REVIEW ARTICLE. Extended Esophagectomy With 3-Field Lymph Node Dissection for Esophageal Cancer

REVIEW ARTICLE Extended Esophagectomy With 3-Field Lymph Node Dissection for Esophageal Cancer Mitsuo Tachibana, MD; Shoichi Kinugasa, MD; Hiroshi Yoshimura, MD; Dipok Kumar Dhar, MD; Naofumi Nagasue, MD Objective: To review the surgical outcomes of extended esophagectomy with 3-field lymph node dissection (3FLND) for esophageal cancer. Data Sources: Only articles written in English and written after 1980 were selected from MEDLINE. The following terms were identified: 3FLND, extensive or extended lymph node dissection (lymphadenectomy), radical lymph node dissection, cervical lymph node dissection, and extended or radical esophagectomy in esophageal cancer. Study Selection: There were no exclusion criteria for published information relevant to the topic. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. Data Extraction: Twenty-six articles were finally collected from MEDLINE. Eleven articles were also selected from reference lists of the pertinent literature. Data Synthesis: The collected information was organized. Conclusions: The conclusions drawn from those articles showed that extended esophagectomy with 3FLND would be a safe procedure in experienced hands, with low morbidity and acceptable mortality rates. When strict patient selection criteria were maintained, this procedure reduced locoregional recurrence and improved longterm survival rates. Although the therapeutic value of 3FLND is unproved in a randomized trial, extended esophagectomy with 3FLND would be the treatment of choice in selected patients. Arch Surg. 2003;138:1383-1389 From the Second Department of Surgery, Shimane Medical University, Shimane, Japan. THE WORLDWIDE incidence of esophageal cancer is increasing, particularly for adenocarcinoma of the lower esophagus, gastroesophageal junction, and gastric cardia. 1,2 At diagnosis, most esophageal carcinomas are in an advanced stage; thus, surgery is inappropriate in 40% to 60% of patients, mainly because of the inability to resect incurable nodes, the presence of distant metastases, or the high operative risk. 3 See Invited Critique at end of article The long-term survival rate of patients who have undergone esophagectomy remains low. A collected review 4 of 83783 patients treated between 1953 and 1978 showed that the overall 5-year survival of patients referred for surgery was only 4%. Another review 5 of 43692 patients treated between 1980 and 1988 showed only a marginal improvement in the 5-year overall survival during this period (4%-10%). In an attempt to improve the surgical results, preoperative (neoadjuvant) and postoperative (adjuvant) multimodal treatments are used. Two reviews 6,7 showed that multimodal treatments have little impact on patient prognosis and no definite conclusions could be drawn regarding the efficacy of neoadjuvant radiochemotherapy. Among the various treatment modalities, surgery remains the mainstay for the treatment of patients with potentially curable disease. Long-term survival is, however, disappointing when the disease extends through the esophageal wall or when it is diagnosed with widespread lymph node involvement. 3,8,9 The operative approach for esophageal cancer, thus, varies from conventional transthoracic esophagectomy, chiefly for palliation, 10,11 to limited esophagectomy without thoracotomy, 12-14 to en bloc esophagectomy, 15-17 and to extended esophagectomy with 3-field lymph node dissection 1383

Only articles written in English and written after 1980 were selected from MEDLINE. The following terms were identified (number of citations): 3FLND (36), extensive or extended lymph node dissection (lymphadenectomy) (27), radical lymph node dissection (lymphadenectomy) (16), cervical lymph node dissection (lymphadenectomy) (10), and extended or radical esophagectomy (11) in esophageal cancer. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. After check and evaluation, 26 articles were finally collected from the previously mentioned MEDLINE database; 11 articles were also selected from reference lists of the pertinent literature. Sixteen articles were excluded. In evaluating the statistical analysis of the complications in the reported literature, a collective method was used. HISTORY (3FLND) for curative purposes. 18 In an attempt to obtain accurate post operative staging and to improve the surgical results, extended esophagectomy with 3FLND has been proposed and performed in selected Japanese institutions. This review examines the results of extended esophagectomy for esophageal cancer. DATA SOURCES Group 1 Group 2 Group 3 Group 4 Group 5 Lymph node mapping of esophageal cancer. Three-field lymph node dissection includes removal of the 5 groups of lymph nodes: group 1, bilateral cervical lymph nodes; group 2, superior mediastinal lymph nodes; group 3, middle mediastinal lymph nodes; group 4, inferior mediastinal lymph nodes; and group 5, abdominal lymph nodes. Lymph node involvement is an important prognostic indicator in esophageal carcinoma, 8,9 and treatment failure is mostly related to locoregional recurrence, including lymph node recurrence. In gastric cancer surgery, because extended radical surgery was recommended to improve the outcome, 19 radical lymph node dissection has become an integral part of the surgical treatment in Japan. 20 The number of dissected lymph nodes increased with the proportion of patients with lymph node involvement. If the lymph node examination is insufficient, the nodal stage can be erroneously assessed at an earlier stage (stage migration). Extended lymph node dissection and routine microscopic examination of all resected nodes, thus, can provide accurate lymph node information and tumor staging. The lymphatic channels of the esophagus run vertically along the axis of the esophagus, and some of them drain into the cervical lymph glands upwards and into the abdominal glands downwards. 21,22 Therefore, it is logical to conclude that not only the mediastinal lymph nodes but also the cervical and upper abdominal (subdiaphragmatic, celiac, and hepatic artery) groups of lymph glands are part of the regional lymphatic drainage of the esophagus; metastatic deposits in these nodes should not be considered as distant metastasis. 23 Three-field lymph node dissection should be considered as a curative procedure during esophagectomy in the same way that the D2/D3 lymph node dissection 20 is indicated during treatment for gastric carcinoma. EXTENT OF LYMPH NODE DISSECTION Esophagectomy and 3FLND are performed through a right-sided thoracotomy, laparotomy, and bilateral cervical collar incision. The azygous vein and right bronchial artery are ligated, but in some selected cases, the right bronchial artery could be preserved to prevent occasional tracheal ischemia and/or necrosis. The superior vena cava, the innominate artery, the right subclavian artery, the pulmonary branch of the right vagal nerve, and the bilateral recurrent laryngeal nerves are carefully exposed and preserved. A full 3FLND involves removal of 5 anatomical groups of lymph nodes (Figure). The cervicothoracic lymph node dissection around the left recurrent laryngeal nerve is technically the most difficult step. Fatty tissues containing the lymph nodes should be carefully dissected around the laryngeal nerves by the thoracic and cervical approaches. In fact, after completion of the transthoracic lymph node dissection around the bilateral recurrent laryngeal nerves, the surgeon can easily recognize the upper side of the dissected lines from the cervical approach. Some surgeons prefer taping the recurrent laryngeal nerve to make lymph node dissection easier, but controversy exists about whether taping this nerve may cause transient or permanent paralysis. We believe the bilateral laryngeal nerves should be taped from the thoracic and cervical approaches by 1384

beginners and that taping could be avoided when surgeons become more confident. Because of anatomical reasons, complete lymph node dissection around the bilateral laryngeal recurrent nerves could not be performed by the en bloc procedure. Most surgeons believe that malignant tumors should be resected with a complete covering of the resectable surrounding healthy tissues. Therefore, en bloc esophagectomy (en bloc lymph node dissection) is theoretically an ideal procedure, 16,17 but is anatomically and technically difficult around the laryngeal recurrent nerves. INCIDENCE OF CERVICOTHORACIC NODE METASTASIS A nationwide study in Japan 18 showed that the rate of lymph node metastasis was 27.4% in the cervical nodes (group 1), 55.8% in the mediastinal nodes (groups 2-4), and 43.8% in the abdominal nodes (group 5). Among cervical lymph node metastasis, 12.8% was on the right and 13.9% was on the left, suggesting a similar degree of metastasis on both cervical sides. According to tumor location and rate of nodal metastases, a good correlation between adjacent regional nodal involvement and tumor location was found. Among patients with upper thoracic cancer, the rates of nodal metastasis were 42.3% in the cervical nodes, 63.1% in the mediastinal nodes, and 19% in the abdominal nodes. The respective rates were 27.5%, 55.8%, and 41% among patients with middle thoracic cancer, and 10.9%, 43.5%, and 67.4% among patients with lower thoracic cancer. Thereportedincidenceoflymphnodemetastasisaround the bilateral recurrent laryngeal nerves and bilateral deep cervicalregionsisshownin Table 1. Theincidencesoflymph node metastasis around the recurrent laryngeal nerve are between 26.7% and 48.6%, and those around the deep cervix arebetween16.7% and35%. Theincidencesofcervicallymph node metastasis are not different between adenocarcinoma and squamous cell carcinoma. 31-33 Is it possible for the surgeon to determine the necessity of 3FLND during transthoracic esophagectomy depending on the state of lymph node metastasis? It seems that recurrent lymph node involvement is significantly associated with the presence of cervical nodal metastasis. Therefore, assessment of recurrent or paratracheal nerve node metastasis may be useful in predicting cervical nodal metastasis and the necessity of 3FLND. 30,34,35 Preoperative mediastinoscopy or intraoperative endodissection of the upper mediastinum and upper esophagus are other optional staging methods for evaluating recurrent or paratracheal nerve node metastasis. Most Japanese surgeons, however, decide the indication of 3FLND preoperatively, because the presence or absence of small-node metastasis or micrometastasis around the laryngeal nodes cannot be correctly diagnosed, even by intraoperative frozen section. PATIENT SELECTION In general, 3FLND is indicated for potentially curable thoracic esophageal cancers (except Tis) in patients with a good general medical condition. Table 1. Incidence of Recurrent Laryngeal Nerve Node and Cervical Lymph Node Metastasis Source No. of Patients Age, general risk condition, and depth of tumor penetration are the criteria that should be considered for 3FLND. Patients younger than 70 years 36 or 75 years 25,27,37 are suitable for 3FLND. Age itself is not, however, a contraindication now; thus, 3FLND can be performed safely in elderly patients (those older than 70 years) with satisfactory long-term results. 38,39 Three-field lymph node dissection can be performed with acceptable morbidity and mortality rates in patients with a low general risk factor. 25,27,36,37 The presence of liver cirrhosis is a risk factor for extended esophagectomy and is sometimes considered a contraindication. 16,37 Child-Turcotte class A and B cirrhosis of the liver may not, however, contraindicate curative esophagectomy with 3FLND. 40 SURGICAL OUTCOMES Operative and Hospital Mortality The operative mortality (death within 30 days after the operation regardless of discharge from the hospital) after 3FLND was reported to be between 0% and 3.7% 18,25-27,36,41-43 (Table 2). The overall hospital mortality (death during the hospital stay) from the collected literature that showed the detailed complications was 4.0% (21 of 522 patients) (Table 3). A pulmonary complication (pneumonia) was the main cause of death, followed by a septic complication associated with leakage. Other causes were cardiac, hepatic, and renal failure (1 instance each) and early tumor progression (3 instances). Tracheal necrosis that was a specific complication to 3FLND happened in 2 patients. Morbidity Incidence of Metastasis, % Recurrent Laryngeal Nerve Node Cervical Lymph Node Kato et al, 24 1991 77 ND 20 Okuma et al, 25 1993 68 ND 29.4 Akiyama et al, 26 1994 290 38.1 ND Baba et al, 27 1994 106 43.4 34 Nishimaki et al, 28 1994 145 ND 29.4 Matsubara et al, 29 1998 276 48.6 16.7 Tabira et al, 30 2000 86 26.7 19.8 Altorki and Skinner, 31 1997 30 35 35 Lerut et al, 32 1999 37 ND 29.7 Abbreviation: ND, not determined. The overall morbidity was 44.8% (158 of 353 patients), varying from 37.7% to 46.7%, depending on the different definition of miscellaneous complications (Table 3). A septic complication was the most common cause (26.8%); more than half of the septic complications (96 instances) were anastomotic leakages, and most were defined as minor leakage and healed spontaneously with 1385

Table 2. Surgical Results of 3-Field Lymph Node Dissection Source No. of Patients Histological Type (SCC/AC/Other), % Resectability, % Patients With Mortality, % Stage I Cancer Operative Hospital 5-y Survival, % % 5-y OS, % Recurrence, %* Kato et al, 24 1991 77 90.9/2.6/6.5 78.0 ND 2.6 48.7 27.3 ND 23.4 Okuma et al, 25 1993 68 100/0/0 ND 0 2.9 35.2 13.2 ND ND Akiyama et al, 26 1994 324 100/0/0 70.3 2.2 5.2 55 14.3 94.1 ND Baba et al, 27 1994 106 97.2/0/2.8 82.7 3.7 10.3 30.8 7.5 60 46.2 Fujita et al, 36 1995 63 100/0/0 77.9 0 1.6 40 7.9 ND 33.3 Matsubara et al, 29 1998 276 100/0/0 ND ND 2.5 50 ND ND ND Nishimaki et al, 41 1998 190 93.7/0/6.3 ND 1.6 4.7 41.5 9.5 91.7 41.6 Tachibana et al, 42 1999 129 100/0/0 80.9 ND 9.8 45.8 ND 100 28.7 Tabira et al, 37 1999 40 100/0/0 ND ND ND 42 ND ND ND Ando et al, 43 2000 116 93/4/3 73.5 1.7 7.9 40 18 88 ND Isono et al, 18 1991 1791 ND ND 2.8 ND 34.3 ND ND ND Altorki and Skinner, 31 30 50/50/0 ND ND 3.3 ND ND ND ND 1997 Lerut et al, 32 1999 37 59.5/40.5/0 ND ND 0 21 ND ND ND Abbreviations: AC, adenocarcinoma; ND, not determined; OS, overall survival; SCC, squamous cell carcinoma. *The type of recurrence (locoregional, systemic, locoregional and systemic, or cervical) was not determined or not applicable in most articles. In the article by Baba et al, 27 36% of the patients experienced locoregional recurrence, 29% experienced systemic recurrence, and 23.6% experienced cervical recurrence; locoregional and systemic recurrence was not determined. This was 90-day mortality. These were R0 and R1/2 cases. nutritional support within 1 month. The rate of anastomotic leakage after 3FLND seems to be somewhat high (19%-30%). This is partly attributable to the skeletonizing lymph node dissection around the cervical part of the esophagus compromising blood circulation of the stump and subsequent leakage. A pulmonary complication was the next common cause; about two thirds were pneumonia, including aspiration pneumonia due to laryngeal recurrent nerve paralysis. Two patients developed fatal tracheal necrosis, and another 23 developed tracheal ischemia or ulcer formation because of the poor vascular supply of the tracheobronchial trees. Great care should be taken to preserve the right and left bronchial arteries if the tumor does not directly invade these arteries and not to dissect the fibrous membranous sheath of the trachea to avoid tracheal devascularization. A cardiac complication was less common (4.8%) in the Japanese reports. 24,27,29,36 Arrhythmia was the major cause of cardiac complications (14 instances). A fatal cardiac complication was cardiac failure in 1 of 10 instances. Miscellaneouscomplicationsdevelopedin48.5% ofthe patients (253 instances). Among those patients, more than half developed recurrent laryngeal nerve paralysis. Swallowing, breathing, speaking, and coughing are all impaired after damage to the recurrent laryngeal nerve. When bilateral paralysis occurs, this leads to asphyxia, necessitating urgent reintubation/tracheotomy.recurrentnerveparalysisoccurred more frequently after 3FLND than after 2-field lymph node dissection(2flnd), 18,36 indicatingthatnervepalsywascaused bylymphnodedissectionaroundtherecurrentnerves 44 rather than by the cervical phase to prepare the cervical esophagus for anastomosis. 45 Does recurrent nerve paralysis deterioratepostoperativequalityoflifeafteresophagectomy? Pulmonary complications frequently occurred in patients with vocal cord paralysis, leading to significantly more reintubations, a prolonged ventilation time, and a stay in the intensive care unit. 45 Vocal cord paralysis produced debilitation in performance status, abilities to go upstairs, and swallowing. 44 As a result, aspiration pneumonia happened more frequentlyafter3flndthan2flnd.greatcareshouldbetaken, again, during aggressive lymph node dissection to avoid the use of electrocautery close to the recurrent laryngeal nerve and pulling the nerve by means of a vessel tape. Five-Year Overall Survival and Prognostic Factors Several researchers in Japan reported an excellent overall 5-year survival, varying from 30.8% to 55% after R0 46 esophagectomy with 3FLND * (Table 2). Again, a nationwide study 18 showed a better 5-year survival (34.3%) following 3FLND compared with that (26.7%) following 2FLND (P.001). Well-known prognostic factors of survival are as follows: R0 resection, 40 stage category, 26,27,41-43,49 tumor category, 27,37,42,43 and node category. 26,27,36,41 For the node category, the number of involved nodes clearly affects survival in the following categories: 0 or 1 vs 2 or more, 42 0or1vs 2 to 7 vs 8 or more, 50 1 to 4 vs 5 or more, 30,37,41,51 and1to 7 vs 8 or more. 26 The metastatic lymph node ratio 52 (the ratio of invaded removed lymph nodes) is also an independent prognostic indicator in patients with distant lymph node metastases. 53 The presence or absence of laryngeal recurrent nerve node, 27 cervical node, 25-27,30,41 and celiac node metastasis 26 are also useful prognosticators. Other prognostic indicators are anatomical extent of lymph node metastasis 41,50,51 and number of dissected mediastinal nodes. 43 Sex, 43 age, 27,37 tumor location, 42 amount of blood transfusions, 54 presence or absence of postoperative com- *References 24-27,29,36,37,41-43,47,48 1386

Table 3. Mortality and Morbidity of 3-Field Lymph Node Dissection Complication Kato et al, 24 1991 (n = 77)* Baba et al, 27 1994 (n = 106)* Fujita et al, 36 1995 (n = 63)* Matsubara et al, 29 1998 (n = 276)* Total Fatal 2.6 (2) 10.4 (11) 1.6 (1) 2.5 (7) 4.0 (21/522) Tracheal necrosis 0 1.9 (2) 0 0 2 Cardiac failure 0 0 0 0.4 (1) 1 Renal failure 0 0.9 (1) 0 0 1 Liver failure 0 0 0 0.4 (1) 1 Leaks 0 3.8 (4) 0 0 4 Pneumonia 2.6 (2) 3.8 (4) 0 0.4 (1) 7 Splenic artery aneurysm 0 0 0 0.4 (1) 1 Recurrence 0 0 1.6 (1) 1.1 (3) 4 Nonfatal 37.7 (29) ND ND 46.7 (129) 44.8 (158/353) Bleeding 0 3.8 (4) 4.8 (3) 1.4 (4) 11 Pulmonary 10.4 (8) 28.3 (30) 61.9 (39) 12.3 (34) 21.3 (111/522) Pneumonia 9.1 (7) 23.6 (25) 33.3 (21) 4.7 (13) 66 Empyema 1.3 (1) 0.9 (1) 7.9 (5) 2.5 (7) 14 Chylothorax 0 0.9 (1) 1.6 (1) 0.7 (2) 4 Pulmonary embolism 0 0 0 0.7 (2) 2 Tracheal perforation 0 1.9 (2) 0 0 2 Tracheal ulcer 0 0 17.5 (11) 3.6 (10) 21 Tracheomalacia 0 0 1.6 (1) 0 1 Cardiac 1.3 (1) 13.2 (14) 0 3.6 (10) 4.8 (25/522) AMI 1.3 (1) 0 0 0 1 Arrhythmia 0 13.2 (14) 0 0 14 CHF 0 0 0 3.6 (10) 10 Septic 35.1 (27) 28.3 (30) 46.0 (29) 19.6 (54) 26.8 (140/522) Sepsis 0 0 9.5 (6) 0 6 All Abdomen 1.3 (1) 0 1.6 (1) 0 2 Leaks 33.8 (26) 28.3 (30) 33.3 (21) 6.9 (19) 96 Anastomotic All 0 0 0 10.5 (29) 29 Catheter related 0 0 0 2.2 (6) 6 DIC 0 0 1.6 (1) 0 1 Miscellaneous 48.1 (37) 76.4 (81) 100.0 (63) 26.1 (72) 48.5 (253/522) RNP 14.3 (11) 41.5 (44) 69.8 (44) 14.5 (40) 139 Wound infection 6.5 (5) 0 0 0 5 Liver failure 2.6 (2) 0 0 2.2 (6) 8 Renal failure 5.2 (4) 3.8 (4) 1.6 (1) 1.8 (5) 14 Intestinal obstruction 2.6 (2) 0 3.2 (2) 1.4 (4) 8 Anastomotic stricture 10.4 (8) 0 7.9 (5) 0 13 Hyperbilirubinemia 0 31.1 (33) 0 0 33 Hepatitis 0 0 12.7 (8) 0 8 Horner syndrome 0 0 1.6 (1) 0 1 Osteomyelitis 0 0 6.3 (4) 1.1 (3) 7 Common carotid rupture 0 0 1.6 (1) 0 1 Others 6.5 (5) 0 0 5.1 (14) 19 Abbreviations: AMI, acute myocardial infarction; CHF, congestive heart failure; DIC, disseminated intravascular coagulopathy; ND, not determined; RNP, recurrent laryngeal nerve paralysis. *Data are given as percentage (number) of patients who experienced the specific complication. Data are given as total number of patients who experienced the specific complication unless otherwise indicated. Data are given as percentage (number affected/total number) of patients who experienced the specific complication. plications, 43 and blood vessel invasion 42 are other possible prognosticators. The number of lymph node metastases determined by preoperative ultrasonography and endoscopic ultrasonography is useful for predicting the number of involved nodes by pathological examination and, thus, the prognosis of patients. 55 Although metastatic lymph nodes are enlarged, metastases are occasionally found in small lymph nodes; hence, it can be difficult to correctly diagnose nodal metastasis during the operation. With respect to macroscopic examination during the operation, the correct diagnostic rate was only 15% in cases of metastatic lymph nodes smaller than 15 mm at the widest diameter in patients with gastric cancer. 56 IS THE CERVICOTHORACIC LYMPH NODE RECURRENCE RATE REALLY LOW AFTER 3FLND? Recurrence was most frequent on the left side of the cervicothoracic nodes, 57,58 where complete lymph node dissection is technically difficult. The cervical lymph node recurrence rate was, however, significantly lower with 3FLND (10%) than with 2FLND (19%). 59 Locoregional 1387

recurrence was correlated with the number of involved lymph nodes, whereas distant recurrence was associated with vascular invasion. 58 From these data, it seems that even after 3FLND recurrence is still frequent around the upper mediastinal region, particularly on the left side, indicating that 3FLND in its present form may not be enough to reduce the lymph node recurrences. More radical 3FLND (eg, a complete upper mediastinal lymphadenectomy through a median sternotomy) may need to be developed to control the lymph node recurrence; however, this radical procedure was only reported in the Japanese congress. Sentinel lymph node mapping of an esophageal carcinoma 60 may properly point out the necessity of lymph node dissection in the near future. MINIMUM NUMBER OF DISSECTED LYMPH NODES FOR A PROPER NODAL EVALUATION The Union Internationale Contre le Cancer/TNM classification 46 recommended 6 or more retrieved lymph nodes for an accurate nodal classification of esophageal cancer, 15 or more nodes for gastric cancer, and 12 or more nodes for colorectal cancer. From the viewpoint of number of lymph nodes dissected in patients who underwent 3FLND, the average number of retrieved nodes was reported to be 40 or more, 53 69, 24 and 74 (range, 27-159), 41 respectively; in one report, 43 the mean (SD) number of mediastinal lymph nodes dissected was 20 (12). At least 12 nodes dissected was proposed as a new threshold for accurately defining the pn category in patients with esophageal cancer who underwent 2FLND. 61 These data may suggest that the minimum number of dissected lymph nodes for accurate nodal staging for 3FLND is 12 or more. 2FLND VS 3FLND A nationwide multicenter study 18 in Japan compared the results of 3FLND with those of 2FLND. The 30-day operative mortality was 2.8% for 3FLND and 4.6% for 2FLND. The 5-year survival of patients who underwent 3FLND was 34.3%, whereas that of patients who underwent 2FLND was 26.7% (P.001). The result of this study probably shows that the survival advantage of 3FLND is attributable to different patients selection between 3FLND and 2FLND centers and to advancement of perioperative management and superior surgical outcomes of the experienced institutions in which 3FLND is performed. A randomized study 24 compared 3FLND with 2FLND. The average age of patients undergoing 3FLND was 4 years younger than that of patients undergoing 2FLND. The operative mortality after 3FLND was 2.6%, compared with 12.3% after 2FLND (P.05). The 5-year survival was 48.7% after 3FLND and 33.7% after 2FLND (P.01). The result of this study, however, seems invalid because genuine randomization of the patients was not performed. Nishihira et al 62 compared 3FLND with 2FLND in a prospective randomized study. Because they followed strict criteria, only 27.6% of the patients satisfied the inclusion criteria. The 5-year survival was 64.8% after 3FLND and 48.0% after 2FLND (P=.19). The researchers intended to conclude that 3FLND might prolong survival, but it did not reach statistical significance. Taken together, these results show that no definite survival advantage of 3FLND is proved compared with 2FLND. The patients with thoracic esophageal cancer have a high incidence of upper mediastinal and cervical lymph node metastasis (Table 1). Because surgeons tend to remove the cancer-containing tissues completely by surgery, it is important to develop their surgical technique by having them perform not only standard esophagectomy but also extended esophagectomy, such as 3FLND and en bloc esophagectomy. To our knowledge, there are no large series of prospective randomized studies to prove the survival advantage of 3FLND. Assuming a 1-tailed log-rank test with a significance level of.05 and a power of 0.90, then more than 1000 patients are needed for a 5-year survival of about 40% to 50% for the limited dissection group vs obtaining a statistically significant difference between the limited dissection group and the 3FLND group. A statistical randomization of patients to analyze the effects of extensive lymph node dissection against lymph node metastasis is difficult to estimate accurately in a prospective study. Most surgeons, therefore, prefer to perform extensive lymph node dissection. CONCLUSIONS All results regarding the extended esophagectomy with 3FLND are reported from experienced institutions; this technique is not widely adopted in the world. These results show low mortality rates with acceptable morbidity rates and low locoregional recurrence rates following extended esophagectomy. To our knowledge, the therapeutic value of 3FLND is unproved in randomized trials; however, the better long-term survival rates reported by experienced centers after 3FLND, with acceptable morbidity and mortality rates, are encouraging. No definite conclusions should be drawn universally regarding the efficacy of extended esophagectomy, because this technically difficult surgical procedure is not always safe until the surgeon becomes familiar with the technique and postoperative management. The combination of chemotherapy and radiotherapy has an established role in cancer treatment, such as treatment for anal cancer, 63 but has neither shown its effect nor replaced surgery as the first-line therapy in esophageal cancer treatments. 6,7 Because surgery still remains the gold standard against esophageal cancer and surgeons can do their best to remove the potentially curable primary and metastatic tumors, extended esophagectomy with 3FLND is the preferred treatment of choice in selected patients. Early diagnosis, standardization of surgery, including routine lymph node dissection, and postoperative management of patients have all led to better survival rates after extended esophagectomy for esophageal cancer. Accepted for publication April 5, 2003. Corresponding author and reprints: Mitsuo Tachibana, MD, Second Department of Surgery, Shimane Medical University, Enya-cho 89-1, Izumo 693-8501, Shimane, Japan (e-mail: nigeka35@shimane-med.ac.jp). 1388

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