Japanese Journal of Clinical Oncology 32:310-314 (2002)
© 2002 Foundation for Promotion of Cancer Research
A Case of Advanced Esophageal Cancer with Extensive Lymph Node Metastases Successfully Treated with Multimodal Therapy
Departments of 1 Gastroenterological Surgery, Transplant and Surgical Oncology and 2 Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Advanced esophageal cancer patients with extensive lymph node metastases show extremely poor prognosis and the long-term outcome is poorer with the involvement of more lymph nodes. We report here a long-surviving case of advanced esophageal cancer with histologically 34 lymph node metastases, in which surgical resection with three-field lymphadenectomy followed by adjuvant chemotherapy and radiotherapy was performed. A 53-year-old male was diagnosed as advanced middle esophageal cancer with multiple regional lymph node metastases such as paraesophageal, pretracheal, tracheobronchial and bifurcational lymph nodes and three intramural metastatic lesions. Subtotal esophagectomy with three-field lymphadenectomy was performed for the tumor. Histopathologically, the tumor was poorly differentiated squamous cell carcinoma and 34 lymph nodes including ligamentum arteriosum lymph nodes and pretracheal lymph nodes were proved to be metastatic. Numerous tumor cells were found in the lymphatic vessels near the metastatic lymph nodes. Chemotherapy [3000 mg of 5-fluorouracil (5-FU), 50 mg of cisplatin (CDDP) and 30 mg of methotrexate (MTX)] was administered in two courses, followed by radiation therapy (field size 21 x 20 cm in mediastinum, 10 MV X-rays, 2 Gy/fr, 5 fr/week, total 46 Gy). Subsequently, 1000 mg of 5-FU and 200 mg of CDDP were administered every 3–4 months without any significant toxicities. The patient has been alive and well without recurrence for 5 years following operation. For treatment of advanced esophageal cancer with extensive lymph node metastases, a wide resection of the tumor and regional lymph nodes should be performed, followed by adjuvant chemotherapy and radiotherapy.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Esophageal cancer is most often found as advanced cancer with metastatic lesions, with extremely poor patient prognosis. In recent years, several strategies involving combination therapy have been tried to improve this prognosis (1,2), but with little success. In this paper, we report a case of advanced esophageal cancer with histological metastasis of 34 lymph nodes, who showed a good response to 5-fluorouracil (5-FU), cisplatin (CDDP) and methotrexate (MTX) combination chemotherapy followed by radiotherapy after curative resection. He has been alive and well for 5 years after surgery.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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A 53-year-old male was referred to our hospital for further examination of X-ray abnormalities including elevated lesion in the esophagus. On admission, he was 168 cm tall and weighed 56 kg, and no specific clinical findings were noted. There were no abnormal findings in laboratory data except for slight elevation of
-GTP. Tumor markers on admission were carcinoembryonic antigen (CEA) 2.29 ng/ml and squamous cell carcinoma antigen (SCC) 0.72 ng/ml. Endoscopy revealed an elevated lesion 31–34 cm from the incisor teeth, at the left-anterior wall of the middle esophagus (Fig. 1a). An ‘unstained area’ delineated the lesion and the surrounding flat lesion on iodine staining (Fig. 1b). We diagnosed the tumor as type Ip (polypoid type) + 0–IIc (slightly depressed type), according to endoscopic classification based on the Guide Lines for Clinical and Pathologic Studies of the Japanese Society for Esophageal Disease (3). Three lesions detected 27 and 29 cm from the incisor teeth were suspected to be intramural metastases. Specimens taken from the tumor revealed poorly differentiated squamous cell carcinoma.
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Radiological examination of the upper gastrointestinal tract showed an elevated lesion, measuring 3.0 x 2.4 cm, with uneven surface and distinct margins (Fig. 2). Another smaller elevation was detected in its proximal region.
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Cervical and chest computed tomography (CT) images suggested multiple regional lymph nodes, such as paraesophageal lymph nodes (Fig. 3a and b), pretracheal lymph nodes (Fig. 3a and 3c), tracheobronchial lymph nodes (Fig. 3c) and bifurcational lymph nodes (Fig. 3c), to be metastatic.
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Based on these findings, the case was classified as a T3N1M0, Stage III advanced esophageal cancer, according to the TNM Classification of Malignant Tumors (4).
On thoracotomy, the tumor was located mainly at the middle esophagus and direct invasion of the surrounding tissue could not be identified. Metastases into multiple lymph nodes, including No. 106 pre (pretracheal lymph nodes) and No. 103 (peripharyngeal lymph nodes), according to the Guide Lines for Clinical and Pathologic Studies of the Japanese Esophageal Cancer Society (3), were suspected. Accordingly, subtotal esophagectomy with three-field lymphadenectomy was performed and with reconstruction with a gastric tube via the retromediastinal route.
The tumor was 3.5 x 2.6 cm in diameter and presented as type 1p (Fig. 4), and three intramural metastatic lesions were revealed. Histopathological examination showed a poorly differentiated squamous cell carcinoma, pT3, INF ß, ly2, v1, pN4(2c), according to the Guide Lines (3). One of two harvested nodes of light cervical esophageal lymph nodes (No. 101L), one of two light supraclavicular lymph nodes (No. 104L), one of three right recurrent nerve lymph nodes (No. 106 recR), four of four left recurrent nerve lymph nodes (No. 106 recL), four of four upper thoracic paraesophageal lymph nodes (No. 105), 13 of 17 No. 106 pre (Fig. 5a), two of two left tracheobronchial lymph nodes (No. 106 tbL), two of six middle thoracic paraesophageal lymph nodes (No. 108) and six of six ligamentum arteriosum lymph nodes (No. 113) were positive for metastasis (Fig. 6). Tumor cells were found in the lymphatic vessels near the metastatic lymph nodes (Fig. 5b) and intramural metastatic lesions.
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Four weeks after surgery, the patient was treated with a course of 5-FU at 1000 mg/day on days 1–3, together with CDDP at 50 mg/day on day 1 and MTX at 30 mg/day on day 1, and received the same course 2 weeks later. From the 67th postoperative day, he received radiotherapy for bilateral supraclavicular and superior mediastinal nodes (field size 21 x 20 cm, 10 MV X-rays, 2 Gy/fr, 5 fr/week), a total dose of radiotherapy of 46 Gy. After this therapy, mild leukopenia falling to 3200/µl and mild anorexia developed but no serious side effects were observed. After discharge, the patient was treated with a course of 5-FU at 500 mg/day on days 1 and 2, together with CDDP at 20 mg/day on day 1. This combination chemotherapy was continued further with close follow-up examinations and such treatment was repeated every 3–4 months without any severe adverse effects. The patient has remained alive and well 5 years after surgery without an apparent recurrent tumor.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Stage IV esophageal cancer usually shows a very poor prognosis and cases with long-term survival have rarely been reported (5). In our institute, between 1990 and 1998, 179 patients with primary esophageal cancer underwent esophagectomy. Among them, 5-year survival rate of 28 stage IVa cases (15.9%) was 14.9%. Moreover, only two cases among 15 pN4 cases survived for four or more years.
It has been reported that the number of nodes involved influences patient survival independently. Kawahara et al. (6) and Kimura et al. (7) reported that the long-term outcome was poorer with the involvement of more lymph nodes and that the 5-year survival rate was significantly poor in patients with four or more metastatic lymph nodes. In the latest edition of the Guide Lines for Clinical and Pathologic Studies of the Japanese Society for Esophageal Diseases (3), the degree of lymph node metastasis was modified by the number of metastatic lymph nodes to define new pN categories: the degree of lymph node metastasis of carcinomas with 4–7 metastatic regional nodes as the number with one added to the number of metastatic lymph nodes group and with eight or more metastatic regional nodes as the number with two added.
Clinical results for esophageal cancer have become relatively more favorable than those for other gastrointestinal cancers. Several drugs such as CDDP, mytomycin C, vindesine, MTX and 5-FU have shown antitumor activity against esophageal cancer, with a response rate of over 20% in single-agent therapy (2). Although combinations of these drugs have provided response rates of 40–60%, most of them were limited to partial response and did not improve survival (2,8). 5-FU and CDDP are the two basic agents in combination chemotherapy for esophageal cancer and the reported objective response rates have been 35–60% (9–11). In loco-regional esophageal cancer, chemotherapy, mostly a combination of 5-FU with CDDP (9,10), together with radiation therapy (12,13) has curative potential. However, for patients with metastatic disease, chemotherapy yields few complete response results and hence is unlikely to have any impact on survival (14). Therefore, a standard therapy for metastatic esophageal carcinoma has yet to be established.
In the present case, postoperative histopathological examinations showed 34 lymph nodes with metastasis among 49 harvested nodes and the case was considered to have a poor prognosis. The present case report documents that curative surgery with nodal dissection followed by combination therapy with CDDP, 5-FU and irradiation contributed to long-term survival without any significant toxicities and recurrence. Further studies are warranted to evaluate the combined effects of CDDP, 5-FU and irradiation.
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FOOTNOTES |
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+ For reprints and all correspondence: Kaori Shigemitsu, Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, 2–5–1 Shikata-cho, Okayama City, Okayama 700-8558, Japan
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REFERENCES |
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Received February 14, 2002; accepted May 14, 2002
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