Esophageal cancer

Difficult to swallow
Didn't play the corresponding interactive case or want to try it again? Click here to do so.

Diagnosis and reasoning

This middle aged caucasian man has presented with a history of progressive dysphagia and weight loss; this is a worrisome presentation which mandates a careful evaluation. Generally, dysphagia can be divided into two broad categories: oropharyngeal dysphagia and esophageal dysphagia. Individuals with oropharyngeal dysphagia often report symptoms such as choking, aspiration, nasal regurgitation; these arise very quickly when attempting to swallow, because the fundamental problem lies in initiating the swallowing mechanism. Esophageal dysphagia, on the other hand, typically presents with difficulty swallowing after the initial swallowing mechanism, and can cause symptoms similar to what this patient has, with food getting stuck in the "chest". Esophageal dysphagia can be further divided into dysphagia with solids and liquids, or dysphagia with solids alone. The former is usually suggestive of motility problems such as achalasia, diffuse esophageal spasm or scleroderma-related esophageal dysmotility. Conversely, dysphagia with solids alone, as seen here, is more suggestive of a mechanical obstruction in the esophagus; this could be due to either intrinsic or extrinsic structural lesions. The progressive nature and temporality of dysphagia in combination with patient factors (e.g. prior history of GERD, history of scleroderma, etc) can help us further narrow down the diagnosis. In this patient, the rapidly progressive nature of the dysphagia is worrisome of an esophageal malignancy. However, given the history of 'heartburn', the possibility of peptic ulcer disease (PUD) causing strictures should also be (briefly) entertained. Note also that he has multiple red flags for an expedited upper GI endoscopy to rule out esophageal malignancy; these include age over 50, progressive dysphagia, and weight loss, as well as risk factors for esophageal malignancy including obesity, smoking, and (very likely) untreated GERD. Other red flags for expedited endoscopy, not present in this patient, would include odynophagia, personal or family history of GI malignancy, palpable organomegaly or lymphadenopathy, anemia from GI bleeding, or prior history of peptic ulcer disease. In turn, endoscopy reveals an intraluminal ulcerating mass in the distal third of the esophagus; biopsies show this to be a poorly differentiated adenocarcinoma, clinching the diagnosis. Note that barium esophagography has now been mostly supplanted by endoscopy in the evaluation of patients with suspected esophageal cancer, and is not of additional value here. CT of the thorax, abdomen, and pelvis should be ordered next, so as to stage the malignancy. Fortunately, there is no evidence of distal metastasis, although more than half of patients with esophageal adenocarcinoma are diagnosed with incurable locally advanced or metastatic disease at the time of presentation. Note also that as some evidence suggests that CT scans are not very sensitive for ruling out locoregional spread, endoscopic ultrasound (EUS) can be used to further evaluate these individuals before planning definitive management. There is no clear rationale for H. pylori serology in this patient; even if PUD was a significant consideration, the fact that endoscopy is already indicated for other reasons means that gastric biopsies could have been easily obtained, allowing for more accurate diagnosis of infection. His management, as with all individuals with malignancies, depends on the stage of the disease, his functional status, and personal preferences. The first of these is based on the TNM classification of the disease, and histologic grade. This man has a T3N0M0 score combined with grade 3 histology and a lower esophageal tumor location, which categorizes him as having stage IIA disease. Although there are varying institutional practices, recent evidence suggests that neoadjuvant chemoradiotherapy with surgery improves survival compared to surgery alone in patients with stage II, stage III, and selected patients with stage I T3 disease. Note that endoscopic dilatation and stenting is mainly a palliative modality, and is not an ideal therapeutic option here.


Esophageal cancer is the 8th most common malignancy and 6th highest cause of cancer-related mortality worldwide; in the United States alone, 17,460 new cases were reported in 2012. The malignancy is most often encountered in individuals between 50 to 60 years of age; it is 8 times more common in men, and 5 times more common in Caucasians vis-a-vis persons of African descent. The majority of these cases (57%) are adenocarcinomas in nature; squamous cell carcinomas are the next most common, accounting for 37% of cases. While the pathogenesis of esophageal cancer is still yet to be fully elucidated, there is a proven association between adenocarcinoma and Barrett's esophagus secondary to untreated gastroesophageal reflux disease (GERD). In the latter condition, chronic reflux of gastric acid and bile results in injury to the distal one-third of the esophagus, with subsequent replacement of the stratified squamous epithelium which normally lines the esophagus by columnar epithelium. With repeated injury, dysplastic transformation occurs, ultimately culminating in esophageal adenocarcinoma. As can be surmised, the principal risk factor for esophageal adenocarcinoma is Barrett's esophagus; both obesity and smoking are other well-known risk factors. Low consumption of vegetables and fruits, genetic factors, white race, and the male gender have also been linked to a higher risk. Progressive dysphagia and/or odynophagia are the most common presenting complaints; these will often have been present for several months before the time of first presentation. Unintentional loss of over 10% of the body weight commonly occurs in less than six months. Late manifestations include chest or back pain when swallowing, persistent substernal chest pain, halitosis, clubbing, hoarseness from recurrent laryngeal nerve involvement, Horner syndrome, and supraclavicular adenopathy. Where carcinoma of the esophagus is suspected, endoscopy is the preferred initial diagnostic modality; aside from allowing accurate identification of the site and size of the tumor, biopsies thus obtained facilitate histopathologic diagnosis. Where biopsies are diagnostic for malignancy, the tumor should be staged via further imaging studies. In persons without metastatic disease, endoscopic ultrasound (EUS) allows for more accurate staging; furthermore, where locoregional spread is suspected, either computed tomography (CT) or positron emission tomography (PET) is essential. Note that barium esophagography has been mostly supplanted by endoscopy; however, it is of value in certain situations - especially if the endoscope cannot be passed through the esophagus due to obstruction by tumor, or malignant stricture formation. Staging of esophageal cancer is via the TNM system; treatment is dictated by stage, tumor location, and the patients' medical fitness for receiving a particular therapeutic modality. In this respect, key treatment options include local mucosal resection or ablation for superficial disease, and esophagectomy, chemotherapy, and radiation therapy for more advanced tumors. Superficial tumors involving only the mucosa (T1a) are candidates for endoscopic mucosal resection, radiofrequency ablation, cryotherapy, and photodynamic therapy. Close endoscopic surveillance is essential post-treatment. On the other hand, tumors involving the submucosa (T1b) require esophagectomy without induction therapy; those involving the muscularis layer (T2N0M0) benefit from definitive chemoradiation and esophagectomy. Tumors which have nodal involvement may benefit from induction chemoradiation followed by surgical resection or esophagectomy. Where metastatic disease is present, palliative therapy include chemotherapy and supportive care is preferred; radiation or endoscopic dilatation and stenting may palliate dysphagia or bleeding from tumors. Unfortunately, esophageal cancer has an extremely poor prognosis; the overall 5-year survival is just 17%; this is because half of patients already have metastases at the time of diagnosis, while another third have locally advanced disease.

Take home messages

  1. Cancer of the esophagus classically presents with progressive dysphagia in a background of significant weight loss.
  2. Key modifiable risk factors include untreated gastrointestinal reflux disese (GERD), smoking, and obesity.
  3. Upper gastrointestinal (GI) endoscopy is the diagnostic investigation of choice; contrast studies are now mainly used in exceptional circumstances.
  4. Unfortunately these patients have a very poor 5-year survival rate, as the majority have locally advanced or metastatic disease by the time of diagnosis.

Insightful, fun cases to improve your diagnostic skills

Use your detective skills, strengthen fundamentals faster, and access a wealth of knowledge.

  1. BERRY MF. Esophageal cancer: staging system and guidelines for staging and treatment. J Thorac Dis [online] 2014 May:S289-97 [viewed 03 April 2016] Available from: doi:10.3978/j.issn.2072-1439.2014.03.11
  2. CHEN X.. Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention. [online] 2001 August, 22(8):1119-1129 [viewed 01 April 2016] Available from: doi:10.1093/carcin/22.8.1119
  3. D'AMICO TA. Outcomes After Surgery for Esophageal Cancer Gastrointest Cancer Res [online] 2007/01/01 00:00, 1(5):188-196 [viewed 04 April 2016] Available from:
  4. D'JOURNO XB, THOMAS PA. Current management of esophageal cancer J Thorac Dis [online] 2014/05/01 00:00, 6(Suppl 2):S253-S264 [viewed 02 April 2016] Available from: doi:10.3978/j.issn.2072-1439.2014.04.16
  5. DOMPER ARNAL MJ, FERRáNDEZ ARENAS Á, LANAS ARBELOA Á. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol [online] 2015 Jul 14, 21(26):7933-43 [viewed 01 April 2016] Available from: doi:10.3748/wjg.v21.i26.7933
  6. INGELFINGER JULIE R., RUSTGI ANIL K., EL-SERAG HASHEM B.. Esophageal Carcinoma. N Engl J Med [online] 2014 December, 371(26):2499-2509 [viewed 22 March 2016] Available from: doi:10.1056/NEJMra1314530
  7. LAYKE JC, LOPEZ PP. Esophageal cancer: a review and update. Am Fam Physician [online] 2006 Jun 15, 73(12):2187-94 [viewed 22 March 2016] Available from:
  8. NAPIER KYLE J. Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities. WJGO [online] 2014 December [viewed 01 April 2016] Available from: doi:10.4251/wjgo.v6.i5.112
  9. RICE TW, RUSCH VW, APPERSON-HANSEN C, ALLEN MS, CHEN LQ, HUNTER JG, KESLER KA, LAW S, LERUT TE, REED CE, SALO JA, SCOTT WJ, SWISHER SG, WATSON TJ, BLACKSTONE EH. Worldwide esophageal cancer collaboration. Dis Esophagus [online] 2009, 22(1):1-8 [viewed 22 March 2016] Available from: doi:10.1111/j.1442-2050.2008.00901.x
  10. WALLACE MB, NIETERT PJ, EARLE C, KRASNA MJ, HAWES RH, HOFFMAN BJ, REED CE. An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy. Ann Thorac Surg [online] 2002 Oct, 74(4):1026-32 [viewed 22 March 2016] Available from: