Location, Location, Location: Approaches to Retroperitoneal Vascular Leiomyosarcoma

January 15, 2020

Sarcomas are relatively rare malignant tumors that arise from mesenchymal cells and therefore encompass a variety of histologies and can occur in any anatomic compartment. The incidence of sarcoma is estimated at 1% of all new cancer diagnoses in the United States annually. Approximately 15% of soft tissue sarcomas occur in the retroperitoneum, with about 1600 new retroperitoneal sarcoma cases diagnosed in the United States each year.

Leiomyosarcoma, one of the most common soft tissue sarcomas, can occur anywhere in the body, but it is frequently found in the abdomen and retroperitoneum. When arising in the retroperitoneum, anatomic constraints can have a profound effect on treatment, particularly when these tumors abut or involve the inferior vena cava. Although there have been improvements in systemic and locoregional therapies for leiomyosarcomas, surgery remains the mainstay for management. Herein describes our approach to these tumors.

Introduction

Sarcomas are relatively rare malignant tumors that arise from mesenchymal cells and therefore encompass a variety of histologies and can occur in any anatomic compartment. The incidence of sarcoma is estimated at 1% of all new cancer diagnoses in the United States annually.1 Approximately 15% of soft tissue sarcomas occur in the retroperitoneum, with about 1600 new retroperitoneal sarcoma cases diagnosed in the United States each year.2

Leiomyosarcoma

Leiomyosarcomas, a subset of soft tissue sarcomas, are malignant smooth muscle neoplasms that account for approximately 5% to 10% of all sarcomas. Natural history is dependent on the anatomic location in which they arise. About 50% arise in the retroperitoneum/abdomen and these include visceral, uterine, and retroperitoneal, with the uterus being the most common location. Given the frequent large size and location of these tumors, abdominal pain, nausea, vomiting, anorexia, weight loss, fatigue, and malaise are common presenting symptoms.3 At the time of diagnosis, leiomyosarcomas were likely present for a period of weeks to years. Incidence is most common during adulthood and in women, particularly when the tumor is located in the retroperitoneum.3-5 Grossly, they appear as firm, nodular masses with a scar-like consistency and usually have sharply demarcated borders. Histologically, they are ordinarily composed of spindled cells. Tumor grade is a significant prognostic factor, with higher tumor grade being associated with progression to both metastasis and death.5 Metastases are most common to the lungs and liver and develop in an estimated 50% of patients.

Leiomyosarcomas of the Inferior Vena Cava

Vascular leiomyosarcomas are derived from smooth muscle cells within the medial layer of blood vessels. These tumors more commonly occur within veins rather than arteries and most often originate from the inferior vena cava (IVC).6 Leiomyosarcomas originating from the IVC account for approximately 0.5% of soft tissue sarcomas; about 300 of these tumors have been reported in this location in the literature.6 As with leiomyosarcoma in general, leiomyosarcoma of the IVC typically manifests during middle adulthood, predominantly in women.

Patient symptoms vary with the location of the tumor in the IVC. Leiomyosarcomas arising in the middle portion of the IVC (ie, infrahepatic, suprarenal) are the most frequent at about 40%, and symptoms may include a palpable abdominal mass, abdominal or visceral pain, and bilateral lower extremity edema. High suspicion is warranted for tumor extension with associated partial or complete thrombosis of the renal vein(s) in patients with renal dysfunction. Leiomyosarcomas involving the lower portion of the IVC (ie, infrarenal) are the second most common in frequency at approximately 30%. Patients present with similar symptoms of an abdominal mass and lower extremity edema, but they may also have flank pain. Patients with leiomyosarcoma of the superior portion of the IVC (ie, suprahepatic), which has an estimated frequency of 25%, can present with symptoms of the Budd-Chiari syndrome such as jaundice, ascites, and hepatomegaly.

Vascular IVC leiomyosarcomas are relatively slow-growing tumors that are typically attached to the wall of the vena cava and exhibit extraluminal growth. Some will project into the vessel lumen, which may ultimately cause vascular thrombosis. Intraluminal tumor thrombi may course along the IVC and extend into the renal veins, hepatic veins, or even extend cephalad to the level of the right atrium. These tumors may also extend outward into the retroperitoneum and involve surrounding structures. Given that many of these tumors have a delayed presentation due to the vagueness of symptoms, they have a wide range in size at diagnosis, with reported cases ranging from 2 to 30 cm and an average size of approximately 10 cm.6

Diagnosis

For imaging, a contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis is preferred to evaluate the primary disease site as and a chest CT to evaluate the presence of metastatic disease to the lungs. CT is advantageous over magnetic resonance imaging (MRI) for the following reasons: it better defines the relationship of the primary tumor to surrounding structures; it can evaluate for the presence of peritoneal or liver metastasis; and most importantly, it provides the appearance of the primary tumor which may suggest histologic subtype and grade. Often a CT or MRI venogram is obtained in addition to standard studies to define the anatomic detail of the tumor for surgical planning. The anatomic structures that are evaluated in particular with this imaging modality are those intimately involved with the IVC, including the aorta, iliac veins, the renal hilum, pedicle, ureter, and other immediately adjacent structures. To evaluate perihepatic structures, an MRI with liver protocol can be a useful adjunct, particularly when tumors involve the retrohepatic IVC. This modality is useful to evaluate the extent of liver and hepatic vein involvement. The role for positron emission tomography with fluorodeoxyglucose in the initial staging evaluation is not clearly established; however, and we do not routinely recommend its use.

Although imaging can be highly suggestive of certain diagnoses, imaging features alone are not adequate to determine histology.7 As the majority of IVC leiomyosarcomas are exophytic, image-guided needle biopsy is safe and should be performed to ascertain diagnosis. Additionally, the information gained can assist in determining multimodality treatment planning and allow for consideration of neoadjuvant therapies and clinical trials. A fear of tumor seeding via core biopsy is unsubstantiated.8

Treatment

To date, the majority of knowledge in treating IVC leiomyosarcoma has come from case reports and case series. Surgical resection offers the best chance at long-term survival and potential for cure.9 Remarkably, 5-year disease-free survival in patients who underwent resection was between 30% and 60%; however, in those who did not undergo surgery, survival was often less than 1 year.6,10-15 Even after surgical resection, recurrence is rather common. Given this and the poor prognosis associated with recurrence, traditional adjuvant chemotherapies are often employed. The efficacy of such chemotherapies, however, has never been shown to definitively lengthen survival. No clear benefit has been established with radiation therapy, although current research is investigating its utilization.16 Nevertheless, even with systemic and locoregional therapy being studied in the adjuvant setting, we tend to favor neoadjuvant chemotherapy with or without preoperative radiation therapy because the risk of metastatic disease is relatively high. This decision is best made by a multidisciplinary tumor board that can consider grade, size, and extent of surgery. We do not recommend adjuvant chemotherapy outside the setting of a clinical trial. To that end, if available, we suggest participation in ongoing clinical trials.

Determining resectability largely depends on the extension of the tumor and what surrounding structures it involves. Classically, findings from imaging that generally deem the tumor unresectable include: diffuse peritoneal implants or distant metastases not able to be completely resected, spinal cord involvement, bilateral renal involvement requiring bilateral nephrectomies, extensive liver hilum involvement, and envelopment of the mesenteric root. A relative contraindication is vascular involvement, because reconstructive options vary given tumor location and tissue involvement.17 Liberal en bloc resection of adjacent viscera, however, may allow a subset of patients, who might otherwise have been considered unresectable, to achieve wide, macroscopically negative surgical margins.

Operative Approach

When proceeding with operative planning, the primary oncologic goal is to obtain a microscopically negative margin (R0) resection. Given the location and sometimes large size of the tumor, it is difficult, if not impossible to obtain wide margins. As the size of IVC leiomyosarcomas can be significant, en bloc resection of surrounding structures may be required to clear all disease. Organs frequently involved include the right kidney, colon, liver, and aorta. Remarkably, several case series have reported relatively low perioperative death rates after surgery for IVC leiomyosarcomas, ranging from 0% to 20%.6,10-15 Leiomyosarcomas can have far extension into the inguinal canal, pelvic foramina, or across the diaphragm. As a result, many times, even though the tumor is grossly removed, the margins are microscopically positive (ie, R1 resection). Prior to resection with intent to cure, the patient should undergo appropriate metastatic disease workup, which includes imaging of the chest, abdomen, and pelvis.

The IVC leiomyosarcoma may originate from a narrow pedicle of the IVC allowing primary closure or vein patch for reconstruction. Small segments may be closed primarily or can be patched with a vein patch such as a saphenous or internal jugular vein. Alternatively, the leiomyosarcoma may be firmly attached to a broad section of the IVC, requiring segmental resection and ligation or prosthetic graft interposition of the IVC, depending on the patency of the IVC. Below the renal veins, the vena cava is often amenable to ligation because many patients with IVC leiomyosarcoma have developed extensive venous collaterals. Preoperative CT imaging may be able to suggest the amount of collateralization. Ligation can typically be performed after tumor excision in the setting of preoperative IVC occlusion for the same reason. If flow is present preoperatively, however, IVC repair should be attempted.18-20 Larger segments, whether circumferential or longitudinally oriented, will require IVC reconstruction with a prosthetic tube graft material such as polytetrafluoroethylene. The size of the graft will vary depending on the native IVC, but the most common graft size typically ranges from 16 to 22 mm. Cadaveric tissue and autologous tissue grafting from a variety of donor sites are also possible conduits and may offer advantages if the surgical site is contaminated, as when enteric resection is necessary.18-20

The operative approach depends on which segment of the IVC is affected. The IVC can be divided into 3 segments as described previously: the lower segment (below the renal veins to the origin of the IVC), middle segment (below the hepatic veins to the renal veins), and the upper segment (from the right atrium to the hepatic veins). In middle and lower segment tumors, superior control of the IVC is achieved by mobilizing the right lobe of the liver or via an anterior approach by transecting the caudate lobe. The renal vessels are medically isolated and preserved. In preparation for a segmental IVC resection, the anesthesia team is alerted and the IVC superior to the tumor is clamped to check for hemodynamic response. If the patient tolerates this, the segmental IVC resection can proceed. If the right kidney is being resected, the right renal artery can be divided. The left renal vein should be divided proximal to the left gonadal vein to preserve drainage, but if only 1 kidney is to remain, an interposition graft of the renal vein to the IVC should be considered to preserve optimal function. This can similarly be considered for preservation of 1 or both kidneys if the tumor extends to the os of the vein but does not involve a significant length of vein. Autotransplantation of a kidney can also be utilized to preserve renal function and render a tumor resectable.

IVC leiomyosarcoma in the middle segment extending to the upper segment may require hepatic resection when the tumor involves retrohepatic caval tumors. Techniques often employed include total hepatic vascular exclusion and venovenous bypass.6,21 Total hepatic vascular occlusion can be performed by first creating a plane between the liver and diaphragm. Isolation of the IVC superior to the liver can be done at the junction of the hepatic veins and IVC or via a transdiaphragmatic pericardial window to isolate and loop the intrapericardial IVC. A Pringle maneuver is employed around the hepatoduodenal ligament containing the portal triad. The infrahepatic IVC is also isolated and looped. Total hepatic vascular occlusion can be completed by clamping of the portal triad, suprahepatic IVC, and infrahepatic IVC.22 The retrohepatic IVC can then be exposed by a liver hanging technique, which allows the IVC to be exposed without complete mobilization of the right liver. This technique consists of lifting the liver during parenchymal transection by an umbilical tape or similar material passed between the anterior surface of the IVC and the posterior surface of the liver. Parenchymal dissection along this plane can proceed in a relatively safe fashion due to the presence of a longitudinal avascular compartment guided by the tape.23 Venovenous bypass involves the extracorporeal circulation of blood from the venous system below the IVC isolation clamps (ie, the inferior mesenteric vein and femoral veins) with return to the central veins (ie, the axillary or internal jugular veins). Upper segment tumors may require cardiopulmonary bypass and circulatory arrest.

An example of the extent of dissection and collateral resection needed for extensive IVC leiomyosarcoma tumors in difficult locations is exemplified by the tumor shown in Figure 1. This IVC leiomyosarcoma tumor extended from immediately beneath the hepatic veins along the retrohepatic IVC to the level of the renal veins, involving the left lobe of the liver, caudate lobe, and the right renal vein. After receiving neoadjuvant chemotherapy that led to a decrease in the size of the tumor, this patient underwent exploratory laparotomy, left hepatectomy, right nephrectomy, and resection of the involved IVC with reconstruction using a synthetic interposition graft. The liver hanging technique was utilized to expose the retrohepatic IVC. Preparations for venovenous bypass were made preoperatively by placing appropriate cannulas after the induction of anesthesia; however, it was not necessary to utilize the circuit as there was an adequate cuff of IVC below the hepatic veins for reconstruction. The surgical specimen and the reconstruction are depicted in Figure 2 and Figure 3, respectively. This procedure required collaboration from a surgical team including sarcoma, hepatobiliary, and vascular surgeons.

Conclusions

Leiomyosarcomas of the IVC overall have a more indolent course than other locations of this histology. Many of the usual predictors of prognosis such as size and grade may not apply because the anatomic constraints of location determine surgical resectability, the mainstay of treatment. Careful preoperative planning with imaging and preparation for reconstruction with a surgical team of experts is required. This often requires a multispecialty team of surgeons including those in surgical oncology, vascular surgery, urology, and transplant.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

FIVE KEY REFERENCES

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