relatively rare condition, it carries a risk of complications, including aspiration pneumonia and oesophageal cancer. The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia, however the absolute excess risk is small. Therefore, it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective.