Prevention Strategies for Esophageal Cancer—An Expert Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Epidemiology
3. Risk Factors and Primary Prevention
3.1. Esophageal Squamous-Cell Carcinoma
3.2. Esophageal Adenocarcinoma
4. Secondary Prevention
4.1. Esophageal Squamous Carcinoma
4.2. Esophageal Adenocarcinoma
4.2.1. Endoscopic Screening
4.2.2. Chemoprevention of Barrett’s Esophagus
4.2.3. Barrett’s Treatment
Drug | Mechanism of Action | Type of Study | Main Findings and Reported Relative Risks or Odds Ratios (OR), | Recommendations |
---|---|---|---|---|
Statins | Vitro and animal studies:
| Observational [66,83,84,85,86,87,88,90] Meta-analysis [82,89,93] | A significant reduction in the risk of esophageal cancer among patients who took statins (adjusted OR, 0.72; 95% CI, 0.60–0.86). In BE patients, statins were associated with a significant (41%) decrease in the risk of EAC (adjusted OR, 0.59; 95% CI, 0.45–0.78) [93] Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus [adjusted OR 0.62 (95% confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95% CI 0.21–0.89)] [82]. Statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95% CI 0.51–0.77)] [82] | Statin use is not recommended as a chemo-preventive agent |
Proton Pump Inhibitors Use |
| Observational [63,64,65] Meta-analysis [67] | The use of PPIs included in the study or during the follow-up period reduced the risk of neoplastic progression (Hazard ratio, 0.41; 95% confidence interval, 0.18–0.93 and hazard ratio, 0.21; 95% confidence interval, 0.07–0.66) [64] | Once daily PPI therapy have to be assumed |
NSAID and aspirin |
| Observational [71,72,73,74,75,76,77,78,79] Meta-analysis [80] | Statistical pooling showed a protective association between any use of aspirin/NSAID and esophageal cancer (OR 0.57; 95% CI 0.47– 0.71). Both intermittent (OR 0.82; CI, 0.67–0.99) and frequent medication use were protective (OR 0.54; CI, 0.43–0.67), with greater protection with more frequent use. Stratified by medication type, aspirin use was protective (OR 0.5; CI, 0.38–0.66), and NSAIDs had a borderline protective association (OR 0.75; CI 0.54–1.0). Any use was protective against both esophageal adenocarcinoma (OR 0.67; CI, 0.51–0.87) and squamous cell carcinoma (OR 0.58; CI, 0.43–0.78) [80] | Aspirin and NSAIDs are not recommended as chemo-preventive agents |
Metformin |
| Observational [95] | - | Metformin is not recommended as a chemo-preventive agent |
Anti-Reflux Surgery |
| Observational [96] RCT [100] Meta-analysis [97,98,99] | In patients with Barrett’s esophagus, the corresponding IRR was 0.46 (95% CI 0.20–1.08) and 0.26 (95% CI 0.09–0.79) when restricted to publications after 2000 [99] | Anti-reflux surgery may prevent EAC better than medical therapy in patients with Barrett’s esophagus |
Barrett’s Treatments |
| Observational [101,103,105] RCT [102] Meta-analysis [104] | The progression of BE-LGD to either HGD or EAC was significantly lower in patients treated with RFA compared with endoscopic surveillance (OR: 0.17, 95% CI: 0.04–0.65, p = 0.01). The progression to HGD alone was significantly lower in patients treated with RFA vs. endoscopic surveillance (OR: 0.23, 95% CI: 0.08–0.61, p= 0.003). Progression to EAC alone was numerically lower in RFA compared with endoscopic surveillance without statistical significance (OR: 0.44, 95% CI: 0.17–1.16, p = 0.09) [104] | It is recommended endoscopic eradication therapy with RFA, PDT or EMR in Barrett esophagus with high grade dysplasia |
5. Tertiary Prevention
5.1. Surveillance for ESCC
5.2. Incidence of ESCC after Surgery of Achalasia
5.3. Endoscopic Surveillance for BE
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Risk Factor | Squamous-Cell Carcinoma | Adenocarcinoma | Note |
---|---|---|---|
Tobacco use | +++ | ++ | Tobacco contains carcinogens and promotes inflammation Tobacco and alcohol use are two factors that work synergistically. |
Alcohol use | +++ | − | Tobacco and alcohol use are two factors that work synergistically |
Mutations of enzymes that metabolize alcohol | Genetic susceptibility, e.g., loci at PLCE1, C20orf54, ADH1B and ALDH2 coupled with alcohol consumption and smoking | ||
Barrett’s esophagus | − | ++++ | |
Weekly reflux symptoms | − | +++ | |
Obesity | − | ++ | It increases gastroesophageal reflux and inflammatory cytokines |
Poverty | ++ | − | |
Achalasia | +++ | − | |
Caustic injury to the esophagus | ++++ | − | |
Non-epidermolytic palmoplantar keratoderma (tylosis) | ++++ | − | |
Plummer-Vinson Syndrome | ++++ | − | |
History of head and neck cancer | ++++ | − | |
History of breast cancer treated with radiotherapy | +++ | +++ | |
Frequent consumption of extremely hot beverages | + | − | |
Prior use of beta-blockers, anticholinergic agents, or aminophylline | − | ± | |
HPV 16 and 18 in some areas | − |
Lifestyle and Clinical Factors | Mechanism of Action | Type of Study | Main Findings and Reported Relative Risks (RR) or Odds Ratios (OR) | Recommendations |
---|---|---|---|---|
Smoking |
| Observational [24,25,26,27,31] | Tobacco smoking cessation < 10 y: OR, 0.82; 95% CI, 0.60–1.13 [31] Tobacco smoking cessation ≥10 y: OR, 0.71; 95% CI, 0.56–0.89 [31] | Abstinence from smoking. The synergic action with alcohol is important to know and to correct. |
Food |
| Observational [25] Meta-analysis [30] | The overall pooled RR of EC and the confidence intervals for the groups with the highest versus the lowest levels of intake were as follows: 0.99 (95% CI: 0.85–1.15) for total meat; 1.40 (95%CI: 1.09–1.81) for red meat; 1.41 (95%CI: 1.13–1.76) for processed meat; 0.87 (95%CI: 0.60–1.24) for poultry; 0.80 (95%CI: 0.64–1.00) for fish [30] | Avoidance of meat, processed food intake, hot beverages High fruit/vegetable intake Abstinence from betel quid chewing |
Alcohol |
| Observational [21,24,25,26,27] | Abstinence from alcohol consumption. It is important to correct the synergic action with tobacco |
Cancer | Suggested Surveillance Methods | Suggested Surveillance Intervals | ||||||
---|---|---|---|---|---|---|---|---|
ESGE | AGA | ASGE | BSG | ESGE | AGA | ASGE | BSG | |
Esophageal adenocarcinoma | Endoscopy or ultrathin nasal endoscopy with biopsy | High-definition white-light endoscopy and 4-quadrant biopsy specimens taken every 1–2 cm of Barrett’s mucosa, depending on the degree of dysplasia | Endoscopy with biopsy | Endoscopy with biopsy/HRE in BE. Adherence to a quadrant, 2 cm biopsy protocol in addition to sampling any visible lesions. Expert HRE should be carried out in all Barrett patients with biopsy-detected HGD | No dysplasia: every 5 years LGD: every 3 years in long-segment BE | No dysplasia: every 3–5 years LGD: every 6–12 months HGD: in the absence of eradication therapy every 3 months | No dysplasia: Consider no surveillance. If surveillance is elected, every 3 to 5 years LGD: after the repeat endoscopy in 6 months to confirm LGD, every year. HGD: every 3 months in selected patients. | No dysplasia: after the repeat endoscopy to confirm the diagnosis, patients with BE shorter than 3 cm and IM should receive endoscopic surveillance every 3–5 years. If repeat endoscopy confirms the absence of IM, discharge from surveillance is encouraged Patients with segments of 3 cm or longer should receive surveillance every 2–3 years. LGD: every 6 months |
Esophageal squamous-cell carcinoma | Endoscopy with biopsy | Endoscopy with biopsy | Endoscopy with biopsy | Full assessment with enhanced imaging and/or Lugol’s chromo-endoscopy is required | Surveillance intervals vary from 2 to 5 years | The interval for surveillance of these patients has not been established, but yearly investigations would seem to be reasonable | Tylosis: screening at 30 years of age or at the recognition of the disease and then every 1 to 3 years. Caustic injury: screening should begin approximately 10 to 20 years after the insult, and then every 2 to 3 years |
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Marabotto, E.; Pellegatta, G.; Sheijani, A.D.; Ziola, S.; Zentilin, P.; De Marzo, M.G.; Giannini, E.G.; Ghisa, M.; Barberio, B.; Scarpa, M.; et al. Prevention Strategies for Esophageal Cancer—An Expert Review. Cancers 2021, 13, 2183. https://doi.org/10.3390/cancers13092183
Marabotto E, Pellegatta G, Sheijani AD, Ziola S, Zentilin P, De Marzo MG, Giannini EG, Ghisa M, Barberio B, Scarpa M, et al. Prevention Strategies for Esophageal Cancer—An Expert Review. Cancers. 2021; 13(9):2183. https://doi.org/10.3390/cancers13092183
Chicago/Turabian StyleMarabotto, Elisa, Gaia Pellegatta, Afscin Djahandideh Sheijani, Sebastiano Ziola, Patrizia Zentilin, Maria Giulia De Marzo, Edoardo Giovanni Giannini, Matteo Ghisa, Brigida Barberio, Marco Scarpa, and et al. 2021. "Prevention Strategies for Esophageal Cancer—An Expert Review" Cancers 13, no. 9: 2183. https://doi.org/10.3390/cancers13092183