Kitakanto Med J 2002 ; 52 : 189-193 189 A Proposed Strategy for Treatment of Superficial Carcinoma in the Thoracic Esophagus Based on an Analysis of Lymph Node Metastasis Susumu Kawate,' Susumu Ohwada,' Tetsushi Ogawa,' Takao Okano,' Seiji Nakamura,' Yoshiyuki Kawasima,' Naoki Tomizawa,' Izumi Takeyoshi,' Osamu Kawamura,2 Motoyasu Kusano2 and Yasuo Morishita 1 Background and Aims : To determine the optimal treatment of superficial carcinoma of the thoracic esophagus, we retrospectively analyzed the site and prevalence of lymph node metastases in three-field dissection specimens removed during radical esophagectomy. Methods : We reviewed the medical charts and surgical and histopathological reports of 34 patients with superficial carcinoma of the thoracic esophagus, who were treated with esophagectomy and three-field lymph node dissection. Results : Lymph node metastases were found in 14 of 34 patients (41%). None of five cases with tumor invasion of only the pep or plpm had lymph node metastases. However, the prevalence of lymph node metastases from tumors that invaded the pmm or psm was 22% and 60%, respectively. Even when the cancer was located in the lower esophagus, the prevalence of cervical lymph node metastases was 20%. Two of three (67%) patients had cervical lymph node metastases even when there were no metastases in mediastinal nodes ("jumping lymph node metastases"). The 5-year survival rates in patients with and without lymph node metastases were 83% and 100%, respectively. Conclusions : A radical esophagectomy with three-field lymph node dissection should be performed on patients who have superficial carcinoma of the thoracic esophagus that invades the pmm or deeper. (Kitakanto Med J 2002 ; 52 : 189-193) Key Words : Superficial esophageal carcinoma, Three-field dissection, Lymph node metastasis Introduction Esophageal carcinoma has a poor prognosis. Lymph node metastasis is an important factor in the prognosis.1,2 An extended radical lymphadenectomy has been advocated, but its efficacy has not been demonstrated in well-controlled, randomized trials. The presence or absence of lymph node metastasis is the key factor in determining the treatment of superficial carcinoma of the esophagus. Endoscopic mucosal resection (EMR) is the standard treatment for esophageal carcinoma that invades only the intraepithelial (pep) or lamina propria mucosae (plpm), because lymph node metastases from such tumors are rare. However, there is no accepted standard for treating esophageal carcinoma that invades the muscularis mucosae (pmm) or the submucosa (psm). The purpose of this study was to analyze the site and prevalence of lymph node metastases from superficial carcinoma of the thoracic esophagus, in specimens from radical esophagectomy with three-field lymph node dissection, in order to determine an optimal treatment. Patients and Methods Between June 1979 and October 2001, 150 patients with thoracic esophageal carcinoma underwent a thoracic esophagectomy through a right thoracotomy at the Second Department of Surgery, Gunma University 1 Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi,Gunma 371-8511, Japan 2 Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan Received : March 5, 2002 Address : SUSUMU OHWADA Second Department of Surgery, Gunma University Faculty of Medicine, Showa-machi 3-39-22, Maebashi, Gunma 371-8511, Japan
190 Strategy for Superficial Esophageal Carcinoma Hospital. Between February 1986 and October 2001, 96 of these patients had three-field lymph node dissection, and 36 of those patients had histologically proven superficial carcinoma. We reviewed the medical charts and surgical and histopathological reports of those 36 patients. Two patients who received preoperative adjuvant chemotherapy were excluded from the Table 1. Patient characteristics study. Data from the charts of the remaining 34 patients were analyzed (Table 1). All variables were expressed in the terminology of the Japanese Society for Esophageal Diseases.4 There were 27 males and 7 females, with a mean age of 65 years (range 50 to 79). Seven patients had carcinoma in the upper part (Ut), 22 in the middle part (Mt), and 5 in the lower part (Lt) of the thoracic esophagus. A curative resection was intended in all cases. A retrosternal route for reconstruction was selected for 18 patients, and a posterior mediastinal route for 16. The stomach was used for esophageal replacement in 23 patients, the colon in 7 and the jejunum in 4. The histological depth of tumor invasion was the pep in one patient, the plpm in 4, the pmm in 9 and the psm in 20. Five patients had EMR prior to radical esophagectomy. Submucosal cancer invasion was classified as sm 1 in the upper third, sm2 in the middle third, and sm3 in the lower third of the submucosa. The histological classification of the primary tumors of 32 patients was squamous cell carcinoma, well differentiated in 12, moderately differentiated in 14, and poorly differentiated in 6. The histological classification was adeno-squamous cell carcinoma in one patient and undifferentiated carcinoma in another. The designation for identifying resected lymph nodes in three-field dissection specimens is presented in Figure 1. All lymph nodes dissected from resection Fig. 1. Lymph node number is that used by the Japanese Society for Esophageal Disease.
191 Table 2. Lymph node metastasis in relation to tumor location and depth of invasion Table 3. Field of lymph node metastases in relation to location of primary tumor Table 4. Patients with cervical lymph node metastases without metastases to the upper mediastinum specimens were examined histologically after formalin fixation. Statistical analysis was performed using the StatView J-5.0 program (SAS Institute Inc., Cary, NC). The chi-square test and Fisher's exact test were used for group comparison. Cancer-related survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to compare the curves. P ƒ 0.05 was considered statistically significant. Results Lymph node metastases Lymph node metastases were found in 14 of 34 patients (41 %) who underwent three-field dissection for a superficial carcinoma of the thoracic esophagus. The relationship between lymph node metastases and the location and depth of the tumor is presented in Table 2. The prevalence of lymph node metastases from tumors of the Ut, Mt, and Lt were 29%, 45%, and 40%, respectively. There was no correlation between prevalence of metastasis and location of the primary tumor. None of the five patients whose tumors invaded only the pep or plpm layers had lymph node metastases. However, the prevalence of lymph node metastases from tumors that had invaded the pmm or psm was 22% and 60%, respectively. The prevalence of lymph node metastases from tumors with invasion depths of sm 1, sm2, and sm3 was 50%, 60%, and 69%, respectively. As the depth of tumor invasion increased beyond the level of the plpm, the prevalence of lymph node metastases also increased. Table 3 lists the relationship of the percent of cases with lymph node metastases in each field with the location of the primary cancer. The prevalence of lymph node metastases in the neck, thorax, and abdomen was 9%, 21%, and 21%, respectively. Metastases to cervical lymph nodes were even found in one of 5 patients (20%) with a primary tumor in the Lt. Two of 3 patients (67%) with cervical lymph node metastases had no metastases in mediastinal nodes ("jumping lymph node metastases") (Table 4). Jumping lymph node metastases to cervical nodes even occurred from a tumor located in the Lt. Survival rates Cancer-related survival data of patients who underwent three-field lymph node dissection is shown in Fig. 2. The median follow-up time was 3.2 years (range : 3 months to 11.3 years). Five-year survival rates in patients with and without lymph node metastasis were 83% and 100%, respectively.
192 Strategy for Superficial Esophageal Carcinoma Survival Curve positron emission tomography with 18-F-fluorodeoxy-D-glucose (FDG-PET) are used to estimate the depth of invasion and identify lymph node metastasis.5 `7 EUS is one of the most useful modalities for the estimation of tumor depth, but accurate and sensitive preoperative diagnosis is often difficult.5 `7 EMR, another technique used to evaluate the depth of tumor invasion, has also been used for curative treatment of superficial esophageal carcinoma limited to the plpm. When feasible, EMR is the treatment of choice for superficial carcinoma that has invaded the pmm or psm. The final decision to perform an esophagectomy should be based on histological evidence of tumor invasion depth and vascular invasion from EMR specimens (diagnostic EMR). If there is tumor invasion of the pmm without vascular involvement, a Fig. 2. Cancer-related survival curves of patients who had threefield lymph node dissection. careful evaluation of patient status and detailed informed consent are necessary in order to plan an esophagectomy after EMR. A radical esophagectomy Tumor recurrence All patients who had no microscopic evidence of lymph node metastases are recurrence-free. Cancer subsequently recurred in 3 of 14 patients (21%) with lymph node metastases. One patient developed metastasis in a cervical lymph node, another one had metastases to the peritoneum and pleura, and the third had bone metastasis. Discussion In this study, the prevalence of lymph node metastases in patients with a superficial carcinoma of the thoracic esophagus was 43% at the time of esophagectomy. There was no difference in the prevalence of metastases from primary tumors in the upper, middle, or lower esophagus. Extensive metastases to the cervical, thoracic, and abdominal nodes occurred not only from deeply invasive, advanced carcinoma, but also from superficial tumors. One of the five patients (20%) with cancer of the lower esophagus had cervical lymph node metastases. In addition, 67% of the patients who had metastases in cervical lymph nodes had no metastasis in upper mediastinal nodes. We recommend, therefore, that cervical lymph nodes should be removed, even if the primary tumor is located in the lower esophagus, and even if there is no histologic evidence of metastases in the upper paraesophageal (# 105) or paratracheal (# 106) lymph nodes. In our study, the prevalence of lymph node metastasis was high when a tumor had invaded the pmm. Thus, an accurate determination of the depth of tumor invasion is the crucial factor on which treatment of superficial esophageal carcinoma is based. CT and MRI scans, endoscopic ultrasonography (EUS), and with three-field lymph node dissection is recommended for superficial esophageal carcinoma that involves the pmm or psm, because the risk of lymph node metastases is high. The overall survival of patients who undergo threefield lymph node dissection is reported to be better than that of patients who have only two-fields removed, but there have been no randomized controlled studies.8-10 On the other hand, three-field dissection has been reported to increase mortality and morbidity, particularly recurrent laryngeal nerve damage and leakage of anastomoses.9 `11 In our previous study, mortality rates and postoperative courses were similar for patients who had radical esophagectomy with either two- or three-field lymph node dissection.12 Indeed, in that series of patients with superficial esophageal carcinoma, anastomosis leakage or laryngeal nerve paralysis occurred in only two patients (3% of the study population). In conclusion, an esophagectomy with three-field lymph node dissection should be performed when a superficial carcinoma of the thoracic esophagus invades into or below the pmm. References 1. Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus : A summary of responses to a questionnaire on superficial cancer of the esophagus in Japan. Surgery 1998 ; 123 : 432-439. 2. Tajima Y, Nakanishi Y, Ochiai A, et al. Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma : Analysis of 240 surgically resected tumors. Cancer 2000 ; 15 : 1285-
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