Endovascular Treatment of Inferior Vena Cava Thrombosis in Metastatic Malignancy: A Case Report and Review of Literature
Vascular and Endovascular Surgery 1-5
@ The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1538574419857992 journals.sagepub.com/home/ves SAGE
Kayle S. Shapero, MD, PhD’o, Qurat-UI-Ain Jelani, MD2, and Carlos Mena, MD2
Abstract
Inferior vena cava (IVC) thrombosis is a specific form of thromboembolism that occurs at a rate of 1.5% in all patients hospitalized with a deep vein thrombosis. Malignant IVC thrombosis may occur due to compression from a tumor mass or metastasis or may also occur through tumor invasion of the venous vasculature. Obstruction of the IVC can lead to IVC syndrome, marked by ascites, lower extremity edema, and even congestive hepatic failure. We present a case of extensive IVC thrombosis in a 69-year- old female with metastatic adrenal cell carcinoma, presenting with severe bilateral lower extremity edema and ascites. Computed tomography showed IVC compression by the caudate lobe due to a metastatic liver mass and extensive clot burden of the IVC extending from the renal veins to the right atrium (RA). She underwent percutaneous IVC stenting with 4 stents placed in tandem from the IVC to the RA. Her hospital course was complicated by gastrointestinal bleed requiring clipping, acute liver failure, and hypophysitis due to trial therapy. Although her IVC symptoms were partially relieved with percutaneous intervention, her acute liver failure worsened and she was ultimately transitioned to hospice care.
Keywords
deep vein thrombosis, tumor thrombus, inferior vena cava, inferior vena cava thrombus, endovascular stent, endovascular treatment, angiography
Introduction
Venous thromboembolism is a frequent complication of malignancy that most often presents as peripheral deep vein thrombosis or pulmonary embolism. Inferior vena cava (IVC) thrombosis is a specific form of thromboembolism that is esti- mated to occur at a rate of 1.5% of all patients hospitalized with a deep vein thrombosis.2 Malignant IVC thrombosis may occur due to compression from a tumor mass or metastasis or may also occur through tumor invasion of the venous vasculature. The presence of an IVC thrombus has been reported in several type of malignancies, most commonly renal cell carcinoma,3 hepa- tocellular carcinoma (HCC),4 and adrenal carcinoma (ACC).5 Obstruction of the IVC can lead to IVC syndrome, marked by ascites, lower extremity edema, and even congestive hepatic failure.6 Treatments for malignant causes of deep vein throm- bosis had previously been restricted to surgical, chemotherapy, or radiation treatments, but endovascular therapies have started to emerge. The 2011 American Heart Association guidelines even recommend the use of catheter-directed thrombolysis or percutaneous transluminal venous angioplasty and stenting for the treatment of iliofemoral deep vein thrombosis (class IIa recommendation).” We present the case of a female patient with metastatic adrenal cortical carcinoma who presents with IVC
tumor thrombus extending to the right atrium (RA) who under- went IVC stenting as palliative treatment of her IVC syndrome.
Case Report
Our patient is a 69-year-old female with a past medical history of metastatic adrenocortical carcinoma with metastasis to the liver and lungs who was found on computed tomographic angiography (CTA) to have extensive IVC thrombosis. She was first diagnosed with adrenocortical carcinoma 8 months ago requiring left adrenalectomy and nephrectomy leading to Cushing disease and associated edema treated with mitotane and metyrapone. Four months after diagnosis, she was found to have hepatic metastasis requiring treatment with carboplatin/
‘Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
2Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
Corresponding Author:
Kayle S. Shapero, Department of Internal Medicine, Yale New Haven Hospital, Yale University, New Haven, CT 06510, USA.
Email: kayle.shapero@yale.edu
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Adriamycin, etoposide, and most recently phase I anti-B7-H4 Ab. She then developed shortness of breath, bilateral lower extremity edema, and ascites. A CTA of the abdomen and pelvis showed a filling defect in the IVC at the level of the right renal vein and almost complete occlusion at the hepatic IVC level from external compression by the metastatic mass in the liver (Figure 1A and B). Given her symptoms, we decided to perform venography and possible endovascular intervention in order to improve patient’s quality of life.
Venography was carried out via right common femoral vein access using a 20F sheath. Angiographic images revealed mod- erate-severe stenosis of the IVC extending from the right renal vein to the junction of the IVC with RA (Figure 2). Intravas- cular ultrasound (IVUS) performed during the catheterization demonstrated extrinsic compression of the IVC (Figure 3). Palliative angioplasty was performed using four 50-mm-long Palmaz XL 5010 stents (Cordis, Milpitas, California) mounted on a 24-mm balloon-in-balloon system. The stents were serially implanted in an overlapping fashion from just above the right renal vein to the RA-IVC junction. Stent sizing was determined using IVUS images of the normal vessel where there was no evidence of compression or thrombus (Figure 3A and B). Final venographic images showed excellent angiographic result with restoration of normal luminal diameter and blood flow (Figure 4, Supplemental Videos 1 and 2).
After the procedure, she was started on clopidogrel and apixaban, but her course was complicated by acute upper gas- trointestinal bleeding due to a mucosal tear in the stomach plus a nonbleeding esophageal ulcer (both of which were clipped)
IFI
and duodenal erosions consistent with pill esophagitis. Follow- ing the gastrointestinal bleed, her liver function tests, ammonia levels, and international normalized ratio continued to worsen,
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which were thought to be a combination of tumor progression, metyrapone/mitotane side effect causing a drug-induced liver injury, and autoimmune hepatitis induced by the phase I trial medication. A vascular ultrasound of the abdomen was also performed, which showed a patent IVC stent and no other vascular pathology, suggesting that her worsening condition was attributed to her underlying malignancy as opposed to her recent stent placement.
Given worsening acute liver failure, she was started on N-acetylcysteine and rifaximin with minimal improvement. Her mental status continued to decline, and ultimately, she was transitioned to hospice and died 2 days later.
Discussion
In this case report, we present a unique approach to the endo- vascular treatment of an IVC thrombus from metastatic
adrenocortical adenocarcinoma. Thrombosis of the IVC may be due to a variety of disorders including congenital IVC anomalies, coagulopathies (antiphospholipid antibody syn- drome), pregnancy, IVC filter thrombosis, radiation fibrosis, and malignancy.8 Inferior vena cava thrombus may present with bilateral lower extremity edema and dilation of the superficial abdominal vessels and/or ascites depending on the level of involvement, or symptomatic pulmonary embo- lism in some cases.8 Malignant obstruction is often due to compression from an adjacent tumor, commonly due to hepatic primary masses (hepatoma, HCC) or hepatic involvement of metastasis.6,9 In addition to compression, IVC thrombus may also occur from direct invasion or extension of a tumor into the vasculature, which is commonly seen in malignancies such as renal cell carcinoma or HCC.1º This process of thrombus formation is thought to be due to endothelial dam- age and subsequent thrombosis incurred from tumor inva- sion into the IVC wall as well as the general prothrombotic state of malignancy.11
With this patient, the cause of IVC thrombus was due to adrenal cell carcinoma, a rare form of malignancy present with 0.5 to 2 cases per million.12 Because of the location and lack of symptoms, many ACCs are often diagnosed at an advanced stage with metastatic disease. The incidence of an IVC thrombus either through direct invasion of adreno- cortical adenocarcinoma or secondary to compression is rare and is limited by several case studies with varying treatment approaches. 13,14
Historically, treatment approaches to IVC thrombus have involved surgical resection of the offending obstruction and/ or graft placement. Surgical resection can relieve the tumor burden but involves aggressive, open surgeries requiring car- diac bypass and resulting in high morbidity and mortality rates due to blood loss, prolonged procedural time, and other surgical complications.15 In many situations, this approach is not fea- sible due to large tumor burden, debilitating symptoms, or poor surgical candidacy. In certain situations, radiation or che- motherapy is considered, but often the benefit is significantly delayed, and symptoms are exacerbated by treatment prior to improvement. Therefore, endovascular approach has been introduced as a recent alternative to conventional surgery. Inferior vena cava stenting has emerged as a technique for treating malignant caval obstruction with rapid relief of obstruction and improvement in symptoms in 78% to 100% of patients.11 The existing literature involving endovascular stenting of IVC thrombus due to malignancy is limited to case reports and one small case series. The 4 case reports include IVC thrombus due to HCC and colon cancer and were treated palliatively with suprarenal stent placement and improvement in symptoms.6,16,17 The case series by Razavi et al included 17 cases of IVC thrombi, with 3 cases due to malignant compres- sion (liver metastasis with unknown primary, HCC, and hepatic angiosarcoma), all of which were treated with suprarenal IVC stents and subsequent patency of the IVC.18 As an adjunct to these endovascular interventions, IVUS has become a neces- sary tool to provide alternative imaging to traditional
venography. Intravascular ultrasound provides an image of the vessel lumen and wall structures that complements catheter-based procedures and allows for identification of specific landmarks or abnormalities such as thrombi, fibro- sis, or external compression.
Our patient in this study was a poor surgical candidate with progression of metastatic disease on mitotane and metyrapone. Her acute presentation with IVC syndrome was treated with an aggressive endovascular approach. Given the extent of her dis- ease, the procedure was performed primarily for palliative pur- poses to improve volume overload. In our patient’s situation, her thrombus did not propagate into the RA, and therefore, she did not require extension of the stent placement from the IVC to SVC as has been previously reported.17
With regard to other complications, rarely IVC stenting has been associated with several complications including stent migration, thrombosis, fevers, or bleeding. Cardiac complications of stent migration have resulted in arrhythmias, aorto-atrial fistula formation, perforation and resulting hemopericardium,
plications have decreased with improved endovascular tech- niques and approaches. These risks are particularly relevant in cases where the tumor thrombus extends into the RA, wherein stent migration can cause protrusion of the free end of the stent into the heart. To avoid this complication, the technique of a trans-right atrial approach was developed, where the overlap- ping stents are placed from the SVR to the IVC through the RA.17 This approach avoids the potential cardiac complica- tions of leaving the end of a free stent in the RA.
Despite these complications, the use of endovascular treat- ment for palliative treatment of IVC thrombus has largely been successful from a palliative approach. One case report demon- strated the need for reintervention to create a portocaval shunt between the right portal vein and IVC to relieve portal venous obstruction, which ultimately improved the patient’s symp- toms. In the cited literature, the underlying disease process ultimately limited overall survival, which ranged from 1 month to 19.5 months. With regard to symptoms, in this case, as well as the cited case reports, all patients achieved at least initial relief of volume overload and venous congestion.6,16,1
One complication of stent placement in IVC thrombus which may have contributed to progressive liver failure in our patient is the development of Budd-Chiari syndrome in patients with inadequate collateral venous drainage, depending on their anatomy and the extent of obstruction. Although relief of the thrombus obstruction will often restore hepatic venous drai- nage, in several reports, portal decompression (eg, stent place- ment in left hepatic vein) was required to avoid this complication and worsening liver failure.6,17 In this particular case, the patient’s worsening liver function was ultimately attributed to drug-induced liver injury and autoimmune hepa- titis induced by her phase I trial medication as opposed to Budd-Chiari syndrome, given that the liver function decline occurred days after her procedure, and there was no evidence of Budd-Chiari on subsequent imaging. It should also be noted that initial endovascular stenting was pursued as a palliative
treatment to improve quality of life, and the patient was too unstable to undergo more invasive procedures.
Conclusion
This case represents one of the first instances of endovascular treatments of IVC thrombosis due to adrenocortical adenocar- cinoma. Endovascular treatment of venous disorders has been gaining traction as an approach for deep vein thrombosis (DVT) management, from iliofemoral DVT19 to May- Thurner syndrome.20 This new approach is compared to the conventional management options of anticoagulation, systemic thrombolytic therapy, or surgical thrombectomy techniques, which can be associated with incomplete recanalization, bleed- ing, or other serious complications. Endovascular interventions have shown comparable recanalization rates using techniques of balloon angioplasty, venous stent implantation, catheter- directed thrombolysis, percutaneous aspiration, or mechanical thrombectomy.21 The endovascular approach has the added appeal of improved safety and fewer bleeding risks as com- pared to open surgical techniques and may provide an option for symptom management in patients, such as the one discussed in this case, who are not ideal surgical candidates.
Authors’ Note
Consent has not been obtained because the patient is deceased.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Carlos Mena: Abbott, Bard, Boston Scientific, COOK, Medtronic, Gore, Cardinal health.
Funding
The author(s) received no financial support for the research, author- ship, and/or publication of this article.
ORCID iD
Kayle S. Shapero DD https://orcid.org/0000-0002-7747-4410
Supplemental Material
Supplemental material for this article is available online.
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