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Background: There are controversies regarding the extent of lymphadenectomy necessary during the course of esophagectomy for submucosal esophageal cancer. The purpose of this study was to examine the long-term outcomes after esophagectomy with extended lymphadenectomy in patients with submucosal esophageal cancer and to investigate the prognostic factors in these patients., Materials: A prospectively maintained database identified 105 previously untreated patients with submucosal esophageal cancer who underwent transthoracic esophagectomy with three-field or two-field lymphadenectomy. Median follow-up was 101 months., Results: All patients received R0 resection. Ninety-eight patients had squamous cell carcinoma, and seven had adenocarcinoma. Lymph node metastasis was present in 38 patients (36.2%), of whom 9 patients (23.7%) had positive cervical nodes. Thirty-five patients (33.3%) had other primary malignancies. The overall 5- and 10-year survival rates were 74.4 and 57.4%, respectively. The cause of death was recurrent disease in 16 patients, other malignancy in 12, and noncancer-related disease in 18. Univariate analyses demonstrated that other primary malignancy (P = 0.0041), poor differentiation (P = 0.0203), and angiolymphatic invasion (P = 0.0347) significantly affected overall survival. There was no difference in survival between patients with lymph node metastasis and those without (P = 0.9809). Multivariate analysis found other primary malignancy to be the only independent prognostic factor (hazards ratio, 2.295; 95% confidence interval, 1.201-4.386; P = 0.0119)., Conclusions: Esophagectomy with extended lymphadenectomy for submucosal esophageal cancer results in 57.4% survival at 10 years. Other primary malignancy is the only independent predictor affecting long-term survival. Patients should be examined rigorously for other primary malignancy as well as recurrent disease during long-term follow-up.

Here, we report a case of long-term survival after resection of an adenocarcinoma in Barrett's esophagus with metastasis to Virchow's node. A 71-year-old woman was referred to our hospital with a tumor in the lower third of the thoracic esophagus, located just beneath the tracheal bifurcation because of an hiatal hernia. On admission, she had a palpable lymph node in Virchow's node. The esophageal tumor and this lymph node were biopsied. They were pathologically found to be an adenocarcinoma in the esophagus which had metastasised to the lymph node. She underwent transthoracic esophagectomy with three-field lymph node dissection. The pathological diagnosis was adenocarcinoma in Barrett's esophagus with the UICC stage classification of pT1, pN1, pM1-LYM, Stage IVB. She received postoperative chemotherapy of cisplatin combined with 5-fluorouracil. The patient is well without recurrence at 14 years to date after surgery. We recommend thoracoabdominal esophagectomy with three-field lymphadenectomy for an advanced carcinoma in the upper and middle thoracic esophagus regardless of histological types.

Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer.

Purpose: The authors evaluated the efficacy of extended radical (three-field) lymphadenectomy for esophageal cancer compared with less radical (two-field) lymphadenectomy. STUDY SUBJECTS AND ANALYTIC METHODS: The mortality and morbidity rates, postoperative courses, and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991. Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991., Results: Three-field dissection resulted in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection. The mortality rates, postoperative courses and quality of life were the same for both procedures., Conclusions: Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival, acceptable mortality and morbidity rates, and good postoperative course and quality of life.

In the past 20 years, 403 patients with thoracic esophageal carcinoma underwent radical surgery. The aim of this study was to determine whether extended lymph node dissection improved the prognosis of these patients. All of the patients were divided into 4 groups every 5 years from group A to group D. Group A (n = 39) underwent radical esophagectomy with lower mediastinal and abdominal lymphadenectomy by the left thoracoabdominal approach. Majority cases in Group B (n = 94) also underwent radical esophagectomy with right upper, lower mediastinal and abdominal lymphadenectomy (incomplete 2-field dissection) by the right thoraco-abdominal approach. About 40% cases in Group C underwent radical esophagectomy with extended cervicothoraco-abdominal lymph node dissection (3-field dissection) and almost all of the others had radical esophagectomy with 2-field dissection. About 60% of the cases in group D underwent radical esophagectomy with 3-field dissection and the majority of the others had complete 2-field dissection (i.e.) radical lymphadenectomy around bilateral upper, lower mediastinal and abdominal lymph nodes. The five-year survival rate was 21% in group A, 23% in group B, 37% in group C and 55% in group D. The survival curve was improved according to the extent of lymph node dissection. Especially significant improvements of survival rate were found in group C and D compared with those in group A and B. Furthermore, group D showed significantly better survival than that of group C. Complete 2-field and 3-field dissection resulted in a better prognosis than incomplete 2-field dissection, while no significant difference in prognosis was found between complete 2-field and 3-field dissection. However, neither 2-field nor 3-field dissection resulted in improved prognosis in cases involving 7 or more positive lymph node metastases. These results suggest that radical esophagectomy and lymph node dissection involving bilateral upper mediastinal area are important factors to improve postoperative prognosis in patients with thoracic esophageal carcinoma. However, more effective adjuvant therapy is needed for the patients with many positive node metastases.

To evaluate significant postoperative prognostic factors for esophageal carcinoma, clinicopathological findings and several markers for biological malignant potential were studied, including cell nuclear DNA contents, EGF receptor, p53 protein, MMP-2, Ki-67 positive cell rate, and tumors infiltrating Leu 7 cells. The subjects of this study were 96 patients with thoracic esophageal carcinoma, who underwent radical surgery with extended lymphadenectomy. In the pathological findings, the postoperative survival rate significantly correlated with depth of invasion (pT1(-2) vs. pT3, p = 0.003), lymph node involvement (pNo vs. pN1, p = 0.0002), vascular invasion (-vs. +, p = 0.0003), stage (pSt. 1-2A vs. 3, p = 0.0018), and the number of node involvements (1-3 vs. more than 4, p = 0.025). Analyzing the markers for the malignancy, a significant difference in postoperative mortality due to the relapse was recognized with p value of 0.0009 between Ki-67 positive (under 1%) and Ki-67 negative (over 1%) tumor. Ki-67 positive tumor significantly correlated with the mortality in both cases with pNo (p = 0.024) and pN1 (p = 0.020). Low-grade tumor infiltrating Leu 7 cells significantly correlated with the mortality (Grade 1+ vs. 2+, p = 0.013; Grade 1+ vs. 3+, p = 0.008). These results suggest that Ki-67 study is a useful prognostic factor after radical surgery for thoracic esophageal carcinoma.

The indication, efficacy, and extent of extended lymphadenectomy for a carcinoma in the thoracic esophagus remain controversial and under clinical investigation. Here we report the frequency and mode of lymph node metastasis at operation and of lymph node recurrence after operation in 70 patients who underwent three-field dissection and 75.7% of whom suffered from metastasis or recurrence in the lymph nodes (metastasis in 71.4% and recurrence in 21.4%). Metastasis or recurrence in the cervical and cervicothoracic nodes were found in 18.6% and 41.4%, respectively. The frequency of cervical and cervicothoracic lymph node metastasis or recurrence was, respectively, 40.0% and 90.0% for a carcinoma in the upper thoracic esophagus, 21.6% and 37.8% for a carcinoma in the middle thoracic esophagus, and 4.3% and 26.1% for a carcinoma in the lower thoracic esophagus. Lymph node metastasis at operation was most frequently found in the right recurrent nerve nodes, right paracardiac nodes, periesophageal nodes, and lesser curvature nodes, whereas lymph node recurrence after operation was found in the left upper recurrent nerve nodes and the right supraclavicular, celiac, and abdominal paraaortic nodes. Metastasis or recurrence was rarely found in the internal jugular, pretracheal, greater curvature, common hepatic, or splenic nodes. This finding suggests the need for recurrent nerve node dissection for all cases and for three-field dissection for a carcinoma in the upper or middle thoracic esophagus.

Lymph node metastasis is well-known as the most important prognostic indicator for esophageal carcinomas, and an accurate assessment of positive metastasis can only be made after total lymphadenectomy around the esophagus. However, prior to the development of 3-field lymph node dissection in Japan, no such operation existed for ascertaining the full positivity distribution. We report herein the results of a retrospective study conducted on 70 patients who underwent subtotal esophagectomy with 3-field dissection to discover the patterns of lymph node metastasis from carcinoma in the thoracic esophagus. Lymph node metastases tended to have an orderly spreading pattern in relation to the tumor location, even though the lymph node metastasis varied widely from the lower neck to the upper abdomen. The nodes along the right recurrent nerve and the paracardiac nodes were most frequently found to be positive for metastasis. In contrast, no metastasis was found in the internal jugular nodes, the pretracheal nodes, the common hepatic nodes, or the splenic nodes. Patients with carcinoma in the upper thoracic esophagus rarely had metastasis in the abdominal nodes, while those with carcinoma in the lower thoracic esophagus rarely had metastasis in the cervical nodes. Thus, surgical extirpation of the lymph nodes during 3-field dissection is effective not only to determine the correct tumor staging for the planning of adequate adjuvant therapies postoperatively, but also to produce a guideline for prospective lymphadenectomy for esophageal carcinomas.

The efficacy of an extended radical lymph node dissection for carcinoma in the thoracic esophagus is controversial. Results of a multivariate analysis using clinical data from 127 cases collected from 1982 to 1988 are reported. Twenty-seven of these patients underwent an extended radical (cervico-thoraco-abdominal: 3 fields) lymph node dissection which was recently developed in Japan, while others underwent a standard (thoraco-abdominal: 2 fields) lymph node dissection. They all had a locally-curative resection of the tumor through a right thoracotomy. In this study, 13 factors commonly affecting prognosis were examined: sex, age, cancer location, tumor length, radiographic type, depth of invasion, lymph node metastasis, tumor differentiation, postoperative radiotherapy, chemotherapy, operative risk, postoperative complications, and 3-field or 2-field dissection. Based on the survival-rate curves using Kaplan-Meier's statistics, the 3-field dissection was superior to the 2-field dissection. Moreover, when other prognostic factors were adjusted using Cox's proportional hazards general linear model, the same result was obtained from survival-rate curves. From this analysis, it can be concluded that a 3-field dissection is a better approach for management of carcinoma in the thoracic esophagus.

Nowadays, surgery for a thoracic esophageal carcinoma is accomplished safely, however, there still remain many problems concerning curative resection. Cancerous recurrences of the lymph node is still high against to lymph node dissection around thoracoabdominal region. Therefore, surgery should endeavour to prevent such lymphatic recurrences. In the patients with a carcinoma in the upper or middle third of the esophagus, who underwent extended radical esophagectomy, a significantly high incidence of metastasis in the recurrent nerve lymphatic chain was noted in comparison with that in patients with that in those who underwent standard radical resection. Complete resection of the recurrent nerve lymphatic chain is generally difficult through the thoracic approach alone, and such approach might be the factor causing the poor prognosis after standard radical surgery for an upper or middle thoracic esophageal carcinoma. Accordingly, extended radical surgery by the cervicothoracoabdominal approach can produced improved surgical curability for an upper or middle thoracic esophageal carcinoma. On the other hand, pulmonary complications are still a major postoperative complication following radical esophagectomy due to extended radical lymphadenectomy around the paratracheobronchial region. So, it is now clear that we should preserve the right bronchial artery and pulmonary nerves branched from the vagus nerve during the thoracic procedure, if these unaffected by cancerous invasion. Adopting this procedure resulted in a marked decrease in the incidence rate of postoperative severe pulmonary complications. Finally, in the near future we expect to develop criteria to select the best treatment for each specific individual based on preoperative studies of the biological characteristics of the carcinoma.

Over the period from 1982 to 1988, 127 cases with carcinoma in the thoracic esophagus underwent curative resection through a right thoracotomy. Cervicothoracic-abdominal lymph node dissection was performed in twenty-seven cases. No operative death occurred and only one hospital death (4%) was recorded. The only postoperative complication was recurrent laryngeal nerve palsy. Based on the adjusted survival-rate curves using Cox's method, there was significant difference in prognosis in favor of these 27 cases that received cervicothoracic-abdominal lymph node dissection over those that did not. The survival rate of all curatively operated cases was noticeably improved by using this procedure. Of those that underwent dissection only, or dissection with postoperative radiotherapy or chemotherapy, the best prognosis could be reached by a combination of the cervicothoracic-abdominal lymph node dissection and postoperative chemotherapy. From follow-up data regarding recurrence rates, a more extended dissection and complete removal of lymph nodes in the left upper mediastinum and retroperitoneum should further improve the long-term prognosis.