Cancer of the Oesophagus
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Cancer of the Oesophagus

The oesophagus (US spelling: esophagus) or gullet is a long hollow muscular tube which connects the throat to the stomach. Oesophageal cancer is a disease where malignant (cancerous) cells arise in the tissues of the oesophagus. The most common symptom is difficulty in swallowing. It can also be associated with weight loss and sometimes pain or discomfort behind the breast bone or in the back - these symptoms should be checked by a doctor but not are sure signs of cancer. There are two main types of oesophageal cancer (depending on how the cells appear under the microscope); approximately half are classed as "squamous cell carcinomas" and half as "adenocarcinomas". People with frequent gastric reflux leading to Barrett's Oesophagus have an increased risk of developing oesophageal cancer.

In 2010, 8,477 people in the UK were diagnosed with oesophageal cancer (Source: Cancer Research UK)

This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Cancer of the Oesophagus Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (8 links)

Information for Health Professionals / Researchers (4 links)

  • PubMed search for publications about Esophageal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Esophageal Cancer
    MeSH term: Esophageal Neoplasms
    International US National Library of Medicine
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Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Qureshi YA, Dawas KI, Mughal M, Mohammadi B
Minimally invasive and robotic esophagectomy: Evolution and evidence.
J Surg Oncol. 2016; 114(6):731-735 [PubMed] Related Publications
Esophageal cancer has a poor prognosis, with little improvement in outcomes in recent years. Surgery maintains its pivotal role in cure, but this involves two or three compartment dissection with associated high risks. Chiefly, pulmonary complications following surgery are most common, and can be life-threatening. As a consequence, minimally invasive and robotic esophagectomy have been performed with improving efficacy and equivalent oncological outcomes. This is a review of the pertinent literature regarding these techniques. J. Surg. Oncol. 2016;114:731-735. © 2016 Wiley Periodicals, Inc.

Rice TW, Chen LQ, Hofstetter WL, et al.
Worldwide Esophageal Cancer Collaboration: pathologic staging data.
Dis Esophagus. 2016; 29(7):724-733 [PubMed] Related Publications
We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Warren S, Partridge M, Bolsi A, et al.
An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.
Int J Radiat Oncol Biol Phys. 2016; 95(1):199-207 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans.
METHODS AND MATERIALS: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant.
RESULTS: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose.
CONCLUSIONS: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.

Moorcraft SY, Fontana E, Cunningham D, et al.
Characterising timing and pattern of relapse following surgery for localised oesophagogastric adenocarcinoma: a retrospective study.
BMC Cancer. 2016; 16:112 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Oesophagogastric adenocarcinoma (OGA) has a poor prognosis, even for patients with operable disease. However, the optimal surveillance strategy following surgery is unknown.
METHODS: We performed a retrospective review of all patients with OGA who had undergone surgery with radical intent at the Royal Marsden between January 2001 and December 2010.
RESULTS: Of the 360 patients with OGA who underwent potentially curative surgery, 100/214 patients (47%) with oesophageal/gastro-oesophageal junction (GOJ) adenocarcinoma and 47/146 patients (32%) with gastric adenocarcinoma developed recurrent disease. 51, 79 and 92% of relapses occurred within 1, 2 and 3 years respectively and the majority of patients relapsed at distant sites. Of the patients who relapsed, 67% (67/100) with oesophageal/GOJ adenocarcinoma and 72% of patients with gastric cancer (34/47) were symptomatic at the time of relapse. The majority of asymptomatic relapses were first detected by a rise in tumour markers. There was no difference in disease-free survival between asymptomatic and symptomatic patients, but asymptomatic patients were more likely to receive further treatment and had a longer survival beyond relapse.
CONCLUSION: The majority of relapses occur within the first 3 years and at distant sites. Monitoring of tumour markers should be considered as part of a surveillance program.

Alexandre L, Clark AB, Bhutta HY, et al.
Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study.
Gastroenterology. 2016; 150(4):854-65.e1; quiz e16-7 [PubMed] Related Publications
BACKGROUND & AIMS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed in the primary and secondary prevention of cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer-specific and all-cause mortality.
METHODS: We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics datasets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer-specific and all-cause mortality.
RESULTS: The median survival time of the entire cohort was 9.2 months (interquartile range [IQR], 3.7-23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1-52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3-20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44-0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58-0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (HR, 0.61; 95% CI 0.38-0.96) and all-cause mortality (HR, 0.63; 95% 0.43-0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis.
CONCLUSIONS: In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer-specific and all-cause mortality.

Xie SH, Lagergren J
A model for predicting individuals' absolute risk of esophageal adenocarcinoma: Moving toward tailored screening and prevention.
Int J Cancer. 2016; 138(12):2813-9 [PubMed] Related Publications
Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and poor prognosis, stressing the need for preventive and early detection strategies. We used data from a nationwide population-based case-control study, which included 189 incident cases of EAC and 820 age- and sex-matched control participants, from 1995 through 1997 in Sweden. We developed risk prediction models based on unconditional logistic regression. Candidate predictors included established and readily identifiable risk factors for EAC. The performance of model was assessed by the area under receiver operating characteristic curve (AUC) with cross-validation. The final model could explain 94% of all case patients with EAC (94% population attributable risk) and included terms for gastro-esophageal reflux symptoms or use of antireflux medication, body mass index (BMI), tobacco smoking, duration of living with a partner, previous diagnoses of esophagitis and diaphragmatic hernia and previous surgery for esophagitis, diaphragmatic hernia or severe reflux or gastric or duodenal ulcer. The AUC was 0.84 (95% confidence interval [CI] 0.81-0.87) and slightly lower after cross-validation. A simpler model, based only on reflux symptoms or use of antireflux medication, BMI and tobacco smoking could explain 91% of the case patients with EAC and had an AUC of 0.82 (95% CI 0.78-0.85). These EAC prediction models showed good discriminative accuracy, but need to be validated in other populations. These models have the potential for future use in identifying individuals with high absolute risk of EAC in the population, who may be considered for endoscopic screening and targeted prevention.

Hecht JR, Bang YJ, Qin SK, et al.
Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.
J Clin Oncol. 2016; 34(5):443-51 [PubMed] Related Publications
PURPOSE: To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma.
PATIENTS AND METHODS: Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population.
RESULTS: A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea.
CONCLUSION: Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation.

Macfarlane TV, Murchie P, Watson MC
Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer.
Cancer Epidemiol. 2015; 39(6):1015-22 [PubMed] Related Publications
BACKGROUND: Aspirin and other NSAIDs are widely used as analgesics and the former is a preventative agent for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the mortality in patients with upper aerodigestive tract cancer (UADT) are insufficient. The aim of this study was to investigate the effect of aspirin and other NSAIDs on survival in UADT cancer patients.
METHODS: An observational cohort study of patients with UADT cancer was undertaken using Primary Care Clinical Informatics Unit (PCCIU) database of electronic medical records in Scotland. Information was available on all prescriptions of aspirin and other NSAIDs before and after diagnosis. The main outcome measure was all-cause mortality. Cox regression was used for statistical data analysis.
RESULTS: There were 2392 patients diagnosed with UADT cancer between 1996 and 2010. Mean age of patients was 66 years (SD 12) and most were male (63%). Median survival in head and neck (HNC) patients was 94 months, while median survival in oesophageal cancer patients was 10 months. For HNC improved survival was observed with aspirin prescription (ever vs never hazard ratio (HR) 0.56 95% Confidence Interval (CI) 0.44, 0.71), there was no association with Cyclooxygenase 2 Inhibitors (COX-2) prescriptions. Improved survival was observed with other NSAIDs prescription (ever vs never HR 0.74 95% CI 0.60, 0.90). For oesophageal cancer patients, improved survival was observed with aspirin prescriptions (ever vs never HR 0.54 95% CI 0.45, 0.64), COX-2 prescriptions (HR 0.78 95% CI 0.62, 0.98) and other NSAIDs (HR 0.67 95% CI 0.56, 0.80).
CONCLUSIONS: Aspirin and other NSAIDs prescriptions after diagnosis are associated with a reduced all-cause mortality in UADT cancer patients.

Matula K, Collie-Duguid E, Murray G, et al.
Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer.
BMC Cancer. 2015; 15:762 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Resistance to chemotherapy is common in gastroesophageal cancer. Mechanisms of resistance are incompletely characterised and there are no predictive biomarkers in clinical practice for cytotoxic drugs. We used new cell line models to characterise novel chemotherapy resistance mechanisms and validated them in tumour specimens to identify new targets and biomarkers for gastroesophageal cancer.
METHODS: Cell lines were selected for resistance to oxaliplatin, cisplatin and docetaxel and gene expression examined using Affymetrix Exon 1.0 ST arrays. Leads were validated by qRT-PCR and HPLC of tumour metabolites. Protein expression and pharmacological inhibition of lead target SPHK1 was evaluated in independent cell lines, and by immunohistochemistry in gastroesophageal cancer patients.
RESULTS: Genes with differential expression in drug resistant cell lines compared to the parental cell line they were derived from, were identified for each drug resistant cell line. Biological pathway analysis of these gene lists, identified over-represented pathways, and only 3 pathways - lysosome, sphingolipid metabolism and p53 signalling- were identified as over-represented in these lists for all three cytotoxic drugs investigated. The majority of genes differentially expressed in chemoresistant cell lines from these pathways, were involved in metabolism of glycosphingolipids and sphingolipids in lysosomal compartments suggesting that sphingolipids might be important mediators of cytotoxic drug resistance in gastroeosphageal cancers . On further investigation, we found that drug resistance (IC50) was correlated with increased sphingosine kinase 1(SPHK1) mRNA and also with decreased sphingosine-1-phosphate lysase 1(SGPL1) mRNA. SPHK1 and SGPL1 gene expression were inversely correlated. SPHK1:SGPL1 ratio correlated with increased cellular sphingosine-1-phosphate (S1P), and S1P correlated with drug resistance (IC50). High SPHK1 protein correlated with resistance to cisplatin (IC50) in an independent gastric cancer cell line panel and with survival of patients treated with chemotherapy prior to surgery but not in patients treated with surgery alone. Safingol a SPHK1 inhibitor, was cytotoxic as a single agent and acted synergistically with cisplatin in gastric cancer cell lines.
CONCLUSION: Agents that inhibit SPHK1 or S1P could overcome cytotoxic drug resistance in gastroesophageal cancer. There are several agents in early phase human trials including Safingol that could be combined with chemotherapy or used in patients progressing after chemotherapy.

Xie SH, Lagergren J
The Male Predominance in Esophageal Adenocarcinoma.
Clin Gastroenterol Hepatol. 2016; 14(3):338-347.e1 [PubMed] Related Publications
The incidence of esophageal adenocarcinoma (EAC) has increased rapidly during the past 4 decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastroesophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9:1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, whereas androgens might increase the risk of EAC. However, continuing research efforts are still needed to fully understand the reasons for the male predominance of EAC.

Messager M, de Steur WO, van Sandick JW, et al.
Variations among 5 European countries for curative treatment of resectable oesophageal and gastric cancer: A survey from the EURECCA Upper GI Group (EUropean REgistration of Cancer CAre).
Eur J Surg Oncol. 2016; 42(1):116-22 [PubMed] Related Publications
INTRODUCTION: EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe.
METHODS: Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included.
RESULTS: United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%.
CONCLUSION: This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.

Schaafsma T, Wakefield J, Hanisch R, et al.
Africa's Oesophageal Cancer Corridor: Geographic Variations in Incidence Correlate with Certain Micronutrient Deficiencies.
PLoS One. 2015; 10(10):e0140107 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The aetiology of Africa's easterly-lying corridor of squamous cell oesophageal cancer is poorly understood. Micronutrient deficiencies have been implicated in this cancer in other areas of the world, but their role in Africa is unclear. Without prospective cohorts, timely insights can instead be gained through ecological studies.
METHODS: Across Africa we assessed associations between a country's oesophageal cancer incidence rate and food balance sheet-derived estimates of mean national dietary supplies of 7 nutrients: calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn). We included 32 countries which had estimates of dietary nutrient supplies and of better-quality GLOBCAN 2012 cancer incidence rates. Bayesian hierarchical Poisson lognormal models were used to estimate incidence rate ratios for oesophageal cancer associated with each nutrient, adjusted for age, gender, energy intake, phytate, smoking and alcohol consumption, as well as their 95% posterior credible intervals (CI). Adult dietary deficiencies were quantified using an estimated average requirements (EAR) cut-point approach.
RESULTS: Adjusted incidence rate ratios for oesophageal cancer associated with a doubling of mean nutrient supply were: for Fe 0.49 (95% CI: 0.29-0.82); Mg 0.58 (0.31-1.08); Se 0.40 (0.18-0.90); and Zn 0.29 (0.11-0.74). There were no associations with Ca, Cu and I. Mean national nutrient supplies exceeded adult EARs for Mg and Fe in most countries. For Se, mean supplies were less than EARs (both sexes) in 7 of the 10 highest oesophageal cancer ranking countries, compared to 23% of remaining countries. For Zn, mean supplies were less than the male EARs in 8 of these 10 highest ranking countries compared to in 36% of other countries.
CONCLUSIONS: Ecological associations are consistent with the potential role of Se and/or Zn deficiencies in squamous cell oesophageal cancer in Africa. Individual-level analytical studies are needed to elucidate their causal role in this setting.

Lagergren J, Andersson G, Talbäck M, et al.
Marital status, education, and income in relation to the risk of esophageal and gastric cancer by histological type and site.
Cancer. 2016; 122(2):207-12 [PubMed] Related Publications
BACKGROUND: Marital status, income, and education might influence the risk of esophageal and gastric cancer, but the literature is limited. A large study addressing subtypes of these tumors was used to clarify these associations.
METHODS: A nationwide, Swedish population-based cohort study from 1991 to 2010 included individuals who were 50 years old or older. Data on exposures, covariates, and outcomes were obtained from well-maintained registers. Four esophagogastric tumor subtypes were analyzed in combination and separately: esophageal adenocarcinoma, esophageal squamous cell carcinoma, cardia adenocarcinoma, and noncardia gastric adenocarcinoma. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Analyses were stratified by sex and adjusted for confounders.
RESULTS: Among 4,734,227 participants (60,634,007 person-years), 24,095 developed esophageal or gastric cancer. In comparison with individuals in a long marriage, increased IRRs were found among participants who were in a shorter marriage or were never married, remarried, divorced, or widowed. These associations were indicated for each tumor subtype but were generally stronger for esophageal squamous cell carcinoma. Higher education and income were associated with decreased IRRs in a seemingly dose-response manner and similarly for each subtype. In comparison with the completion of only primary school, higher tertiary education rendered an IRR of 0.64 (95% CI, 0.60-0.69) for men and an IRR of 0.68 (95% CI, 0.61-0.75) for women. Comparing participants in the highest and lowest income brackets (highest 20% vs lowest 20%) revealed an IRR of 0.74 (95% CI, 0.70-0.79) for men and an IRR of 0.83 (95% CI, 0.76-0.91) for women.
CONCLUSIONS: Divorce, widowhood, living alone, low educational attainment, and low income increase the risk of each subtype of esophageal and gastric cancer. These associations require attention when high-risk individuals are being identified. Cancer 2016;122:207-212. © 2015 American Cancer Society.

Vogtmann E, Corley DA, Almers LM, et al.
Oral Bisphosphonate Exposure and the Risk of Upper Gastrointestinal Cancers.
PLoS One. 2015; 10(10):e0140180 [PubMed] Free Access to Full Article Related Publications
The association between oral bisphosphonate use and upper gastrointestinal cancer has been controversial. Therefore, we examined the association with esophageal and gastric cancer within the Kaiser Permanente, Northern California population. A total of 1,011 cases of esophageal (squamous cell carcinoma and adenocarcinoma) and 1,923 cases of gastric adenocarcinoma (cardia, non-cardia and other) diagnosed between 1997 and 2011 from the Kaiser Permanente, Northern California cancer registry were matched to 49,886 and 93,747 controls, respectively. Oral bisphosphonate prescription fills at least one year prior to the index date were extracted. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between prospectively evaluated oral bisphosphonate use with incident esophageal and gastric cancer diagnoses with adjustment for potential confounders. After adjustment for potential confounders, no significant associations were found for esophageal squamous cell carcinoma (OR 0.88; 95% CI: 0.51, 1.52), esophageal adenocarcinoma (OR 0.68; 95% CI: 0.37, 1.24), or gastric non-cardia adenocarcinoma (OR 0.83, 95% CI: 0.59, 1.18), but we observed an adverse association with gastric cardia adenocarcinoma (OR 1.64; 95% CI: 1.07, 2.50). In conclusion, we observed no association between oral bisphosphonate use and esophageal cancer risk within a large community-based population. A significant association was detected with gastric cardia and other adenocarcinoma risk, although this needs to be replicated.

Wilson LF, Green AC, Kendall BJ, et al.
Cancers prevented in Australia in 2010 through the consumption of aspirin.
Aust N Z J Public Health. 2015; 39(5):414-7 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To estimate the proportion and number of cancers in Australia in 2010 that may have been prevented from occurring due to daily use of aspirin in the population.
METHODS: We calculated the Prevented Fraction (PF) of colorectal and oesophageal cancers using standard formulae. The PF is the proportion of the hypothetical total load of cancer in the population that was prevented by exposure to aspirin. The formula incorporates estimates of the prevalence of aspirin use in Australian adult populations, the relative risks associated with aspirin use and cancer incidence.
RESULTS: An estimated 335 colorectal cancers, 22 oesophageal adenocarcinomas and 29 oesophageal squamous cell carcinomas (SCC) were potentially prevented due to daily aspirin use. These figures equate to 2.2%, 3.1% and 5.4% of all colorectal cancers, oesophageal adenocarcinomas and oesophageal SCCs, respectively, that would otherwise have occurred but were potentially avoided due to the daily use of aspirin pertaining in the Australian population.
CONCLUSIONS: At current levels of consumption, a small but measurable reduction in cancer incidence can be attributed to daily aspirin use.
IMPLICATIONS: Assuming the benefits outweigh the harms of known gastrointestinal toxicity and other hazards, aspirin use may be considered for some people to prevent the development of particular gastrointestinal cancers.

Ferdousi M, Azmi S, Petropoulos IN, et al.
Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.
PLoS One. 2015; 10(10):e0139394 [PubMed] Free Access to Full Article Related Publications
There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

Ek WE, Lagergren K, Cook M, et al.
Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.
Int J Cancer. 2016; 138(5):1146-52 [PubMed] Free Access to Full Article Related Publications
The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

Lagergren K, Ek WE, Levine D, et al.
Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
PLoS One. 2015; 10(9):e0138738 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.
METHODS: This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS).
RESULTS: Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.
CONCLUSION: Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Coletta M, Sami SS, Nachiappan A, et al.
Acetic acid chromoendoscopy for the diagnosis of early neoplasia and specialized intestinal metaplasia in Barrett's esophagus: a meta-analysis.
Gastrointest Endosc. 2016; 83(1):57-67.e1 [PubMed] Related Publications
BACKGROUND AND AIMS: Barrett's esophagus (BE) surveillance with random biopsies is time-consuming, invasive, and can lead to sampling error. Acetic acid chromoendoscopy (AAC) with targeted biopsies has been proposed as an effective alternative. The aim of this study was to assess the diagnostic accuracy of AAC for the detection of early neoplasia (high-grade dysplasia [HGD] or early cancer [EC]) and specialized intestinal metaplasia (SIM) in patients with BE.
METHODS: We performed a meta-analysis of all primary studies that compared AAC-based diagnoses (index test) with histopathology as the reference standard. The data were extracted on a per-patient, per-area, and per-procedure basis whenever available.
RESULTS: Thirteen prospective studies met the inclusion criteria. For the diagnosis of HGD/EC, the pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for all included studies (9 studies, 1379 patients) were 0.92 (95% confidence interval [CI], 0.83-0.97), 0.96 (95% CI, 0.85-0.99), 25.0 (95% CI, 5.9-105.3), and 0.08 (95% CI, 0.04-0.18), respectively. Results were not significantly different when considering only studies with a per-patient analysis. For the characterization of SIM, the pooled sensitivity, specificity, LR+, and LR- for all the included studies (8 studies, 516 patients) were 0.96 (95% CI, 0.83-0.99), 0.69 (95% CI, 0.54-0.81), 3.0 (95% CI, 2.0-4.7), and 0.06 (95% CI, 0.01-0.26), respectively. No significant sources of heterogeneity were identified on subgroup analysis.
CONCLUSION: AAC has an overall high diagnostic accuracy for detecting HGD/EC in patients with BE. For SIM characterization, AAC sensitivity is very high but has poor specificity, suggesting that histological confirmation is necessary when AAC is positive.

Lee E, Stram DO, Ek WE, et al.
Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.
Cancer Epidemiol Biomarkers Prev. 2015; 24(11):1801-3 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.
METHODS: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.
RESULTS: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.
CONCLUSIONS: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.
IMPACT: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus.

Ypsilantis PP, Siddique M, Sohn HM, et al.
Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.
PLoS One. 2015; 10(9):e0137036 [PubMed] Free Access to Full Article Related Publications
Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

Anbalagan S, Biasoli D, Leszczynska KB, et al.
In Vitro Radiosensitization of Esophageal Cancer Cells with the Aminopeptidase Inhibitor CHR-2797.
Radiat Res. 2015; 184(3):259-65 [PubMed] Related Publications
With the increased incidence of esophageal cancer, chemoradiotherapy continues to play an important role in the management of this disease. Developing potent radiosensitizers is therefore critical for improving outcomes. The use of drugs that have already undergone clinical testing is an appealing approach once the side effects and tolerated doses are established. Here, we demonstrate that the aminopeptidase inhibitor, CHR-2797/tosedostat, increases the radiosensitivity of esophageal cancer cell lines (FLO-1 and OE21) in vitro in both normoxic and physiologically relevant low oxygen conditions. To our knowledge, the effective combination of CHR-2797 with radiation exposure has not been reported previously in any cancer cell type. The mechanism of increased radiosensitivity was not dependent on the induction of DNA damage or DNA repair kinetics. Our data support the need for further preclinical testing of CHR-2797 in combination with radiotherapy for the treatment of esophageal cancer.

Varghese S, Newton R, Ross-Innes CS, et al.
Analysis of dysplasia in patients with Barrett's esophagus based on expression pattern of 90 genes.
Gastroenterology. 2015; 149(6):1511-1518.e5 [PubMed] Related Publications
BACKGROUND & AIMS: Diagnoses of dysplasia, based on histologic analyses, dictate management decisions for patients with Barrett's esophagus (BE). However, there is much intra- and inter-observer variation in identification of dysplasia-particularly low-grade dysplasia. We aimed to identify a biomarker that could be used to assign patients with low-grade dysplasia to a low- or high-risk group.
METHODS: We performed a stringent histologic assessment of 150 frozen esophageal tissues samples collected from 4 centers in the United Kingdom (from 2000 through 2006). The following samples with homogeneous diagnoses were selected for gene expression profiling: 28 from patients with nondysplastic BE, 10 with low-grade dysplasia, 13 with high-grade dysplasia (HGD), and 8 from patients with esophageal adenocarcinoma. A leave-one-out cross-validation analysis was used identify a gene expression signature associated with HGD vs nondysplastic BE. Functional pathways associated with gene signature sets were identified using the MetaCore analysis. Gene expression signature sets were validated using gene expression data on BE and esophageal adenocarcinoma accessed through National Center for Biotechnology Information Gene Expression Omnibus, as well as a separate set of samples (n = 169) collected from patients who underwent endoscopy in the United Kingdom or the Netherlands and analyzed histologically.
RESULTS: We identified an expression pattern of 90 genes that could separate nondysplastic BE tissues from those with HGD (P < .0001). Genes in a pathway regulated by retinoic acid-regulated nuclear protein made the largest contribution to this gene set (P < .0001); the transcription factor MYC regulated at least 30% of genes within the signature (P < .0001). In the National Center for Biotechnology Information Gene Expression Omnibus validation set, the signature separated nondysplastic BE samples from esophageal adenocarcinoma samples (P = .0012). In the UK and Netherlands validation cohort, the signature identified dysplastic tissues with an area under the curve value of 0.87 (95% confidence interval: 0.82-0.93). Of samples with low-grade dysplasia (LGD), 64% were considered high risk according to the 90-gene signature; these patients had a higher rate of disease progression than those with a signature categorized as low risk (P = .047).
CONCLUSIONS: We identified an expression pattern of 90 genes in esophageal tissues of patients with BE that was associated with low- or high-risk for disease progression. This pattern might be used in combination with histologic analysis of biopsy samples to stratify patients for treatment. It would be most beneficial for analysis of patients without definitive evidence of HGD but for whom early endoscopic intervention is warranted.

Bibby BA, Reynolds JV, Maher SG
MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.
PLoS One. 2015; 10(7):e0134180 [PubMed] Free Access to Full Article Related Publications
Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC.

Markar S, Gronnier C, Duhamel A, et al.
Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?
J Clin Oncol. 2015; 33(33):3866-73 [PubMed] Related Publications
PURPOSE: The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome.
PATIENTS AND METHODS: Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from SALV for persistent (n = 234) versus recurrent disease (n = 74) were compared. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics.
RESULTS: SALV versus NCRS groups: In-hospital mortality was similar in both groups (8.4% v 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and surgical site infection, which were both more frequent in the SALV group. At 3 years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free survival (39.2% v 32.8%; P = .232) after matching, along with a similar recurrence pattern. Persistent versus recurrent disease groups: There were no significant differences between groups in incidence of in-hospital mortality or major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease-free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease group.
CONCLUSION: The results of this large multicenter study from the modern era suggest that SALV can offer acceptable short- and long-term outcomes in selected patients at experienced centers. Persistent cancer after definitive chemoradiotherapy seems to be more biologically aggressive, with poorer survival compared with recurrent cancer.

Markar SR, Gronnier C, Duhamel A, et al.
Significance of Microscopically Incomplete Resection Margin After Esophagectomy for Esophageal Cancer.
Ann Surg. 2016; 263(4):712-8 [PubMed] Related Publications
OBJECTIVE: The objectives of this study were to establish if R1 resection margin after esophagectomy was (i) a poor prognostic factor independent of patient and tumor characteristics, (ii) a marker of tumor aggressiveness and (iii) to look at the impact of adjuvant treatment in this subpopulation.
METHODS: Data were collected from 30 European centers from 2000 to 2010. Patients with an R1 resection margin (n = 242) were compared with those with an R0 margin (n = 2573) in terms of short- and long-term outcomes. Propensity score matching and multivariable analyses were used to compensate for differences in baseline characteristics.
RESULTS: Independent factors significantly associated with an R1 resection margin included an upper third esophageal tumor location, preoperative malnutrition, and pathological stage III. There were significant differences between the groups in postoperative histology, with an increase in pathological stage III and TRG 4-5 in the R1 group. Total average lymph node harvests were similar between the groups; however, there was an increase in the number of positive lymph nodes seen in the R1 group. Propensity matched analysis confirmed that R1 resection margin was significantly associated with reduced overall survival and increased overall, locoregional, and mixed tumor recurrence. Similar observations were seen in the subgroup that received neoadjuvant chemoradiation. In R1 patients adjuvant therapy improved survival and reduced distant recurrence however failed to affect locoregional recurrence.
CONCLUSIONS: This large multicenter European study provides evidence to support the notion that R1 resection margin is a prognostic indication of aggressive tumor biology with a poor long-term prognosis.

Haidry RJ, Lipman G, Banks MR, et al.
Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.
Endoscopy. 2015; 47(11):980-7 [PubMed] Related Publications
BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry.
PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached.
RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01).
CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

Wiggins T, Markar SR, Arya S, Hanna GB
Anastomotic reinforcement with omentoplasty following gastrointestinal anastomosis: A systematic review and meta-analysis.
Surg Oncol. 2015; 24(3):181-6 [PubMed] Related Publications
Anastomotic leak is a potentially devastating complication following gastrointestinal anastomosis. Some surgeons believe that reinforcing the anastomosis with omentum reduces the incidence and severity of anastomotic leak. A comprehensive electronic search of EMBASE, Medline, Web of Science and Cochrane databases was performed. Pooled odds ratios (POR) were calculated for discrete variables. There were six studies investigating esophageal anastomosis and 3 studies investigating colorectal anastomosis identified by the literature search. A total of 2296 patients were included, 1073 with omentoplasty and 1223 without. In esophageal surgery omentoplasty significantly reduced the rate of anastomotic leak (2.9% vs 10.5% (POR = 0.28; 95% CI = 0.17 to 0.47; P < 0.0001), but there was no significant effect upon in-hospital mortality (2.3% vs. 2.5%; POR = 0.911 [95% CI 0.439-1.887]; P = 0.802) or anastomotic stricture between the two groups (6.6% vs 9.1%; POR = 0.842 [95% CI 0.331 to 2.145]; P = 0.720). In colorectal surgery there was no significant difference in anastomotic leak rate (5.0% vs 8.4%; POR: 0.50; 95% CI 0.21 to 1.17) or in-hospital mortality (4.2% vs 4.1%; POR: 0.90; 95% CI 0.34 to 2.41). The results of this analysis show that omentoplasty significantly reduced the rate of anastomotic leak following esophageal anastomosis but these results were not observed in colorectal anastomosis. Omentoplasty could be used as an adjunct technique to reduce the incidence of anastomotic leak in oesophageal anastomosis.

Buas MF, Onstad L, Levine DM, et al.
MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.
PLoS One. 2015; 10(6):e0128617 [PubMed] Free Access to Full Article Related Publications
Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.

Hashemian M, Poustchi H, Abnet CC, et al.
Dietary intake of minerals and risk of esophageal squamous cell carcinoma: results from the Golestan Cohort Study.
Am J Clin Nutr. 2015; 102(1):102-8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Dietary factors have been hypothesized to affect the risk of esophageal cancer via different mechanisms, but the intake of minerals is understudied and the evidence is conflicting.
OBJECTIVE: The objective was to evaluate the associations of dietary intake of minerals with risk of esophageal squamous cell carcinoma (ESCC).
DESIGN: We used data from the Golestan Cohort Study, which was launched in a high-risk region for esophageal cancer in Iran. Participants were enrolled in 2004-2008 and were followed to 2014. Intakes of minerals were assessed with a validated food-frequency questionnaire. A Cox proportional hazards model was used to estimate HRs and 95% CIs of ESCC for dietary intakes of selected minerals.
RESULTS: We identified 201 ESCC cases among 47,405 subjects. Calcium intake was significantly inversely associated with the risk of ESCC (HR per 100-mg/d increase: 0.88; 95% CI: 0.81, 0.96; P = 0.005; quartile 4 vs. quartile 1 HR: 0.49; 95% CI: 0.29, 0.82; P-trend = 0.013). Zinc intake was also inversely associated with ESCC, but the quartile association did not reach significance (HR per 1-mg/d increase: 0.87; 95% CI: 0.77, 0.98; P = 0.027; quartile 4 vs. quartile 1 HR: 0.56; 95% CI: 0.28, 1.12; P-trend = 0.097). The relations between dietary intakes of selenium, magnesium, and copper and risk of ESCC were nonlinear (P-nonlinear trend = 0.001, 0.016, and 0.029, respectively). There was no relation between dietary intake of manganese and the risk of ESCC.
CONCLUSION: The results suggest that higher intakes of calcium and zinc are associated with a lower risk of ESCC in a high-risk region of Iran.

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