2.1 Lung Cancer Surgery Sidhu P. Gangadharan, Philip A. Linden,

2.1 Lung Cancer Surgery

Sidhu P. Gangadharan, Philip A. Linden, and David J. Sugarbaker

S. P. Gangadharan, MD

Chief Resident in Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115-6195, USA P. A. Linden, MD

Instructor in Surgery, Harvard Medical School, and Associate Surgeon, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115-6195, USA

David J. Sugarbaker, MD

The Richard E. Wilson Professor of Surgical Oncology Harvard Medical School and Chief, Division of Thoracic Surgery, Brigham and Women’s Hospital,75 Francis Street, Boston, MA 02115-6195, USA and Phillip E. Lowe Senior Surgeon Chief, Department of Surgical Services Dana Farber Cancer Institute

CONTENTS

2.1.1 Introduction 47

2.1.2 Preoperative Assessment 47 2.1.2.1 Diagnosis 47

2.1.3 Staging 48 2.1.3.1 T Stage 48 2.1.3.2 N Stage 49 2.1.3.3 M Stage 50

2.1.4 Preoperative Fitness 51 2.1.5 Operative Strategy 51

2.1.5.1 Nomenclature and Anatomy 51 2.1.5.2 Extent of Resection 52 2.1.6 Technique of Resection 53 2.1.6.1 Postoperative Course 53

2.1.7 Video-Assisted Thoracoscopic Surgery 54 2.1.8 Radiation Therapy for Patients Undergoing

Lung Resection – T3 Tumors 55 References 55

2.1.1 Introduction

Lung cancer is the most common cancer in the world, with an incidence of 1.2 million cases and 1.1 mil- lion deaths in the year 2000 (Parkin et al. 2001).

In the United States alone an estimated 171,000 new cases and 157,000 deaths from lung cancer occurred in 2003 (Jemal et al. 2003). It is estimated that lung cancer accounts for nearly 13% of cancers (exclud- ing non-melanoma skin cancer) worldwide, compris- ing 18% of new cancers for men and 7% for women

(Parkin et al. 1999). The United States has seen a modest improvement in 5-year survival to approxi- mately 15% over the interval between 1974 and 1998, although death from lung cancer still exceeds that from all other cancers (Jemal et al. 2003).

The World Health Organization has classifi ed the histologic subtypes of lung cancer (Brambilla et al.

2001). Surgical resection represents the best chance for cure of epithelial non-small-cell lung cancers.

However, perhaps up to three-quarters of patients presenting with lung cancer have lesions that are unresectable because of locally advanced tumor or systemic spread (Anonymous 1995; Ginsberg et al. 1997). This chapter provides an overview of the important surgical aspects of lung cancer therapy, including preoperative assessment of resectability, operative strategy, adjuvant and neoadjuvant therapy, and challenging lung cancers, such as tumors invad- ing the mediastinum or chest apex (superior sulcus tumors).

2.1.2

Preoperative Assessment

2.1.2.1 Diagnosis

Patients presenting with lung cancer are usually

symptomatic, describing a history of cough, weight

loss, or dyspnea in 60%–75% of cases (Beckles et

al. 2003a). Hemoptysis, chest or bone pain, fever, or

weakness occur somewhat less frequently (Beckles

et al. 2003a). Physical examination may elicit signs

of advanced disease including the following: lymph-

adenopathy in the supraclavicular or cervical regions,

percussion dullness from an effusion, and neck vein

distension from superior vena cava obstruction. After

radiologic confi rmation of the presence of tumor, a

pathological diagnosis may be obtained by means

of sputum cytology, bronchial washings or brush-

ings, or fi ne needle aspiration. Bayesian theory has

been applied to the undiagnosed pulmonary nodule

to estimate likelihood of malignancy (Gurney et al.

1993; Gurney 1993; Cummings et al. 1986). This ap- proach considers the resulting pre-test probability of malignancy, in conjunction with the patient’s opera- tive risk, and stratifi es the patient into one of three categories: observation, further non-resectional diag- nostic testing (e.g., sputum cytology, bronchial wash- ings or brushings, fi ne needle aspiration, PET scan), or surgical resection (Ost et al. 2003). The patient’s pre-test probability is highly dependent upon age, smoking history, and CT scan characteristics of the lesion (i.e., size greater than 2 cm, spiculations, and recent lesion growth).

2.1.3 Staging

Once the diagnosis of pulmonary malignancy has been made or, conversely, the pre-test probability is suffi cient to warrant resection without preopera- tive tissue diagnosis, the patient undergoes a staging work-up to assign prognosis and determine the most appropriate therapy. The staging system for non- small cell lung cancer is based on TNM classifi cation (Table 2.1.1) (Mountain 1997). Verifi cation of stage is accomplished both invasively (i.e., fi ne needle bi- opsy, resection) and non-invasively (i.e., CT scan, PET scan). Stages I and II non-small cell lung cancers are treated with surgical resection. Patients with locally

advanced Stage III tumors are potential candidates for surgery, depending on the specifi c aspects of local invasion (e.g., tumor infi ltration into the chest wall or carina versus involvement of great vessels or heart) or level of nodal metastasis. Stage IV cancers exhibit- ing extensive metastatic spread are generally outside the realm of the thoracic surgeon, except for pal- liative measures, although solitary metastases may not preclude a potentially curative lung resection.

Patients whose poor medical condition precludes a pulmonary resection may still benefi t from interven- tions to restore and maintain airway patency through bronchoscopic debridement of tumor, photodynamic therapy, airway stenting, or brachytherapy.

2.1.3.1 T Stage

T1 tumors are less than 3 cm in diameter and exhibit invasion no more proximal than a lobar bronchus.

These lesions are completely surrounded by lung parenchyma. T2 tumors are greater than 3 cm in di- ameter or exhibit invasion into the visceral, but not parietal, pleura. The extent of proximal invasion may be as far as a main stem bronchus, but no closer than within 2 cm of the carina. Atelectasis or pneumonitis resulting from T2 tumors may extend to the hilum, but not involve an entire lung.

T3 tumors are locally invasive and involve the parietal pleura, chest wall, diaphragm, mediastinal pleura, parietal pericardium, or a main stem bron- chus less than 2 cm from the carina. There may be atelectasis or pneumonitis involving an entire lung.

T4 tumors exhibit invasion of the carina, trachea, mediastinum, great vessels, heart, or esophagus. A malignant pericardial or pleural effusion conveys T4 status. In addition, satellite tumor nodules within the same lobe as the primary tumor are considered T4 lesions. There are two important points regarding resectability of T3/T4 tumors. First, it is essential to realize that an ipsilateral effusion termed T4 may not be a pathologic T4 tumor. Thoracoscopy with pleu- ral biopsy often demonstrates a benign effusion sec- ondary to lobar collapse. Second, clinical T4 tumors from a secondary nodule in the same lobe have a bet- ter prognosis (3-year survival of 66.5%) than other pathologic T4 tumors, and patients should be offered resection (Battafarano et al. 2002).

CT scanning has been considered a mainstay of tumor staging, but may incompletely distinguish the T1/T2 from T3/T4 tumors, a distinction that may af- fect the extent of surgical resection (Webb et al. 1991).

Recent studies show that CT alone may incorrectly

Table 2.1.1. Non-small cell lung cancer staging

Stage TNM subset

IA T1N0M0 IB T2N0M0 IIA T1N1M0 IIB T2N1M0 T3N0M0 IIIA T1N2M0 T2N2M0 T3N1M0 T3N2M0 IIIB T1N3M0 T2N3M0 T3N3M0 T4N0M0 T4N1M0 T4N2M0 T4N3M0

IV Any T, any N, M1

stage tumors up to one-quarter of the time (Antoch et al. 2003; Lardinois et al. 2003). Integrated PET-CT scan may prove more accurate, yielding 98% correct tumor staging when compared to the fi nal histopath- ological staging (Lardinois et al. 2003). In terms of airway invasion, although radiologic reconstruction of the bronchi and trachea are useful adjuncts to operative planning, our policy is to always perform bronchoscopy to assess the airway before any consid- eration of surgical resection. Determination of the proximal extent of endobronchial tumor invasion (i.e., distance from carina) may be accomplished, in addition to assessment for anatomic abnormali- ties, which might infl uence the surgical resection.

Intraoperatively, frozen section analysis may be use- ful to determine extrapulmonary tumor involvement versus infl ammation or adhesion in some cases (i.e., confi rm T3 or T4 status).

2.1.3.2 N Stage

The lymph node drainage of the lung has been de- scribed previously (Asamura et al. 1999; Naruke et al. 1978). In 1997, a revised lymph node map was agreed upon by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) (Fig. 2.1.1) (Mountain and Dresler 1997). N0 cancers have no demonstrable metastases to regional lymph nodes. N1 represents metastasis to the ipsilateral peribronchial lymph nodes, ipsilat- eral hilar lymph nodes, or both, and intrapulmonary nodes involved by direct extension of the primary tumor (lymph nodes with double-digit numbering).

N2 lymph nodes are metastases to ipsilateral medias- tinal lymph nodes, subcarinal lymph nodes (single- digit lymph nodes), or both. N3 designates lymph

Fig. 2.1.1. Regional lymph node staging system for non-small cell lung cancer. [Reproduced with permission from Mountain CF and Dresler CM (1977) Regional lymph node classifi cation for lung cancer staging Chest June 111(6):1718–

1723, Figure 1, p. 1719]

Superior Mediastinal Nodes 1 Highest Mediastinal 2 Upper Paratracheal

3 Pre-vascular and Retrotracheal 4 Lower Paratracheal

(including Azygos Nodes)

N₂ = single digit, ipsilateral

N₃ = single digit contralateral or supraciavicular

Aortic Nodes

Inferior Mediastinal Nodes

N

Nodes

5 Subaortic (A-P window) 6 Para-aortic (ascending aorta or phrenic)

7 Subcarinal 8 Paraesophageal (below carina) 9 Pulmonary Ligament

10 Hilar 11 Interlobar 12 Lobar 13 Segmental 14 Subsegmental

Phrenic n.

3 Ligamentum

arteriosum

L. pulmonary a.

6

Ao

5 PA Brachiocephalic

(innominate) a.

Azygos v.

2R

4R

Ao

10R PA

11R

12,13,14R

10L 11L

12,13,14L 9

8 7

Inf. pulm. ligt.

4L

node metastasis to contralateral mediastinal or hilar lymph nodes, or ipsi- or contralateral scalene or su- praclavicular lymph nodes.

Non-invasive lymph node staging can be per- formed using CT scan, PET scan, MRI, or endoscopic ultrasound (EUS). A meta-analysis of studies utilizing these various modalities revealed a pooled sensitivity of 57% for CT, 84% for PET, 100% for MRI, and 78%

for EUS. Specifi cities were 89% for CT, 82%–95% for PET, 91% for MRI, and 71% for EUS. Further study of MRI is warranted, however, as the results were drawn from a single report of only 20 patients (Toloza et al. 2003). Currently, MRI would not be considered the standard imaging modality for evaluation of lymph nodes in lung cancer. The accuracy of CT or PET scan with regard to lymph node staging may be enhanced by the integration of these two technologies, although combined CT-PET scanners are not currently avail- able in all facilities (Lardinois et al. 2003; Weng et al. 2000).

Invasive lymph node staging can be accomplished by transthoracic needle biopsy, EUS needle biopsy, mediastinoscopy, or thoracoscopy. Meta-analysis of the fi rst four techniques reveals that cervical medi- astinoscopy yields the best performance profi le, with a sensitivity of 81% and negative predictive value of 91% (Toloza et al. 2003). Half of the nodes missed were not accessible through cervical mediastinos- copy, because this technique only permits evaluation of the paratracheal and subcarinal lymph node sta- tions. Further enhancement of sensitivity may be ac- complished with the addition of extended cervical or anterior mediastinotomy techniques (Ginsberg et al.

1987; McNeill and Chamberlain 1966). Therefore, mediastinoscopy is the recommended nodal staging technique except in the instance of extensive tumor infi ltration into the mediastinum, where radiologic staging may suffi ce and needle aspiration or bron- choscopy may be enough to obtain pathologic con- fi rmation of diagnosis (Kramer and Groen 2003;

Detterbeck et al. 2003). The utility of thoracoscopic lymph node staging has not been fully elucidated (Gossot et al. 1996; Landreneau et al. 1993).

We use cervical mediastinoscopy as the last preop- erative staging step before planned surgical resection.

To minimize the likelihood that lymph nodes will read as falsely negative for tumor metastasis, we send the specimens for permanent section analysis by pa- thology, instead of relying on frozen section analysis.

Thus, the planned pulmonary resection is deferred to a second operative setting. The surgical approach to cervical mediastinoscopy and lymph node sampling commences with a small incision above the sternal

notch, followed by dissection between the strap mus- cles until the pre-tracheal fascia may be breached.

Blunt dissection is then used to enter the medias- tinum, and the paratracheal and subcarinal lymph nodes are exposed and removed with a biopsy forceps under direct vision (Reed and Sugarbaker 1996).

The morbidity of the procedure is minimal (Park et al. 2003; Luke et al. 1986). Determination of IIIB dis- ease (contralateral mediastinal lymph node involve- ment, N3) would preclude surgical resection. Our al- gorithm for positive N2 nodes involves preoperative chemoradiation or chemotherapy alone, followed by re-staging imaging to ascertain response. If there is no progression of disease, we recommend pulmo- nary resection with radical lymphadenectomy.

2.1.3.3 M Stage

M0 connotes no distant metastasis; M1 reports the presence of distant metastasis. A patient who is deemed to have M1 disease by virtue of a nodule in a separate lobe should be diagnosed by limited resection. The patient may be a candidate for curative resection, as these patients have a better prognosis than patients with distant M1 disease. In one study, the 3-year survival of T1-T2/N0/M1 resected tumors was 63.6% (Battafarano et al. 2002). The absence of clinical fi ndings may preclude the need to exten- sively scan the asymptomatic early-stage lung cancer patient, as neither survival nor recurrence rates are affected (Tanaka et al. 1999; Ichinose et al. 1989).

Some authors have recommended radiologic investi- gation for extrathoracic disease (e.g., bone scan, head CT, abdominal CT) only if it is warranted by clinical evaluation or in the case of advanced disease (stage IIIA or IIIB) (Silvestri et al. 2003). Unnecessary thoracotomy, however, may be prevented by routine extensive extrathoracic workup (Anonymous 2001).

In addition to head CT, we have also started using whole body integrated PET-CT scanning to further clarify the presence of metastatic disease, and the effect of this new technology on survival and recur- rence is yet to be prospectively determined.

Patients with either solitary brain metastases

(Patchell et al. 1990; Burt et al. 1992; Magilligan

et al. 1986) or solitary adrenal metastases (Luketich

and Burt 1996; Porte et al. 2001) may benefi t from

surgical resection of the primary lung tumor in addi-

tion to the metastatic lesion. Our strategy is to com-

bine a metastatic workup with cervical mediastinos-

copy. If contralateral nodal disease is not found, then

the patient may undergo resection of the solitary

brain or adrenal metastasis, followed by pulmonary resection as above.

2.1.4

Preoperative Fitness

Once a patient is determined to be resectable, it is imperative to assess overall fi tness to undergo sur- gery. In addition to a careful history and physical that might reveal the presence of heart failure, coronary insuffi ciency, or other co-morbidities, all patients considered for surgical resection at our institution undergo pulmonary function testing (PFT) and de- termination of the diffusing capacity of the lung for carbon monoxide (DL

). In addition, a modi- fi ed stair-climbing test is sometimes used to assess a patient’s suitability for surgery (Brunelli et al.

2002, 2004).

A preoperative forced expiratory volume (FEV1) >2L (60% predicted) and DL

>60% pre- dicted value suggest that the patient will tolerate pulmonary resection, including pneumonectomy.

The threshold to tolerate a lesser resection is com- mensurately reduced: FEV1 >1L for lobectomy and FEV1 >0.6L for wedge resection (Miller et al. 1981).

At our institution we rely heavily on the percent of predicted values, as these account for individual vari- ability in age or size. Despite some variance in the literature regarding the effi cacy of FEV1 or DL

in predicting outcome after lung surgery (Stephan et al. 2000; Ferguson et al. 1988), further testing to stratify postoperative risk should be undertaken if the FEV1 or DL

is less than the thresholds cited above (Datta and Lahiri 2003).

Calculation of a predicted postoperative FEV1 (ppoFEV1) may be accomplished either by estimation, using the formula of Juhl and Frost [ppoFEV1 = pre- operative FEV1 × (1-[S×5.26]/100); S: number of segments to be resected] (Juhl and Frost 1975), or by quantitative VQ scanning modifi ed after Wernly and colleagues (1980) [ppoFEV1 = preoperative FEV1 × (1-[% perfusion contributed by affected lung/100 × S/total number of segments in affected lung])]. A ppoFEV1 >40% predicted and DL

>40%

predicted have been suggested as threshold values (Datta and Lahiri 2003; Beckles et al. 2003b). Our group has recently demonstrated that by using a va- riety of minimally invasive techniques, limited resec- tions, and concomitant lung volume reduction, with advanced anesthetic and perioperative care, curative resections can be performed in patients with preop- erative FEV1 <35% predicted with a mortality of 1%

and serious morbidity under 5% (Linden et al. 2004).

The determination of operability should be made by a thoracic surgeon skilled in these techniques. Exercise testing and calculation of VO

represents the next level of testing should the predicted postoperative values be below threshold values. VO

>20 ml/

kg/min designates an acceptable risk group for sur- gery. VO

<10 ml/kg/min confers signifi cantly in- creased risk for postoperative death or cardiopulmo- nary complications following lung surgery (Datta and Lahiri 2003; Beckles et al. 2003b).

In patients who are scheduled to undergo pneu- monectomy or who may present with cardiac comor- bidity, we obtain a preoperative echocardiogram to evaluate ventricular and valvular function, as well as to investigate any pre-existing pulmonary hyperten- sion. Occasionally, right heart catheterization and pulmonary artery balloon occlusion are used to de- termine further a patient’s physiologic response to lung resection.

2.1.5

Operative Strategy

2.1.5.1

Nomenclature and Anatomy

The scope of surgical resection ranges from ‘wedge

resection’ to ‘pneumonectomy’. The wedge resection

represents a non-anatomic resection of the target le-

sion, with a variable margin of lung parenchyma. The

terminology ‘non-anatomic’ refers to the lack of dis-

section of any of the branches of the three broncho-

pulmonary structures – pulmonary vein, pulmonary

artery or bronchus – or the attendant draining lym-

phatics or lymph nodes. ‘Segmentectomy’ describes

an anatomic resection of the bronchopulmonary seg-

ment (Fig. 2.1.2). The right upper lobe is comprised

of apical, anterior, and posterior segments; the right

middle lobe is comprised of the lateral and medial

segments; and the right lower lobe is comprised of

the superior segment, as well as the medial, anterior,

lateral, and posterior basal segments. The left upper

lobe is divided into the upper division comprising

the apicoposterior and anterior segments, and the

lingula, which contains a superior and inferior seg-

ment. The left lower lobe is comprised of the superior

segment, and the anteromedial, lateral, and posterior

basal segments. ‘Lobectomy’ entails removal of an en-

tire lobe and its lobar pulmonary artery, pulmonary

vein, and bronchus, with attendant lymphatic basin.

‘Bilobectomy’ involves resection of two lobes from the same lung. ‘Sleeve resection’ denotes the removal of a circumferential portion of the airway in conjunc- tion with the parenchymal resection. The remaining lung requires a bronchial anastomosis in order to re-establish airway continuity. A sleeve resection can also be performed on the pulmonary artery, should it be necessary to resect a circumferential portion of the vessel with the specimen. Similarly, bronchoplasty or arterioplasty in conjunction with a pulmonary resec- tion describe the techniques by which the bronchus or pulmonary artery is reconstructed after removal of a non-circumferential portion of the structure during resection. Pneumonectomy can be intraperi- cardial or extrapericardial, in reference to the site of division of the pulmonary vessels. ‘Extrapleural pneumonectomy’ or ‘pleuropneumonectomy’ refer to the en bloc removal of the parietal pleura with the entire lung. En bloc chest wall resection describes the removal of a portion of the parietal pleura, ribs, and intercostal musculature attached to the primary specimen of resected lung.

2.1.5.2

Extent of Resection

The fi rst lobectomy for lung cancer using a tech- nique of individual ligation of the hilar structures was performed by Davies in 1912 (Davies 1913).

Churchill refi ned lung resection with the introduc- tion of the technique of individual ligation of the

bronchopulmonary structures (Churchill and Belsey 1939). Graham reported the fi rst successful pneumonectomy for lung cancer in 1933 (Graham and Singer 1933). Pneumonectomy remained the operation of choice for lung cancer until Churchill’s report in 1950, which detailed long-term survival following lobectomy (Churchill et al. 1950). The issue of whether sub-lobar or non-anatomic resec- tion might similarly suffi ce was raised by Jensik and colleagues in 1973. Subsequent investigators have concluded that a lesser resection in the setting of impaired cardiopulmonary reserve or advanced age might be justifi ed (Landreneau et al. 1997; Errett et al. 1985). One argument against applying a strategy of limited resection more broadly to any patient with early stage lung cancer has been that it may under- stage cancers by virtue of inadequate lymph node sampling. Takizawa and colleagues (1998) found a 17% incidence of metastases to N1 and N2 lymph nodes with radical lymphadenectomy after resection of small (1.1-2.0 cm) peripheral lung adenocarcino- mas, suggesting that an adequate assessment of the draining lymph node basin may be important even in these distal T1 tumors. The other area of conten- tion is whether limited resection could effect a local and systemic cure. A randomized trial of lobectomy versus segmentectomy or wedge resection for T1 N0 non-small cell lung cancers was reported by the Lung Cancer Study Group in 1995. Although no statisti- cally signifi cant difference in survival was found, in- vestigators did fi nd that the overall recurrence rate

Fig. 2.1.2. Surgical anatomy of the lung. [Reproduced with permission from Elsevier Science, Inc, JB Putnam Lung (including pulmonary embolism and thoracic outlet syndrome) In: Townsend CM (ed) Sabiston Textbook of Surgery, 16th edition, Chapter 55, 2001. Figure 1]

Right lat. Right ant.

Right Key:

1 Apical 2 Posterior 3 Anterior 4 Lateral 5 Medial 6 Superior 7 Medial (basal) RLL 8 Anterior basal 9 Lateral basal 10 Posterior basal

upper lobe middle lobe

lower lobe

Left

1– 2 Apical posterior 3 Anterior

4 Superior of lingula 5 Inferior of lingula 6 Superior

7, 8 Anterior-medial basal 9 Lateral basal 10 Posterior basal

upper lobe

lower lobe

Left ant. Left lat.

펂펂 펂

펂 펂

was increased 75% in the limited resection group, and that the locoregional recurrence was increased three-fold (Ginsberg and Rubinstein 1995). This increased recurrence after sub-lobar resection echoed the fi ndings of Warren and Faber (1994).

Landreneau and colleagues (1997) examined the outcomes of lobectomy and wedge resection, both video-assisted and via open thoracotomy, and found a signifi cant improvement in 5-year survival curves after lobectomy, although this was explicable by an excess of non-cancer-related deaths in the limited resection group.

At our institution, we reserve pneumonectomy for cases in which tumors are too central to fully resect with lobectomy, and where bronchoplasty or sleeve resection still would not allow an adequate margin with parenchymal sparing. Similarly, extensive in- volvement of the pulmonary vessels may necessitate pneumonectomy, if arterioplasty is not feasible. Also, in cases where the cancer crosses the fi ssure on the left or crosses the major fi ssure, involving the upper and lower lobes on the right, pneumonectomy is con- sidered in patients with suitable reserve.

Conversely, limited resection for lung cancer is re- served at our institution for patients with marginal medical status, advanced age, poor pulmonary re- serve, or in some instances of second primary lung cancer. In all cases, the tumor stage is T1. Every effort is made to adequately stratify risk preoperatively, to ensure that all potential candidates for anatomic re- section are identifi ed.

2.1.6

Technique of Resection

We have previously described in detail the steps for the major pulmonary resections (Sugarbaker et al.

2001). In brief, after the induction of general anes- thesia, bronchoscopy is performed to assess the air- way for unexpected tumor progression or anatomic abnormality that would alter the planned resection.

Subcutaneous heparin and prophylactic antibiotics are administered. Single-lung ventilation is then ac- complished using a double-lumen endotracheal tube or single-lumen tube with a bronchial blocker. The patient is positioned in thoracotomy position – a lat- eral decubitus position – with the operative side up.

A number of incisions may be used to access the pleural space. For most anatomic resections, we uti- lize a posterolateral thoracotomy incision which be- gins at a point midway between the lower half of the scapula and the spine, and extends to the anterior

border of the latissimus dorsi muscle. The serratus muscle is usually spared, the latissimus muscle is usu- ally divided. The fi fth intercostal space is entered at the superior border of the sixth rib. Occasionally the sixth space is used, or a rib may be removed partially or entirely in order to widen the access to the chest.

An anterolateral thoracotomy, usually in the fourth intercostal space, is another alternative. Suffi cient analgesia for these incisions is achieved with long- acting local anesthetic plus narcotic via a thoracic epidural catheter placed preoperatively.

The hilar structures are individually dissected and divided. Our preference is to divide both vessels and bronchi using a stapler. Smaller pulmonary arterial branches are doubly ligated if they are not amenable to stapler division. Incomplete fi ssures are also di- vided using a stapling device. Lymphadenectomy is performed.

The margins are inspected by a pathologist upon removal of the specimen to assure a negative bron- chial margin. The integrity of the bronchial stump is checked by testing the stump with ventilatory pres- sure up to 30 cm of H

O. When the patient has re- ceived neoadjuvant radiation or may receive postop- erative radiation, it is our preference to buttress the bronchial stump with an intercostal muscle pedicle, a pericardial or pleural fl ap, or a thymic fat pad. We also buttress after pneumonectomy or bilobectomy.

2.1.6.1

Postoperative Course

Mortality for lung cancer surgery ranges from 2%

to 4% in modern series, with postoperative morbid- ity occurring approximately 15%–30% of the time (Deslauriers et al. 1989; Ginsberg et al. 1983;

Knott-Craig et al. 1997; Myrdal et al. 2001; Yano

et al. 1997). Myrdal and colleagues (2001) reviewed

their experience of 616 patients undergoing lung can-

cer surgery and found an overall 30-day postoperative

mortality rate of 2.9%, with pneumonectomy confer-

ring a higher risk (5.7%) than lobectomy (0.6%). The

rate of major complication (defi ned as postoperative

bleeding leading to exploration, respiratory failure,

bronchopleural fi stula, myocardial infarction, stroke,

heart failure, or renal failure) was 8.8%, with a higher

rate seen after pneumonectomy (18.5%) than lobec-

tomy (5.7%). Minor events occurred in 22%, with

supraventricular arrhythmias accounting for half of

these complications (Myrdal et al. 2001). The mor-

tality and complication rates after bilobectomy have

been previously reported to be comparable to that of

pneumonectomy (Deneuville et al. 1992). However,

more recent series do not report excess mortal- ity or morbidity after bilobectomy (Damhuis and Schutte 1996; Cerfolio et al. 2000; Carbognani et al. 2001).

At the Brigham and Women’s Hospital we use post- operative clinical pathways to standardize care after pulmonary resection and to reduce length of stay.

Implementation of patient care pathways for lobec- tomy has been reported to reduce both length of stay and hospital cost (Cerfolio et al. 2001; Wright et al. 1997). Although 1-day stays after lobectomy have been reported (Tovar et al. 1998), a length of stay in the 5- to 7-day range is more common (Tschernko et al. 1996; Kirby et al. 1995). At our institution all patients are transferred to a specialized thoracic sur- gery intermediate care unit after lobectomy or lesser resection. After 1–3 days in this setting, to permit in- vasive hemodynamic monitoring, continuous oxygen monitoring, and frequent pulmonary toilet/ambula- tion, patients are transferred to a regular fl oor bed on the thoracic surgical unit, which provides continued specialized nursing care. After pneumonectomy, our patients are recovered fi rst in a specialized thoracic intensive care unit, which allows even more extensive monitoring such as pulmonary artery catheteriza- tion, if indicated. Both hospital and surgeon-specifi c experience infl uence postoperative mortality for lo- bectomy and pneumonectomy, with higher volume correlating with better outcomes in several large studies (Birkmeyer et al. 2002, 2003; Hannan et al.

2002).

The 5-year survival for non-small cell lung can- cer was reported by Mountain in 1997. For Stage I tumors the 5-year survival is 67% (T1N0) and 57%

(T2N0). Stage II tumors are 55% (T1N1), 39% (T2N1), and 38% (T3N0). In Stage IIIA, the 5-year survival is 38% (T3N1) and 23% (T1-3N2). The rate drops in Stage IIIB to 3% (T1-3N3) and 6% (T4AnyN). M1 disease confers an overall 5-year survival of 1%.

2.1.7

Video-Assisted Thoracoscopic Surgery

Video-assisted thoracoscopic surgery (VATS) utilizes small port accesses to the chest and a videoscope for visualization, thereby avoiding a full thoracot- omy incision. The ability to perform pulmonary re- sections with VATS techniques has provided a less invasive method to safely diagnose and treat lung cancers (DeCamp et al. 1995). Initial videoscopic thoracic surgery was diagnostic or limited to treat- ment of pneumothorax, pleural effusion, or other be-

nign conditions (Kopp et al. 1979; Oldenburg and Newhouse 1979; Rodgers et al. 1979; Kapsenberg 1981; Boutin et al. 1982; Fritsch et al. 1975). VATS lobectomies for lung cancer were fi rst reported in 1993 (Walker et al. 1993; Kirby and Rice 1993).

We have described our technique of VATS lobec- tomy in detail elsewhere (Sugarbaker et al. 2001).

A small incision in the anterior seventh interspace is used to place a port for a 5- or 10-mm videoscope.

The entirety of the pleural space and lung may be in- spected for unexpected local or metastatic spread. For wedge resections, second and third ports are placed so that a triangulation is achieved over the tumor, and instruments can be introduced to retract, dissect, and staple the lung. For formal lobectomies or seg- mentectomies we use a 4- to 6-cm fourth interspace accessory incision in the anterior axillary line which allows access to the hilar structures. In addition, we employ one posterior port near the tip of the scapula for retraction. Dissection and division of the pulmo- nary vein, pulmonary artery, and bronchial struc- tures are accomplished with endoscopic staplers in a similar manner to our open lobectomy. Mediastinal lymphadenectomy is also performed. The specimen is removed via an endoscopic bag to avoid seeding the port sites with shed tumor cells.

The operative mortality for wedge resection for lung cancer has been reported to be negligible (Landreneau et al. 1997; Kodama et al. 1997). For elderly patients undergoing VATS wedge resection, we have previously shown that the mortality is <1%, with a morbidity of 9%. VATS lobectomy also has been accomplished with minimal mortality and morbidity (Gharagozloo et al. 2003; Tatsumi and Ueda 2003;

Morgan et al. 2003; Lewise et al. 1999; McKenna 1998). A recent representative report by Morgan and colleagues (2003) describes their experience with 158 patients undergoing VATS lobectomy. They report an 11% rate of conversion to open thoracotomy, second- ary to extent of disease and bleeding in most cases.

The in-hospital mortality rate was 0.6%, with an overall 30-day mortality rate of 1.8%.

The oncologic validity of VATS lobectomy has not been addressed in a randomized prospective trial, but retrospective studies report 5-year survival rates for Stage I and II non-small cell lung cancers ranging from 60% to 90%, and locoregional recurrence rates around 5% (Tatsumi and Ueda 2003; Walker et al.

2003; Sugi et al. 2000; McKenna et al. 1998). Freedom

from cancer-related or associated death has been re-

ported to be 78% for Stage I cancers, 51% for Stage

II, and 29% for Stage III (Walker et al. 2003). An

adequate lymph node dissection appears to be pos-

sible during VATS lobectomy (Asamura et al. 1999;

Morikawa et al. 1998).

An initial randomized trial of VATS versus open lobectomy did not demonstrate a statistically sig- nifi cant difference in length of stay (Kirby et al.

1995). A subsequent randomized trial and several non-randomized trials, however, were able to show a reduction in length of stay with the minimally inva- sive technique (Tschernko et al. 1996; Demmy and Curtis 1999; Ohbuchi et al. 1998). These same trials have also reported a signifi cant difference in the level of pain associated with VATS lobectomy (Tschernko et al. 1996; Morikawa et al. 1998; Demmy and Curtis 1999; Landreneau et al. 1993). Walker and associ- ates (1996) have shown that the incidence of chronic pain following VATS lobectomy is 1.2%.

2.1.8

Radiation Therapy for Patients

Undergoing Lung Resection – T3 Tumors

Adjuvant and neoadjuvant chemotherapy with or without radiation has been studied extensively for stage IIIA (N2) and stage IIIB (N3) disease.

Radiation therapy, without chemotherapy, does little to help these patients. For locally invasive, T3, tumors, radiation therapy alone may make the dif- ference between clear margins and positive mar- gins. In general, T3 tumors invading the chest wall are treated with surgical excision with wide mar- gins alone, without the need for radiation therapy.

Several retrospective trials have shown either no benefi t, or a detriment to adding preoperative ra- diation therapy to patients with simple chest wall invasion (Piehler et al. 1982; Albertucci et al.

1992). Exceptions to this fi nding are tumors abut- ting or involving the vertebral bodies. If the tumor is close to the vertebral body, the surgeon may con- sider preoperative radiation in order to shrink the tumor and lessen the chance that resection of the vertebral body will be required.

Superior sulcus tumors (Pancoast tumors) rep- resent a unique subset of tumors which invade the chest apex. The tumor may involve vertebral bodies, subclavian vessels, or the brachial plexus. Pancoast tumors are preoperatively staged by CT, and some- times MRI, as T3 or T4 depending on the level of in- vasion. Lymph node staging and metastatic workup are undertaken as for other non-small cell lung can- cers. Positive N2 and N3 nodes are associated with a 5-year survival of less than 10% (Detterbeck 1997;

Deslauriers et al. 1994).

Treatment of Pancoast tumors begins with neo- adjuvant therapy. These tumors were initially ap- proached with preoperative radiotherapy alone (Shaw et al. 1961). Recently, however, retrospective studies (Wright et al. 2002; Attar et al. 1998) as well as a prospective randomized trial (Martin et al.

2001) have shown potential benefi t to combining che- motherapy with preoperative radiation for superior sulcus tumors.

Surgical approaches to superior sulcus tumors include extended posterolateral thoracotomy and anterior cervicothoracic incisions (Shaw et al. 1961;

Dartevelle et al. 1993). Resection usually comprises the following steps: (1) resection of the chest wall in- cluding fi rst rib and, at times, portions of involved vertebral bodies; (2) resection of involved nerve roots, up to the fi rst thoracic nerve root; (3) resection of the thoracic sympathetic chain; (4) resection of upper lobe or wedge of involved lung; and (5) lymph node dissection. Incomplete resection yields a sur- vival rate which is comparable to that of no resection (Rusch et al. 2000; Detterbeck 1997).

T3 tumors involving the mediastinum are very diffi cult to cure. Burt and colleagues (1987) re- viewed 225 patients accrued over an 11-year period at Memorial Sloan Kettering. The 5-year survival for patients with T3N2 disease was 8%, which is similar to survival of patients with lower T stage tumors and N2 disease. Patients with T3N0 tumors invading the mediastinum fared no better, with 5-year survival of 10%. Although prospective trials do not exist, this subset of patients may very well benefi t from neoad- juvant radiation or chemoradiation.

References

Albertucci M, DeMeester TR, Rothberg M et al (1992) Surgery and the management of peripheral lung tumors adherent to the parietal pleura. J Thorac Cardiovasc Surg 103:8-13 Anonymous (1995) Chemotherapy in non-small cell lung

cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group (see comment). BMJ 311:899-909

Anonymous (2001) Investigating extrathoracic metastatic dis- ease in patients with apparently operable lung cancer. The Canadian Lung Oncology Group. Ann Thorac Surg 71:425- 433; discussion 433-434

Antoch G, Stattaus J, Nemat AT et al (2003) Non-small cell lung cancer: dual-modality PET/CT in preoperative stag- ing. Radiology 229:526-533

Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T (1999) Lobe-specifi c extent of systematic lymph node dis- section for non-small cell lung carcinomas according to a

retrospective study of metastasis and prognosis (see com- ment). J Thorac Cardiovasc Surg 117:1102-1111

Attar S, Krasna MJ, Sonett JR et al (1998) Superior sulcus (Pan- coast) tumor: experience with 105 patients (see comment).

Ann Thorac Surg 66:193-198

Battafarano RJ, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA (2002) Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival. Ann Thorac Surg 74:988-994

Beckles MA, Spiro SG, Colice GL, Rudd RM (2003a) Initial eval- uation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes. Chest 123:97S-104S

Beckles MA, Spiro SG, Colice GL, Rudd RM, American College of Chest Physicians (2003b) The physiologic evaluation of patients with lung cancer being considered for resectional surgery. Chest 123:105S-114S

Birkmeyer JD, Siewers AE, Finlayson EV et al (2002) Hospital volume and surgical mortality in the United States (see comment). N Engl J Med 346:1128-1137

Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL (2003) Surgeon volume and operative mor- tality in the United States (see comment). N Engl J Med 349:2117-2127

Boutin C, Viallat JR, Cargnino P, Rey F (1982) Thoracoscopic lung biopsy. Experimental and clinical preliminary study.

Chest 82:44-48

Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y (2001) The new World Health Organization classifi cation of lung tumours. Eur Respir J 18:1059-1068

Brunelli A, Al Refai M, Monteverde M, Borri A, Salati M, Fianchini A (2002) Stair climbing test predicts cardiopul- monary complications after lung resection. Chest 121:1106- 1110

Brunelli A, Monteverde M, Al Refai M, Fianchini A (2004) Stair climbing test as a predictor of cardiopulmonary compli- cations after pulmonary lobectomy in the elderly. Ann Thorac Surg 77:266-270

Burt M, Pomerantz A, Bains MS et al (1987) Results of surgical treatment of stage III lung cancer invading the mediasti- num. Surg Clin North Am 67:987-1000

Burt M, Wronski M, Arbit E, Galicich JH (1992) Resection of brain metastases from non-small-cell lung carcinoma.

Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. J Thorac Cardiovasc Surg 103:399-410; discussion 410-411

Carbognani P, Tincani G, Solli P et al (2001) The bilobectomies for lung cancer. J Cardiovasc Surg 42:421-424

Cerfolio RJ, Holman WL, Katholi CR (2000) Pneumoperito- neum after concomitant resection of the right middle and lower lobes (bilobectomy). Ann Thorac Surg 70:942-946;

discussion 946-947

Cerfolio RJ, Pickens A, Bass C, Katholi C (2001) Fast-tracking pulmonary resections. J Thorac Cardiovasc Surg 122:318- 324

Churchill ED, Belsey HR (1939) Segmental pneumonectomy in bronchiectasis: lingula segment of the upper lobe. Ann Surg 109:481

Churchill ED, Sweet RH, Sutter L, Scannel JG (1950) The surgi- cal management of carcinoma of the lung: a study of cases treated at the Massachusetts General Hospital from 1930- 1950. J Thorac Cardiovasc Surg 20:349-365

Cummings SR, Lillington GA, Richard RJ (1986) Estimating the

probability of malignancy in solitary pulmonary nodules.

A Bayesian approach. Am Rev Respir Dis 134:449-452 Damhuis RA, Schutte PR (1996) Resection rates and postop-

erative mortality in 7,899 patients with lung cancer. Eur Respir J 9:7-10

Dartevelle PG, Chapelier AR, Macchiarini P et al (1993) Ante- rior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet (see comment).

J Thorac Cardiovasc Surg 105:1025-1034

Datta D, Lahiri B (2003) Preoperative evaluation of patients undergoing lung resection surgery. Chest 123:2096-2103 Davies HM (1913) Recent advances in the surgery of the lung

and pleura. Br J Surg 1:228-231

DeCamp MM Jr, Jaklitsch MT, Mentzer SJ, Harpole DH Jr, Sug- arbaker DJ (1995) The safety and versatility of video-tho- racoscopy: a prospective analysis of 895 consecutive cases.

J Am Coll Surgeons 181:113-20

Demmy TL, Curtis JJ (1999) Minimally invasive lobectomy directed toward frail and high-risk patients: a case-control study. Ann Thorac Surg 68:194-200

Deneuville M, Regnard JF, Coggia M, Rojas-Miranda A, Dartevelle P, Levasseur P (1992) The place for bilobectomy in broncho- genic carcinoma. Eur J Cardio Thorac Surg 6:446-451 Deslauriers J, Ginsberg RJ, Dubois P, Beaulieu M, Goldberg M,

Piraux M (1989) Current operative morbidity associated with elective surgical resection for lung cancer. Can J Surg 32:335-339

Deslauriers J, Ginsberg RJ, Piantadosi S, Fournier B (1994) Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest 106:329S-330S Detterbeck FC, DeCamp MM Jr, Kohman LJ, Silvestri GA,

American College of Chest Physicians (2003) Lung cancer.

Invasive staging: the guidelines. Chest 123:167S-175S Detterbeck FC (1997) Pancoast (superior sulcus) tumors. Ann

Thorac Surg 63:1810-1818

Errett LE, Wilson J, Chiu RC, Munro DD (1985) Wedge resec- tion as an alternative procedure for peripheral broncho- genic carcinoma in poor-risk patients. J Thorac Cardiovasc Surg 90:656-661

Ferguson MK, Little L, Rizzo L et al (1988) Diffusing capacity predicts morbidity and mortality after pulmonary resec- tion. J Thorac Cardiovasc Surg 96:894-900

Fritsch A, Kokoschka R, Mach K (1975) Results of thoraco- scopic sympathectomy in hyperhidrosis of the upper extremities (author’s translation). Wiener Klein Wochen- schr 87:548-550

Gharagozloo F, Tempesta B, Margolis M, Alexander EP (2003) Video-assisted thoracic surgery lobectomy for stage I lung cancer. Ann Thorac Surg 76:1009-1014; discussion 1014-1015 Ginsberg RJ, Rubinstein LV (1995) Randomized trial of lobec- tomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group (see comment). Ann Thorac Surg 60:615-622; discussion 622-623

Ginsberg RJ, Hill LD, Eagan RT et al (1983) Modern thirty-day operative mortality for surgical resections in lung cancer. J Thorac Cardiovasc Surg 86:654-658

Ginsberg RJ, Rice TW, Goldberg M, Waters PF, Schmocker BJ (1987) Extended cervical mediastinoscopy. A single staging procedure for bronchogenic carcinoma of the left upper lobe. J Thorac Cardiovasc Surg 94:673-678

Ginsberg RJ, Vokes EE, Raben A (1997) Non-small cell lung cancer. In: Rosenberg SA (ed) Cancer: principles and prac- tice of oncology, vol 2. Lippincott, Philadelphia

Gossot D, Toledo L, Fritsch S, Celerier M (1996) Mediastinos- copy vs thoracoscopy for mediastinal biopsy. Results of a prospective nonrandomized study. Chest 110:1328-1331 Graham EA, Singer JJ (1933) Successful removal of the entire

lung for carcinoma of the bronchus. J Am Med Assoc 101:1371-1374

Gurney JW (1993) Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis, part I. Theory. Radiology 186:405-413

Gurney JW, Lyddon DM, McKay JA (1993) Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis, part II. Application. Radiology 186:415-422

Hannan EL, Radzyner M, Rubin D, Dougherty J, Brennan MF (2002) The infl uence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 131:6-15 Ichinose Y, Hara N, Ohta M et al (1989) Preoperative exami-

nation to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer.

Chest 96:1104-1109

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ (2003) Cancer statistics, 2003. Ca Cancer J Clin 53:5-26 Jensik RJ, Faber LP, Milloy FJ, Monson DO (1973) Segmental

resection for lung cancer. A fi fteen-year experience. J Thorac Cardiovasc Surg 66:563-572

Juhl B, Frost N (1975) A comparison between measured and calculated changes in the lung function after operation for pulmonary cancer. Acta Anaesthesiol Scand [Suppl] 57:39- 45

Kapsenberg PD (1981) Thoracoscopic biopsy under visual control. Poumon et Le Coeur 37:313-316

Kirby TJ, Rice TW (1993) Video-assisted pulmonary lobec- tomy. Semin Thorac Cardiovasc Surg 5:316-320

Kirby TJ, Mack MJ, Landreneau RJ, Rice TW (1995) Lobec- tomy–video-assisted thoracic surgery versus muscle-spar- ing thoracotomy. A randomized trial. J Thorac Cardiovasc Surg 109:997-1001; discussion 1001-1002

Knott-Craig CJ, Howell CE, Parsons BD, Paulsen SM, Brown BR, Elkins RC (1997) Improved results in the management of surgical candidates with lung cancer. Ann Thorac Surg 63:1405-1409; discussion 1409-1410

Kodama K, Doi O, Higashiyama M, Yokouchi H (1997) Inten- tional limited resection for selected patients with T1 N0 M0 non-small-cell lung cancer: a single-institution study. J Thorac Cardiovasc Surg 114:347-353

Kopp C, Perruchoud A, Schwander R, Herzog H (1979) Thora- coscopy as a diagnostic and therapeutic precaution in lung and pleural diseases. Schweiz Med Wochenschr / J Suisse Med 109:478-480

Kramer H, Groen HJ (2003) Current concepts in the mediasti- nal lymph node staging of nonsmall cell lung cancer. Ann Surg 238:180-188

Landreneau RJ, Hazelrigg SR, Mack MJ et al (1993a) Thora- coscopic mediastinal lymph node sampling: useful for mediastinal lymph node stations inaccessible by cervical mediastinoscopy. J Thorac Cardiovasc Surg 106:554-558 Landreneau RJ, Hazelrigg SR, Mack MJ et al (1993b) Postop-

erative pain-related morbidity: video-assisted thoracic sur- gery versus thoracotomy. Ann Thorac Surg 56:1285-1289 Landreneau RJ, Sugarbaker DJ, Mack MJ et al (1997) Wedge

resection versus lobectomy for stage I (T1 N0 M0) non-

small-cell lung cancer. J Thorac Cardiovasc Surg 113:691- 698; discussion 698-700

Lardinois D, Weder W, Hany TF et al (2003) Staging of non- small-cell lung cancer with integrated positron-emission tomography and computed tomography (see comment). N Engl J Med 348:2500-2507

Lewis RJ, Caccavale RJ, Bocage JP, Widmann MD (1999) Video- assisted thoracic surgical non-rib spreading simultane- ously stapled lobectomy: a more patient-friendly oncologic resection. Chest 116:1119-1124

Linden PA, Jaklitsch MT, Bueno R, Chang M, Colson YL, Lukanich JM, Mentzer SJ, Sugarbaker DJ (2004) Lung tumor resection in patients with severely compromised lung func- tion with low mortality or major morbidity. American Jour- nal of Respiratory and Critical Care Medicine. 169:A341 Luke WP, Pearson FG, Todd TR, Patterson GA, Cooper JD

(1986) Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 91:53-56

Luketich JD, Burt ME (1996) Does resection of adrenal metas- tases from non-small cell lung cancer improve survival?

Ann Thorac Surg 62:1614-1616

Magilligan DJ Jr, Duvernoy C, Malik G, Lewis JW Jr, Knighton R, Ausman JI (1986) Surgical approach to lung cancer with solitary cerebral metastasis: twenty-fi ve years’ experience.

Ann Thorac Surg 42:360-364

Martin J, Ginsberg RJ, Abolhoda A et al (2001) Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy. Ann Thorac Surg 72:1149- 1154

McKenna RJ Jr (1998) The current status of video-assisted tho- racic surgery lobectomy. Chest Surg Clin North Am 8:775- 785, viii; discussion 787-788

McKenna RJ Jr, Wolf RK, Brenner M, Fischel RJ, Wurnig P (1998) Is lobectomy by video-assisted thoracic surgery an adequate cancer operation? Ann Thorac Surg 66:1903-1908

McNeill TM, Chamberlain JM (1966) Diagnostic anterior mediastinotomy. Ann Thorac Surg 2:532-539

Miller JI, Grossman GD, Hatcher CR (1981) Pulmonary func- tion test criteria for operability and pulmonary resection.

Surg Gynecol Obstet 153:893-895

Morgan JA, Ginsburg ME, Sonett JR, Argenziano M, Walker WS (2003) Thoracoscopic lobectomy using robotic technology.

Heart Surg Forum 6:233-244

Morikawa T, Katoh H, Takeuchi E, Ohbuchi T (1998) Tech- nical feasibility of video-assisted lobectomy with radical lymphadenectomy for primary lung cancer. Surg Laparosc Endosc 8:466-473

Mountain CF (1997) Revisions in the international system for staging lung cancer (comment). Chest 111:1710-1717 Mountain CF, Dresler CM (1997) Regional lymph node clas-

sifi cation for lung cancer staging (see comment). Chest 111:1718-1723

Myrdal G, Gustafsson G, Lambe M, Horte LG, Stahle E (2001) Outcome after lung cancer surgery. Factors predicting early mortality and major morbidity. Eur J Cardio Thorac Surg 20:694-699

Naruke T, Suemasu K, Ishikawa S (1978) Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg 76:832-839

Ohbuchi T, Morikawa T, Takeuchi E, Kato H (1998) Lobectomy:

video-assisted thoracic surgery versus posterolateral tho- racotomy. Jpn J Thorac Cardiovasc Surg 46:519-522

Oldenburg FA Jr, Newhouse MT (1979) Thoracoscopy. A safe, accurate diagnostic procedure using the rigid thoracoscope and local anesthesia. Chest 75:45-50

Ost D, Fein AM, Feinsilver SH (2003) Clinical practice. The solitary pulmonary nodule (see comment). N Engl J Med 348:2535-2542

Park BJ, Flores R, Downey RJ, Bains MS, Rusch VW (2003) Management of major hemorrhage during mediastinos- copy. J Thorac Cardiovasc Surg 126:726-731

Parkin DM, Pisani P, Ferlay J (1999) Estimates of the world- wide incidence of 25 major cancers in 1990. Int J Cancer 80:827-841

Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153-156 Patchell RA, Tibbs PA, Walsh JW et al (1990) A randomized

trial of surgery in the treatment of single metastases to the brain (see comment). N Engl J Med 322:494-500

Piehler J, Pairolero P, Weiland L et al (1982) Bronchogenic car- cinoma with chest wall invasion: factors affecting survival following en bloc resection. Ann Thorac Surg 34:684-691 Porte H, Siat J, Guibert B et al (2001) Resection of adrenal

metastases from non-small cell lung cancer: a multicenter study. Ann Thorac Surg 71:981-985

Putnam JB (2001) Lung (including pulmonary embolism and thoracic outlet syndrome). In: Townsend CM (ed) Sabis- ton textbook of surgery, 16th edn. Saunders, Philadelphia, chap 55

Reed MF, Sugarbaker DJ (1996) Mediastinal staging of lung cancer. In: Pass HI (ed) Lung cancer: principles and practice.

Lippincott-Raven, Philadelphia, xviii, 982, [8] of plates Rodgers BM, Moazam F, Talbert JL (1979) Thoracoscopy. Early

diagnosis of interstitial pneumonitis in the immunologi- cally suppressed child. Chest 75:126-130

Rusch VW, Parekh KR, Leon L et al (2000) Factors determin- ing outcome after surgical resection of T3 and T4 lung cancers of the superior sulcus. J Thorac Cardiovasc Surg 119:1147-1153

Shaw RR, Paulson DL, Kee JL (1961) Treatment of the supe- rior sulcus tumor by irradiation followed by resection. Ann Surg 154:29-40

Silvestri GA, Tanoue LT, Margolis ML, Barker J, Detterbeck F, American College of Chest Physicians (2003) The noninva- sive staging of non-small cell lung cancer: the guidelines.

Chest 123:147S-156S

Stephan F, Boucheseiche S, Hollande J et al (2000) Pulmonary complications following lung resection: a comprehen- sive analysis of incidence and possible risk factors. Chest 118:1263-1270

Sugarbaker DJ, Swanson SJ, Shen RK (2001) Pulmonary resec- tion. In: Fischer JE (ed) Mastery of surgery, vol 2. Lippincott Williams and Wilkins, Philadelphia, xxxi, 2223, 73 Sugi K, Kaneda Y, Esato K (2000) Video-assisted thoracoscopic

lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer. World J Surg 24:27-30; discussion 30-31

Takizawa T, Terashima M, Koike T et al (1998) Lymph node metastasis in small peripheral adenocarcinoma of the lung.

J Thorac Cardiovasc Surg 116:276-280

Tanaka K, Kubota K, Kodama T, Nagai K, Nishiwaki Y (1999)

Extrathoracic staging is not necessary for non-small-cell lung cancer with clinical stage T1-2 N0. Ann Thorac Surg 68:1039-1042

Tatsumi A, Ueda Y (2003) Video-assisted thoracic surgery for lung cancer: is it a feasible operation for stage I lung cancer? Jpn J Thorac Cardiovasc Surg 51:646-650

Toloza EM, Harpole L, McCrory DC (2003a) Noninvasive stag- ing of non-small cell lung cancer: a review of the current evidence. Chest 123:137S-146S

Toloza EM, Harpole L, Detterbeck F, McCrory DC (2003b) Invasive staging of non-small cell lung cancer: a review of the current evidence. Chest 123:157S-166S

Tovar EA, Roethe RA, Weissig MD, Lloyd RE, Patel GR (1998) One-day admission for lung lobectomy: an incidental result of a clinical pathway. Ann Thorac Surg 65:803-806 Tschernko EM, Hofer S, Bieglmayer C, Wisser W, Haider W

(1996) Early postoperative stress: video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy.

Chest. 109:1636-1642

Walker WS, Carnochan FM, Tin M (1993) Thoracoscopy assisted pulmonary lobectomy. Thorax 48:921-924

Walker WS, Pugh GC, Craig SR, Carnochan FM (1996) Con- tinued experience with thoracoscopic major pulmonary resection. Int Surg 81:255-258

Walker WS, Codispoti M, Soon SY, Stamenkovic S, Carnochan F, Pugh G (2003) Long-term outcomes following VATS lobectomy for non-small cell bronchogenic carcinoma. Eur J Cardio Thorac Surg 23:397-402

Warren WH, Faber LP (1994) Segmentectomy versus lobec- tomy in patients with stage I pulmonary carcinoma. Five- year survival and patterns of intrathoracic recurrence. J Thorac Cardiovasc Surg 107:1087-1093; discussion 1093- 1094

Webb WR, Gatsonis C, Zerhouni EA et al (1991) CT and MR imaging in staging non-small cell bronchogenic carcinoma:

report of the Radiologic Diagnostic Oncology Group. Radi- ology 178:705-713

Weng E, Tran L, Rege S et al (2000) Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol 23:47-52

Wernly JA, DeMeester TR, Kirchner PT, Myerowitz PD, Oxford DE, Golomb HM (1980) Clinical value of quantitative ven- tilation-perfusion lung scans in the surgical management of bronchogenic carcinoma. J Thorac Cardiovasc Surg 80:535-543

Wright CD, Menard MT, Wain JC et al (2002) Induction chemo- radiation compared with induction radiation for lung cancer involving the superior sulcus. Ann Thorac Surg 73:1541-1544

Wright CD, Wain JC, Grillo HC, Moncure AC, Macaluso SM, Mathisen DJ (1997) Pulmonary lobectomy patient care pathway: a model to control cost and maintain quality. Ann Thorac Surg 64:299-302

Yano T, Yokoyama H, Fukuyama Y, Takai E, Mizutani K, Ichi- nose Y (1997) The current status of postoperative compli- cations and risk factors after a pulmonary resection for primary lung cancer. A multivariate analysis. Eur J Cardio Thorac Surg 11:445-449