Neurogenic Tumors of the Mediastinum Treatment & Management

Treatment selection for a given mediastinal tumor or cyst depends on the diagnosis of the lesion being investigated. ^[22]  Surgical resection is the primary treatment of choice in a large percentage of cases of neurogenic tumors.

Surgical resection is the treatment of choice for tumors originating from nerve sheath tissue, including neurilemmoma, neurofibroma, and neurogenic sarcoma. Complete resection of the more malignant forms of these tumors may not be possible, and additional treatment modalities may be required.

Primary resection is the treatment of choice for neurogenic tumors of paraganglionic origin, which include paraganglionoma, chemodectoma, and mediastinal pheochromocytoma. Approximately 10% of pheochromocytomas are malignant and may not be entirely resectable. Some, even though benign, may be incompletely resected because of their location and increased vascularity. Preoperative treatment including alpha and beta blockade to prevent malignant hypertension during dissection is critical to excision of these tumors.

Peripheral neuroectodermal tumors (PNETs), otherwise known as Askin tumors, are rare tumors occurring in the posterior sulcus or chest wall of adolescent and young adult patients. They are believed to develop from intercostal nerve tissue. Standard therapy includes en-bloc resection, with accompanying radiation therapy (RT) and chemotherapy if complete resection is not possible.

Treatment varies for neurogenic tumors originating from autonomic nervous tissues. Ganglioneuroma, the most mature and benign form of autonomic nerve tumor, is treated with surgical resection. Neuroblastoma and ganglioneuroblastoma identified at an early stage of disease also may be treated with primary resection. Advanced stages of these diseases are treated primarily with chemotherapy, and surgical resection is rarely indicated.

Surgical removal is not indicated as primary treatment for some specific mediastinal tumors and cysts. Advanced stages of neuroblastoma and ganglioneuroblastoma are the tumors of neurogenic origin for which surgical resection is not considered as primary treatment.

Whereas most tumors and cysts of the mediastinum are treated surgically, medical therapy is the primary form of treatment in several diseases.

Benign schwannomas and neurofibromas

Treatment for these lesions is surgical resection. ^[23] This includes the plexiform varieties and melanotic schwannoma.

Granular cell tumors

Treatment for this rare lesion is surgical in nature.

Malignant schwannoma and neurofibrosarcoma

Surgical resection is the primary mode of therapy. Radiation therapy may be used postoperatively to control residual disease, but the benefit of this is unknown. No known chemotherapeutic regimens are effective against these tumors.

Ganglioneuroma

Treatment is surgical in nature.

Neuroblastoma

Treatment of mediastinal neuroblastoma is based on the evaluation of a number of risk factors that are used to assign a stage to the disease according the International Neuroblastoma Staging System (INSS; see Staging). This is identical to the staging system used for neuroblastoma occurring elsewhere in the body.

Patients at INSS stages 1 and 2 are considered candidates for resection. For patients with more advanced disease (INSS stage 3, 4, or 4S), a combination of surgery and chemotherapy is recommended. High-risk patients rarely benefit from surgery. Intense chemotherapy with whole-body irradiation or myeloablative chemotherapy is administered, followed by autologous bone marrow transplant.

Neuroblastoma occurs much less frequently in adults than in children and infants but is a much more aggressive disease. Stage 1 disease is treated surgically, while irradiation is recommended for stage 2 disease. Chemotherapy has been tried for disseminated disease in adults, although no proven benefit has been observed.

Ganglioneuroblastoma

These tumors are also graded using the INSS. Surgical resection is indicated in those with early disease, and chemotherapeutic therapy is added for those with more advanced disease.

Melanotic progonoma

Surgical resection is the only recommended treatment.

Askin tumor

Surgical resection followed by RT and chemotherapy is recommended in all cases. Some studies have used myeloablative chemotherapy or whole-body irradiation followed by autologous bone marrow transplant, but to date, benefits of this aggressive therapy have not been identified.

Chemodectomas are primarily treated with surgical resection. Preoperative embolization may be indicated because of the excessive vascularity of these tumors. RT has also been used and is an acceptable alternative to surgical resection.

In cases of benign neoplasms, complete excision of the lesion itself is generally sufficient. ^[24] Benign neurofibroma requires some resection in addition to the lesion itself, that being resection of the associated nerve. All benign neoplasms that are encapsulated should be resected without violation of the capsule. Resection via video-assisted thoracoscopic surgery (VATS) is now commonplace for these benign tumors. Shorter hospital stay and more rapid return to work have been demonstrated with this method.

Robotic approaches have been described as well. ^[25]  A study (N = 20; median age, 41.2 y) by Asaf et al described the use of of the da Vinci robotic system to excise neurogenic tumors of the posterior mediastinum. ^[5]  Average operating time was 110 minutes; average blood loss was 30 mL; and average postoperative hospital stay was 2.4 days. Two patients experienced complications. At a median follow-up of 36 months (range, 6-48), all patients except one were free of recurrence.

When surgical resection of malignant neoplasms of the mediastinum is the primary treatment, en-bloc resection of the tumor should be performed whenever possible. Regional lymphadenectomy should accompany surgical resection of operable neuroblastomas.

Preparation for surgery

Standard preoperative management applicable to all chest surgical cases applies to the preoperative management of individuals undergoing resection of mediastinal tumors.

Airway management is of paramount importance in dealing with tumors that can produce a mass effect on these structures. For safe management of the airway distorted or narrowed by a mediastinal mass, it is important to consider detailed preoperative assessment of the airway and ensure adequate visualization and readily available supplementary equipment (eg, flexible bronchoscope). Placement of a double-lumen endotracheal tube to provide single-lung ventilation is usually preferred for any procedure in which a thoracotomy approach is used.

Some mediastinal tumors may necessitate extensive resection of adjacent tissues, and blood loss may be substantial in these cases. Adequate intravenous (IV) access, appropriate monitoring capability, and easy availability of necessary blood products (all of paramount importance) should be provided before surgery is begun.

Involvement of associated intrathoracic structures by tumor may mandate their resection. Pulmonary resection, excision of nervous structures (eg, phrenic, vagus, sympathetic chain), or even resection of major vascular structures (eg, superior vena cava [SVC]) may be required. Importantly, the surgeon must be prepared for this and the patient must be informed preoperatively that such resection may be required because this may have an additional impact on recovery and perioperative risk.

Several mediastinal tumors can produce important effects that should be taken into account preoperatively. Neurogenic tumors that secrete catecholamines require special consideration.

Pheochromocytoma

Preoperative treatment should be performed on individuals with pheochromocytoma in order to prevent a catecholamine surge and an intraoperative hypertensive crisis.

Most authors recommend the administration of the alpha blocker phenoxybenzamine. This medication is initiated approximately 2 weeks preoperatively, beginning at doses of 10 mg twice a day and increasing the dose every other day until a normotensive or near-normotensive state, with minimization or elimination of paroxysmal episodes, is achieved. Most patients require 40-120 mg/day to achieve this effect. Because of the prolonged half-life of this agent, reduction of the dose 24-48 hours before surgery is recommended; otherwise, postoperative hypotension may occur after the source of excess catecholamine production is removed.

Other drugs that may be used instead are prazosin (a selective alpha blocker) or labetalol (an alpha and beta blocker). Alpha-methylparatyrosine has been used successfully in a few patients who cannot tolerate alpha blockade with other agents.

Preoperative beta blockade can also be performed but is indicated only if persistent tachycardia or supraventricular arrhythmias are present. Beta blockade should be started only after alpha blockade is stabilized to prevent unopposed beta blockade.

Atropine should not be given with preoperative medication. Anesthetic induction with good oxygenation should be rapid and unimpaired. Most commonly, thiopentone is used for induction; however, fentanyl and alfentanil can also be used because they do not result in histamine release, as do other agents. The choice of muscle relaxant is important because some (eg, tubocurarine, atracurium) can cause histamine release and others (eg, pancuronium) can release catecholamine stores. Vecuronium is the drug of choice because it produces none of these effects.

Pheochromocytomas are highly vascular tumors. Adequate availability of blood products is a key feature in the treatment of these patients.

Operative details

As with all thoracic surgery, the patient must be properly positioned for the indicated procedure. Tumors or cysts located in the anterior mediastinum are generally approached through a median sternotomy. This approach is used for tumors of the thymus. Those located in the posterior or middle mediastinum and paravertebral sulci, such as most neurogenic tumors and foregut cysts, are approached through a VATS incision or a posterolateral thoracotomy. ^{[26, 27]}

Standard single-lumen endotracheal intubation is appropriate for resections performed via a median sternotomy. Use of a double-lumen endotracheal tube for single-lung ventilation is preferable for those procedures performed through a thoracotomy and for all procedures performed via VATS.

Specific management of neurogenic tumors with intraspinal extension should be mentioned. Evaluation of all patients with tumors of the posterior mediastinum preoperatively is essential to rule out intraspinal extension. Combined management by neurosurgical and thoracic surgical teams is warranted when intraspinal extension is suggested.

If intraspinal extension is first identified at the time of thoracotomy and was not considered beforehand, the outcome could prove disastrous. The approach to these tumors usually requires laminectomy for resection of the intraspinal portion of the tumor and thoracotomy for the intrathoracic portion. In cases where laminectomy must be performed at multiple levels, some form of stabilization of the vertebral column is undertaken. Laminectomy combined with VATS and thoracoscopy has also been reported for neurogenic tumors involving the spinal column.

A consideration for the resection of pheochromocytomas is that manipulation of a pheochromocytoma during surgical resection may result in a sudden introduction of catecholamines into the circulation. This can occur even in the presence of preoperative preparation with alpha and beta blockers. Early in the dissection, care must be taken during surgery to manipulate these tumors as little as possible and to control venous outflow.

Care of patients after resection or biopsy of mediastinal tumors is similar to that of patients who have undergone any other noncardiac surgery of the chest.

Extubation can be performed at the completion of the case or shortly thereafter in the postanesthesia recovery area. Some patients require ventilatory support for a longer time and should be managed accordingly.

Pulmonary toilet is an essential part of postoperative management after any kind of chest surgery to prevent atelectasis and to mobilize and clear any bronchial secretions. Various methods to assist with pulmonary toilet are available.

Pain control is a critical factor in postoperative management after thoracic surgery. Adequate cough effort and ventilatory excursion cannot be maintained without satisfactory pain control. The administration of analgesic agents via a thoracic epidural catheter is an excellent and highly effective method of pain management. Lumbar or thoracic epidural catheters can also be used and, with proper choice of analgesic agents, can provide good pain relief.

Patient-controlled analgesia (PCA) is another widely used method and is preferred to traditional intramuscular or IV administration of narcotics and other agents. PCA is not as efficient for pain control as epidural analgesia.

Continuous infusion of 0.25% bupivacaine at 4 mL/hr through the ON-Q elastomeric infusion pump is a safe and effective adjunct to pain management after thoracotomy. ^[28] The use of the ON-Q Pain Relief System results in decreased narcotic use and lower pain scores compared with continuous epidural infusion. At some point after oral intake has begun, pain medication can be converted to oral analgesic agents.

Wound management is straightforward. Operative dressings are removed after 24 hours in most cases. Thoracic surgical incisions heal well and have an extremely low rate of dehiscence and infection.

Chest tubes are managed in the same way as those used in other forms of thoracic surgery. Most cases of mediastinal tumor or cyst resection or biopsy do not involve pulmonary or esophageal resection. Chest tubes are maintained on –20 cm of water-seal suction, and drainage from the tubes is measured daily. Intermittent chest radiographs are obtained and evaluated for findings of residual undrained collections, complete pulmonary expansion, lobar atelectasis and infiltrates, and other abnormalities.

When drainage from the chest tubes is less than 400 mL in 24 hours, no air leak is present, and the chest radiograph shows full pulmonary expansion with no collections on the operated side, the chest tubes may be removed.

Complications that occur after resection of mediastinal tumors are similar to those that can occur after any thoracic surgical procedure.

As with any thoracic surgical procedure, postoperative pulmonary complications are most common. Atelectasis is a common postoperative complication and can develop into pneumonia if not treated aggressively. Aggressive pulmonary toilet and pain management are the key factors in the prevention of these complications.

Wound infections after sternotomy or thoracotomy are rare. The chest wall has an excellent blood supply and, with few exceptions, healing occurs readily. In addition, existing intrathoracic infection is generally not a factor during resection of any of the noted mediastinal tumors, and these operations are considered clean procedures. The exception to this may be in cases of resection of some foregut cysts that may have secondary infection present.

Appropriate preoperative, intraoperative, and postoperative antibiotic coverage is warranted. Sternal dehiscence occurs very rarely after sternotomy performed for noncardiac procedures. If it occurs without the presence of infection, simple washout, debridement, and rewiring can be performed. If infection is present, aggressive debridement of devascularized bone and cartilage should be performed along with a vigorous washout. Cases where significant infection is present are best treated with rotation of muscle flaps (eg, pectoralis major and rectus abdominis) to cover the wound.

Injury to the phrenic nerve can occur, resulting in temporary or permanent diaphragmatic paresis. This can cause the patient to have symptomatic dyspnea and atelectasis on the affected side.

Individuals with marginal pulmonary status from underlying pulmonary disease or those with neuromuscular abnormalities causing weakness of the muscles of respiration can experience significant respiratory difficulties from this complication.

Injury to a vagus nerve can also occur during surgery of the mediastinum. Usually, only one vagus nerve is injured, and the remaining intact nerve maintains parasympathetic input to the gut without symptoms. If both vagus nerves are injured, difficulties with gastric emptying may occur because the innervation to the pylorus is disrupted.

Patients who undergo resection of benign neoplasms or mediastinal cysts can be followed for a short time (3-6 mo) postoperatively while wound healing and progression of patient activity is being monitored.

Because of the heterogeneity and small numbers of malignant tumors found in the mediastinum, no single specific method has been described for the follow-up of patients who undergo intended curative resection of a malignant neoplasm. Optimal follow-up treatment for patients with thoracic malignancy has not been demonstrated in randomized controlled trials. ^[29]  Computed tomography (CT) of the chest has been suggested as a surveillance tool for children with high-risk neuroblastoma. ^[30]