Journal of Surgical Oncology 51:89-93 (1992)
Inferior Vena Cava Leiomyosarcoma MARC L. DEMERS, MD, STEVEN A. CURLEY, MD, AND MARVIN M. ROMSDAHL, MD, PhD From the Department of General Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ~
~
Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M. D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy. 0 1992 Wiley-Liss, Inc.
KEYWORDS:sarcoma, neoadjuvant chemotherapy, micrometastasis
INTRODUCTION Leiomyosarcomas of the inferior vena care are rare malignancies, but they have been reported with greater frequency in recent years. Like other retroperitoneal neoplasms, these tumors are often large before the onset of symptoms or signs of a mass on physical examination. A recent review of the literature describes 144 cases of these tumors and has confirmed the importance of radical resection as the only hope for cure [ 11. Our report reaffirms this and suggests that chemotherapy given before resection may be of benefit. The potential advantages of preoperative chemotherapy include reduction of tumor size, assessment of the tumor response to chemotherapy to help in selection of appropriate postoperative chemotherapy, and control of micrometastases elsewhere in the body. We report herein an additional four cases of leiomyosarcoma of the vena cava with an emphasis on surgical management and preoperative chemotherapy.
Case 1 A 42-year-old woman experienced the onset of right flank pain and bilateral lower extremity edema over a 1-month period. Two months following the onset of flank pain, she underwent exploratory laparotomy at another hospital. Resection was attempted and abandoned, as the mass was seen to involve the aorta and right ureter. The patient had three postoperative courses of cyclophosphamide, doxorubicin, and dacarbazine as well as radiation therapy. The cyclophosphamide (600 mg/m2) was given on day 1 and the doxorubicin (15 mg/m2/day) and dacarbazine (250 mg/m2/day) on days 2-5 by continuous infusion. The dose, field, and fractionation of radiation is not known. On a repeat computed tomographic scan following the three cycles of chemotherapy the mass had decreased in size by 40%. She was referred to M. D. Anderson Cancer Center. At operation she underwent en bloc resection of a sarcoma involving the infrarenal aorta, inferior vena cava, and right kidney, and vascular reconstruction using an aortoiliac interposition graft. The vena PATIENTS AND METHODS cava was ligated. Gross examination of the tumor reThe case records of all patients with the diagnosis of vealed that it arose from the inferior vena cava with leiomyosarcoma treated at The University of Texas involvement of the aorta. Microscopic examination reM. D. Anderson Cancer Center between 1980 and 1991 vealed a grade 111leiomyosarcoma encasing the inferior were reviewed retrospectively. Only those patients with vena cava. Approximately 50% of the tumor was neclear pathologic evidence of origin from the wall of the crotic. The tumor extended to the iliopsoas and parainferior vena cava were selected for this review. AddiAccepted for publication June 18, 1992 tionally, only patients who received definitive surgical Address reprint requests to Steven A . Curley, MD, Department of treatment at M. D. Anderson Cancer Center have been Surgery, Box 106, The University of Texas M. D. Anderson Cancer Center, 15 15 Holcombe Blvd., Houston, TX 77030. included. 0 1992 Wiley-Liss, Inc.
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spinous muscles, and resection margins were positive in the muscles. One month after discharge, she required ultrasound-guided drainage of a fluid collection, but otherwise had an uneventful recovery. Seventeen months following her sarcoma resection, she had a local recurrence and underwent tumor debulking and resection of involved transverse colon. The patient died from tumor recurrence 6 months after the second resection.
Case 2 A 73-year-old woman developed nausea and vomiting with intermittent epigastric distress and a 20 Ib weight loss. Five months after the onset of her symptoms, she was noted to have a large abdominal mass. Fine needle aspiration revealed a spinal cell neoplasm consistent with smooth muscle. A CT scan showed a mass involving the left and caudate lobes of the liver, as well as the inferior vena cava and the left hepatic vein. The pancreas was displaced. A visceral angiogram revealed that the mass derived blood supply from the hepatic artery, branches of gastric arteries, and the dorsal pancreatic and pancreaticoduodenal arteries. The tumor had invaded the retrohepatic inferior vena cava; the portal and splenic veins were patent. She underwent laparotomy with resection of a retroperitoneal sarcoma and the vena cava, a superficial inferior hepatic wedge resection, and oversewing of the suprarenal inferior vena cava and infrahepatic inferior vena cava. In the postoperative period the patient developed a bile leak and required reoperation for bile drainage, but was discharged from the hospital 4 weeks after her first operation. The specimen showed that the tumor originated in the inferior vena cava. Microscopic examination revealed that the leiomyosarcoma had 15 mitoses per high power field, scattered atypical mitoses, focal marked atypia, and large foci of necrosis. The tumor invaded the entire wall of the inferior vena cava and the capsule of the liver, although the hepatic parenchyma was free of tumor. Seven months after discharge the patient was found to have bilobar liver metastases. She was treated with ifosfamide (2 g/m2). She died 2 years after her first operation.
Fig. 1 . CT scan of a large leiomyosarcoma of the inferior vena cava involving the right kidney.
sion over 72 hours. Follow-up CT scan showed stable disease in the retroperitoneum. At operation the mass was seen to involve the right kidney and to arise from the inferior vena cava. She underwent en bloc right nephrectomy, partial right adrenalectomy, and excision of part of the inferior vena caval wall with primary repair. She was discharged from the hospital on the 9th postoperative day. Upon microscopic examination the tumor was found to involve the wall of the inferior vena cava. The one lymph node described had no tumor present. The patient died 3 years after her operation of an unrelated condition.
Case 4 A 24-year-old woman was noted to have a 10 cm intraabdominal mass during a total abdominal hysterectomy and bilateral salpingoophorectomy for pelvic inflammatory disease at another hospital. Partial resection of the tumor revealed a leiomyosarcoma. The patient was referred to M. D. Anderson Cancer Center and began three cycles of cyclophosphamide, doxorubicin, and dacarbazine. Cyclophosphamide (600 mg/rn2) was administered on the 1st day of each cycle, and doxorubicin (60 mg/m2) and dacarbazine (1,000 mg/m2) were given by Case 3 continuous infusion over the following 72 hours. A CT A 71-year-old woman with a history of multiple my- scan following the third course of chemotherapy revealed eloma, which had been in remission for 4 years following a residual retroperitoneal tumor, 5 cm X 8 cm X 4 cm in chemotherapy (vincristine, cyclophosphamide, pred- size. A cavagram showed occlusion of the inferior vena nisone, and melphalan), noted a fullness in her right cava by tumor (Fig. 2). She underwent exploratory lapflank. A CT scan suggested a right renal mass consistent arotomy with resection of the tumor, which arose from with renal cell carcinoma (Fig. 1). Visceral angiography the anterior wall of the inferior vena cava. Excision with and inferior vena cava venography showed some irregu- primary closure of the inferior vena cava was performed. larity of the wall of the inferior vena cava. A percutane- The tumor mass was 8 cm in its greatest diameter. Microous biopsy was obtained, and a high-grade leiomyosar- scopic evaluation revealed that it had high mitotic activcoma was diagnosed. The patient began two cycles of ity, showing up to 15 mitoses per high power field. Her preoperative chemotherapy with doxorubicin (75 mg/m2) postoperative course was uneventful, and she underwent and dacarbazine (750 mg/m2), each by continuous infu- three more cycles of chemotherapy. The patient did well
Inferior Vena Cava Leiomyosarcoma
91
cause of chemotherapy in our patients. The impact of preoperative chemotherapy on perioperative morbidity appears to be minimal, as postoperative courses were uniformly short. The shortest time intervals to first evidence of tumor recurrence were found in a patient with grossly positive margins in the retroperitoneal muscles (case 1 ) and a patient with contiguous involvement of the liver who received no chemotherapy (case 2). They died of local recurrence and liver metastases, respectively. Tumor recurrence frequently portends a shortened survival, and this was evident in our patients (cases 1 and 2). This slow-growing tumor can be associated with longer survival if aggressive therapy is used, as was seen in one patient (case 4) who survived for 42 months following her initial tumor recurrence.
Fig. 2. A cavagram demonstrates occlusion of the inferior vena cava at the contluence of the common iliac veins with extensive collateral venous channels.
for 30 months following her surgery, until a CT scan showed a recurrent tumor within her abdomen. The tumor was thought to be unresectable, so the patient had a seventh cycle of chemotherapy and then a debulking operation. At laparotomy she underwent sarcoma resection, removal of several tumor modules (periaortic and periportal), and excision of a small portion of her duodenum. After surgery she required percutaneous drainage of right flank and pelvic abscesses. She died of metastatic disease 6 years after her initial sarcoma resection.
RESULTS Three of the four patients we report with inferior vena cava leiomyosarcomas received combination chemotherapy before definitive tumor resection (cases 1, 3, and 4) (see Table I). Two of them (cases 1 and 4) also underwent tumor dissection or partial resection at other hospitals before radical tumor resection. Although the preoperative chemotherapy did cause neutropenic fevers necessitating hospital admission and intravenous antibiotics (cases 3 and 4), as well as one instance of catheter sepsis, no treatments were interrupted or operations postponed be-
DISCUSSION Leiomyosarcoma of the inferior vena cava is a rare tumor. The first case, found at autopsy, was reported by Per1 in 1871 [2]. Since then, a total of 144 cases have been reported and reviewed [ 11. In earlier reports, these were correctly diagnosed at autopsy, but more recently angiography and CT scanning have allowed earlier detection and management [3,4]. Inferior vena cava leiomyosarcomas can grow large before detection, like other retroperitoneal tumors. They can also invade contiguous structures, and involvements of the right atrium [5], liver, hepatic veins, aorta, renal veins, and stomach have been described [6]. The physical signs and symptoms are often vague and can include weight loss, abdominal pain, and abdominal or flank mass [ l ] . Lower extremity edema, renal insufficiency, and the Budd-Chiari syndrome can occur because of encroachment upon the inferior vena cava, renal veins, or hepatic veins by the tumor [7]. More unusual presentations have included tricuspid valve obstruction and pulmonary embolism [5,8]. Radical surgical resection is the only potentially curative modality available for patients with inferior vena cava leiomyosarcomas. Adjuvant therapy has not been shown to provide any significant impact upon survival, but good responses have allowed resection with some success in individual cases [ 1,9]. Some surgeons have described the location of the tumors as being either upper segment (above the hepatic veins), middle segment (between the hepatic veins and renal veins), or lower segment (below the renal veins) [ 101. Tumors of the upper segment have been less amenable to radical surgical excision than those originating in the lower segments of the inferior vena cava because of proximity to the hepatic veins and the technical difficulty of providing adequate venous drainage for the liver in the face of caval resection above the hepatic veins [ 1 11. Most tumors have a primarily extraluminal growth pattern, and over half the patients have a patent vena cava at diagnosis [I]. However, up to 68% of patients have either neoplastic thrombus or in-
92
Demers et al.
TABLE I. Patterns of Failure for Patients With Leiomyosarcoma of the Inferior Vena Cava*
Case 1
2 3 4
Age at diagnosis 42 73 71 24
Sex F F F
F
Date of surgery
Chemotherapy
3/16/87 12128187 12128187 3/22/82
Preop Postop Preop Pre- and postop
*Preop = before definitive tumor resection; Postop
=
Irradiation
Location of first failure
Time to first failure (months)
Postop None None None
Local Liver n.a. Local
20 14 n.a. 33
Survival (months) 23 18 38 75
following definitive tumor resection; n.a. = not applicable
traluminal growth, leading to varying degrees of inferior vena cava insufficiency. The development of venous collaterals allows for caval interruption below the hepatic veins, with few adverse sequelae in most cases. Radical surgical resection is superior to other therapies even when cure is not achieved and should be aggressively pursued where possible. Although the rate of recurrence is high (52.4% at a median of 25 months), the 5-year survival rate is 28% for patients undergoing radical resection, whereas patients who cannot undergo radical resection die within several months [I]. The impact of adjuvant chemotherapy and radiation upon recurrence rates and survival is unlikely to undergo systematic evaluation, as the rarity of this particular tumor precludes subjecting patiens to clinical trials. Neoadjuvant therapies may be of benefit in selected cases before definitive resection. The theoretical virtues of preoperative chemotherapy are the control of micrometastases, reduction in size of lesions before resection, and in situ evaluation of tumor response to chemotherapy to determine if continuation of the chemotherapeutic agents as adjuvant chemotherapy is appropriate [ 121.
CONCLUSIONS Leiomyosarcoma of the vena cava is a rare, slowgrowing malignancy. Like other sarcomas of the retroperitoneum, it is rarely discovered at a stage when true radical resection with negative margins can be accomplished. Modern imaging techniques have allowed clear identification of these tumors and have provided better operative planning than had been previously available, so that more patients come to operation without evident distant spread. Nonetheless, the majority of patients ultimately suffer tumor recurrence either as local failure, distant metastases, or both. With better diagnostic modalities and perioperative support, the operative challenge is to provide complete resection with pathologically negative margins at the first laparotomy , avoiding debulking procedures or inadequate resection whenever possible. In this small group of patients we found that preoperative chemotherapy did not adversely affect operative outcomes or survival. It can be used as a means of downstaging tumors of marginal resectability and may delay the
onset of tumor recurrence by eliminating or controlling micrometastatic foci.
ACKNOWLEDGMENTS The authors wish to thank Ms. Kathryn L. Hale for her editorial assistance. In addition the authors acknowledge support from the Del and Dennis McCarthy Fund for Surgical Oncology Research and The RGK Foundation Fund for Sarcoma Research. REFERENCES I . Mingoli A , Feldhaus R, Cavallaro A, Stipa S: Leiomyosarcoma of the inferior vena cam: analysis and search of world literature on 141 patients and report of three new cases. J Vasc Surg 14:688699, 1991. 2. Per1 L Ein fall von sarkom dcr Vena cava inferior. Virchows Arch [A] 531378-383, 1871. 3. Castleman B, McNeely B (eds): Case records of the Massachusetts General Hospital. Case 17-1971. N Engl J Med 284:967974, 1971. 4. Friedrich M, Tung L, Dieneniann D: D d S leiomyosarkom der vena cava inferior. Diagnostik-thcrapie-prognose.Radiologie 27:3642, 1987. 5 . Demoulin .I, Sambon Y , Baudinet V, et al.: Leiomyosarcoma of the inferior vena cava: an unusual cause of pulmonary embolism. Chest 66597-599, 1974. 6. Kevorkian J . Cento D: Leiomyosarcoma of large arteries and veins. Surgery 73:390-400, 1973. 7. Lok A , Wong K, Lee P, et al.: Radiological diagnosis of leiomyosarcoma of the inferior vena cava. Clin Radio1 37:403405, 1986. 8. Hoffbrand AV, Lloyd-Thomas HG: Leiomyosarcoma of the inferior vena cava leading to obstruction of the tricuspid valve. Br Heart J 26:709-715, 1964. 9. Picard JD, Denis P, Chambeyron Y, et al.: Les Ieiomyosarcomes de la veine cave inferieure. La place des examens complementaires apropos de deux cas. Chirurgie 109:30&309, 1983. 10. Adeyemi E, Scheibal V: Leiomyosarcoma of the inferior vena cava. A case report with a review of the literature. Postgrad Med J 5 8 ~ 15-5 5 19, 1982. 11. Brewster D, Athanasoulis C, Darling R: Leiomyosarcoma of the inferior vena cava. Arch Surg 111:1081-1085, 1976. 12. Pezzi CM, Pollock RE, Evans HL, et al.: Preoperative chemotherapy for soft-tissue sarcomas of the extremities. Ann Surg 211:476481, 1990.
EDITORIAL COMMENTS Neoadjuvant chemotherapy is an interesting concept for soft tissue sarcomas and specifically leiomyosarcomas of the inferior vena cava. It is the standard of treatment for osteogenic sarcomas. However, although the
Inferior Vena Cava Leiomyosarcoma
objective response rate in soft tissue sarcomas with combination chemotherapy is quoted in some reports to be as high as about 50% [ 11, the rate of bona fide, substantial objective responses may not be higher than about 30%. Therefore in administering neoadjuvant chemotherapy, one should be aware that in at least half of the patients the tumor will be larger after two courses and even less resectable. However, neoadjuvant chemotherapy should be considered for a patient with a tumor that is already considered unresectable. The other major modality of treatment is radiation. As far as local control at the primary site is concerned, the combination of preoperative radiation (to partially shrink the tumor and sterilize its periphery) and surgical resection, or that of marginal resection followed by intraoperative or postoperative radiation (to destroy microscopic residual) seems to be very effective in securing local control in the management of primary soft tissue sarcomas [2,3]. In high grade sarco-
93
mas due to their tendency to metastasize, a systemic adjuvant therapy is obviously desirable. However, the goal of establishing the effectiveness of adjuvant chemotherapy in soft tissue sarcomas, although certainly laudable, has remained so far elusive. Constantine P. Karakousis, MD Roswell Park Cancer Institute Buffalo, New York 14263
REFERENCES 1. Elias AD, Antman K, Ryan L: Doxorubicin (DOX), ifosfamide
(IFF), and DTlC with mesna uroprotection for advanced untreated sarcoma. Proc ASCO 6: 137, 1987. 2. Lindberg RD, Martin RG, Ronsdahl MM, Barkley HT: Conservative surgery and postoperative radiotherapy in 300 adults with soft tissue sarcomas. Cancer 47:2391-2397, 1981. 3 . Karakousis CP, Emrich LJ, Rao U, Khalil M: Limb salvage in soft tissue sarcomas with selective combination of modalities. Eur J Surg Oncol 17:7 1-80, 1991.
Inferior Vena Cava Leiomyosarcoma MARC L. DEMERS, MD, STEVEN A. CURLEY, MD, AND MARVIN M. ROMSDAHL, MD, PhD From the Department of General Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ~
~
Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M. D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy. 0 1992 Wiley-Liss, Inc.
KEYWORDS:sarcoma, neoadjuvant chemotherapy, micrometastasis
INTRODUCTION Leiomyosarcomas of the inferior vena care are rare malignancies, but they have been reported with greater frequency in recent years. Like other retroperitoneal neoplasms, these tumors are often large before the onset of symptoms or signs of a mass on physical examination. A recent review of the literature describes 144 cases of these tumors and has confirmed the importance of radical resection as the only hope for cure [ 11. Our report reaffirms this and suggests that chemotherapy given before resection may be of benefit. The potential advantages of preoperative chemotherapy include reduction of tumor size, assessment of the tumor response to chemotherapy to help in selection of appropriate postoperative chemotherapy, and control of micrometastases elsewhere in the body. We report herein an additional four cases of leiomyosarcoma of the vena cava with an emphasis on surgical management and preoperative chemotherapy.
Case 1 A 42-year-old woman experienced the onset of right flank pain and bilateral lower extremity edema over a 1-month period. Two months following the onset of flank pain, she underwent exploratory laparotomy at another hospital. Resection was attempted and abandoned, as the mass was seen to involve the aorta and right ureter. The patient had three postoperative courses of cyclophosphamide, doxorubicin, and dacarbazine as well as radiation therapy. The cyclophosphamide (600 mg/m2) was given on day 1 and the doxorubicin (15 mg/m2/day) and dacarbazine (250 mg/m2/day) on days 2-5 by continuous infusion. The dose, field, and fractionation of radiation is not known. On a repeat computed tomographic scan following the three cycles of chemotherapy the mass had decreased in size by 40%. She was referred to M. D. Anderson Cancer Center. At operation she underwent en bloc resection of a sarcoma involving the infrarenal aorta, inferior vena cava, and right kidney, and vascular reconstruction using an aortoiliac interposition graft. The vena PATIENTS AND METHODS cava was ligated. Gross examination of the tumor reThe case records of all patients with the diagnosis of vealed that it arose from the inferior vena cava with leiomyosarcoma treated at The University of Texas involvement of the aorta. Microscopic examination reM. D. Anderson Cancer Center between 1980 and 1991 vealed a grade 111leiomyosarcoma encasing the inferior were reviewed retrospectively. Only those patients with vena cava. Approximately 50% of the tumor was neclear pathologic evidence of origin from the wall of the crotic. The tumor extended to the iliopsoas and parainferior vena cava were selected for this review. AddiAccepted for publication June 18, 1992 tionally, only patients who received definitive surgical Address reprint requests to Steven A . Curley, MD, Department of treatment at M. D. Anderson Cancer Center have been Surgery, Box 106, The University of Texas M. D. Anderson Cancer Center, 15 15 Holcombe Blvd., Houston, TX 77030. included. 0 1992 Wiley-Liss, Inc.
90
Demers et al.
spinous muscles, and resection margins were positive in the muscles. One month after discharge, she required ultrasound-guided drainage of a fluid collection, but otherwise had an uneventful recovery. Seventeen months following her sarcoma resection, she had a local recurrence and underwent tumor debulking and resection of involved transverse colon. The patient died from tumor recurrence 6 months after the second resection.
Case 2 A 73-year-old woman developed nausea and vomiting with intermittent epigastric distress and a 20 Ib weight loss. Five months after the onset of her symptoms, she was noted to have a large abdominal mass. Fine needle aspiration revealed a spinal cell neoplasm consistent with smooth muscle. A CT scan showed a mass involving the left and caudate lobes of the liver, as well as the inferior vena cava and the left hepatic vein. The pancreas was displaced. A visceral angiogram revealed that the mass derived blood supply from the hepatic artery, branches of gastric arteries, and the dorsal pancreatic and pancreaticoduodenal arteries. The tumor had invaded the retrohepatic inferior vena cava; the portal and splenic veins were patent. She underwent laparotomy with resection of a retroperitoneal sarcoma and the vena cava, a superficial inferior hepatic wedge resection, and oversewing of the suprarenal inferior vena cava and infrahepatic inferior vena cava. In the postoperative period the patient developed a bile leak and required reoperation for bile drainage, but was discharged from the hospital 4 weeks after her first operation. The specimen showed that the tumor originated in the inferior vena cava. Microscopic examination revealed that the leiomyosarcoma had 15 mitoses per high power field, scattered atypical mitoses, focal marked atypia, and large foci of necrosis. The tumor invaded the entire wall of the inferior vena cava and the capsule of the liver, although the hepatic parenchyma was free of tumor. Seven months after discharge the patient was found to have bilobar liver metastases. She was treated with ifosfamide (2 g/m2). She died 2 years after her first operation.
Fig. 1 . CT scan of a large leiomyosarcoma of the inferior vena cava involving the right kidney.
sion over 72 hours. Follow-up CT scan showed stable disease in the retroperitoneum. At operation the mass was seen to involve the right kidney and to arise from the inferior vena cava. She underwent en bloc right nephrectomy, partial right adrenalectomy, and excision of part of the inferior vena caval wall with primary repair. She was discharged from the hospital on the 9th postoperative day. Upon microscopic examination the tumor was found to involve the wall of the inferior vena cava. The one lymph node described had no tumor present. The patient died 3 years after her operation of an unrelated condition.
Case 4 A 24-year-old woman was noted to have a 10 cm intraabdominal mass during a total abdominal hysterectomy and bilateral salpingoophorectomy for pelvic inflammatory disease at another hospital. Partial resection of the tumor revealed a leiomyosarcoma. The patient was referred to M. D. Anderson Cancer Center and began three cycles of cyclophosphamide, doxorubicin, and dacarbazine. Cyclophosphamide (600 mg/rn2) was administered on the 1st day of each cycle, and doxorubicin (60 mg/m2) and dacarbazine (1,000 mg/m2) were given by Case 3 continuous infusion over the following 72 hours. A CT A 71-year-old woman with a history of multiple my- scan following the third course of chemotherapy revealed eloma, which had been in remission for 4 years following a residual retroperitoneal tumor, 5 cm X 8 cm X 4 cm in chemotherapy (vincristine, cyclophosphamide, pred- size. A cavagram showed occlusion of the inferior vena nisone, and melphalan), noted a fullness in her right cava by tumor (Fig. 2). She underwent exploratory lapflank. A CT scan suggested a right renal mass consistent arotomy with resection of the tumor, which arose from with renal cell carcinoma (Fig. 1). Visceral angiography the anterior wall of the inferior vena cava. Excision with and inferior vena cava venography showed some irregu- primary closure of the inferior vena cava was performed. larity of the wall of the inferior vena cava. A percutane- The tumor mass was 8 cm in its greatest diameter. Microous biopsy was obtained, and a high-grade leiomyosar- scopic evaluation revealed that it had high mitotic activcoma was diagnosed. The patient began two cycles of ity, showing up to 15 mitoses per high power field. Her preoperative chemotherapy with doxorubicin (75 mg/m2) postoperative course was uneventful, and she underwent and dacarbazine (750 mg/m2), each by continuous infu- three more cycles of chemotherapy. The patient did well
Inferior Vena Cava Leiomyosarcoma
91
cause of chemotherapy in our patients. The impact of preoperative chemotherapy on perioperative morbidity appears to be minimal, as postoperative courses were uniformly short. The shortest time intervals to first evidence of tumor recurrence were found in a patient with grossly positive margins in the retroperitoneal muscles (case 1 ) and a patient with contiguous involvement of the liver who received no chemotherapy (case 2). They died of local recurrence and liver metastases, respectively. Tumor recurrence frequently portends a shortened survival, and this was evident in our patients (cases 1 and 2). This slow-growing tumor can be associated with longer survival if aggressive therapy is used, as was seen in one patient (case 4) who survived for 42 months following her initial tumor recurrence.
Fig. 2. A cavagram demonstrates occlusion of the inferior vena cava at the contluence of the common iliac veins with extensive collateral venous channels.
for 30 months following her surgery, until a CT scan showed a recurrent tumor within her abdomen. The tumor was thought to be unresectable, so the patient had a seventh cycle of chemotherapy and then a debulking operation. At laparotomy she underwent sarcoma resection, removal of several tumor modules (periaortic and periportal), and excision of a small portion of her duodenum. After surgery she required percutaneous drainage of right flank and pelvic abscesses. She died of metastatic disease 6 years after her initial sarcoma resection.
RESULTS Three of the four patients we report with inferior vena cava leiomyosarcomas received combination chemotherapy before definitive tumor resection (cases 1, 3, and 4) (see Table I). Two of them (cases 1 and 4) also underwent tumor dissection or partial resection at other hospitals before radical tumor resection. Although the preoperative chemotherapy did cause neutropenic fevers necessitating hospital admission and intravenous antibiotics (cases 3 and 4), as well as one instance of catheter sepsis, no treatments were interrupted or operations postponed be-
DISCUSSION Leiomyosarcoma of the inferior vena cava is a rare tumor. The first case, found at autopsy, was reported by Per1 in 1871 [2]. Since then, a total of 144 cases have been reported and reviewed [ 11. In earlier reports, these were correctly diagnosed at autopsy, but more recently angiography and CT scanning have allowed earlier detection and management [3,4]. Inferior vena cava leiomyosarcomas can grow large before detection, like other retroperitoneal tumors. They can also invade contiguous structures, and involvements of the right atrium [5], liver, hepatic veins, aorta, renal veins, and stomach have been described [6]. The physical signs and symptoms are often vague and can include weight loss, abdominal pain, and abdominal or flank mass [ l ] . Lower extremity edema, renal insufficiency, and the Budd-Chiari syndrome can occur because of encroachment upon the inferior vena cava, renal veins, or hepatic veins by the tumor [7]. More unusual presentations have included tricuspid valve obstruction and pulmonary embolism [5,8]. Radical surgical resection is the only potentially curative modality available for patients with inferior vena cava leiomyosarcomas. Adjuvant therapy has not been shown to provide any significant impact upon survival, but good responses have allowed resection with some success in individual cases [ 1,9]. Some surgeons have described the location of the tumors as being either upper segment (above the hepatic veins), middle segment (between the hepatic veins and renal veins), or lower segment (below the renal veins) [ 101. Tumors of the upper segment have been less amenable to radical surgical excision than those originating in the lower segments of the inferior vena cava because of proximity to the hepatic veins and the technical difficulty of providing adequate venous drainage for the liver in the face of caval resection above the hepatic veins [ 1 11. Most tumors have a primarily extraluminal growth pattern, and over half the patients have a patent vena cava at diagnosis [I]. However, up to 68% of patients have either neoplastic thrombus or in-
92
Demers et al.
TABLE I. Patterns of Failure for Patients With Leiomyosarcoma of the Inferior Vena Cava*
Case 1
2 3 4
Age at diagnosis 42 73 71 24
Sex F F F
F
Date of surgery
Chemotherapy
3/16/87 12128187 12128187 3/22/82
Preop Postop Preop Pre- and postop
*Preop = before definitive tumor resection; Postop
=
Irradiation
Location of first failure
Time to first failure (months)
Postop None None None
Local Liver n.a. Local
20 14 n.a. 33
Survival (months) 23 18 38 75
following definitive tumor resection; n.a. = not applicable
traluminal growth, leading to varying degrees of inferior vena cava insufficiency. The development of venous collaterals allows for caval interruption below the hepatic veins, with few adverse sequelae in most cases. Radical surgical resection is superior to other therapies even when cure is not achieved and should be aggressively pursued where possible. Although the rate of recurrence is high (52.4% at a median of 25 months), the 5-year survival rate is 28% for patients undergoing radical resection, whereas patients who cannot undergo radical resection die within several months [I]. The impact of adjuvant chemotherapy and radiation upon recurrence rates and survival is unlikely to undergo systematic evaluation, as the rarity of this particular tumor precludes subjecting patiens to clinical trials. Neoadjuvant therapies may be of benefit in selected cases before definitive resection. The theoretical virtues of preoperative chemotherapy are the control of micrometastases, reduction in size of lesions before resection, and in situ evaluation of tumor response to chemotherapy to determine if continuation of the chemotherapeutic agents as adjuvant chemotherapy is appropriate [ 121.
CONCLUSIONS Leiomyosarcoma of the vena cava is a rare, slowgrowing malignancy. Like other sarcomas of the retroperitoneum, it is rarely discovered at a stage when true radical resection with negative margins can be accomplished. Modern imaging techniques have allowed clear identification of these tumors and have provided better operative planning than had been previously available, so that more patients come to operation without evident distant spread. Nonetheless, the majority of patients ultimately suffer tumor recurrence either as local failure, distant metastases, or both. With better diagnostic modalities and perioperative support, the operative challenge is to provide complete resection with pathologically negative margins at the first laparotomy , avoiding debulking procedures or inadequate resection whenever possible. In this small group of patients we found that preoperative chemotherapy did not adversely affect operative outcomes or survival. It can be used as a means of downstaging tumors of marginal resectability and may delay the
onset of tumor recurrence by eliminating or controlling micrometastatic foci.
ACKNOWLEDGMENTS The authors wish to thank Ms. Kathryn L. Hale for her editorial assistance. In addition the authors acknowledge support from the Del and Dennis McCarthy Fund for Surgical Oncology Research and The RGK Foundation Fund for Sarcoma Research. REFERENCES I . Mingoli A , Feldhaus R, Cavallaro A, Stipa S: Leiomyosarcoma of the inferior vena cam: analysis and search of world literature on 141 patients and report of three new cases. J Vasc Surg 14:688699, 1991. 2. Per1 L Ein fall von sarkom dcr Vena cava inferior. Virchows Arch [A] 531378-383, 1871. 3. Castleman B, McNeely B (eds): Case records of the Massachusetts General Hospital. Case 17-1971. N Engl J Med 284:967974, 1971. 4. Friedrich M, Tung L, Dieneniann D: D d S leiomyosarkom der vena cava inferior. Diagnostik-thcrapie-prognose.Radiologie 27:3642, 1987. 5 . Demoulin .I, Sambon Y , Baudinet V, et al.: Leiomyosarcoma of the inferior vena cava: an unusual cause of pulmonary embolism. Chest 66597-599, 1974. 6. Kevorkian J . Cento D: Leiomyosarcoma of large arteries and veins. Surgery 73:390-400, 1973. 7. Lok A , Wong K, Lee P, et al.: Radiological diagnosis of leiomyosarcoma of the inferior vena cava. Clin Radio1 37:403405, 1986. 8. Hoffbrand AV, Lloyd-Thomas HG: Leiomyosarcoma of the inferior vena cava leading to obstruction of the tricuspid valve. Br Heart J 26:709-715, 1964. 9. Picard JD, Denis P, Chambeyron Y, et al.: Les Ieiomyosarcomes de la veine cave inferieure. La place des examens complementaires apropos de deux cas. Chirurgie 109:30&309, 1983. 10. Adeyemi E, Scheibal V: Leiomyosarcoma of the inferior vena cava. A case report with a review of the literature. Postgrad Med J 5 8 ~ 15-5 5 19, 1982. 11. Brewster D, Athanasoulis C, Darling R: Leiomyosarcoma of the inferior vena cava. Arch Surg 111:1081-1085, 1976. 12. Pezzi CM, Pollock RE, Evans HL, et al.: Preoperative chemotherapy for soft-tissue sarcomas of the extremities. Ann Surg 211:476481, 1990.
EDITORIAL COMMENTS Neoadjuvant chemotherapy is an interesting concept for soft tissue sarcomas and specifically leiomyosarcomas of the inferior vena cava. It is the standard of treatment for osteogenic sarcomas. However, although the
Inferior Vena Cava Leiomyosarcoma
objective response rate in soft tissue sarcomas with combination chemotherapy is quoted in some reports to be as high as about 50% [ 11, the rate of bona fide, substantial objective responses may not be higher than about 30%. Therefore in administering neoadjuvant chemotherapy, one should be aware that in at least half of the patients the tumor will be larger after two courses and even less resectable. However, neoadjuvant chemotherapy should be considered for a patient with a tumor that is already considered unresectable. The other major modality of treatment is radiation. As far as local control at the primary site is concerned, the combination of preoperative radiation (to partially shrink the tumor and sterilize its periphery) and surgical resection, or that of marginal resection followed by intraoperative or postoperative radiation (to destroy microscopic residual) seems to be very effective in securing local control in the management of primary soft tissue sarcomas [2,3]. In high grade sarco-
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mas due to their tendency to metastasize, a systemic adjuvant therapy is obviously desirable. However, the goal of establishing the effectiveness of adjuvant chemotherapy in soft tissue sarcomas, although certainly laudable, has remained so far elusive. Constantine P. Karakousis, MD Roswell Park Cancer Institute Buffalo, New York 14263
REFERENCES 1. Elias AD, Antman K, Ryan L: Doxorubicin (DOX), ifosfamide
(IFF), and DTlC with mesna uroprotection for advanced untreated sarcoma. Proc ASCO 6: 137, 1987. 2. Lindberg RD, Martin RG, Ronsdahl MM, Barkley HT: Conservative surgery and postoperative radiotherapy in 300 adults with soft tissue sarcomas. Cancer 47:2391-2397, 1981. 3 . Karakousis CP, Emrich LJ, Rao U, Khalil M: Limb salvage in soft tissue sarcomas with selective combination of modalities. Eur J Surg Oncol 17:7 1-80, 1991.
