TITLE: HYPOPHARYNGEAL CANCER
SOURCE: UTMB Dept. of Otolaryngology Grand Rounds
DATE: March 5, 1997
RESIDENT PHYSICIAN: Carl Schreiner, MD
FACULTY PHYSICIAN: Francis B. Quinn Jr., MD
SERIES EDITOR: Francis B. Quinn, Jr., MD

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"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion."


ANATOMY OF THE HYPOPHARYNX

The hypopharynx extends from its juncture with the oropharynx at the tip of the epiglottis (or level of the hyoid bone) superiorly to the inferior border of the cricoid cartilage. It can be divided into three sites: the pyriform sinus, the postcricoid area, and the posterior pharyngeal wall.

The pyriform sinus is a funnel shaped structure that begins superiorly at the glossoepiglottic fold and extends inferiorly with its apex at the level of the cricopharyngeus. It is bounded laterally by the thyroid lamina and posteriorly by the lateral wall of the hypopharynx. Its medial boundary is the lateral surface of the arytenoid.

The second region is the posterior pharyngeal wall, which extends from a plane drawn at the level of the tip of the epiglottis (some describe at the level of the vallecula or hyoid) to a plane at the inferior border of the cricoid. The superior and inferior margins of the hypopharynx blend with the posterior wall of the oropharynx and esophagus, respectively.

The third area is the postcricoid area. This includes the posterior surface of the aryepiglottic fold and posterior surface of the arytenoid to the inferior border of the cricoid cartilage. This area is the most difficult to examine by both mirror exam and direct laryngoscopy.

The lining of the hypopharynx is stratified squamous epithelium and has a rich submucosal network of lymphatics that exit superiorly through the thyrohyoid membrane into the superior and middle jugular nodes. Inferiorly, the lymphatics drain to the paratracheal and low jugular nodes.

The hypopharynx functions as a dynamic conduit for food that helps prevent aspiration. As the food bolus is propelled past the epiglottis, contraction of the constrictor muscles propel the food towards the cricopharyngeus. The cricopharyngeus relaxes as the food enters the esophagus, where peristaltic action propels the food to the stomach. Motor innervation of the superior and middle constrictors is by the superior pharyngeal nerve and the pharyngeal branches of the vagus and glossopharyngeal nerves. Innervation of the inferior constrictor is from the external and recurrent branches of the vagus nerve. Sensory innervation of the pyriform sinus is from the internal branch of the superior laryngeal nerve. This complex muscular coordination is disrupted by major surgical reconstruction in this area and may result in severe aspiration even when the laryngeal sphincter is intact.

INCIDENCE AND RISK FACTORS

Cancer of the hypopharynx is not common but generally has a very poor prognosis. Laryngeal cancer is three times as common as hypopharyngeal cancers and often presents earlier due to hoarseness. Almost all cancers of the hypopharynx are squamous cell carcinomas and the vast majority of patients present with at least stage III disease. This is likely due to a combination of the lack of symptoms with smaller lesions, the propensity for early submucosal spread and skip lesions, and the lack of definitive anatomic boundaries to prevent early spread of the cancer.

Most patients who develop cancer of the hypopharynx have a history of heavy smoking and drinking. Males are about eight times more susceptible to cancer of the hypopharynx but a certain group of females have an increased incidence of cancer of the postcricoid area. These females are of Irish and Scandinavian descent and have the Plummer-Vinson syndrome. This syndrome is characterized by esophageal webs, iron deficiency anemia, glossitis and an increased incidence of esophageal cancer. The malignancy usually develops just proximal to the web and is felt to be due to chronic irritation. Progressive dysphagia is characteristic of the disorder and can be reversed if treated early with iron replacement, esophageal dilation and vitamin therapy.

DIAGNOSIS

Many patients with hypopharyngeal cancer have been treated at a primary care facility for many months before referral. Chronic inflammatory changes of the pharynx due to smoking often leads to a diagnosis of chronic pharyngitis and multiple courses of antibiotic are common. Referred otalgia by Arnolds nerve (a branch of CN X) may also be a presenting symptom. Twenty percent of patients with hypopharyngeal cancer will present with an asymptomatic neck mass, usually in level II or III. With advanced disease, severe weight loss and nutritional deficiencies are common . The physical exam should include a thorough head and neck exam and attention to the oral cavity and general appearance for signs of severe nutritional deficiencies. A hot potato voice or hoarseness due to vocal cord paralysis may be present. The mirror and fiberoptic exam should look for pooling of secretions in the pyriform sinus or vocal cord paralysis and should include a search for a second primary. The neck exam should include a search for metastasis and fine needle aspiration is indicated.

RADIOLOGY

When a diagnosis of a hypopharyngeal malignancy is suspected, a CT scan is essential, due to the possibility of submucosal spread. It is not uncommon for the CT scan to demonstrate more extensive disease than appreciated by indirect or direct laryngoscopy. The finding of edema on CT scan may be more suggestive of submucosal infiltration than biopsy. CT also aids in the ability to stage the lesion and look for cartilage or preepiglottic space invasion and determine if direct extension into the neck, usually between the middle and inferior constrictors has occurred.

CT evaluation of the neck, especially of the contralateral neck in cases of palpable ipsilateral adenopathy, may also affect treatment planning. Carotid involvement may also be an issue but MRI and ultrasound may be better at predicting carotid artery involvement.

Other essential radiologic tests include a chest x-ray to rule out metastasis or a second lung primary, a barium swallow or modified barium swallow to determine the dynamic effects of the tumor on swallowing and the status of the upper esophagus. Bone scans are not routinely indicated in hypopharyngeal cancer.

STAGING ENDOSCOPY

The single most important goal of the staging endoscopy is to determine the inferior extent of the tumor, and its relation to the pyriform apex, esophageal inlet, and the cervical esophagus. The evaluation should be performed under general anesthesia with complete paralysis after the barium swallow and CT have been performed. Identification of the inferior extent of tumor spread can be facilitated by passing a small laryngoscope, such as an anterior commissure scope, into the postcricoid area on the opposite side of the tumor and gently withdrawing the scope to look for the inferior margin of the tumor. Whether the apex of the pyriform is involved also has important treatment implication as will be discussed later. Esophagoscopy and biopsies should be performed after mapping the tumor and complete evaluation of the esophagus down to the gastroesophageal junction is mandatory. If gastric interposition is planned, then complete gastroscopy is indicated.

PATHOLOLGY

Over 95% of malignancies of the hypopharynx are squamous cell carcinomas. Most of the remaining 5% are adenocarcinomas. Most hypopharyngeal carcinomas arise in the pyriform fossa, followed by the posterior hypopharyngeal wall and lastly, the postcricoid area. Of the tumors that involve the pyriform sinus, approximately 90% involve the apex of the sinus.

A prominent feature of hypopharyngeal tumor is submucosal spread, and this has been often related to treatment failure. This characteristic appears to be more common as the tumor approaches the cervical esophagus, likely due to the increased submucosal lymphatics in this area. Satellite tumors are also common in this area and whether they represent micrometastases or separate primary tumors is controversial.

Lateral wall pyriform sinus tumors have been shown to invade the thyroid cartilage and extend directly into the thyroid or metastasize to the thyroid. Ipsilateral thyroidectomy is usually indicated in these cases even if the thyroid is not clinically involved. Most authors consider pyriform apex or thyroid cartilage involvement a contraindication for partial laryngectomy. Tumors of the medial wall of the pyriform tend to extend towards the supraglottis and preepiglottic space resection should be done if partial laryngectomy is performed. The status of surgical margins appears to have a profound affect on survival, which is in contrast to supraglottic tumors, where close or positive margins have not been shown to affect survival. One study correlated positive inferior margins in hypopharyngeal cancer with a 5% 5 year survival.

Tumor size was also correlated with positive neck disease, with 50% positive neck metastasis in tumors less than 4cm in size and 85% metastasis in tumors larger than 4 cm. As stated earlier, most (about 75%) cases present with positive neck disease.

Vocal cord paralysis can occur through several mechanisms. Pyriform sinus tumors can infiltrate into the posterior cricoarytenoid muscle. Involvement of the cricoarytenoid joint or direct invasion of the recurrent laryngeal nerve may also occur.

PROGNOSIS

The overall survival of patients with hypopharyngeal cancer is about 40%. The site, size and status of the neck have significant affects on outcome. In patients with cervical metastasis, there is a 20 to 25% incidence of distant metastasis within 2 years of treatment. Stage I and II posterior hypopharyngeal wall cancers have an excellent prognosis. In contrast, even small pyriform sinus cancers are notorious for metastasizing early and carry a poor prognosis. Postcricoid lesions usually present as advanced lesions with extensive paratracheal and mediastinal metastasis and has a poor prognosis.

MANAGEMENT

Radiation therapy
Primary radiation therapy is can be curative for small (T1) lesions of the hypopharynx, particularly exophytic tumors that involve the medial wall of the pyriform sinus and do not extend to the apex. Radiation therapy for T2 lesions, leaving surgery for salvage is controversial. Signs of recurrent disease include persistent arytenoid edema, pain, and vocal cord fixation. Radiation therapy may also be preferable for small tumors of the posterior hypopharyngeal wall or for palliation with larger stage III and IV tumors. Planned preoperative or postoperative radiation therapy is the most common technique for using radiation therapy in the treatment of hypopharyngeal cancer.
Suprahyoid pharyngotomy
This approach can be used for lesions localized to the posterior hypopharyngeal wall. It involves a direct approach above the hyoid bone into the vallecula. The hyoid bone can be removed for exposure once the pharyngotomy is made. The incision of the posterior pharyngeal wall is usually carried down to the pervertebral fascia in most cases, but prevertebral muscles may be excised if necessary. Reconstruction can usually be performed with a bolstered skin graft which can be removed transorally in 10 to 14 days.
Partial laryngopharyngectomy or Extended supraglottic laryngectomy
Conservation surgery for small tumors of the posterior hypopharyngeal wall has been described by Ogura in 1960 and was expanded to include pyriform sinus tumors if certain criteria are met. The three most important criteria include: normal vocal cord mobility, no extension of the tumor to the apex of the pyriform sinus, and no thyroid cartilage involvement. The operation is an extension of the supraglottic laryngectomy concept and involves the combination of suprahyoid and lateral pharyngotomy approaches. Interarytenoid and aryepiglottic cuts allow excision of the ipsilateral arytenoid and pyriform sinus with cuts similar to a supraglottic laryngectomy on the contralateral side. In general, these operations are oncologically unsafe for anterior pyriform sinus and aryepiglottic fold cancers. Laccourreye noted a 41% failure rate at the lateral margin with the lateral supraglottic laryngopharyngectomy and has abandoned the procedure.
Supracricoid Hemilaryngopharyngectomy (SCHLP)
In contrast to the partial laryngopharyngectomy, the supracricoid hemilaryngopharyngectomy resects the entire ipsilateral thyroid ala and arytenoid which allows more adequate resection of the pyriform sinus. T2 lesions of the pyriform fossa without pyriform apex or postcricoid involvement are candidates for SCHLP. The main advantage of SCHLP is that the cricoid cartilage is preserved and thus decannulation is possible. Sphinteric functional recovery with airway protection and swallowing is possible due to the remaining mobile arytenoid and vocal cord.

Determining the feasibility of SCHLP depends on both tumor and patient factors. Due to the possibility of significant aspiration, the patient must have a thorough pulmonary evaluation preoperatively and be informed of the possibility of either intraoperative conversion to a total laryngectomy or delayed laryngectomy for chronic aspiration. As stated earlier, vocal cord fixation with bulky pyriform sinus involvement usually indicates paraglottic space involvement and either cricoarytenoid joint or posterior cricoarytenoid muscle involvement. Such patients are not candidates for SCHPL. On the other hand, impaired cord mobility due to tumor bulk without invasion of the cricoarytenoid muscles may still be amenable to SCHPL. In these cases CT and MRI may help evaluate the paraglottic space and cricoarytenoid joint. Other contraindications include involvement of the postcricoid area, interarytenoid area, posterior pharyngeal wall, tonsillar pillar (due to possible infiltration of the stylopharyngeus muscle) and involvement of the preepiglottic space, although the latter is controversial because both the ipsilateral and contralateral preepiglottic fat pad can be resected.

As described by Laccourreye, the operation is performed under general anesthesia with direct laryngoscopy to confirm suitability of the tumor for SCHLP. A tracheotomy is performed and a standard apron incision is made with adequate exposure for a neck dissection. A radical or modified radical neck dissection is performed with resection of the ipsilateral hemithyroid and the larynx is exposed from the hyoid to trachea. The posterior border of the ipsilateral infrahyoid muscles is identified and retracted medially, exposing the posterior border of the thyroid cartilage. The perichondrium is incised and elevated medially towards the midline as a musculoperichondrial flap. The hyoid may be resected or preserved depending on the location of the tumor. The superior laryngeal pedicle is ligated and a midline thyrotomy is performed with extension through the cricothryroid membrane.

The incision is carried through the preepiglottic space and epiglottis, including the contralateral preepiglottic fat pad. Resection is continued laterally above the hyoid, exposing the tumor and pyriform sinus. Under direct vision, the posterior margin is taken caudally through the interarytenoid area. This cut is taken close to the contralateral arytenoid to avoid mucosal excess and edema. The cricoarytenoid joint is disarticulated, releasing the lower pyriform sinus from the cricoid. The inferior margin is taken where the cricothryroid membrane attaches to the cricoid. The mucosa is closed over the arytenoid and the superior border of the cricoid is left exposed. Two options exist for closure and creating a buttress for the remaining arytenoid. The remaining lateral pharyngeal wall can be sutured to the medial laryngeal remnant or the musculoperichondrial flap can be directly sutured to the lateral pharyngeal wall.

Postoperatively, decannulation is usually performed within a week and oral feeding is started at about 2 weeks. Prolonged feeding difficulties are common and may take up to a year for resolution. Aspiration is a chronic risk following SCHLP and is likely partially due to resection of the ipsilateral superior laryngeal nerve. Laccourreye noted a 20% aspiration pneumonia rate and 11 of 233 patients required conversion to a total laryngopharyngectomy. 20 patients required gastrostomy for impaired swallowing and aspiration. Overall 87% of patients recovered satisfactory swallowing without aspiration. Ten local recurrences (5.2%) were noted and occurred most frequently in the pharynx. No pharyngocutaneous fistulas occurred.

Near-Total Laryngopharyngectomy (NTLP)
Near-total laryngopharyngectomy (NTLP) can be performed for selected hypopharyngeal cancers for which total laryngopharyngectomy is considered. It differs from the SCHLP in that tumors with cord fixation and pyriform apex involvement can be included, but the ipsilateral cricoid is resected so a permanent tracheostoma is required.

The nomenclature concerning near-total laryngectomy is confusing. Hemicricolaryngectomy, as described by Krespi is a more specific description of a similar operation. The near-total laryngectomy was initially described by Pearson at the Mayo Clinic in 1980 as an extended hemilaryngectomy but this led to confusion as the term hemilaryngectomy usually refers to conservative operations that preserve the cricoid. Also, near-total laryngectomy is not to be considered a typical conservation operation such as a supraglottic or vertical partial laryngectomy because it requires a permanent stoma, but a lung powered voice is still possible.

NTLP can be considered in patients with T2 and T3 lesions of the pyriform sinus in which total laryngectomy is contemplated. According to Pearson, it is not meant to replace total laryngectomy, but it just reduces the indications. The key to a NTLP is an bloc resection of the paralaryngeal space, including the ipsilateral cricoid. Conservation procedures preserve the cricoid ring, but in the case of pyriform apex involvement, resection would require stripping the mucosa off the cricoid, preventing an en bloc resection. Similarly, pyriform sinus cancers cause vocal cord fixation early due to paralaryngeal space invasion. Therefore, vocal cord fixation is not a contraindication to a NTLP as opposed to the supracricoid laryngectomy. In fact, can be thought of as indications for NTLP. NTLP is not recommended for radiation failures, postcricoid or interarytenoid tumors, bilateral cord fixation, tumors approaching the midline posteriorly and in cases with bilateral palpable nodes. Some consider NTLP safe in cases of pyriform apex involvement but Krespi sites a lack of a cartilagenous barrier to prevent submucosal spread across the midline and recommends total laryngectomy in these cases.

The resected specimen from a NTLP includes the entire hermilarynx from the base of tongue to the trachea, pyriform sinus and part of the posterior pharyngeal wall if indicated. If the resulting defect requires reconstruction with a flap, near-total laryngectomy can still be performed. The remaining contralateral posterior glottic tissues are reconstructed to form a semirigid glottic shunt to allow phonation and effective swallowing. Reconstruction of the pharyngeal defect with a skin graft or pectoralis myocutaneous flap is usually necessary to prevent pharyngeal stenosis.

Advocates for NTLP claim good speech with NTLP and site problems with tracheoesophageal speech such as leakage and the need for frequent care and changing the prosthesis. Despite reported functional successes and oncologic safety, in general, the NTLP has not been accepted as a viable alternative to total laryngectomy outside the Mayo Clinic. This may be in part due to technical problems with the speaking shunt, including mucosal breakdown, aspiration, stenosis and fistulae and a general acceptance of total laryngectomy with tracheoesophageal speech.

Other Procedures for Hypopharyngeal Cancer
Total laryngectomy should still be considered the baseline procedure for hypopharyngeal cancer for which all lesser procedures should be measured. Indications for total laryngectomy are the same as contraindications for NTLP previously described. Other techniques for reconstructing circumferential defects of the hypopharynx (myocutaneous flaps, gastric pull-up and jejunal free flap) have been discussed in a previous grand rounds.

REFERENCES

Teshima, T. et al Radiation Therapy for carcinoma of the hypopharynx with special to nodal control Laryngoscope 98:564-567, May 1988

Marks, JE et al Pharyngeal wall cancer Arch Otolaryngol 111:79-85, Feb 1985

Spector, JG et al. Squamous cell carcinoma of the pyriform sinus: a nonrandomized comparison of therapeutic modalities and long-term results. Laryngoscope 105:397-405

Badawi, SA, Goeppert, H. Squamous cell carcinoma of the pyriform sinus. Laryngoscope 92:357-364.

Adams, GL Malignant neoplasms of the hypopharynx in Otolaryngology - Head and Neck Surgery. Cummings, CW Mosby 1993. 1955-1973.

Schecter, GL Hypopharyngeal cancer. in Head and Neck Surgery-Otolaryngology, edited by Byron J Bailey. Lippencott, Philadelphia. 1993:1286-1303.

Barzan, L. Hemilpharyngectomy and hemilaryngectomy for pyriform sinus cancer: Reconstruction with remaining larynx and hypopharynx and with tracheostomy. Laryngoscope 103:82-86. Jan 1993.

Levine, PA Pearson near-total larynectomy: a reproducible speaking shunt. Head and Neck 323-325, July/Aug 1994

Krespi, YP. Voice preservation in pyriform sinus carcinoma by hemicricolaryngopharyngectomy Ann Otol Rhino Laryngol 93:306-310, 1984.

Laccourreye, O. Supracricoid hemilaryngopharyngectomy in selected pyriform sinus carcinoma staged as T2. Laryngoscope 103:1373-1379. Dec 1993.

Laccourreye, H. Supracricoid hemilaryngopharyngectomy. Analysis of 240 cases Ann Otol Rhino Layngol 96: 217-221. 1987