National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett's oesophagus and stage I oesophageal adenocarcinoma.

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.

Para-conduit diaphragmatic hernia following esophagectomy-the new price of minimally invasive surgery?

Esophageal Cancer is the seventh commonest cancer worldwide with poor overall survival. Significant morbidity related to open esophagectomy has driven practice toward hybrid, totally minimally invasive and robotic procedures. With the increase in minimally invasive approaches, it has been suggested that there might be an increased incidence of subsequent para-conduit diaphragmatic hernia. To assess the incidence, modifiable risk factors and association with operative approach of this emerging complication, we evaluated outcomes following esophagectomy from two Australian Centers. Prospectively collected databases were examined to identify patients who developed versus did not develop a para-conduit hernia. Patient characteristics, disease factors, treatment factors, operative and post-operative factors were compared for these two groups. A total of 24 of 297 patients who underwent esophagectomy were diagnosed with a symptomatic para-conduit diaphragmatic hernia (8.1%). The significant risk factor for hernia was a minimally invasive abdominal approach (70.8% vs. 35.5%; P = 0.004, odds ratio = 12.876, 95% CI 2.214-74.89). Minimally invasive thoracic approaches were not associated with increased risk. Minimally invasive abdominal approaches to esophagectomy doubled the risk of developing a para-conduit diaphragmatic hernia. Effective operative solutions to address this complication are required.

Esophageal cancer epidemiology, diagnosis, and management in Sudan - A review.

INTRODUCTION: In Sudan, cancer a common health challenge, is the leading cause of death after malaria and viral pneumonia. The aim of the review is to determine the risk factors associated with esophageal cancer (EC) among Sudanese population. METHODS: All published online data concerning EC epidemiology, diagnosis, and management in Sudan were studied. RESULTS: The prevalence of EC in Sudan is ranked fourth among cancer types in males and fifth in females. The squamous cell carcinoma is more predominant than adenocarcinoma. The dietary, dysplasia and teeth loss, cigarette smoking, age, sex, GERD, genetic and environmental interactions remain a risk for developing EC in clinical practice. A significant challenge for treatment is that most of EC patients were often diagnosed in advanced stages due to the lack of early clinical symptoms. Management of EC depends on patient fitness and tumor stage, endoscopic removal was used for early tumors, while chemotherapy, chemo-radiotherapy, surgical resection, or combinations of these were used for advanced tumors. Despite improvements in the management and treatment of EC patients, the general outcome remains very poor. Furthermore, using molecular techniques to better understand the etiology of EC, it may assist in identifying complicated and critical issues and improve therapy towards a new treatment strategy. CONCLUSION: The remarkable factors associated with EC among Sudanese are geographical variation, environmental factors, ethnic differences, dietary and social habits.

Changing trends in the disease burden of esophageal cancer in China from 1990 to 2017 and its predicted level in 25 years.

BACKGROUND: Nearly half of the cases of esophageal cancer in the world were in China, but the corresponding burden in China has not been estimated for the past decades or for the near future. METHODS: Data on the incidence, mortality, and disability-adjusted life years (DALYs) rates owing to esophageal cancer in China from 1990 to 2017 were extracted from the Global Burden of Disease Study 2017. To reflect the trend in the disease burden, we calculated the estimated annual percentage change (EAPC) in the age-standardized rates of these three outcomes in China from 1990 to 2017. RESULTS: The age-standardized incidence rate (ASIR) for esophageal cancer decreased from 19.38/100,000 in 1990 to 12.23/100,000 in 2017, with an EAPC of -2.53 (95%CI: -2.90, -2.16), but the number of cases of esophageal cancer increased from 164,473 to 234,624. The age-standardized rates of esophageal cancer in females were always lower than they were in males during the study period, and there was a downward trend that was more pronounced among females than males. The most common risk factors for males were smoking and alcohol consumption, while the most common risk factors for females were a diet low in fruits and a high body mass index (BMI). New cases of, and deaths from esophageal cancer are predicted to increase by about 1.5 times in the coming 25 years. CONCLUSION: Although the age-standardized burden of esophageal cancer has been declining, the number of new cases of, and deaths from esophageal cancer have increased in China over the past 30 years, and they will continue to increase in the near future. Hence, national policies should be adopted to promote the prevention and management of known risk factors for it, especially smoking and excessive caloric intake.

Cost-effectiveness analysis of nivolumab in the second-line treatment for advanced esophageal squamous cell carcinoma.

Background: To investigate the cost-effectiveness of nivolumab versus chemotherapy in the second-line treatment for advanced esophageal squamous cell carcinoma. Materials & methods: A Markov model reflecting the patients in the ATTRACTION-3 trial was established. Weibull survival model was employed to fit the Kaplan-Meier progression-free survival and overall survival probabilities of the nivolumab and chemotherapy strategy, respectively. Meanwhile, one-way and PSA were performed to test the uncertainty in the model. Results: Overall, the incremental effectiveness and cost of nivolumab versus chemotherapy were 0.107 quality-adjusted life-years and $14,627.90, resulting in an incremental cost-effectiveness ratio of $136,709.35/quality-adjusted life-year. Conclusion: Nivolumab is not a cost-effective treatment option compared with chemotherapy from the perspective of Chinese society.

Systematic review and meta-analysis of esophageal cancer in Africa: Epidemiology, risk factors, management and outcomes.

BACKGROUND: Esophageal cancer (EC) is associated with a poor prognosis, particularly so in Africa where an alarmingly high mortality to incidence ratio prevails for this disease. AIM: To provide further understanding of EC in the context of the unique cultural and genetic diversity, and socio-economic challenges faced on the African continent. METHODS: We performed a systematic review of studies from Africa to obtain data on epidemiology, risk factors, management and outcomes of EC. A non-systematic review was used to obtain incidence data from the International Agency for Research on Cancer, and the Cancer in Sub-Saharan reports. We searched EMBASE, PubMed, Web of Science, and Cochrane Central from inception to March 2019 and reviewed the list of articles retrieved. Random effects meta-analyses were used to assess heterogeneity between studies and to obtain odds ratio (OR) of the associations between EC and risk factors; and incidence rate ratios for EC between sexes with their respective 95% confidence intervals (CI). RESULTS: The incidence of EC is higher in males than females, except in North Africa where it is similar for both sexes. The highest age-standardized rate is from Malawi (30.3 and 19.4 cases/year/100000 population for males and females, respectively) followed by Kenya (28.7 cases/year/100000 population for both sexes). The incidence of EC rises sharply after the age of 40 years and reaches a peak at 75 years old. Meta-analysis shows a strong association with tobacco (OR 3.15, 95%CI: 2.83-3.50). There was significant heterogeneity between studies on alcohol consumption (OR 2.28, 95%CI: 1.94-2.65) and on low socioeconomic status (OR 139, 95%CI: 1.25-1.54) as risk factors, but these could also contribute to increasing the incidence of EC. The best treatment outcomes were with esophagectomy with survival rates of 76.6% at 3 years, and chemo-radiotherapy with an overall combined survival time of 267.50 d. CONCLUSION: Africa has high incidence and mortality rates of EC, with preventable and non-modifiable risk factors. Men in this setting are at increased risk due to their higher prevalence of tobacco and alcohol consumption. Management requires a multidisciplinary approach, and survival is significantly improved in the setting of esophagectomy and chemoradiation therapy.

A suggested framework for conducting esophageal cancer screening in China.

Esophageal cancer is one of the most prevalent malignant tumors worldwide. Because of its challenging clinical characteristics, esophageal cancer is a major disease burden on the economy, society, and individuals. There is an urgent need to establish a beneficial policy to reduce the burden and to improve the health-related quality of life of patients. Primary prevention with smoking cessation and reduction of drinking alcohol are highly recommended. Screening, early diagnosis and treatment are suggested. This study intended to establish a modified future screening model from the social perspective that deploys different strategies for different populations. Risk assessment and community-based screening are proposed for high-risk populations. Health education in low-risk areas could help promote primary prevention to mitigate lifestyle factors and to increase public awareness and potentially to increase screening and early detection.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

Screening and Surveillance for Barrett's Esophagus: Is It Cost-Effective?

The cost-effectiveness of screening and surveillance for Barrett's esophagus continues to evolve as the incidence of esophageal adenocarcinoma increases, biomarkers enhance the identification of individuals at highest risk for developing cancer, and endoscopic eradication of Barrett's esophagus improves. Screening to detect Barrett's esophagus may be cost-effective in selected high-risk groups based on age, race, sex and other factors such as symptoms of heartburn. Currently, endoscopic eradication therapy for Barrett's esophagus and high-grade dysplasia is a cost-effective intervention, while endoscopic therapy for non-dysplastic Barrett's esophagus is not a cost-effective strategy. As diagnosis of low-grade dysplasia improves, endoscopic eradication therapy may also prove to be a cost-effective intervention.

How to get the most out of costly Barrett's oesophagus surveillance.

Current endoscopic surveillance protocols for Barrett's oesophagus have several limitations, mainly the poor cost-effectiveness and high miss rate. However, there is sufficient evidence that patients enrolled in a surveillance program have better survival chances of oesophageal cancer due to earlier tumor stages at diagnosis compared to patients with de novo diagnosed oesophagus cancer. Risk stratifications aim to identify patients at highest risk of developing adenocarcinoma of the oesophagus; most of them base on the length of the Barrett's segment and the presence of dysplasia. This review discusses prognostic factors and provides practical guidance on how to improve the efficacy and outcome in Barrett's surveillance programs.

Comparative oesophageal cancer risk assessment of hot beverage consumption (coffee, mate and tea): the margin of exposure of PAH vs very hot temperatures.

BACKGROUND: Consumption of very hot (> 65 °C) beverages is probably associated with increased risk of oesophageal cancer. First associations were reported for yerba mate and it was initially believed that high content of polycyclic aromatic hydrocarbons (PAH) might explain the risk. Later research on other beverage groups such as tea and coffee, which are also consumed very hot, found associations with increased risk of oesophageal cancer as well. The risk may therefore not be inherent in any compound contained in mate, but due to temperature. The aim of this study was to quantitatively assess the risk of PAH in comparison with the risk of the temperature effect using the margin of exposure (MOE) methodology. METHODS: The human dietary benzo[a]pyrene (BaP) and PAH4 (sum of benzo[a]pyrene, benzo[a]anthracene, chrysene, and benzo[b]fluoranthene) exposure through consumption of coffee, mate, and tea was estimated. The oesophageal cancer risk assessment for both PAH and temperature was conducted using the MOE approach. RESULTS: Considering differences in the transfer of the PAH from the leaves of mate and tea or from the ground coffee to the infusion, and considering the different preparation methods, exposures may vary considerably. The average individual exposure in µg/kg bw/day arising from consumption of 1 cup (0.2 L) of infusion was highest for mate (2.85E-04 BaP and 7.22E-04 PAH4). The average per capita exposure in µg/kg bw/day was as follows: coffee (4.21E-04 BaP, 4.15E-03 PAH4), mate (4.26E-03 BaP, 2.45E-02 PAH4), and tea (8.03E-04 BaP, 4.98E-03 PAH4). For all individual and population-based exposure scenarios, the average MOE for BaP and PAH4 was > 100,000 independent of beverage type. MOE values in this magnitude are considered as a very low risk. On the contrary, the MOE for the temperature effect was estimated as < 1 for very hot drinking temperatures, corroborating epidemiological observations about a probable oesophageal cancer risk caused by this behaviour. CONCLUSIONS: The temperature effect but not PAH exposure may pose an oesophageal cancer risk. Consumer education on risks associated with consumption of 'very hot' beverages and policy measures to threshold serving temperatures should be discussed.

Evaluation of a novel infra-red endoscopy system in the assessment of early neoplasia in Barretts esophagus: pilot study from a single center.

Infrared endoscopy (IRE) has been shown to be useful in detecting submucosal (SM) invasion in early gastric cancer. Its role in the endoscopic assessment of Barrett's neoplasia has not been reported to date. We aimed in this study to evaluate the role of IRE in the detection and characterization of early neoplastic lesions within Barrett's esophagus (BE). The secondary aim was to explore its usefulness for the assessment of the presence of submucosal invasion in these early neoplastic Barrett's lesions. We included in the study patients with dysplastic BE who were referred to our institution for endoscopic therapy of a previously diagnosed early Barrett's neoplasia. An examination with white light high resolution endoscopy (HRE) and near IRE after intravenous injection of indocyanine green was performed for all patients using an infrared endoscope prototype. Staining on IRE and correlation with final histological staging by endoscopic mucosal resection/surgery or histological diagnosis on mapping biopsies was analyzed. A total of 23 patients were enrolled in our study: 17 of them with 19 visible lesions and 6 patients with flat BE and no lesions. Staining on IRE was noted in 18 cases: 17 (94%) had at least high grade dysplasia (HGD). No stain was noted in 7 cases: final histology was

Barrett's oesophagus: Current controversies.

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.

Effectiveness and Cost-Effectiveness of Endoscopic Screening and Surveillance.

Guidelines for the screening and surveillance of Barrett's esophagus continue to evolve as the incidence of esophageal adenocarcinoma increases, identification of individuals at highest risk for cancer improves, and management of dysplasia evolves. This article reviews related studies and economic analyses. Advances in diagnosis offer promising strategies to help focus screening efforts on those individuals who are most likely to develop esophageal adenocarcinoma.

Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: An analysis of SEER-Medicare data.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk and increases the risk of Barrett esophagus, which is the precursor lesion of esophageal adenocarcinoma (EA), primarily in the absence of gastroesophageal reflux disease (GERD). However, to the authors' knowledge, little is known regarding whether MetS is associated with the risk of EA. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, the authors evaluated whether MetS was associated with EA. A total of 3167 cases of EA were compared with individually matched population controls (5:1); a subset of 575 EA cases were able to be individually matched with 575 Barrett esophagus controls. MetS was defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in the period 1 to 3 years before the diagnosis of EA or control selection. Unconditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. Potential effect modification by GERD symptoms and sex was examined in stratified models. RESULTS: EA was found to be significantly associated with MetS (odds ratio, 1.16; 95% confidence interval, 1.06-1.26) compared with population controls. In males, the association was restricted to those individuals without prior GERD; however, in females, MetS was found to be associated with EA regardless of GERD status. Effect modification by sex was observed (P for interaction = .01). MetS was not found to be associated with EA risk when compared with Barrett esophagus controls. CONCLUSIONS: In this older population, MetS was found to be associated with an increased risk of EA in males without GERD and females regardless of GERD status. Given the lack of an association when compared with Barrett esophagus controls, MetS may impact EA risk by primarily increasing the risk of the precursor lesion, Barrett esophagus. Cancer 2017;123:657-665. © 2016 American Cancer Society.

Healthcare Cost of Over-Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus.

INTRODUCTION: Published reports have demonstrated that many Barrett's esophagus patients are over-diagnosed as low-grade dysplasia (BE-LGD). We performed an analysis of the surveillance and treatment costs associated with the over-diagnosis of BE-LGD. METHODS: As the principal cost variables, we used endoscopic and histologic procedures performed during the recommended surveillance intervals for patients with BE-LGD, the national average Medicare reimbursement for the Current Procedural Terminology codes of the procedures performed, and a spreadsheet-based tool we created to determine the overall healthcare cost associated with the over-diagnosis of BE-LGD in the US population. RESULTS: The average excess cost (range) for every patient in the US who is over-diagnosed with BE-LGD is estimated to be $5557 ($3115 to $8072). The principal contributors to the excess cost of over-diagnosis of BE-LGD in these patients are: endoscopy ($2626 to $4639), pathologist biopsy review ($275 to $2185), and esophagogastroduodenoscopy-guided endoscopic ablation ($214 to $1249). CONCLUSIONS: The healthcare cost of over-diagnosis of BE-LGD is significant. To reduce the overall healthcare cost impact of over-diagnosis of BE-LGD, strict adherence to the recommendations of the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy that pathology review of all BE biopsy specimens be performed by a gastrointestinal pathologist is warranted.

Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients With Barrett's Esophagus for Esophageal Adenocarcinoma Screening.

Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past decades in Western countries. As a premalignant lesion, Barrett's esophagus (BE) is an established risk factor of EAC. This study estimated the impact of surveillance endoscopy for BE on population's survival upon EAC by a whole-population cost-effectiveness analysis among modeled Western population. Possibilities and survival payoffs were retrieved through literature searching based on PubMed database. Patients with BE were classified as adequate surveillance (AS), inadequate surveillance (IAS), and no surveillance groups. Direct cost of endoscopy per person-year was estimated from diagnosis of BE to before diagnosis of EAC in the whole-population model, whereas the payoff was 2-year disease-specific survival rate of EAC. AS for patients with BE had lower cost-effectiveness ratio (CER) than that of IAS group, as well as lower incremental cost-effectiveness ratio (6116 ∈/% vs 118,347 ∈/%). Prolonging the surveillance years could decrease the yearly cost in whole population and also relevant CERs, despite increased total cost. Increasing the proportion of participants in AS group could improve the survival benefit. The maximal payoff was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra ∈ 1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE subpopulation plan can reduce yearly budget. Attempt to increase the proportion of AS participants can induce decline in population mortality of EAC, despite extra but acceptable expenditure. However, regarding optimal cost-effectiveness, further studies are still required to identify a high-risk subpopulation out of BE patients for endoscopic surveillance.

Caustic oesophagitis in children: prevalence, the corrosive agents involved, and management from primary care through to surgery.

PURPOSE OF REVIEW: Caustic substance ingestion (CSI) remains a major health issue, particularly in developing countries, where laws are not effectively enforced. This review offers a thorough analysis of the current epidemiology, clinical features, management, treatment, and long-term complications of CSI in children. RECENT FINDINGS: Strong alkalis sold in liquid and granular forms, particularly crystalline grease cleaners (concentrated sodium hydroxide), are the principal causes of severe oesophageal damage. Currently, early endoscopy to assess the gastro-oesophageal mucosa is not considered necessary for all CSI cases. Oesophageal stricture is a major complication developing after CSI, and should be diagnosed and treated earlier, 10-14 days after CSI via commencement of a dilation program. Fluoroscopically guided oesophageal balloon dilatation seems to be safe, with a low frequency of complications and a high success rate. However, it should commence earlier than is currently the case, and should be performed gently, using balloons of gradually increasing diameter. If dilation fails after a few months, oesophageal replacement surgery should be performed. SUMMARY: Unfortunately, neither dilatation treatment nor oesophageal bypass surgery can prevent the development of oesophageal carcinoma, the incidence of which is high after CSI. The continuing unacceptably high incidence of CSI accidents would be reduced if corrosive materials were sold in their original childproof containers, highlighting the need for preventive and adult education programmes.

Out-of-field organ doses and associated radiogenic risks from para-aortic radiotherapy for testicular seminoma.

PURPOSE: The aims of this study were to (a) calculate the radiation dose to out-of-field organs from radiotherapy for stage I testicular seminoma and (b) estimate the associated radiogenic risks. METHODS: Monte Carlo methodology was employed to model radiation therapy with typical anteroposterior and posteroanterior para-aortic fields on an anthropomorphic phantom simulating an average adult. The radiation dose received by all main and remaining organs that defined by the ICRP publication 103 and excluded from the treatment volume was calculated. The effect of field dimensions on each organ dose was determined. Additional therapy simulations were generated by introducing shielding blocks to protect the kidneys from primary radiation. The gonadal dose was employed to assess the risk of heritable effects for irradiated male patients of reproductive potential. The lifetime attributable risks (LAR) of radiotherapy-induced cancer were estimated using gender- and organ-specific risk coefficients for patient ages of 20, 30, 40, and 50 years old. The risk values were compared with the respective nominal risks. RESULTS: Para-aortic irradiation to 20 Gy resulted in out-of-field organ doses of 5.0-538.6 mGy. Blocked field treatment led to a dose change up to 28%. The mean organ dose variation by increasing or decreasing the applied field dimensions was 18.7% ± 3.9% and 20.8% ± 4.5%, respectively. The out-of-field photon doses increased the lifetime intrinsic risk of developing thyroid, lung, bladder, prostate, and esophageal cancer by (0.1-1.4)%, (0.4-1.1)%, (2.5-5.4)%, (0.2-0.4)%, and (6.4-9.2)%, respectively, depending upon the patient age at exposure and the field size employed. A low risk for heritable effects of less than 0.029% was found compared with the natural incidence of these defects. CONCLUSIONS: Testicular cancer survivors are subjected to an increased risk for the induction of bladder and esophageal cancer following para-aortic radiotherapy. The probability for the appearance of any other malignant disease to out-of-field organs was slightly elevated in respect to the nominal cancer incidence rates.