Esophageal cancer is one of the most malignant tumors,

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1 Patterns of Lymph Node Metastasis and Survival for Upper Esophageal Squamous Cell Carcinoma Hee-Jin Jang, MD,* Hyun-Sung Lee, MD, PhD,* Moon Soo Kim, MD, Jong Mog Lee, MD, and Jae Ill Zo, MD, PhD Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea Background. This study evaluated the clinical results, nodal metastatic patterns, and overall efficacy of esophagectomy with three-field lymph node dissection for upper esophageal squamous cell carcinoma (SCC). Methods. Between 2001 and 2008, esophagectomy was performed in 497 esophageal cancer patients, of whom 93 underwent esophagectomy with three-field lymph node dissection, without neoadjuvant treatment for upper esophageal SCC. Results. Of these 93 patients, 91 (97.8%) were men, the median age was 65.0 years, and 82 (88.2%) underwent R0 resection with curative intent. In-hospital mortality was 4.3%. PathologicTNMstages were stage I, 8.6%; stage II, 16.1%; stage III, 75.3%; and stage IV, 0%. The mean numbers of total lymph nodes dissected and, of those, total metastatic lymph nodes per patient were and , respectively. Metastases occurred to the recurrent laryngeal lymph nodes in 43.3%, to the cervical lymph nodes in 46.2%, and to abdominal lymph nodes in 24.7% of patients. Overall 5-year and disease-free survival rates were 43.5% and 34.3%, respectively, and were 50.1% and 37.6%, respectively, for R0 resection. Conclusions. Recurrent laryngeal lymph node chains are those most commonly affected by nodal metastasis, and the prevalence of cervical lymph node involvement is high, at more than 40%. Esophagectomy with threefield lymph node dissection in patients with upper esophageal SCC can be performed with acceptable morbidity and mortality. Curative R0 resection for upper esophageal SCC achieved a satisfactory 5-year survival rate. (Ann Thorac Surg 2011;92:1091 8) 2011 by The Society of Thoracic Surgeons Accepted for publication March 21, *Hee-Jin Jang and Hyun-Sung Lee equally contributed to this article. Address correspondence to Dr Zo, Center for Lung Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu Goyang-si, Gyeonggi-do , Republic of Korea; jaylzo@ncc.re.kr. Esophageal cancer is one of the most malignant tumors, and despite improvements in treatment, its prognosis remains disappointing. Recent reports on the long-term results of chemoradiation therapy have been positive [1 3], but radical resection with extended lymph node dissection remains the mainstay treatment for resectable esophageal cancer. Although the long-term survival rate associated with esophageal cancer remains approximately 15% worldwide [4], or below 30% [5 7] in Western countries, some recent reports have claimed improvements in 5-year survival rates of 40% or more [8 13]. However, upper thoracic esophageal cancer still carries a poor prognosis [14 16], and many surgeons consider its prognosis to be poorer than the prognoses of middle and lower thoracic esophageal cancers [17] due to its anatomic position and tendency for early lymphatic metastasis. Several surgeons have made efforts to improve the surgical results of esophageal cancer. In particular, extended esophagectomy with three-field lymph node dissection (3FLND) has been performed in Japan to enable accurate staging with a view toward improving surgical results [18 22]. However, 3FLND remains controversial, with available evidence insufficient to make recommendations regarding the role of 3FLND in upper esophageal cancer [23]. We performed 3FLND in upper esophageal squamous cell carcinoma (SCC) because cervical lymph node metastasis is commonly present in these patients [24, 25]. The relative rarity of upper esophageal cancer has meant that few reports are available on treatment outcomes. Thus, we initiated this retrospective study to evaluate the clinical results and nodal metastatic patterns after esophagectomy with 3FLND for upper esophageal SCC and to determine the overall efficacy of 3FLND. Patients and Methods This retrospective observational study was approved by the Institutional Review Board of the National Cancer Center Korea (No. NCCNCS ), and agreed to waive informed consent due to the retrospective study. We initially evaluated 497 patients with esophageal cancer who underwent esophagectomy with lymph node dissection from 2001 to 2008 at the National Cancer Center Korea. Of the 117 patients with upper thoracic esophageal cancer, 108 were diagnosed pathologically with SCC. We excluded 6 patients who received neoadjuvant treatment and 9 who underwent conventional lymph node dissection. The study cohort comprised the remaining 93 patients who underwent esophagectomy with 3FLND for upper esophageal SCC by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 1092 JANG ET AL Ann Thorac Surg 3FLND FOR UPPER ESOPHAGEAL CANCER 2011;92: Preoperative evaluations included routine blood examination, esophagogastroduodenoscopy with biopsy, endoscopic ultrasonography, chest and abdominal computed tomography (CT), pulmonary function test, electrocardiography, positron emission tomography (PET)-CT, bronchoscopy, and, if necessary, cardiac function testing. When stomach was unavailable for an esophageal replacement conduit, mesenteric arterial angiography and a colonoscopy were also performed. Upper esophageal cancer was diagnosed when the proximal margin was located 20 to 25 cm from an upper incisor, as measured by esophagoscopy. 3FLND was routinely performed in patients with upper thoracic esophageal cancer, with the exception of those with poor performance status or serious comorbidity. Surgical Approach All patients underwent esophagectomy through a right thoracotomy, median laparotomy, and bilateral cervical U-shaped incisions. The stomach was used as the conduit in 92 patients, and the colon was used as the conduit in 1 patient who had previously undergone a gastric operation. The conduit was pulled up through a posterior mediastinal route. Anastomotic sites were selected according to the tumor location. A cervical anastomosis was performed when the proximal tumor margin was located above 22 to 23 cm from an upper incisor by endoscopy. A cervical anastomosis was performed using a circular stapler or a modification of the Orringer method. When the proximal margin was located below 22 to 23 cm from an upper incisor, an intrathoracic anastomosis could be performed using a circular stapler at the level of the highest thoracic inlet. The anastomosis was performed at the level of the thoracic inlet in 57 patients and at the left side of the neck in the remaining 36. During the operation for upper esophageal SCC, direct invasion of adjacent organs, including the tracheobronchial tree or aorta by a tumor or metastatic lymph node, was found in 11.8% of patients, although the preoperative evaluations revealed no evidence of adjacent organ invasion. A palliative esophagectomy and 3FLND was performed in these patients as originally planned to improve oral dietary intake and to reduce the tumor burden before definitive chemoradiotherapy or radiotherapy. Lymph nodes were retrieved from surgical specimens, assigned a location number, fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin. Lymph nodes were classified as cervical, thoracic, or abdominal. All 93 patients were extubated in the operating room immediately after the operation and remained in intensive care for 1 day. Adjuvant chemotherapy was performed in patients with pathologic stage II or higher and with an Eastern Cooperative Oncology Group performance status of 0 or 1. Adjuvant radiotherapy was performed in patients who underwent palliative resection. Follow-Up The median follow-up for the 93 patients in the cohort was 25.0 months (range, 0.6 to 93.1 months). Follow-up was conducted by telephone or mail twice a year, during the months of April and October. Survival time was defined as the time elapsed between the operation and death or between the operation and the most recent follow-up. A gastric emptying study and chest CT were routinely performed during the first follow-up after discharge. All patients were regularly seen at 3-month intervals for the first 2 years; a routine blood examination, chest roentgenogram, and chest CT were performed on these occasions. Subsequently, all patients were monitored annually. PET-CT and esophagogastroduodenoscopy were performed annually or more frequently if required by clinical history and clinical examination findings. Local recurrence was defined as recurrence at the anastomotic site, regional recurrence was defined as recurrence at any site within the operative field, and systemic recurrence was defined as recurrence at any site outside the operative field. Statistics The clinicopathologic data analyzed included curative and palliative resection data, survival analysis was performed using the Kaplan-Meier method for patients who underwent curative R0 resection, and intergroup survival comparisons were performed using the log-rank test. Statistical significance was accepted for values of p All statistical analyses were performed using STATA 11.0 software (StataCorp, College Station, TX). In-hospital mortality was included in the survival analysis. To evaluate the effect of various clinicopathologic parameters on long-term survival, univariate analysis was used to identify potential prognostic factors. Identified factors underwent multiple stepwise regression analysis using a Cox regression model. Results Clinicopathologic Characteristics Of the 93 study subjects, 91 were men, the patients were a median age of 65 years (range, 44 to 93 years), and 82 (88.2%) underwent R0 resection with curative intent. The most common esophageal reconstructive procedure adopted was gastric pullup through a posterior mediastinal route. Concurrent adenocarcinoma of the stomach was found in 6 patients, of whom 5 underwent gastric mucosal resection, and 1 underwent total gastrectomy and esophago-colo-jejunostomy. Clinicopathologic characteristics are summarized in Table 1. Adjuvant chemotherapy was administered to 18 patients, and 11 patients underwent radiotherapy. Patterns of Lymph Node Metastasis A total of 5740 lymph nodes were dissected. Mean numbers of lymph nodes and metastatic lymph nodes dissected per patient were and ,

3 Ann Thorac Surg JANG ET AL 2011;92: FLND FOR UPPER ESOPHAGEAL CANCER 1093 respectively. Frequencies and patterns of nodal metastasis are illustrated in Figure 1. The rate of positive nodal metastasis was found to increase gradually with T status (p 0.01, Kruskal-Wallis). Cervical lymph node metastasis was present in 43 patients (46.2%), recurrent laryngeal lymph node chain involvement in 44 (47.3%), and abdominal lymph node metastasis in 23 (24.7%). The mediastinum (74.2%) was most affected, followed by the cervical lymph nodes (46.2%). Lymph node metastasis was confined to one field in 44 patients (47.3%), to two fields in 26 (28.0%), and was in three fields in 2. The rate of regional lymph node metastasis alone in the cohort was 44% (41 patients), and that of cervical nodal involvement alone, without other lymph node metastasis, was 8.6% (8 patients). The mean number of metastatic cervical lymph nodes per patient was Postoperative Mortality and Morbidity Three postoperative deaths occurred within 30 days of the operation for a 30-day mortality rate of 3.2%. The in-hospital death rate was 4.3% (4 patients). Causes of death were postoperative acute respiratory distress syndrome in 2 patients and postoperative sepsis due to a tracheal-pleural fistula in 1. In addition, 1 patient died of pneumonia and sepsis on postoperative day 37. Postoperative complications occurred in 65 patients Table 1. Clinicopathologic Characteristics Variable No. (%) Male sex 91 (97.8) Tumor differentiation Well 3 (3.2) Moderate 76 (81.7) Poor 14 (15.1) Pathologic T status T1 15 (16.1) T2 10 (10.8) T3 57 (61.3) T4a 2 (2.2) T4b 9 (9.7) Pathologic N status N0 21 (22.6) N1 21 (22.6) N2 33 (35.5) N3 18 (19.4) Pathologic TNMstage IA 1 (1.1) IB 7 (7.5) IIA 0 (0) IIB 15 (16.1) IIIA 22 (23.7) IIIB 21 (22.6) IIIC 27 (29.0) IV 0 (0) Fig 1. Patterns of nodal metastasis are shown in patients who underwent three-field lymph node dissection for upper esophageal squamous cell carcinoma. Cervical lymph node metastasis was present in 43 patients (46.2%), the recurrent laryngeal lymph node chain was involved in 44 (47.3%; right side in 32, left side in 26), and abdominal lymph node metastasis was present in 23 (24.7%). Subcarinal lymph node metastasis was present in 14 patients, and supraclavicular lymph nodes were involved in 24. Cervical paraesophageal, deep cervical, and supraclavicular lymph nodes were involved in 25, 6, and 17 patients with a right-sided tumor and in 11, 5, and 14 patients with a left-sided tumor, respectively. The common hepatic, celiac, lesser curvature, and cardiac lymph nodes were involved in 2, 2, 12, and 10 patients, respectively. LN lymph node; RLN recurrent laryngeal nerve. (69.9%) and are listed in Table 2. The most common were pulmonary complications (35.5%) and vocal cord paralysis (35.5%). Vocal cord paralysis developed in 33 patients (35.5%). Recurrent laryngeal nerves were sacrificed in 14 patients during the operation due to the direct tumor Table 2. Postoperative Complications Variable No. (%) Medical Pulmonary complication 33 (35.5) Supraventricular 5 (5.4) tachycardia Acute renal failure 3 (3.2) Pleural effusion, chest tube 6 (6.5) required Empyema 1 (1.1) Sepsis 3 (3.2) Surgical Leakage at anastomotic site 11 (11.8) Vocal cord paralysis 33 (35.5) Unilateral 23 (24.7) Bilateral 10 (10.8) Chylothorax 2 (2.2) Wound problem 5 (5.4) Persistent air leakage 3 (3.2) Graft failure 1 (1.1)

4 1094 JANG ET AL Ann Thorac Surg 3FLND FOR UPPER ESOPHAGEAL CANCER 2011;92: Fig 2. (A) Overall survival and (B) diseasefree survival for curative (solid line) and palliative (dashed line) resection. invasion or extranodal invasion of recurrent laryngeal nerve chains. Of the 10 patients (10.8%) with bilateral vocal cord paralysis, pneumonia developed in 7, and 5 underwent tracheostomy. Pneumonia developed in 7 of the 23 patients (24.7%) with unilateral paralysis, and a tracheostomy was required. Vocal cord paralysis improved or resolved at a mean 5.4 months postoperatively in 14 patients (8 patients with unilateral and 6 with bilateral vocal cord paralysis). Patterns of Recurrence Locoregional recurrence developed in 24 patients (25.8%), distal metastases developed in 24 (25.8%), and locoregional recurrence and distal metastases both developed in 13 (14.0%). Local recurrence at the anastomotic site was found in only 1 patient. Locoregional recurrence developed at the paratracheal lymph nodes in 10 patients: 7 at the gastric lymph nodes in the intrathoracic stomach and 3 at the cervical lymph nodes. Of the 24 patients with distant metastases, pulmonary metastasis developed in 14 and liver metastases developed in 7. Survival The median follow-up was 25.0 month. The overall 5-year survival rate was 43.5%, with a median survival of 32.0 months. The disease-free survival rate was 34.3%, and the median disease-free survival time was 15.7 months. In the subset of 82 patients who underwent R0 resection, the 5-year and disease-free survival rates were 50.1% and 37.6%, respectively (Fig 2). For the 82 patients who underwent R0 resection, the overall 5-year and disease-free survival rates were significantly associated with TNMstatus (p and p 0.001, respectively; Fig 3). Significant predictors of overall survival after R0 resection by univariate analysis were T N M classification (p 0.001), depth of tumor invasion (T stage; p 0.015), regional lymph node metastasis (N stage; p 0.001), presence of a postoperative pulmonary complication (p 0.003), postoperative pleural effusion requiring an additional chest tube insertion (p 0.003), and postoperative sepsis (p 0.001). However, tumor grade, vocal cord Fig 3. (A) Overall and (B) disease-free survival by stage I (solid line), stage II (dashed line), and stage III (dotted line) after R0 resection.

5 Ann Thorac Surg JANG ET AL 2011;92: FLND FOR UPPER ESOPHAGEAL CANCER 1095 Table 3. Univariate and Multivariate Analysis of Overall Survival by Cox Regression Analysis Variables Univariate p Value Analysis Multivariate OR (95% CI) p Value Sex Age Pulmonary ( ) complication Vocal cord paralysis Cardiac complication Anastomotic leakage Pleural effusion ( ) Chylothorax Sepsis ( ) T stage ( ) N stage ( ) Grade ( ) CI confidence interval; OR odds ratio. paralysis, and adjuvant treatment were not found to influence overall survival. Multivariate analysis using a Cox proportional hazard model revealed the development of a postoperative pulmonary complication or sepsis and regional lymph node metastasis (N stage) to be independent risk factors of poorer survival (Table 3). In the 63 patients with lymph node metastasis who underwent R0 resection, 5-year and disease-free survival rates were 44.4% and 31.1%, respectively, for the 23 patients without cervical metastasis, and were 29.8% and 22.0%, respectively, for the 38 patients with cervical nodal metastasis. However, cervical nodal metastasis did not influence these rates in patients with lymph node metastasis who underwent R0 resection (p and p 0.270, respectively; Fig 4). Comment Cervical and upper thoracic esophageal cancers are considered to be the most aggressive because these tumors often involve adjacent structures, such as the airway, aortic arch, or the recurrent laryngeal nerve, which often prevents the complete excision of locally advanced tumors. Kato and colleagues [17] reported that patients with esophageal cancer above the carina had a significantly poorer survival curve than those with cancer below the carina. They also reported a 5-year survival rate after 3FLND curative or palliative procedures of 44.5% for patients with esophageal cancer above the carina. Shimada and colleagues [26] evaluated patients with upper thoracic esophageal SCC and found a 5-year survival rate of 35% after 3FLND. The 93 patients in the present study had an overall 5-year survival rate of 44%, which was comparable with the results of studies in Japan on the curative resection of upper esophageal SCC. Akiyama and colleagues [18] reported the frequencies of cervical and abdominal lymph node metastasis in Fig 4. (A) Overall survival and (B) disease-free survival stratified by the presence of cervical lymph node metastasis among patients with lymph node metastasis after R0 resection.

6 1096 JANG ET AL Ann Thorac Surg 3FLND FOR UPPER ESOPHAGEAL CANCER 2011;92: upper esophageal cancer to be 46.3% and 12.2%, respectively, whereas cervical lymph node metastasis in patients with middle or lower esophageal cancer was approximately 30% [18]. In addition, they found the frequency of cervicothoracic lymph node metastasis, particularly in recurrent nerve lymphatic chains, to be much higher in upper esophageal cancer than in middle or lower esophageal cancer. Chen and colleagues [27] analyzed the frequency of lymphatic spread in esophageal SCC by tumor location and found that 49.5% of the 289 patients with upper esophageal cancer had cervical lymph node metastasis and 8% had abdominal lymph node metastasis. In upper esophageal SCC, predominant lymph node metastasis occurred above carina in 76.9%, above and below carina in 20.4%, and below carina in 2.7%. In the present study, the cervical lymph node metastasis rate was comparable with rates reported previously, whereas the abdominal lymph node metastasis rate was higher than in other reports. This finding shows that lymph node metastasis can occur in any direction and that cervical lymph node metastasis is common in upper esophageal cancer. Altorki and colleagues [24] reported that the frequency of cervicothoracic node metastasis is influenced by nodal status within the abdomen or mediastinum, or both. Recurrent lymph node involvement also appears to be significantly associated with the presence of cervical node metastasis. Therefore, assessments of recurrent nerve node metastasis may be useful for predicting cervical node metastasis and for determining the need for 3FLND [12]. Most Japanese surgeons, however, determine the need for 3FLND preoperatively, because the presence or absence of nodal micrometastasis in recurrent laryngeal nerve nodes cannot be accurately determined, even using intraoperative frozen sections. However, Tachibana and colleagues [28] reported that no patient with cervicothoracic nodal involvement alone had lower thoracic esophageal carcinoma [28]. These results indicate that 3FLND is necessary in patients with esophageal cancer located in the upper mediastinum. In our study, recurrent laryngeal nerve lymph node metastasis did not correlate with cervical node involvement, and 8 patients (8.6%) had cervical nodal involvement without any other form of lymph node metastasis. Furthermore, our survival analysis among patients with lymph node metastasis showed no significant difference between those with and those without cervical lymph node involvement, suggesting that cervical lymph nodes should be regarded as regional lymph nodes and that cervical lymph node dissection should be included in standard lymph node dissection for upper esophageal squamous cell carcinoma. In the seventh edition of the American Joint Committee on Cancer (AJCC) staging system for esophageal cancer [29], N stage is subclassified according to the number of regional lymph nodes containing metastasis, and regional lymph nodes are defined as extending from periesophageal cervical nodes to celiac nodes. Our study supports this revision of the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Lymph node dissection in esophageal cancer was first advocated in the 1960s [30], but many surgeons avoid extensive lymph node dissection because of the risks of surgical and postoperative complications. Igaki and colleagues [20] evaluated the outcomes of 2FLND and 3FLND in patients with lower thoracic SCC. Operative morbidity was 68.0% and in-hospital mortality was 2.6%, and the most common postoperative complication after 3FLND was anastomotic leakage (39%), followed by vocal cord palsy (9%), pneumonia (8%), and wound infection (8%). Fujita and colleagues [31] reported surgical outcomes according to the extent of lymph node dissection for potentially resectable SCC in the thoracic esophagus and observed recurrent nerve paralysis in 122 patients (69%) who underwent transthoracic esophagectomy with 3FLND. The incidence of recurrent nerve paralysis was significantly higher after more radical lymph node dissections. Tachibana and colleagues [28] observed that recurrent laryngeal nerve paralysis developed in 40 patients (28.4%) after 3FLND, including 7 patients with bilateral nerve paralysis and 33 with unilateral nerve paralysis. In the present study, postoperative complications, such as pulmonary problems and vocal cord palsy, seemed to be high at over 30%. However, this study enrolled only patients with upper esophageal cancer. Table 1 reports the prevalence of T3/T4 lesions exceeded 70% and more than 70% of patients had stage III cancers. Esophageal operations for advanced tumors must overcome high postoperative morbidity. During the procedure, the location of the tumor makes it very difficult to save the bronchial artery, the pulmonary branch of the vagus nerve, and the recurrent laryngeal nerves. The sacrifice of these anatomic structures is associated with a higher rate of postoperative complications. Despite a high rate of postoperative complications, however, this study had an acceptable postoperative mortality rate, and the 5-year overall survival of stage III tumors exceeded 30%. Improving postoperative care can help us confront this aggressive tumor and prolong patient survival. We have recently used vocal cord injections to treat unilateral vocal cord paralysis by fixing the paralyzed vocal cord to the median. In summary, nodal metastasis is most prevalent in recurrent laryngeal lymph node chains, and the prevalence of cervical node involvement is high ( 40%). These results suggest 3FLND to be a prerequisite for the accurate staging of esophageal SCC. In the present study, overall survival after curative R0 resection with 3FLND for upper esophageal SCC reached 50%, which is comparable with previously reported survival rates. Furthermore, esophagectomy with 3FLND for upper esophageal SCC can be performed with acceptable morbidity and mortality. This study also supports the notion that cervical lymph nodes should be regarded as the regional lymph nodes affected in upper esophageal SCC.

7 Ann Thorac Surg JANG ET AL 2011;92: FLND FOR UPPER ESOPHAGEAL CANCER 1097 References 1. Bedenne L, Michel P, Bouche O, et al. Randomized phase III trial in locally advanced esophageal cancer: radiochemotherapy followed by surgery versus radiochemotherapy alone (FFCD 9102)[Abstract]. Proc Am Soc Clin Oncol Proc Am Soc Clin Oncol 21: Shitara K, Muro K. Chemoradiotherapy for treatment of esophageal cancer in Japan: current status and perspectives. Gastroint Cancer Res 2009;3: Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005;23: Jemal A, Siegel R, Ward E, et al. Cancer statistics, CA Cancer J Clin 2008;58: Ellis F, Heatley G, Krasna M, Williamson W, Balogh K. Esophagogastrectomy for carcinoma of the esophagus and cardia: a comparison of findings and results after standard resection in three consecutive eight-year intervals with improved staging criteria. 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Am J Surg 2005;189: Edge S, Byrd D, Carducci M, Compton C. AJCC cancer staging manual. New York, NY: Springer; Logan A. The surgical treatment of carcinoma of the esophagus and cardia. J Thorac Cardiovasc Surg 1963;46: Fujita H, Sueyoshi S, Tanaka T, et al. Optimal lymphadenectomy for squamous cell carcinoma in the thoracic esophagus: comparing the short-and long-term outcome among the four types of lymphadenectomy. World J Surg 2003;27: INVITED COMMENTARY The authors [1] present excellent surgical results in a selected patient cohort with a preponderance of locallyadvanced squamous cell cancers of the upper thoracic esophagus. Given that there is waning interest in treating these types of patients with up-front surgery, and some institutions omit surgery completely, evidence that longterm survival can be achieved in a significant percentage of patients with this treatment paradigm is welcome. This manuscript emphasizes some important points. Regional lymph nodes are contained within cervical and recurrent laryngeal nerve (RLN) chains for upper thoracic tumors and, therefore, should be considered when planning treatment. Secondly, aggressive surgery is capable of delivering locoregional control and reasonable survival results in patients with high thoracic esophageal cancers. In fact, these results are similar to previous publications indicating that selected patients with intermediate-stage adenocarcinoma or squamous histol by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur