Malignant Tumors of the Postcricoid Area 

Updated: Feb 25, 2016
Author: Douglas B Villaret, MD; Chief Editor: Arlen D Meyers, MD, MBA 

Overview

Background

The postcricoid region, pyriform sinus, and posterior hypopharyngeal wall comprise the hypopharynx. Tumors rarely appear in the posterior pharyngeal wall or postcricoid region without also involving the pyriform sinus. The lack of anatomic barriers between these sites and a propensity for these tumors to develop in the pyriform sinus and spread outward account for this phenomenon.

Overall prognosis for these tumors is poor. Because of the rich organic lymphatic and vascular networks, aggressive growth and early cervical metastases (compared with cancers at other head and neck sites) characterize these cancers.

Additionally, the nerve supply is relatively nonlocalizing (similar to that in the abdomen), which most often yields vague symptoms of discomfort as the initial presenting signs until the tumor has grown to an impressive size. Because of these factors, hypopharyngeal cancers are discovered at a later stage than other head and neck cancers. The delay in diagnosis from symptom onset averages 10 months. This fact requires that health care professionals investigate vague symptoms of a "lump in the throat" and swallowing difficulty more carefully if symptoms do not respond quickly to conservative intervention.

For excellent patient education resources, visit eMedicineHealth's Cancer Center. Also, see eMedicineHealth's patient education article Cancer of the Mouth and Throat.

See the image below.

Postcricoid cancer. Postcricoid cancer.

History of the Procedure

In the early part of the 20th century, x-ray technology was insufficiently advanced for applications in cancer treatment; thus, surgery was the only option. Coutard applied the maturing field of radiobiology to the hypopharynx in the 1920s, and his methods were improved into the 1950s. The development of megavoltage radiation enhanced cure rates to a significant degree, but surgery remained the mainstay of all major protocols. The issue of preoperative versus postoperative radiation delivery was addressed in the early 1970s, with strong evidence favoring the better survival and lower complication rates associated with postoperative radiation. In current practice, the postoperative radiation dose is usually 66-72 Gy. Delivery schedules have been the subject of much discussion, with many studies showing an advantage for hyperfractionated therapy (120 Gy/dose, twice/d) and other studies showing no difference for once-daily treatments at 180-200 Gy/dose.

Problem

Postcricoid cancer is an insidious disease that usually manifests late in its course, making treatment difficult and good cure rates hard to achieve. At present, surgery and radiation are needed to attain the highest cure rates, although improvements are being made with conservative therapy of radiation and concomitant chemotherapy.

Epidemiology

Frequency

In the United States, the postcricoid cancer frequency rate is 2.4-3.1% of all hypopharyngeal cancers, which places its overall prevalence at approximately 0.01 cases per 100,000 persons. The rate is higher in the United Kingdom and India, with figures quoted from 3.5-40% of all hypopharyngeal tumors.

Etiology

Many factors influence the eventual progression to cancer in the postcricoid region. The most obvious of these is the well-known synergistic influence of tobacco and alcohol, whose combined carcinogenic effect promotes cancer in this region. More than 90% of patients with hypopharyngeal cancers smoke tobacco, and figures indicate 60-70% abuse alcohol. These data are extrapolated from hypopharyngeal studies because well-constructed inquiries addressing tobacco and alcohol involvement specifically with postcricoid carcinomas have not emerged.

Radiation therapy has also been implicated in hypopharyngeal tumor growth (after a 10- to 20-y delay). Moreover, a geographical component for this disease seems apparent, with such tumors most common in Anglo-Saxon countries and India but rare in Mediterranean countries and the United States.

The more-celebrated etiological association is with a condition called Plummer-Vinson syndrome (alternately termed Paterson-Brown-Kelly syndrome). This syndrome is associated with hypochromic (iron-deficient) anemia, usually below 12 g/dL. The syndrome includes a history of dysphagia elicited by hypopharyngeal webs, usually centered in the postcricoid area. Other aspects include glossitis, angular stomatitis, koilonychia, and microglossia. The latter abnormalities are encountered with much less frequency than dysphagia brought about by the webs and hypochromic anemia.

Various studies place the rate of Plummer-Vinson syndrome and postcricoid cancer coincidence at 4-16%. This number ranges quite widely, even within studies from the same country. Coincidence seems highest in the United Kingdom and areas with populations of Scandinavian descent and lowest in the United States and Asia. However, reports from India indicate increased coincidence of postcricoid carcinoma and variable Plummer-Vinson syndrome.

The sex of the patient sex also may increase the risk for postcricoid cancer. This is most notable in areas with relatively high rates of Plummer-Vinson syndrome. In these countries, women develop the disease more often than men by a female-to-male ratio of approximately 3:1. However, other countries demonstrate a slight male predominance.

Pathophysiology

The genesis of postcricoid carcinoma mirrors that of other head and neck cancers. Initial insults with carcinogens, generally from the synergistic effects of tobacco and alcohol, result in genetic alterations. Most commonly, TP53 obtains a mutation that makes it ineffective in controlling the cell growth rate. After this early event, a promoting event is thought to occur before these cells truly become cancerous. Much work has been accomplished to study the course of genetic events leading to carcinogenesis in the head and neck. Many studies focus on alterations on chromosomes 9 and 11. Ultimately, cancer cells form that escape host immunological surveillance and begin to grow as a tumor.

Presentation

Most patients report a globus or foreign-body sensation in the throat for months to years before diagnosis. This is the single common finding in all cases of postcricoid carcinoma. Generally, this dysphagia progresses to limit intake of solids and, eventually, liquids. As the tumor becomes more pronounced, generalized dysphagia turns into odynophagia, and a focal area of pain can often be elicited. An ominous sign at this point is referred otalgia; the stimulus initiates from the tumor and courses along the sensory distribution of the vagus nerve, where it meets with the Arnold nerve in the middle ear.

Extrapolating from hypopharyngeal data, up to 25% of these tumors are diagnosed initially based on the presence of an asymptomatic mass in the neck that proves to be metastatic disease to the cervical lymph nodes. Up to 75% of patients have cervical lymph node metastases at the time of presentation, with 10% having bilateral disease. The postcricoid area tends to spread into the paratracheal area and into the inferior jugular nodes. Occult metastases may occur in up to 80% of patients without clinically obvious nodes.

A less frequent presentation is hoarseness, which stems from growth of the tumor anteriorly into the posterior cricoarytenoid muscles or directly into the recurrent laryngeal nerve, thus interfering with vocal cord motion.

Indications

Once the tumor has been verified as a cancer, usually squamous cell carcinoma, it is assessed for conservative management. Many centers use neoadjuvant chemotherapy to determine whether laryngeal and hypopharyngeal tumors will respond to radiotherapy. Tumor volume can also be used; tumors of less than 6 cm3 often respond to radiation alone, provided cartilage destruction is insignificant. Therefore, any cancerous tumor unresponsive to chemotherapy or greater than 6 cm3 should undergo appropriate resection as the initial treatment.

Radiation treatment can be used alone in patients with low-volume T1 and T2 cancers and is added to surgery if the tumor is evaluated as stage III or IV. Additionally, perineural, perivascular, or soft tissue invasion (noted on final pathology results) or multiple positive nodes and/or extracapsular extension all indicate radiation treatment. Patients who are not surgical candidates but who have advanced disease that is potentially curable are best treated with concomitant chemotherapy and irradiation.

Relevant Anatomy

The postcricoid region of the hypopharynx includes the mucosa and submucosa extending from the inferior aspect of the arytenoids to the bottom of the cricoid cartilage. The lateral margins merge with the medial wall of each pyriform sinus at approximately that level where the cricoid cartilage makes an anterior bend. The nerve supply is from the pharyngeal plexus, which derives from the vagus and glossopharyngeal nerves (cranial nerves X and IX). The blood supply comes from both the external carotid system (ie, superior thyroid artery to superior laryngeal artery, ascending pharyngeal artery) and the thyrocervical trunk (ie, ascending cervical artery, inferior thyroid artery to inferior laryngeal artery).

The hypopharynx is shaped like a funnel with its most anterior segment missing. This corresponds to the introitus to the larynx. The hypopharynx is covered by mucosa of stratified squamous epithelium intermixed with goblet cells. It begins at the level of the hyoid bone and extends laterally along the pharyngoepiglottic fold. The posterior hypopharynx is divided from the oropharynx superiorly by a line drawn horizontally from the hyoid bone and is divided from the cervical esophagus inferiorly by a line drawn horizontally from the bottom of the cricoid cartilage. The pyriform sinuses are folds of the hypopharynx that encompass the larynx on its lateral edges. This sinus is tucked into a small area between the aryepiglottic folds of the larynx and the thyroid ala. The postcricoid region fills out the hypopharynx.

Contraindications

Several factors can make a postcricoid cancer unresectable. For tumors extending into the soft tissues of the neck, most surgeons use carotid encasement as an indicator of unresectability. While the technical aspects are not daunting, the overall survival rate after carotid resection is so poor that potential sequelae (eg, stroke, mental status changes, death) do not justify the small percentage of salvage cases. Extension into the prevertebral musculature, while rare, is also a contraindication for surgery. Finally, distant metastases preclude the possibility of surgical cure.

Relative contraindications include a patient with the inability to withstand lengthy anesthesia, whether due to cardiac (eg, poor ejection fraction, severe cardiomyopathy), pulmonary (eg, severe chronic obstructive pulmonary disease), renal, or a host of other causes. Reports from the 1970s also mention a size limit of 5 cm (vertical length) as the largest tumor amenable to cure, with a patient survival rate of 0% at 18 months for tumors exceeding this size. These reports ignore different radiotherapy delivery methods and/or the addition of chemotherapy. Advanced age no longer contraindicates treatment because successful operations (including repair with free flaps) on patients in their 90s have been performed.

 

Workup

Laboratory Studies

Lab studies used in the assessment of patients with postcricoid cancer include the following:

  • Hematology: Obtain a CBC count for all patients to evaluate white blood cell and platelet levels and to check for possible hypochromic anemia.

  • Metabolic: The authors' standard practice requires a renal profile (Chem-7) to evaluate for diabetes and any unknown metabolic derangement that necessitates correction prior to surgery or radiation. Because these patients are often malnourished, aberrancies in this profile are common.

  • Metastatic profile: Past standards called for liver function testing and bone profiles, but these tests are no longer required unless specific findings (eg, jaundice, bone pain) dictate they be performed.

Imaging Studies

CT scanning

Computed tomography (CT) scanning is best for delineating the laryngeal and hypopharyngeal interface and, with direct laryngoscopy, is the authors' basis for most clinical decisions. If performed with contrast material, CT scans also allow evaluation of the neck for metastases. When the patient is positioned in a plane horizontal to the true vocal cords, axial images offer a very detailed view of tumor extent. (See the image below.)

Postcricoid cancer. Postcricoid cancer.

Use CT scans to evaluate (1) cricoid cartilage invasion, (2) tumor progression inferior to the cricopharyngeus (into the cervical esophagus), (3) tongue base involvement, and (4) the possibility of resection, dependent on the relationship of the tumor to the deep neck structures.

MRI

Magnetic resonance imaging (MRI) is best used to determine any tongue base extension. In patients with very large tumors, removal of some or the entire tongue base may become an issue.

While CT scans often provide significant information, MRI is superior for examining muscular planes, although motion artifact in the airway sometimes complicates interpretation.

Modified barium swallow

Barium studies offer a better 3-dimensional representation of tumors. Secondary to collapse of the tissues in this area, study results are sometimes difficult to evaluate if the tumor is coming off anterior or posterior walls of the hypopharynx according to the CT scan images. Barium swallow also shows small mucosal irregularities better than the other imaging choices. This allows superior determination of the extent of resection required.

Even with these excellent attributes, the authors now rarely obtain barium swallows because of improvements in CT imagery. Furthermore, the authors' standard practice of panendoscopy before surgical resection renders the barium swallow unnecessary.

PET scanning

Positron emission tomography (PET) scanning may be useful in detecting lung metastases in patients with high-volume neck disease.

Diagnostic Procedures

Before definitive treatment (eg, surgery, radiation), evaluate the extent of the disease by performing a panendoscopy and a biopsy. Biopsy results confirm the pathologic diagnosis, while panendoscopy aids in the evaluation of the tumor for resectability with reasonable margins.

A study by Ni et al indicated that in patients undergoing laryngoscopic examination prior to surgery for hypopharyngeal cancer, the hypopharynx, including the extent to which the cancer has invaded the posterior pharyngeal wall and postcricoid area, can be successfully displayed using a combined strategy of anterior cervical skin traction and execution of the Valsalva maneuver by the patient. In the study, the investigators found that the hypopharynx was revealed in 106 of 113 patients (93.8%), using this technique.[1]

Histologic Findings

Almost all tumors in this region are squamous cell carcinomas. The histology of squamous cell carcinoma shows cells ranging from polygonal to cuboidal, with an increased nuclear-to-cytoplasmic ratio, varying amounts of cellular polymorphism, and nuclear atypia (with cells undergoing mitosis at an increased rate). More specific to squamous cells are intracellular bridging and keratin pearl formation, depending on the degree of tumor differentiation (well-differentiated tumors have increased keratin formation). Other potential tumors in this area include (1) adenocarcinomas, with some rudimentary glandular formation seen within the tumor; (2) sarcomas, usually with a spindle-shape component to the cells; (3) lymphangioma with thin-walled vessels; and (4) mucosal melanoma with small, round, blue cells that stain positive for melanoma markers and S-100.

Staging

The staging system used is derived from the American Joint Committee on Cancer, as updated in 2002, for hypopharyngeal cancer.

TNM definitions

Primary tumor (T)

Definitions are as follows:

  • TX - Primary tumor cannot be assessed

  • T0 - No evidence of primary tumor

  • Tis - Carcinoma in situ

  • T1 - Tumor limited to 1 subsite* of the hypopharynx and is less than or equal to 2 cm in greatest dimension

  • T2 - Tumor invades more than 1 subsite of the hypopharynx or an adjacent site, or measures more than 2 cm but less than or equal to 4 cm in greatest diameter without fixation of hemilarynx

  • T3 - Tumor measures more than 4 cm in greatest dimension or with fixation of hemilarynx

  • T4a - Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissue, which includes prelaryngeal strap muscles and subcutaneous fat

  • T4b - Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

    • *Subsites of the hypopharynx are as follows:

      • Pharyngoesophageal junction (ie, the postcricoid area), extending from the level of the arytenoid cartilages and connecting folds to the inferior border of the cricoid cartilage

      • Pyriform sinus, extending from the pharyngoepiglottic fold to the upper end of the esophagus, bounded laterally by the thyroid cartilage and medially by the surface of the aryepiglottic fold and the arytenoid and cricoid cartilages

      • Posterior pharyngeal wall, extending from the level of the floor of the vallecula to the level of the cricoarytenoid joints

Regional lymph nodes (N)

Definitions are as follows:

  • NX - Regional lymph nodes cannot be assessed

  • N0 - No cervical metastases

  • N1 - Metastasis in a single ipsilateral lymph node, less than or equal to 3 cm in greatest dimension

  • N2 - Metastasis in a single ipsilateral lymph node, more than 3 cm but less than or equal to 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, less than or equal to 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, less than or equal to 6 cm in greatest dimension

    • N2a - Metastasis in a single ipsilateral lymph node more than 3 cm but less than or equal to 6 cm in greatest dimension

    • N2b - Metastasis in multiple ipsilateral lymph nodes, less than or equal to 6 cm in greatest dimension

    • N2c - Metastasis in bilateral or contralateral lymph nodes, less than or equal to 6 cm in greatest dimension

  • N3 - Metastasis in a lymph node more than 6 cm in greatest dimension

In clinical evaluation, the actual size of the nodal mass should be measured, and allowance should be made for intervening soft tissues. Most masses more than 3 centimeters in diameter are not single nodes but confluent nodes or tumors in soft tissues of the neck. There are 3 stages of clinically positive nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but recommended. Midline nodes are considered homolateral nodes.

Distant metastasis (M)

Definitions are as follows:

  • MX - Distant metastasis cannot be assessed

  • M0 - No distant metastasis

  • M1 - Distant metastasis

AJCC stage groupings

Stages are defined as follows:

  • Stage 0 - Tis, N0, M0

  • Stage I - T1, N0, M0

  • Stage II - T2, N0, M0

  • Stage III

    • T3, N0, M0

    • T1, N1, M0

    • T2, N1, M0

    • T3, N1, M0

  • Stage IVA

    • T4a, N0, M0

    • T4a, N1, M0

    • T1, N2, M0

    • T2, N2, M0

    • T3, N2, M0

    • T4a, N2, M0

  • Stage IVB

    • T4b, any N, M0

    • Any T, N3, M0

  • Stage IVC - Any T, any N, M1

 

Treatment

Medical Therapy

Treatment for postcricoid cancer has undergone a transformation similar to that of the laryngopharyngeal area as a whole. Lately, researchers have sought ways to avoid the perceived morbidity of total laryngectomy.[2] Many centers are relinquishing the primary surgery-postoperative radiation approach for an organ-preservation protocol. The scientific rationale for this model received support from a large US Department of Veterans Affairs laryngeal-preservation trial. This was a randomized study of more than 330 patients who received cisplatin and 5-fluorouracil chemotherapy delivered in a neoadjuvant setting. Patients with at least a partial response (>50%) also received radiation treatment. Nonresponders underwent total laryngectomy and postoperative radiation therapy. Overall survival rates for both methods were similar, and two thirds of survivors retained their larynx.

The European Organization for Research and Treatment of Cancer performed a similar trial for the hypopharynx, with stricter chemotherapy-response criteria. Only complete responders proceeded directly to radiation, while incomplete responders received total laryngectomy and partial or total pharyngectomy. Again, no significant survival difference was noted, and 42% of survivors retained their larynx.

To evaluate the effect of chemotherapy, a French group randomized a group of patients who had pyriform sinus cancer. The 2 arms of the study were neoadjuvant chemotherapy followed by radiation (regardless of tumor response) and standard surgery followed by postoperative radiation. Results showed that survival rates in the chemotherapy arm were almost half those of the surgical arm, suggesting that chemotherapy did not treat cancer, but that it acted mostly as a selection tool for cancers that would respond well to radiation.

The University of Florida treats T1 and favorable T2 tumors 6cc or less with hyperfractionated radiation to a total tumor dose of 74 Gy. T3-T4 and/or N2-N3 tumors often receive concomitant chemotherapy (if patient health status allows) or primary surgical management followed by postoperative radiation therapy. IMRT using the concomitant boost technique may be advantageous to irradiate postcricoid carcinomas in patients with a low-lying larynx and a short neck.

Surgical Therapy

Surgical excision followed by postoperative radiation is the treatment of choice for cancers not amenable to a conservation protocol (ie, tumors destroying cartilage, tumors too bulky for control with primary radiation). Some patients, if their functional disability is significant, choose this route even with smaller tumors, and a total laryngectomy offers improved swallowing and, rarely, improved vocalization. The minimum operation recommended is a total laryngectomy and partial pharyngectomy with a central (level 6) node dissection.

The hypopharynx is special in that studies show extensive submucosal spread of tumor and even skip lesions in this region. For these reasons, the surgeon must be more aggressive and obtain wider margins than in other areas of the head and neck. If the tumor is staged as a T2 or higher, perform a neck dissection (usually bilaterally because the postcricoid area is a midline structure that can send metastases to either side of the neck). The extent of neck dissection is debated widely and depends on various factors, including primary tumor extent and nodal metastases. Most commonly, perform a bilateral lateral neck dissection (level 2-4) with the inclusion of level 6. Often, a primary tracheoesophageal puncture is placed to allow early feeding via a Levine tube and eventual voice restoration.

Reconstruction of the resultant defect, as seen in the image below, varies widely and depends on the extent of resection of the hypopharyngeal mucosa. Because these tumors often manifest late in their course, total laryngopharyngectomies are common. For small lesions in which only a small amount of mucosa is resected, primary closure may be attempted. If this procedure fails, several options are available, provided a 2-cm wide (or wider) strip of mucosa remains in continuity with the cervical esophagus.

See the image below.

Malignant tumors of the postcricoid area. Surgical Malignant tumors of the postcricoid area. Surgical defect (after a total laryngopharyngectomy). The endotracheal tube is in the trachea; sutures are on the cut end of the esophagus.

The most common closure for this defect is the pectoralis major musculocutaneous rotational flap, with the skin paddle facing into the lumen of the hypopharynx as seen in the images below.

Malignant tumors of the postcricoid area. Harvesti Malignant tumors of the postcricoid area. Harvesting a pectoralis major myocutaneous flap.
Malignant tumors of the postcricoid area. Insettin Malignant tumors of the postcricoid area. Insetting a pectoralis major myocutaneous flap after a total laryngopharyngectomy.

If a smaller strip of mucosa remains or if the pectoralis flap cannot be used, the next most common reconstruction is the radial forearm fasciocutaneous free flap. Advantages of this procedure include increased tissue pliability (because of decreased muscle bulk) and greater positioning ease (because the flap is not tethered by a muscular pedicle). Unfortunately, this procedure increases the operative time and hospital course. Some studies suggest that the tubed forearm flap yields better swallowing results than the partially tubed pectoralis rotational flap.

Several repair options are available for total laryngopharyngectomy defects. Historically, the Wookey flap was used to restore pharyngeal-esophageal continuity. The procedure consists of internalizing the cervical skin and, through multiple operations, tubing this skin and reconnecting the gullet. Disadvantages include multiple operations and high fistula and stricture rates.

The Wookey flap was replaced by the Bakamjian flap, which uses the rotated deltopectoral fasciocutaneous flap pedicled on the first 3 perforators from the internal mammary system. This method also requires several operations, and, while more reliable than the Wookey flap, it tends to stricture at the distal anastomosis. The tubed pectoralis major flap based on the thoracoacromial artery eventually displaced the Bakamjian flap because this is a one-stage procedure using a very reliable flap with a lower failure rate. The major disadvantage of this flap is the difficulty of completely tubing the skin, subcutaneous fat, and muscle from the chest, especially in women and large individuals.

The advent of free tissue transfer techniques allows a more customized and functional reconstruction in a single stage. The 2 most common are the radial forearm fasciocutaneous flap based on the radial artery and the jejunal free flap based on a mesenteric artery as depicted in the images below.

Malignant tumors of the postcricoid area. Inset of Malignant tumors of the postcricoid area. Inset of a radial forearm fasciocutaneous free flap after a partial pharyngectomy and total laryngectomy.
Malignant tumors of the postcricoid area. Inset of Malignant tumors of the postcricoid area. Inset of jejunal free flap after total laryngopharyngectomy. Forceps are on the monitor paddle.

Each has advantages and disadvantages. The jejunum is part of the alimentary tract; thus, it is already lubricated and tubed, eliminating the need for a vertical suture line. However, entering the abdomen to harvest the flap creates an ileus and further slows the recovery process. The forearm flap is more reliable but must undergo metaplasia to a more respiratory-type mucosa, and it needs a vertical suture line to complete the tube. The stricture rate is low for each flap.

For individuals who simply reject the procedure, who are poor candidates for free flaps (because of an inability to tolerate extended general anesthesia or because of vascular problems), or who have tumor extending to the cervical esophagus, the correct reconstructive procedure becomes the gastric pull-up. This entails a mediastinal dissection, complete removal of the esophagus, and passage of the stomach into the neck via the posterior mediastinum as depicted in the image below.

Malignant tumors of the postcricoid area. Specimen Malignant tumors of the postcricoid area. Specimen from total laryngopharyngoesophagectomy.

This procedure can be performed from an open abdominal approach or endoscopically as seen the image below.

Malignant tumors of the postcricoid area. Surgeons Malignant tumors of the postcricoid area. Surgeons performing endoscopic gastric pull-up.

The risks include proximal necrosis of the stomach (with resultant separation), dumping syndrome into the duodenum, and uncontrolled reflux into the neopharynx.

Preoperative Details

Obtain a full oncologic workup to include a complete history, physical examination, head and neck examination, and review of systems. The full workup then includes a CBC count, Chem-7, blood type and screen, chest radiograph, ECG, CT scan, and interventions indicated based on the review of systems. If a radial forearm flap is a reasonable option, perform an Allen test on each arm. A bowel preparation is often used if a jejunal free flap or gastric pull-up is planned. If possible, present the patient's case at a tumor board forum to receive input from all involved physicians. Ensure that voice therapists counsel the patient preoperatively to assist in the transition to alaryngeal speech and to address the difficulties of learning to swallow again. Finally, after the patient has received a full explanation of the procedure, obtain signed consent.

Intraoperative Details

Intubate the supine patient. Prepare the patient with povidone-iodine (Betadine) scrub, and paint to include the lower ears, upper lip, and neck (along the edge of the trapezius). Always prepare the chest in case a pectoralis flap is needed, and include a thigh for a potential split-thickness skin graft. Prepare other areas (eg, forearm, abdomen) if those flaps are planned. Alert the anesthetist that the airway circuit will be changed once the trachea is entered.

Incision

The most common type of access is a U-shaped "apron" flap extending from one mastoid process to the other and crossing the midline approximately 2 cm above the sternal notch. Then, complete the neck dissections in standard fashion. Generally, lateral neck dissections are performed; the submandibular area is not removed, and the sternocleidomastoid muscle, the spinal accessory nerve, and internal jugular vein are all left in the patient. This results in the removal of lymph nodes from levels 2-4.

Tumor removal

Remove attachments of the inferior and middle pharyngeal constrictors to the thyroid cartilage to skeletonize the larynx. Partially free the pyriform mucosa from the thyroid ala. Next, mobilize the hyoid bone by removing all suprahyoid attachments down to the hyoepiglottic ligament. Remove the soft tissues down to the trachea; the thyroid gland can be included or excluded from this dissection. Resect the tumor if it encroaches on a lobe of the thyroid gland. If oncologically possible, preserve at least a portion of thyroid and parathyroid glands. Establish the airway by incision into the larynx, and transfer the anesthesia circuit. Place a Deaver retractor into the mouth, and pass it to the vallecula, which has been inspected previously to ensure an absence of tumor.

If feasible, enter the pharynx on the side opposite the tumor. Cut through the pharyngeal mucosa to expose the tip of the retractor. Under direct visualization, perform pharyngeal cuts around the larynx. This step may include a circumferential or partial pharyngectomy. Remove the larynx by cutting through the back wall of the trachea at the previous incision site. Remove the tumor, achieving a pharyngeal mucosa margin of at least 3 cm.

Reconstruction

If primary closure can be performed, use a running Connell stitch. This stitch is designed to invert the mucosa for a watertight seal. If a strip of mucosa is left in continuity (cranial-caudal), a musculocutaneous pectoralis major flap can be tunneled into the neck, and closure can be performed by suturing the mucosa to the skin paddle. If only a small strip of mucosa remains or if a total pharyngectomy has been performed, a tubed radial forearm free flap can be placed. The authors usually suture the vertical limb while the flap is still pedicled in the forearm. If a total pharyngectomy had been planned, the authors prefer a jejunal flap for reconstruction.

A second team concomitantly harvests the free flap while the resection nears completion. Then, bring the tubed forearm or jejunum flap into the neck and suture the posterior aspect of the superior and inferior anastomosis to the pharyngeal mucosa with interrupted 3-0 polyglycolic sutures. Place the anterior sutures followed by anastomosis of the vascular pedicles. Allow up to a 3- or 4-hour period of ischemia for the jejunal and forearm flaps, respectively. Copiously irrigate the site, and bring down the skin flaps while maturing the tracheostoma with 3-0 monofilament sutures.

Postoperative Details

The first postsurgical night usually entails intensive care unit admission, especially with free-flap reconstructions. The authors monitor the free flap every 4 hours for 3 days with a pinprick using a 25-gauge needle (see Complications). Incline the head of the bed 30�, and obtain vital signs hourly. After the first night, transfer the patient to a step-down unit with nurses specifically trained in the care of patients with airway issues. Continue antibiotic coverage while drains are in place.

Airway

If the underlying pulmonary system allows, extubate at the end of surgery without placing a stent in the tracheostoma. Deliver cool mist via a face tent positioned over the stoma, and add oxygen to keep oxygen saturation above 90%. Commence suctioning every 2-4 hours and as needed.

Nutrition

Begin tube feeding on postoperative day 1 unless the abdomen has been entered for a gastric pull-up or a jejunal free flap, in which case hold feeding until the ileus has resolved. (Food is then delivered via jejunostomy tube.) Stenting of the closure by a feeding tube is unnecessary for either primary approximation of the hypopharynx or flap-assisted closure; thus, the authors use the primary tracheoesophageal puncture site or a gastrostomy tube. The authors rarely use a nasogastric tube. Usually, start oral feeding on postoperative day 6 or 7, provided no serious complication (eg, pharyngocutaneous fistula, flap failure) has occurred. Perform a barium swallow, as seen in the image below, before the initiation of oral alimentation in patients who have received a free flap.

Malignant tumors of the postcricoid area. Barium s Malignant tumors of the postcricoid area. Barium swallow on postoperative day 7, after radial forearm free flap reconstruction.

Pain control

Initially, administer morphine via nursing assessment or, if feasible, by patient-controlled analgesia. Switch to oxycodone elixir as soon as enteral feeding has begun; reserve morphine for breakthrough pain.

Drain management

Leave drains until output decreases to 15 mL in 8 hours or until drains have been in for 1 week. The authors are conservative in leaving drains, especially in patients who have received a free flap.

Discharge

Approve patients for discharge when they can perform daily living activities (eg, bathing, toiletry) and can ingest and tolerate sufficient nutrient energy. Generally, this means oral feeding has begun. Occasionally, the feeding tube must be continued, usually due to fistula formation. In addition, uncontrolled infection must be absent. These conditions are usually met at approximately postoperative day 7-10 in patients who have not been irradiated.

Follow-up

Follow-up depends on the type of closure used to repair the neopharynx. Home nursing affords patients an early discharge while maintaining medical oversight. A home nurse also may assist with the management of wounds and tracheostoma. If a free flap has been used, normally schedule the first clinic visit at postoperative day 7-14, depending on postoperative complications.

Once the acute healing process is completed, patients often receive radiation treatments, if not previously administered. Thereafter, follow up every 4-6 weeks the first year, every 8-10 weeks the second year, every 12 weeks the third year, and then annually. Obtain a CT scan at 6 months, sometimes at 1 year, and then only as symptoms indicate. If a tracheoesophageal puncture has been performed, insert the prosthesis after 2 weeks and commence speech therapy.

Complications

Intraoperative

Several complications can occur intraoperatively. They can be divided into technical and nontechnical problems. Nontechnical complications relate to general anesthesia and include malignant hyperthermia, vascular embolus, and diabetes insipidus. Technical complications include excessive hemorrhage, incomplete tumor removal, loss of airway, and excessive operating time.

Postoperative

The most common serious complication is pharyngocutaneous fistula. This usually results from a technical error in suturing the pharynx (with or without a flap), from leaving tumor at the margin, or from radiated tissue with poor blood supply (predisposed to necrose at the distal tip). Fistulas occur in approximately 10-15% of cases. Conservative management yields more satisfactory results than covering the fistula with more tissue. The authors' approach medullizes the fistula from the carotids by opening the tissues further in this direction and then packing the opening with quarter-inch gauze. Over the next few weeks, granulation tissue forms and slowly closes the fistula.

One of the more serious preventable problems is loss of airway. This occurs by mucous plugging, crusting over from the tissue edges, or foreign bodies lodging in the upper airway. Loss of airway can be avoided with attentive nursing care and by strategically placing susceptible patients in rooms near the nursing station.

Carotid blowout is often fatal problem and occurs after the carotid artery is exposed to saliva for some time. Emergent management includes holding pressure over the wound, establishing 2 large-bore intravenous lines, and ordering replacement volume or blood—all while transporting the patient to the operating room. Ligate the carotid as far inferior as possible, then rotate it in a vascularized flap to cover the stump. Attempt to divert the saliva, but the tissues are generally friable and hold sutures poorly. This complication is rare with newer reconstructive techniques.

A chylous fistula can occur but is related to neck dissection. (Essentially, the thin-walled lymph system suffers violation without recognition during surgery.) For output of less than 500 mL/d, place a pressure dressing and change the tube feeding to a medium-weight triglyceride solution. For greater outputs, institute total parenteral nutrition. If drainage fails to slow, then reexplore the wound and oversew the area. Additionally, rotate a muscular pedicled flap from the scalenes to give a second-layer closure to the area.

Flap failure is always possible because of an insufficiency in the arterial or venous pedicle. For free flaps, the problem usually lies in a thrombus formation at the venous anastomosis. Rarely, compression or clotting occurs in the arterial system, leading to insufficient blood flow to the flap. With either case, most major centers achieve a success rate of 93-96%. Maintain vigilant flap inspection during the first 72 hours, when most complications occur. Check flaps every 4 hours during this critical period using the pinprick method (ie, a 25-gauge needle used to express blood from the flap).

Bright red arterial blood indicates a normal system, whereas venous blood indicates early venous pedicle obstruction. No bleeding suggests a backup that halts all ingress of blood. Another method uses Doppler signals (internally or externally) to check flow in the vascular pedicle. Immediately upon discovering the problem, perform emergent exploration and revision of the anastomosis. Approximately 50% of such flaps can be salvaged with an emergent operation.

Various postoperative medical conditions, influenced by patient health state and operation duration, may occur. Fever in the immediate postoperative course is usually due to atelectasis of the lungs, but this may progress to pneumonia. Also, deep venous thromboses may occur, possibly leading to pulmonary emboli. To reduce this possibility, leave compression boots on the patient. Early ambulation helps prevent both problems.

Outcome and Prognosis

Survival figures for postcricoid carcinoma vary widely. This divergence, in part, may be ascribed to early literature written during the transition of radiation treatments from kilovoltage to megavoltage. Additionally, treatment philosophies differ from country to country and even within the United States. The treatment protocol at the University of Florida uses twice-a-day hyperfractionated radiotherapy to a total dose of 68-72 Gy. Many other centers in the United States administer single-daily fractions of approximately 2 Gy but achieve total doses in the same 68- to 72-Gy range. India and Great Britain tend to use daily doses of 3 Gy to a total dose of 50-55 Gy. These treatment philosophies seem to reflect the collective opinion that hyperfractionated therapy improves survival.

With this in mind, the large retrospective studies dedicated to postcricoid carcinoma emanate from the United Kingdom and India. Reported overall 5-year survival rates range from 7.8-43%. Cited mortality rates of untreatable disease are 50% at 9 weeks and 95% at 30 weeks. The reports define untreatability as tumors larger than 5 cm in longest dimension with true vocal cord fixation, paravertebral muscle invasion, and carotid invasion.

Using tumor stage as a stratification factor, Farrington et al (with a 40- to 50-patient sample for each stage) found a 5-year survival rate of 48% for T1, 23% for T2, 5% for T3, and 5% for T4 disease.[3] Pradhan reported slightly higher figures, although his endpoint was 18-month survival—approximately two thirds of the patients in his study presented with stage III or IV disease.[4] Nodal status also adversely affects survival. Axon et al reported the highest 5-year survival rate (63%) in patients with negative cervical nodes who received surgery as primary treatment.[5] However, other reports place rates as low as 20%. N1 disease survival rates ranged from 9-20%, and N2 or higher disease was always fatal.

The primary treatment modality also has a significant effect on overall survival. While evaluating 146 patients, Pradhan noted a 24% recurrence rate after surgery but found that 92% of patients treated with primary radiation had a recurrence.[4] Stell et al and Axon et al came to a similar conclusion, although the disparity in 5-year survival rates between radiation (23%) and surgery (45%) was more modest.[6, 5]

A retrospective study by Kadapa et al indicated that organ-preserving treatment of locally advanced T3 postcricoid carcinoma with radiotherapy or concurrent chemoradiotherapy produces poor results, suggesting instead that radical surgery with reconstruction and postoperative radiotherapy offers better control and survival outcomes. According to the study, which included 59 patients, the 2-year rates of locoregional control, disease-free survival, and overall survival for nonsurgical treatment were 8.98%, 8.59%, and 15.71%, respectively.[7]

In the United States, overall survival rates for postcricoid carcinoma were estimated best by a voluntary questionnaire developed by the Commission on Cancer's National Cancer Data Committee (reported by Hoffman et al in 1997).[8] Postcricoid carcinoma contributed to only 2.4-3.1% of all cases of hypopharyngeal carcinoma. The 5-year disease-free survival rate, at 45.4%, was slightly better than rates for piriform sinus cancer. (Treatment methods were not noted.) Spector et al showed that surgery followed by postoperative radiation could achieve 5-year survival rates as high as 65%.[9] In contrast, Gluckman showed a 40% survival for T1 and T2 lesions that initially were treated with surgery, while Clayman reported a 52% survival rate in early-stage hypopharyngeal cancer treated primarily with radiation.[10]

As noted earlier and as evidenced from the above data, varying survival rates have been reported for this disease. Factors that influence these rates include the percentage of patients who have advanced disease, extent of submucosal spread, percentage of patients with regional and distant metastases, and treatment protocol. To evaluate the efficacy of surgery over radiation as primary treatment, remember that the volume of disease and the tumor response to chemotherapy have proved predictive of a good response to primary radiation, thus, in certain cases avoiding the morbidity of surgery.

Future and Controversies

Certainly, the most controversial subject surrounding treatment of postcricoid carcinoma is whether to initiate treatment with radiation or surgery. The desire to use radiation derives from morbidity associated with total laryngectomy with possible total pharyngectomy. With average 5-year survival rates hovering in the range of 25-40%, treating the cancer as aggressively as possible seems prudent, which means surgery followed by radiation.

The literature supports both premises. Reports from the United Kingdom and India show a survival advantage to surgery as the initial treatment, but their radiation doses are lower than modern standards (55 Gy vs 70 Gy). In contrast, several studies show equal cure rates using radiation therapy alone, absent cartilage invasion. While surgical salvage is successful only approximately 20% of the time, complications with this approach are not excessive.

The addition of chemotherapy to the treatment protocol improves cure rates by 2 mechanisms. If given in the neoadjuvant setting, chemotherapy selects tumors responsive to radiation therapy but apparently contributes no survival advantage itself. When given concomitantly with radiation, the different mechanism of cell death complements the effect of radiation and seems to improve overall survival, although earlier studies indicate no difference. A different chemotherapy delivery method calls for supradose intra-arterial cisplatin delivery with systemic neutralization using thiosulfate delivered once per week for 4 weeks during radiation treatment. While long-term data are still pending, impressive locoregional control rates (with average 18-mo follow-up) have been published.

The future of cancer treatment almost certainly includes some form of gene therapy. Numerous trials are evaluating different genes (eg, TP53, E1A, MHC class II), yet none has found significant advantage. This may be because these trials are approved for end-stage patients, and overall survival parameters are hard to improve. Other endpoints (eg, time to recurrence, slower tumor progression) are equally valid parameters, and significant improvement would justify widespread use of that gene. Other issues requiring clarification include delivery vehicles (eg, plasmid vs viral vector vs naked deoxyribonucleic acid), delivery methods, and timing of delivery.

Finally, immunomodulators will probably be used once underlying mechanisms are understood. Immunomodulators might include cancer vaccines (similar to breast cancer treatments using HER/neu), antibodies that block the epidermal growth factor receptor, or lymphocytes that target tumors. Steven Rosenberg, MD, PhD, at the National Institute of Health helped pioneer the coadministration of patients' own tumor-invading lymphocytes and various cytokine cocktails for patients with melanoma. Newer strategies use allogeneic immune systems to target cancer. So far, this approach has been used only in hematogenous cancers, but application to solid tumors is under investigation.