Eur J Cardiothorac Surg 1999;16:471-474
© 1999 Elsevier Science NL
Bronchial arterial infusion with cisplatin followed by irradiation successfully treats recurrent stage IVb thymic large cell carcinoma
Shizuka Kasedaa,
Kunihiko Shimizub,
Takashi Yamanec,
Hitoshi Sugiurad
a Department of Thoracic Surgery, Saiseikai Kanagawa-ken Hospital, Yokohama 221-8601, Japan
b Department of Internal Medicine, Saiseikai Kanagawa-ken Hospital, Yokohama 221-8601, Japan
c Radiology, Saiseikai Kanagawa-ken Hospital, Yokohama 221-8601, Japan
d Department of Pathology, Clinical Research Laboratories, Kawasaki Municipal Kawasaki Hospital, Kawasaki 210-0013, Japan
Corresponding author. Tel.: +81-45-432-1111; fax: +81-45-432-1119
e-mail: kaseda{at}ra2.so-net.ne.jp
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Abstract
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A 48-year-old female was treated with three courses of chemotherapy combined with bronchial arterial infusion (BAI) with cisplatin and intravenous drip infusion with bleomycin and vinblastine for a recurrent thymic large cell carcinoma seen 1 year after the initial operation. The patient had subsequently undergone irradiation. No sign of recurrence has been noted with a follow-up period of 6 years after the initial operation. This is the first reported case of survival from recurrence of thymic large cell carcinoma. BAI combined with irradiation should be considered as one of the treatments of choice in a recurrence like we present herein.
Key Words: Thymus • Thymic carcinoma • Large cell carcinoma • Bronchial artery • Chemotherapy • Irradiation
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1. Introduction
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Undifferentiated carcinoma of the thymus is a very rare neoplasm arising from the thymic gland associated with poor prognosis. We encountered a case of thymic tumor where the histological diagnosis as large cell carcinoma was established. We report on a successful result with bronchial arterial infusion (BAI) followed by irradiation.
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2. Case report
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In July 1992, a 48-year-old female with a mass in the anterior mediastinum was referred to our hospital. On admission, CT scan revealed a tumor 70 mm in diameter in the anterior mediastinum, and a nodule in the left upper lobe. The operation was performed by median sternotomy under a diagnosis of invasive thymoma. Intraoperative findings revealed that the main tumor had invaded adjacent structures including the pulmonary artery, pericardium, phrenic nerve and left upper lobe. Furthermore, a metastatic nodule was noticed in the upper lobe separately from the primary lesion. The tumor was excised combined with the surrounding structures; when the pulmonary artery, which had been partially invaded by the main tumor, was dissected, it was temporarily clamped with a vascular clamp, and sutured with Prolene 5-0 (ETHICON, Inc., USA). Additionally partial resection of left upper lobe was carried out to remove the metastatic lesion. The pathological diagnosis for the main tumor and the nodule in the left upper lobe was thymic large cell carcinoma (Fig. 1). Post-operative diagnosis was stage IVb following Masaoka's classification [1]. Postoperatively, the patient received 3 courses of chemotherapy with cisplatin (125 mg/body), vinblastine (5 mg/body) and bleomycin (10 mg/body).
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Fig. 1. The tumor consists of solid nests of large polygonal cells with large vesicular nuclei and prominent nucleoli, pale-staining cytoplasm, and ill-defined cell borders. There is no differentiation microscopically toward any specific cell type, such as squamous cells, mucin-producing cells, or small neuroendocrine cells. Note the presence of many pyknotic cells in a cell nest. Hematoxylin and eosin.
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One year after the operation, the patient complained of chest pain. CT scan revealed lymph node enlargement in Botallo's region (Fig. 2A). Under a diagnosis of local tumor recurrence, selective bronchial arteriography (BAG) was performed with a 5F large curved catheter in the Seldinger technique. On BAG, the subaortic lymph node was hypervascular and was supplied by the common trunk of the bronchial artery (Fig. 2B). However, the common trunk had no anastomotic connection to the posterior intercostal arteries or anterior spinal artery. Cisplatin mixed with saline (100 mg/200 ml) was administered over more than 20 min with a hand syringe via a catheter positioned in the common trunk. Intravenous infusion of vinblastine (5 mg/body) and bleomycin (10 mg/body) were performed subsequently to a bronchial arterial infusion (BAI) of cisplatin. Following completion of the three courses of chemotherapy at 3 week intervals, CT imaging revealed almost complete disappearance of the tumor (Fig. 2C). The patient received sequential irradiation up to 60 Gy; 2 Gy per fraction at the rate of 5 fractions a week. As of May 1999, 6 years after the initial operation, the patient was alive and well without any sign of recurrence.
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Fig. 2. Arrow heads indicate: (A) lymph node enlargement in Botallo's region; (B) bronchial arterial angiogram revealing tumor stain in the lymph node; (C) almost complete disappearance of the tumor.
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3. Comment
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In the earlier literature, thymic carcinoma was included under the category of malignant thymoma [2]. However, Levine et al. [3] distinguished thymic carcinoma from thymoma, and Shimosato et al. classified thymic carcinoma into nine categories: the squamous cell carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, basaloid carcinoma, adenocarcinoma, lymphoepithelioma-like carcinoma, small cell carcinoma, large cell carcinoma and sarcomatoid carcinoma [4]. Among these nine types of histology, the prognosis of the poorly differentiated carcinomas, including large cell carcinoma, is poorer compared with those of other histological types because of its aggressive nature involving invasion of the mediastinal structures and active metastasis to other organs and structures. Thus, complete resection of the primary lesion combined with the neighboring structures followed by adjuvant chemotherapy should be attempted to obtain a good prognosis. However, to our knowledge, the data regarding effective chemotherapy for undifferentiated thymic carcinoma are scant. Carlson [5] and Weide [6] reported a case of undifferentiated thymic carcinoma which responded to cisplatin-based chemotherapy.
Although the usefulness of arterial infusion has been reported in other organs than the lung [7–9], BAI therapy is also recognized as one of the local therapies [10]. Since a high concentration of anti-cancer drug is infused into the lesion, there is a high feasibility that it eradicates localized lesions, particularly when it is combined with subsequent irradiation. We therefore performed irradiation after the metastasized lymph nodes had almost disappeared following three courses of the above-mentioned chemotherapy. During the subsequent follow-up period, no sign of relapse has been noticed.
Although no definitive recommendations have been made regarding the optimal chemotherapy for undifferentiated thymic carcinoma, our result suggests that combination chemotherapy including cisplatin, bleomycin and vinblastine should be considered as the first-line chemotherapy for undifferentiated thymic carcinoma. It should be stated, however, that in our case BAI therapy alone may not have been the most contributing factor in controlling the recurrent lesion, since three-modality procedures, BAI with cisplatin, systemic drip infusion of vinblastine and bleomycin, and external irradiation, were adopted alternately. However, BAI therapy should be considered as one of the strong alternatives to drip infusion therapy when treating localized lesions such as the present case, especially when combined with subsequent irradiation.
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Acknowledgments
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We wish to thank Professor Chikao Torikata, National Defense Medical College, for an important advice.
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References
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Received March 15, 1999;
received in revised form June 23, 1999;
accepted June 29, 1999.
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Abstract
1. Introduction
