Commentary (Wakefield): Diagnosis of Venous Thromboembolic Disease in Cancer Patients

This article by Marcelo Gomes, MD, and Steven Deitcher, MD, is a well conducted, thorough, and scholarly review of the diagnostic methods for venous thromboembolism in cancer patients. The authors have specifically looked at upperand lower-extremity deep venous thrombosis (DVT), pulmonary embolism, and rarer conditions including thrombosis of the inferior vena cava (IVC), pelvic veins, and even the portal vein. They offer descriptions of the various tests available, address the pros and cons of those tests, and provide the reader with algorithms for the diagnosis of DVT and pulmonary embolism, including two for pulmonary embolism-one based on ventilation/perfusion (V/Q) scanning and one based on helical computed tomography (CT) scanning.

Venography vs Duplex Ultrasound

As the authors have suggested, for the diagnosis of extremity DVT in cancer patients, "the combination of high venous thromboembolism incidence, pronounced recurrent venous thromboembolism rates, and higher rates of hemorrhage while receiving anticoagulant therapy makes venous thromboembolism management in the cancer patient a challenge." The authors consider venography the "gold standard" and consider duplex ultrasound imaging to be quite useful for acute femoropopliteal DVT but less impressive in the setting of upperextremity DVT.

Likewise, the authors feel that duplex ultrasound imaging lacks adequate sensitivity when used for screening of asymptomatic individuals. However, asymptomatic individuals with abovethe- knee femoropopliteal DVT can be successfully imaged with duplex ultrasound, and a negative scan in an asymptomatic patient virtually rules out DVT with 98% specificity.[1,2] The category that is most troublesome for duplex ultrasound imaging is the asymptomatic patient with calf vein thrombosis.

Although contrast venography may still be the gold standard at some centers, at my own institution, the number of contrast venograms that are performed for the diagnosis of DVT is extremely small. Thus, at my institution, duplex ultrasound imaging has become the gold standard against which all other tests are compared.

'Aging' the Thrombus

I take some exception to the discussion of the usefulness of duplex ultrasound imaging in a patient with recurrent DVT. I certainly agree that in some situations, determining acute from subacute or acute from chronic DVT can be difficult. However, I do not believe that it is necessary to pursue contrast venography in the great majority of cases of suspected DVT recurrence, and duplex ultrasound imaging often is accurate enough that decisions can be made on this assessment alone.

Criteria that have been used to "age" the thrombus include echogenicity, compressibility, adherence, vein size, and the status of the collaterals.[ 2] Acute thrombosis is associated with enlargement of the vein, a hypoechoic thrombus, lack of sizable collaterals, and vein incompressibility. Chronic thrombosis is associated with a small shrunken vein, presence of significant collaterals, a hyperechoic thrombus, and again, vein incompressibility. Newer ultrasound techniques should allow for an even greater improvement in the ability of duplex imaging to age a thrombus in the future.

Concerning magnetic resonance venography (MRV) for extremity DVT, one technique that was not mentioned in the review is the use of gadolinium enhancement to define the age of the thrombus.[3] In the initial clinical evaluation of gadolinium- enhanced magnetic resonance venography, the ability for gadolinium to extravasate and enhance the vein wall appeared to differentiate acute (< 14-day-old) thrombus from chronic (> 14-day-old) thrombus. Thus, in a situation in which duplex ultrasound imaging has a difficult time determining the age of the thrombus due to a mixture of the criteria mentioned above, MRV with gadolinium can provide these data. It is also important to mention that in the presence of recurrent DVT, contrast venography has its own limitations in its ability to distinguish acute from chronic disease.

Diagnosing Pulmonary Embolism

Concerning the diagnosis of pulmonary embolism, I believe that the authors have nicely summarized the current literature. They mention that although helical (spiral) CT scanning in many institutions has become a routine test for the diagnosis of pulmonary embolism, the overall sensitivity and specificity rates for the diagnosis of pulmonary embolism vary widely. This observation is likely due to the fact that some studies have been performed with older technologies.

A national study called the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II is currently recruiting patients. This study should provide information on the appropriate use of helical CT scanning for the diagnosis of pulmonary embolism and help to establish when it should be used. This information should define the usefulness of this test in the same way the first PIOPED defined the usefulness of V/Q scanning for the diagnosis of pulmonary embolism.[4] The authors have also given a reasonable summary of the current status of the usefulness of D-dimer assays for cancer patients being evaluated for possible venous thromboembolism.

Finally, concerning IVC and other abdominal vein DVT, the authors do not mention duplex ultrasound as a diagnostic possibility because of the inability to compress the central veins. Duplex ultrasound imaging has been found to be able to successfully follow IVC filters, determine flow in the main IVC,[5] and be useful for placing IVC filters in up to 90% of cases.[6] Indeed, duplex ultrasound imaging of the IVC should prove to be a useful technique in certain clinical situations.

Conclusions

Overall, I believe that this is a very valuable article. Certainly in the cancer setting the diagnosis of venous thromboembolism is extremely important, as the patient's overall outcome is often adversely affected by such thrombosis. This article very nicely summarizes the current literature. Although the emphasis on contrast venography in the article is an area of controversy and one with which I have some disagreement, I believe that, overall, the authors have provided a useful review that the practicing oncologic physician can incorporate into his or her daily practice for the diagnosis of venous thromboembolic disease.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1.

Mattos MA, Londrey GL, Leutz DW, etal: Color-flow duplex scanning for the surveillanceand diagnosis of acute deep venous thrombosis.J Vasc Surg 15:366-376, 1992.

2.

Douglas MG, Sumner DS: Duplex scanningfor deep vein thrombosis: Has it replacedboth phlebography and noninvasive testing?Semin Vasc Surg 9:3-12, 1996.

3.

Froehlich JB, Prince MR, Greenfield LJ,et al: "Bulls-eye" sign on gadolinium-enhancedmagnetic resonance venography determinesthrombus presence and age: Apreliminary study. J Vasc Surg 26:809-816,1997.

4.

PIOPED Investigators: Value of the ventilation/perfusion scan in acute pulmonary embolism.Results of the Prospective Investigationof Pulmonary Embolism Diagnosis (PIOPED).JAMA 263:2753-2759, 1990.

5.

Kazmers A, Groehn H, Meeker C: Duplexexamination of the inferior vena cava. Am Surg66:986-989, 2000.

6.

Conners MS, Becker S, Guzman RJ, et al:Duplex scan-directed placement of inferior venacaval filters: A five-year institutional experience.J Vasc Surg 35:286-291, 2002.