Japanese Journal of Clinical Oncology Advance Access originally published online on September 25, 2006
Japanese Journal of Clinical Oncology 2006 36(11):735-738; doi:10.1093/jjco/hyl087
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© 2006 Foundation for Promotion of Cancer Research
A Case of Resected Huge Ileocolonic Mesenteric Liposarcoma which Responded to Pre-operative Chemotherapy using Doxorubicin, Cisplatin and Ifosfamide
Colorectal Surgery Division, National Cancer Center Hospital, Tokyo, Japan
For reprints and all correspondence: Seiichiro Yamamoto, Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji Tyuo-ku, Tokyo 104-0045, Japan. E-mail: sishigur{at}ncc.go.jp
Received February 13, 2006; accepted June 15, 2006
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Abstract |
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Primary mesenteric liposarcoma is a rare entity that has been reported only 14 times in English literature. The treatment strategy for mesenteric liposarcoma is, if no distant metastases are detected, surgical resection with a wide surgical margin, often followed by radiation and/or adjuvant chemotherapy for high-risk patients. However, the efficacy of pre-operative chemotherapy is unknown. If the tumor is shrunk by pre-operative chemotherapy, we could achieve complete surgical resection, which is difficult when the tumor is too large or is invading neighboring organs. We herein describe a case of huge mesenteric liposarcoma that showed significant tumor shrinkage by pre-operative chemotherapy using doxorubicin, cisplatin and ifosfamide, allowing a margin-negative operation.
Key Words: mesenteric liposarcoma • preoperative chemotherapy • doxorubicin • ifosfamide
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INTRODUCTION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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Primary mesenteric liposarcoma is a rare entity which has been reported only 14 times in English literature (1–3), the treatment strategy for which is so far undetermined. Generally, if no distant metastases are detected, the treatment of choice is surgical resection with a wide surgical margin, often followed by radiation and/or adjuvant chemotherapy for high-risk patients. Although it is controversial whether pre-operative chemotherapy is effective, it has two oncological merits: a higher possibility of complete resection if the tumor shrinks, and the possibility of gaining pathological information about the anti-tumor effect of drugs in order to select chemotherapy drugs. Here we describe a case of huge mesenteric liposarcoma that showed significant tumor shrinkage by pre-operative chemotherapy using doxorubicin, cisplatin and ifosfamide, resulting in a margin-negative operation.
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CASE REPORT |
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A 30-year-old man noticed abdominal distention in January 2003. He underwent a CT scan at a local hospital, which revealed a huge mass in the abdominal cavity. Fine needle biopsy was performed and the pathological diagnosis of myxoid liposarcoma was made. He was referred to our hospital in April 2003. Physical examination showed a remarkably distended abdomen. Based on the radiological data, the clinical diagnosis was made as myxoid liposarcoma in the retroperitoneum; however, the tumor was considered too huge to resect out completely because of the possibility of invasion to intestine, right kidney and abdominal wall (Fig. 1). Therefore, our treatment of choice was systemic chemotherapy. The patient underwent two courses of chemotherapy with doxorubicin (50 mg/m2/day, on days 1–2) and cisplatin (50 mg/m2/day, on days 1–2) every 4 weeks, followed by ifosfamide (4.9 mg/m2/day, on days 1–5) every 5 weeks with an intention of further tumor shrinkage. After another two cycles of ifosfamide, the CT scan showed a remarkable reduction of the tumor volume, about a 50% decrease in the longest diameter of the target lesion, which was assessed as partial response. At that time, we considered that the tumor might be resectable with some combined resection (Fig. 2). After one more additional course of doxorubicin and cisplatin chemotherapy, the operation was performed in September 2003. At laparotomy, the tumor was actually located in the mesentery of the terminal ileum and right-sided colon, not in the retroperitoneum. It was a yellowish soft tumor with a diameter of 30 cm and was involved in the mesentery from the ascending colon to the middle of the transverse colon. There was no peritoneal dissemination, no ascites, or no invasion to adjacent organs in the abdominal cavity. After mobilization of the right-sided colon and proximal ligation of ileocolic vessels and the right branch of the middle colic vessels, the large mesenteric tumor was resected with no macroscopic margin, in combination with the terminal ileum and right-sided colon. The post-operative course was uneventful. Histological diagnosis of the resected specimen was myxoid liposarcoma, and the proliferation of spindle cells with microcyctic stromal change and adipocytic differentiation was observed. Tumor necrosis was found in less than 50%. The surgical margin was negative and there was no lymph-node involvement. However, a macroscopically sufficient surgical margin around where the feeding artery came off the superior mesenteric artery was not obtained; therefore, the patient underwent post-operative irradiation of 45 Gy along the superior mesenteric artery. The patient was well without any evidence of recurrence for 26 months after the operation; however, he has now developed abdominal recurrence and is receiving systemic chemotherapy with the same drugs, because the resected specimen showed moderate necrosis.
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DISCUSSION |
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Liposarcoma is the second most common soft tissue sarcoma in adults. The two major locations of liposarcama are the extremities and the retroperitoneum (4–7). Liposarcoma of the mesentery is rare, only 14 cases of which have been reported to date, based on the search in PubMed (1966–December 2005) with the keywords sarcoma, liposarcoma, or mesentery (1–3).
Liposarcoma is currently classified into three groups: well-differentiated liposarcoma with or without dedifferentiation, myxoid and round cell/cellular myxoid liposarcoma, and plemorphic liposarcoma (8). Among all liposarcomas, myxoid liposarcoma is the most common type, found in approximately 50% of cases. These histologic subtypes correlate well with the prognosis of the patient. Evans reported that the median survival of patients with the well-dedifferentiated type, the myxoid type, the dedifferentiated type and plemorphic type was 119, 113, 59 and 24 months, respectively. Myxoid liposarcoma has definite metastatic potential but a relatively indolent natural history (9).
Basically, the treatment strategy for mesenteric liposarcoma is the same as that for retroperitoneal liposarcoma (10). The treatment of choice for such liposarcoma is surgical resection with sufficient surgical margin (6,7), often followed by radiation and/or adjuvant chemotherapy with a high risk of relapse, such as for large tumors or low-grade tumors. The key chemotherapy drug is doxorubicin. Meta-analysis of 14 randomized trials of adjuvant therapy for soft tissue sarcoma in adults showed evidence that adjuvant doxorubicin-based chemotherapy significantly improves the time to local and distant recurrence and overall recurrence-free survival, and tends to improve overall survival (11). Patel et al. reported the efficacy of systemic chemotherapy using doxorubicin and dacarbazine for 21 patients with myxoid liposarcoma. The objective response rate was 44% (21–67%, 95% confidence interval), which was similar to that reported in many other studies on soft tissue sarcomas. They concluded that doxorubicin and dacarbazine-based chemotherapy was effective in treating myxoid liposarcoma (4). Ifosfamide is also an active chemotherapeutic agent in the treatment of sarcomas. Both doxorubicin and ifosfamide have been demonstrated to show a dose–response relationship (12,13). A phase II study to evaluate the efficacy of dose-intensive doxorubicin plus ifosfamide for metastatic sarcoma or primary sarcomas with a high-risk of metastasis showed a high response rate. Patel et al. (doxorubicin 90 mg/m2, ifosfamide 12.5 g/m2 or doxorubicin 70 mg/m2, ifosfamide 10 g/m2) reported a response rate of 66% (46–82%, 95% confidence interval) (14) and De Pas et al. (doxorubicin 60 mg/m2, ifosfamide at 10 g/m2 with granulocyte colony-stimulating factor) showed a response rate of 50% (23–77%, 95% confidence interval) (15). This high-dose combination chemotherapy, anthracycline and ifosfamide, is thought to be the most hopeful regimen for soft tissue sarcoma and many studies using these drugs have been conducted (16,17). In the case of our patient, we adopted combination therapy of cisplatin and doxorubicin in the hope of further tumor reduction, because cisplatin is commonly used for the treatment of soft tissue sarcoma (18–20) as in our routine treatment.
There is relatively little data for the use of pre-operative chemotherapy in the treatment of soft tissue sarcomas. Casper et al. reported the outcome of a prospective trial of pre-operative and post-operative adjuvant combination chemotherapy for adults with high-grade soft tissue sarcoma (21). Twenty-nine patients with primary or recurrent soft tissue sarcoma were treated with two pre-operative cycles of cyclophosphamide 500 mg/m2, doxorubicin 60 mg/m2 and dacarbazine 1000 mg/m2 before definitive surgery and radiation. Only one patient demonstrated a clinical partial response. However, intratumoral hemorrhage, cystic necrosis and liquefaction were noted regularly in the resected specimens with three tumors showing more than 90% necrosis. Most patients did not receive post-operative chemotherapy. The median time free from distant metastasis was 28 months; median survival was 35 months. These results were not superior to historical studies with no chemotherapy, or with post-operative doxorubicin. Other retrospective studies showed outcomes that responders to chemotherapy had a better overall survival than no responders; however, there was no evidence of survival improvement with pre-operative chemotherapy (22,23).
Complete surgical resection at the time of primary presentation is likely to give a chance for long-term survival (6,7,10,24–26) as well as distant recurrence-free survival (24), and positive surgical margins are the main predictors of local relapse (27,28). Because most mesenteric and retroperitoneal sarcoma are large, it is difficult to obtain adequate margins of resection and the presence of normal organs such as the gastrointestinal tract, kidney and liver make the delivery of therapeutic doses of radiation therapy either difficult or impossible. Although pre-operative chemotherapy might give no evident survival benefit, it is possible to spare adjacent normal organs and to facilitate margin-negative surgery if the primary tumor shrinks. In addition, pre-operative chemotherapy can guide post-operative treatment based on a pathologic review of the tissue after chemotherapy. This patient developed recurrence 26 months after the operation. Because the chemotherapy administered pre-operatively was effective from the histological findings of the resected specimen, which showed some extent of necrosis, we have been giving him the same combination chemotherapy. In our case, we considered before surgery that it was impossible to resect the large tumor completely. However, remarkable shrinkage of the tumor by means of pre-operative chemotherapy enabled us to perform margin-negative surgery without combined resection of adjacent organs. No patient can be considered as a candidate for long-term survival without macroscopically complete resection and this patient clearly had a chance to benefit from pre-operative chemotherapy. Although it remains unknown what kind of drugs are the most effective and how long the drugs should be administered in this pre-operative setting, we think that pre-operative chemotherapy is likely to be worth trying for patients with large liposarcoma of the abdominal and retro-abdominal cavity.
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References |
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