Leiomyosarcoma of the Inferior Vena Cava

Abstract:

From 1979 to 2004, 22 patients were seen with leiomyosarcomas of the inferior vena cava (IVC). Twenty were treated surgically. Involvement of the IVC included the infrarenal segment in 3 cases, the suprarenal and/or retrohepatic segment in 13, and the suprahepatic segment in 4. Nineteen patients underwent wide tumor resection followed by ligation of the IVC in 5 cases, replacement with a PTFE prosthesis in 13, and cavoplasty in 1. An intracardiac tumor extension was resected during hypothermic circulatory arrest in 1 patient. Vascular exclusion of the liver was used in 5 cases and simple clamping of the IVC in 13 cases. There were 1 intraoperative death due to cardiac failure and 3 postoperative deaths due to multiple organ failure, liver failure, and duodenal fistula after treatment of a bleeding ulcer. Fifteen of the 16 surviving patients underwent adjuvant chemotherapy associated with radiation therapy in 4 cases. One patient was lost from follow-up at 10 months. Four patients including one with metastasis are still alive with a mean follow-up of 18.3 months. Eleven patients died after a mean follow-up period of 43.7 months due to local recurrence and/or distant metastasis in 9 cases and complications of chemotherapy in 2. The 3- and 5-year mean actuarial survival rates in patients who underwent resection were 52.0% and 34.8%, respectively. Leiomyosarcoma of the IVC is a serious disease. Although surgical resection combined with chemotherapy is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.

A single-center surgical experience with 22 leiomyosarcomas of the IVC is presented. Although surgical resection, combined with chemotherapy, is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.

Although rare, leiomyosarcoma of the inferior vena cava (IVC) is the most common primary malignancy of the IVC. It has an extremely poor prognosis. According to the international register established by Mingoli et al,¹ the 5- and 10-year actuarial malignancy-free survival rates after wide surgical resection are 31.4% and 7.4%, respectively. However with the exception of that register and of a few large series,^2–4 most reported cases have involved isolated cases or small series, including only a few cases often with short follow-up. We reviewed our experience with 22 cases seen over a period of 25 years to evaluate surgical treatment modalities as well as middle- and long-term prognosis. Seven of these patients were described in a previous report.⁵

PATIENTS AND METHODS

From 1979 to 2004, we have seen 22 patients with leiomyosarcoma of the IVC. There were 16 women (73%) and 6 men (27%) with a mean age of 59.5 ± 13.2 years (range, 28–80 years; median, 61 years).

The most common presenting symptom was pain in the right flank that was observed in all but 1 patient (96%). This symptom was often long-standing and misled diagnosis. Edema of the lower extremities was an inconsistent finding observed in 7 patients (32%). Two patients presented Budd-Chiari syndrome with hepatomegaly, ascites, and jaundice that developed acutely in 1 case and chronically in the other.

Noninvasive imaging techniques included abdominal ultrasound in 22 patients (100%), CT scan in 21 patients (96%), and MRI in 8 recent patients (36%). Ascending cavography by the femoral route often in association with retrograde cavography by the jugular route was performed in 20 patients (91%) to delineate the involvement of major branches (renal and hepatic veins) of the IVC. Selective arteriography of the celiac trunk was performed in 7 patients (32%), ie, all patients in whom associated hepatic invasion or metastasis was suspected. Transesophageal echocardiography was performed in 6 patients (27%) in whom intracardiac extension was suspected.

Based on the findings of these examinations, tumor involvement was classified into 3 groups according to level in the IVC: segment I, infrarenal; segment II, inter- and supra-renal up to but not including the main suprahepatic veins; and segment III, suprahepatic with possible intracardiac extension (Fig. 1). The upper limit of the tumor was in segment I in 3 patients, segment II in 14 patients, and segment III in 5 patients, including 2 with intracardiac extension. The tumor extension was confined to either segment I in 3 cases or segment II in 11 cases and covered segments I and II in 3 cases, segments II and III in 4 cases, and segments I, II, and III in 1 case. Tumor development was predominantly extracaval in 16 patients (73%), accounting for the frequent absence of edema of the lower extremity (Fig. 2). Complete obstruction of the IVC was observed in 6 patients (27%) (Fig. 3). Mean maximum tumor diameter was 20.6 ± 7.5 cm (range, 8–37 cm; median, 21 cm). Liver invasion by contiguity or metastasis was found in 5 patients (23%), including 2 limited to the right liver and 2 to the left liver (Fig. 4). Extension to the infrarenal abdominal aorta was observed in 3 patients (Fig. 5). One patient presenting chronic Budd-Chiari syndrome with an intracardiac tumor extension had a supra-diaphragmatic extension to the right lung that was totally destroyed.

FIGURE 1. Extent and upper limit of 22 leiomyosarcomas according to the classification of the IVC into 3 segments.

FIGURE 2. Cavography showing predominantly extracaval development in 2 retrohepatic leiomyosarcomas.

FIGURE 3. CT scan and cavography showing intracaval development of an infrarenal leiomyosarcoma.

FIGURE 4. A, CT scan showing invasion by contiguity of the left liver by a retrohepatic leiomyosarcoma. B, Cavography showing extension up to the hepatic veins. C, Postoperative cavography through the proximal arteriovenous fistula showing patency of the prosthetic replacement of the IVC.

FIGURE 5. CT scan (A) and aortography (B) showing extension to the aortic bifurcation by an infrarenal leiomyosarcoma. Note involvement of the right renal pedicle resulting in a destroyed kidney.

Preoperative histologic diagnosis was achieved in 16 patients (80%) by percutaneous biopsy in 6 cases (37%) and laparotomy in 10 cases (63%). Six of the laparotomized patients underwent only biopsy, but 4 patients had undergone partial resection procedures and were referred to our department for further treatment or early recurrence.

Six patients (37%) in whom preoperative diagnosis was achieved underwent preoperative chemotherapy using adriamycin-ifosfamide. Only 1 of these patients underwent preoperative radiation therapy.

Two patients (9%) did not undergo operative treatment. One of these patients who presented multiple hepatic metastases and was contraindicated for liver transplantation died within 6 months. Another patient died immediately before surgery due to occlusion of the tricuspid valve by the upper tip of the tumor. Otherwise, no patients were excluded from surgery, whatever local extension of the tumor or general condition.

Twenty patients (91%) underwent operative treatment. In 12 cases (60%), the procedure was performed by a strictly abdominal approach: median laparotomy in 3 cases and right subcostal incision in 9 cases. In 8 cases (40%), the procedure was performed by the thoracoabdominal route: thoracophrenotomy combined with laparotomy in 2 cases and sternotomy combined with laparotomy in 6 cases, including 2 partial sternotomies.

Wide tumor resection was performed in all but 1 case in which mesoatrial bypass was used for palliation of acute Budd-Chiari syndrome. The intervention was limited to resection of the IVC without reestablishment of continuity in 5 patients (25%). For 1 of these patients with a tumor limited to segment I, it was deemed preferable not to use a prosthesis after dissection as close to the duodenopancreatic area required placement of a small-intestine patch on the duodenum at the end of the procedure. In the other 4 patients, the tumor was localized or extended to segment II. Concurrent right nephrectomy was performed due to tumor invasion of the right renal vein in patients with satisfactory collateral run-off from the left kidney via the genital, middle capsular, and reno-azygo-lumbar veins (Fig. 6).

FIGURE 6. Operative specimen (A) and diagram (B) showing a leiomyosarcoma localized in segments I and II treated by caval resection without reconstruction and right nephrectomy. The collateral run off from the left kidney is sufficient for appropriate venous drainage.

Resection followed by placement of a PTFE prosthesis (diameter range, 14–20 mm) was performed in 13 patients (Fig. 7). A reinforced prosthetic graft was used in all but 1 patient treated at the beginning of our experience. Anastomosis was performed using everting sutures with 4 or 5.0 polypropylene. Partial resection of the inter-renal IVC followed by plasty using the infrarenal IVC was performed in 1 patient presenting a localized leiomyosarcoma on the anterior aspect of the inter-renal IVC.

FIGURE 7. A, Operative photography showing ringed PTFE replacement of the infrarenal IVC in combination with proximal calibrated arteriovenous fistula. B, Postoperative cavography through the arteriovenous fistula showing patency of the prosthetic replacement of the IVC.

Among the 14 patients who had reconstructive surgery of the IVC, simple clamping of the infrarenal IVC was performed in 8 cases (57%). Vascular exclusion of the liver was performed by clamping of the portal pedicle and IVC above and below the liver in 5 patients (36%) presenting retrohepatic or suprahepatic tumors. The mean duration of clamping was reduced to 25.4 minutes by fashioning the distal anastomosis at or near the level of suprahepatic veins first then reestablishing hepatic circulation, removing the clamp from the suprahepatic IVC, and introducing a balloon catheter to occlude the prosthetic graft. In one patient (7%) with intracardiac extension, cardiopulmonary bypass with deep hypothermia, and circulatory arrest at 18° for 28 minutes was used to allow fashioning of both caval anastomoses and reimplantation of the left and middle hepatic veins on the prosthesis.

Eighteen patients (90%) underwent concurrent procedures, including creation of an arteriovenous fistula in 7 of the 13 patients (54%) who underwent resection followed by prosthetic replacement. For this purpose, a segment of the great saphenous vein was harvested at the crural level, reinforced by placing a short PTFE prosthesis (diameter, 4 or 5 mm) over the middle part, and anastomosed between the aorta and IVC or common iliac vein proximal to the bypass. The anastomosis was calibrated to control inflow into the fistula and, if necessary, to close the fistula by releasing an occlusive balloon into the dilated proximal segment of the venous graft without repeat exposure.

Right nephrectomy was performed because of tumor involvement of the right renal vein in 12 patients (60%). In 1 patient (5%) whose tumor brushed against the ostium of the vein, it was possible to perform autotransplantation of the right kidney into the right iliac fossa. Reestablishment of continuity with the left kidney for satisfactory venous return was deemed necessary in only 3 of the 11 patients who underwent prosthetic replacement of the interrenal IVC. In the remaining 8 patients, collateral circulation was trusted to provide satisfactory venous return. Extended hepatectomy, including the Spiegel lobe (2 right, 2 left), was performed in 4 patients with contiguous tumor infiltration of the liver.

The other concurrent procedures involved prosthetic replacement of the aortic bifurcation in 3 cases, right pneumonectomy in 1 case, extensive resection of the right diaphragm followed by replacement with a Dacron mesh in 2 cases, resection-anastomosis of the superior mesenteric artery in 1 case, and placement of a duodenal patch using an Y-shaped intestinal loop in 1 case.

RESULTS

The 2 patients who did not undergo surgical treatment died. One death occurred the night before scheduled surgical treatment due to occlusion of the tricuspid valve by the tip of the intracardiac tumor. The other death occurred 6 months after discovery of the tumor due to multiple metastases.

Four of the 20 patients (20%) that underwent surgical treatment died during the postoperative period. One death occurred in a patient presenting chronic Budd-Chiari syndrome, an intracardiac extension, and destruction of the right lung due to pulmonary extension. The procedure consisted of wide resection with cardiopulmonary bypass and hypothermic circulatory arrest. The cause of death was right cardiac insufficiency resulting from pulmonary artery hypertension probably due to suppression of the shunt effect resulting from destruction of the lung. This patient could not be weaned from cardiopulmonary bypass. Another postoperative death occurred in a 72-year-old woman in whom resection was associated with extended hepatectomy. The cause of death was multiple organ failure on postoperative day 3. Another postoperative death involved the patient who underwent meso-atrial bypass for palliation of acute Budd-Chiari syndrome. The cause of death was liver failure on postoperative day 7. The fourth postoperative death occurred on postoperative day 46 due to duodenal fistula following surgical treatment of a bleeding hemorrhagic ulcer.

Fifteen of the 16 patients (94%) who survived the procedure underwent postoperative adjuvant treatment, ie, chemotherapy using adriamycin-ifosfamide in 11 patients and chemotherapy combined with radiation therapy in 4 patients.

One patient who was lost from follow-up at 10 months was free of local recurrence and distant metastasis at the time of the last examination. The other 15 patients were reviewed in September and October 2004. Four patients (27%) were still alive after a mean follow-up of 18.3 ± 11.3 months. Three of these 3 patients were recurrence-free at 3, 4, and 24 months, and 1 presented metastasis at 42 months. Eleven patients (73%) had died after a mean follow-up of 43.7 ± 35.3 months (range, 10–132 months; median, 36 months). The causes of death were local recurrence and/or metastasis in 9 cases and complications of chemotherapy in 2 cases. Actuarial survival rates at 1, 3, and 5 years for the 15 patients surviving the operation with complete follow-up were 93.0 ± 0.7, 52.0 ± 0.14, and 34.8 ± 0.14, respectively (Fig. 8).

FIGURE 8. Actuarial survival curve for 15 patients with leiomyosarcomas of the IVC surviving the operation with complete follow-up.

In the subgroup of 10 patients that survived procedures involving placement of a PTFE prosthesis, late patency of the IVC was assessed by ultrasound in 4 patients and CT scan in 6 patients. Only 1 patient developed graft thrombosis at 36 months in relation with locoregional recurrence. In this case performed at the beginning of our experience, grafting of the IVC was performed following extended right hepatectomy using a nonreinforced prosthesis without creation of an arteriovenous fistula.

None of the patients in the subgroup of 7 patients that survived procedures including creation of arteriovenous fistulas developed right cardiac insufficiency. Closure of the fistula was not required in any case.

DISCUSSION

Together with the series reported by Hines et al² (14 cases), Hollenbeck et al³ (25 cases), and Dzsinich et al⁴ (8 cases), this series is one of the largest series of patients presenting leiomyosarcoma of the IVC published up to now. Findings are in agreement with most data described in the register of Mingoli et al¹ with regard to female predilection, mean age in the sixth decade, frequency of abdominal pain as presenting symptom, inconsistent association with edema of the lower extremities, and potential for development of Budd-Chiari syndrome and intracardiac extension. The main difference was the higher incidence of tumors involving the interrenal and retrohepatic IVC (segment II) in our series. The incidence of leiomyosarcoma involving segment I (infrarenal IVC) was 15% (3 patients) in our series versus 36.7% in the compiled series of Mingoli et al.¹ Patient recruitment is the most likely explanation for the difference with our findings. The predominance of segment II tumors was also observed by Hines et al² and Hollenbeck et al.³

Tumors involving segment II and especially segment III raise special challenges for operative treatment. If the upper end of the tumor does not extend beyond the lower edge of the liver, a strictly abdominal approach by laparotomy or preferably by right subcostal incision can be used. Exposure of the infrahepatic and retrohepatic IVC using the subcostal approach can be optimized by extending the incision into a lombotomy with the patient in a slightly lateral decubitus position. Use of a thoracoabdominal approach is mandatory if the tumor extends to the retrohepatic or suprahepatic part of the IVC. We prefer combining laparotomy with sternotomy than with thoracophrenotomy. With midline incision of the phrenic center, this route provides excellent exposure of the suprahepatic IVC and, after section of the ligament attachments of the liver, of the retrohepatic IVC. Combining sternotomy with laparotomy has two additional benefits. The first is to provide good conditions for establishing cardiopulmonary bypass⁶ for treatment of intracardiac extension if present. The second is to be better tolerated than combined thoracophrenotomy with laparotomy from a respiratory standpoint since extensive phrenotomy is not performed and sternotomy can often be limited to the lower end.

Unlike Mingoli et al,⁷ we agree with Hollenbeck et al³ in recommending wide tumor resection at a safe distance from the tumor. Partial resection of the IVC followed by direct suture or prosthetic patch angioplasty is rarely sufficient to be curable. We never used this limited operation. In most cases, complete resection of the IVC is necessary, thereby raising the question of reestablishing caval continuity. Simple ligation is possible after complete or subtotal resection of the infra-renal IVC (segment I) and/or retrohepatic portion of the IVC (segment II) in association with resection of the right kidney. This can be explained by difference in collateral circulation on the left where collaterals (capsular, genital, reno-azygo-lumbar veins) are generally sufficient for satisfactory venous return without occurrence of kidney insufficiency (even transiently) and the right where there are no effective collaterals. Ligation can also be required following incomplete obstruction of the IVC if the procedure involves the digestive tract, thereby raising the risk of prosthetic infection. In such cases, pressure monitoring must be performed to rule out excessive venous hypertension during clamping. As a general rule, a proximal pressure reading of 30 mm Hg or more indicates caval reconstruction to avoid postoperative edema of the lower extremity.

Thanks to advances in surgical techniques for venous reconstruction, prosthetic replacement of the IVC is now feasible whenever considered necessary. Based on experience reported by many authors,^8–10 the material of choice for caval replacement is reinforced PTFE. Creation of an arteriovenous fistula is strongly recommended to ensure patency. The presence of a fistula eliminates the need for long-term anticoagulation therapy. Our arteriovenous fistula technique with banding of the venous graft rules out late cardiac complications and allows easy closure by balloon occlusion if necessary.

Simple clamping is sufficient for infrahepatic IVC reconstruction. Complications such as arterial hypotension or proximal venous hypertension are uncommon and can be treated by associated clamping of the infrarenal aorta or supraceliac aorta. Vascular exclusion is indicated for tumors extending to the retrohepatic portion of the IVC.¹¹ Exclusion makes it possible to perform the upper anastomosis of the prosthesis near the infrahepatic veins easily so that hepatic circulation can be reestablished quickly. In this way, hepatic ischemia time can be reduced to only 15 to 20 minutes, which is compatible with normothermic operating conditions. Vascular exclusion also allows associated right or left extended hepatectomy. Venovenous shunting with selective hypothermic hepatic perfusion can be useful for surgical treatment of tumors involving the suprarenal segment of the IVC.^12,13 These modalities provide ample time for anastomosis of the prosthesis flush with the right atrium and for reimplantation of a patch containing the suprahepatic veins.

Cardiopulmonary bypass is necessary in the rare cases involving tumors with intracardiac extension. Venous cannulations should be placed through the tip of the right atrium for the territory drained by the superior vena cava and in the femoral vein or infrarenal IVC for the territory drained by the IVC. We prefer to perform hypothermic circulatory arrest at 18°C rather than normothermic cardiopulmonary bypass because hypothermic circulatory arrest provides a blood-free operating field.

Right nephrectomy is frequently required for tumors involving segment II of the IVC, even if the kidney is not directly involved. If the tumor only brushes the ostium of the right kidney vein, autotransplantation of the right kidney can be performed into the right iliac fossa. This procedure requires prosthetic reconstruction of the IVC.

Attitudes on the use of adjuvant treatment have changed over the last 10 years. Up to now, numerous authors considered that chemotherapy and radiotherapy were ineffective and thus useless.^1,4,13 However, at the present time, radical resection followed by adjuvant chemotherapy is considered the optimal therapeutic strategy for tumors without metastasis at the time of initial diagnosis. One study² suggests that new radiation therapy techniques, especially applicable to tumors involving the infrahepatic part of the IVC, may prolong survival after surgical resection.

The long-term outcome of surgery for leiomyosarcoma of the IVC has been disappointing. In the international register of Mingoli et al,¹ actuarial survival rates at 5 and 10 years were 49.4% and 29.5%, respectively, but the cancer-free actuarial survival rates at 5 and 10 years were 31.4% and 7.4%, respectively. However, the usefulness of these figures is greatly impaired by the fact that 60 patients (46.4%) were lost from follow-up. In the three series with sufficiently large populations and satisfactory follow-up, actuarial survival rates at 5 years after radical resection with curative intent were 53.3% (Hines),² 33% (Hollenbeck),³ and 34.8% (present series). It is also noteworthy that some surviving patients present local recurrence or distant metastases responding to various degrees to adjuvant treatment.

However, these poor results should be put in perspective with the highly unfavorable natural course of leiomyosarcoma of the IVC.¹ Surgery, whether performed alone or in combination with chemotherapy and possibly radiation therapy, is generally not curative, but it constitutes the only hope of prolonged survival. For this reason, we recommend aggressive surgical management using modern vascular surgical and oncology techniques.