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Risk factors for the development of hypopharyngeal and cervical esophageal carcinoma include chronic alcohol and tobacco use, older age, geographic location, and family history of upper aerodigestive tract cancers.10 Environmental exposure to polycyclic aromatic hydrocarbons, asbestos, and welding fumes may increase the risk of pharyngeal cancer.11 Nutritional deficiencies and infectious agents (especially papillomavirus and fungi) also play a significant role.10 Chronic irritation of the esophagus appears to participate in the process of carcinogene-sis, particularly in patients with thermal and/or mechanical injury, achalasia, esophageal diverticu-lum, chronic lye stricture, or who have undergone radiation therapy.10 Plummer-Vinson syndrome, characterized by dysphagia, iron-deficiency anemia and esophageal webs, as well as celiac disease, tylo-sis and scleroderma are associated with hypophar-ynx and cervical esophagus cancer.12

The principal signs and symptoms of carcinoma of the hypopharynx and cervical esophagus are dys-phagia, hoarseness, odynophagia, neck mass and weight loss. Patients are typically older and may also complain of unexplained oropharyngeal bleeding, hemoptysis or hematemesis. Referred otalgia, mediated via the tympanic branch of the glossopharyngeal nerve (Jacobson's nerve), is a frequent presenting complaint.13 Of these symptoms, the most frequent is odynophagia in over half of patients.13 Dysphagia may be the first sign of recurrence and can precede clinically detectable recurrent tumors by several months.14 The most common site of origin of malignancies within the hypopharynx is the pyriform sinus (Figure 10—1).13 Seventy percent of patients either present with or develop neck metastases during their course of treatment.15 Tumors have extended beyond the hypopharynx in the majority of patients at initial presentation (Figure 10—2).13 The hypopharynx and cervical esophagus are also common occult primary sites in patients with a diagnosis of metastatic squa-mous carcinoma of the neck (excluding the supra-clavicular fossa) from an occult primary tumor.

Post-cricoid Region

Post-cricoid Region

Figure 10-1. Site distribution of carcinoma in the hypopharynx.

Patients who are referred for evaluation of these symptoms require a complete medical history and careful physical examination. A thorough head and neck examination is critical to accurate assessment and staging. Most patients can be examined with a flexible laryngoscope under topical anesthesia (Figure 10-3 and 10-4). The extent of disease at the primary site, the status of lymph nodes in the neck, and evaluation for metastatic disease are vital to appropriate treatment planning. Endoscopic examination of the primary site under anesthesia with biopsy remains the definitive procedure to establish the diagnosis and accurately assess the primary tumor.

The most common histology in patients with hypopharynx and cervical esophagus cancer is squa-mous cell carcinoma. The physical appearance of these lesions can be confused with benign lesions, such as necrotizing sialometaplasia and ectopic gastric mucosa. Other less common histologies include neuroendocrine carcinomas, extrapulmonary bron-chogenic carcinoma, typical and atypical carcinoid tumors, adenocarcinoma and adenosquamous carcinoma, basosquamous cell carcinoma, and lym-phoepithelioma. Invasion of the aerodigestive tract by papillary adenocarcinoma of the thyroid occurs in 1 to 6.5 percent of cases and may manifest as a hypopharyngeal or cervical esophageal lesion.16

The indications for routine oral panendoscopy for the detection of second primary malignancies shows a significant geographic variation which is not based on differences in patient or tumor characteristics.17 There is substantial disagreement in the literature about the value of endoscopic screening for synchronous tumors. The incidence of second primary malignancy of the upper aerodigestive tract varies from 3 percent to 15 percent, and the majority of tumors are detected within 2 years of initial presen-tation.18 Second primary malignancies are more common in patients with hypopharynx and esophageal carcinoma relative to other head and neck sites.18 A higher detection rate is reported for patients undergoing routine panendoscopy.18 Others recommend routine interval endoscopic intervention within 2 years of treatment for optimum detection of second primary cancers. Critics of routine screening esophagoscopy and bronchoscopy point out the low yield, potential for increased morbidity, questionable

impact on expected survival and outcome and high cost in support of their position.19 Therefore, the decision regarding routine panendoscopy in the evaluation of hypopharynx and cervical esophagus cancer is currently left to the discretion of the clinician.

The combination of clinical exam and computed tomography (CT) scan is more accurate than physical exam alone in the evaluation of the primary site and

Figure 10-3. Fiberoptic endoscopic appearance of a carcinoma of the posterior phyaryngeal wall.

neck with tumors of the hypopharynx (Figure 10—5).20 Open neck exploration is superior to CT when evaluating pre-vertebral muscle invasion by squamous cell carcinoma.21 Of the radiographic criteria used to evaluate laryngeal involvement, sclerosis of the thyroid cartilage is the most sensitive and extra-laryngeal tumor and erosion is the most specific.22 Computed tomography and magnetic resonance

Figure 10-4. Flexible endoscopic appearance of a carcinoma of the pyriform sinus.
Figure 10-5. CT scan demonstrating invasion of the thyroid cartilage from a carcinoma of the left pyriform sinus.

imaging (MRI) are comparable in the radiologic evaluation of the neck for regional lymph node metastases relative to clinical exam.23 Diagnostic imaging can also provide information about submucous tumor extension and cartilage involvement, leading to upstaging in many cases. MRI tends to be superior to CT in predicting tumor invasion and is valuable in the selection of candidates for conservation surgery.24 Any patient considered for chemoradiation protocols should undergo baseline CT as lesions that are reduced by 50 percent or less at 4-month follow-up CT are highly suspicious for treatment failure.25

Patients who present at an advanced stage are at increased risk for distant metastases. The hypophar-ynx has the highest incidence of distant metastases (60%) relative to other head and neck sites. The lung is the most common site of distant metastases (80%), followed by mediastinal nodes (34%), liver (31%), and bone (31%).26 The standard initial evaluation for distant metastases includes a chest radiograph and serum chemistries. Chest radiographs have an approximate sensitivity and specificity of 50 percent and 94 percent, respectively, for the detection of pulmonary metastases.27 Elevated serum levels of alkaline phosphatase are highly specific for the presence of bone metastases, but the sensitivity is low (20%).27 Although serum liver function tests assess hepatic function, abnormal values are found in almost half of patients with head and neck cancer, due to chronic alcohol use, and therefore are of little value in identifying patients with liver metastases during initial assessment.28 Moderate elevation of liver function tests does not always require further investigation to exclude hepatic metastases.28 In general, a chest CT should be obtained with an abnormal chest x-ray, a bone scan in the event of an elevated alkaline phos-phatase or patient symptoms, and either an ultrasound or CT/MRI scan of the liver when significant elevation of liver function tests is present, depending on tumor stage and associated co-morbidities.27

Positron emission tomography (PET) is a new imaging technique which provides absolute and comparable quantitative data on tumor metabolism before and after chemotherapy. Radiolabeled fluoro-deoxyglucose (FDG) is used to measure metabolic activity. As tumor cells consume more glucose relative to surrounding normal cells, a difference in signal intensity can be identified. The presence of PET activity correlates with pathologic findings in patients with head and neck cancer.29 Elevated or rising PET activity after radiation therapy strongly suggests persistent or recurrent disease that may not be detected by CT or MRI. Patients with hypophar-ynx or cervical esophagus cancer who are candidates for chemoradiation protocols should undergo PET scans as part of their preoperative evaluation.

Although gender and performance status do not correlate with treatment outcome, certain clinical and histologic parameters have prognostic implications for patients with hypopharyngeal or cervical esophageal squamous cell carcinoma. Perineural invasion, vascular invasion, positive nodal status, extracapsular spread, contralateral, bilateral or fixed nodes, level IV to V positive nodes, and N2 disease are all significant predictors of lower survival, higher incidence of neck recurrences, greater risk of distant metastases, and poorer outcome.30 Cervical esophageal carcinomas are notorious for extensive submucosal spread, increasing the risk of positive margins following resection. Disease extension outside the cervical esophagus is present in more than 75 percent of patients.31 Tracheal invasion and vocal cord paralysis occur in up to one-third of patients and is associated with significantly decreased survival.31

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