Review Article

Esophageal Cancer: An Updated Review

Authors: Michael DiSiena, MD, Alexander Perelman, DO, John Birk, MD, Houman Rezaizadeh, MD

Abstract

Abstract: The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett’s esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.

 
Posted in: Esophageal Disease2

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References

1. American Cancer Society. Colorectal Cancer Facts & Figures 2017-2019. Atlanta, GA: American Cancer Society; 2017. 2. Siegel R, Miller K, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30. 3. PDQ Screening and Prevention Editorial Board. PDQ esophageal cancer screening. https://www.cancer.gov/types/esophageal/hp/esophagealscreening-pdq. Updated February 22, 2019. Accessed August 6, 2019. 4. World Health Organization-International Agency for Research on Cancer. Global cancer data—Globocan 2018. https://www.uicc.org/news/global-cancer-data-globocan-2018#:~:text=GLOBOCAN%202018%20is%20an%20online,for%20all%20cancer%20sites%20combined. Accessed January 13, 2021. 5. Thrift AP. The epidemic of the oesophageal carcinoma: where are we now? Cancer Epidemiol 2016;41:88–95. 6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34. 7. Islami F. Incidence trends of esophageal and gastric cancer subtypes by race, ethnicity, and age in the United States, 1997–2014. Clin Gastroenterol Hepatol 2019;17:429–439. 8. Pandeya N, Olsen CM, Whiteman DC. Sex differences in the proportion of esophageal squamous cell carcinoma cases attributable to tobacco smoking and alcohol consumption. Cancer Epidemiol 2013;37:579–584. 9. Wang QL, Xie SH, Li WT, et al. Smoking cessation and risk of esophageal cancer by histological type: systematic review and meta-analysis. J Natl Cancer Inst 2017;109: doi: 10.1093/jnci/djx115. 10. Sun X, Elston R, Barnholtz-Sloan J, et al. A segregation analysis of Barrett’s esophagus and associated adenocarcinomas. Cancer Epidemiol Biomarkers Prev 2010;19:666–674. 11. Contini S, Scarpignato C. Caustic injury of the upper gastrointestinal tract: a comprehensive review. World J Gastroenterol 2013;19:3918–3930. 12. Lindor NM, Greene MH. The concise handbook of family cancer syndromes. Mayo Familial Cancer Program. J Natl Cancer Inst 1998;90:1039–1071. 13. Lindor NM, McMaster ML, Lindor CJ, et al. Concise handbook of familial cancer susceptibility syndromes—second edition. J Natl Cancer Inst Monogr 2008;(38):1–93. 14. Wheeler JB, Reed CE. Epidemiology of esophageal cancer. Surg Clin North Am 2012;92:1077–1087. 15. Chen Q, Zhuang H, Liu Y. The association between obesity factor and esophageal cancer. J Gastrointest Oncol 2012;3:226–231. 16. Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood 2003;101:822–826. 17. Velleuer E, Dietrich R. Fanconi anemia: young patients at high risk for squamous cell carcinoma. Mol Cell Pediatr 2014;1:9. 18. Ellis NA, German J. Molecular genetics of Bloom’s syndrome. Hum Mol Genet 1996;5(Spec No):1457–1463. 19. Petrick JL, Wyss AB, Butler AM, et al. Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis. Br J Cancer 2014;110:2369–2377. 20. Islami F, Boffetta P, Ren JS, et al. High-temperature beverages and foods and esophageal cancer risk—a systematic review. Int J Cancer 2009;125:491–524. 21. Islami F, Ren JS, Taylor PR, et al. Pickled vegetables and the risk of oesophageal cancer: a meta-analysis. Br J Cancer 2009;101:1641–1647. 22. Akhtar S, Sheikh AA, Qureshi HU. Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of oesophageal squamous-cell carcinoma in South Asians: a multicentre case-control study. Eur J Cancer 2012;48:655–661. 23. Steevens J, van den Brandt PA, Goldbohm RA, et al. Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study. Gastroenterology 2010;138:1704–1713. 24. Cross AJ, Freedman ND, Ren J, et al. Meat consumption and risk of esophageal and gastric cancer in a large prospective study. Am J Gastroenterol 2011;106:432–442. 25. Liu J, Wang J, Leng Y, et al. Intake of fruit and vegetables and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies. Int J Cancer 2013;133:473–485. 26. Chang-Claude J, Becher H, Blettner M, et al. Familial aggregation of oesophageal cancer in a high incidence area in China. Int J Epidemiol 1997;26:1159–1165. 27. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119:1447–1453. 28. Iwaya T, Maesawa C, Ogasawara S, et al. Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer. Gastroenterology 1998;114:1206–1210. 29. Sherman SK, Maxwell JE, Qian Q, et al. Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations. Cancer Genet 2015;208:41–46. 30. Sandler RS, Nyrén O, Ekbom A, et al. The risk of esophageal cancer in patients with achalasia. A population-based study. JAMA 1995;274:1359–1362. 31. Appelqvist P, Salmo M. Lye corrosion carcinoma of the esophagus: a review of 63 cases. Cancer 1980;45:2655–2658. 32. Ruol A, Rampado S, Parenti A, et al. Caustic ingestion and oesophageal cancer: intra- and peri-tumoral fibrosis is associated with a better prognosis. EurJ Cardiothorac Surg 2010;38:659–664. 33. Novacek G. Plummer-Vinson syndrome. Orphanet J Rare Dis 2006;1:36. 34. Chisholm M. The association between webs, iron and postcricoid carcinoma. Postgrad Med J 1974;50:215–219. 35. Itskoviz D, Tamary H, Krasnov T, et al. Endoscopic findings and esophageal cancer incidence among Fanconi anemia patients participating in an endoscopic surveillance program. Dig Liver Dis 2019;51:242–246. 36. Alter BP. Fanconi's anemia, transplantation, and cancer. Pediatr Transplant 2005;9(suppl 7):81–86. 37. Han Y, Chen W, Peiwei L, et al. Association between coeliac disease and risk of any malignancy and gastrointestinal malignancy. Medicine (Baltimore) 2015;94:e1612. 38. Bonifazi M, Tramacere I, Pomponio G, et al. Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies. Rheumatology 2013;52:143–154. 39. Lagergren J, Bergström R, Lindgren A, et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825–831. 40. Bytzer P, Christensen PB, Damkier P, et al. Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study. Am J Gastroenterol 1999;94:86–91. 41. Lagergren J, Ye W, Lagergren P, Lu Y. The risk of esophageal adenocarcinoma after antireflux surgery. Gastroenterology 2010;138:1297–1301. 42. Qumseya B, Sultan S, Bain P, et al. ASGE guideline on screening and surveillance of Barrett’s esophagus. Gastrointest Endosc 2019;90:335–359.e2. 43. Chakraborty S, Iyer PG. Predictors of progression in Barrett’s esophagus. Curr Treat Options Gastroenterol 2019;17:18–31. 44. Parasa S, Vennalaganti S, Gaddam S, et al. Development and validation of a model to determine risk of progression of Barrett’s esophagus to neoplasia. Gastroenterology 2018;154:1282–1289.e2. 45. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med 2011;365:1375–1383. 46. Desai TK, Krishnan K, Samala N. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett’s oesophagus: a meta-analysis. Gut 2012;61:970–976. 47. Hoyo C, Cook MB, Kamangar F, et al. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium. Int J Epidemiol 2012;41:1706–1718. 48. Thrift AP, Shaheen NJ, Gammon MD, et al. Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study. J Natl Cancer Inst 2014;106:dju252. 49. Freedman ND, Murray LJ, Kamangar F, et al. Alcohol intake and risk of oesophageal adenocarcinoma: a pooled analysis from the BEACON Consortium. Gut 2011;60:1029–1037. 50. Liao LM, Vaughan TL, Corley DA, et al. Nonsteroidal anti-inflammatory drug use reduces risk of adenocarcinomas of the esophagus and esophagogastric junction in a pooled analysis. Gastroenterology 2012;142:442–452.e5. 51. Sun L, Yu S. Meta-analysis: non-steroidal anti-inflammatory drug use and the risk of esophageal squamous cell carcinoma. Dis Esophagus 2011;24:544–549. 52. Corley DA, Kerlikowske K, Verma R, et al. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and metaanalysis. Gastroenterology 2003;124:47–56. 53. Whiteman DC, Parmar P, Fahey P, et al. Association of Helicobacter pylori infection with reduced risk for esophageal cancer is independent of environmental and genetic modifiers. Gastroenterology 2010;139:73–83. 54. Rezaizadeh H, McCarty TR, Njei B, et al. Daily proton pump inhibitors are cost-effective in reducing Barrett’s induced esophageal adenocarcinoma mortality: 2016 ACG Presidential Poster Award. Am J Gastroenterol 2016;111:S211. 55. Sasaki Y, Tamura M, Koyama R, et al. Genomic characterization of esophageal squamous cell carcinoma: insights from next-generation sequencing. World J Gastroenterol 2016;22:2284–2293. 56. Cameron AJ, Lomboy CT, Pera M, et al. Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology 1995;109:1541–1546. 57. Paraf F, Fléjou JF, Pignon JP, et al. Surgical pathology of adenocarcinoma arising in Barrett’s esophagus. Analysis of 67 cases. Am J Surg Pathol 1995;19:183–191. 58. Cavallin F, Scarpa M, Cagol M, et al. Esophageal cancer clinical presentation: trends in the last 3 decades in a large Italian series. Ann Surg 2018;267:99–104. 59. Fang TC, Oh YS, Szabo A, et al. Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer. Dis Esophagus 2016;29:642–648. 60. Graham DY, Schwartz JT, Cain GD, et al. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma. Gastroenterology 1982;82:228–233. 61. Park J, Cho YK, Kim JH. Current and future use of esophageal capsule endoscopy. Clin Endosc 2018;51:317–322. 62. Keller J, Fibbe C, Volke F, et al. Remote magnetic control of a wireless capsule endoscope in the esophagus is safe and feasible: results of a randomized, clinical trial in healthy volunteers. Gastrointest Endosc 2010;72:941–946. 63. Oka A, Amano Y, Kusunoki R, et al. Superficial esophageal cancer observed with the PillCam ESO 2 in combination with the flexible spectral imaging color enhancement system. Dig Endosc 2011;23:195–196. 64. Yim S, Gultepe E, Gracias DH, et al. Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving untethered microgrippers. IEEE Trans Biomed Eng 2014;61:513–521. 65. Wang X, Kambhampati S, Cheng Y, et al. Methylation biomarker panel performance in EsophaCap cytology samples for diagnosing Barrett’s esophagus: a prospective validation study. Clin Cancer Res 2019;25:2127–2135. 66. Rusch VW, Appelman HD, Blackstone E, et al. Esophagus and esophagogastric junction. In AJCC Cancer Staging Manual, 7th ed. Chicago: AJCC; 2010:103–115. 67. Puli SR, Reddy JB, Bechtold ML, et al. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J Gastroenterol 2008;14:1479–1490. 68. Catalano MF, Van Dam J, Sivak MVJr. Malignant esophageal strictures: staging accuracy of endoscopic ultrasonography. Gastrointest Endosc 1995;41:535–539. 69. Wiersema MJ, Vilmann P, Giovannini M, et al. Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997;112:1087–1095. 70. Sun F, Chen T, Han J, et al. Staging accuracy of endoscopic ultrasound for esophageal cancer after neoadjuvant chemotherapy: a meta-analysis and systematic review. Dis Esophagus 2015;28:757–771. 71. Overholt BF, Wang KK, Burdick JS, et al. International photodynamic group for high-grade dysplasia in Barrett’s esophagus. Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett’s high-grade dysplasia. Gastrointest Endosc 2007;66:460–468. 72. Canto MI, Shaheen NJ, Almario JA, et al. Multifocal nitrous oxide cryoballoon ablation with or without EMR for treatment of neoplastic Barrett’s esophagus (with video). Gastrointest Endosc 2018;88:438–446.e2. 73. Attwood SE, Lewis CJ, Caplin S, et al. Argon beam plasma coagulation as therapy for high-grade dysplasia in Barrett’s esophagus. Clin Gastroenterol Hepatol 2003;1:258–263. 74. Shaheen NJ, Overholt BF, Sampliner RE, et al. Durability of radiofrequency ablation in Barrett’s esophagus with dysplasia. Gastroenterology 2011;141: 460–468. 75. Ell C, May A, Pech O, et al. Curative endoscopic resection of early esophageal adenocarcinomas (Barrett’s cancer). Gastrointest Endosc 2007;65:3–10. 76. Pouw RE, van Vilsteren FG, Peters FP, et al. Randomized trial on endoscopic resection-cap versus multiband mucosectomy for piecemeal endoscopic resection of early Barrett’s neoplasia. Gastrointest Endosc 2011;74:35–43. 77. Pech O, Behrens A, May A, et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett’s oesophagus. Gut 2008;57:1200–1206. 78. Lewis JJ, Rubenstein JH, Singal AG, et al. Factors associated with esophageal stricture formation after endoscopic mucosal resection for neoplastic Barrett’s esophagus. Gastrointest Endosc 2011;74:753–760. 79. Ono S, Fujishiro M, Niimi K, et al. Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. Gastrointest Endosc 2009;70:860–866. 80. Takahashi H, Arimura Y, Masao H, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc 2010;72:255–264. 81. Repici A, Hassan C, Carlino A, et al. Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series. Gastrointest Endosc 2010;71:715–721. 82. Sohda M, Kuwano H. Current status and future prospects for esophageal cancer treatment. Ann Thorac Cardiovasc Surg 2017;23:1–11. 83. Tanaka T, Ishiguro H, Kuwabara Y, et al. Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res 2010;29:83. 84. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383:31–39. 85. Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: a global phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-IVBE). J Clin Oncol 2014;32(suppl 3):LBA7. 86. Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 2016;17:717–726. 87. Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. J Clin Oncol 2018;36:61–67. 88. Kojima T, Muro K, Francois E, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study. J Clin Oncol 2019;37(suppl 4):abstr 2. 89. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–2454. 90. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366: 2455–2465. 91. Njei B, McCarty TR, Birk JW. Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis. J Gastroenterol Hepatol 2016;31:1141–1146. 92. Chang DT, Chapman C, Shen J, et al. Treatment of esophageal cancer based on histology: a surveillance epidemiology and end results analysis. Am J Clin Oncol 2009;32:405–410. 93. Sepesi B, Watson TJ, Zhou D, et al. Are endoscopic therapies appropriate for superficial submucosal esophageal adenocarcinoma? (An analysis of esophagectomy specimens). J Am Coll Surg 2010;210:418–427. 94. Holscher AH, Bollschweiler E, Schroder W, et al. Prognostic impact of upper, middle, and lower third mucosal or submucosal infiltration in early esophageal cancer. Ann Surg 2011;254:802–808. 95. Akutsu Y, Uesato M, Shuto K, et al. The overall prevalence of metastasis in T1 esophageal squamous cell carcinoma: a retrospective analysis of 295 patients. Ann Surg 2013;257:1032–1038. 96. Conio M, Repici A, Battaglia G, et al. A randomized prospective comparison of self-expandable plastic stents and partially covered self-expandable metal stents in the palliation of malignant esophageal dysphagia. Am J Gastroenterol 2007;102:2667–2677. 97. Madhusudhan C, Saluja SS, Pal S, et al. Palliative stenting for relief of dysphagia in patients with inoperable esophageal cancer: impact on quality of life. Dis Esophagus 2009;22:331–336. 98. Ahmed O, Bolger JC, O’Neill B, et al. Use of esophageal stents to relieve dysphagia during neoadjuvant therapy prior to esophageal resection: a systematic review. Dis Esophagus 2020;33:doz090. 99. Ligthart-Melis GC, Weijs PJ, te Boveldt ND, et al. Dietician-delivered intensive nutritional support is associated with a decrease in severe postoperative complications after surgery in patients with esophageal cancer. Dis Esophagus 2013;26:587–593. 100. Kim KR, Shin JH, Song HY, et al. Palliative treatment of malignant esophagopulmonary fistulas with covered expandable metallic stents. AJR Am J Roentgenol 2009;193:W278–W282. 101. Evans JA, Early DS, Fukami N, et al. The role of endoscopy in Barrett’s esophagus and other premalignant conditions of the esophagus. Gastrointest Endosc 2012;76:1087–1094. 102. Kopacova M, Tacheci I, Rejchrt S, et al. Peutz-Jeghers syndrome: diagnostic and therapeutic approach. World J Gastroenterol 2009;15:5397–5408. 103. Sudo K, Taketa T, Correa AM, et al. Locoregional failure rate after preoperative chemoradiation of esophageal adenocarcinoma and the outcomes of salvage strategies. J Clin Oncol 2013;31:4306–4310. 104. Gupta N, Bansal A, Wani SB, et al. Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis. Gastrointest Endosc 2011;74:610–624. 105. Shaheen NJ, Falk GW, Iyer PG, et al. ACG Clinical Guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016;111:30–50. 106. Wani S, Qumseya B, Sultan S, et al. Endoscopic eradication therapy for patients with Barrett’s esophagus-associated dysplasia and intramucosal cancer. Gastrointest Endosc 2018;87:907–931.