Malignant Tumors of the Postcricoid Area Treatment & Management

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

Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous