Research On The Pathophysiology Of Saphenofemoral Recurrence And The Role Of Neovascularization

The ultimate answer to the question, does neovascularization at the ligated SFJ really exist? still has to be given. Because animals do not suffer from varicose veins, an animal experiment is hardly possible to prove the existence of neovascularization. Therefore it can be proved only in an indirect way. Observations made in patients prospectively studied after varicose vein operations with duplex scan are very useful. Moreover in patients operated upon because of recurrent varicose veins preoperative duplex findings can be compared with visual inspection at the previous ligation site during reexploration and histological examination of the excised tissue blocks from the scar tissue in the groin. Although findings from such studies may be suggestive for neovascularization, none of them is conclusive. This means that further observational studies will not definitely answer this question.

More fundamental research should focus on the potential pathophysiological mechanisms that could explain how new veins can develop after correct SFJ ligation: angiogenic stimulation in the free endothelium of the ligated stump, transnodal lymphovenous connection, dilation of small adventitial vessels in the vasa vasorum of the femoral vein, or disturbed venous drainage of the ligated tributaries of the SFJ. All of these occur on a background of the normal wound-healing process, in which angiogenesis is an important component, potentially giving rise to a more generalized, field-related neovascularization in the groin.

Angiogenic Stimulation in the Free Endothelium of the Saphenous Stump

After surgical ligation and transection of the GSV, angio-genic stimulation in the free endothelium of the ligated stump has been claimed to be one of the most important triggers for the onset of the neovascularization process. Such stump-related neovascularization might originate from hypoxia-induced activation of endothelial cells distal to the stump ligature, which could be mediated by growth factors.16 Another cause of stump-related neovascularization could be inflammation related to ligature, particularly those of absorb-able material, or to the results of dissection in the immediate area. Irrespective of its original impetus, stump-related neovascularization is the mechanism most compatible with the duplex-imaging morphology of recurrent SFJ reflux. It offers a simple, axiomatic solution to reduce the incidence of neovascularization: "no stump, no stump-related neovascularization."

Transnodal Lymphovenous Connection

Lefebvre-Vilardebo17 has focused on the important role of the lymph nodes in the neighborhood of the ligated saphe-nous stump. At postoperative duplex examination of the groin he described the presence of tiny (1 to 4 mm) refluxing veins passing through the surrounding lymph nodes, which could be indicative for possible evolution to recurrent varicose veins. Study of the lymph nodes by means of high definition ultrasound before and after surgery at the SFJ may help to clarify the role of lymph nodes and lymphovenous connections. In previous studies histological examination mainly focused on excised tissue blocks from the scar tissue in the groin at reoperation.81315 To improve our understanding of the histological alterations in recurrent varicosis, it might be interesting to investigate primary and recurrent varicose veins, normal vessels of the saphenofemoral area, and lymph nodes and lymph vessels of this area, and compare these findings with those at other localizations.

Dilation of Small Adventitial Vessels in the Vasa Vasorum

Theoretically, dilation of small adventitial vessels in the vasa vasorum of the femoral vein could be responsible for new connections between the deep and superficial venous system. Venous endoscopy of the femoral vein, done to assess valve function, occasionally has shown extremely small medial or lateral orifices near the entrance of the GSV. These have been thought to be the openings of tiny tributaries that are too small to show on phlebography or duplex sonography. The observers, for this reason, cannot be certain that these are not just vasa vasorum serving the vein wall and having no external connections, but they have postulated that these tiny orifices might enlarge, to become conduits of blood refluxing to the superficial veins.

Disturbed Venous Drainage of Ligated Tributaries

Disturbed venous drainage of the ligated tributaries of the SFJ has recently been cited as a potential pathophysiological mechanism to explain recurrence in the groin. Chandler et al.18 have suggested that neovascularization might be driven not only by angiogenic stimuli inherent to the wound healing process, but also by localized venous hypertension, or "frustrated venous drainage" secondary to ligation of tributaries. This tributary ligation might interfere with normal venous drainage of the superficial tissues of the lower abdomen and pudendum. The presence of neovascular cross-groin collaterals (small veins passing from the anterior abdominal wall, across the groin, toward the thigh) in some cases at postoperative duplex examination, or reoperation could be an illustration of this hypothesis. Moreover, the idea that localized venous hypertension might be a trigger for neovascularization is supported by the findings in the recently developed alternative techniques consisting of ablation of the saphenous vein by radiofrequency or laser energy without a groin incision. These procedures were not associated with neovascularization in the groin according to duplex scan follow-up.19 Opposite to the situation of "frustrated venous drainage" following ligation of tributaries in the groin, leaving open these tributaries could reduce the stimulus to neovascularization as the normal venous drainage of the lower abdominal and pudendal tissues would have been preserved. Further studies will be needed to elucidate this pathophysiological issue.

Constitutional Risk Factors

In addition to all the previously mentioned pathophysiological mechanisms, constitutional risk factors, which potentially could enhance the tendency to recurrence, should also be further examined. The importance of risk factors such as female gender, left-sided disease, associated deep vein incompetence, severe chronic venous disease (C4-6 of the CEAP classification), obesity, subsequent pregnancies after surgery, which all have been claimed to promote recurrence, should be prospectively studied.

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