Prosthetic Replacement of the Infrahepatic Inferior Vena Cava for Leiomyosarcoma FREE

Leiomyosarcoma of the inferior vena cava (IVC) is a rare tumor of mesenchymal origin and is most commonly found in women.^1- 2 It accounts for 5% to 15% of all retroperitoneal tumors,³ and owing to its slow growing pattern, it may reach fairly large dimensions before becoming symptomatic and being detected.^1,4

Since the first described segmental resection of the IVC for leiomyosarcoma in 1928,⁵ radical surgical resection en bloc with the affected venous segment remains the only therapeutic option associated with prolonged survival.^1,6- 7 Standard surgical resection of leiomyosarcoma en bloc with the affected portion of the IVC should attain the goals of complete excision of the tumor, prevention of recurrence, and preservation of venous return.^6,8 Preservation of venous return is increasingly being obtained through expanded polytetrafluoroethylene (PTFE) graft replacement of the IVC.^9- 10

Tumor involvement of the IVC can be classified as infrahepatic, ie, below the caudate lobe, or retrohepatic, ie, above the caudate lobe. When dealing with tumors of the infrahepatic IVC, the main indication to its reconstruction is to provide a conduit to renal venous outflow and, secondarily, to iliac veins. Standardization of the requirement for IVC reconstruction is difficult, as the rarity of this tumor does not allow for prospective studies or comparisons of large individual series.^1,4

Reconstruction of the infrarenal IVC alone may be neglected with the assumption that after IVC ligation, venous outflow from the lower limbs is usually assured by collaterals, and prosthetic replacement of the infrarenal IVC may be followed by complications overwhelming the expected benefits.^4,11

Nevertheless, edema of the lower limbs following IVC ligation may be very disabling.^1,9- 10 Good results have been obtained with radical resection of tumors arising from the infrahepatic IVC and its prosthetic reconstruction to improve both survival and postoperative quality of life.^9- 10,12 These results encouraged us to systematically perform prosthetic graft reconstruction of the infrahepatic IVC after a potentially radical resection of infiltrating retroperitoneal tumors en bloc with the affected caval wall.

The aim of our study was to evaluate the results of this method, limited to leiomyosarcoma, to establish whether it should become part of the standard treatment of this tumor.

From October 1, 1993, to October 31, 2004, 11 consecutive patients underwent prosthetic replacement of the infrahepatic IVC after curative resection for primary leiomyosarcoma in the “Francesco Durante” Department of Surgery, Rome University Hospital, Rome, Italy, and 1 affiliated center. This sample represents 58% of 19 patients undergoing laparotomy for retroperitoneal tumors involving the IVC at both centers in the same period. The study was approved by the local ethics committee; informed consent was obtained from all of the patients. There were 8 women and 3 men, with a mean age of 51 years (age range, 30-72 years). The presenting symptoms and signs were abdominal pain in 7 patients (64%), a palpable abdominal mass in 9 (82%), lower limb edema in 5 (45%), and abdominal distention in 3 (27%).

All of the patients underwent a computed tomography (CT) scan of the chest, abdomen, and pelvis with intravenous and oral contrast as part of their preoperative workup (Figure 1). No patient presented with evident metastatic disease at the time of operation. The tumor involved the infrarenal portion of the IVC in 8 patients (73%) and the interrenal and suprarenal portion in 3 (27%). The growth pattern of the tumor was mainly extraluminal in all of the patients. However, in all of the cases, some form of intraluminal growth of the neoplasm as well as a partially patent IVC existed at the time of presentation.

All of the patients underwent complete gross resection of the tumor en bloc with the involved segment of IVC. In 2 of 3 cases with involvement of the interrenal and suprarenal caval portion, organ removal en bloc with the primary tumor included the right kidney and adrenal gland.

The patients received intravenous heparin prior to exclusion of the venous segment affected by the tumor. Heparin was not reversed with protamine sulfate at the end of the operation. The resected caval segment was replaced with a PTFE graft (W. L. Gore and Associates, Flagstaff, Ariz). The venous reconstruction was cavocaval in 10 cases (91%), with the graft's diameter ranging from 14 to 18 mm. The left renal vein was implanted end to side on the graft in 3 cases. In 1 case (9%), resection included the confluence of the iliac veins, which was reconstructed with a 14/7 mm PTFE bifurcated graft. An adjuncted arteriovenous fistula (AVF) was not performed in any patient. In 8 cases, the greater omentum could be brought down through the transverse mesocolon to separate the graft from the bowel as previously described.¹³ The surgical procedures are summarized in Figure 2.

Gross examination of the resected specimens showed tumors with both intraluminal and extraluminal growth, with a mean largest diameter of 15 cm (range, 7-22 cm). Histological analysis revealed a leiomyosarcoma with negative tumor margins on the resected IVC in all of the patients.

Postoperatively, the patients received a regimen of low-molecular-weight heparin for 6 weeks and were then prescribed 100 mg/d of oral aspirin; oral anticoagulation was prescribed only when thrombosis of the graft and consequent edema of the lower limbs occurred. Before discharge from the hospital, patency of IVC reconstruction was assessed with duplex ultrasonography.

Local and distant recurrence of the disease as well as patency of the graft were assessed with a CT scan of the chest, abdomen, and pelvis every 6 months in the first 2 postoperative years, then on a yearly basis or earlier if deemed necessary. Chemotherapy and/or radiation therapy were not administered on a systematic basis but only when local or distant recurrence of the disease appeared on the CT scan.

As main results, disease-specific survival, disease-free survival, and graft patency were considered. They were expressed by a standard life-table analysis.¹⁴ Disease-specific survival was defined as patients' survival minus any death due to recurrent disease. Disease-free survival was defined as the absence of any local recurrence or distant metastasis at CT scan of the chest, abdomen, and pelvis. Graft patency was defined as the absence of thrombosis of the graft at CT scan (Figure 3).

No patient died in the postoperative period. Nonfatal complications included 1 case of acute renal insufficiency, 1 case of respiratory distress syndrome, and 1 case of dehiscence of the abdominal wound, and these complications were successfully managed with appropriate medical or local treatment.

In all of the 5 patients with legs swelling preoperatively, edema of the lower limb postoperatively resolved. Neither edema of new onset nor acute thrombosis of the venous reconstruction was observed in any patient in the postoperative period.

The mean estimated blood loss was 1220 mL (range, 520-3800 mL), and an average of 3 units of red blood cells (range, 0-6 units) were transfused intraoperatively or perioperatively. The mean length of operation was 4 hours (range, 3.5-6 hours). The mean postoperative length of stay was 14 days (range, 9-22 days). The patients were followed up for a mean period of 40 months (range, 12-108 months).

No graft-enteric fistula, graft infection, or clinical symptoms of pulmonary embolism were observed. One patient was lost to follow-up at 48 months while free from disease and with a patent graft. Five late deaths occurred; of 4 deaths (36%) due to recurrent disease, 3 were related to lung or liver metastases and 1 to unresectable local recurrence. One late death was due to hemorrhagic stroke. The cumulative (SE) disease-specific survival rate was 66% (17%) at 36 months and 53% (21%) at 60 months (Figure 4). In addition to the 4 patients who died from recurrent disease, 1 patient was alive with pulmonary metastases at 27 months of follow-up. Overall, 5 recurrences (45%) occurred during follow-up; there were 4 distant recurrences (36%) and 1 local recurrence (9%). The cumulative (SE) disease-free survival rate was 56% (17%) at 36 months and 44% (19%) at 60 months (Figure 5).

Four grafts (36%) thrombosed during follow-up, with consequent edema of the lower limbs. Two patients were prescribed elastic stockings and received oral anticoagulation. The other 2 patients had thrombosed grafts at the time of the disease's extensive metastatic spread and did not receive anticoagulation. No patient with a patent graft developed late edema of the lower limbs.

The cumulative (SE) graft patency rate was 67% (17%) at 36 months and 67% (22%) at 60 months (Figure 6).

The essential data and outcome of the patients are summarized in the Table.

Curative surgical resection remains the current treatment of choice for primary leiomyosarcoma of the IVC. When the infrahepatic segment of the IVC is involved, the pattern of neoplastic growth is usually both intraluminal and extraluminal. Since the growth itself is slow, symptoms of venous obstruction affect about half of the patients, and diagnosis is made when the tumor reaches a considerable mass. Despite its large diameter, however, the mass tends to be confined to its capsule, and aspects of compression overwhelm those of infiltration toward adjacent organs, particularly when the infrarenal IVC is involved.^6- 7 Complete removal of the mass, en bloc with the involved segment of the IVC, is often possible. A major surgical issue is the need for venous reconstruction after resection of the tumor with the affected segment of the IVC. When the interrenal or suprarenal portion of the IVC is involved, prosthetic reconstruction of the IVC and reimplantation of the renal vein(s) in the graft represent a reliable method for preserving caval and renal venous outflow. In our series, the interrenal portion was involved in 3 cases, and in all of the 3 cases, reimplantation on the graft involved the left renal vein. Alternatively, ligation of the left renal vein can also be considered, assuming that no significant impairment of venous return and renal function will ensue owing to its length and abundant collaterals.² Nevertheless, ligation of the left renal vein may still be followed by renal infarction and postoperative death due to renal failure, particularly when a right nephrectomy is associated¹⁵; efforts toward its preservation are therefore advised. Reconstruction of right renal outflow is mandatory owing to the short length and lack of collaterals of the right renal vein.

When dealing with the infrarenal IVC, simple ligation has been found to yield good functional results with the assumption that the slowly growing tumor allows sufficient collaterals to develop.^2,4,11 Nevertheless, the occurrence of significant symptoms of venous insufficiency of the lower limbs after ligation of the IVC has also been described.^1,9- 10 Furthermore, it may be anticipated that radical resection of a large retroperitoneal tumor often disrupts venous collaterals, thus precipitating postoperative symptoms of venous obstruction requiring elastic compression and long-term anticoagulation.^9,12,15

In our experience, systematic reconstruction of the resected infrahepatic IVC was associated with a satisfactory patency rate, which is in agreement with the results of other series.^9,12 Despite the expectation that asymptomatic thrombosis of an infrarenal graft may occur,¹² no patient with a patent graft in this series experienced limb edema whereas all of the grafts' thromboses were followed by leg swelling, and all of the patients with preoperative lower limb edema had their symptoms relieved by venous reconstruction. Two of 4 late grafts' occlusions in this series occurred in association with advanced recurrent tumor; the thrombophilic status associated with terminal disease may significantly contribute to a graft's thrombosis. Graft-related major complications, such as pulmonary embolism, sepsis, and graft-enteric fistula,^4,11,16- 17 were not observed in this series.

Ring-reinforced PTFE grafts have been used as IVC substitutes with the rationale that they would resist respiratory compression and graft collapse that may promote thrombosis.^10,12,18 Rigid grafts, however, may be poorly incorporated and may be exposed to fistulas in the duodenum, particularly if radiation therapy is to be administered.¹⁹ In our series, stretch PTFE grafts of a diameter ranging from 14 to 18 mm were used for IVC reconstruction, resulting in a patency rate comparable to that of other studies,^9,12 and there was no occurrence of enteroprosthetic fistula throughout the entire period of follow-up. Performing an epiploplasty to isolate the graft from the bowel in the majority of the patients may have also significantly contributed to the absence of graft-enteric fistulas in this series.

The adjunct of an AVF at the groin to improve the patency of the grafts has been proposed.²⁰ At the moment, there is no definite evidence that patency of graft reconstruction of the IVC is really improved by the adjunct of an AVF.¹² On the other hand, cases of persistence of edema in the lower limbs despite the graft's patency have been attributed to the presence of the AVF itself.¹⁰ In our series, satisfactory patency of the grafts could be obtained without the adjunct of an AVF, which is in agreement with the experience of others.¹²

Oral anticoagulants may also be administered as a contribution to durable patency of the caval reconstruction.⁹ Nevertheless, satisfactory patency rates of prosthetic replacement of the IVC have been obtained without oral anticoagulation in our series as well as in other series.^2,10,12 For now, we would recommend an oral anticoagulant only in cases of thrombosis of the venous reconstruction, ligation of the IVC, or thrombosis of the iliac veins.

In the case of associated deep lower limb or iliac venous thrombosis at the time of operation, prosthetic reconstruction of the IVC is obviously not indicated.¹² Histopathological grading of the tumor has not been correlated with survival.^8,21- 22 The role of neoadjuvant or adjuvant therapy is still unclear,⁴ and statistical evidence of any benefit from radiation therapy and chemotherapy in reducing recurrences is still lacking.^6,23- 24

Several malignancies of different origin may extend to the infrahepatic IVC, including lymphoma, renal cell carcinoma, Wilms tumor, adrenal tumors, hepatic carcinoma, retroperitoneal metastatic lymph nodes, and different retroperitoneal sarcomas.^1,9,25- 29 Among all of them, leiomyosarcoma is associated with good survival despite its vascular origin and emanation from a potentially major conduit for metastatic dissemination.⁶ Five-year survival rates ranging from 33% to 56% and local recurrence rates ranging from 9% to 33% have been reported.^4,6- 7 The results of this series, with a disease-specific survival rate greater than 50% at 5 years and a local recurrence rate of 9%, compare favorably with these data, although the small number of involved patients limits their statistical significance.

Overall, long-term survival with leiomyosarcoma of the IVC is possible.⁶ Therefore, any effort should be made to perform a curative surgical resection and restore IVC patency to obtain good quality of survival. The results of this study support radical resection followed by prosthetic reconstruction of infrahepatic IVC for the treatment of primary leiomyosarcoma.

Correspondence: Giulio Illuminati, MD, Via Vincenzo Bellini 14, 00198 Rome, Italy (giulio.illuminati@uniroma1.it).

Accepted for Publication: July 12, 2005.