- Author: Keith M Baldwin, DO; Chief Editor: N Joseph Espat, MD, MS, FACS more...
Esophageal cancer is a disease in epidemiologic transition. Until the 1970s, the most common type of esophageal cancer in the United States was squamous cell carcinoma, which has smoking and alcohol consumption as risk factors; since then, there has been a progressive increase in the incidence of esophageal adenocarcinoma, for which the most common predisposing factor is gastroesophageal reflux disease (GERD). See the image below.
Signs and symptoms
Presenting signs and symptoms of esophageal cancer include the following:
- Dysphagia (most common); initially for solids, eventually progressing to include liquids
- Weight loss (second most common)
- Epigastric or retrosternal pain
- Bone pain with metastatic disease
- Persistent cough
Physical findings include the following:
- Typically, normal examination results unless the cancer has metastasized
- Hepatomegaly (from hepatic metastases)
- Lymphadenopathy in the laterocervical or supraclavicular areas (reflecting metastasis)
See Clinical Presentation for more detail.
Laboratory studies focus principally on patient factors that may affect treatment (eg, nutritional status).
Imaging studies used for diagnosis and staging include the following:
- Esophagogastroduodenoscopy (allows direct visualization and biopsies of the tumor)
- Endoscopic ultrasonography (EUS; most sensitive test for T and N staging)
- Computed tomography of the abdomen and chest (for assessing lung and liver metastasis and invasion of adjacent structures)
- Positron emission tomography (PET) scanning (for staging)
- Bronchoscopy (to help exclude invasion of the trachea or bronchi)
- Laparoscopy and thoracoscopy (for staging regional nodes)
- Barium swallow (very sensitive for detecting strictures and intraluminal masses, but now rarely used)
Current TNM classification is as follows (staging is detailed in Table 1, below):
- Tis - Carcinoma in situ/high-grade dysplasia
- T1 - Lamina propria or submucosa
- T1a - Lamina propria or muscularis mucosae
- T1b - Submucosa
- T2 - Muscularis propria
- T3 - Adventitia
- T4 - Adjacent structures
- T4a - Pleura, pericardium, diaphragm, or adjacent peritoneum
- T4b - Other adjacent structures (eg, aorta, vertebral body, trachea)
- N0 - No regional lymph node metastasis
- N1 - 1-2 regional lymph nodes (N1 is site dependent)
- N2 - 3-6 regional lymph nodes
- N3 - More than 6 regional lymph nodes
- M0 - No distant metastasis
- M1 - Distant metastasis (M1a and M1b are site dependent)
Table 1. Staging Classification. (Open Table in a new window)
|Stage IV||Any T||Any N||M1|
See Workup for more detail.
Treatment of esophageal cancer varies by disease stage, as follows:
- Stage I – Consideration for endoscopic therapy (eg, mucosal resection or submucosal dissection), particularly for Tis and T1aN0 by EUS; consideration for initial surgery for T1b and any N
- Stages II-III – Consideration for chemoradiation followed by surgery (trimodality therapy)
- Stage IV – Chemotherapy or symptomatic and supportive care
Indications for surgical treatment of esophageal cancer include the following:
- Diagnosis of esophageal cancer in a patient who is a candidate for surgery
- High-grade dysplasia in a patient with Barrett esophagus that cannot be adequately treated endoscopically[1, 2]
Contraindications for surgical treatment include the following:
- Metastasis to N2 (celiac, cervical, supraclavicular) nodes or solid organs (eg, liver, lungs)
- Invasion of adjacent structures (eg, recurrent laryngeal nerve, tracheobronchial tree, aorta, pericardium)
- Severe associated comorbid conditions (eg, cardiovascular disease, respiratory disease)
- Impaired cardiac or respiratory function
Surgical options include the following:
- Transhiatal esophagectomy (THE)
- Transthoracic esophagectomy (TTE)
- Minimally invasive esophagectomy
- Endoscopic mucosal resection (EMR)
Neoadjuvant therapy for esophageal cancer is as follows:
- Combination of radiotherapy and chemotherapy
- Usually administered over a 45-day period, with esophageal resection after approximately 4 weeks
- Most chemotherapy agents for esophageal cancer are used off-label
Palliative care options for patients who are not candidates for surgery are as follows:
- Laser therapy
Esophageal cancer is a devastating disease. Although some patients can be cured, the treatment for esophageal cancer is protracted, diminishes quality of life, and is lethal in a significant number of cases.
The principal histologic types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. As squamous cells line the entire esophagus, squamous cell carcinoma can occur in any part of the esophagus; it often arises, however, in the upper half of the esophagus. Adenocarcinoma typically develops in specialized intestinal metaplasia (Barrett metaplasia) that develops as a result of gastroesophageal reflux disease (GERD); thus, adenocarcinoma typically arises in the lower half of the distal esophagus. (See Pathophysiology and Etiology.)
The most common presenting symptom of esophageal cancer is dysphagia (see Presentation). Esophagogastroduodenoscopy allows direct visualization and biopsies of the tumor, while endoscopic ultrasonography is the most sensitive test for determining the depth of penetration of the tumor and the presence of enlarged periesophageal lymph nodes. In patients who appear to have localized esophageal cancer, positron emission tomography (PET) scanning may be useful as part of the baseline staging. Other imaging studies may be valuable in selected patients. (See Workup.)
Surgery has traditionally been the treatment for esophageal carcinoma. The first successful resection was performed in 1913 by Torek. In the 1930s, Ohsawa in Japan and Marshall in the United States were the first to perform successful single-stage transthoracic esophagectomies with continent reconstruction.[4, 5] Nonoperative therapy is usually reserved for patients who are not candidates for surgery because of clinical conditions or advanced disease. (See Treatment.)
The ideal treatment for localized esophageal cancer is sometimes debated across practice cultures and subspecialties. Defendants of surgical treatment argue that resection is the only treatment modality to offer curative intent; defendants of the nonsurgical approach claim that esophagectomy has a prohibitive index of mortality and that esophageal cancer is an incurable disease.
Esophageal lesions other than cancer can cause dysphagia. These include peptic strictures from gastroesophageal reflux and benign esophageal tumors (principally esophageal leiomyoma). Imaging studies help to differentiate these lesions from esophageal cancer. Other differentials include the following
The esophagus is a muscular tube that extends from the level of the 7th cervical vertebra to the 11th thoracic vertebra. The esophagus can be divided into the following anatomic parts:
- Cervical esophagus
- Thoracic esophagus
- Abdominal esophagus
The blood supply of the cervical esophagus is derived from the inferior thyroid artery, while the blood supply for the thoracic esophagus comes from the bronchial arteries and the aorta. The abdominal esophagus is supplied by branches of the left gastric artery and inferior phrenic artery.
Venous drainage of the cervical esophagus is through the inferior thyroid vein, while the thoracic esophagus drains via the azygous vein, the hemiazygous vein, and the bronchial veins. The abdominal esophagus drains through the coronary vein.
The esophagus is characterized by a rich network of lymphatic channels in the submucosa that can facilitate the longitudinal spread of neoplastic cells along the esophageal wall. Lymphatic drainage is to cervical nodes, tracheobronchial and mediastinal nodes, and gastric and celiac nodes.
The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure.[6, 7, 8] The oncosuppressor gene TP53 and various oncogenes, particularly erb -b2, have been studied as potential markers.
Casson and colleagues identified mutations in the TP53 gene in patients with Barrett epithelium associated with adenocarcinoma. In addition, alterations in p16 genes and cell cycle abnormalities or aneuploidy appear to be some of the most important and well-characterized molecular changes.
The etiology of esophageal carcinoma is thought to be related to exposure of the esophageal mucosa to noxious or toxic stimuli, resulting in a sequence of dysplasia to carcinoma in situ to carcinoma. In Western cultures, retrospective evidence has implicated cigarette smoking and chronic alcohol exposure as the most common etiologic factors for squamous cell carcinoma. High body mass index, GERD, and resultant Barrett esophagus are often the associated factors for esophageal adenocarcinoma.
Nutritional deficiencies have been recognized as contributing factors. In high-risk regions such as parts of China and Iran, deficiencies in vitamins (eg, riboflavin) or micronutrients may play a role in causation.
A variety of other factors may promote esophageal cancer. These include the following:
- Caustic injuries
- Certain foodstuffs (eg, betel nut)
- Drinking scalding-hot liquids
- Environmental contributors (eg, nitrosamines in soil)
- Certain fungi, molds, or yeasts
- Acquired conditions (eg, achalasia)
A genome-wide association study by Wu et al identified seven susceptibility loci on chromosomes 5q11, 6p21, 10q23, 12q24, and 21q22, suggesting the involvement of multiple genetic loci and gene-environment interaction in the development of esophageal cancer. Individuals with the genetic disorder tylosis palmaris et plantaris are at very high risk for esophageal cancer. Plummer-Vinson syndrome also increases its risk.
Bisphosphonate use can result in esophagitis and has been suggested as a risk factor for esophageal carcinoma. However, a large study found no significant difference in the frequency of esophageal or gastric cancers between the bisphosphonate cohort and the control group.
Smoking and alcohol use
The Netherlands Cohort Study, a prospective study in 120,852 participants, demonstrated the combined effects of smoking and alcohol consumption on risk of squamous cell carcinoma of the esophagus. Among participants who drank 30 g or more of ethanol daily, the multivariable adjusted incidence rate ratio (RR) for esophageal squamous cell carcinoma was 4.61 compared with abstainers. The RR for current smokers who consumed more than 15 g/day of ethanol was 8.05 when compared with nonsmokers who consumed less than 5 g/day of ethanol.
No associations were found between alcohol consumption and esophageal adenocarcinoma.
In contrast, the risk of squamous cell carcinoma and adenocarcinoma of the esophagus was increased among current smokers.
A study by Steevens et al found that among current smokers, increased consumption of specific groups of vegetables and fruits were inversely associated with esophageal squamous cell carcinoma and esophageal adenocarcinoma risk. Total vegetable consumption nonsignificantly reduced the risk for both esophageal cancer types. Consumption of raw vegetables and of citrus fruits was inversely associated with risk for esophageal adenocarcinoma.
Human papillomavirus (HPV) infection has been recognized as a contributing factor to esophageal cancer. However, Sitas et al reported limited serologic evidence of an association between esophageal squamous cell carcinoma and HPV in a study of more than 4000 subjects. The study could not exclude the possibility that certain HPV types may be involved in a small subset of cancers, although HPV does not appear to be an important risk factor.
Helicobacter pylori infection, which can cause stomach cancer, has not been associated with esophageal cancer.
Adenocarcinoma and GERD
GERD is the most common predisposing factor for adenocarcinoma of the esophagus. Adenocarcinoma may represent the last event of a sequence that starts with irritation caused by the reflux of acid and bile and progresses to specialized intestinal (Barrett) metaplasia, low-grade dysplasia, high-grade dysplasia, and finally adenocarcinoma. Approximately 10-15% of patients who undergo endoscopy for evaluation of GERD symptoms are found to have Barrett epithelium. (See the chart below.)
In 1952, Morson and Belcher published the first description of a patient with adenocarcinoma of the esophagus arising in a columnar epithelium with goblet cells. In 1975, Naef et al emphasized the malignant potential of Barrett esophagus. The risk of adenocarcinoma among patients with Barrett metaplasia has been estimated to be 30-60 times that of the general population.
A nationwide population-based case-control study performed in Sweden found an odds ratio of 7.7 for adenocarcinoma among persons with recurrent symptoms of reflux, as compared with persons without such symptoms, and an odds ratio of 43.5 among patients with long-standing and severe symptoms of reflux.
Although the annual risk of developing esophageal adenocarcinoma in people with GERD has been reported at 0.5%, some studies have found lower risk. Data from the Northern Ireland Barrett Esophagus Register, which is one of the largest population-based registries in the world, found that the malignant progression among patients with Barrett esophagus was 0.22% per year. This suggests that current surveillance approaches may not be cost effective.
A study by Hvid-Jensen et al examined a large Danish registry (11,028 patients over a median of 5.2 y) and found the incidence of esophageal adenocarcinoma to be 1.2 cases per 1000 person-years (or 0.12% annual risk). Low-grade dysplasia detected on index endoscopy was associated with an incidence rate of 5.1 cases per 1000 person-years, compared with 1 per 1000 person-years among those without dysplasia.
United States statistics
The American Cancer Society estimates that 17,990 new cases of esophageal cancer (14,440 in men and 3,550 in women) will occur in the United States in 2013; 15,210 persons (12,220 men and 2,990 women) are expected to die of the disease.
The incidence rate of adenocarcinoma of the esophagus in the United States showed an average annual increase of 1.7% in men and 1.9% in women from 1999 to 2008. The incidence of esophageal carcinoma is approximately 3-6 cases per 100,000 persons, although certain endemic areas appear to have higher per-capita rates. The age-adjusted incidence is 5.8 cases per 100,000 persons.
The epidemiology of esophageal carcinoma has changed markedly over the past several decades in the United States. Until the 1970s, squamous cell carcinoma was the most common type of esophageal cancer (90-95%). It was located in the thoracic esophagus and most frequently affected African-American men with a long history of smoking and alcohol consumption.
Over the last 4 decades, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction has increased progressively. Currently, it accounts for more than 70% of all the new cases of esophageal cancer.
Esophageal cancer is the seventh leading cause of cancer death worldwide. In some regions, such as areas of northern Iran, some areas of southern Russia, and northern China, the incidence of esophageal carcinoma may be as high as 800 cases per 100,000 population. Unlike in the United States, squamous cell carcinoma is responsible for 95% of all esophageal cancers worldwide.
Sex- and age-related demographics
Esophageal cancer is generally more common in men than in women. The male-to-female ratio is 3-4:1.
Esophageal cancer occurs most commonly during the sixth and seventh decades of life. The disease becomes more common with advancing age; it is about 20 times more common in persons older than 65 years than it is in individuals below that age.
Survival in patients with esophageal cancer depends on the stage of the disease. Squamous cell carcinoma and adenocarcinoma, stage-by-stage, appear to have equivalent survival rates.
Lymph node or solid organ metastases are associated with low survival rates. In 2001-2007, the overall 5-year survival rate for esophageal cancer was 19%. Patients without lymph node involvement have a significantly better prognosis and 5-year survival rate than patients with involved lymph nodes. Stage IV lesions are associated with a 5-year survival rate of less than 5%. (See the table below.)
A report of 1085 patients who underwent transhiatal esophagectomy for cancer showed that the operation was associated with a 4% operative mortality rate and a 23% 5-year survival rate. A better 5-year survival rate (48%) was identified in a subgroup of patients who had a complete response (ie, disappearance of the tumor) following preoperative radiation and chemotherapy (ie, neoadjuvant therapy).
Transhiatal and transthoracic esophagectomies have equivalent long-term survival rates.[24, 25]
Imaging and prognosis
Suzuki et al found that a higher initial standardized uptake value on positron emission tomography (PET) scanning is associated with poorer overall survival among patients with esophageal or gastroesophageal carcinoma receiving chemoradiation. The authors suggested that PET scanning may become useful for individualizing therapy.
A study by Gillies et al also found that PET-computed tomography (CT) scanning can be used to predict survival; in this study, the presence of fluorodeoxyglucose (FDG)-avid lymph nodes was an independent adverse prognostic factor.
HER-2 and prognosis
A study by Prins et al of human epidermal growth factor 2 (HER-2) protein overexpression and HER-2 gene amplification in esophageal carcinomas found that HER-2 positivity and gene amplification are independently associated with poor survival. In their study, which involved 154 patients with esophageal adenocarcinoma, HER-2 positivity was seen in 12% of these patients and overexpression was seen in 14% of them.
Edwards MJ, Gable DR, Lentsch AB, et al. The rationale for esophagectomy as the optimal therapy for Barrett's esophagus with high-grade dysplasia. Ann Surg. 1996 May. 223(5):585-9; discussion 589-91. [Medline].
Ferguson MK, Durkin A. Long-term survival after esophagectomy for Barrett's adenocarcinoma in endoscopically surveyed and nonsurveyed patients. J Gastrointest Surg. 2002 Jan-Feb. 6(1):29-35; discussion 36. [Medline].
Torek F. The first successful resection of the thoracic portion of the esophagus for carcinoma. Surg Gynecol Obstet. 1913. 16:614-17.
Ohsawa T. Surgery of the esophagus. Arch Jpn Chir. 1933. 10:605-8.
Marshall SF. Carcinoma of the esophagus: successful resection of lower end of esophagus with reestablishment of esophageal gastric continuity. Surg Clin North Amer. 1938. 18:643.
Tilanus HW. Changing patterns in the treatment of carcinoma of the esophagus. Scand J Gastroenterol Suppl. 1995. 212:38-42. [Medline].
Jankowski JA, Wright NA, Meltzer SJ, et al. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol. 1999 Apr. 154(4):965-73. [Medline].
Koppert LB, Wijnhoven BP, van Dekken H, et al. The molecular biology of esophageal adenocarcinoma. J Surg Oncol. 2005 Dec 1. 92(3):169-90. [Medline].
Casson AG, Manolopoulos B, Troster M, et al. Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer. Am J Surg. 1994 Jan. 167(1):52-7. [Medline].
Lagergren J, Bergstrom R, Lindgren A, et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999 Mar 18. 340(11):825-31. [Medline].
Wu C, Hu Z, He Z, et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet. 2011 Jun 5. 43(7):679-84. [Medline].
Steevens J, Schouten LJ, Goldbohm RA, van den Brandt PA. Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study. Gut. 2010 Jan. 59(1):39-48. [Medline].
Steevens J, Schouten LJ, Goldbohm RA, van den Brandt PA. Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. Int J Cancer. 2011 Dec 1. 129(11):2681-93. [Medline].
Sitas F, Egger S, Urban MI, et al. InterSCOPE study: associations between esophageal squamous cell carcinoma and human papillomavirus serological markers. J Natl Cancer Inst. 2012 Jan 18. 104(2):147-58. [Medline]. [Full Text].
Morson BC, Belcher JR. Adenocarcinoma of the oesophagus and ectopic gastric mucosa. Br J Cancer. 1952 Jun. 6(2):127-30. [Medline].
Naef AP, Savary M, Ozzello L. Columnar-lined lower esophagus: an acquired lesion with malignant predisposition. Report on 140 cases of Barrett's esophagus with 12 adenocarcinomas. J Thorac Cardiovasc Surg. 1975 Nov. 70(5):826-35. [Medline].
Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2011 Jul 6. 103(13):1049-57. [Medline].
Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med. 2011 Oct 13. 365(15):1375-83. [Medline].
American Cancer Society. Cancer Facts & Figures 2013. Available at http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf. Accessed: February 6, 2013.
Kirby TJ, Rice TW. The epidemiology of esophageal carcinoma. The changing face of a disease. Chest Surg Clin N Am. 1994 May. 4(2):217-25. [Medline].
Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy: clinical experience and refinements. Ann Surg. 1999 Sep. 230(3):392-400; discussion 400-3. [Medline].
Chang AC, Ji H, Birkmeyer NJ, et al. Outcomes after transhiatal and transthoracic esophagectomy for cancer. Ann Thorac Surg. 2008 Feb. 85(2):424-9. [Medline].
Chu KM, Law SY, Fok M, et al. A prospective randomized comparison of transhiatal and transthoracic resection for lower-third esophageal carcinoma. Am J Surg. 1997 Sep. 174(3):320-4. [Medline].
Suzuki A, Xiao L, Hayashi Y, et al. Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy. Cancer. 2011 Nov 1. 117(21):4823-33. [Medline]. [Full Text].
Gillies RS, Middleton MR, Han C, et al. Role of positron emission tomography–computed tomography in predicting survival after neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma. Brit J Surg. Feb 2012. 99(2):239-45.
Prins MJ, Ruurda JP, van Diest PJ, van Hillegersberg R, Ten Kate FJ. The significance of the HER-2 status in esophageal adenocarcinoma for survival: an immunohistochemical and an in situ hybridization study. Ann Oncol. 2013 Jan 18. [Medline].
Nelson R. New Clinical Guidelines Issued for Esophageal Cancer. Medscape Medical News. Available at http://www.medscape.com/viewarticle/807141. Accessed: July 16, 2013.
Varghese TK Jr, Hofstetter WL, Rizk NP, Low DE, Darling GE, Watson TJ, et al. The society of thoracic surgeons guidelines on the diagnosis and staging of patients with esophageal cancer. Ann Thorac Surg. 2013 Jul. 96(1):346-56. [Medline].
Dittler HJ, Siewert JR. Role of endoscopic ultrasonography in esophageal carcinoma. Endoscopy. 1993 Feb. 25(2):156-61. [Medline].
O'Donovan PB. The radiographic evaluation of the patient with esophageal carcinoma. Chest Surg Clin N Am. 1994 May. 4(2):241-56. [Medline].
Rice TW, Rusch VW, Ishwaran H, Blackstone EH. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer. 2010 Aug 15. 116(16):3763-73. [Medline]. [Full Text].
Hofstetter W, Correa AM, Bekele N, et al. Proposed modification of nodal status in AJCC esophageal cancer staging system. Ann Thorac Surg. 2007 Aug. 84(2):365-73; discussion 374-5. [Medline].
Herbella FA, Del Grande JC, Colleoni R. Japanese Society for Disease of the Esophagus. Anatomical analysis of the mediastinal lymph nodes of normal Brazilian subjects according to the classification of the Japanese Society for Diseases of the Esophagus. Surg Today. 2003. 33(4):249-53. [Medline].
NCCN Clinical Practice Guidelines in Oncology. Esophageal and Esophagogastric Junction Cancers (Excluding the proximal 5 cm of the stomach). Available at http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Accessed: May 14, 2012.
Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5. 281(17):1623-7. [Medline].
Forastiere AA, Orringer MB, Perez-Tamayo C, et al. Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report. J Clin Oncol. 1993 Jun. 11(6):1118-23. [Medline].
Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011 Jul. 12(7):681-92. [Medline].
Le Prise E, Etienne PL, Meunier B, et al. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer. 1994 Apr 1. 73(7):1779-84. [Medline].
Leichman L, Steiger Z, Seydel HG, et al. Preoperative chemotherapy and radiation therapy for patients with cancer of the esophagus: a potentially curative approach. J Clin Oncol. 1984 Feb. 2(2):75-9. [Medline].
Nygaard K, Hagen S, Hansen HS, et al. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg. 1992 Nov-Dec. 16(6):1104-9; discussion 1110. [Medline].
Reynolds JV, Muldoon C, Hollywood D, Ravi N, Rowley S, O'Byrne K, et al. Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer. Ann Surg. 2007 May. 245(5):707-16. [Medline]. [Full Text].
Schomas DA, Quevedo JF, Donahue JM, Nichols FC 3rd, Romero Y, Miller RC. The prognostic importance of pathologically involved celiac node metastases in node-positive patients with carcinoma of the distal esophagus or gastroesophageal junction: a surgical series from the Mayo Clinic. Dis Esophagus. 2010 Apr. 23(3):232-9. [Medline].
Gluch L, Smith RC, Bambach CP, et al. Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for esophageal carcinoma. World J Surg. 1999 Mar. 23(3):271-5; discussion 275-6. [Medline].
Goldminc M, Maddern G, Le Prise E, et al. Oesophagectomy by a transhiatal approach or thoracotomy: a prospective randomized trial. Br J Surg. 1993 Mar. 80(3):367-70. [Medline].
Hankins JR, Attar S, Coughlin TR Jr, et al. Carcinoma of the esophagus: a comparison of the results of transhiatal versus transthoracic resection. Ann Thorac Surg. 1989 May. 47(5):700-5. [Medline].
Stiles BM, Altorki NK. Traditional techniques of esophagectomy. Surg Clin North Am. 2012 Oct. 92(5):1249-63.
Dai Y, Chopra SS, Kneif S, Hunerbein M. Management of esophageal anastomotic leaks, perforations, and fistulae with self-expanding plastic stents. J Thorac Cardiovasc Surg. 2011 May. 141(5):1213-7. [Medline].
Martin LW, Swisher SG, Hofstetter W, et al. Intrathoracic leaks following esophagectomy are no longer associated with increased mortality. Ann Surg. 2005 Sep. 242(3):392-9; discussion 399-402. [Medline].
Patti MG, Corvera CU, Glasgow RE, et al. A hospital's annual rate of esophagectomy influences the operative mortality rate. J Gastrointest Surg. 1998 Mar-Apr. 2(2):186-92. [Medline].
Nguyen NT, Roberts P, Follette DM, et al. Thoracoscopic and laparoscopic esophagectomy for benign and malignant disease: lessons learned from 46 consecutive procedures. J Am Coll Surg. 2003 Dec. 197(6):902-13. [Medline].
Uenosono Y, Arigami T, Yanagita S, et al. Sentinel node navigation surgery is acceptable for clinical T1 and N0 esophageal cancer. Ann Surg Oncol. 2011 Jul. 18(7):2003-9. [Medline].
Ngamruengphong S, Wolfsen HC, Wallace MB. Survival of Patients With Superficial Esophageal Adenocarcinoma After Endoscopic Treatment vs Surgery. Clin Gastroenterol Hepatol. 2013 Nov. 11(11):1424-1429.e2. [Medline].
Brooks M. Endoscopic Therapy a Good Option in Early Esophageal Cancer. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814817. Accessed: November 25, 2013.
Novak B. Salvage endoscopy viable for some esophageal cancers. Medscape Medical News. January 29, 2014. [Full Text].
Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6. 355(1):11-20. [Medline].
Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009 Oct 20. 27(30):5062-7. [Medline].
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31. 366(22):2074-84. [Medline].
Brooks M. Preop chemoradiation benefits confirmed in esophageal cancer. Medscape Medical News. January 16, 2014. [Full Text].
Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, et al. Patterns of Recurrence After Surgery Alone Versus Preoperative Chemoradiotherapy and Surgery in the CROSS Trials. J Clin Oncol. 2014 Jan 13. [Medline].
Mamon HJ, Tepper JE. Combination Chemoradiation Therapy: The Whole Is More Than the Sum of the Parts. J Clin Oncol. 2014 Jan 13. [Medline].
Rohatgi PR, Swisher SG, Correa AM, Wu TT, Liao Z, Komaki R, et al. Failure patterns correlate with the proportion of residual carcinoma after preoperative chemoradiotherapy for carcinoma of the esophagus. Cancer. 2005 Oct 1. 104(7):1349-55. [Medline]. [Full Text].
Rao S, Welsh L, Cunningham D, et al. Correlation of overall survival with gene expression profiles in a prospective study of resectable esophageal cancer. Clin Colorectal Cancer. 2011 Mar 1. 10(1):48-56. [Medline].
Alexander BM, Wang XZ, Niemierko A, Weaver DT, Mak RH, Roof KS, et al. DNA repair biomarkers predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Int J Radiat Oncol Biol Phys. 2012 May 1. 83(1):164-71. [Medline].
Fietkau R, Lewitzki V, Kuhnt T, et al. A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial. Cancer. 2013 Jun 13. [Medline].
Tailored Enteral Formula During Chemoradiotherapy Curbs Body Mass Loss. Medscape. Jun 21 2013. [Full Text].
[Guideline] Wong RK, Malthaner RA, Zuraw L, Rumble RB,. Combined modality radiotherapy and chemotherapy in nonsurgical management of localized carcinoma of the esophagus: a practice guideline. Int J Radiat Oncol Biol Phys. 2003 Mar 15. 55(4):930-42. [Medline].
Chustecka Z. Second-line docetaxel affirmed for esophagogastric cancer. Medscape Medical News. Jan 23, 2013. Available at http://www.medscape.com/viewarticle/778031. Accessed: January 28, 2013.
Ford H, Marshall A, Wadsley J, et al. Cougar-02: a randomized phase III study of docetaxel versus active symptom control in advanced esophagogastric adenocarcinoma. J Clin Oncol. 2012. 30:(suppl 34 abstr LBA4).
Homs MY, v d Gaast A, Siersema PD, et al. Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction. Cochrane Database Syst Rev. 2006 Oct 18. CD004063. [Medline].
Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11. 326(24):1593-8. [Medline].
Folkert MR, Cohen GN, Wu AJ, et al. Endoluminal high-dose-rate brachytherapy for early stage and recurrent esophageal cancer in medically inoperable patients. Brachytherapy. 2013 Feb 20. [Medline].
Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, et al. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. 2011 Aug. 141(2):460-8. [Medline]. [Full Text].
Conroy T, Galais MP, Raoul JL, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar. 15(3):305-14. [Medline].
Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007 Mar. 8(3):226-34. [Medline].
Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31. 339(27):1979-84. [Medline].
Knyrim K, Wagner HJ, Bethge N, Keymling M, Vakil N. A controlled trial of an expansile metal stent for palliation of esophageal obstruction due to inoperable cancer. N Engl J Med. 1993 Oct 28. 329(18):1302-7. [Medline].
Lowry F. FOLFOX: More convenient for esophageal cancer?. Medscape Medical News. April 2, 2014. [Full Text].
Scheer RV, Fakiris AJ, Johnstone PA. Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer. Int J Radiat Oncol Biol Phys. 2011 Jul 15. 80(4):996-1001. [Medline].
|Stage IV||Any T||Any N||M1|
|Stage IV||Any T||Any N||M1|