Fatigue, Weight Loss, and Dysphagia in an Older Man

For 1 month, a 60-year-old white man has had increasing fatigue, generalized weakness, and exertional dyspnea. He becomes short of breath after he walks only 100 to 150 yards on level ground or climbs only 1 flight of stairs. In addition, he has unintentionally lost 12 lb in the past month and has experienced intermittent dysphagia with solid foods. He attributes this last symptom to long-standing gastroesophageal reflux disease (GERD), for which he regularly takes over-the-counter omeprazole.

He denies fever, rigor, chills, night sweats, rashes, arthralgias, headaches, vision problems, paresthesias, weakness, and ataxia. He has no cough, chest pain, or palpitations, but he has minimal ankle swelling in the evening. His appetite has been poor, resulting in decreased caloric intake, but he does not have nausea, vomiting, diarrhea, constipation, abdominal distention, hematemesis, or jaundice. He has noted no increased bleeding tendency or urinary symptoms.

History. He has had no surgeries. He has smoked 1 or 2 cigars a day for the past 20 years; he does not drink alcohol. He has no history of foreign travel, blood transfusion, or allergies. His father has type 2 diabetes, and his mother died of breast cancer.

Examination. The patient is pale but is not in undue distress at rest. Heart rate is 104 beats per minute; respiration rate, 20 breaths per minute; and blood pressure, 140/76 mm Hg. He is afebrile and well hydrated. No adenopathy is noted. His thyroid gland is not palpable. There is 1+ bilateral ankle edema.

Jugular venous pressure is normal and peripheral pulses are strong. The apex feels normal, and both heart sounds are clearly audible. A musical, grade 2 systolic murmur can be heard over the entire precordial area; however, no gallop is audible. Lungs are clear and abdomen is normal. Results of a rectal examination are normal; results of a guaiac stool test are positive. The patient is neurologically intact.

Laboratory studies. A complete blood cell count reveals a hemoglobin level of 6 g/dL. Laboratory evaluation reveals the following levels: serum iron, 30 μg/dL; total iron binding capacity, 510 μg/dL; and serum ferritin, less than 12 μg/L. Other laboratory values are normal, as are urinalysis results.

A chest radiograph shows no acute infiltrates. Results of a tuberculin skin test are negative. No pathogens are isolated from 2 blood cultures.

Based on the clinical picture and laboratory and endoscopy findings, what is the most likely diagnosis?

•Esophageal candidiasis.
•Barrett esophagitis.
•Cancer of the esophagus.
•Hiatal hernia.
•Herpes esophagitis.

(Answer on next page.)

WHAT’S WRONG
Endoscopy reveals a large esophageal mass extending 4 inches above the gastroesophageal junction and also extending into the stomach, where it involves the lesser curvature and the gastric cardia. In a middle-aged man with severe iron deficiency anemia, weight loss, and dysphagia, this endoscopic finding strongly suggests cancer of the esophagus.

Esophageal candidiasis usually occurs in immunocompromised patients. Affected persons typically have increasing dysphagia and characteristic diffuse white plaques throughout the esophagus, which are visible on endoscopy. Biopsy and culture of the plaques result in the growth of Candida species.

Barrett esophagitis usually occurs in patients with a long-term history of GERD. Those affected may be asymptomatic, or they may have typical symptoms of GERD, such as dyspepsia. Endoscopy usually shows an erythematous lesion in the lower esophagus, and biopsy reveals characteristic findings.

The typical presentation of hiatal hernia is of an obese patient who has reflux symptoms with dysphagia, a burning sensation in the retrosternal area, and recurrent pneumonia. Endoscopy and radiographs show the hernia, unaccompanied by any mass-like lesion.

Herpes esophagitis also occurs in immunocompromised patients (eg, those with advanced HIV infection). Affected patients usually present with progressive dysphagia and weight loss; endoscopy shows multiple small ulcerations.

Hospital course. A biopsy of the esophageal mass showed poorly differentiated adenocarcinoma. A CT scan of the chest revealed a mass lesion in the lower esophagus without any spread. Positron emission tomography (PET) scanning showed no evidence of metastasis.

The patient was given 3 units of packed erythrocytes, which increased his hemoglobin level to 9.5 g/dL. He was evaluated by an oncologist; chemotherapy was initiated, with surgery planned after reduction in the size of the lesion.
 

EPIDEMIOLOGY OF ESOPHAGEAL CANCER
Esophageal cancers occur most commonly in the sixth or seventh decade of life; they account for about 14,300 deaths in the United States each year.¹ Men are affected more often than women.

There are 2 main histological types of esophageal cancer: squamous cell carcinoma (SCC) and adenocarcinoma. Until the 1970s, SCC accounted for 90% of esophageal cancers in the United States.² However, over the past several decades, the incidence of adenocarcinoma has risen dramatically, especially in white men. SCC is more common in blacks than whites and is strongly associated with the long-term use of alcohol and tobacco. Other risk factors for SCC include long-term frequent ingestion of hot liquids; exposure to nitrosamines in certain foods (eg, pickled vegetables, smoked fish, preserved meat); and nutritional and vitamin deficiencies, such as folic acid or vitamin C deficiency. Barrett esophagus, typically a consequence of long-standing GERD, is associated with an increased risk of adenocarcinoma. For unknown reasons, obesity appears to be another risk factor for adenocarcinoma.

CLINICAL MANIFESTATIONS
Esophageal cancer is often detected late in the course of the disease. Solid food dysphagia is the most common presenting symptom; dysphagia for liquids occurs as the disease progresses. Weight loss occurs in up to 75% of patients.³ Retrosternal or epigastric pain may be present. Hoarseness, resulting from invasion of the recurrent laryngeal nerve, indicates advanced disease.

The physical examination is often unrevealing. The presence of supraclavicular or cervical adenopathy indicates metastatic disease. Laboratory findings are nonspecific but may include anemia from iron deficiency or chronic disease as in this patient.

DIAGNOSIS AND STAGING
A double-contrast barium swallow is often the initial study performed in patients who present with dysphagia. If an abnormality is found, endoscopy with biopsy/brushings is recommended; this strategy allows direct visualization of a tumor and confirmation of the diagnosis. Accurate staging of esophageal cancers is important for guiding therapy and determining disease prognosis.

A CT scan of the chest and abdomen is initially performed to detect lymphadenopathy, local tumor extension, and distant metastasis. Endoscopic ultrasonography has become a valuable tool in the staging of esophageal cancers, and it has largely replaced CT for this purpose. It is more accurate than CT in determining the depth of esophageal wall invasion and in detecting regional lymph node involvement. PET scanning is helpful in finding small distant occult metastases not identified on CT.

TREATMENT AND PROGNOSIS
Treatment of esophageal cancer should be individualized, based on tumor stage and the patient’s preferences and functional status. However, the optimal treatment approach is currently a subject of controversy.

Unfortunately, 50% of patients present with extensive local tumor spread or metastasis; their disease is considered incurable.⁴ In such patients, palliative care to relieve dysphagia and pain is the goal; surgery is not indicated. Combination chemoradiotherapy offers the best chance of relieving dysphagia. For patients who fail to respond to or who are poor candidates for chemoradiation, endoscopic interventions, such as dilation, stenting, laser therapy, or photodynamic therapy, may be appropriate.

Early or superficial esophageal cancer with no regional lymph node involvement offers the best chance for cure. Esophagectomy is recommended in patients considered to be good surgical candidates, and neoadjuvant chemoradiotherapy appears to be helpful. Chemoradiotherapy alone is an alternative for those unable to undergo surgery. In patients with local node-positive disease, preoperative chemoradiotherapy may be benefibeneficial, although no randomized trials demonstrate such a benefit. The effectiveness of adjuvant therapy after resection remains unproved.

Despite the widespread use of endoscopy, advances in treatment, and better postoperative outcomes, the 5-year overall survival in patients with esophageal cancer is less than 20%.⁵ Biologic agents that target carcinogenesis and newer chemotherapeutic agents are currently being investigated and hold promise for the future.

References:

REFERENCES:

1.

Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96.

2.

Lightdale CJ. Esophageal cancer. American College of Gastroenterology. Am J Gastroenterol. 1999;94:20-29.

3.

Wang KK, Wongkeesong M, Buttar NS. American Gastroenterological Association technical review on the role of the gastroenterologist in the management of esophageal carcinoma. Gastroenterology. 2005;128:1471-1505.

4.

Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241-2252.

5.

Khushalani NI. Cancer of the esophagus and stomach. Mayo Clin Proc. 2008; 83:712-722.