A 54-year-old man presents for evaluation of pain and difficulty with swallowing, and weight loss. The patient states that over the past 4 to 5 weeks, he has noticed a decrease in the ability to tolerate solid foods; he has been having pain and discomfort with swallowing, along with a sensation of “the food being stuck in his chest.” Because of these symptoms, he has switched over to a liquid diet essentially consisting of soups, juices, and tea that he has tolerated reasonably well. During this period of time the patient has noticed a 20-lb (9.1-kg) weight loss. His past medical history is significant for hypertension, and his medications include metoprolol and proton pump inhibitor (PPI) (over the counter). The patient appears thin with significant temporal wasting. His vital signs are normal, there is no evidence of adenopathy, and the remainder of the physical examination is unremarkable. His white blood cell count is normal, hemoglobin is 12 g/dL, and hematocrit is 40%. His serum electrolytes, liver enzymes, and glucose are within normal limits.
What is the most likely mechanism causing this process?
What is the most appropriate next diagnostic step?
What are the risk factors associated with this process?
ANSWERS TO CASE 54: Esophageal Carcinoma
Summary: A previously healthy 54-year-old man presents with dysphagia and weight loss.
• Most likely mechanism: Mechanical obstruction from a neoplastic process.
• Most appropriate next step in diagnosis: Esophagoscopy with biopsy.
• Risk factors associated with this process: Known risk factors associated with squamous cell carcinoma of the esophagus include caustic burns, alcohol consumption, tobacco smoking, and nitrite- and nitrate-containing food. Gastroesophageal reflux disease (GERD) is a known risk factor associated with gastroesophageal junction (GEJ) adenocarcinoma (odds ratio of 7.7), and other suspected risk factors are Western diet and acid suppression medications.
ANALYSIS
Objectives
1. Learn the approach to local and systemic staging of esophageal and proximal stomach carcinoma.
2. Learn to apply staging information and clinical assessment to help determine the optimal treatment course for patients with esophageal carcinoma.
Considerations
This patient describes dysphagia to solid foods that has developed over a fairly short time period (several weeks). The timing of symptom progression along with a history of self-medicating with PPI suggests that he may have had a history of GERD and has now developed adenocarcinoma of the distal esophagus. If the patient were to describe a more protracted course (months to years) of dysphagia, the differential diagnoses would also include benign strictures, congenital malformations, and achalasia; however, given the fairly rapid onset and progression of symptoms, a neoplastic process is the most likely cause.
The most important initial evaluation is to determine the nature and location of the blockage, and this can best be accomplished by esophagogastroduodenoscopy (EGD) and tissue biopsy. If the biopsy should demonstrate the presence of esophageal cancer, the next step would be tumor staging, which includes the assessment of local disease with endoscopic ultrasound and evaluation for possible metastatic disease with computed tomography (CT) of the chest and abdomen. In some institutions, positron emission tomography (PET) CT scan has replaced standard CT as the staging modality of choice. It is important to bear in mind that carcinoma of the esophagus and proximal stomach may produce very similar clinical pictures but would require different treatment approaches; therefore, EGD, endoscopic ultrasound, and CTs are extremely important to help pinpoint the tumor location. Precise localization of the tumor is essential not only for the surgical planning, but also may influence the selection of palliation for patients who are not candidates for surgery.
Early on during the evaluation process, it is important to assess and optimize the patient’s nutritional status. Initial nutritional assessment involves the quantification of weight loss and measurement of serum albumin level. For this individual, who is still tolerating liquids, it would be possible to initiate nutritional supplementation with high-protein, high-calorie liquid supplements to help replenish his losses and meet his ongoing metabolic needs. If this patient is unable to tolerate adequate oral intake, it may be necessary to initiate enteral nutritional support, which can be accomplished with the placement of a feeding access distal to the obstructive process. Because there is no contraindication to enteral nutrition, total parenteral nutrition (TPN) is not indicated.
APPROACH TO: Esophageal and Proximal Gastric Cancers
DEFINITIONS
ENDOSCOPIC ULTRASONOGRAPHY (EUS): EUS is currently the most accurate imaging modality for identifying the depth of tumor invasion (T stage) and for identifying regional nodal disease (N stage). In patients in whom lymphadenopathy is visualized, EUS-directed fine-needle aspiration of the nodes can help confirm regional nodal metastasis. EUS results can be highly operator dependent.
SIEWERT CLASSIFICATION OF GE JUNCTION ADENOCARCINOMAS (TYPE I-III): Type I tumors are located more than 1 cm above the GE junction (surgical treatment would generally consist of esophagectomy); type II tumors are located within 1 cm proximal and 2 cm distal to the GE junction (surgical treatment would consist of esophagectomy with partial resection of the proximal stomach); type III tumors are located more than 2 cm distal to the GE junction (surgical treatment would consist of total gastrectomy).
TRANSTHORACIC ESOPHAGECTOMY (TTE): This resection is traditionally done through an incision in the abdomen (or laparoscopic approach) and a separate incision through the right chest. The proximal esophagus is divided at approximately the level of the azygos vein and distal transection is usually at the level of the proximal stomach. The stomach is then brought into the mediastinum and anastomosed to the proximal esophagus. TTE has the disadvantages of having an anastomosis in the mediastinum and is associated with a high rate of pulmonary complications due to pain from incisions in both the chest and upper abdomen.
TRANSHIATAL ESOPHAGECTOMY: This resection is done through an abdominal incision (or by laparoscopic approach) and a cervical incision. Through the abdominal approach, the stomach is mobilized and the distal esophagus is dissected after enlargement of the hiatal opening. Through the cervical incision, the cervical esophagus is mobilized and the proximal thoracic esophagus is dissected, and the entire thoracic esophagus and the proximal stomach are resected, and the gastric conduit is brought up through the posterior mediastinum and anastomosed to the cervical esophagus in the neck. The major advantages of this approach are reduction in pulmonary complications compared to TTE and reduced mortality and morbidity-associated cervical anastomotic leaks.
CLINICAL APPROACH
The incidence of esophageal cancer has increased sixfold over the past 25 years, where this tumor is the sixth most common malignancy encountered in the United States. Although squamous cell carcinoma continues to account for the majority of esophageal cancers encountered in developing countries, adenocarcinoma is the predominant tumor encountered in North America (~70%).
Curative Therapy
Overall, cancers of the esophagus and GE junction carry a poor prognosis with a 5-year survival of less than 20% for all affected patients, and cancer stage has been established as one of the best determinants of survival (Table 54–1). Because early-stage cancers are curable, it is important to identify the disease in the treatable stages, such as by identifying Barrett changes in patients with reflux and the identification of dysplasia or cancerous changes through surveillance. Unfortunately, because of tumor local extension, the presence of metastatic disease, and poor host conditions, fewer than 50% of patients presenting with esophageal cancers are eligible for surgical resection. In the past, palliative resections had been routinely performed for the relief of dysphagia; however, with recent advances in palliative therapy, the majority of surgical resections are now performed with curative intentions. While patients with stage I (T1 N0) cancers may require surgical resection only, surgery + chemotherapy ± radiation therapy are the multimodality treatment approaches currently recommended for the majority of patients with potentially curable cancers. There have been a number of clinical trials evaluating preoperative chemoradiation therapy + surgery versus surgery alone in patients with stages I and II squamous cell carcinoma, and despite prolongation in survival with preoperative chemoradiation, no long-term survival advantages have been demonstrated. In contrast to the marginal survival difference reported for patients with esophageal squamous cell carcinoma, there is good evidence supporting the use of pre- and postoperative chemotherapy in the treatment of patients with adenocarcinoma of the esophagus and stomach. In a trial reported by Cunningham et al in the New England Journal of Medicine in 2006, patients with esophageal (14%), GE junction (12%), and gastric adenocarcinoma (74%) were randomized to pre- and postoperative chemotherapy (epirubicin, cisplatin, 5-FU [5-fluorouracil]) versus surgery alone, where the combined therapy patients benefited with higher rate of curative resections and improved survival. It is important to bear in mind that during this trial, the majority of the patients had gastric adenocarcinoma (74%), and esophageal carcinoma and GE junction carcinoma patients made up only 26% of the entire study population; therefore, one must remain cautiously optimistic when extrapolating these study findings to patients with esophagus and GE junction adenocarcinoma.
Table 54–1 • AMERICAN JOINT COMMITTEE ON CANCER (AJCC) ESOPHAGEAL CARCINOMA STAGING AND SURVIVAL BASED ON STAGING
The benefits of targeted molecular therapy in addition to chemotherapy have been recently examined in the Trastuzumab for Gastric Cancer (ToGA) trial. During this trial, patients with gastric cancers and GE junction adenocarcinomas that demonstrated overexpression of human epidermal growth factor receptor 2 (HER2) proteins by either immunohistochemistry or gene amplification by fluorescence in situ hybridization were randomized to combination chemotherapy or chemotherapy + trastuzumab (a monoclonal antibody against HER2). Patients who received trastuzumab + chemotherapy had increased survival with minimal increase in treatment-related toxicities; therefore, combination therapy has become the new standard for patients with HER2 overexpression adenocarcinoma. Most groups have reported that roughly 15% of the gastric and/or esophageal adenocarcinomas have overexpression of HER2.
Palliative Therapy
Palliation for patients with esophageal carcinoma is directed at preserving the quality of life for patients in whom cure would not be possible. Because the most common complaint that affects patients’ quality of life is dysphagia, the primary goal of palliative care is rapid relief of dysphagia with minimal hospitalization and with the preservation of swallowing function. Secondarily, palliative care may be directed at the prevention of bleeding, perforation, and tracheoesophageal fistula (TEF) formation.
In general, palliative modalities include endoscopic therapy (stent placement, laser, and photocoagulation), radiation therapy (external beam or intraluminal), chemotherapy, and feeding tube placement. Factors that determine the selection of palliative therapy for any given patient include the availability of technology, local expertise, patient conditions, tumor location and characteristics, and the expected length of survival. Table 54–2 contains the pros and cons of the available palliative modalities.
Table 54–2 • PALLIATIVE MODALITIES FOR ESOPHAGEAL CARCINOMA
COMPREHENSION QUESTIONS
54.1 A 45-year-old man is diagnosed with an exophytic adenocarcinoma of the distal esophagus that penetrates to but does not penetrate through the muscularis propria. A CT scan of the chest does not demonstrate evidence of distant metastases. Which of the following is the most appropriate treatment?
A. Placement of endoscopic stent to relieve obstruction and initiate chemotherapy
B. Initiation of chemotherapy followed by endoscopic resection of the tumor, if tumor shrinkage is achieved
C. Initiation of chemotherapy followed by esophagectomy and additional postoperative chemotherapy
D. Nutritional therapy followed by esophagectomy
E. Combined chemoradiation
54.2 Which of the following is a major limitation to endoscopic stent placement for the palliation of esophageal carcinoma?
A. Recurrent esophageal obstruction.
B. Patients often have a several-week delay before symptom improvement occurs after the therapy.
C. Endoscopic stent placement eliminates the possibility of later surgery.
D. The presence of TEF is a contraindication.
E. Endoscopic stent placement is helpful in limiting gastroesophageal reflux.
54.3 Which of the following statements regarding squamous cell carcinoma of the esophagus is true?
A. Squamous cell carcinoma of the esophagus is increasing.
B. Gastroesophageal reflux is a risk factor.
C. This tumor is most amendable to surgical resection when located in the cervical esophagus.
D. The 5-year survival is excellent following complete resection.
E. This tumor is highly responsive to radiation therapy.
ANSWERS
54.1 C. The patient described here most likely has a T2 N0 M0 (stage IIA) adenocarcinoma of the esophagus. Given the clinical and radiographic staging information, the patient’s tumor is potentially curable, and the recent randomized prospective trial data (Cunningham et al, New England Journal of Medicine, 2006) suggest that survival may be improved over surgery alone if this patient is treated with initial induction chemotherapy followed by esophagectomy and postoperative chemotherapy. Stent placement and chemotherapy would be appropriate, if the patient has metastatic disease or if his overall condition precludes operative treatment. Endoscopic ablation or resection as definitive therapy is appropriate only for selective patients with intramucosal lesions.
54.2 A. Recurrent obstruction may develop due to tumor progression and stent migration following stent placement. Esophageal obstruction is often immediately improved following endoscopic stenting. Esophagectomy following stent placement is generally not a problem. TEF is not a contraindication to stent placement; in fact, TEF is preferentially treated with the placement of endoscopic covered stents. Placement of endoscopic stents across the GE junction may contribute to GE reflux, and GE reflux is less of a problem with newer stent models.
54.2 E. Squamous cell carcinoma of the esophagus is highly sensitive to radiation therapy. Patients receive excellent palliation from radiation treatments. Unfortunately, tumor recurrence is common after radiation therapy. In Western societies, the frequency of squamous cell carcinoma of the esophagus is decreasing. Tobacco, alcohol use, and chemical burns are risk factors for development of esophageal squamous cell carcinoma.
CLINICAL PEARLS
The incidence of adenocarcinoma of the esophagus and GE junction is rapidly growing in westernized, developed countries.
Treatment outcome of esophageal carcinoma is improved with multimodality treatment.
Esophagectomy is primarily performed in patients with potentially curable esophageal cancers.
REFERENCES
Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687-697.
Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Eng J Med. 2006;355:11-20.
Homs MYV, Kuipers EJ, Siersema PD. Palliative therapy. J Surg Oncol. 2005;92:246-256.
Jobe BA, Hunter JG, Peters JH. Esophagus and diaphragmatic hernia. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:803-887.