Surgical treatment of varicose veins and venous malformations in Klippel

Abstract

Background

Klippel–Trenaunay syndrome (KTS) is a mixed mesenchymal malformation characterised by varicose veins, venous and capillary malformations, and hypertrophy of soft tissue and bone. The purpose of this study was to evaluate the surgical outcomes in KTS patients to provide standards for comparison with endovenous therapy.

Methods

The clinical data of consecutive patient with KTS who underwent open venous surgical treatment between January 1987 and December 2008 were reviewed. Demographics, clinical presentation, operative data, and clinical outcomes were recorded. Follow-up information was obtained from the medical records, mailed questionnaires and phone calls. Descriptive statistics, the Kaplan–Meier method and Log-rank statistics were used where appropriate.

Results

Twenty-seven females and 22 males, (mean age 26.5 years, range 7.7–55.8) were included in this study. All had varicose veins, 36 (73%) had limb hypertrophy, and 33 (67%) had capillary malformations, with two of three clinical features present in all. The most frequent symptom was pain (N = 43, 88%). Forty-nine patients underwent operations on 53 limbs. Stripping of the GSV, small and accessory saphenous and lateral embryonic veins was performed in 17 (32%), 10 (19%), 9 (17%), and 15 (28%) limbs, respectively. Two patients developed deep vein thrombosis, one had pulmonary embolism (PE), and one patient had peroneal nerve palsy. Freedom from disabling pain at 1, 3 and 5 years was 95%, 77% and 59%, respectively, and freedom from secondary procedures was 78% at 3 years, and 74% at 5 years. At the last follow-up visit, the venous clinical severity score had decreased from 9.48 ± 3.27 to 6.07 ± 3.20 (P < 0.001).

Conclusions

In selected symptomatic patients with KT syndrome, open surgical treatment is safe and durable. Three-fourths of the patients remain free of disabling pain at five years, but secondary procedures are required in one-fourth of the patients. These data can serve as standards for comparison of endovenous therapy for KT syndrome.

Keywords

Venous syndromes Klippel–Trenaunay syndrome varicose veins surgery

Introduction

Klippel–Trenaunay syndrome (KTS) is a rare mixed malformation characterised by congenital varicose veins, low flow venous malformations, hypertrophy of soft tissue and bone, and capillary malformation. Malformations of the deep veins and associated lymphatic malformations are frequently present. Congenital varicose veins are frequently atypical in location and large lateral incompetent embryonic veins can also be present.^1–3

Management of KTS is most often conservative, mainly by compression therapy of the involved limb. In patients with symptoms attributed to superficial varicose veins and venous malformations, interventional treatment can be considered. Results can widely vary due to the complexity and rarity of the disease. Outcome of treatment of varicose veins with surgery or endovascular interventions in patients with KTS has been reported in several series.^4–11 Outcomes of our first 20 patients treated with surgery with shorter follow-up were reported earlier and have shown good results.^7,8

The purpose of this study was to evaluate long-term outcomes of open surgical treatment of patients with KTS to provide standards for comparison with studies that investigate outcome after less invasive endovenous therapies.

Methods

The clinical data of consecutive patients who underwent open surgical treatment for varicose veins and venous malformations between January 1987 and December 2008 were retrospectively reviewed. Demographic data and clinical presentations were recorded, the C class of the CEAP (Clinical Presentation, Etiology, Anatomy and Pathology) classification as well as the Venous Clinical Severity Score (VCSS) were obtained from medical records.^12–14 Imaging studies, including duplex scanning, contrast venographies, computed tomographic (CT), magnetic resonance (MR) imaging and venographies were re-reviewed by one of the investigators (RDM) and an independent radiologist (TV) to document patency of deep veins, the extent of superficial and deep venous malformations, the presence or absence of lateral embryonic veins, and to determine incompetence of the superficial, perforating and deep system.

Details of any surgical procedures were documented, including high ligation and division of the great or small saphenous vein or lateral embryonic veins, with or without stripping, excision of varicose veins and venous malformations. Any deep vein reconstruction or perforator interruption with open or endoscopic technique (SEPS) was annotated. The use of a thigh tourniquet and any placement of an inferior vena cava (IVC) filter, if indicated because of thrombophilia, history of deep vein thrombosis (DVT), thrombophlebitis of a major superficial embryonic vein or pulmonary embolism (PE) was recorded. All patients received perioperative DVT prophylaxis with either unfractionated or low-molecular weight heparin. Postoperatively all patients were prescribed compression stockings and were educated with regard to skin care.

To obtain follow-up information the medical records of the patients were reviewed. If late follow-up information was not available, the patients were contacted by mailed follow-up form using the Aberdeen varicose vein questionnaire.¹⁵ If no response was received, patients or family members were contacted with a phone interview.

Statistical analysis

Survival curves were estimated by Kaplan–Meier method and P < 0.05 was considered statistically significant. All statistical analyses were performed using JMP 7.01 SAS (SAS Institute, Cary, NC).

Results

Forty-nine patients, 27 females and 22 males (mean age 26.5 years, range 7.7–55.8) were included in this study. All had varicose veins, 36 (73%) had limb hypertrophy confirmed with long bone X-ray films (mean difference in limb length of 1.7 cm, ranging from 0.3 to 3.4 cm). Thirty-three patients (67%) had capillary malformations (Table 1). All patients had at least two of the three clinical features of KTS, and all three were present in 27 patients (55%). The most frequent symptom was disabling pain (Figure 1) (N = 43, 88%) for which 36 patients (73%) used pain medications twice or more times a week prior to surgery.

Table 1.

Clinical presentation of 49 patients with KTS.

Signs and symptoms	No. of patients (%)
Varicosities	49 (100)
Limb hypertrophy	36 (73)
Capillary malformation (port wine stain)	33 (67)
Complete triad	27 (55)
Pain	43 (88)
Edema	39 (80)
History of superficial thrombophlebitis	8 (16)
History of bleeding from varicosity	5 (10)

Figure 1.

45-year-old KT patient with disabling right lower extremity pain. (a) remarkable port-wine stain, (b,c) lateral embryonic vein is also present, (d) venography depicts the lateral embryonic vein and patent deep veins, (e) the involvement of soft tissue is further delineated using MR imaging.

Eight patients (16%) had previous thrombophlebitis and five (10%) had bleeding from varicose veins (Table 1). Two patients had a history of DVT, one had previous PE. Figure 2 depicts the initial CEAP scores. Mean preoperative clinical score of the CEAP classification was 3.27 ± 0.91. Mean preoperative VCSS score was 9.48 ± 3.27.

Figure 2.

Initial clinical CEAP score of 49 surgical patients with KTS.

All patients underwent duplex ultrasound scanning, contrast venography or both to evaluate deep vein patency and deep, superficial or perforating vein reflux. Twenty-seven (55%) patients had great saphenous vein (GSV) incompetence and 20 (41%) had a persistent lateral embryonic vein (Table 2). Deep veins were partially obstructed in two patients due to congenital bands, and deep venous valve incompetence was documented in 22 (45%) (Table 2).

Table 2.

Anatomical findings in 53 limbs of 49 patients with KTS.

	No. of limbs (%)
GSV incompetence	27 (55)
SSV incompetence	5 (11)
Deep vein incompetence	22 (45)
Lateral embryonic vein	20 (41)

Note: GSV = great saphenous vein, SSV = small saphenous vein.

Fifty-three limbs were treated in 49 patients. Both limbs were operated in four (8%) patients. Stripping of the GSV, small and accessory saphenous and lateral embryonic veins was performed in 17 (32), 10 (19%), 9 (17%), and 15 (28%) limbs, respectively. Fifty limbs (94%) underwent excision or avulsion of varicose veins and venous malformations. To obtain a bloodless field, the limb was exsanguinated with an Esmarch bandage and a thigh tourniquet was inflated to 300 mmHg pressure in 39 limbs (74%). Mean tourniquet time was 56 ± 24 min. Limbs (11%) were treated with subfascial endoscopic perforator surgery (SEPS) procedure, one (2%) had deep vein reconstruction and one (2%) limb had above the knee amputation because of extensive venous malformation and recurrent bleeding and infections (Table 3).

Table 3.

Details of surgery performed on 53 limbs in 49 patients with KTS.

	No. of limbs (%)
Number of limbs	53 (100)
General anesthesia	50 (94)
GSV stripping	17 (32)
SSV stripping	10 (19)
Stripping other veins	9 (17)
Lateral vein stripping	15 (28)
SEPS	6 (11)
Avulsion/excision varicose veins	50 (94)
Popliteal vein release	2 (4)
Deep vein reconstruction	1 (2)
Preoperative IVC filter	6 (11)
Amputation	1 (2)
Intraoperative tourniquet	39 (74)
Tourniquet time, min	56 ± 24
Operative time, min	150 ± 61

Note: GSV = great saphenous vein, SSV = small saphenous vein, SEPS = Subfascial Endoscopic Perforator Surgery.

Early outcomes

There was no mortality. Two (4%) patients developed DVT and one (2%) of them had a PE. One (2%) patient had peroneal nerve palsy. Additionally, 14 (28%) minor postoperative complications occurred. Seven (14%) limbs developed thrombophlebitis, five (10%) had cellulitis, and two (4%) had bleeding that could be controlled with local compression.

Late outcomes

Follow-up averaged 73 months (range, 4 months to 18 years). No patient died during follow-up. Reoperation for recurrent symptomatic varicose veins or venous malformations was performed in 15 limbs of 13 patients. Thirty-three (70%) patients were compliant with instructions and reported daily use of compressing stockings after surgery. Seventeen (50%) reported significant pain relief but not complete relief, eight (25%) some relief, and eight (25%) no relief after more than three months of compression therapy. Freedom from disabling pain at 1, 3 and 5 years was 95%, 77% and 59%, respectively (Figure 3a). Freedom from secondary procedures was 78% at 3 years, and 74% at 5 years (Figure 3(b)). The patient who had peroneal palsy had partial recovery of motor function at the last follow-up visit at 17 months after surgery.

Figure 3.

(a) cumulative five-year survival free from secondary vein procedures in 49 surgical patients with KTS, (b) cumulative five-year survival free from disabling pain in 49 surgical KT patients.

At the last follow-up visit, the VCSS score had decreased from 9.48 ± 3.27 to 6.07 ± 3.20 and the C score of the CEAP classification decreased from 3.27 ± 0.91 to 2.42 ± 1.23 (P < 0.001, P < 0.001). Figure 4 depicts the pre- and postoperative CEAP and VCSS.

Figure 4.

Pre- and postoperative assessment based on CEAP score and VCSS of 49 surgical KT patients.

Discussion

Classification of congenital vascular malformations has evolved in recent years.^16,17 KTS is classified as a complex mixed vascular malformation which in its classic form includes venous malformation (VM), capillary malformation (CM), and soft tissue or bony overgrowth (Figure 1).¹⁶ Incomplete forms of KTS, when only two of the classic three clinical features have been recognised were classified in our paper as having KTS in order to distinguish them from other, simple or complex low flow venous malformations. Additionally, in KTS lymphatic malformation is often seen in the form of congenital lymphedema, but deep vein malformations, such as aneurysms, segmental absence or hypoplasia can also be present. Although efforts to discontinue eponyms have been emphasised repeatedly in the cardiovascular literature, the term Klippel–Trenaunay syndrome is widely accepted by many experts and it is extensively used even in the public press, just like Milroy’s disease, Marfan syndrome, Ehlers Danlos syndrome or Budd Chiari syndrome.¹⁸

Our study focused on open surgical treatment of the venous anomalies of KTS. Although a large number of different surgical procedures were performed, indications and techniques were very similar since all patients were operated on in a single surgical service at the Mayo Clinic. Since KTS is a rare disease and treatment is primarily conservative, the series spans two decades, an enrollment into this study stopped at the time new endovenous ablation techniques (laser, radiofrequency, foam) became available in this service. Therefore, this series can serve as a historical cohort for comparison to assess results of recent, less invasive endovenous therapies for KTS.

Before ablation of the superficial veins using any technique, the presence of patent deep veins has to be confirmed. While earlier in this study contrast venography was the gold standard for assessing deep vein patency, currently duplex scanning and MR venography are routinely performed before an intervention is done in patients with KTS.

Signs and symptoms vary greatly in patients with KTS, including severe pain and painful varicosities, recurrent thrombophlebitis, bleeding from skin lesions and venous malformations, and frank venous ulcerations. Chronic venous insufficiency with C3–C6 class was noted in all limbs in our study. Surgical technique of removing large embryonic veins has continuously evolved during the study. A tourniquet is essential to minimise blood loss. High ligation is performed with segmental stripping through short incisions to double ligate and divide large tributaries and perforating veins of the lateral vein to minimise bleeding complications of blind inversion stripping. Deep vein reconstruction using the contralateral saphenous vein was needed in one patient with C6 disease who had absent femoral vein. One patient with advanced disease required above knee amputation.

A clinically important outcome measure, apart from the improvement achieved by surgery, is the safety of the procedure. In our study, minor complications occurred in a little less than a third of patients. While this is higher than rates reported for patients operated on for primary varicose veins, it seems acceptable in view of the severity of disease in KT patients selected for treatment, and the mild and temporary nature of the reported complications.

Because of DVT in two patients and one PE we observed in this series, a temporary IVC filter was selectively placed preoperatively in the last decade of the study in patients with history of DVT, PE or superficial thrombophlebitis in the large embryonic veins, or in patients with known thrombophilia. It is known that patients with congenital vascular malformations, especially those with extensive venous malformation, are at a higher risk for venous thromboembolism (VTE).¹⁹ The most relevant reason for thromboembolic events is localised intravascular coagulopathy (LIC).²⁰ This imbalance in coagulation factors within the malformed vessels predisposes patients to development of systemic disseminated intravascular coagulopathy (DIC) in the presence of a stimulating factor such as surgical trauma. Therefore, an optimal perioperative VTE prophylaxis therapy in every patient is mandatory.

There are several difficulties inherent to assessing the outcome of treatment in KTS. Treatment in many patients will not completely alleviate symptoms, but it will improve their quality of life and delay progression of chronic venous disease. This is difficult to assess in KT studies because of its rarity and widely varying natural history. We used the American Venous Forum recommended VCSS to assess outcome.¹³ The C score was also recorded and showed improvement in 41% at three months after surgery, but the CEAP classification is a static instrument and it is not suitable to reliably assess outcome of therapy over time.

It is usually not possible to remove all affected vessels because of the extent of the varicose veins in KTS patients. In an earlier series, we recorded recurrence in 50% of the limbs.⁸ One quarter of patients had a repeat intervention on long-term follow-up, which is similar to reported rates in patients after surgical treatment of varicose veins.²¹

Pain was reported to have reoccurred by 40% of our patients at five years. It is important to outline that pain in KTS can occur due to recurrent varicose veins which indicate the need for repeat surgical treatment or pain can be caused by concomitant neuropathy which is nonoperative and has been reported as a cause of pain in other venous malformations.²²

This is retrospective study of a large experience with surgical treatment for KTS. Since different operations were performed in a study that spanned to two decades it is difficult to assess surgical outcomes, therefore our study has several limitations. Based on the rarity of the disease and very strict criteria for operation only a limited number of patients could be gathered over a 20-year period, which reduce the statistical power of our analysis. By far, the measurement of late outcomes was one of the most difficult portions of our research because venous clinical scores were elaborated after our experience with surgical KTS patients had already started. The CEAP score was retrospectively obtained and it is relatively an immobile score, which was not designed to measure improvement in follow-up, as it does not allow betterment of scores once permanent skin changes or ulcers occur. To remediate the lack of immobility of CEAP and to further detail the late outcomes the VCSS was included. Despite significant efforts made to provide a solid report to serve for comparison in future research, these scores might still under- or overestimate overall clinical improvement relevant to the patient to some degree.

In conclusion, surgical treatment of patients with KTS is limited to cases with severe symptoms. If done with expertise and careful selection after documenting patency of the deep system and gauging if the patient is fit for surgery, ablation of the incompetent superficial system including large embryonic veins can be performed safely together with phlebectomy, usually using a tourniquet to provide a bloodless field. Selective use of a retrievable IVC filter must effectively decrease major PE in these patients. Surgical treatment is safe and effective with improvement of symptoms in many patients for more than five years after surgery. Results of new, minimally invasive endovenous procedures should match these surgical outcomes before they are widely accepted to treat patients with KTS.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Surgical treatment of varicose veins and venous malformations in Klippel–Trenaunay syndrome

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Statistical analysis

Results

Early outcomes

Late outcomes

Discussion

Footnotes

Declaration of Conflicting Interests

Funding

References