Year : 2014 | Volume
: 24 | Issue : 1 | Page : 18--22
An insight into the inferior vena cava leiomyosarcoma
Bhupinder Singla1, Anshuma Bansal2,
1 Department of General Surgery, Government Medical College and Hospital 32, Chandigarh, India
2 Department of Radiotherapy, PGIMER, Chandigarh, India
Department of General Surgery, Government Medical College and Hospital 32, Chandigarh - 160 012
Primary vascular leiomyosarcoma (LMS) is a rare tumor accounting for 2% of all LMSs, with the most common site being inferior vena cava (IVC). Overall prognosis is poor, with a median survival of 2 years only. Definitive treatment strategy has not been defined yet, due to the availability of small case series or reports only. However, extrapolating from the treatment of other sarcomas, definitive surgery followed by adjuvant treatment in the form of radiation and chemotherapy is usually followed. This review article focuses on presentation, diagnostic workup, the treatment options for IVC LMS, and their effect on the outcome, so that optimal management can be planned for individual cases. For this, a literature PubMed/Medline search was performed from January 1995 to December 2013 and reviewed to define the rare presentation of these vascular tumors, diagnostic workup, surgical options and reconstruction methods available, and the indications for the use of adjuvant chemotherapy and radiation.
|How to cite this article:|
Singla B, Bansal A. An insight into the inferior vena cava leiomyosarcoma.Niger J Surg Sci 2014;24:18-22
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Singla B, Bansal A. An insight into the inferior vena cava leiomyosarcoma. Niger J Surg Sci [serial online] 2014 [cited 2021 Sep 25 ];24:18-22
Available from: https://www.njssjournal.org/text.asp?2014/24/1/18/134535
Leiomyosarcoma (LMS) of the inferior vena cava (IVC) are rare tumors known to have aggressive behavior. The diagnosis is made based on imaging, intra-operative details and histopathology report and after excluding primary LMS arising from other retroperitoneal structures. Definitive treatment strategy has not been defined yet, due to the availability of small case series or reports only. We carried out a literature search from January 1995 to December 2013, through the PubMed/Medline central database at National Center for Biotechnology Information website (http://www.ncbi.nlm.nih.gov/pmc) using the search terms, "LMS, IVC", "reconstruction", "management". This review article focuses on presentation, diagnostic workup, the treatment options for IVC LMS and their effect on the outcome, so that optimal management can be planned for individual cases. Besides, this article also highlights the need for vascular reconstruction, and brings out the rationale and the indications for the use of adjuvant treatment in the form of chemotherapy and radiation therapy.
Primary vascular LMS is a rare tumor that originates from smooth muscle cells of tunica media.  It accounts for 2% of all LMS, with the most common site being IVC.  It was first reported by Perl in German literature in 1871.  About 400 cases have been reported in the literature so far.  It is seen in the sixth decade of life, with female preponderance (male:female = 1:4).
Tumors of the IVC can be either primary or secondary in origin. Primary tumors originate from within the vessel wall, while secondary tumors originate in the adjacent tissue and surround, compress, or invade the IVC. Three main growth patterns can be identified: Extraluminal (62%), intraluminal (5%), and both extra-and intra-luminal (33%). 
Kieffer et al.  classified IVC LMS into three groups according to localization: Infrarenal IVC (Segment I - between the confluence of common iliac veins and renal veins), suprarenal IVC (Segment II - between the renal and hepatic veins), and suprahepatic IVC (Segment III - between hepatic veins and the right atrium). The percentages of upper, middle, and lower section involvement are 24%, 42%, and 34%, respectively (most frequent in the middle section). 
Symptoms of IVC LMS vary according to size, growth pattern, and localization of tumor.  They are usually non-specific and may precede the diagnosis by several years. The three most common presenting symptoms are abdominal pain (52%), distention (20%), and deep venous thrombosis (DVT) (12%). Patients with infrarenal involvement can present with lower extremity edema. Budd-Chiari syndrome and Nephrotic syndrome can be seen if suprarenal/retrohepatic segment is involved. Patients with suprahepatic involvement can present with cardiac arrhythmias, syncope, and pulmonary embolism. Additional non-specific symptoms may include fever, weakness, anorexia, nausea, vomiting, night sweat, and dyspnea, some of which may be a result of metastasis.
Pattern of spread
IVC LMS is a slow-growing progressive tumor. It is usually fatal because of the late presentation. It tends to enlarge through intraluminal or extraluminal growth rather than by infiltration. It spreads locally to the liver, pancreas, and the porta hepatis. Systemic metastasis occurs in late stages in <50% cases, mainly involving liver, lung, lymph nodes, or bone. 
Since the tumor grows slowly and remains asymptomatic for a prolonged period of time, discovery is made incidentally in 10.5% of patients and at autopsy in 33%.  Cross-sectional imaging plays an important role in early diagnosis, origin, extension, and evaluating resectability of tumor. The sensitivity and specificity of contrast enhanced computed tomography (CECT) in assessment of tumors are 78% and 96%, respectively and even higher with contrast enhanced magnetic resonance imaging (CEMRI) (95-100%).  Heterogeneous contrast enhancement is a characteristic feature in CECT chest and abdomen. It also helps in differentiating the tumor from a blood thrombus. Doppler ultrasonography and CEMRI can demonstrate tumor vascularity, and dilatation of the IVC is an important finding of a tumor. Cavography is another investigation which detects a filling defect/or compression and deviation of the IVC due to intraluminal or extraluminal growth.  It is possible to perform transluminal biopsy through this type of angiography. It also demonstrates collateral flow and plan appropriate surgery. Biopsy gives accurate pre-operative diagnosis, and can be performed intravenously, fluoroscopic CT guided, or a duplex-guided biopsy.
IVC LMS are encapsulated tumors, consisting of lobulated whorls, with typical spindle-shaped bundles of cells with varying degree of mitotic activity. Immunohistochemistry can demonstrate the smooth muscle origin by positive staining for desmin, vimentin, h-caldesmon and smooth muscle actin. 
Histological grading and classification has been done by various authors, but no standardization exists at the moment. Mitoses per high power field and extent of necrosis are two most important factors in defining grade, and help differentiate benign tumor from LMS.  American Joint Committee of cancers 2010 staging uses four tiered grading system, while Musculoskeletal Tumor Society Surgical Staging System utilizes only low- and high-grade classification.
The differential diagnosis includes tumor thrombus, intravascular leiomyomatosis (myxoma), other vascular tumors (hemangioendothelioma, angiosarcoma, and fibrosarcoma). Extraluminal extension of IVC LMS might be mistaken for primary LMS arising from retroperitoneal smooth muscle.  However, these should be classified as IVC LMS if they have predominantly intraluminal growth and a segment of the involved IVC needs to be resected with extraluminal tumor. 
Prognosis depends on size, site and existence of metastasis. Favorable factors include abdominal pain, the presence of a mass and the ability to achieve clear resection margins. , Poor prognostic indicators include high-grade tumors, suprahepatic tumors and presentation with IVC occlusion or Budd-Chiari syndrome.
Overall prognosis is poor. Mean survival is around 2 years. 
The optimal treatment regimen has not been established, due to limited experience. Various approaches are surgery, radiation and chemotherapy.  When possible, surgical resection seems to offer the best chance for survival. The role of radiation and chemotherapy is not well-defined. ,
Whilst there is no strong evidence base for the management of IVC LMS, the treatment of choice based on the available literature is radical en-bloc surgical excision with a view to obtain negative resection margins. Goal of surgery is to achieve local control, maintain venous return, and prevent recurrences.  Rationale for surgery is that IVC LMS has a slow growth pattern and low metastatic potential. Furthermore, complete resection is feasible and associated with improved survival. Surgical resection was first reported in 1928 by Melchior.  It includes complete resection of the tumor and consequently resection of IVC leading to the need for venous reconstruction. Ligation of the IVC has been reported by some authors. However, preferred approach is reconstruction by primary repair or patch repair or segmental replacement with tube grafting, with synthetic (polytetrafluoroethylene [PTFE], Teflon, or Dacron) or biological materials autografts such as pericardium, peritoneofascial grafts composed of the peritoneum and posterior rectus fascia, or autogeneous vein grafts (mainly great saphenous vein). ,, This is because graft replacement avoids complications of IVC ligation such as DVT, ascites, lower extremity edema, and renal dysfunction. 
Ringed PTFE prostheses are the preferred grafts for caval replacement rather than biological grafts.  It provides the best results, given the length of the missing segment and the need for strength to resist compression in the abdomen. Collapse of the graft may be an important factor in thrombosis. Many authors prefer a 20-mm-diameter graft for best congruency with the native vessel.  Others recommend smaller grafts (14-16 mm) for infrarenal replacement to increase blood velocity.  Bovine pericardial grafts, fresh IVC allografts, and banked venous homografts have also been mentioned as other options for the reconstruction of the IVC. ,
Different surgical techniques for tumors involving different segments of IVC have been advocated in the literature. For infrahepatic tumors (Segments I and II not involving renal veins), no IVC reconstruction is usually required due to the presence of abundant collateral circulation, and also lower extremity edema after ligation of the IVC is well-tolerated. Therefore, simple ligation or clamping is sufficient.
For retrohepatic tumors (Segment II), radical resection of level II tumor requires consequent vascular reconstruction due to the frequent involvement of renal veins. If right renal vein is involved, right renal venous flow should be conserved by the reimplantation of the right renal vein on the vena cava or caval graft or by renal autotransplantation in the right iliac fossa, as there are no effective collaterals.  In contrast, the left renal vein has sufficient collaterals (lumbal, gonadic, and adrenal veins) for satisfactory venous return without the occurrence of renal insufficiency, so can be ligated only.
For suprarenal tumors, venovenous shunting with selective hypothermic hepatic perfusion can be useful. In rare cases involving tumors with intracardiac extension, cardiopulmonary bypass may be required.
Operative management for tumors involving Segment II and especially Segment III are challenging. If the superior border of the tumor does not extend beyond the inferior hepatic edge, an abdominal approach is usually used, either by conventional laparotomy or preferably by right subcostal incision. 
If the subcostal approach is used, exposure of the infrahepatic and retrohepatic IVC can be optimized by extending the incision into a lobotomy with the patient in a slightly lateral decubitus position. 
A thoracoabdominal approach is preferred if the tumor extends to the retrohepatic or suprahepatic part of the IVC.
Kieffer et al. mentions of the advantage of combining laparotomy with sternotomy over thoracophrenotomy.  With midline incision of the phrenic center, this route gives good exposure of the suprahepatic IVC as well as of the retrohepatic IVC after sectioning of the hepatic ligaments. Sternotomy combined with laparotomy has the added benefit of providing good conditions for establishing cardiopulmonary bypass for treatment of intracardiac extension if present. ,
Mingoli et al.  analyzed 218 patients of IVC LMS, 134 of whom underwent R0 resection. 5 year and 10 year overall survival were 49.4% and 29.5%, respectively. Other studies , also show overall survival ranging from 33% to 50% with R0 resection (excision with negative resection margins).
It is evident from the clinical results of surgery alone, , that more than 50% patients develop a late recurrence, even after R0 resection. With radical resection, the 5- and 10-year survival rates were 49.4% and 29.5%, respectively.  However, the cancer-free actuarial survival rates at 5 and 10 years were 31.4% and 7.4%, respectively.  Local recurrences occur in 13-33% of patients, while distant metastasis in 30-50% of patients.  This suggests an indication for giving both local and systemic therapy as adjuvant treatment.
Though sarcomas are radio-resistant tumors, but due to its propensity of showing high local recurrences even after complete surgical resection, local radiation is indicated to increase local control. Indications of adjuvant radiotherapy are tumor size >5 cm, mitotic activity >5 high power field, poorly differentiated histology (Grades 2 and 3), R1/R2 resection (excision with microscopic or gross residual), and infiltration of adjacent structures. Dose required is 45-50 Gy delivered in 25 fractions in 5 weeks at 1.8-2 Gy/fraction. Target volume to be treated includes tumor bed, regional lymph nodes and adjacent infiltrated structures.
However, there are many difficulties in radiotherapy planning. Sarcomas require doses >60 Gy for control. Critical structures in abdomen limit the doses required for treating sarcomas. The mean tolerance dose of kidney should not be more than 18 Gy. The volume of kidney receiving 30 Gy and 23 Gy should not be more than 20% and 30% respectively (V 30 Gy <20%) (V 23 Gy <30%).  For liver, mean dose should not be more than 28 Gy (1/3 rd volume of the liver should not receive more than 30 Gy). Dose maximum for spinal cord is 45 Gy. However, nowadays, these limitations can be overcome by use of conformal techniques like three-dimensional conformal radiation therapy and intensity modulated radiotherapy planning which helps in sparing critical normal organs like kidneys and spinal cord), which could not be possible with conventional large anteroposterior fields.
Hines et al.  treated 14 patients with R0 resection. 12 patients who received post-operative radiation with a dose of 50 Gy delivered in 25 fractions in 5 weeks had a median survival of 51 months compared to 2 months only in two patients treated with surgery alone. No local recurrences were seen. However, three patients died of distant metastasis.
Since IVC LMS has aggressive natural course, with high rates of distant metastasis (30-50%), the use of chemotherapy has a rationale in that it treats subclinical metastatic disease and decrease distant failures.
Regimens most commonly used are V = Vincristine, A = Adriamycin, C = Cyclophosphamide (VAC), I = Ifosphamide, E = Etoposide (IE), Ifosphamide, M = Mesna, A = doxorubicin, I = Ifosphamide D = Dacarbazine and VAC alternating with IE. Studies by Kieffer et al.  and Ito et al.  indicate that with the use of combined modality, the median survival ranged from 45 to 55 months, compared to 5 months only with surgery alone.
Neoadjuvant chemotherapy has also been utilized by some studies. Rationale for its use is to downsize the tumor and to increase the resectability rates. However, studies have not shown benefit in terms of control rates.
Follow-up of these patients should continue because of slow tumor growth and possibility of early recurrence which can be salvaged with good long-term results. Post-operative anticoagulation therapy is controversial, but some recommend this for 6 months post-operative in order to allow for good re-endothelization of prosthesis. At that time, anti-aggregant prophylaxis can be substituted.
LMS of IVC is a rare tumor. The variability of presentation and lack of clinical symptoms precludes an early stage at presentation. Surgery is the standard treatment of choice, followed by adjuvant local radiation ± chemotherapy. Delivery of standard radiation doses needs technical expertise and sophisticated equipments, in order to save critical structures. Role of adjuvant chemotherapy is not well-defined, however can be given on an individual case to case basis. However, all of these recommendations need further confirmation since the results may vary according to the individuals involved in the case.
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