Japanese Journal of Clinical Oncology 31:203-208 (2001)
© 2001 Foundation for Promotion of Cancer Research
Comparison of Surgical Management of Thoracic Esophageal Carcinoma Between Two Referral Centers in Japan and China
1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai, China and 2Department of Surgery, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: Comparison was made between two referral centers, the National Cancer Center Hospital (NCCH) in Japan and Shanghai Chest Hospital (SCH) in China. The aim was to detect the possible differences between surgical management of thoracic esophageal carcinoma in these two countries and to shed some light on how to improve the therapeutic outcomes at similar institutions.
Methods: A total of 98 patients (50 from NCCH and 48 from SCH) with squamous cell carcinoma of the thoracic esophagus treated by a single surgeon at either center during January 1997 to July 1999 were retrospectively reviewed.
Results: Lugol staining and endoscopic ultrasonography were applied routinely at NCCH only. More early diseases, multiple lesions and synchronous tumors of the digestive tract were detected in the NCCH group than in the SCH group. Significantly more stations of lymph nodes were dissected and higher metastatic rates to certain stations were found after more extensive lymphadenectomy in the NCCH group. Operation time was prolonged with significantly more postoperative complication but amount of blood loss or in-hospital mortality was not increased. There was a tendency toward better survival in the NCCH group at 2-year follow-up (70.9% NCCH vs. 56.2% SCH, p = 0.052).
Conclusions: Lugol staining is useful in detecting early diseases or multiple lesions and endoscopic ultrasonography in increasing the knowledge of preoperative evaluation and thus should be recommended. Attention should be paid to more thorough lymph node dissection, especially those lymph node stations with high metastatic rates within the chest and the abdomen and meanwhile avoiding major postoperative complications, so as to improve further the accuracy of tumor staging and therapeutic outcome.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Compared with other parts of the world, both Japan and China have relatively higher occurrences of esophageal cancers. Both consist mainly of squamous cell carcinomas located mostly in the thoracic esophagus, while adenocarcinoma in the distal part of the esophagus has increasingly become the major pathological type found in Europe and North America. In the past two decades, with widespread application of Lugol staining and endoscopic ultrasonography (EUS) and the introduction of extended lymph node dissection, better results have been reported by Japanese surgeons (1–6), compared either with historical data or with those from other countries. In China, as in most Western countries, esophagectomy with lymph node sampling or limited dissection still remains the mainstay of treatment and the therapeutic outcomes are similar (7,8). We present here a comparison of data from two major referral centers, the National Cancer Center Hospital (NCCH) in Japan and Shanghai Chest Hospital (SCH) in China. Our aim was to elucidate the possible differences between surgical management of thoracic esophageal carcinoma in these two countries and to shed some light on how to improve the therapeutic outcomes at institutions sharing similar concern around the world.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients treated for thoracic esophageal carcinoma by a single surgeon (H.K. at NCCH and W.C. at SCH) during January 1997 to July 1999 were retrospectively reviewed. Only cases with a pathological type of squamous cell carcinoma and those operated on with curative intention met the selection criteria. Thus, a total of 98 cases (48 from SCH and 50 from NCCH) were included in this study.
All patients underwent preoperative evaluation with esophagram, endoscopy and CT scans of the chest and abdomen. Preoperative staging was made according to the UICC (1997) classification (9). However, Lugol staining under endoscopy was carried out only in the NCCH group. Moreover, ultrasonography and CT scan of the neck and EUS were routinely performed in the Japanese group.
The operative procedures at both centers were subtotal esophagectomy, with the upper digestive tract reconstructed with stomach tube through the retrosternal route. In the case of patients whose stomach was not available, reconstruction was made with colon through the subcutaneous route. All anastomoses were located in the neck. The major difference between the two centers lay in the extent of lymph node dissection. An extended cervical, mediastinal and abdominal (three-field) dissection, as described previously (1), was carried out routinely at NCCH. At SCH, however, this was limited to the mediastinum and the abdomen. Also, lymph nodes at the cervicothoracic junction and those along the celiac trunk, the common hepatic and the splenic artery were not dissected unless clearly visible or palpable (two-field dissection).
At both centers, radiotherapy was given to patients with residual tumor after palliative resection. Some patients were also offered chemotherapy or chemoradiotherapy according to on-going clinical trials. All patients that survived operation were under follow-up. Results from the two groups were processed statistically, using the 
2 test for frequencies and grouped t-test for continuous data. Survival curves were calculated by the Kaplan–Meier method and the difference between the groups was examined with a log-rank test. A p value <0.05 was considered of statistical significance.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The demographic characteristics of the two groups are listed in Table 1. The patients treated at SCH were somewhat younger than those at NCCH, including fewer cases over 70 years of age owing to a stricter indication for operation. Most patients presented with dysphagia or even chest pain at SCH with only one asymptomatic case (2.1%), whereas in the NCCH group 16 (32.0%, p < 0.001) patients showed no subjective symptoms upon presentation, all of them having superficial lesions identified under endoscopic check-up with the help of Lugol staining. Accordingly, the duration from the onset of symptoms to diagnosis of the disease was much longer in the SCH group (6.7 vs 2.3 months, p = 0.002). On the other hand, nine patients in the NCCH group were found to carry synchronous tumors in other parts of the alimentary tract, seven of them gastric cancers, one colon cancer and one hypopharyngeal cancer.
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Both groups had most of the tumors located in the middle part of the thoracic esophagus (see Table 1). As stated above, 12 (24%) cases in the NCCH group were diagnosed as early diseases (T1N0M0 stage I) by EUS before operation. In the SCH group, only two (4.1%) cases were estimated as clinically T1 or stage I, both of them after neoadjuvent therapy (p < 0.001). Meanwhile, cervical lymph node involvement was suspected in three patients at NCCH, which would be considered as a contraindication to surgical treatment at SCH. Also, one or more multiple lesions in the esophagus were detected in 12 (24.0%) patients at NCCH, mainly with the help of Lugol staining under endoscopy. As this method was not routinely used at SCH, only one obvious separate lesion was noted in a single case (2.1%, p = 0.006).
The rate of complete resection was around 90% in both groups (see Table 2). At SCH, all reconstruction was carried out with the stomach, except in one case (2.1%) with the colon, through the retrosternal route. At NCCH, colon was used as a substitute for resected esophagus in eight (16.0%) patients; five of them received one-staged gastrectomy for concurrent cancer and the other three had had their stomach resected previously (p = 0.018). A subcutaneous route was used in 15 patients (30.0%, p < 0.001) either because of colon substitution or if the patient was considered at a high risk of leakage. It was of no surprise that significantly more stations of lymph nodes were harvested in the NCCH group, not only from the addition of cervical dissection, but also from the extended range of dissection within the chest and the abdomen (see Table 2). Accordingly, the mean operation time at NCCH was twice that at SCH. However, there was no significant difference between the amount of blood loss during operation at the two centers.
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Compared with SCH, significantly more postoperative complications were seen in the NCCH group (see Table 2) with morbidity rates of 41.7 and 64.0%, respectively (p = 0.027). Anastomotic leakage and vocal cord paralysis were the most common complications seen at both centers. After operation, one patient died of ileus and toxic shock at SCH and two died of empyema and a cerebral vascular event at NCCH, rendering in-hospital mortality 2.1 and 4.0%, respectively (p = 0.582).
In accordance with preoperative evaluation, more patients were proved to have early-stage tumors at NCCH than those at SCH (see Table 3). Although there was no significant difference in overall rate of lymph node metastasis, there tended to be more stations of lymph nodes found positive for metastasis on pathological examination at NCCH. The rates of metastases to different sites of lymph nodes are listed in Table 4. The lymph node stations often involved (more than 10% positive rate) at both centers were the right recurrent nerve nodes, the middle paraesophageal nodes, the lower mediastinal nodes, the tracheal bifurcation and pulmonary hilar nodes, the paracardiac nodes and the left gastric artery nodes. Moreover, metastasis to cervical lymph nodes, the left recurrent nerve nodes and the infra-aortic nodes were >10% at NCCH and were almost significantly or definitely significantly higher than those at SCH. Correspondingly, eight (16.0%) patients in the NCCH group were diagnosed as M1 because of metastasis to cervical or celiac lymph nodes (M1-Lym) whereas this was found only in two (4.2%) patients in the SCH group (p = 0.053). Hence there was a significant difference between the pathological staging of the two groups, with more stage I, IIb and IV-Lym diseases at NCCH and relatively more stage IIa and III lesions at SCH (p = 0.013).
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There were 14 patients at SCH and seven patients at NCCH who received radiotherapy and/or chemotherapy after operation (p = 0.113). The 1- and 2-year survival of patients who survived operation in the NCCH and the SCH groups were 89.4, 70.9% and 73.7, 56.2%, respectively (p = 0.052) (see Fig. 1). Median survival has not been reached yet in the NCCH group and in the SCH group it was 740 days. Because of the discrepancy in depth of invasion of tumors and extent of lymphadenectomy, survivals stratified according to pathological T status were further compared (see Table 5). There was a tendency toward better survival in T1–3 patients in the NCCH group than those in the SCH group but the differences were not statistically significant. The 2-year survivals of T4 patients in both groups were similarly poor (20.0% vs 21.4%, p = 0.711).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Esophageal carcinoma has been considered to carry an extremely poor prognosis, with less than 20% of the patients who could be expected showing long-term survival even after surgical resection (10,11). In Japan, extended lymph node dissection was introduced in the early 1980s. At the same time, an increasingly higher percentage of early tumors were detected, owing to the wide application of panendoscope and Lugol staining of the esophageal mucosa. With the help of EUS, tumors limited to the membranous layers without lymph node metastasis were identified and subjected to endoscopic local resection. Patients having lesions invading into or beyond the submucosal layer would undergo esophagectomy and systemic lymphadenectomy. These approaches led to reports of 5-year survivals around the 50% level (2–5,12,13), the best results ever achieved against this once formidable disease. While there remains the argument of racial difference that might theoretically constitute a selection bias between the East and the West, this should obviously not be a major problem in the current study. Therefore, we believe that a comparison between two major referral centers in Japan and China could be made on the assumption of a similar background of tumor biology.
Our results showed that there were more early-stage diseases, more cases of multiple lesions and more synchronous tumors at other parts of the digestive tract detected at NCCH. With the extension of lymph node dissection, more lymph nodes were harvested, rendered in a higher rate of metastasis, especially in certain regions. The operation time was prolonged, with elevated risk of postoperative complications. However, the mortality rate was not increased and there seemed to be a tendency toward better survival during short-term follow-up.
The 30% level of tumors found at NCCH with their depth limited to the submucosal layer is consist with other reports from Japan (5). The differences between the two groups concerning the presence and duration of symptoms upon diagnosis, as well as the result of tumor staging, reflect clearly the situation in these two countries. Routine application of Lugol staining helps to identify early superficial lesions which carries a much better prognosis, although early detection relies mainly on primary institutions rather than special referral centers as involved in this study. Besides, it may have a major role in searching for multiple lesions, be it skip metastasis (14) or multicentric carcinogenesis (15,16). Both are characteristic to the esophagus, tend to be superficial but may be of prognostic significance. Synchronous multiple tumors in the digestive tract are also a well known but often neglected condition (17). Both surgeons and radiologists or endocopists should always bear in mind the possibility of the existence of other occult tumors.
Up to now, EUS has been considered the most reliable measure for non-invasive evaluation of the thoracic esophageal cancers (18,19). It can differentiate the separate layers of the esophageal wall, which is impossible on CT scan, and thus give a relatively clear knowledge about tumor invasion. Especially with superficial lesions, EUS is the only method available at present in defining the depth of tumor. Also, the lymph nodes along almost the entire length of the esophagus could be examined with EUS and evaluated not only by their size but by other indexes, such as their shapes, borders and echo types. All these aspects have given it a much higher accuracy than CT in preoperative staging (18,19). Because of the constitutional differences between the two groups in this study, comparing the accuracy in preoperative diagnosis of lymph node metastasis is inapplicable. However, the difference in the accuracy of preoperative T staging (60.4% SCH vs 78.0% NCCH, p = 0.095, not shown) indicates that the use of EUS may help improve the correctness of clinical evaluation and thereby selection of therapy (18).
With the addition of cervical dissection, it was of no surprise that more stations of lymph nodes were harvested and found positive for metastasis in the NCCH group. However, it was interesting that the number of stations of lymph nodes dissected within the mediastinum or the abdomen at NCCH was also significantly higher than that at SCH. Rates of metastasis to stations dissected routinely at both centers were very similar. The right recurrent nerve nodes, the middle paraesophageal nodes, the lower mediastinal nodes, the tracheal bifurcation and pulmonary hilar nodes, the paracardiac nodes and the left gastric artery nodes had metastasis rates of >10% in both groups. However, the rate of metastasis to lymph nodes around the cardia was almost significantly higher in the NCCH group in the SCH group. Also, metastasis to the left recurrent nerve nodes and the infra-aortic nodes was >10% in the NCCH group and of significantly higher than that in the SCH group, where they were not dissected routinely. This strongly indicates that more attention be needed in these areas in the future.
It has been proposed that the merit of systemic lymphadenectomy lies mainly in providing more precise staging and better chance of cure (20,21). In almost all related studies N1 disease appeared to be an important prognostic factor (19). Considering the different constitution of T staging in the current study, if lymph node metastasis is correlated with the depth of tumor invasion, as has been proved (2,6), we should expect comparatively more N1 diseases in the SCH patients. However, our results showed that it turned out to be 10% less than in the NCCH group. This was in coincidence with a nationwide study carried out in Japan comparing the results of two- and three-field lymphadenectomy, which also showed a 10% lower metastatic rate in the former group, even after stratification by location or depth of tumor invasion (6). Further, significantly more stations of lymph nodes were found to be involved in the disease on pathological examination of the NCCH group.
It has been shown that the increased risk of tumor-related mortality due to lymph node metastasis might be reduced drastically with extended lymphadenectomy (20). Although there have been few prospective randomized trials comparing the outcome of systemic lymphadenectomy and lymph node sampling, a review of the literature showed that almost all reports of three-field lymphadenectomy claimed long-term survivals of ~40–50% (2–4,20), whereas a result hardly over 30% was observed after lymph node sampling. This in itself should be considered sound proof of the merit of systemic lymph node dissection. The above-mentioned nationwide study also demonstrated a significant survival advantage of extended lymphadenectomy (6). In the current study, the 1- and 2-year survivals were 15% higher in the NCCH group than in the SCH group, a difference almost statistically significant with a p value of 0.052. To exclude the potential influence of stage migration caused by lymphadenectomy, we further compared survivals stratified according to T status. Again, all survival rates at 1 or 2 years of T1–T3 diseases in the NCCH group were ~15% higher than those in the SCH group, although no statistical significance was reached owing to the small size of the study and the short duration of follow-up. Only in T4 diseases were the results from the two groups similarly poor. Obviously surgical intervention in this setting should be questioned as there appear to be more appropriate approaches for this special group of patients (22).
In this study, the morbidity after three-field lymphadenectomy at NCCH was higher than that after limited two-field dissection at SCH. Except for increased trauma due to extended dissection and consequently prolonged operation time, the higher age of the patients in the NCCH group might also be responsible. Leakage was the most commonly seen complication in both groups, but no fatal anastomosis failure occurred in either group. This is understandable as at both centers a retrosternal route was preferred and anastomosis was located high in the neck. However, the leakage rate at NCCH was more than 10% higher than that at SCH, which showed at least room for improvement. Vocal cord paralysis due to recurrent laryngeal nerve palsy ranked second in postoperative complications in patients at both centers. Apart from these, there was little difference in blood loss during operation in the two groups and the mortality rates were similarly low. All these aspects indicate that extended lymphadenectomy might carry with it a relatively higher risk but within the acceptable range.
In conclusion, through the comparison between surgical management of thoracic esophageal carcinomas at two referral centers in Japan and China, certain diagnostic measures should be recommended, including Lugol staining for detecting early diseases or multiple lesions and EUS for more accurate clinical evaluation, which is of critical importance in therapeutic decision making. Also, more effort is needed in dissecting lymph nodes with a high frequency of metastasis, at least in the range of the mediastinum and the abdomen, while avoiding postoperative complications such as anastomosis leakage or recurrent laryngeal nerve palsy at the same time, so that further improvements leading to higher accuracy of tumor staging and better therapeutic outcome might be expected.
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FOOTNOTES |
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+ For reprints and all correspondence: Hoichi Kato, Department of Surgery, National Cancer Center Hospital, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: hckato@ncc.go.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1 Kato H, Tachimori Y, Watanabe H, Iizuka T, Terui S, Itabashi, et al. Lymph node metastasis in thoracic esophageal carcinoma. J Surg Oncol 1991;48:106–11.[Medline]
2 Akiyama H, Tsurumaru M, Udagawa H, Kajiyama Y. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg 1994;220:364–73.[Web of Science][Medline]
3 Kato H, Watanabe H, Tachimori Y, Iizuka T. Evaluation of neck lymph node dissection for thoracic esophageal carcinoma. Ann Thorac Surg 1991;51:931–5.[Abstract]
4 Tabira Y, Okuma T, Kondo K, Kitamura N. Indications for three-field dissection followed by esophagectomy for advanced carcinoma of the thoracic esophagus. J Thorac Cardiovasc Surg 1999;117:239–45.
5 Japanese Society for Esophageal Diseases. Comprehensive Registry of Esophageal Cancer in Japan (1988–1994), 1st ed. Tokyo: Japanese Society for Esophageal Diseases 2000.
6 Isono K, Sato H, Nakayama K. Results of a nationwide study on three-field lymph node dissection of esophageal cancer. Oncology 1991;48:411–20.[Web of Science][Medline]
7 Zhang DW, Cheng GY, Huang GJ, Zhang RG, Lin XY, Mao YS, et al. Operable squamous esophageal carcinoma: current results from the East. World J Surg 1994;18:347–54.[Medline]
8 Watson A. Operable squamous esophageal cancer: current results from the West. World J Surg 1994;18:361–6.[Web of Science][Medline]
9 International Union Against Cancer. TNM Classification of Malignant Tumors, 5th ed. New York: Wiley-Liss, 1997.
10 Earlam R, Cunha-Melo JR. Oesophageal squamous cell carcinoma I: a critical review of surgery. Br J Surg 1980;67:381–90.[Web of Science][Medline]
11 Muller JM, Erasmi H, Stelzner M, Zieren U, Pichlmaier H. Surgical therapy of oesophageal carcinoma. Br J Surg 1990;77:845–57.[Web of Science][Medline]
12 Kato H, Tachimori Y, Watanabe H, Igaki H, Nakanishi Y, Ochiai A. Recurrent esophageal carcinoma after esophagectomy with three-field lymph node dissection. J Surg Oncol 1996;61:267–72.[Medline]
13 Bhansali MS, Fujita H, Kakegawa T, Yamana H, Ono T, Hikita S, et al. Pattern of recurrence after extended radical esophagectomy with three-field lymph node dissection for squamous cell carcinoma in the thoracic esophagus. World J Surg 1997;21:275–81.[Web of Science][Medline]
14 Kato H, Tachimori Y, Watanabe H, Itabashi M, Hirata T, Yamaguchi H, et al. Intramural metastasis of thoracic esophageal carcinoma. Int J Cancer 1992;50:49–52.[Medline]
15 Pesko P, Rakic S, Milicevic M, Bulajic P, Gerzic Z. Prevalence and clinicopathologic features of multiple squamous cell carcinoma of the esophagus. Cancer 1994;73:2687–90.[Web of Science][Medline]
16 Mizobuchi S, Kato H, Tachimori Y, Yamaguchi H, Itabashi M. Multiple primary carcinoma of the oesophagus. Surg Oncol 1993;2:249–53.[Web of Science][Medline]
17 Kato H, Tachimori Y, Watanabe H, Mizobuchi S, Igaki H, Yamaguchi H, et al. Esophageal carcinoma simultaneously associated with gastric carcinoma: analysis of clinicopathologic features and treatment. J Surg Oncol 1994;56:122–7.[Medline]
18 Rice TW, Adelstein DJ. Precise clinical staging allows treatment modification of patients with esophageal carcinoma. Oncology 1997;11(suppl 9):58–61.
19 Reed CE. Surgical management of esophageal carcinoma. Oncologist 1999;4:95–105.
20 Lerut T, de Leyn P, Coosemans W, van Raemdonch D, Scheys I, LeSaffre E. Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy. Ann Surg 1992;216:583–9.[Web of Science][Medline]
21 Altorki NK, Skinner DB. Occult cervical nodal metastasis in esophageal cancer: preliminary results of three-field lymphadenectomy. J Thorac Cardiovasc Surg 1997;113:540–4.
22 Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S, et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 1999;17:2915–21.
Received October 10, 2000; accepted February 5, 2001.
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