eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Management of the N3 Neck

Niels Kokot, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine of the University of Southern California
Gregory S Weinstein, MD, FACS, Professor and Vice-Chairman, Department of Otorhinolaryngology-Head and Neck Surgery, Director of Division of Head and Neck Surgery, Director of Head and Oncology Fellowship, Director of Otorhinolaryngology-Head and Neck Clinic, Co-director of The Center for Head and Neck Surgery, University of Pennsylvania School of Medicine

Updated: Apr 8, 2009

Introduction

Squamous cell carcinoma (SCCA) of the aerodigestive tract is the most frequently encountered malignancy of the head and neck. Regional metastases to cervical lymph nodes are common. A patient with N3 disease of the neck is defined as having a single lymph node measuring greater than 6 cm. This patient is automatically categorized as having stage 4b disease. Therefore, diagnosing an N3 neck must be supported by clinical or radiologic measurement of the node in accordance with nodal classifications of the American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC; see Staging).

Levels of metastasis to cervical lymph nodes.

• Patient - Medical condition and risk factors
• Performance status and nutrition
• Pathology - Histology, stage of the disease, location, extent of the disease, and resectability
• Patient's realistic expectations
• Procedure - Curative versus palliative
• Post-treatment survival expectation, locoregional control rates, and quality of life

• Surgical resection of the primary tumor and neck dissection (if operable and resectable), followed by radiation or chemoradiation therapy
• Concurrent chemoradiation therapy followed by planned neck dissection, regardless of nodal response (This option is applicable if the primary tumor has a complete response to chemoradiation therapy based on clinical examination, endoscopic examination, and biopsy of the primary lesion.)
• Concurrent chemoradiation therapy followed by surgical resection of persistent or recurrent disease

History of the Procedure

Surgery followed by radiation has long been the criterion standard treatment option for advanced stage squamous cell carcinoma (SCCA) of the head and neck. Treatment has consisted of resection of the primary site, radical neck dissection, reconstruction as needed, and postoperative radiotherapy. To minimize the morbidity of radical neck dissection, Bocca (1967) introduced the concept of modified radical neck dissection, preserving the sternocleidomastoid muscle, internal jugular vein, and spinal accessory nerve, when possible.²

However, a modified radical neck dissection is often not possible in the N3 neck. Given the potential morbidity associated with radical surgery, surgeons and oncologists alike began looking for nonsurgical options for treating advanced stage head and neck cancer. Many chemoradiation trials have been conducted, with the Department of Veterans Affairs Laryngeal Cancer Study Group (1991) trial beginning the push for nonsurgical treatment of advanced stage head and neck cancer. To this end, many centers consider organ preservation chemoradiation as the standard treatment for advanced stage head and neck cancer.

Problem

A patient with N3 disease of the neck is automatically categorized as having stage IVb disease, and the average 2-year survival rate, considering all head and neck sites, is approximately 20%.¹ Patients with N3 disease also have a high rate of distant metastasis, up to 30%.³ In addition, both radical surgery and concurrent chemoradiation bring morbidity to the patient. The goal of treatment in most patients with this degree of disease is palliation, but cure may still be possible.

Frequency

N3 neck disease is uncommon. The rate of patients presenting with the N3 neck ranges from 1.7-9.5% in large series.^4,3,1

Etiology

Squamous cell carcinoma (SCC) arising from the aerodigestive tract is the most common cause of cervical metastases. Primary tumors of the major and minor salivary glands can also present with cervical lymphadenopathy. The histopathology of malignant salivary gland tumors that have frequent neck disease include high-grade mucoepidermoid carcinoma, squamous cell carcinoma, carcinoma ex-pleomorphic, and high-grade adenocarcinoma. Thyroid carcinomas also manifest with cervical metastases, most commonly from papillary or medullary thyroid carcinomas. In addition, lymphoma can present with bulky lymphadenopathy.

Pathophysiology

As mentioned previously, N3 neck disease usually results from squamous cell carcinoma arising from the aerodigestive tract. Although the disease usually involves only structures in the neck, depending on the location of the involved node, it may extend into surrounding structures such as the skull base, clavicles, or mediastinum. In addition, patients presenting with N3 neck disease are at high risk for distant metastases. The lungs (83.4%), bone (31.3%), and liver (6%) are the most common site of distant metastasis, although the brain and other sites have been reported in the surgical literature.⁵

Presentation

Aside from evaluation of the primary tumor, patients with an N3 neck disease present in the following clinical scenarios:

• N3 neck disease that has not been treated
• N3 neck disease after chemoradiation or radiation with no response or partial response
• N3 neck disease after chemoradiation with complete response
• N3 neck disease with unknown primary tumor

Indications

The goals of treatment include palliation, improved quality of life, and cure, if possible. If the tumor is histologically proven to be squamous cell carcinoma based on findings of either fine-needle aspiration (FNA) of lymph node or biopsy of the primary tumor, the factors that influence treatment include operability and resectability of the both the primary tumor and the neck, the presence of distant metastases, as well as the presence of synchronous second primary tumors of either the head and neck or the lung. The exception to these considerations is nasopharyngeal carcinoma, which is treated with primary chemoradiation, regardless of the status of the neck. This should be the first step in assessing these patients.

The term operable refers to a reasonable degree of safety and chance of success. The term resectable refers to the ability to completely resect the tumor with adequate or clear surgical margins. Tumors that are inoperable or unresectable may still be treatable or even curable with nonsurgical therapy.

The treatment for the primary tumor dictates the management of neck disease. Therefore, if the primary tumor is treated surgically, then the neck disease will also be treated initially with neck dissection. If chemoradiation is the initial choice of therapy for the primary site, then the neck will also be treated with chemoradiation followed by completion neck dissection. However, if the goal is palliation, multimodality management (surgery, radiation, chemotherapy) is used to alleviate suffering and to minimize morbidity.

Operable primary tumors and N3 neck disease may be managed with surgical resection followed by radiation, with or without chemotherapy, to achieve the best chance of locoregional control.

Based on the head and neck surgeon's realistic and mature surgical judgment, and after the risk, benefits, alternative treatments, and potential complications are weighed, the ultimate decision concerning tumor resectability can sometimes be determined only at the time of surgery. During surgery, the surgeon should bear in mind that the execution of extended neck dissection, in which vital structures have to be sacrificed, has no benefit to the patient if the tumor cannot be completely resected.⁶

The indications for concurrent chemoradiation are as follows:

• Inoperable and unresectable primary tumor and/or nodal disease
• Organ preservation
• Patient refuses surgical treatment

Relevant Anatomy

The cervical lymphatics have been divided into levels based on the patterns of spread of the primary tumor from different sites of the aerodigestive digestive site.⁷ Classification of the neck levels have helped to standardize surgical treatment of the neck as well as serve as a prognostic indicator of outcomes. The neck levels are as follows:

• Level Ia - Submental triangle
• Level Ib - Submandibular triangle
• Level IIa - Jugulodigastric nodes from the skull base to the hyoid bone, anterior to CN IX
• Level IIb - Jugulodigastric nodes from the skull base to the hyoid bone, posterior to CN IX
• Level III - Jugulodigastric nodes from the hyoid bone to the cricoid cartilage
• Level IV - Jugulodigastric nodes from the cricoid cartilage to the clavicle
• Level Va - Posterior triangle nodes superior to the horizontal plane of the cricoid cartilage
• Level Vb - Posterior triangle nodes inferior to the horizontal plane of the cricoid cartilage (supraclavicular nodes)

Classically, the N3 neck, if treated surgically, requires a radical neck dissection. This operation includes removal of neck levels I-V, as well as removal of the internal jugular vein, sternocleidomastoid muscle, and the spinal accessory nerve. Bocca (1967) introduced the concept of the modified radical neck dissection, sparing the jugular vein, sternocleidomastoid muscle, and the spinal accessory nerve. Although a modified neck dissection may be possible in some cases, the classic radical neck dissection will be necessary in most cases of the N3 neck.

The surgeon must also consider involvement of other structures in the N3 neck. Specific nerve palsies indicate involvement of following nerves: the hypoglossal nerve, vagus nerve, phrenic nerve, brachial plexus, or sympathetic trunk. The carotid artery may be encased by tumor, and the paraspinous muscles of the neck may also be involved. Finally, depending on the location of the nodal disease, it may extend to involve the skull base or mediastinum. An extended neck dissection includes the removal of standard nodal levels, plus involved structures that are not typically included in a radical neck dissection.

Contraindications

The following are contraindications to surgical management of N3 neck disease:

• Carotid artery encasement
• Paraspinous muscle invasion
• Vertebral column invasion
• Skull base invasion and/or extension
• Horner syndrome
• Phrenic nerve palsy
• Brachial plexus palsy
• Uncontrolled primary tumor site

Workup

Laboratory Studies

Standard laboratory tests in the work-up of the patient with N3 neck disease include a complete metabolic panel and a complete blood count. Liver function tests, as a part of the metabolic panel, may be used to identify liver metastasis. However, they are nonspecific and are not sensitive. Elevated results of liver function tests may reflect associated alcoholic liver disorders. Electrolyte abnormalities may reflect tumor-induced syndrome of inappropriate antidiuretic hormone (SIADH). Pre-albumin, albumin, and transferrin provide information about the nutritional status of the patient. Patients undergoing surgery should also have coagulation panel, including prothrombin time (PT) and partial thromboplastin time (PTT), as well as a blood type and cross.

Imaging Studies

• Evaluation of N3 neck disease is as follows:  
  • CT scan with contrast is useful in determining resectability and the extent of the primary tumor and nodal disease.
  • MRI with gadolinium can demonstrate soft tissue changes and reveal perineural spread.
  • Positron emission tomography (PET)–CT fusion study may be helpful in patients who present with N3 nodes with an unknown primary tumor. PET-CT scans were able to reveal an unknown primary tumor in 57% of cases compared with CT scan alone, which identified the unknown primary tumor in 23% of cases. Despite the increased ability of PET-CT scanning to reveal unknown primary sites, 43% of the primary sites were not identified.⁸
• Evaluation for lung metastasis is as follows:
  • Patients with N3 neck disease are at increased risk for developing distant metastasis. Garavello et al (2006) found patients with N3 disease developed distant metastases 29.55% of the time and had a 10.7 times increased risk of developing distant metastases.
  • The lung is the most common site of distant metastasis in head and neck cancer, as supported by both clinical and autopsy studies. Chest radiographs had been the standard in the pretreatment evaluation of patient with head and neck cancer; however, its sensitivity is only 50%, while its specificity is 94%.⁹
  • The incidence of pulmonary malignancy in head and neck cancer is 4.5-14%. Secondary lung malignancy is a high risk if the primary tumor originated from the larynx or pharynx.
  • The lifetime risk in developing secondary malignancy in patients with head and neck cancer can be as high as 20%.
  • CT scan is the single most sensitive imaging study used to reveal lung metastasis and, therefore, should be the modality of choice, at least in high-risk patients (stage 4 disease, T4 tumor, N2 or N3 nodal disease, tumors that arise from the oropharynx, larynx, hypopharynx, or supraglottis).¹⁰

Other Tests

• Evaluation for liver metastasis
  • Liver metastasis usually presents in association with other metastases, especially lung metastasis. Liver metastasis alone is rare. Screening tests used to identify liver metastasis are nonspecific and are not sensitive. Elevated results of liver function tests may reflect associated alcoholic liver disorders.
  • Although ultrasonography, CT scanning, and MRI are sensitive imaging modalities for liver metastasis, if the index of suspicion is high, especially in the presence of lung metastasis, a liver ultrasound or CT scan can be performed to confirm clinical suspicion.¹¹
• Evaluation for bone metastasis
  • Bone metastasis is invariably associated with lung metastasis; 50% of cases of bone metastasis involve multiple bony sites. The spine is the most common site of metastasis (12.7%), followed by the skull (4.2%), the rib (3.1%), and axial bone (femur, humerus [2.1%]).⁵
  • Alkaline phosphatase is sensitive for osteoblastic bone metastasis. It is not sensitive for revealing bone metastasis in head and neck squamous cell cancer head because this type of bone metastasis is osteolytic.
  • Bone scan is sensitive in the diagnosis of bone metastasis; however, it is useful only if the patient is clinically symptomatic. Routine bone scan is not necessary.
• Carotid artery evaluation
  • MR studies have shown that, if the carotid artery is surrounded by tumor in 270° or less, no carotid artery invasion has occurred.¹² Yoo et al compared preoperative CT findings with histologic findings in patients who underwent carotid artery resection.¹³ If the carotid artery was encircled more than 180° by the tumor on CT scan, then the tumor invaded the elastic lamina of the carotid artery and patients had poorer outcomes.
  • In patients who have undergone chemotherapy or radiation treatment, surgical planes between the carotid artery and the tumor are obscured. In these cases, CT scanning or MRI are less accurate in predicting carotid artery invasion.¹²
  • Planned carotid artery resection or embolization requires preoperative testing to assure adequate collateral blood flow through the contralateral carotid artery and/or vertebral artery system. In addition, the presence or absence of carotid stenosis must be assessed. The following tests may be indicated in these situations:
    1. Baseline neurologic examination
    2. Functional assessment of cerebral blood flow (CBF) under the following conditions:
       1. At rest
       2. Upon cerebral vasodilatory conditions by inducing hypercapnia, administering acetazolamide, or using hand movements (normal value, increase CBF)
       3. CBF/CBF vasodilatory ratio
       4. PET scanning to measure quantitative CBF and metabolic parameters
    3. Balloon occlusion test
    4. Balloon occlusion test with hypotensive challenge, with or without
       single-photon emission computed tomography (SPECT)
    5. Magnetic resonance angiography (MRA)
    6. Carotid Doppler to reveal carotid stenosis and evaluate for concomitant atherosclerotic plaque
    7. Angiography
    8. Xenon CT scan
    9. Carotid stump back pressure

Discussing the different indications and contraindications, complications, and advantages of each test is beyond the scope of this chapter. Invasive tests used to evaluate collaterals of the carotid artery can cause neurologic complications post-procedure. Several studies have conclusively shown that severe hemodynamic impairment is a strong predictor of stroke in patients who undergo carotid artery occlusion. In the St Louis Carotid Occlusion Study, a prospective study that evaluated cerebral hemodynamic and stroke risk, more than half of the symptomatic and asymptomatic patients had a normal oxygen extraction fraction.¹⁴

Diagnostic Procedures

• Biopsy is necessary to confirm the diagnosis. Fine-needle aspiration biopsy (FNAB) of the neck mass is the only required test for the diagnosis. If readily available, a biopsy procedure can be performed on the primary tumor. The use of core biopsy has also been reported.¹⁵
• The use of an open biopsy procedure is necessary only if the diagnosis cannot be attained with FNAB and a lymphoma is suspected.
• Patients with head and neck carcinoma are at risk for synchronous primary tumors. Panendoscopy, including direct laryngoscopy, bronchoscopy, and esophagoscopy, has classically been performed to assess the both the primary tumor and to identify the presence of synchronous primary tumors. 

Histologic Findings

As mentioned above, squamous cell carcinoma is the most common cause of carcinoma of the aerodigestive tract with cervical metastasis. Histologic diagnosis is based on either FNAB of the neck mass or incisional biopsy of the primary tumor. For patients who undergo surgical treatment of their disease, the histologic features of the primary tumor and neck dissection are important for determining the need for adjuvant therapy.

At the primary site, the surgeon and pathologist alike are interested in the size of the tumor, the presence of positive surgical margins, perineural or lymphovascular invasion, and invasion of surrounding structures. In addition, the pathologist will comment on the grade of differentiation of the tumor, ranging from well differentiated, to moderately differentiated, and poorly differentiated.

However, in squamous cell carcinoma, the grade of the tumor in general does not impact prognosis. On the other hand, the grade of the tumor is important in salivary gland carcinomas. In the neck, features of interest include the size of the tumor, the number and location of involved nodes, and the presence of extracapsular extension of the tumor outside the lymph node.

High-risk features that have long been considered indications for postoperative radiotherapy include advanced T stage, perineural invasion, and multiple positive lymph nodes. Bernier et al (2005), in their meta-analysis studying the benefit of postoperative chemoradiation, found positive surgical margins and extracapsular extension to be the most significant indicators for adjuvant chemoradiation.¹⁶

Staging

The reader is referred to the current AJCC (6^th edition) and UICC guidelines for T staging of the primary tumor at the individual head and neck sites.  

AJCC and UICC nodal categories (except thyroid and nasopharyngeal carcinoma) are as follows:

• Nx - Regional lymph nodes that cannot be assessed
• N0 - No regional node metastasis
• N1 - Metastasis in a single ipsilateral lymph node, 3 cm or smaller
• N2 - Metastasis in a single ipsilateral lymph node, larger than 3 cm but not larger than 6 cm in greatest dimension is found; multiple ipsilateral lymph nodes, none larger than 6 cm; bilateral or contralateral lymph nodes, none larger than 6 cm
• N2a - Metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm
• N2b - Metastasis in multiple ipsilateral lymph nodes, none larger than 6 cm
• N2c - Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm
• N3 - Metastasis in a lymph node larger than 6 cm

• Mx - Distant metastasis cannot be assessed
• M0 - No distant metastasis
• M1 - Distant metastasis

Treatment

Medical Therapy

Local control with chemoradiation therapy has been reported to be as high as 90%. Clinical response, however, does not correlate with pathologic response. Although studies have shown that no clinical or pathologic parameters are able to predict a response to chemoradiation therapy, studies suggest that a tumor volume of less than 20 mL, tumor grade, lower epidermal growth factor receptor (EGFR) overexpression, and response to induction chemotherapy predict response to chemoradiation.

Concurrent chemoradiation therapy has survival rates that are similar to those of surgical therapy and preserves the function of important structures. Surgical therapy, however, carries better locoregional control rates. Although chemoradiation reduces nodal positivity and extracapsular spread, pathologic nodes are still found in 38-56% of cases after chemoradiation, thus necessitating neck dissection for the N2 and the N3 neck.

Complete response to chemoradiation therapy requires a complete disappearance of all clinical, radiologic, and pathologic (if applicable) evidence of disease. Anything less than a complete response requires surgery of the primary site and the neck nodes, if possible.

Treatment of the neck following chemoradiation is controversial. In the presence of a partial or incomplete response in the neck to chemoradiation, a completion neck dissection is mandatory (assuming the primary site is controlled or is resectable). In the presence of a complete response in the neck to chemoradiation, reports vary regarding the need for planned neck dissection. Lau et al (2008) did not plan a neck dissection following chemoradiation for patients with N2-N3 neck disease and achieved a 95% 2-year locoregional recurrence-free survival.¹⁷

On the other hand, Brizel et al (2004) found a higher rate of regional rate of relapse in patients with N2-N3 neck disease following chemoradiation who did not undergo planned neck dissection compared with those patients who did have neck dissection.¹⁸ Results of most studies are difficult to apply to the patient with N3 neck disease because most studies combine N2 and N3 neck disease because of the small number of patients with N3 disease.

The following complications are associated with chemoradiation therapy:

1. Feeding tube (required in 32% of patients)
2. Mucositis
3. Neutropenia
4. Carotid stenosis (range, 30-50% of patients)¹⁹
5. Renal insufficiency
6. Ototoxicity
7. Esophageal stricture

Surgical Therapy

The type of neck dissection chosen is dictated by what structures are involved, as follows:

• Radical neck dissection - Removal of the spinal accessory, sternocleidomastoid muscle (SCM), and internal jugular vein
• Modified neck dissection
  • Type 1: The spinal accessory nerve is preserved and the SCM and the internal jugular vein are resected.
  • Type 2: The spinal accessory nerve and the SCM are preserved and the internal jugular vein is resected.
  • Type 3: The spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle are preserved.
• Extended neck dissection – Resection of structures other than those that are routinely removed in a neck dissection.

Carotid artery resection is controversial. A 13-year retrospective study by Freeman et al (2004) reported on 41 patients whose carotid arteries were resected and reconstructed and 11 patients who underwent preoperative embolization or intraoperative ligation of the carotid artery.²⁰ The median disease-specific survival and the median disease-free interval were both 12 months. Distant metastasis developed in 24% of patients, and 20% of patients had recurrence within 6 months of the resection. Eight of 41 patients (20%) who underwent resection and reconstruction of the carotid artery developed stroke postoperatively. Three of the 11 patients (27.7%) who underwent embolization or ligation of the carotid artery developed stroke postoperatively.

Cancer seldom invades the lumen of the carotid artery; based on a study by Huvos et al, only 42% of patients had invasion of the adventitia and external elastic membrane.²¹

The treatment options in the management of cervical metastasis that involves the carotid artery are as follows:

• Permanent occlusion can be performed if collateral circulation is adequate.
• Resection with carotid shunt and reconstruction can be performed if collateral circulation is inadequate.
• Nonsurgical palliation is an option if collaterals are inadequate and reconstruction is not possible.
• Nussbaum et al (2000) developed a unique technique in the management of carotid involvement in head and neck cancer.²² Endovascular stenting of the carotid artery is initially placed and followed by a staged neck dissection after 1 month of placement. Because the neoendothelial barrier has formed in the stent and prevents bleeding, dissection of the arterial wall with neck dissection can be performed. This is a technical case report that is currently under investigation.

Lore and Boulos reported that one third of their patients who underwent carotid artery resection lived longer than 2 years after the procedure, and meta-analysis on carotid resection by Snyderman showed improved local control.^23,24 The decision to resect the carotid artery depends on the risk-benefit ratio in relation to local control, survival, stroke risk, quality of life, mortality, and available expertise.

The external carotid artery should be resected as needed; however, the authors' view is that resection of the carotid bulb or internal carotid artery is rarely, if ever, indicated. This is because the chance for cure is exceedingly low. The hypoglossal and or vagus nerve can also be invaded aside from the carotid artery. Resection of both the hypoglossal and vagus nerves increases the morbidity and mortality. Stroke is a risk, even when results of balloon occlusion studies are favorable. Even with resection of the carotid, the median survival is only 12 months.

Preoperative Details

Consider the primary site during treatment planning. Generally, primary site management dictates the plan for the neck. Patients who will undergo surgery for the primary site must also have resectable neck disease. As discussed previously, incomplete resection of the neck disease is of no benefit to the patient  (see Contraindications). Careful inspection of preoperative imaging is critical to making this assessment. 

Certain patients may not have an operable primary tumor and would not normally undergo a neck dissection. However, they may have morbidity associated with advanced neck disease and could benefit from a palliative neck dissection. This situation includes patients with the following:

• Nonhealing ulcer
• Bleeding neck mass not attached to vascular structure     
• Unresponsive to conservative wound care
• Unresponsive tumor embolization
• Neck mass is operable, resectable, and adequate margins can be achieve

This highly selected subset of patient may be a candidate for palliative neck dissection. However, one must carefully weigh the risks of creating a worse wound and having the patient hospitalized for his or her remaining life against potential quality-of-life improvements.

Intraoperative Details

Intraoperatively, the surgeon must assess whether the N3 neck is completely resectable. Involvement of structures not normally included in the standard neck dissection must be assessed and resected as needed to achieve a complete resection. However, unless the tumor is completely resectable, resecting important neurovascular structures, causing unnecessary morbidity, is not advisable. (See Relevant Anatomy and Surgical Therapy.) 

Postoperative Details

When possible, patients benefit from adjuvant therapy following neck dissection for advanced neck disease. Chan et al (2003) showed that patients with N3 disease treated with surgery and postoperative radiotherapy had improved survival when compared with surgery and preoperative radiotherapy or surgery alone.²⁵ Patients with advanced neck disease derive additional benefit from postoperative concurrent chemoradiation.¹⁶  

Follow-up

Following treatment for the N3 neck, patients require close follow-up, as they are at high risk for both regional recurrence and distant metastases. The risk of relapse is highest in the first 2 years following treatment. Many surgeons advocate monthly physical examinations, and imaging every 3 months in the first year following treatment. 

Complications

The following are complications associated with surgical resection of the N3 neck:

• Perioperative stroke (range, 0.2-4.8%)
• Wound complications (range, 8-35%)
• Fistula
• Bleeding
• Infection
• Carotid artery rupture
• Chyle leak

Carotid artery rupture is a dreaded complication of advance neck disease. Rupture may be preceded by a sentinel bleed, wherein a patient has a short-lived episode of bleeding from the mouth, neck, or stoma. After bleeding subsides, all may appear to be well, but hospitalized patients may need to be placed on carotid artery precautions unless the patient refuses resuscitation. Precautions include a prepositioned stretcher to quickly take the patient to the operating room (OR) and rolled gauze bandages to obtain adequate pressure to the artery. Make no attempt to clamp the vessel. The following are the appropriate sequence of events in the management of carotid blowout:

(1) Apply pressure and volume support.

(2) Transfer the patient to the OR immediately.

(3) Manage the condition either by endovascular stent graft or by surgically obtaining proximal and distal control followed by surgical repair or ligation, depending on hemodynamic status and condition of the tissue.

Outcome and Prognosis

Outcomes are best when combined modality therapy is used. However, patients with the N3 neck have overall poor outcomes as a result of developing regional recurrence and distant metastases. Assessing the outcomes of the N3 neck is sometimes difficult because these patients frequently are grouped with patients with N2 neck disease.

Several recent studies have specifically addressed the outcomes of patients with N3 neck disease. Carvalho et al (2005) achieved the best regional control of 73% using surgery and postoperative radiotherapy, although overall 3-year survival was still poor at 17.9% in this group of patients.²⁶ Chan et al (2003) also found the best results in the N3 patient by treating with surgery followed by radiation.²⁵ Their 1-year, 3-year, and 5-year neck control rates in this group were 92.3%, 46.1%, and 46.1%, respectively. The overall disease free survival rates in their patients at 1, 3, and 5 years was 44.4%, 25%, and 22.2%, respectively.    

Ballonoff et al (2008) reported their results in patients with N3 neck disease treated with primary chemoradiation, with or without planned neck dissection.²⁷ Their rates of locoregional control and distant control were 88% and 56%, respectively. Actuarial overall survival and disease-free survival at 2 years were 51% and 29%, respectively. 

Future and Controversies

The following methods for local control of recurrent tumor in the neck are currently under investigation:

• Radiofrequency ablation²⁸
• Microwave interstitial hyperthermia (915 MHz)^29,30
• Intratumoral administration of cisplatin and epinephrine³¹
• Interstitial photodynamic therapy^32,33
• Intratumoral administration of ONYX-015 adenovirus and chemotherapy³⁴
• Reirradiation therapy and chemotherapy with amifostine³⁵
• Electroporation with chemotherapy³⁶

The role of PET with (¹⁸ F)-labeled fluorodeoxyglucose (PET-FDG) in predicting the necessity for postradiation or postchemoradiation therapy neck dissection in locally advanced head and neck squamous cell carcinoma that has completely responded to treatment is still being investigated. A large prospective randomized clinical study and longer follow-up is needed to determine whether FDG-PET will change local control, incidence of distance metastasis, and survival.

Selection criteria for planned neck dissection versus observation among patients who have had a complete response to chemoradiation therapy need to be established. Yao et al (2004) correlated residual pathology in postradiation or postchemoradiation neck specimens to the standard uptake value (SUV) in post-treatment FDG PET-CT scans.³⁷ They found that an SUV of less than 3.0 had a negative predictive value of 100% and a positive predictive value of 80% for the residual tumor in the neck specimen.

Other authors have found that FDG PET-CT scanning adds little value over traditional CT scanning in determining who requires a postchemoradiation neck dissection for advanced neck disease.³⁸ The exact role of FDG PET-CT is still unclear and requires further investigation.

Multimedia

Media file 1: Levels of metastasis to cervical lymph nodes.

References

1. Spiro RH, Alfonso AE, Farr HW, Strong EW. Cervical node metastasis from epidermoid carcinoma of the oral cavity and oropharynx. A critical assessment of current staging. Am J Surg. Oct 1974;128(4):562-7. [Medline].

2. Bocca E, Pignataro O. A conservative technique in radical neck dissection. Ann Otol Rhinol Laryngol. 1967;76(5):975-87.

3. Garavello W, Ciardo A, Spreafico R, Gaini RM. Risk factors for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. Jul 2006;132(7):762-6. [Medline].

4. Buck G, Huguenin P, Stoeckli SJ. Efficacy of neck treatment in patients with head and neck squamous cell carcinoma. Head Neck. Jan 2008;30(1):50-7. [Medline].

5. Ferlito A, Shaha AR, Silver CE, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. ORL J Otorhinolaryngol Relat Spec. Jul-Aug 2001;63(4):202-7. [Medline].

6. Ferlito A, Silver CE, Shaha AR, Rinaldo A. Management of N3 neck. Acta Otolaryngol. Mar 2002;122(2):230-3. [Medline].

7. Robbins KT, Clayman G, Levine PA, et al. Neck dissection classification update: revisions proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. Jul 2002;128(7):751-8. [Medline].

8. Freudenberg LS, Fischer M, Antoch G, et al. Dual modality of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract. May-Jun 2005;14(3):155-60. [Medline].

9. Troell RJ, Terris DJ. Detection of metastases from head and neck cancers. Laryngoscope. Mar 1995;105(3 Pt 1):247-50. [Medline].

10. Loh KS, Brown DH, Baker JT, Gilbert RW, Gullane PJ, Irish JC. A rational approach to pulmonary screening in newly diagnosed head and neck cancer. Head Neck. Nov 2005;27(11):990-4. [Medline].

11. Keski-Santti HT, Markkola AT, Makitie AA, Back LJ, Atula TS. CT of the chest and abdomen in patients with newly diagnosed head and neck squamous cell carcinoma. Head Neck. Oct 2005;27(10):909-15. [Medline].

12. Yousem DM, Hatabu H, Hurst RW, et al. Carotid artery invasion by head and neck masses: prediction with MR imaging. Radiology. Jun 1995;195(3):715-20. [Medline].

13. Yoo GH, Hocwald E, Korkmaz H, et al. Assessment of carotid artery invasion in patients with head and neck cancer. Laryngoscope. Mar 2000;110(3 Pt 1):386-90. [Medline].

14. Grubb RL Jr, Powers WJ, Derdeyn CP, Adams HP Jr, Clarke WR. The Carotid Occlusion Surgery Study. Neurosurg Focus. Mar 15 2003;14(3):e9. [Medline].

15. Howlett DC, Menezes L, Bell DJ, et al. Ultrasound-guided core biopsy for the diagnosis of lumps in the neck: results in 82 patients. Br J Oral Maxillofac Surg. Feb 2006;44(1):34-7. [Medline].

16. Bernier J, Bentzen SM. Radiotherapy for head and neck cancer: latest developments and future perspectives. Curr Opin Oncol. May 2006;18(3):240-6. [Medline].

17. Lau H, Phan T, Mackinnon J, Matthews TW. Absence of planned neck dissection for the N2-N3 neck after chemoradiation for locally advanced squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. Mar 2008;134(3):257-61. [Medline].

18. Brizel DM, Prosnitz RG, Hunter S, et al. Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. Apr 1 2004;58(5):1418-23. [Medline].

19. Abayomi OK. Neck irradiation, carotid injury and its consequences. Oral Oncol. Oct 2004;40(9):872-8. [Medline].

20. Freeman SB, Hamaker RC, Borrowdale RB, Huntley TC. Management of neck metastasis with carotid artery involvement. Laryngoscope. Jan 2004;114(1):20-4. [Medline].

21. Huvos AG, Leaming RH, Moore OS. Clinicopathologic study of the resected carotid artery. Analysis of sixty-four cases. Am J Surg. Oct 1973;126(4):570-4. [Medline].

22. Nussbaum ES, Levine SC, Hamlar D, Madison MT. Carotid stenting and "extarterectomy" in the management of head and neck cancer involving the internal carotid artery: technical case report. Neurosurgery. Oct 2000;47(4):981-4. [Medline].

23. Lore JM Jr, Boulos EJ. Resection and reconstruction of the carotid artery in metastatic squamous cell carcinoma. Am J Surg. Oct 1981;142(4):437-42. [Medline].

24. Snyderman CH, D'Amico F. Outcome of carotid artery resection for neoplastic disease: a meta-analysis. Am J Otolaryngol. Nov-Dec 1992;13(6):373-80. [Medline].

25. Chen KY, Mohr RM, Silverman CL. Interstitial iodine 125 in advanced recurrent squamous cell carcinoma of the head and neck with follow-up evaluation of carotid artery by ultrasound. Ann Otol Rhinol Laryngol. Dec 1996;105(12):955-61. [Medline].

26. Carvalho AL, Kowalski LP, Agra IM, Pontes E, Campos OD, Pellizzon AC. Treatment results on advanced neck metastasis (N3) from head and neck squamous carcinoma. Otolaryngol Head Neck Surg. Jun 2005;132(6):862-8. [Medline].

27. Ballonoff A, Raben D, Rusthoven KE, et al. Outcomes of patients with n3 neck nodes treated with chemoradiation. Laryngoscope. Jun 2008;118(6):995-8. [Medline].

28. Owen RP, Silver CE, Ravikumar TS, Brook A, Bello J, Breining D. Techniques for radiofrequency ablation of head and neck tumors. Arch Otolaryngol Head Neck Surg. Jan 2004;130(1):52-6. [Medline].

29. Serin M, Erkal HS, Cakmak A. Radiation therapy, cisplatin and hyperthermia in combination in management of patients with recurrent carcinomas of the head and neck with metastatic cervical lymph nodes. Int J Hyperthermia. Sep-Oct 1999;15(5):371-81. [Medline].

30. Wust P, Stahl H, Dieckmann K, et al. Local hyperthermia of N2/N3 cervical lymph node metastases: correlationof technical/thermal parameters and response. Int J Radiat Oncol Biol Phys. Feb 1 1996;34(3):635-46. [Medline].

31. Castro DJ, Sridhar KS, Garewal HS, et al. Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America. Head Neck. Sep 2003;25(9):717-31. [Medline].

32. Jäger HR, Taylor MN, Theodossy T, Hopper C. MR imaging-guided interstitial photodynamic laser therapy for advanced head and neck tumors. AJNR Am J Neuroradiol. May 2005;26(5):1193-200. [Medline].

33. Lou PJ, Jager HR, Jones L, Theodossy T, Bown SG, Hopper C. Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer. Br J Cancer. Aug 2 2004;91(3):441-6. [Medline].

34. Lamont JP, Nemunaitis J, Kuhn JA et al. Intratumoral ONYX-O15 adenovirus and chemotherapy for recurrent squamous cell carcinoma of head and neck. Ann surg oncol. 2000, Sept;7(8):588-92.

35. Machtay M, Rosenthal DI, Chalian AA, et al. Pilot study of postoperative reirradiation, chemotherapy, and amifostine after surgical salvage for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys. May 1 2004;59(1):72-7. [Medline].

36. Allegretti JP, Panje WR. Electroporation therapy for head and neck cancer including carotid artery involvement. Laryngoscope. Jan 2001;111(1):52-6. [Medline].

37. Yao M, Graham MM, Hoffman HT, et al. The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. Jul 15 2004;59(4):1001-10. [Medline].

38. Tan A, Adelstein DJ, Rybicki LA, et al. Ability of positron emission tomography to detect residual neck node disease in patients with head and neck squamous cell carcinoma after definitive chemoradiotherapy. Arch Otolaryngol Head Neck Surg. May 2007;133(5):435-40. [Medline].

39. Adelstein DJ, Lavertu P, Saxton JP, et al. Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer. Feb 15 2000;88(4):876-83. [Medline].

40. AJCC Staging Manual. 6.

41. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. Oct 2005;27(10):843-50. [Medline].

42. Brisman MH, Sen C, Catalano P. Results of surgery for head and neck tumors that involve the carotid artery at the skull base. J Neurosurg. May 1997;86(5):787-92. [Medline].

43. Chan SW, Mukesh BN, Sizeland A. Treatment outcome of N3 nodal head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. Jul 2003;129(1):55-60. [Medline].

44. Conley BA. Treatment of advance head and neck cancer: what lessons have we learned? J of Clin Oncology. 2006, March;24(7):1023-1024.

45. Dagum P, Pinto HA, Newman JP, et al. Management of the clinically positive neck in organ preservation for advanced head and neck cancer. Am J Surg. Nov 1998;176(5):448-52. [Medline].

46. Dare AO, Gibbons KJ, Gillihan MD, Guterman LR, Loree TR, Hicks WL Jr. Hypotensive endovascular test occlusion of the carotid artery in head and neck cancer. Neurosurg Focus. Mar 15 2003;14(3):e5. [Medline].

47. Derdeyn CP, Grubb RL Jr, Powers WJ. Indications for cerebral revascularization for patients with atherosclerotic carotid occlusion. Skull Base. Feb 2005;15(1):7-14. [Medline].

48. Doweck I, Denys D, Robbins KT. Tumor volume predicts outcome for advanced head and neck cancer treated with targeted chemoradiotherapy. Laryngoscope. Oct 2002;112(10):1742-9. [Medline].

49. Ferlito A, Buckley JG, Rinaldo A, Mondin V. Screening tests to evaluate distant metastases in head and neck cancer. ORL J Otorhinolaryngol Relat Spec. Jul-Aug 2001;63(4):208-11. [Medline].

50. Gavilan J, Herranz-Gonzalez J, Lentsch EJ. Cancer of the neck. In: Cancer of the head and neck. 4th edition: Saunder Co; 2003:407-430.

51. Giatromanolaki A, Koukourakis MI, Georgoulias V, Gatter KC, Harris AL, Fountzilas G. Angiogenesis vs. response after combined chemoradiotherapy of squamous cell head and neck cancer. Int J Cancer. Mar 15 1999;80(6):810-7. [Medline].

52. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med. Jun 13 1991;324(24):1685-90. [Medline].

53. Lesley WS, Chaloupka JC, Weigele JB, Mangla S, Dogar MA. Preliminary experience with endovascular reconstruction for the management of carotid blowout syndrome. AJNR Am J Neuroradiol. May 2003;24(5):975-81. [Medline].

54. McHam SA, Adelstein DJ, Rybicki LA, et al. Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?. Head Neck. Oct 2003;25(10):791-8. [Medline].

55. Moore MG, Bhattacharyya N. Effectiveness of chemotherapy and radiotherapy in sterilizing cervical nodal disease in squamous cell carcinoma of the head and neck. Laryngoscope. Apr 2005;115(4):570-3. [Medline].

56. Morrissey DD, Andersen PE, Nesbit GM, Barnwell SL, Everts EC, Cohen JI. Endovascular management of hemorrhage in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. Jan 1997;123(1):15-9. [Medline].

57. Okamoto Y, Inugami A, Matsuzaki Z, et al. Carotid artery resection for head and neck cancer. Surgery. Jul 1996;120(1):54-9. [Medline].

58. Pellitteri PK, Ferlito A, Rinaldo A, et al. Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?. Head Neck. Feb 2006;28(2):166-75. [Medline].

59. Pitman KT, Bradley PJ. Management of the N3 neck. Curr Opin Otolaryngol Head Neck Surg. Apr 2003;11(2):129-33. [Medline].

60. Shah J. Cervical lymph nodes. In: Head and Neck Surgical Oncology. Mosby Co. 2003;353-393.

61. Stell PM. Fixed, bilateral cervical nodes. J Laryngol Otol. Sep 1983;97(9):851-6. [Medline].

62. Thompson SK, McKinnon JG, Ghali WA. Perioperative stroke occurring in patients who undergo neck dissection for head and neck cancer: unanswered questions. Can J Surg. Oct 2003;46(5):332-4. [Medline].

63. Thompson SK, Southern DA, McKinnon JG, Dort JC, Ghali WA. Incidence of perioperative stroke after neck dissection for head and neck cancer: a regional outcome analysis. Ann Surg. Mar 2004;239(3):428-31. [Medline].

Keywords

neck disease, advanced neck disease, lymph nodes neck, n3 neck, neck cancer, squamous cell carcinoma, neck treatment, head neck cancer, cancer treatment, cancer management, SCCA, inoperable cancer of the neck, N3 disease of the neck, stage IV disease, tonsil cancer, cancer of the tonsil

Contributor Information and Disclosures

Author

Niels Kokot, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine of the University of Southern California
Niels Kokot, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Gregory S Weinstein, MD, FACS, Professor and Vice-Chairman, Department of Otorhinolaryngology-Head and Neck Surgery, Director of Division of Head and Neck Surgery, Director of Head and Oncology Fellowship, Director of Otorhinolaryngology-Head and Neck Clinic, Co-director of The Center for Head and Neck Surgery, University of Pennsylvania School of Medicine
Gregory S Weinstein, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Laryngological Association, American Laryngological Rhinological and Otological Society, American Medical Association, American Radium Society, American Society for Head and Neck Surgery, Pennsylvania Medical Society, Philadelphia County Medical Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Nothing to disclose.

Medical Editor

William M Lydiatt, MD, Professor and Division Director, Head and Neck Surgical Oncology, Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center
William M Lydiatt, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, and Nebraska Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Karen Hall Calhoun, MD, Professor, Department of Otolaryngology-Head and Neck Surgery, The Ohio State University
Karen Hall Calhoun, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Medical Association, American Rhinologic Society, Association for Research in Otolaryngology, Society of University Otolaryngologists-Head and Neck Surgeons, Southern Medical Association, Texas Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
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