权威参考医学：Lung, Chest Wall, Pleura, and Mediastinum

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CHAPTER 58

The term thorax refers to the area between the neck and abdomen enclosed by the ribs, sternum and vertebrae radially, the thoracic inlet superiorly, and the diaphragm inferiorly. The chest or thorax supports and protects the internal thoracic organs, pro-vides for the negative inspiratory force that initiates ventilation and the positive expiratory force needed for vocalization, and creates a frame for the neck, upper extremities, thoracic struc-tures, and abdomen. The major thoracic structures include the heart and lungs, chest wall, including the overlying musculature, ribs, sternum, vertebrae, diaphragm, trachea, and great vessels.ANATOMY

The thoracic organs are protected by the bony thorax and overly-ing chest musculature. The parietal pleura, the internal lining of the chest wall, is separated from the visceral pleura, the outer lining of the lung, by a small amount of pleural fluid. The pari-etal pleura covers the chest wall, mediastinum, diaphragm, and pericardium. The visceral pleura covers the lung and separates the lobes from one another. The pleural space is a potential space that may compress the lungs or heart with fluid, tumor, or infec-tion. The right and left pleural spaces are separated from one another by the mediastinum.

The bony thorax is covered by three groups of muscles—the primary and secondary muscles for respiration and those attaching the upper extremity to the body (Fig. 58-1). The primary muscles include the diaphragm and intercostal muscles. The intercostal muscles of the intercostal spaces include the external, internal, and transverse or innermost muscles. Eleven intercostal spaces, each associated numerically with the rib supe-rior to it, contain the intercostal bundles (vein, artery, and nerve) that travel along the lower edge of each rib. All intercostal spaces are wider anteriorly and each intercostal bundle falls away from the rib posteriorly to become more centrally located within each space. The intercostal muscle layers assist with respiration and protect the thoracic structures. The extrinsic muscles of the chest, latissimus dorsi muscle, serratus anterior muscle, pectora-lis major and minor muscles, and cervical muscles (sternocleido-mastoid, scalene muscles) attach to the bony thorax, protect the chest wall itself, and may assist with ventilatory efforts in those with chronic obstructive pulmonary disease (COPD).

The secondary muscles consist of the sternocleidomastoid, serratus posterior, and levatores costarum. The third muscle group attaches the upper extremity to the body. The pectoralis major and minor muscles lie anteriorly and superficially. Poste-rior superficial musculature includes the trapezius and latissimus dorsi. Deep muscles include the serratus anterior and posterior, levatores, and major and minor rhomboids. These superficial and deep muscles help hold the scapulae to the chest wall. In respiratory distress, the deltoid, pectoralis, and latissimus dorsi muscles form a tertiary system for ventilatory assistance through fixation of the upper extremities.

The bony thorax consists of 12 ribs peripherally extending from the vertebrae posteromedially, to the sternum or costal arch anteriorly (Fig. 58-2). The 11th and 12th ribs are floating ribs and are not attached directly to the sternum. Ribs 1 to 5 are directly attached to the sternum by costal cartilages. The lower ribs (6 to 10) coalesce into the costal arch. The first rib is rela-tively flat, dense, and travels from the first thoracic vertebra to the manubrium to create the thoracic inlet (Fig. 58-3). Through this relatively small area pass the great vessels, trachea, esopha-gus, and innervation to the upper extremity, diaphragm, and larynx. T rauma to this area, manifested by a first rib fracture, is the consequence of a significant mechanical force with likeli-hood of injury to one or more of these structures. Other struc-tures within the thoracic inlet include the phrenic nerve, recurrent laryngeal nerve in the tracheoesophageal groove, which recurs around the aorta at the ligamentum arteriosum on the left and around the innominate artery on the right, and insertion of the thoracic duct posteriorly at the junction of the left sub-clavian with the left internal jugular veins. The remaining ribs gradually slope downward. Each rib is composed of a head, neck, and shaft. Each head has an upper facet, which articulates with

the vertebral body above it, and a lower facet, which articulates

PLEURA, AND MEDIASTINUM

Joe B. Putnam, Jr.

Lung, Chest WaLL, PLeura, and MediastinuM Chapter?58?1565

1988.)

FIGURE 58-2 the relationships of the lobes of the lung to the ribs and the pleural reflections with respiration. the topographic anatomy and the relationship of the fissures of the lobes to specific ribs in inspiration and expiration are important in evaluation of the routine postero-anterior and lateral chest film.

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increase after that time. There are 23 generations of bronchi between the trachea and terminal alveoli. In the lung, 80% of its volume is air, 10% is blood, and approximately 10% is solid tissue. Alveoli make up approximately 50% of the entire lung volume.

The lungs are broadly divided into five lobes, with multiple segments in each lobe (Fig. 58-4). The right lung is composed of three lobes, the upper, middle, and lower. T wo fissures sepa-rate these lobes. The major, or oblique, fissure separates the lower lobe from the upper and middle lobes. The minor or horizontal fissure separates the upper lobe from the middle lobe. The left lung has two lobes—the upper lobe and lower lobe. The lingula corresponds embryologically to the right middle lobe. A single oblique fissure separates the lobes.

The bronchopulmonary segments are divisions of each lobe that contain anatomically separate arterial, venous, and bron-chial supplies. There are 10 bronchopulmonary segments on the right and eight bronchopulmonary segments on the left.

The blood supply of the lung is twofold. Unoxygenated blood circulates from the right ventricle through the pulmonary artery to each lung. After oxygenation in the lung, the blood is returned to the left atrium through the pulmonary veins. Blood supply to the bronchi is from the systemic circulation via bron-chial arteries arising from the superior thoracic aorta or the aortic arch, either as discrete branches or in combination with the intercostal arteries.

Lymphatic vessels are present throughout the lung paren-chyma and pleura and gradually coalesce toward the hilar areas of the lungs. Generally, lymphatic drainage from the lung affects the ipsilateral lymph nodes; however, flow of lymph from the left lower lobe may drain to the right mediastinal (paratracheal) lymph nodes. Lymphatic drainage within the mediastinum moves cephalad. The pulmonary parenchyma does not contain a nerve supply.

The visceral pleura is separated from the parietal pleura by a small amount of pleural fluid that allows almost frictionless movement during respiration. The blood supply of the parietal pleura comes from the systemic arteries and veins, including the posterior intercostal, internal mammary, anterior mediastinal, and superior phrenic arteries, and corresponding systemic veins. The blood supply of the visceral pleura is systemic and pulmo-nary. The lymphatic drainage of the parietal pleura is into

with the corresponding thoracic vertebra to that rib, establishing the costovertebral joint. The neck of the rib has a tubercle with an articular facet; this articulates with the transverse process, creating the costotransverse joint and imparting strength to the posterior rib cage.

The sternum is flat, 15 to 20 cm in length, approximately 1.0 to 1.5 cm in thickness, and comprised of the manubrium, body, and xiphoid. The manubrium articulates with each clavicle and the first rib. The manubrium joins the body of the sternum at the angle of Louis, which corresponds to the anterior aspect of the junction of the second rib. The angle of Louis is a super-ficial anatomic landmark for the level of the carina. The anterior cartilaginous attachments of the true ribs to the sternum, along with intercostal muscles and the hemidiaphragms, allow for movement of the ribs with respiration.

The trachea in adults is approximately 12 cm in length, with 18 to 22 cartilaginous rings. The internal diameter is 2.3 cm laterally and 1.8 cm anteroposteriorly. The larynx ends with the inferior edge of cricoid cartilage. The cricoid is the only complete cartilaginous ring in the trachea. The trachea begins approximately 1.5 cm below the vocal cords and is not rigidly fixed to surrounding tissues. Vertical movement is easily possi-ble. The most rigid point of fixation is where the aortic arch forms a sling over the left mainstem bronchus. The innominate artery crosses over the anterior trachea in a left inferolateral to high right anterolateral direction. The azygos vein arches over the proximal right mainstem bronchus as it travels from poste-rior to anterior to empty into the superior vena cava. The esoph-agus is closely applied to the membranous trachea and lies to the left of the midline of the trachea. The recurrent laryngeal nerves run in the tracheoesophageal groove on both the right and left. The blood supply to the trachea is lateral and segmental from the inferior thyroid, internal thoracic, supreme intercostal, and bronchial arteries. Circumferential dissection more than 1 to 2 cm during tracheal reconstruction may lead to vascular insufficiency, with necrosis or anastomotic dehiscence.

Lung development begins at approximately 21 to 28 days’ gestation. The true alveolar stage, with air sacs surrounded on all sides by capillaries, occurs from approximately 7 months to term. Alveolar proliferation continues after birth. There are approximately 20 million alveoli at birth, which increase to approximately 300 million by age 10 years, with no more FIGURE 58-3 relationship of the neurovascular bundle to the scalenus muscles, clavicle, and first rib. (From urschel hC: thoracic outlet syndromes. in Baue ae, geha as, hammond gL, et al [eds]: glenn’s thoracic and Cardiovascular surgery, ed 6, stamford, Ct, appleton & Lange, 1996, p 567

.)

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the aortic arch. The recurrent laryngeal nerve arises from the vagus nerve, loops around under the ligamentum arteriosum, continues superiorly under the aorta, and lies in the tracheo-esophageal groove as it innervates the left recurrent laryngeal nerve. The left vagus continues posteriorly within the mediasti-num posteriorly along the esophagus to innervate the trachea and esophagus.

The posterior mediastinum contains those structures between the heart and pericardium and trachea anteriorly, and the vertebral column and paravertebral spaces posteriorly. The posterior mediastinum contains the esophagus, descending aorta, azygos and hemiazygos veins, thoracic duct, sympathetic chain, and lymph nodes. The thoracic duct originates from the cisterna chyli in the abdomen. It enters the chest through the aortic hiatus in an anterolateral position, and travels superiorly just to the right of midline in the chest along the anterolateral surface of the vertebral column. At approximately the level of T5, it crosses over to the left and continues superiorly to empty, posteriorly, into the junction of the left jugular and subclavian veins.

The inferior border of the mediastinum is the diaphragm, which separates the abdominal contents from the thorax. Hernias through the esophageal hiatus (paraesophageal hernias), or through the foramen of Bochdalek (posteriorly) or the foramen of Morgagni (anteriorly), may be initially identified as a mediastinal mass.

Each spinal root exits the neural foramina of the vertebral body and bifurcates to form a branch to the intercostal nerve, to innervate the skin and intercostal musculature, and a branch to the sympathetic ganglion. Intercostal nerves innervate the skin and musculature of the intercostal muscles. The spinal root divides as it exits the neural foramina. One branch goes to the intercostal nerve and one lies in the posterior vertebral gutter to form the sympathetic ganglion. The thoracic sympathetic trunk is composed of several ganglia that lie along the ribs. The most superior ganglion is the stellate ganglion.

regional lymph nodes, including the intercostal, mediastinal, and phrenic nodes. Visceral pleural lymphatics follow the super-ficial lung lymphatics and drain into the mediastinal lymph nodes. The parietal pleura underlying the ribs has rich nerve endings from the intercostal nerves. Generous local anesthesia is therefore necessary for chest tube insertion. The visceral pleura is innervated by vagal branches and the sympathetic system.

The anatomic boundaries of the mediastinum include the thoracic inlet superiorly, diaphragm inferiorly, sternum anteri-orly, vertebral column posteriorly, and medially to the parietal pleura. Thoracic tumors that penetrate through the pleura (by definition) invade the mediastinum. T raditionally, the mediasti-num can be divided into anterosuperior, middle, and posterior compartments. There no specific anatomic planes that define these areas. Fat and lymph nodes are found throughout the mediastinum.

The anterosuperior compartment includes the thymus gland. The right and left lobes of the thymus extend into the cervical areas; these portions of the thymus must be resected to provide for complete extirpation of the gland.

The middle mediastinum contains the heart, pericardium, great vessels, including the descending, transverse, and descend-ing aorta, superior and inferior vena cava, pulmonary artery and veins, trachea and bronchi, and phrenic, vagus, and recurrent laryngeal nerves. The phrenic nerve enters the thorax through the thoracic inlet on the anterior aspect of the anterior scalene muscle.

The vagus nerve enters the thoracic inlet through the carotid sheath. It lies anterior to the subclavian and posterior to the innominate artery on the right. The right recurrent laryngeal nerve loops or recurs around the innominate artery to innervate the right vocal cord. The vagus nerve then continues posteriorly in the tracheoesophageal groove to innervate the trachea and continues down to innervate the esophagus. On the left side, the vagus nerves enters the thorax through the thoracic inlet and, as it exits the carotid sheath, moves along the anterior aspect of FIGURE 58-4 segments of the pulmonary lobes. (adapted from Jackson CL, huber JF: Correlated applied anatomy of the bronchial tree and

lungs with a system of nomenclature. dis Chest 9:319, 1943.)

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Physiologic Evaluation

Before thoracic operations, patients may be evaluated by a com-bination of physiologic studies.5 A plain chest roentgenogram is commonly obtained (Fig. 58-5). Spirometry measures the lung volumes (Fig. 58-6) and mechanical properties of lung elasticity, recoil, and compliance. Pulmonary function testing (Fig. 58-7) also evaluates gas exchange functions, such as D LCO (diffusion of carbon monoxide in the lung).

The predicted postoperative forced expiratory volume (FEV) in 1 second (FEV 1) is the most commonly used indicator of postoperative pulmonary reserve. Most patients with an FEV 1 in excess of 60% predicted will tolerate an anatomic lobectomy, depending on other evaluable factors. If the FEV 1 is less than 60% of predicted, further testing might be considered in an attempt to estimate postoperative FEV 1 (predicted postoperative FEV 1 [ppo-FEV 1]). The quantitative ventilation-perfusion lung

SELECTION OF PATIENTS FOR THORACIC OPERATIONS

The physiologic evaluation of the thoracic surgical patient must be individualized for each patient, but generally emphasizes pulmonary and cardiac function. The assessment of a patient’s ability to tolerate lung resection from a cardiopulmonary stand-point is fundamental to patient selection for surgery. Patients with advanced pulmonary disease and severe pulmonary dys-function may have a prohibitive risk, which may exist in more than one third of patients with otherwise resectable lung disease.1

Cigarette smoking is associated with up to a sixfold increase in the incidence of postoperative pulmonary complications after surgery.2 If the patient is a smoker, he or she must stop smoking immediately. The physician must clearly communicate this message. Although there are few studies specific to pulmonary resection, there is evidence that preoperative smoking abstinence of 4 to 8 weeks’ duration is necessary to reduce the incidence of complications. Ideally, patients are smoke-free for a minimum of 2 weeks and preferably 4 to 8 weeks before surgery,3 although smoking cessation at any time is valuable.4 Smoking cessation programs may be helpful for these patients, and they may need pharmacologic assistance. This combination may have increased efficacy in smoking cessation efforts over counseling alone.

Prior to the operation, and in the perioperative period, deep venous thrombosis prophylaxis is provided by subcutane-ous heparin and/or by sequential compression stockings. Also, perioperative antibiotics are used to minimize complications from infections. Postoperative morbidity may also be minimized by adequate pain control to facilitate early ambulation. Routine use of a thoracic epidural catheter (or patient-controlled analge-sia [PCA]) provides excellent pain control. Incentive spirometry assists in expanding the lung and reducing the incidence of pulmonary morbidity. Nasal bilevel positive airway pressure for patients with obstructive sleep apnea may delay or eliminate the need for intubation or reintubation after pulmonary resection. Early mobilization is essential to avoid most perioperative complications.

FIGURE 58-5 initial chest roentgenogram (CXr). this patient is a 67 year old man with weight loss of 10 pounds in 4 weeks and a 35 pack-year history of cigarette use. he quit smoking 10 years ago. he had left shoulder pain for 4 months with no dyspnea, cough, hemoptysis, or other symptoms. Massage and other musculoskeletal manipulation did not improve his symptoms. a CXr with posterior-anterior (A) and lateral views (B)

demonstrates an 8.4 cm left upper lung mass. some deviation of the distal trachea is noted.

FIGURE 58-6 spirometry with subdivisions of lung volumes. ERV, expiratory reserve volume; FRC, functional residual capacity, that is, lung volume at end-expiration; IC, inspiratory capacity; RV, residual volume, that is, lung volume after forced expiration from FrC; TLC, total lung capacity; VC, vital capacity, that is, the maximal volume of gas inspired from rV; Vt,

tidal volume.

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A postoperative FEV 1 less than 30% predicted carries a greater postoperative risk for oxygen, and even ventilator depen-dence, but a decision to deny surgical resection to this group of patients must be considered on an individual basis because some will do better than expected with careful selection at experienced centers. Finally, in the immediate postoperative period, the objectively calculated ppo-FEV 1 will likely not be realized sec-ondary to limited ambulation, pain, or other emotional or physical factors.

The carbon monoxide diffusing capacity (D LCO ) can be measured by several methods, although the single-breath test is most commonly performed. The D LCO measures the rate at

scan is used to assist in the calculation of postoperative residual pulmonary function after resection. Patients with a ppo-FEV 1 of 35% to 40% should functionally tolerate the operation.

Quantitative radionucleotide perfusion scanning involves the injection of 99m Tc-radiolabeled albumin particles followed by the visual inspection of planar images (Fig. 58-8). Quantita-tive perfusion provides a measurement of the relative function of each lobe and lung, allowing a prediction of pulmonary func-tion after lung resection:

Ppo-FEV preoperative FEV fraction of perfusion to reg 111=×

?(i on of planned resection)FIGURE 58-7 Pulmonary function report. the pulmonary function report provides complete spirometry data based on predicted values for height and weight. in this patient, the forced expiratory volume in 1 second (FeV 1) is 2.26 L after bronchodilators, which is 80% of predicted. the carbon monoxide diffusing capacity (d L CO) is measured as 23.81 mL/min/mm hg which is 105% of predicted. FEF, Forced expiratory flow; FIV 1, forced inspiratory volume in 1 second; FIVC, forced inspiratory vital capacity; FRC, functional reserve capacity; FVC, forced vital capacity; HB, hemoglobin; PEF, peak expiratory flow; SB, single breath; SVC, slow vital capacity; TLC, total lung capacity; VA, alveolar volume; VC, vital

capacity.

1570?SeCtION?XI Chest

heart rate response to exercise, and measurements of minute ventilation and oxygen uptake/min. CPET allows a calculation

of maximum oxygen consumption ( V

O 2max ) and provides insight into overall cardiopulmonary function (the cardiopul-monary axis) that cannot be ascertained from other objective studies. CPET may identify clinically occult cardiac disease and provide a more accurate assessment of pulmonary function than spirometry and D LCO , which tend to overestimate functional loss after resection.

A patient’s risk of perioperative morbidity and mortality

may be stratified by V

O 2max . Those with V O 2max above 20 mL/kg/min are not at increased risk for complications or death after resection of non–small cell lung cancer (NSCLC). A level below 15 mL/kg/min is associated with an increased risk,

and V

O 2max less than 10 mL/kg/min indicates very high risk, generally precluding operation.7,8 Some have advocated stair climbing as a suitable measure of preoperative cardiopulmonary assessment.9 Given the wide availability of more objective and standardized noninvasive tests for cardiopulmonary function, stair climbing performance should not be used as the sole criterion to determine physiologic suitability for lung cancer resection. In patients undergoing evaluation for lung volume reduction surgery or for lung transplantation, a 6-minute walk test is used for a measure of the cardiac and pulmonary reserve. Patients are told to walk as far and as fast as they can during this time period. Distances of more than 1000 feet suggest an uncomplicated course.

Measurement of diaphragm function by fluoroscopy, the sniff test, is needed to determine symmetry of effort and exclude paradoxical movement of the diaphragm. Paradoxical movement—elevation of one hemidiaphragm with active con-traction or retraction of the other diaphragm—suggests paresis or paralysis. This finding may suggest a specific reason for breathlessness. Diaphragm plication may be therapeutic.

No single test result should be viewed as an absolute con-traindication to surgical resection. Although the physiologic assessment for patients undergoing normal spirometry and minimal comorbidity is fairly straightforward, patients with marginal preoperative indices must be considered on an indi-vidual basis.

Thoracic Incisions

The choice of incision depends on the operation, patient’s underlying physiologic condition, and anticipated benefits and limitations of the planned approach.

Video-assisted thoracic surgery (VATS) and other mini-mally invasive techniques have been developed to treat most thoracic problems, including lung cancer, mediastinal tumors, pleural diseases, and parenchymal diseases, and diagnosis and staging of thoracic malignancies. Minimally invasive techniques appear to minimize pain and surgical trauma from the incisions, decrease hospitalization, and improve convalescence. Small inci-sions are made for the camera and other instruments, depending on the location of the tumor. The ribs are not spread. Improved lighting and optics create excellent exposure and visualization.

The posterior or posterolateral thoracotomy is used for operations on a single thorax, pulmonary resection, esophageal surgery or resection, or resection of portions of the chest wall. The patient is placed in a lateral decubitus position. An oblique incision is used posteriorly or a vertical axillary incision is made just anterior to the latissimus dorsi muscle.

which test molecules such as carbon monoxide move from the alveolar space to combine with hemoglobin in the red blood cells. The D LCO is determined by calculating the difference between inspired and expired samples of gas. D LCO levels less than 40% to 50% are associated with increased

perioperative risk.

6

The ratio of FEV 1 in 1 second to forced vital capacity ratio (FEV 1/FVC) describes the relationship between the FEV 1 and the functional lung volume. In obstructive disease, the ratio is low (FEV 1 is low and FVC is high); in restrictive disease, the ratio is approximately normal because both FEV 1 and FVC are reduced.

Flow-volume loops derived from spirometry describe the relationship between lung volume and air flow as the lung volume changes during a forced expiration and inspiration. The typical test consists of tidal breathing at rest, maximal inspira-tory effort to total lung capacity, and maximal expiratory effort to residual volume, concluding with maximal inspiratory effort to total lung capacity.

Cardiopulmonary Exercise Testing

Cardiopulmonary exercise testing (CPET) can be extremely useful for the evaluation of marginal candidates (ppo-FEV 1 or ppo-D LCO <50% predicted) or for patients who appear more disabled than expected from simple spirometry measurements. Formal CPET includes an exercise electrocardiogram (ECG),

Lu Ru

LI Upper zone:Middle Zone:Lower zone:Total lung:

%4.724.013.241.8

Kct 22.66116.9164.20203.77

Left lung

Right lung %9.528.320.358.2

Kct 46.27138.0599.02283.34

RI

FIGURE 58-8 the quantitative perfusion lung scan report provides the lung volume, and the perfusion to each lung. in a patient with a large Left hilar tumor, perfusion may be reduced in the involved left lung compared with the uninvolved right lung. the predicted post–left pneumonectomy right lung function can be obtained by multiplying the right lung percent perfusion (58.2%) by the observed best FeV 1 (2.26 L). the resulting value, 1.31 L, 46.5% predicted, is the predicated postoperative FeV 1 (following left pneumonectomy). this value sug-gests that a left pneumonectomy would be functionally tolerated.

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diverticulum becomes completely separated from the trachea and is frequently found as an asymptomatic mass on routine chest x-rays. Computed tomography (CT) of the chest demon-strates this abnormality as a homogeneous-type mass, well circumscribed, and adjacent to the trachea (Fig. 58-9). The bronchogenic cyst accounts for 10% of mediastinal masses in children and is located in the midmediastinum. T reatment con-sists of excision, even if the patient is asymptomatic, to confirm the diagnosis.

Cystic fibrosis is an autosomal recessive disorder found more commonly in whites. Approximately 20% of patients with cystic fibrosis survive to the age of 30 years. Lung failure is the most frequent cause of death in most patients. Excessively thick mucus leads to inspissation, recurrent infec-tions, bronchitis, and bronchiectasis. Pneumothorax second-ary to air trapping is also found. Fibrosis and cystic changes on pathologic examination are identified. A tension cyst may be a complication of cystic disease. A rapid increase in the size of the cyst may cause mechanical ventilation problems as well as mediastinal shift. Resection, usually lobectomy, cor-rects this problem. Pneumatoceles may develop as a result of childhood Staphylococcus aureus infection. They can be large and may cause mechanical complications, which may resolve completely as the pneumonia resolves. Resection may be needed.

Congenital Bronchopulmonary Malformations

Lobar emphysema 10 is the most commonly resected congenital cystic lesion (50%). The onset of rapidly progressive respiratory distress usually occurs from 4 to 5 days to several weeks after birth. It rarely occurs after 6 months of age. It predominantly affects the upper lobe. Bronchiolitis is probably the most common cause overall. T reatment is lobectomy.

Congenital cystic adenomatoid malformations are the second most commonly resected congenital cystic lesion. They are closely related to a hamartoma without cartilage. T erminal bronchioles proliferate, yielding the adenomatoid malforma-tion. The lung has the appearance of Swiss cheese and feels like a large rubbery mass. With air trapping and overdisten-tion, respiratory distress may occur, which is optimally relieved by lobectomy.

Pulmonary sequestration is an area of embryonic lung tissue, separate from the lung, which receives blood supply from an anomalous systemic artery from the aorta, not the pulmonary artery. This condition occurs secondary to an accessory lung bud caudal to the normal lung, but with a lack of absorption of primitive surrounding splanchnic vessels. During lung development, interlobar sequestration (75%) occurs early. Later, after the pleura forms, extralobar sequestra-tion (ELS) occurs (25%), primarily on the left side (66%), and is completely enclosed by its own pleura. The ELS blood supply is usually from the thoracic or upper abdominal aorta to systemic (azygous or hemiazygous) veins. ELS is more common in males. Resection is recommended. Intralobar sequestration (ILS) mainly occurs within the lower lobes (>95%) and is equally distributed between the right and left lower lobes. ILS blood supply is from the descending thoracic aorta, which usually traverses the pulmonary ligament. Venous drainage is via the pulmonary veins. Ninety-five percent of the systemic blood supply to the pulmonary sequestration comes from the thoracic aorta.

The anterior or anterolateral thoracotomy is created by a curvilinear incision underneath the inferior border of the pec-toralis major muscle at the inframammary fold. A median ster-notomy is performed using a vertical incision from the sternal notch to the xiphoid. A sternal saw is then used to divide the sternum in the midline. With gentle retraction, the sternum can be spread approximately 8 to 10 cm to allow access to the medi-astinum, heart, great vessels, and right and left thorax. The pleura can be opened on either side to explore the hemithorax. The sternum is usually closed with stainless steel wire.

The transverse sternotomy, or clamshell incision, is larger than a median sternotomy and more uncomfortable for the patient. This incision combines two anterior thoracotomy incisions in the inframammary fold with transverse division of the sternum at the fourth intercostal space. Both internal mammary arteries are ligated. This approach is ideal for accessing the right and left hilum, as well as providing addi-tional exposure for large mediastinal tumors, bilateral hilar dissections, bilateral lung transplantation, or posterior-based metastases in both lungs.LUNG

Congenital Lesions

Various congenital lung abnormalities can occur as a conse-quence of disturbed embryogenesis.10 Bilateral agenesis of the lungs is fatal. Unilateral agenesis may occur more frequently on the left (≈70%) than on the right (≈30%), with more than a 2 : 1 male-to-female ratio.

Hypoplasia of the lungs may occur as a result of interfer-ence with the development of the alveolar system during the last 2 months of gestation. Bochdalek’s hernia is the most frequent cause of hypoplasia. Conditions associated with hypoplasia of the lungs include oligohydramnios, prune belly syndrome (defi-ciency in the abdominal musculature, genitourinary abnormali-ties), scimitar syndrome (abnormal pulmonary vein draining into the inferior vena cava, demonstrated as a crescent along the right heart border on a cardiac angiogram), and dextrocardia. Isolated pulmonary hypoplasia is rare.

Hyaline membrane disease (or infant respiratory distress syndrome) is frequent in premature infants (24 to 28 weeks’ gestation) and infants of diabetic mothers. At that point in gesta-tion, infants have an immature surfactant system. Hyaline mem-brane disease develops in the alveoli, causing congestion and a grossly deep purple–appearing lung. Respiratory distress fre-quently ensues, requiring high concentrations of oxygen. Chest x-rays demonstrate a ground glass appearance from the intersti-tial edema. As needs for oxygen and ventilator pressure increase to counteract this interstitial edema, pneumothorax frequently occurs. Of these infants, 10% to 30% do not survive.

Cystic Lesions

Congenital cystic lesions generally occur secondary to separation of the pulmonary remnants from airway branchings. Clinically, about one third of patients are without symptoms, one third have cough, and one third have infection or, rarely, hemoptysis. T reatment may be antibiotics or, for more severe localized cases, resection. Any thoracic cystic lesion that enlarges on serial radio-graphs needs to be considered for resection.

A bronchogenic cyst arises from a tracheal or bronchial diverticulum (see later, “Mediastinal Cysts and T umors ”). This

1572?SeCtION?XI Chest

rule out a mucous plug, adenoma, vascular compression, and

sequestration.

T racheal agenesis is a rare phenomenon and is fatal. The trachea is absent from the larynx to the carina, and bronchi communicate with the esophagus.

T racheal stenosis is also rare and consists of generalized hypoplasia, a funnel-like trachea, and bronchial and segmental malformations. The right upper lobe bronchus may come from the trachea directly and may be associated with an aberrant left pulmonary artery (so-called pulmonary artery sling ). Completely circular vascular rings are common. Repair is by incision of the trachea vertically and widening of the tracheal lumen.

T racheomalacia can be identified by bronchoscopy. The surgeon will notice marked variation of the tracheal lumen with inspiration and expiration. The tracheal rings are ineffective in

Congenital Abnormalities of the Trachea and Bronchi

Esophageal atresia with tracheoesophageal fistula is the most frequent abnormality of the trachea in infants (see later, “T rachea ”) Bronchial atresia is the second most frequent con-genital pulmonary lesion after tracheoesophageal fistula.11 The lung tissue distal to the atresia expands and becomes emphyse-matous as a result of air entry through the pores of Kohn. With no exit for air or mucus because of this blind bronchial stump, emphysema from air trapping or development of a mucocele may develop. Chest x-rays may demonstrate hyperinflation of a lobe or segment. The oval density may be identified between the hyperinflated lung and hilum. The left upper lobe is the most frequently involved of all lobes within the lung. Diagnosis may be confirmed with bronchography or CT. The surgeon must FIGURE 58-9 two chest roentgenograms (A) and a Ct scan (B) of the chest of a patient with a bronchogenic cyst (arrow ).

A

B

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harmful; aortography adds little additional information. Repair is performed through the left chest. Division of the smaller arch, usually the left, is undertaken. The ligamentum is divided and the trachea and esophagus are freed from the surrounding tissues. When a retroesophageal right subclavian artery with left ligament occurs, the patient may complain of dysphagia, which is referred to as dysphagia lusoria. The differential diagnosis includes neuromotor diseases of the esophagus or stricture.LUNG CANCER

Lung cancer is a significant global health problem. In the United States in 2010, there were an estimated 222,550 new cases of cancer of the lung and bronchus.15 Lung cancer is the most frequent cause of cancer death in men and women and accounts for 14.5% of all cancer diagnoses and 27.6% of all cancer deaths in the United States. Lung cancer deaths exceed the combined total deaths of breast, prostate, and colorectal cancer patients. Since 1987, more women have died of lung cancer than breast cancer. In men and women, changes in lung cancer incidence and the mortality rate probably reflect decreasing cigarette smoking over the previous 50 years and potentially earlier detec-tion of smaller and asymptomatic lung cancers. However, smoking cessation in women has lagged behind smoking cessa-tion in men, and the incidence of lung cancer in women con-tinues to increase. African American men have the highest incidence and highest death rate from cancer of the lung and bronchus.

Cigarette smoking is unequivocally the most important risk factor in the development of lung cancer. Other environmental factors that may predispose to lung cancer include industrial substances such as asbestos, arsenic, chromium, or nickel, organic chemicals, radon, or iatrogenic radiation exposure, air pollution, and other factors, such as secondary smoke in nonsmokers.

Radon is the second leading cause of lung cancer in the United States and is associated with approximately 18,000 lung cancer deaths/year.16 Radon is a natural radioactive gas released from the normal decay of uranium in the soil. Inhalation is associated with a health risk. Inexpensive test kits are available to determine the amount of radon present in a person’s home.

Optimal treatment of lung cancer requires accurate diag-nosis and clinical staging before treatment begins. The anatomic basis for staging (tumor, lymph nodes, metastases) includes the physical properties of the tumor and presence of regional or systemic metastases. The biologic basis for staging (molecular markers prognostic for survival, as well as indicators predictive for response to therapy) will be incorporated into staging systems of the future. Clinical trials are available for patient enrollment to better understand and evaluate various treatments.17 The National Cancer Institute Clinical T rials Cooperative Group Program conducts clinical trials for patients with lung cancer and other malignancies throughout the United States.18

Pathology

The pathology of lung cancer has been recently reviewed in detail.19 Development of lung cancer follows a progression of histologic changes that results from smoking and includes the following: (1) proliferation of basal cells; (2) development of atypical nuclei with prominent nucleoli; (3) stratification; (4) development of squamous metaplasia; (5) carcinoma in situ; and (6) invasive carcinoma.

maintaining the lumen of the trachea and, with negative intra-thoracic pressure, the trachea collapses. With the positive pres-sure exerted by exhalation, the trachea expands. Respiratory difficulty ensues from the intermittently collapsing trachea. Relief of the extrinsic compression is needed. Stent placement in adults or primary repair may be required. This condition may have a congenital predisposition but is most often seen in adults with COPD.

Congenital Vascular Disorders

Congenital vascular disorders of the lungs may occur.12 In Swyer-James-Macleod syndrome, there is an idiopathic hyper-lucent lung. This problem develops from chronic pulmonary infections such as bronchiectasis. As the consolidation persists, decreased pulmonary artery blood supply may cause a so-called autopneumonectomy and hyperlucent lung.

Scimitar syndrome is associated with a hypoplastic right lung, with drainage of the pulmonary vein to the inferior vena cava. Usually, the anomaly is corrected using extracorporeal cardiopulmonary support. A patch from the pulmonary vein to the left atrium via an atrial septal defect corrects this problem.

Pulmonary arteriovenous malformations may exist as one or more pulmonary arteries to pulmonary vein connections, bypassing the pulmonary capillary bed. This connection results in a right-to-left shunt. Approximately one third of these patients have hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). Approximately 50% of the malformations are small (<1 cm) and tend to be multiple. Also, 50% are larger than 1 cm, usually smaller than 5 cm, and tend to be subpleural. These lesions need to be considered in the differential diagnosis of any patient with hemoptysis that is unexplained on the basis of bronchoscopy or routine imaging. Local resection or catheter embolization of these lesions can be curative.

A pulmonary vascular sling consists of an anomalous or aberrant left pulmonary artery, which causes airway obstruction and is associated with other anomalies. The aberrant left pulmo-nary artery arises from the right (main) pulmonary artery and courses between the trachea and esophagus to supply the left lung. More than 90% of patients have wheezing and stridor. Esophagoscopy will show the anomalous vessel anterior to the esophagus; bronchoscopy or bronchography will demonstrate the vessel posterior to the trachea. Surgical correction requires exploration of the left chest, division of the artery, and oversew-ing of the vessel as far as possible distally within the mediasti-num. Reanastomosis to the main pulmonary artery is then performed.

Vascular rings 13 represent 7% of all congenital heart prob-lems.14 The most common vascular ring is a double aortic arch, which occurs in 60% of all cases. The right, or posterior, arch is the larger and gives rise to the right carotid and right subclavian arteries. The ring wraps around the trachea and esophagus. A posterior indentation is noted in the esophagus on barium swallow. Simple division corrects the anomaly. A right aortic arch with retroesophageal left subclavian artery and left ligamen-tum arteriosum occurs in approximately 25% to 30% of patients with vascular rings. Intracardiac defects occur with double aortic arch. Most of these infants require operation within the first weeks or months of life.

Most patients with vascular rings require only a careful history and barium swallow for diagnosis. Typically, one does not need bronchoscopy or esophagoscopy because it may be

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(FDG-PET), brain CT or magnetic resonance imaging (MRI), and mediastinoscopy. Mediastinal metastases on clinical staging suggest advanced disease best treated with chemoradiotherapy.

Lung cancers commonly metastasize to the pulmonary and mediastinal lymph nodes (lymphatic spread). Hematogenous spread of lung cancer is indiscriminate and almost all areas of the body are at risk. Metastases to the adrenal glands, brain, lung, and bone are common. ACA is more likely to metastasize to the CNS. Bone metastases are osteolytic. Extrathoracic metas-tases may occur without hilar nodes or mediastinal metastases.Screening

Patients with lung cancer often are seen with advanced-stage disease and symptoms at initial presentation. The pulmonary parenchyma does not contain nerve endings and tumors may grow undetected until symptoms of pain, hemoptysis, or obstructive pneumonia develop. With the increased use of CT in the United States, smaller asymptomatic lung cancers are being identified.

Screening for lung cancer reduces lung cancer mortality.22 The National Lung Screening T rial (NLST) randomized partici-pants to undergo three annual screenings with either low dose helical computed tomography or chest radiography; 53,454 patients were enrolled. Participants were between the ages of 55 and 74 years, and current or former heavy smokers (≥30 pack years of cigarette smoking at the beginning of the trial). Partici-pants had no signs or symptoms of lung cancer on trial entry. Fewer lung cancer deaths occurred in the CT group (n = 356) compared to the CXR group (n = 443). The NLST demon-strated that low-dose helical CT screening in high-risk patients reduced the death rate from lung cancer by 20% (95% CI, 6.8-26.7; p = 0.004), and reduced all-cause mortality by 6.7% (95% CI, 1.2-13.6; p = 0.02). The study was closed early given the significant difference between the two arms.

At present, mass screening for early lung cancer detection in asymptomatic individuals is not recommended. However, patients with significant tobacco history, and falling within the eligibility characteristics of the NLST, may elect to undergo testing for early stage lung cancer on an individual basis based upon consultation and evaluation by their personal physicians—the shared-decision making model. Screening of asymptomatic patients may identify nonspecific findings causing unnecessary anxiety in the patient and family. Patients in areas of endemic histoplasmosis with a smoking history and a newly discovered pulmonary nodule can be particularly challenging. An update related to shared-decision making for testing for early lung cancer is not planned until the results of prospective clinical trials are available.

Diagnosis

The diagnosis of lung cancer can be challenging.23 Many benign conditions mimic lung cancer. Physical examination should focus on the cardiorespiratory system. In addition, the presence of supraclavicular lymph nodes, identified by careful examina-tion of the cervical and supraclavicular lymph nodes, suggests advanced disease (N3 status for NSCLC) and therapy other than resection is recommended. Paraneoplastic syndromes are distant manifestations of lung cancer (not metastases) as revealed in extrathoracic nonmetastatic symptoms. The lung cancer affects these extrathoracic sites by producing one or more biologic or biochemical substances.

Adenocarcinoma (ACA) of the lung 20 is the most frequent histologic type and accounts for approximately 45% of all lung cancers. ACA of the lung develops from the mucus-producing cells of the bronchial epithelium. Microscopic features consist of cuboidal to columnar cells with adequate to abundant pink or vacuolated cytoplasm and some evidence of gland formation. Most of these tumors (75%) are peripherally located. ACA of the lung tends to metastasize earlier than squamous cell carci-noma (SCCA) of the lung and more frequently to the central nervous system (CNS). Bronchioloalveolar carcinoma (BAC) is a type of ACA but can sometimes be a more indolent disease. It is well differentiated and spreads along alveolar walls without invasion of stroma, blood vessels, or pleura. BAC may present as a solitary nodule, multiple nodules, or diffuse parenchymal infiltrates. Most ACAs, including those with a BAC component would be categorized as ACA, mixed subtype, because invasive components would be present.21 BAC may require resection to confirm the diagnosis. A solitary focus is treated in a manner similar to ACA. Multifocal disease generally is not amenable to surgical resection.

SCCA of the lung occurs in approximately 30% of patients with lung cancer. Approximately two thirds of these tumors are centrally located and tend to expand against the bronchus, causing extrinsic compression. These tumors are prone to undergo central necrosis and cavitation. SCCA tends to metastasize later than ACA. Microscopically, keratinization, stratification, and intercellular bridge formation are exhibited. SCCA may be more readily detected on sputum cytology than ACA.

A diagnosis of large cell undifferentiated carcinoma may be made in approximately 10% of all lung tumors. Specific cyto-logic features of SCCA or ACA are lacking. These tumors tend to occur peripherally and may metastasize relatively early. Micro-scopically, these tumors show anaplastic pleomorphic cells, with vesicular or hyperchromatic nuclei and abundant cytoplasm. Neuroendocrine histopathology in ACA can also portend a poorer prognosis and is somewhat more common in the large cell variant.

Small cell lung cancer represents approximately 20% of all lung cancers; approximately 80% are centrally located. The disease is characterized by an aggressive tendency to metastasize. It often spreads early to mediastinal lymph nodes and distant sites, especially bone marrow and brain. Small cell lung cancer appears to arise in cells derived from the embryologic neural crest. Microscopically, these cells appear as sheets or clusters of cells, with dark nuclei and little cytoplasm. This oatlike appear-ance under the microscope gives the term oat cell carcinoma to this disease. Neurosecretory granules are evident on electron microscopy. This tumor is staged as limited stage (disease restricted to an ipsilateral hemithorax within a single radiation port) and extensive stage (obvious metastatic disease). These tumors are often advanced at presentation, with an aggressive tendency to metastasize. Chemoradiotherapy is generally used for treatment. Prophylactic cranial irradiation needs to be con-sidered if the patient with limited- or extensive-stage disease responds well to first-line therapy. Complete responses may occur in approximately 30% of patients; however, the 5-year survival rate is only 5%. Patients with clinical early-stage disease (e.g., <3 cm in size, no nodal metastases, and no extra-thoracic metastases) may be considered for surgical resection, followed by adjuvant systemic therapy. Preresection staging includes 18F-fluorodeoxyglucose positron emission tomography

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NSCLC typically occurs in patients who are 50 to 70 years of age who have a history of cigarette smoking. Patients develop symptoms based on the physical impact of tumor growth within the lung parenchyma. Symptoms such as cough, dyspnea, chest wall pain, and hemoptysis are related to the physical presence of the tumor and its interactions with the structures of the lung and chest wall.24

Pathologic confirmation of NSCLC can assist the patient and physician in discussions of risk and benefit for specific treat-ment options. Guidelines for management of the indeterminate (or solitary) pulmonary nodule (SPN) are available.25 Under certain circumstances, a SPN may be deemed benign with ade-quate confidence in the absence of a pathologic diagnosis. SPNs that are entirely calcified or radiologically stable by CT of the chest for a minimum of 2 years are likely to be benign.26,27 Review of old radiographs or other prior imaging studies will assist in evaluation of changes in the mass.

In patients with a clinically suspicious SPN and nondiag-nostic fiberoptic bronchoscopy (FOB) and/or transthoracic needle aspiration (TTNA) studies, more invasive means for diagnosis are indicated. If histologic information is needed to assess risk and benefit for the patient, the least invasive strategy possible would be required. Newer techniques include naviga-tional bronchoscopy 28 to match CT images of small peripheral lung nodules with guided real-time direction of small broncho-scopic catheters to improve access for biopsy. In a physiologically fit patient with a suspicious SPN nodule, nonanatomic or wedge resection provides diagnosis. Confirmation of NSCLC by the pathologist should be followed by definitive resection in the same setting. For an SPN in the absence of a cancer diagnosis that cannot be removed by wedge resection, a lobectomy can be considered for diagnosis (and treatment). A pneumonectomy is not performed without a cancer diagnosis.

Up to one third of patients with NSCLC have a pleural effusion at the time of presentation. Pleural fluid sampling with thoracentesis is required for cytologic examination.

Malignant pleural effusion (MPE; T4) represents a contra-indication to resection; However, many pleural effusions in this setting may have a sympathetic or reactive cause.

Bronchoscopy is recommended before any planned pulmo-nary resection. The surgeon also will independently assess (via bronchoscopy) the endobronchial anatomy to exclude secondary endobronchial primary tumors and ensure that all known cancer will be encompassed by the planned pulmonary resection. When pneumonectomy or bronchoplastic resection is contemplated for a central tumor, the surgeon’s assessment at bronchoscopy is critical to the determination of whether complete (R0) resection can be achieved.

TTNA guided by CT or fluoroscopy is particularly useful in the evaluation of peripheral lesions smaller than 3 cm in diameter, but is limited by a high rate of nondiagnostic examina-tion. A nondiagnostic TTNA does not completely rule out malignancy; lung cancer can be excluded only in the presence of a specific benign alternative diagnosis. TTNA is not routinely recommended for the patient with good physiologic reserve and otherwise appropriate for surgery (e.g., stage I or II patients). If the patient does have hard palpable lymph nodes in the cervical or supraclavicular area, fine-needle aspiration (FNA) or biopsy may provide an accurate diagnosis of N3 disease. Otherwise, a superficial lymph node biopsy or a scalene node biopsy could be performed to obtain tissue for further evaluation.

Staging

Staging is a description of the extent of the cancer based on similarities in survival for the group of patients with those characteristics. The staging system creates a shorthand descrip-tion of the tumor, nodes, and metastatic characteristics of the patient to facilitate choice of optimal therapy and evaluate outcomes based on the clinical and pathologic stage. The American Joint Committee on Cancer (AJCC) and the Inter-national Union Against Cancer (UICC) have worked to estab-lish and promulgate staging system guidelines. The current international staging system for NSCLC 29 provides the basis for specific patient stage groupings and is used for current treatment recommendations.

The clinician’s responsibility is to ensure the highest pos-sible degree of certainty of the clinical stage or extent of the disease and recommend therapy or a therapeutic combination of greatest efficacy. Optimal staging assists the clinician in pro-viding the best recommendations for therapeutic interventions for the patient. The clinical stage is the physician’s best and final estimate of the extent of disease based on all available informa-tion from invasive and noninvasive studies and prior to the initiation of definitive therapy. The pathologic stage is the deter-mination of the physical extent of the disease based on histologic examination of the resected tissues, including the hilar and mediastinal lymph nodes.

Evaluation of Stages

t?(tumor)?Stage?As the tumor size increases, survival decreases.

Chest x-ray and CT of the chest and upper abdomen, including the liver and adrenals, are the most frequent diagnostic imaging studies performed in patients with lung cancer (Fig. 58-10). The chest x-ray provides information on the size, shape, density, and location of the primary tumor and its relationship to the medi-astinal structures. CT of the chest provides more detail than the chest x-ray on tumor characteristics, and provides information on the relationship of the tumor to the mediastinum, chest wall, and diaphragm, as well as invasion into the vertebrae or medi-astinal structures (clinical T4). MRI may complement CT in these patients (T4). MRI brain imaging may be reserved for patients with stage I or II cancer with new neurologic symptoms only (e.g., vertigo, headache), all patients with stage III or IV cancer,30 and those with small cell carcinoma or superior sulcus tumors (Pancoast tumor), because these patient have a higher incidence of occult brain metastases.

N?(Nodal)?Stage?Determination of metastases to mediastinal

lymph nodes constitutes a critical point in staging and treatment recommendations.30 Mediastinal lymph node metastases are present in 26% to 32% of patients at the time of diagnosis and initially assessed with chest CT. Lymph nodes may be enlarged normally from infection (e.g., histoplasmosis, previous bronchi-tis or pneumonia) or other inflammatory processes. Mediastinal adenopathy is most often defined as lymph nodes with a maximal transverse diameter more than 1 cm on axial tomographic images. In the absence of mediastinal nodes more than 1 cm in diameter, the likelihood of N2 or N3 disease is low. If medias-tinal nodes more than 1 cm are identified, nodal tissue must be examined (e.g., by endoscopic bronchial ultrasound, cervical mediastinoscopy, esophageal ultrasound, VATS) for histologic evidence of metastases before definitive resection.

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Invasive staging includes cervical mediastinoscopy (CME) or mediastinotomy (Chamberlain’s procedure), endoscopic bronchial ultrasound (EBUS), and esophageal ultrasound (EUS).34 CME is traditionally indicated for patients with otherwise operable NSCLC with enlarged paratracheal or sub-carinal lymph nodes, particularly if the cancer is proximal, pneumonectomy is planned, or the patient is at increased risk for the planned resection. CME is commonly performed for the biopsy of bilateral paratracheal (levels 2 and 4) and subcari-nal (level 7) lymph nodes. A mediastinotomy is used to gain access to the mediastinum after resection of the second cos-tosternal cartilage to evaluate the aortopulmonary window (level 5) or anterior mediastinum (level 6) lymph nodes. CME has a negative predictive value (NPV) above 90%, may be per-formed as an outpatient procedure, and is associated with a low rate of significant complications. When pathologic frozen section evaluation fails to demonstrate malignant nodal involve-ment, mediastinoscopy may be followed by resection under the same anesthetic. The use of CME, regardless of radiographic evidence of nodal involvement (routine mediastinoscopy), is not a cost-effective approach, and adds little to the accuracy of staging in patients with an adequate noninvasive preoperative evaluation.35

CT has a reported sensitivity for mediastinal lymph node assessment in NSCLC of 57% to 79%, with a positive predictive value of just 56%.30 No CT size criterion is entirely reliable for the determination of mediastinal lymph node involvement. Larger mediastinal lymph nodes are more likely to be associated with metastasis (>70%); however, normal-sized lymph nodes (<1 cm) have a 7% to 15% chance of containing metastases.

PET 31 may assist in evaluating the local extent and presence of known or occult metastases based on the differential increased metabolism of glucose by cancer cells compared with normal tissues (Fig 58-11). A PET scan is not a cancer-specific study because high cellular glucose metabolism is seen in inflamma-tory processes in addition to malignancy. Histologic confirma-tion of suspicious mediastinal lymph node involvement is indicated prior to final treatment decisions. Other areas of FDG uptake must be considered for the evaluation of histologic evi-dence of NSCLC. FDG-PET coupled with CT may yield increased sensitivity and specificity in determining the stage of patients with lung cancer before treatment interventions.32 Reed and colleagues 33 have determined that PET and CT together are better than either one alone in determining a patient’s suitability for resection. The negative predictive value of PET for medias-tinal lymph node metastases from NSCLC was 87%.FIGURE 58-10 radiographic evaluation for any patient with known or suspected lung cancer includes a plain chest roentgenogram (posterior-anterior (A); and lateral (B). Other studies commonly performed include computed tomography (Ct) of the chest (C). evaluation of the plain films and Ct guides subsequent evaluations. Fdg-Pet with fused Ct (D) provides the ability to correlate metabolic activity with physical find-ings. although Fdg-Pet uses the increased metabolism in most neoplasms to create the Fdg-Pet image, other processes such as infection, inflammation, or sequelae of trauma or fractures can be identified as well. sites of increased metabolism should be carefully evaluated for

metastases.

B

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and reform future revisions.37 The current AJCC descriptions for lung cancer staging reflect the impact of the IASLC lung cancer staging project.38 The IASLC collected over 100,000 NSCLC cases treated between 1990 and 2000. Each patient had a minimum of 5 years of follow-up and all treatment modalities were included. Over 81,000 cases were submitted that were eligible for analysis, including 67,725 patients with NSCLC and 13,290 patients with small cell carcinoma. Sur-vival was calculated by the Kaplan-Meier method. Prognostic groups were created using Cox regression analyses and results were internally and externally validated. Stage groupings were revised to reflect these analyses and internally and externally validated.29 External validation was assessed against the Surveil-lance, Epidemiology and End Results (SEER) program data-base. The data collected were retrospective and an audit of the data was not performed; however, information was provided by credible centers, which facilitated data collection, and analysis of a large patient population. Future directions will most cer-tainly include prospective data collection 39 and proteomic and genomic characteristics.

I have included the TNM definitions (Table 58-1), nodal characteristics (Box 58-1), and stage groupings of the TNM subsets with survival (Table 58-2). Other schematics have been created for the lymph node map 40 and T characteristics.41

The mediastinal and regional lymph node classification scheme is presented in Figure 58-12. This map presents a graphic representation of mediastinal and pulmonary lymph nodes in relation to other thoracic structures for optimal dissection and anatomic labeling by the surgeon.

tumor?(t)?In the IASLC lung cancer staging project, over 18,000

patients had a T1 to T4 tumor with N0 lymph node dissection and R0 resection.42 T1 was divided into T1a (≤2 cm) and T1b (>2 to 3 cm). T2 was divided into T2a (>3 to 5 cm) and T2b (>5 to 7 cm). T2c would have been more than 7 cm; however, these patients had a survival that was statistically similar to the survival of T3 patients. Lung cancers larger than 7 cm are cat-egorized as T3.

Other T2 descriptors, such as visceral pleural invasion and partial atelectasis (less than the entire lung), could not be evalu-ated because of small number of patients and inconsistent data. In the current AJCC staging system, nodules in the same lobe were categorized as T3, nodules in a different lobe were catego-rized as T4, and a nodule in a contralateral lobe would be des-ignated as M1a unless there was compelling evidence to suggest synchronous primary tumors.

T3 tumors may be characterized as a tumor with invasion into the pleura, pericardium, or diaphragm, an endobronchial tumor less than 2 cm from the carina, or an obstructing tumor causing atelectasis of the entire lung and, as noted, two nodules in the same lobe.

T4 tumors would involve the mediastinal structures such as the heart, great vessels, esophagus, and trachea, as well as the vertebral body or carina. T wo nodules, one each in two separate ipsilateral lobes, would also be characterized as T4.

Pleural metastases, or MPE, was changed from T4 (in the AJCC sixth edition) to M1. Patients previously categorized as a clinical T4 based on an MPE, malignant pericardial effusions, or pleural nodules, are now categorized as clinical M1 based on poor survival more closely resembling patients with metastatic disease.

Additional sampling techniques may be helpful.30,34

EBUS may be more sensitive than mediastinoscopy. Combining EBUS and surgical staging may provide greater sensitivity for medias-tinal nodal metastases than surgical staging alone and avoid unnecessary thoracotomies.36 VATS techniques can evaluate enlarged level 5 or 6 lymph nodes, as well as enlarged level 8 or 9 or low-level 7 lymph nodes. EUS-guided aspiration can be easily used for transesophageal needles aspiration of subcarinal and left anteroposterior (AP) window lymph nodes.30

Extrathoracic or distant metastases (M1b) are common in lung cancer. Beyond a thorough history and physical examina-tion, and standard staging techniques, additional evaluation for metastatic disease is indicated only for selected cases.30 If meta-static disease is suspected based on imaging results, a tissue sample should be obtained for diagnosis to confirm the presence or absence of metastases.34 Nodules in the contralateral lung are characterized as metastatic disease (M1a), as are MPE and pleural carcinomatosis.

Metastatic adrenal involvement is present in up to 7% of patients at presentation. The standard CT evaluation of the chest should also include evaluation of the upper abdomen to include the liver and adrenal glands. Indeterminate adrenal lesions on CT may be evaluated further with MRI or CT-guided percuta-neous biopsy.

Current American Joint Committee on Cancer Staging System

The International Association for the Study of Lung Cancer (IASLC) embarked on its lung cancer staging project to include all treatment and diagnostic groups, collect data for analysis,

FIGURE 58-11 a subcarinal Ln has mild Fdg uptake. Based on these findings, additional invasive staging is warranted to include bronchos-copy, and invasive staging of mediastinal lymph nodes. endobronchial ultrasound with transtracheal needle aspiration can be performed with real-time ultrasound guidance to facilitate transtracheal needle placement. Other stations can be biopsied as well. if needed, cervical mediastinoscopy is performed with biopsy of high paratracheal (2r and 2 L), low paratracheal (4r and 4 L), pretracheal (3a), and sub-carinal (7) lymph nodes. if left-sided aortopulmonary lymph nodes were Fdg avid, Chamberlain’s procedure (anterior mediastinotomy), or Vats with biopsy of aortopulmonary (aP) window lymph nodes, or hilar lymph nodes could also be performed. additional evaluation of the patient would be warranted if the patient would be considered

a surgical candidate.

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Lymph?Nodes?(N)?The nodal characteristic and designations did not change in the current AJCC guidelines.43Over 67,000 patients had T, N, and M characteristics as well as a description of histologic type and survival; 38,265 patients had clinical nodal and 28,371 had pathologic nodal staging information. Clinical staging studies included tests such as diagnostic imaging, CT, and mediastinoscopy. Thoracotomy for staging was excluded. PET was not widely used internationally in this cohort during this period. A new international lymph node map was proposed combining the integral aspects of the Japanese-Naruke and the North American–Mountain lymph node maps.44Of special note, the authors proposed radiographic regions for the location of specific mediastinal lymph nodes, particularly for integration with CT, to guide the radiologic staging of patients with NSCLC.Metastases?(M)?Metastases were divided into M1a and M1b.45 Patients with metastasis to the contralateral lung only were des-ignated as M1a and metastases to regions outside the lung or pleura were designated as M1b. A second nodule in the nonpri-mary ipsilateral lobe, previously designated as M1, was changed to T4M0. In this situation, the patient received the benefit of the doubt approach because this might represent a second primary.

Results of Treatment of Lung Cancer

According to Stage

The choice of initial therapy, whether single modality or multi-modality therapy, depends on the patient’s clinical stage at pre-sentation and availability of prospective protocols. However,

Lung, Chest WaLL, PLeura, and MediastinuM?Chapter?58?1579

1580?SeCtION?XI Chest

2. Stage IV disease includes metastatic disease and is not

typically treated by surgery, except for patients requiring surgical palliation. Systemic therapies for metastatic disease are common. Targeted therapies have provided carefully screened patients with excellent results.

3. Resectable stages IIIA and IIIB tumors are locally advanced

tumors with metastasis to the ipsilateral mediastinal (N2) lymph nodes (stage IIIA) or involving mediastinal struc-tures (T4N0M0). These tumors, by their advanced nature, may be mechanically removed with surgery; however, surgery does not consistently control the micrometastases

treatment options may vary, even among different subsets of patients within the same clinical stage. Pretreatment staging remains the critical step before initiating therapy. With current efforts, 5-year survival rates by pathologic stage are 73% for stage IA, 58% for IB, 46% for IIA, 36% for IIB, 24% for IIIA, 9% for IIIB, and 13% for IV.29 T reatment for lung cancer can be roughly grouped into three major categories:

1. Stages I and II tumors are contained within the lung and

may be completely resected with surgery. Recently, stereo-tactic body radiation therapy has had good early results in selected patients not amenable to resection.46

a handbook for staging, imaging, and Lymph node Classification. houston, 1999, Mountain, pp 1–71.)

Superior mediastinal nodes (including azygos nodes) (ascending aorta or phrenic)Inferior mediastinal nodes N1 nodes

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from esophageal or lung carcinoma have a limited life expec-tancy. Palliative care should be considered.

Local Therapy for Early-Stage Non–Small Cell Lung Cancer

Stages I and II NSCLC can be treated safely with surgery and mediastinal lymph node dissection alone and, in most patients, provides long-term survival.47,48 Anatomic resection, lobectomy, with systematic mediastinal lymph node dissection and sam-pling, is the procedure of choice for lung cancer confined to one lobe (Fig. 58-13). The American College of Surgeons Oncology Group (ACOSOG) has defined a systematic sampling strategy for specific mediastinal lymph nodes.49 At a minimum, nodal (not adipose) tissue from stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4 L, 5, 6, 7, 8, and 9 for left-sided cancers should be sampled. Mediastinal lymphadenectomy

that exist in the general area of the operation or systemi-cally. Combinations of chemotherapy and radiotherapy are used for locally advanced disease or prior to resection.Lung carcinoma should be resected when the local disease can be controlled, the patient’s physical condition can tolerate the planned resection and reconstruction, and the anticipated operative mortality is less than the stage-specific 5-year survival. Conditions such as superior vena cava syndrome, tumor inva-sion across the mediastinum into the main pulmonary artery, N3 nodal metastases, malignant pleural or pericardial disease, and extrathoracic metastases carry greater risk than benefit for most patients. Some centers have had good results with resection and reconstruction of the trachea, atrium, great vessels, or other mediastinal or vertebral structures. These are complex operations requiring dedicated teams during the perioperative stage and multidisciplinary care. Patients with tracheoesophageal fistula

FIGURE 58-13 structured pathology report following left lower lobectomy. Lung Carcinoma summary Findings are helpful in identifying factors critical for pathological staging, and which may influence survival subsequently. today, ancillary testing for mutational analysis of egFr, Kras,

and aLK is done routinely. targeted agents exist, and others are being developed, for treatment of tumors with these characteristics.

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should include exploration and removal of lymph nodes from stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4 L, 5, 6, 7, 8 and 9 for left-sided cancers.

Lesser operations such as wedge resection or segmentec-tomy may be considered for patients at greater risk for lobec-tomy.50 Prospective clinical trials are ongoing to evaluate the role of parenchyma-sparing surgery, such as wedge alone compared with lobectomy in select patients with small peripheral NSCLC. These prospective trials are evaluating the role of wedge resection with or without brachytherapy 131I threads, radiofrequency abla-tion, and wedge resection compared with stereotactic body radiation therapy.51 Patients with NSCLC that invade into the chest wall may be resected with lobectomy with en bloc chest wall resection.

Other local control modalities include stereotactic body radiation therapy (SBRT).46T reatment with 54 Gy in three fractions appears to be well tolerated, with good early results. Prospective clinical trials (ACOSOG Z4099/RTOG 1021) are underway to evaluate high-risk patients (unable to tolerate a lobectomy) with early-stage NSCLC randomized between wedge resection and SBRT.

Neoadjuvant and Adjuvant Therapy

Advanced-stage lung cancer, particularly with nodal spread, cannot typically be considered a disease effectively treated with a single modality. Survival following resection may be improved in select patients with adjuvant chemotherapy. The International Adjuvant Lung T rial (IALT)52 enrolled 1867 patients with com-pletely resected stages I to III NSCLC. These patients were randomized to observation or chemotherapy. Radiation therapy was at the discretion of the institution. The treatment group received one of four cisplatin-based doublet adjuvant regimens.53 Survival was increased 5% in the adjuvant chemotherapy group. All patients staged IB to IIB were considered for adjuvant che-motherapy following resection.47

Surgery alone for stage IIIA (N2), IIIB, or IV lung cancer is infrequently performed; however, select patients may benefit from a multidisciplinary approach to treatment.54 Resection for isolated brain metastasis is warranted for improvement in symp-toms, quality of life, and survival rate. The primary lung tumor can then be treated according to T and N stage. Additional treatment beyond resection is needed.

Even with complete resection, patients with resectable NSCLC have poor survival. Preoperative therapy (induction or neoadjuvant) has been evaluated; preoperative paclitaxel and carboplatin followed by surgery was compared with surgery alone in patients with early-stage NSCLC. Median overall sur-vival (OS) was 41 months in the surgery-only arm and 62 months in the preoperative chemotherapy arm (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.60 to 1.06; P= .11). Median progression free survival was 20 months for surgery alone and 33 months for preoperative chemotherapy (HR, 0.80; 95% CI, 0.61 to 1.04; P= .10). OS and progression-free survival (PFS) were both higher with preoperative chemo-therapy, although the differences did not reach statistical significance.55

Induction chemoradiotherapy has been evaluated for the treatment of clinical stage IIIA (N2) NSCLC.56 In one phase III trial, concurrent chemotherapy and radiotherapy followed by resection were compared with standard concurrent chemother-apy and definitive radiotherapy without resection. The median OS was similar in both groups (≈23 months). PFS was better in the surgery group (median, 12.8 versus 10.5 months; P= .017). The authors noted that pneumonectomy was associated with poor outcomes and OS was improved for patients undergoing induction chemoradiotherapy and lobectomy. In selected resect-able stage IIIA NSCLC patients, induction chemoradiotherapy followed by resection is an alternative treatment to chemoradio-therapy alone.

Patients with local extension of lung cancer at the apex of the lung into the thoracic inlet may have shoulder and arm pain, Horner’s syndrome, and occasionally paresthesia in the ulnar nerve distribution of the hand (fourth and fifth fingers; Fig. 58-14). Patients with all these characteristics may be classified as having Pancoast syndrome. Pain comes from the C8 and T1 nerve roots. Sympathetic nerve involvement may result in Horner’s syndrome—miosis, ptosis, anhidrosis, and enophthal-mos. Typically, the first, second, and third ribs are involved and require resection, but the bony spine and intraforaminal spaces can also be involved. MRI is necessary, in addition to CT, to plan the surgical procedure. Preoperative therapy includes chemoradiotherapy.57,58

Treatment of Metastatic Disease

Metastatic disease (stage IV NSCLC) is usually incurable.59 Per-formance and quality of life decline. Patients and families should be informed about the diagnosis and potential outcomes of treatment. T reatment decisions should be respectful of the patient’s and family wishes and realistic expectations should be set and monitored during therapy.

Combination chemotherapy with platinum doublets has been well tolerated and associated with a modest improvement in survival rates.53The additional of bevacizumab (a mono-clonal antibody to the vascular endothelial growth factor receptor) to paclitaxel and carboplatin has improved survival compared with patients treated with paclitaxel and carboplatin alone.60 Induction chemotherapy followed by radiation appears to improve survival rate in patients with locally advanced unresectable lung cancer, as shown in prospective randomized studies.61 In these studies, cisplatin-based combination chemo-therapy improved survival. Additional strategies to identify the molecular characteristics of the tumor as part of the initial staging could also improve survival by creating better models for treatment of NSCLC. Advances in tumor biology have made available predictive markers of response to epidermal growth factor receptor (EGFR) mutations62and anaplastic lymphoma kinase (ALK), a chimeric protein originally identi-fied in anaplastic large cell lymphoma) receptors.63These studies have focused efforts to target specific genetic mutations in specific lung cancers. Mutations in the EGFR gene strongly predict the response to EGFR inhibitors. Clinical trials have shown significant PFS in patients with metastatic NSCLC treated with gefitinib and platinum-based doublet chemo-therapy compared with chemotherapy alone.64,65Targeted therapies in addition to, or alone, may limit toxicity and improve outcomes compared with current chemotherapeutic regimens.

Quality of life issues arise in patients with metastatic NSCLC. Dyspnea from MPE, superior vena cava syndrome, tracheoesophageal fistula, bone metastases, and pain occurs. Nutrition and hydration become significant issues. Palliation from symptoms may be accomplished, with good results.66

Lung, Chest WaLL, PLeura, and MediastinuM Chapter?58?1583

FIGURE 58-14 the patient is a 50-year-old man with a right superior sulcus tumor. diagnostic imaging revealed a right apical mass. transtho-racic biopsy was positive for poorly-differentiated adenocarcinoma (non-small cell lung carcinoma). endobronchial ultrasound for mediastinal staging was negative. induction chemoradiotherapy was given with 48 gy in 24 fractions over one month with chemotherapy (carboplatin auC of 5 + pemetrexed 500 mg/m 2). A, Ct chest demonstrated the mass is present in the apex of the chest with complete destruction of the posterior aspect of the right second rib and cortical erosion of the right t2 vertebral body secondary to the mass. the patient is left hand domi-nant. B, the Mri of the thoracic spine demonstrates a medial right apical lung mass, consistent with a Pancoast tumor involving right lateral aspect of the t2 vertebral body, articular facet, and transverse process. there was also extension into the neural foramen and involvement of the nerve roots on the right at t1-2 and t2-3. there was no extension into the central canal or involvement of the spinal cord; Ct head: no acute findings involving the brain. Complete resection was performed with a two surgeon team: thoracic surgery and neurosurgery. the tumor

was resected with right upper lobectomy en bloc with chest wall and a portion of the vertebral body. spine stabilization was required.

TRACHEA

The trachea’s position can be up to 50% cervical, with hyperex-tension in the young patient. The location of the carina is at the level of the angle of Louis anteriorly and the T4 vertebra poste-riorly. Stenosis of the trachea implies significant functional impairment. A normal 2-cm trachea has a 100% peak expiratory flow rate. A 10-mm opening provides an 80% peak expiratory flow rate. At 5 to 6 mm, only a 30% expiratory flow rate is obtained. T racheostomy is one of the most commonly per-formed operations. Percutaneous tracheostomy is frequent,67 although open procedures may be selected. Infection and inflam-mation are uncommon causes of tracheal obstruction.

Primary neoplasms of the trachea 68,69 include SCCA in approximately two thirds of patients and adenoid cystic carci-noma in other patients. SCCA may be focal, diffuse, or multiple. The physical appearance may be exophytic or ulcerative. One third of these primary tracheal tumors have extensive local spread or metastases at initial presentation. Adenoid cystic car-cinoma (previously called cylindroma ) has a propensity for intra-mural and perineural spread. In adenoid cystic carcinoma, negative margins are important. Margin evaluation with frozen section control is performed for stricture resection. Clinical fea-tures include dyspnea on exertion, wheezing, cough with or without hemoptysis, and recurrent pulmonary infections.

Involvement of the trachea from local extension from bron-chogenic carcinoma may contraindicate resection. Involvement

of the trachea caused by local extension of esophageal carcinoma may require palliative therapy or stenting.

Tracheal Trauma

Penetrating injuries to the trachea are usually cervical; penetrat-ing injuries that involve the mediastinal trachea are often lethal. Penetrating cervical injuries often involve the esophagus, and concurrent esophageal injury needs to be excluded by barium esophagography or esophagoscopy. Neck exploration may be required. Blunt trauma to the neck or trachea can produce lac-erations, transections, or shattering injuries of the cervical and mediastinal trachea. Clinical features of a tracheal injury are suggested by subcutaneous air in the neck, respiratory distress, and hemoptysis. Diagnosis is made by bronchoscopy. Anesthetic management with a laryngeal mask airway may be helpful for initial examination for full visualization of the airway before endotracheal intubation. Primary repair of a tracheal injury may be accomplished with cervical exploration. Bronchial disruption may require thoracotomy. A right thoracotomy provides excel-lent visualization of the carina and proximal left mainstem bronchus.

Postintubation tracheal stenosis may occur because of laryngeal or tracheal irritation from an indwelling endotracheal tube. Low-pressure cuffs on the endotracheal tube have reduced pressure necrosis. T racheal stenosis may present with dyspnea on exertion, stridor, or wheezing, which is easily noted, and perhaps