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Femoral–Popliteal Bypass Graft Thrombosis May Be Sign of Occult Cancer

Key findings

  • This multicenter retrospective study examined data on 517 patients who collectively had 621 femoral-popliteal bypasses and did not have a preexisting cancer diagnosis
  • 36 bypasses (5.8%) were performed in patients who were subsequently diagnosed with cancer within one year
  • Patients with occult cancer were at significantly higher risk of graft thrombosis three months postoperatively (OR, 4.25), six months (OR, 2.70) and one year (OR, 3.34)
  • Occult cancer was a significant predictor of graft thrombosis (OR, 2.03) and major adverse limb events (thrombolysis, thrombectomy or bypass revision) (OR, 1.84)
  • When a patient develops graft thrombosis within one year after femoral–popliteal bypass and there is no clear reason for the bypass to have failed, demographically appropriate cancer screening should be considered

Cancer is known to drive a hypercoagulable state in the arterial system. The risks of myocardial infarction, ischemic stroke and thromboembolism increase even before a formal cancer diagnosis. However, the effect of this thrombotic risk on the patency of lower-extremity bypass grafts has never been studied.

C.Y. Maximilian Png, MD, a 2nd year resident in vascular surgery, and Anahita Dua, MBChB, MSc, MBA, assistant professor of Vascular and Endovascular Surgery, associate director of the Wound Care Center, and co-director of the Peripheral Artery Disease Center at Massachusetts General Hospital, and colleagues have now determined in a large multicenter cohort that occult cancer is associated with a higher rate of thrombosis in femoral–popliteal bypass grafts. In the Journal of Vascular Surgery, they propose when and how patients with thrombosed grafts should be screened for cancer.

Study Methods

Using an internal data registry, the researchers identified 517 patients who collectively had 621 femoral-popliteal bypasses performed at Mass General or two affiliated community hospitals between 2001 and 2018 and did not have a preexisting cancer diagnosis.

36 bypasses (5.8%) were performed in patients who were subsequently diagnosed with cancer within one year. The other patients served as a control group. Follow-up continued through December 2019.

Primary Outcome

Compared with controls, patients with occult cancer had significantly higher rates of graft thrombosis:

  • 1 month postoperatively: 11.1% vs. 3.7% (P=0.03)
  • 3 months: 27.8% vs. 8.0% (P<0.001)
  • 6 months: 30.5% vs. 14.1% (P<0.01)
  • 1 year: 44.4% vs. 19.8% (P<0.001)

Multivariate analysis confirmed patients with occult cancer were at significantly higher risk of graft thrombosis at:

  • 3 months: OR, 4.25
  • 6 months: OR, 2.70
  • 1 year: OR, 3.34

Occult cancer was a significant predictor of graft thrombosis (OR, 2.03).

Secondary Outcomes

Rates of major adverse limb events (thrombolysis, thrombectomy or bypass revision) were significantly higher in patients with occult cancer than controls at every time point studied. Occult cancer was a significant predictor of limb events (OR, 1.84).

There were no differences between occult cancer and control groups in rates of mortality or major amputation at any timepoint.

Characteristics of Grafts That Failed Within One Year

Bypasses were classified as "threatened" if there were worrisome perioperative findings (e.g., no in-line runoff or abnormal postoperative angiogram), worrisome follow-up findings (e.g., significantly elevated velocities on duplex ultrasound) or worrisome history between visits (e.g., orthopedic surgery).

Threatened bypasses constituted 19% of thrombosed bypasses in patients with occult cancer versus 43% in patients without occult cancer. In patients with thrombosed grafts one year postoperatively, there was a negative predictive value of 94% for occult cancer if the bypass was classified as threatened.

How to Respond to Graft Thrombosis

Given the negative predictive value of 94% in this cohort, it's unlikely that a patient with femoral–popliteal bypass graft thrombosis has occult cancer. Still, three steps are sensible when unexplained bypass occlusion occurs up to one year postoperatively:

  1. Test for a hypercoagulable state
  2. Review the patient's perioperative course, postoperative studies and interval medical history
  3. If that review yields no significant findings, consider referral to an oncologist for further workup

5.8%
of femoral–popliteal bypasses were done in patients who had occult cancer at the time

2x
greater risk of femoral–popliteal bypass graft thrombosis in patients with occult cancer

84%
greater risk of major adverse limb events in patients who had occult cancer at the time of femoral–popliteal bypass

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