Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus

Transcription

1 ANNALS OF SURGERY Vol. 236, No. 2, Lippincott Williams & Wilkins, Inc. Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus Nasser Altorki, MD, Michael Kent, MD, Cathy Ferrara, RN, and Jeffrey Port, MD From the Division of General Thoracic Surgery, Weill Medical College, Cornell University, New York, New York Objective To determine the prevalence of occult cervical nodal metastases in patients with squamous cell cancer and adenocarcinoma of the esophagus, and to determine the impact of esophagectomy with three-field lymph node dissection on survival and recurrence rates. Summary Background Data Although esophagectomy with three-field lymph node dissection is commonly practiced in Japan, its role in the surgical management of esophageal cancer in the United States, especially in patients with esophageal adenocarcinoma, is essentially unknown. Methods This is a prospective observational study of esophagectomy with three-field lymphadenectomy. Eighty patients underwent resection between August 1994 and April Clinicopathological information and follow-up data were collected on all patients until death or June Results Hospital mortality and morbidity rates were 5% and 46%, respectively. Metastases to the recurrent laryngeal and/or deep cervical nodes occurred in 36% of patients irrespective of cell type (adenocarcinoma 37%, squamous 34%) or location within the esophagus (lower third 32%, middle third 60%). Overall 5-year and disease-free survival rates were 51% and 46%, respectively. Sixty-nine percent presented with nodal metastases. The 5-year survival rate for node-negative patients was 88%; that for those with nodal metastases was 33%. The 5-year survival rate in patients with positive cervical nodes was 25% (squamous 40%, adenocarcinoma 15%). Conclusions Esophagectomy with three-field lymph node dissection can be performed with a low mortality and reasonable morbidity. Unsuspected metastases to the recurrent laryngeal and/or cervical nodes are present in 36% of patients regardless of cell type or location within the esophagus. Thirty percent of patients were upstaged, mainly from stage III to stage IV. An overall 5-year survival rate of 51% suggests a true survival benefit beyond that achieved solely on the basis of stage migration. Correspondence: Nasser K. Altorki, MD, Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY nkaltork@med.cornell.edu Accepted for publication January 25, DOI: /01.SLA F4 Three-field lymph node dissection (TFD) for carcinoma of the esophagus has been practiced by Japanese surgeons since the early 1980s. 1,2 This effort was prompted by reports that as many as 40% of patients with squamous cell cancer of the esophagus developed isolated cervical nodal metastases following a presumed curative resection. 3 Nearly a decade later, a nationwide Japanese study reported the results of TFD performed at 35 institutions throughout Japan for squamous cell cancer of the esophagus. 4 Approximately one third of patients harbored previously unsuspected metastases to the cervical nodes. Furthermore, the authors reported an improvement in 5-year survival following TFD in comparison to esophagectomy with two-field dissection. These reports were greeted with some skepticism in Europe and in North America. 5 Foremost among the expressed concerns were the unacceptably high rates of recurrent nerve injuries (approaching 70% in some series) as well as the relevance of these findings to a Western patient popu- 177

2 178 Altorki and Others Ann. Surg. August 2002 lation, in whom adenocarcinoma rather than squamous cell carcinoma remains the predominant cell type. 6 However, we observed and reported that following twofield en bloc resection, nearly 18% of node-negative patients with Barrett s adenocarcinoma developed isolated cervical nodal recurrences of their tumors. 7 Similarly, Clark et al reported that 19% of patients with esophageal adenocarcinoma developed nodal recurrence in the upper mediastinum. 8 Accordingly, we initiated a prospective observational study in 1994 to evaluate the feasibility and safety of esophagectomy with TFD and to assess the prevalence of metastases to the cervical lymph nodes in our patient population. In a preliminary report on a small number of patients, we observed that unsuspected metastases to the cervical nodes occurred in nearly one third of patients. 9 The limited period of follow-up precluded a meaningful analysis of survival. The current report has two specific aims: first, to further evaluate the prevalence of cervical nodal metastases in a larger group of patients with squamous cell cancer and adenocarcinoma of the esophagus, and second, to determine the impact of esophagectomy with TFD on survival and recurrence after a median follow-up of nearly 4 years. PATIENTS AND METHODS Between August 1994 and April 2001, 80 patients underwent esophagectomy with TFD at our institution. Patients were eligible for TFD only if the tumor was located within the tubular esophagus, regardless of cell type. Tumors of the lower third of the esophagus were included only if they did not extend past the gastroesophageal junction (Siewert type I). Patients with tumors located precisely at or below the gastroesophageal junction were not considered candidates for TFD (Siewert type II and III). Preoperative Evaluation Initial evaluation included an upper endoscopy with biopsy and a computerized tomogram of the chest and upper abdomen in all cases. More recently we have included endoscopic ultrasonography and positron emission tomography scanning to the staging work-up. Patients were considered for surgical resection if preoperative evaluation revealed no evidence of distant visceral metastases or clear evidence of direct neoplastic invasion of the airway or major vascular structures. All patients underwent evaluation of pulmonary and cardiac function to determine their ability to withstand the planned procedure. Generally, patients with an FEV 1 less than 1.5 liters per second despite aggressive physiotherapy and bronchodilator therapy were considered ineligible for resections. Cardiac disease, if suspected, was carefully assessed using either noninvasive means or angiocardiography if necessary. Perioperative Therapy Sixteen patients were referred for resection after preoperative chemotherapy and four after preoperative chemoradiation. Resection was carried out in 60 patients without any preoperative therapy. Surgical Procedures One patient with a tumor of the upper third of the thoracic esophagus had his resection done through a cervical incision, a partial sternotomy, and a laparotomy. Seventy-nine patients underwent resection through a right thoracotomy followed by a laparotomy and a cervical incision. In the thorax, the tumor-bearing esophagus was resected en bloc within an envelope of adjoining tissues that included both pleural surfaces laterally, the pericardium anteriorly (except in T 1 a lesion), and all lymphovascular tissues wedged dorsally between the esophagus and the spine. The thoracic duct was included with the en bloc resection throughout its course in the posterior mediastinum. For tumors traversing the esophageal hiatus, a 1-inch cuff of diaphragm was resected circumferentially around the tumor. As described, the en bloc resection necessarily included a complete dissection of the middle and lower mediastinal nodes, including the periesophageal, parahiatal, subcarinal, and aortopulmonary window nodes. In the abdomen, an upper abdominal and retroperitoneal node dissection was performed and included resection of the celiac, splenic, common hepatic, left gastric, lesser curvature, and parahiatal nodes. Dissection of the third field was begun during the thoracic portion of the procedure and later completed through a collar neck incision. Dissection of the nodes in the superior mediastinum included the nodes along the right and left recurrent laryngeal nerves throughout their mediastinal course. The paratracheal retrocaval compartment was not disturbed. The left recurrent nerve was exposed from the level of the aortic arch to the thoracic inlet. The nerve was dissected using a no-touch technique, and nodes along its anterior aspect were carefully excised. Notably, there was a paucity of nodal tissue along the left nerve in nearly all whites. The right recurrent nerve was carefully exposed near its origin at the base of the right subclavian artery. The right recurrent nodal chain begins at that level and forms a continuous package that extends through the thoracic inlet to the neck. Again, the nerve was dissected using a strict no-touch technique. Through the cervical incision, the remainder of the recurrent nodes were dissected, as well as the lower deep cervical nodes located posterior and lateral to the carotid sheath. Thus, the third field included a continuous anatomically inseparable chain of nodes that extended from the superior mediastinum to the lower neck. These nodes should be appropriately labeled cervicothoracic nodes rather than cervical nodes and are referred to as such throughout this report. Finally, gastrointestinal

3 Vol. 236 No. 2 Three-Field Lymph Node Dissection 179 reconstruction was achieved by advancing a greater curvature gastric tube to the neck for an esophagogastric anastomosis. Postoperative Care Patients were cared for in an intensive care unit for 24 hours for fluid management and mechanical ventilation. Separation from mechanical ventilation was achieved in all patients by the morning after the procedure. Intense pulmonary hygiene was required, often with repeated bronchoscopy for the first 48 hours after extubation, since most patients had a variable degree of bronchorrhea, which generally resolved on the third or fourth postoperative day. Oral intake was begun once anastomotic integrity was confirmed by a barium study on the sixth or seventh postoperative day. Follow-Up Following hospital discharge, patients were seen at intervals of 3 months for the first 3 years and every 6 months thereafter. Patients from distant geographic locations were followed by contacting their treating physician, as well as direct patient contact. A computed tomogram of the chest and upper abdomen and an upper endoscopy were obtained yearly, but other studies were done only in symptomatic patients. All data were collected and entered prospectively into a computerized database and updated at regular intervals. Complete follow-up information until death or June 2001 was available for all patients. Recurrence Local recurrence was defined as recurrence at the anastomoses or at any site within the operative field. This definition encompasses both local and locoregional failures. Recurrent disease (either local or distant) was histologically confirmed whenever possible. Statistical Analysis Survival time was measured from the time of the procedure until death (including operative mortality and noncancer-related deaths) or June Survival distribution was estimated by the product limit method and compared by the log-rank test. All tests were performed using a P.05 level of significance. RESULTS Clinicopathologic Characteristics Eighty patients underwent resection (57 men, 23 women) with a median age of 61 years (range 35 79). There were 65 whites, 5 African Americans, 7 Asians, and 3 Hispanic Americans. Adenocarcinoma was present in 48 patients (36 of whom had associated intestinal metaplasia) and squamous cell carcinoma in 32 patients. Postsurgical staging was based on the TNM staging system of the American Joint Commission on Cancer and is shown in Table 1. Hospital Mortality Table 1. There were three in-hospital deaths for a hospital mortality of 3.75%. Deaths were the result of pulmonary embolism in one patient, a massive cerebrovascular accident in one patient, and an antibiotic-resistant Pseudomonas pneumonia in one patient. An additional patient died within 2 weeks after discharge from the hospital due to massive hematemesis caused by a penetrating ulcer within the gastric tube. Thus, overall 30-day mortality, including hospital mortality, was 5%. Hospital Morbidity STAGING T-Status T is 3 T 1a 8 T 1b 4 T 2 16 T 3 47 T 4 2 N-Status N 0 25 N 1 55 M-Status M 0 51 M 1a 28 M 1b 1 TNM Stage 0 2 (3.75%) I 9 (11.25%) IIA 13 (16.25%) IIB 7 (8%) III 20 (25%) IV 29 (36%) Thirty-nine patients (49%) had an uneventful postoperative course. Complications occurred in 37 patients. Complications were considered minor in 12 (15%) and major in 25 (31%) (excluding four perioperative deaths). All complications are listed in Table 2. The most frequent morbidity was pulmonary, which developed in 21 patients. Cardiac complications occurred in 12 patients and were exclusively supraventricular arrhythmias, none of which were hemodynamically significant. Anastomotic complications occurred in nine patients, all of which were successfully managed by simple drainage of the cervical wound. Injury to the recurrent nerve occurred in seven patients (9%). Nerve injury was unilateral in six patients and bilateral in one. Four patients had transient injury (including one patient with bilateral injury) and three required surgical medialization of

4 180 Altorki and Others Ann. Surg. August 2002 Table 2. COMPLICATIONS* Respiratory (n 21) Reintubation 13 Tracheostomy 3 Pneumonia 6 Atelectasis 7 Tracheal ischemia 1 Gastrotracheal fistula 1 Cardiac 12 Leak 9 Infection (n 8) Wound 1 Abcess 1 Urinary tract infection 1 Empyema 5 (3 with leaks) Recurrent nerve injury (n 7) Bilateral 1 Unilateral 6 Transient 4 Other (n 7) Chylothorax 1 Hemodialysis 2 Delerium tremens 2 Pulmonary embolism 2 * Excluding postoperative deaths. their paralyzed vocal cord, usually 6 months following discharge. No patient required intubation or tracheostomy as a result of nerve injury. Prevalence of Nodal Disease The median number of resected lymph nodes was 47. Twenty-five patients had node-negative disease, including one patient who had preoperative evidence of nodal metastases on endoscopic ultrasonography and who was downstaged to T 0 N 0 by preoperative therapy. Fifty-five patients (69%) had postsurgical pathologically confirmed nodal metastases, with an average of 6.9 positive nodes per patient (range 1 30). Twenty patients had nodal disease confined to only one field, 17 had two-field involvement, and 18 had metastases in all three fields. The prevalence of nodal metastases increased with increasing depth of tumor penetration into the esophageal wall (Table 3). Notably, no patient with intramucosal cancer (T 1a ) had nodal metastases, while two of four patients with submucosal tumors had node-positive disease. The prevalence of nodal metastases for T 2 and T 3 lesions exceeded 80%. Cervicothoracic Nodal Metastases Twenty-nine patients (36.25%) had metastatic carcinoma in the cervicothoracic nodes, including three who also had celiac nodal disease. Thus, dissection of the third field yielded important staging information in 26 patients (32.5%). Metastases involved the right recurrent nodes in 22 T-Status patients, the left recurrent nodes in 1, and both groups in 4. Metastases to the deep cervical nodes were present in four patients, two of whom also had metastases in the recurrent nodes. The frequency of cervicothoracic nodal disease was independent of cell type or tumor location within the esophagus (Table 4). However, the frequency of cervicothoracic nodal metastases was influenced by the nodal status within the abdomen and/or mediastinum. Forty-three percent (24/ 55) of patients with node-positive disease in the abdomen and/or mediastinum also had nodal metastases in the cervicothoracic region. In contrast, among 30 patients with nodenegative disease in the abdomen and mediastinum, 4 (13%) had isolated metastases in the cervicothoracic nodes. Survival Table 3. PREVALENCE OF NODAL DISEASE INCREASED WITH ADVANCING T-STAGE Positive Nodes Positive Cervicothoracic Nodes T is 1/3 1/3 T 1a 0/8 0/8 T 1b 2/4 2/4 T 2 12/16 5/16 T 3 39/47 20/47 T 4 1/2 1/2 With a median follow-up of 46 months, overall and disease-free 5-year survival rates are 51% and 46%, respectively (Fig. 1). Overall 5-year survival was not influenced by cell type (adenocarcinoma 46% vs. squamous carcinoma 65%, P.1). Predictably, stage of disease was an important determinant of survival (Fig. 2). The 5-year survival rate for node-negative patients was 88% compared to 33% for patients with nodal metastases (P.0007) (Fig. 3). There was no significant difference in survival of nodepositive patients who either received (n 15) or did not receive postoperative chemotherapy. This lack of benefit was noted even when patients receiving preoperative chemotherapy (n 16) were included with the postoperative chemotherapy group for analysis. Table 4. PREVALENCE OF CERVICOTHORACIC NODES BY CELL TYPE AND TUMOR SITE Adenocarcinoma 18 /48 (37.42%) Squamous carcinoma 11 /32 (34.3%) Lower third 18 /55 (32.73%) Middle third 10 /17 (58.82%) Upper third 1 /8 (12.5%)

5 Vol. 236 No. 2 Three-Field Lymph Node Dissection 181 Figure 1. Overall and disease-free 5-year survival. Figure 3. Survival by N-status. Patients with cervicothoracic nodal metastases had 3- and 5-year survival rates of 33% and 25%, respectively (median 17 months). In contrast, patients without cervicothoracic nodal metastases but with positive intrathoracic and/or intraabdominal nodes had 3- and 5-year survival rates of 50% and 43%, respectively (median 44 months). The difference in survival approached but did not achieve statistical significance (P.06) (Fig. 4). Three- and five-year survival rates for patients with positive cervicothoracic nodes with squamous cell carcinoma (n 11) were 40% compared to 29% and 15%, respectively, for patients with adenocarcinoma with metastases to the cervicothoracic nodes (n 18) (Fig. 5). The difference in survival was not statistically Figure 2. Survival by stage. Figure 4. patients. Survival by cervicothoracic nodal status in node-positive

6 182 Altorki and Others Ann. Surg. August 2002 Figure 5. significant (P.1). Similarly, there was no statistically significant difference in 3- and 5-year survival rates between patients with positive cervicothoracic nodes and middle-third and lower-third tumors (P.1). Recurrence Four patients had an incomplete resection. Two had microscopic disease at the surgical margin and two had gross residual disease due to previously unsuspected airway invasion in one patient and liver metastases in one patient. Seventy-six patients had a complete resection, of whom 72 survived beyond 30 days and were evaluable for recurrence. Thirty-eight patients remain disease-free. Twenty-seven patients developed distant metastases, three had locoregional recurrence, and four had both. Locoregional recurrences occurred in the mediastinum in four patients and in the dissected recurrent laryngeal nodal bed in three. Overall, locoregional recurrence occurred in 9.7% of patients who had a complete resection. DISCUSSION Positive cervicothoracic nodes: survival by cell type. Despite the enthusiasm for esophagectomy with TFD in Japan, there has been little interest in evaluating the role of this procedure among Western patients. In 1997 we reported our initial observations in a small number of patients showing an unexpectedly high prevalence of cervical nodal metastases in patients with both squamous cell carcinoma and adenocarcinoma of the esophagus. 9 No survival results were reported due to the small sample size and insufficient follow-up. Lerut et al reported on 37 patients with adenocarcinoma of the thoracic esophagus (n 17) and the gastroesophageal junction (n 20). 10 Metastases to the recurrent laryngeal nodes were found in 35% of patients with esophageal adenocarcinoma and in 20% of those with cancer of the gastroesophageal junction. Sixteen patients with metastases to the cervical nodes had 3- and 5-year survival rates of 22% and 15%, respectively. To our knowledge, the current report represents the largest series reporting on the role of esophagectomy with TFD in Western patients with an emphasis on esophageal adenocarcinoma. We initiated this prospective observational study in 1994 and have acquired follow-up information on 100% of patients. Patients were eligible for the procedure only if they had invasive carcinoma of the tubular esophagus. Patients with tumors of the gastroesophageal junction (so-called Siewert types II and III) were not considered for the procedure. This allowed us to include in the analysis a relatively homogeneous group of patients. The data contained within this report allow us to draw several conclusions. First, clinically unsuspected metastases to the cervicothoracic nodes are present in 36% of patients with esophageal cancer, regardless of cell type. Similarly, metastases to the cervicothoracic nodes were present in 32% of lower-third tumors and 60% of middle-third tumors. Second, there appears to be a progressive increase in the frequency of nodal metastases with increasing depth of tumor penetration into the esophageal wall. Remarkably, there were no instances of nodal metastases in patients with intramucosal cancer, while submucosal invasion signaled a 50% probability of metastatic carcinoma to the cervicothoracic nodes. Although there were only four patients in this category, these data are in accord with a plethora of data from Japan suggesting that the frequency of nodal disease in submucosal tumors is in the range of 30% to 50% The clinical relevance of these data is clear: submucosal disease is not early-stage disease. Third, the probability of cervicothoracic nodal disease is determined to some extent by the presence or absence of nodal metastases in the abdomen and/or mediastinum. In patients with node-positive disease in the abdomen or mediastinum, over 43% had cervicothoracic nodal metastases. The corollary of that finding is that 13% of patients with otherwise no evidence of nodal disease had unsuspected metastases in the cervicothoracic nodes. A possible clinical implication of these findings is that a significant number of patients, especially those with abdominal and/or mediastinal nodal metastases, will be incompletely resected following a two-field dissection. The impact of such an incomplete resection on survival is controversial, but the bulk of the evidence suggests that R2 types of resections are associated with a dismal outcome, with essentially no survivors beyond 2 years Fourth, a substantial number of patients will have their disease restaged following TFD. In this report 32% were upstaged. The majority of stage shifting occurred from stage

7 Vol. 236 No. 2 Three-Field Lymph Node Dissection 183 III to stage IV; however, two patients with stage I disease, one patient with stage II disease, and one with T is N 0 after induction therapy were upstaged to stage IV. Clearly, the stage shift after TFD results in improvement in stage-specific survival. Although we have previously reported the 5-year survival of stage III patients to be 34% following two-field en bloc resection, stage III survival was 53% in this report. 17 This apparent improvement in outcome is at least partly due to stage migration, since stage III patients in this report represent a more homogeneous group. Whether the procedure results in a survival benefit for patients with stage IV disease remains a crucial issue. Some, perhaps many, contend that the presence of metastases in the cervicothoracic region is essentially equivalent to systemic metastases and that cure is simply not possible. 5 Our data, however, argue that such is not the case, particularly in patients with squamous cell carcinoma, for whom the 5-year survival rate is 40%. Among 11 patients with squamous cell carcinoma with positive cervicothoracic nodes, 3 are alive free of disease at 3, 5, and 6 years postoperatively. In contrast, patients with stage IV adenocarcinoma have discouraging 3- and 5-year survival rates of 30% and 15%, respectively. While we would agree that cure is an unlikely event, prolongation of survival is possible and would represent a small but important achievement for these patients. However, this is a subset of patients where novel adjuvant therapies are anxiously awaited. Inevitably, the real question would be whether the procedure carries a survival benefit beyond that imparted by more accurate staging and a stage migration effect. To the extent that randomized trials remain the gold standard for proving therapeutic efficacy, the current study was not designed to resolve that issue. However, most would agree that overall survival rates in surgically resected patients are in the 20% to 30% range. The overall 5-year survival rate of 51% in this report represents essentially a doubling of previously published results. Selection bias, often the culprit in such instances, cannot be inferred by us since the procedure was essentially applied in nearly all patients with cancer of the tubular esophagus who did not have distant metastases. However, a prereferral bias cannot reasonably be excluded. In summary, the current report shows that esophagectomy with three-field lymphadenectomy can be accomplished safely with a low mortality and a morbidity similar to that observed after less extensive resections. Furthermore, the procedure provides the most accurate staging information for patients with this disease, with as many as one third of patients being restaged. Finally, the data suggest that there is good evidence that the procedure has an important survival benefit, although this experience clearly needs to be duplicated in other experienced esophageal centers. References 1. Tanabe G, Nishi M, Kajis T, et al. Analysis of lymph node metastases and surgical treatments for thoracic esophageal cancer: New method of the initial dissection of the cervix and abdomen. Jpn J Gastroenterol Surg 1983; 16: Kato H, Tachimori Y, Watanabe H, et al. Lymph node metastases in thoracic esophageal carcinoma. J Surg Oncol 1991; 48: Isono K, Onoda S, Nakayama K, et al. Recurrence of intrathoracic esophageal cancer. Jpn J Clinical Oncol 1985; 15: Isono K, Sato H, Nakayama K. Results of a nationwide study on three-field lymph node dissection of esophageal cancer. Oncology 1991; 48: Orringer MB. Occult cervical nodal metastases in esophageal cancer: Preliminary results of three-field lymphadenectomy [editorial]. J Thorac Cardiovasc Surg 1997; 113: Fujita H, Kakegawa T, Yamana H, et al. Mortality and morbidity rates, postoperative course, quality of life, and prognosis after extended radical lymphadenectomy for esophageal cancer. Comparison of threefield lymphadenectomy with two-field lymphadenectomy. Ann Surg 1995; 222: Altorki NA, Girardi L, Skinner DB. Extended resections of the thoracic esophagus and cardia. Diseases of the esophagus: Proceedings of the Sixth ISDE World Congress. Current Opinion in General Surgery. Philadelphia: Current Science, 23 26, Clark GWB, Peters JH, Ireland A, et al. Nodal metastasis and sites of recurrence after en bloc esophagectomy for adenocarcinoma. Ann Thorac Surg 1994; 58: Altorki NK, Skinner DB. Occult cervical nodal metastasis in esophageal cancer: Preliminary results of three-field lymphadenectomy. J Thorac Cardiovasc Surg 1997; 113: Lerut T, Coosemans W, De Leyn P, et al. Reflections on three-field lymphadenectomy in carcinoma of the esophagus and gastroesophageal junction. Hepato-Gastroenterology 1999; 46: Akiyama H, Tsurumaru M, Udagawa H, et al. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg 1994; 220: Baba M, Aikou T, Yoshinaka H, et al. Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus. Ann Surg 1994; 219: Matsubara T, Mamoru U, Yanagida O, et al. How extensive should lymph node dissection be for cancer of the thoracic esophagus? J Thorac Cardiovasc Surg 1994; 107: Sugimachi K, Matsuoka H, Ohno S, et al. Multivariate approach for assessing the prognosis of clinical esphageal carcinoma. Br J Surg 1988; 75: Roder JD, Busch R, Stein HJ, et al. Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the esophagus. Br J Surg 1994; 81: Ellis FH Jr, Heatly GJ, Krasna MJ, et al. Esophagogastrectomy for carcinoma of the esophagus and cardia: A comparison and results after standard resection in three consecutive eight-year intervals with staging criteria. J Thorac Cardiovasc Surg 1997; 113: Altorki NA, Girardi L, Skinner DB. En bloc esophagectomy improves survival for stage III esophageal cancer. J Thorac Cardiovasc Surg 1997; 114: