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Eur J Cardiothorac Surg 2007;31:154-160. doi:10.1016/j.ejcts.2006.10.033
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Lymphadenectomy extent is closely related to long-term survival in esophageal cancer

Chang Hyun Kanga,*, Young Tae Kima, Sang-Hoon Jeonb, Sook-Whan Sungb, Joo Hyun Kima

a Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University Hospital, Xenotransplantation Research Center, Clinical Research Institute, Seoul National University College of Medicine, Seoul, South Korea
b Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Kyeonggi-do, South Korea

Received 1 September 2006; received in revised form 16 October 2006; accepted 23 October 2006.

* Corresponding author. Address: Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 28 Yongon-dong, Jongro-gu, Seoul 110-744, South Korea. Tel.: +82 2 2072 3010; fax: +82 2 762 3566. (Email: chkang{at}snu.ac.kr).


    Abstract
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Objective: The optimal extent of lymphadenectomy during esophagectomy for esophageal cancer remains debatable. The aim of this study was to identify the effect of the extent of lymphadenectomy on survival and recurrence after esophagectomy in esophageal cancer. Materials and methods: Two hundred thirty-three patients who were operated on between January 1995 and December 2003 due to esophageal cancer were included. The study subjects were stage I, II, and III esophageal squamous cell carcinoma patients who had undergone curative resection without neoadjuvant chemotherapy or chemoradiation therapy. To analyze the extent of lymphadenectomy, lymph node stations were classified into three regions, namely, paraesophageal, upper thoracic, and abdominal regions, and patients were allocated to one of three groups, i.e., group 1 received lymphadenectomy in one region only, group 2 in two regions, and group 3 in three regions. Results: The pathologic stages were stage I in 57 (24.5%), IIA in 69 (29.6%), IIB in 27 (11.6%), and III in 80 (34.3%). There were 67 patients in group 1, 102 in group 2, and 64 in group 3. The operative mortality rate was 2.1%. Postoperative morbidity rates and hospital stay periods were no different for the three groups. The overall 5-year survivals in groups 1, 2, and 3 were 21.2, 36.3, and 53.7%, respectively, and there were statistically significant differences between groups (p = 0.019). Overall 5-year survival for those with N0 disease was different significantly in the groups (26.7, 56.8, and 74.4% in groups 1, 2, and 3, respectively; p = 0.001). However, overall 5-year survival differences for N1 disease were not significant. Group 1 showed more frequent locoregional recurrence than groups 2 and 3 (34.3 vs 12.7% and 15.6%, p = 0.002). However, distant recurrence was no different in the three groups. Conclusions: A wider extent of lymphadenectomy in esophageal cancer was associated with better long-term survival than limited lymphadenectomy, especially in N0 patients. In addition, increased survival was found to be inversely associated with locoregional recurrence.

Key Words: Esophageal cancer • Lymphadenectomy • Survival


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Lymphatic metastasis in esophageal cancer is characterized by early and widespread dissemination. Metastasis from neck to abdominal cavity can be found irrespective of primary tumor location [1], and lymph node metastasis is closely related with long-term prognosis in patients who undergo esophagectomy, and is considered to be the most important prognostic factor [2–4]. However, no definite consensus has been reached concerning the extent of lymphadenectomy in esophageal cancer, because the precise role of lymphadenectomy has not yet been established. Both radical esophagectomy including three-field lymphadenectomy and transhiatal esophagectomy without radical lymphadenectomy have been performed, and reported to be valuable treatment options for esophageal cancer in the literature. However, the superiority of radial lymphadenectomy is unclear because reported survival benefits vary [5,6].

At our hospital, esophagectomy was performed by laparotomy and right thoracotomy (Ivor-Lewis procedure) in esophageal cancer. However, the lymphadenectomy during esophagectomy was not performed by a standard protocol, and thus, the extent of lymphadenectomy performed at our hospital ranged from limited peritumoral lymphadenectomy to extended two-field lymphadenectomy. Thus, we undertook to identify the effect of lymphadenectomy extent on survival, recurrence, and complications in esophageal cancer patients.


    2. Materials and methods
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
2.1 Patient selection
This retrospective study was conducted on patients with esophageal cancer who had undergone esophagectomy during the 9-year-period from 1995 to 2003. During the study period, 290 patients had undergone esophagectomy for the treatment of esophageal cancer at our hospital. The patients selected had; (1) Squamous cell carcinoma, (2) undergone esophagectomy performed with curative intent, (3) not received neoadjuvant chemotherapy or chemoradiation therapy, and (4) a pathologic stage of I, II, or III. Having applied these selection criteria, 57 patients were excluded because of neoadjuvant chemotherapy or chemoradiation in 39 patients, stage IV esophageal cancer in 13, and other cell types including adenocarcinoma and adenosquamous cell carcinoma in six. Therefore, 233 patients (80.3%) were enrolled for analysis.

2.2 Preoperative evaluation
Preoperative evaluation included history-taking and a physical examination, endoscopy with biopsy, barium swallow esophagography, chest CT scan of the thorax and upper abdomen, abdominal ultrasonography, and bone scan. Those with upper thoracic tumors underwent bronchoscopy for the assessment of possible tracheobronchial invasion. Chest MRI was performed in cases with possible great vessel or cardiac invasion. PET scan and EUS were not performed routinely.

2.3 Study groups
Lymph node stations were categorized into three regions (paraesophageal, upper thoracic, and abdominal) for the analysis. The paraesophageal region included peritumoral, paraesophageal, and subcarinal lymph nodes; the upper thoracic region paratracheal, right recurrent laryngeal, and aortopulmonary lymph nodes; and the abdominal region right and left cardiac, lesser curvature, greater curvature, left gastric, common hepatic, splenic artery, splenic hilum, and celiac lymph nodes. The patients were divided into three study groups according to extent of lymphadenectomy. Patients who had undergone lymphadenectomy in the paraesophageal region only were assigned to group 1; those that received lymphadenectomy of paraesophageal and abdominal or paraesophageal and upper thoracic regions were assigned to group 2 (the paraesophageal and abdominal lymphadenectomy was assigned as group 2a, the paraesophageal and upper thoracic lymphadenectomy group 2b); and those that underwent lymphadenectomy in all three regions were assigned to group 3.

2.4 Surgical procedure
The Ivor-Lewis procedure or extended Ivor-Lewis procedure (cervical anastomosis) according to tumor location are standard procedures for esophagectomy at our hospital. Extended Ivor-Lewis operation was performed in the tumor located above the carina level. Colon was used as an alternative conduit when stomach was unavailable. Lymphadenectomy extent was decided by surgeon's preference. Limited peritumoral lymphadenectomy was performed by one surgeon, and involved the removal of peritumoral, paraesophageal, and subcarinal lymph nodes (group 1). In this limited lymphadenectomy group, abdominal lymphadenectomy was not performed and whole stomach was used as a conduit, therefore, lymphatic chains in the lesser curvature were not removed. A wider range of lymphadenectomy was performed by two other surgeons (groups 2 and 3). Upper thoracic lymphadenectomy involved removal of paratracheal and upper paraesophageal lymph nodes routinely (upper thoracic region). Right recurrent laryngeal and aortopulmonary lymph nodes were removed when metastasis was suspected by preoperative studies or intraoperative gross findings. Abdominal lymphadenectomy involved removal of cardiac, lesser curvature, and left gastric lymph nodes routinely (abdominal region). Common hepatic, splenic, splenic hilum, and celiac lymph nodes were removed when metastasis was suspected by preoperative studies or intraoperative gross findings. In the case of abdominal lymphadenectomy, lesser curvature and gastroesophageal junction were resected and stomach was fashioned as a slender tube.

2.5 Follow-up
Postoperative follow-up was performed at the attending surgeon's outpatient clinic. Follow-up data till December 2005 was collected for analysis. Data were obtained by reviewing medical records, telephone contacts, or by consulting the national database of death statistics. The data collection on survival status was possible in 230 patients (98.7%). However, cause of death was not identified in 11 patients. Therefore, complete follow-up was possible in 219 patients (94.0%). The median period of follow up was 29 months (1–128 months).

2.6 Statistical analysis
Statistical analyses were performed using SPSS software (version 11.0, SPSS Inc. Chicago, IL). Continuous variables are expressed as means ± standard deviation. Discrete variables are described as number and ratio. Comparisons of continuous variables between groups were done using one-way ANOVA, and comparisons of discrete variables using Pearson's chi-square test or Fisher's exact test. Survival rates were calculated using the Kaplan-Meier method and differences between groups were compared using the log-rank test. P values of <0.05 were presumed to indicate statistical significance.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Patients were aged from 33 to 80 years (median age, 62 years), and there were 224 men and nine women tumor locations were upper thoracic in 39 patients (16.7%), mid-thoracic in 143 (61.4%), and lower thoracic or gastroesophageal junction in 51 (21.9%). The operation types were Ivor-Lewis operation in 185 patients (79.4%), extended Ivor-Lewis operation in 39 (16.7%), and colon interposition in nine (3.8%). Complete resection was possible in 221 patients (94.8%). R1 resection (microscopic residual tumor) and R2 resection (gross residual tumor) were performed in 10 (4.3%) and 2 (0.9%) patients, respectively. Combined malignancy in other organs were identified in six patients, which were four stomach cancers, one lung cancer, and one colon cancer. Concomitantly performed operations were cholecystectomy in six patients, total gastrectomy in four, proximal gastrectomy in one, stomach wedge resection in one, colon resection and anastomosis in one, distal pancreatectomy in one, and lobectomy in one. There was no difference in the incidence of concomitantly performed procedure between study groups. Operative mortality (30-day mortality) occurred in five patients (2.1%) and operative complications in 93 patients (39.9%). Mean hospital stay was 25.4 ± 17.0 days (10–182 days).

The demographic and operative data of the three study groups are shown in Table 1 . There were 67 patients in group 1, 102 in group 2 (76 in group 2a and 26 in group 2b), and 64 in group 3. The mean age of group 3 was 64 years and this was statistically significant higher than the mean ages of groups 1 and 2. Tumor location, type of operation, complete resection rate, operative mortality, morbidity, mean hospital stay, and adjuvant treatment were no different between the three study groups. The distribution of T stage was similar in the study groups and T3 constituted more than a half of all three groups (Table 2 ). However, the groups differed in terms of N stage. N0 disease was more frequent in group 1 than in the other two groups. Therefore N1 disease was more frequent in groups 2 and 3 than in group 1 (p = 0.03). Mean total numbers of dissected lymph nodes were 16.9 ± 12.1 in group 1, 21.0 ± 12.5 in group 2, and 33.1 ± 15.7 in group 3, and the difference was significant (p < 0.001). However, numbers of positive lymph nodes in N1 disease were no different in the three groups.


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Table 1. Demographic and operative data of the three study groups
 

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Table 2. Pathologic data of the three study groups
 
One hundred forty-three patients (61.4%) died during the follow-up period. Esophageal cancer-related death occurred in 108 patients (46.4%) and death from other causes in 35. Causes of death other than esophageal cancer were pneumonia in 16, lung cancer in 3, hypopharynx cancer in 2, trauma in 1, stroke in 1, drug intoxication in 1, and unknown causes in 11. The overall 5-year survival was 34.8% for all patients. Overall 5-year survivals according to stage were 58.9% in stage I, 40.8% in stage IIA, 38.8% in stage IIB, and 14.9% in stage III. The overall 5-year survivals by study group were 21.2% in group 1, 36.3% in group 2, and 53.7% in group 3 (p = 0.019; Fig. 1 ). The overall 5-year survivals of group 2a and 2b were 41.8 and 34.0%, and there was no statistically significant difference (p > 0.05). For those with N0 disease, overall 5-year survivals were 26.7% in group 1, 56.8% in group 2, and 74.4% in group 3 and this difference was statistically significant (p = 0.001). However, overall 5-year survivals for N1 disease were 9.1% in group 1, 18.1% in group 2, and 34.9% in group 3 and this was not significant (p = 0.073). Recurrence occurred in 125 patients (53.6%) during follow-up. Median duration of recurrence after operation was 12.5 months (1.6–70 months). Locoregional recurrence occurred in 44 patients (35.2%) and distant metastasis in 81 patients (64.8%). Sites of recurrence differed in the three study groups. Locoregional recurrence was more common in group 1 than in groups 2 and 3, which was primarily caused by a higher rate of regional recurrence. However, recurrence rates at a distant organ were not different for the three groups (Table 3 ). The 5-year disease free survival of all patients was 29.1%, and by study group were; 15.9% in group 1, 32.0% in group 2, and 41.6% in group 3 (p = 0.012; Fig. 2 ). However, there was no difference in 5-year disease free survival between group 2a and 2b (33.8 and 28.2%, respectively). Five-year disease free survivals for N0 disease were; 18.8% in group 1, 53.9% in group 2, and 52.4% in group 3 (p = 0.001), and 5-year disease free survivals for N1 disease were 9.1% in group 1, 13.2% in group 2, and 32.8% in group 3 (p = 0.093).


Figure 1
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Fig. 1. Overall 5-year survival of the study groups.

 

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Table 3. Recurrence patterns after esophagectomy
 

Figure 2
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Fig. 2. Five year disease free survival of the study groups.

 

    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Lymphatic dissemination is an early event in esophageal cancer, and it is generally known that 80% of patients have a positive lymph node at the time of surgery. Lymph node metastasis is found in 30–40% of submucosal tumors [7] and in 40–50% of T2 tumors, and rises to greater than 80% for T3 and T4 tumors [8]. The lymph node involvement is known to be the most important prognostic factor in resectable esophageal cancer. Ellis and colleagues [9] reported that long-term survivals for stage I and IIA were 50.8 and 37.5%, however these reduced to 16.2 and 13.6% for stage IIB and III in their series of 265 esophagectomy patients. They suggested that lymph node metastasis is strongly associated with poor long-term survival. Other reports have concluded that nodal involvement is the single most important prognostic factor for both locoregional and systemic recurrence after complete resection [2–4]. Nakagawa and colleagues [10] also reported that a higher number of positive lymph nodes increased the risk of hematogenous recurrence, which implies that the extent of lymph node involvement is related with prognosis.

The lymphatic drainage of the esophagus pursues a bidirectional cervical and abdominal route. Lymphatic channels of the esophagus form uninterrupted dense plexuses and long channels in submucosal layer [11]. These features enable lymphatic metastasis to occur easily in cranial and caudal directions from a primary tumor. Akiyama and colleagues [1] reported the widespread distribution of positive lymph nodes irrespective of primary tumor location. This wide distribution of lymphatic metastasis occasionally occurs at anatomically distant metastasis than other intrathoracic lymph nodes adjacent to the main tumor, especially in recurrent laryngeal and perigastric lymph nodes [12]. Skip metastasis is also a common phenomenon, whereby nodal metastasis appears at remote sites with no intervening nodal metastasis [11]. Traditionally enlargement of regional lymph nodes was regarded as a positive finding during preoperative imaging studies. However, Schroder and colleagues [13] suggested that there exists no significant correlation between lymph node size and likelihood of nodal metastasis. They reported that the average size of a metastatic lymph node was 6.7 mm and that only 12% of metastatic nodes exceeded 10 mm. Therefore, the widespread, remote, and size-independent lymphatic characteristics of metastatic esophageal cancer make it more difficult to decide on the extent of lymphadenectomy and achieve complete clearance.

Because of these characteristics of the lymphatic metastasis of esophageal cancer, there are two opinions about lymphadenectomy in esophageal cancer. Supporters of extensive lymphadenectomy insist that extensive lymphadenectomy allows accurate staging, reduces locoregional recurrence, and hence increases long-term survival [14]. However, others argue that if a cancer has an invasive nature then it represents systemic rather than local disease. In such cases, it is argued, lymphadenectomy cannot alter the natural disease course and survival will remain unchanged regardless of the extent of resection [15]. Currently, the controversy remains, it is still debatable as to what constitutes optimal lymphadenectomy, and whether lymphadenectomy offers any survival benefit.

The effects of extensive lymphadenectomy on long-term survival are still disputed. Several reports insist that aggressive lymphadenectomy can improve long-term outcome [16,17]. D’Journo and colleagues [18] reported on a comparative study between the groups of standard and extended two-field lymph node dissection in their 102 adenocarcinoma patients. Disease free survivals were found to differ significantly according to lymphadenectomy groups, were 10 and 41% in each group. They also reported that this difference was more significant in N0 patients. Improved survival was also found to be associated with lymphadenectomy extent in a meta-analysis of three-field lymphadenectomy [19]. In this analysis, extensive lymphadenectomy was observed to decrease locoregional recurrence and improve long-term survival.

Conversely, others have found no survival benefit for extensive lymphadenectomy. A randomized comparative study on the comparison between transhiatal esophagectomy and the Ivor-Lewis operation revealed no significant survival improvement and questioned the role of trans-thoracic mediastinal lymphadenectomy [5]. As for three-field lymphadenectomy, one randomized study showed no survival benefit versus two-field lymphadenectomy [6].

Although results about survival benefit according to the extent of lymphadenectomy have failed to concur, extensive lymphadenectomy has several advantages that may influence long-term survival. Accurate staging is a generally accepted advantage of extensive lymphadenectomy. In the present study, group 1 contained a high proportion of N0 patients, whereas the proportions of N0 patients in groups 2 and 3 were lower and not significantly different from each other. Therefore, it may be that a significant proportion of patients in group 1 were understaged and that subsequent incomplete resection was inevitable. In the present study, overall and disease free survivals for N0 patients in group 1 were 28.0 and 17.9%, respectively, which are poor compared with previous reports [16,17]. Moreover, low 5-year survival rates means that limited lymphadenectomy cannot accurately diagnose N0 disease.

The number of positive lymph nodes is a recognized factor of long-term survival. Extensive nodal involvement is considered an indicator of systemic disease and cannot be cured by extensive lymphadenectomy [20]. However, a nodal involvement of less than 4 and a positive lymph node ratio of less than 0.2 are regarded as favorable prognostic factors in N1 disease [21,22]. Therefore, reduced tumor burden in nodal involvement is regarded as an indicator of the likelihood of cure by curative surgical resection of primary tumor and metastatic lymph nodes. The possibility of R0 resection increases in this subset of patients. In this study, some portion of pathologic N0 patients of the lesser lymphadenectomy group might have been understaged and had residual disease in spite of small nodal metastasis. Therefore, a significant proportion of N0 patients in group 1 and a small proportion of N0 patients in group 2 would probably benefit from more extensive lymphadenectomy.

Analyses of recurrence patterns after extensive lymphadenectomy have usually reported about 40% incidence of locoregional recurrence. Locoregional recurrence is frequently found after limited resection, and the mediastinum is a common site of recurrence after transhiatal esophagectomy [23]. After limited lymphadenectomy, the most frequent nodal recurrent site is the superior mediastinum or aortopulmonary window lymph nodes, which are located beyond the dissection area. Altoki and colleagues [24] reported that extensive lymphadenectomy could reduce the local recurrence rate to 8% and increase disease free survival. Recurrences in the present study showed that locoregional recurrence was higher in group 1 than in groups 2 and 3, and that this was attributable mainly to higher regional recurrence. However, recurrence in a distant organ was similar in the three study groups. We suspect that a decrease in the overall recurrence rate due to reduced locoregional recurrence is the main cause of improved survival.

The pitfall of extensive lymphadenectomy is its high morbidity rate. Many studies have focused on the higher morbidity associated with extensive lymphadenectomy over limited lymphadenectomy; especially in literature concerning three-field lymphadenectomy. It is suspected that mediastinal lymphadenectomy can injure the bronchial artery, nerve, tracheobroncial tree, and the recurrent laryngeal nerve [25]. Moreover, it has been reported that extended two-field lymphadenectomy increases complication rates compared with standard two-field lymphadenectomy [18]. In the present study most group 3 patients underwent extended two-field lymphadenectomy, whereas most group 2 patients underwent standard two-field lymphadenectomy, according to the definition of the international consensus conference held in Munich in 1994 [20]. Neither total two-field lymphadenectomy or three-field lymphadenectomy were routinely performed in the present study. Moreover, we found no significant difference between the three study groups in terms of complication rates, and mean hospital stays were also similar. We suspect that this is because we did not perform total two-field or three-field lymphadenectomy and because the extent of lymphadenectomy in many group 3 patients was less than that of normal extended two-field lymphadenectomy.

This study has two limitations. The first is that it is neither prospective nor randomized. In particular, patient selection bias probably influenced long-term survival. For example, patients in group 3 were older than those in groups 2 and 3. However, age is a known poor prognostic factor in esophageal cancer, therefore it is suspected that the improvement of survival in group 3 was not related to the age factor. Stage migration is another factor capable of affecting long-term survival, and can be suspected based on the high proportion of N0 disease and of poor survival in group 1. Stage migration often leads to the misinterpretation of results and to inappropriate conclusions in a diagnostic or therapeutic procedural context. It is our opinion that because survival benefit was identified for all study subjects including all stages, regardless of inevitable stage migration within the study group, that survival was improved by an increased lymphadenectomy extent itself.

The result of this study show that overall and disease free survivals increased according to lymphadenectomy extent. However, because lymphadenectomy was not performed according to an established protocol, it is difficult to conclude that a certain method of lymphadenectomy is superior. Nevertheless, as was reported by Lerut and colleagues [14], who found a linear correlation between the number of resected nodes and survival, it is our opinion that the extent of lymphadenectomy is closely related with the long-term survival of patients with esophageal cancer.


    Appendix A
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Conference discussion

Dr T. Lerut (Leuven, Belgium): Of course I too believe in the value of extended lymphadenectomy as a means to influence the natural course of the disease.

I have two questions. You have 3 groups, but how did you decide on which patients you were doing a 1 compartment, a 2, or a 3 compartment lyphadenectomy?

And then you make a difference between local recurrences and regional recurrences. What is the definition of local recurrence and what is the definition of a regional recurrence?

Dr Kang: The extent of lymphadenectomy was determined by the surgeons who operated on the patients. One surgeon did not want to perform a radical lymphadenectomy. In group 1 patients, one surgeon performed the paraesophageal lymphadenectomy only. The other two surgeons usually performed a more radical lymphadenectomy, including a standard two-field or extended two-field lymphadenectomy. So it was not randomized by a certain study protocol, but it was determined by the surgeon's preference.

What was your next question?

Dr Lerut: Your definition of local and regional.

Dr Kang: In this study, recurrence at the anastomotic site was defined as local recurrence, and regional recurrence was defined as nodal recurrence in the mediastinum or abdominal area.

Dr O. Kshivets (Siauliai, Lithuania): As I understood, you have patients with lower third and middle third the esophagus cancer, not upper third?

Dr Kang: Pardon?

Dr Kshivets: Did you have these patients with localization of cancer in the lower third and middle third of esophagus?

Dr Kang: Yes.

Dr Kshivets: Not upper third.

The second question is, did you perform cervical lymphadenectomy? Did you perform three-field lymphadenectomy, I mean abdominal, intrathoracic, and cervical lymphadenectomy?

Dr Kang: For the second question, three-field lymph node dissection is not the usual procedure performed in our hospital. We have experienced only several cases of three-field node dissection. Three-field node dissection patients are not included in this study.

I beg your pardon, I really didn’t understand your first question. The location of the tumor?

Dr Kshivets: Yes, cancer.

Dr Kang: The type of operation in correlation with the location of the tumor?

Dr Kshivets: My question is, these are patients with lower third of esophagus cancer and middle third? Do you perform the procedure with the upper third of the esophagus cancer?

Dr Kang: Can you explain lower?

Dr Wood (Chairman): He's asking do you have any cervical esophageal cancers in this series or are they all mid and distal third.

Dr Kang: We do not operate on cervical esophageal cancer. We use concomitant chemoradiation.

Dr K. Moghissi (Hull, United Kingdom): I think the first part of my question has already been asked. You might have actually mentioned it, but did you analyze your results according to the histology, adenocarcinoma versus squamous cell carcinoma?

Dr Kang: Analyze what?

Dr Moghissi: Did you analyze your results according to the histology of the lesions, adenocarcinoma versus squamous cell carcinoma?

Dr Kang: Most of the patients in this study are squamous cell carcinoma. About 98% of the patients have squamous cell carcinoma. Adenocarcinoma is very rare in Asian countries.

Dr B. Kubisa (Szczecin, Poland): How can you explain the paradox that the wider extent of lymphadenectomy has a better survival in N0 patients, because the

N0 patients have better survival without extended lymphadenectomy.

Dr Kang: The overall survival in all patients was more superior in group 2 and group 3 than group 1. In subset analysis, survival in N0 patients was superior to N1 patients. We must be very cautious to interpret this data because, in my opinion, many patients are underdiagnosed in group 1, so they may not be true N0 patients. So many people with N0 disease can be included in the N1 disease in group 1. So the difference in survival may show the diverse nature of the N0 group. Stage migration might have occurred in this study group, but, as a result, the overall survival in all patients shows a survival gain. Therefore, I think that a certain effect of the extent of lymphadenectomy may have an effect on overall survival. It can be the explanation for that paradox.


    Footnotes
 
\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.


    References
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 

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