Jpn J Clin Oncol 2002;32(8)310314

2002 Foundation for Promotion of Cancer Research

A Case of Advanced Esophageal Cancer with Extensive Lymph Node
Metastases Successfully Treated with Multimodal Therapy
Kaori Shigemitsu
1
, Yoshio Naomoto
1
, Yasuhiro Shirakawa
1
, Minou Haisa
1
, Mehmet Gunduz
2
and Noriaki Tanaka
1
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
For reprints and all correspondence: Kaori Shigemitsu, Department of
Gastroenterological Surgery, Transplant and Surgical Oncology, Graduate
School of Medicine and Dentistry, Okayama University, 251 Shikata-cho,
Okayama City, Okayama 700-8558, Japan
Received February 14, 2002; accepted May 14, 2002
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 fol-
lowed by adjuvant chemotherapy and radiotherapy was performed. A 53-year-old male was
diagnosed as advanced middle esophageal cancer with multiple regional lymph node metas-
tases such as paraesophageal, pretracheal, tracheobronchial and bifurcational lymph nodes
and three intramural metastatic lesions. Subtotal esophagectomy with three-field lymphade-
nectomy was performed for the tumor. Histopathologically, the tumor was poorly differ-
entiated 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 admin-
istered in two courses, followed by radiation therapy (field size 21 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 34 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.
Key words: esophageal cancer lymph node metastasis adjuvant therapy multimodal therapy
INTRODUCTION
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 resec-
tion. He has been alive and well for 5 years after surgery.
CASE REPORT
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 C-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 3134 cm from the
incisor teeth, at the left-anterior wall of the middle esophagus
(Fig. 1a). An unstained area delineated the lesion and the sur-
rounding flat lesion on iodine staining (Fig. 1b). We diagnosed
the tumor as type Ip (polypoid type) + 0IIc (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
Jpn J Clin Oncol 2002;32(8) 311
be intramural metastases. Specimens taken from the tumor
revealed poorly differentiated squamous cell carcinoma.
Radiological examination of the upper gastrointestinal tract
showed an elevated lesion, measuring 3.0 2.4 cm, with
uneven surface and distinct margins (Fig. 2). Another smaller
elevation was detected in its proximal region.
Cervical and chest computed tomography (CT) images sug-
gested 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 bifurca-
tional lymph nodes (Fig. 3c), to be metastatic.
Figure 1. (a) An elevated lesion 3134 cm from the incisor teeth, at the left-anterior wall of the middle esophagus. (b) An unstained area delineated the lesion
and the surrounding flat lesion on iodine staining.
Figure 2. Radiological examination of the upper gastrointestinal tract showed
an elevated lesion, measuring 3.0 2.4 cm, with uneven surface and distinct
margins.
Figure 3. (a) Cervical and chest CT images suggested the paraesophageal
lymph nodes and pretracheal lymph nodes to be metastatic. (b) Paraesophageal
lymph nodes swelled to be metastatic. (c) Pretracheal, bifurcational and
tracheobronchial lymph nodes swelled to be metastatic.
312 Multimodal therapy for esophageal cancer
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 per-
formed and with reconstruction with a gastric tube via the
retromediastinal route.
The tumor was 3.5 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 >, ly2, v1,
pN4(2c), according to the Guide Lines (3). One of two har-
vested 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 tra-
cheobronchial 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 lym-
phatic vessels near the metastatic lymph nodes (Fig. 5b) and
intramural metastatic lesions.
Four weeks after surgery, the patient was treated with a
course of 5-FU at 1000 mg/day on days 13, 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 supra-
clavicular and superior mediastinal nodes (field size 21 20
cm, 10 MV X-rays, 2 Gy/fr, 5 fr/week), a total dose of radio-
therapy of 46 Gy. After this therapy, mild leukopenia falling to
3200/l 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 chemo-
therapy was continued further with close follow-up examina-
tions and such treatment was repeated every 34 months
without any severe adverse effects. The patient has remained
alive and well 5 years after surgery without an apparent recur-
rent tumor.
DISCUSSION
Stage IV esophageal cancer usually shows a very poor progno-
sis 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 sur-
vived for four or more years.
It has been reported that the number of nodes involved influ-
ences 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 Japa-
nese Society for Esophageal Diseases (3), the degree of lymph
node metastasis was modified by the number of metastatic
Figure 4. The tumor was 3.5 2.6 cm in diameter and presented as type 1pl.
Figure 5. Histological findings. (a) Pretracheal lymph nodes were found to be
metastatic. (b) Tumor cells in lymphatic vessels were revealed.
Jpn J Clin Oncol 2002;32(8) 313
lymph nodes to define new pN categories: the degree of lymph
node metastasis of carcinomas with 47 metastatic regional
nodes as the number with one added to the number of meta-
static lymph nodes group and with eight or more metastatic
regional nodes as the number with two added.
Clinical results for esophageal cancer have become rela-
tively 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 esopha-
geal cancer, with a response rate of over 20% in single-agent
therapy (2). Although combinations of these drugs have pro-
vided response rates of 4060%, 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 3560% (911). 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 exami-
nations 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 sur-
gery with nodal dissection followed by combination therapy
with CDDP, 5-FU and irradiation contributed to long-term sur-
vival 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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