1. Peripheral Venous Reflux - When is Surgical Intervention Necessary?
James D. Brooks, MD, RPVI
MedStar Washington Hospital Center and Georgetown University Hospital
February 23rd, 2016

2. Disclosure
None
Good morning. I have no disclosures related to this talk.

3. Chronic Venous Insufficiency: Scope of the Problem
The most common vascular disorder
~23% of adults have varicose veins; 6% have advanced chronic venous disease
~1-3 billion USD spent per year on direct medical treatment
2-3% of the total healthcare budget
2 million U.S. workdays lost per year
Chronic venous insufficiency represents the most common form of vascular disease. Approximately 23% of individuals have varicose veins, and 6% of individuals have advanced, C4-C6, disease. Approximately one to three billion U.S. dollars are spent annually on direct medical treatment accounting for ~2-3% of healthcare spending and an estimated 2 million U.S. workdays are lost per year.

4. Chronic Venous Insufficiency: History
1891: Trendelenburg advocates mid-thigh great saphenous vein (GSV) ligation for varicose veins
1904: Tavel, and later Homans, promote ligation of the GSV at the saphenofemoral junction (SFJ)
1905-6: Keller and Mayo describe concomitant GSV stripping
s: Linton and Cockett describe perforating vein ligation
Later, Hauer introduced subfascial endoscopic perforator surgery (SEPS) which has supplanted the Linton procedure
s: Experiments on RF ablation of the GSV performed
1999: Boné reports first use of endoluminal laser energy; first RF ablation device approve
2002: First laser ablation device approved
2016: The laser/RF ablation widely used. The advances continue…
To give a sense of how far treatment has come in the past 120 years or so, we’ll start with Trendelenburg advocating mid-thigh GSV ligation for treatment of varicose veins in Dr. Tavel in Bern, Switzerland and later Dr. Homans both promoted ligation of the GSV at the saphenofemoral junction in Reports of adjunctive stripping were described by Drs. Mayo and Keller soon therafter. Surgical management of perforating veins was advanced by Drs. Linton and Cockett during the s which was later replaced by subfascial endoscopic perforator surgery. In the 1960s-70s, the first experiments on RF ablation of the GSV were performed with disastrous results. Refinements were made over time as well as introduction of the first endoluminal laser ablation by Boné in 1999 which have yielded the first devices with FDA approval for RF ablation and endovenous laser ablation in 1999 and 2002, respectively. These techniques have since been widely adopted and applied to the SSV and perforating veins and advances continue using sclerosing agents, mechanochemical ablation and even intraluminal adhesives.

5. Great Saphenous Vein Incompetence
Historically, surgery is the gold standard for treating saphenous reflux varicose veins
1980s-1990s: Trials demonstrate increased efficacy of ligation and stripping versus ligation alone
Dwerryhouse et al. (1999):
Reoperation in 6% of stripped vs 20% of ligated GSV (RRR 72%)
Neovascularization of the SFJ accounted for 10 of 12 cases of reoperation
Relative risk of SFJ reflux secondary to neovascularization was 45% in stripped versus ligated veins
Invagination/inversion techniques are associated with less invasion and blood loss
However, surgical ligation and stripping of the great saphenous vein has been the gold standard in treatment of varicose veins from saphenous reflux. Adjunctive stripping was studied in trials in the 1980s and 1990s and was found to be superior to ligation alone. In one randomized trial by Dwerryhouse and others, reoperation for VV was necessary in only 6% of stripped versus 20% of ligated GSVs, a relative risk reduction of 72%. Most neovascularization occurred at the saphenofemoral junction and the relative risk of reflux secondary to neovascularization was only 45% in stripped versus ligated veins. Finally, regarding vein stripping, this can be performed using a disposable plastic vein stripper in which a bullet of varying sizes is attached to a catheter and pulled through the thigh. Invagination techniques have also been described using the plastic catheter without the bullet or a stainless steel stripper, like that described by Dr. Oesch, and are associated with less tissue invasion and blood loss.

6. Great Saphenous Vein Incompetence
Advantages of surgery include:
Definitive removal of the offending saphenous vein
Ability to perform concomitant stab phlebectomy
Long-term data to support its efficacy
Complications include:
Groin incision non-healing/infection (~1%)
Saphenous nerve damage (~5%)
Bleeding
VTE: DVT (0.5-5%); PE (0.16%)
Complications associated with general anesthesia (if used)
Recurrence is as high as 20-30% at 2 years
The advantages of high ligation and stripping include definitive removal of the saphenous vein causing reflux as well as the ability to perform concomitant stab phlebectomy for varicose veins. Further, the longest-term outcome data exists for saphenous vein ligation and stripping. However, this operation has procedure-specific complications including groin incision non-healing, damage to the saphenous nerve, bleeding into the saphenous vein tract, as well as small risk of VTE. Further, if performed under general anesthesia, the risks inherent in this type of anesthesia apply as well. Despite all of this, recurrence remains as high as ~20-30% at 2 years.

7. Great Saphenous Vein Incompetence
Advent of endovenous ablation using laser, RF or sclerosing agents has challenged surgery for GSV reflux
Initial VNUS Closure data (2000): 92% freedom from GSV reflux at 2 years and no neovascularization
Closure Study Group: 84% occlusion at 5 years in their registry
Min et al. EVLA series: 93% occlusion at 2 years
Emergence and widespread adoption of endovenous ablation techniques have really challenged the role of surgery for saphenous reflux. Early VNUS Closure data revealed 100% closure at 6 months and 92% freedom from GSV reflux at 2 years and no cases of neovascularization. 5 year data from the Closure Study Group revealed durability in 84% of treated limbs. Regarding laser ablation, similar closure rates were observed at two years in multiple studies, including that published by Min and others.

8. Great Saphenous Vein Incompetence
Multiple trials comparing EVLA and high ligation and stripping (HL/S) have demonstrated similar safety and efficacy including similar rates of recurrence at often 1 to 2 years
Gauw et al. (2016): RCT of EVLA vs HL/S
Higher duplex US recurrence in EVLA vs HL/S (49% vs 23%, p=0.02)
Higher clinical recurrence in EVLA vs HL/S (33% vs 17%, p=0.04)
Higher neovascularization of incompetent GSV tributaries at the SFJ in EVLA (31%) vs HL/S (7%)
Equivalent CEAP, QoL, and symptom relief at 5 years
Previous 5-year RCT data by Rasmussen et al. (2013) demonstrated no difference in occlusion or recurrence
Rass, et al. (RELACS, 2015):
Demonstrated significantly higher duplex recurrence in EVLA
No difference in clinical recurrence rate
Significantly higher same-site recurrence in EVLA, however
At this point, multiple trials comparing laser ablation or radiofrequency ablation to high ligation and stripping have been published. Often they publish short- to mid-term data with similar occlusion and recurrence rates at 1-2 years. However, new evidence from a trial published in this month’s issue of JVS wherein EVLA was compared to high ligation and stripping and was found to have significantly higher recurrence rates on duplex ultrasound at 49% and clinically at 5 years, with a higher rate of neovascularization of GSV tributaries in EVLA versus HL/S. Symptoms and quality of life scores remained similar despite these findings. This report is out of line with previous 5-year data for the 980nm laser published by Rasmussen wherein no differences in occlusion or recurrence rates were observed. It is partially in keeping with findings of the RELACS study published last year which found significantly higher duplex recurrence rates in EVLA at 5 years (28% vs 5%, p<0.001) but equivalent rates of recurrent varices. The significant finding of that study was that EVLA was associated with higher rates of same site recurrence (18% vs 5%, p<0.002) compared to HL/S which had significantly higher different site recurrences (50% vs 31%, p<0.002).

9. Great Saphenous Vein Incompetence
Cochrane Database review performed in 2014 comparing ultrasound guided sclerotherapy, RFA, EVLA and HL/S concluded that all of these modalities are “at least as effective” as surgery
Given the body of data supporting the safety and efficacy of endovenous ablation and its significantly lower convalescence and morbidity, SVS guidelines (2011) now recommend endovenous thermal ablation over HL/S
Finally, a Cochrane database review published in updating a prior review in 2011 that compared ultrasound guided foam sclerotherapy, RFA, EVLA and high ligation and stripping found that all of the newer treatment modalities are “at least as effective” as open surgery. In 2011, given the data at the time, based on the promising short and mid-term data for endovenous thermal ablation with respect to reduced recovery time, lower pain and morbidity, they gave a GRADE 1B recommendation for use of RFA or EVLA as a first-line for treatment of the incompetent saphenous vein over high ligation and stripping.

10. Recurrent Varicose Veins after GSV Intervention
Rate of recurrent varicose veins after surgery (REVAS) is published at 20-80% between 5 and 20 years
Cochrane review (2004): Data comparing phlebectomy to sclerotherapy revealed better performance of sclerotherapy within the first year, the benefit declined between 1 and 3 years and surgery was superior at 3 to 5 years
SVS guidelines recommend any available modality-- surgical, endoluminal or sclerotherapy—depending on the cause, location, extent and source
Regarding recurrent varicose veins after saphenous intervention, which is historically reported at 20% at 5 years and up to 80% by 20 year follow-up, a Cochrane review published in 2004 looked at data comparing phlebectomy to sclerotherapy and revealed better intial performance of sclerotherapy, a benefit that declined to inferiority by years 3 through 5 of follow-up with surgical removal being superior. The SVS guidelines make a weak recommendation (2C) based on the observational studies and case reports of all techniques and recommend any modality that is felt to be appropriate based on the etiology, source, location or extent of the recurrent varicosities.

11. Small Saphenous Vein Incompetence
Surgery associated with sural nerve damage (2-4%) and common peroneal nerve damage (5-7%)
No evidence that flush ligation of SSV is superior
Ligation 3-5cm distal to saphenopopliteal junction is recommended with selective invagination stripping of the refluxing segment
EVLA and sclerotherapy associated with ~95% occlusion at 1 year and ~82% occlusion at 6 months, respectively
Sural nerve paresthesias with EVLA reported at 1.3%
SVS guidelines recommend high ligation of the SSV at the knee crease, but offer no supporting rationale
The Achilles’ heel of small saphenous vein ligation and stripping is damage to the sural or common peroneal nerves; the former due to its course alongside the vein, the latter due to exposure of the vein in the popliteal fossa. Evidence does not support flush ligation of the SSV at the saphenopopliteal junction to be superior so ligation ~3-5cm below this level with selective stripping is recommended. Rates of occlusion for EVLA are 95% at 1 year and for sclerotherapy are 82% at 6 months. EVLA is associated with a lower rate of sural nerve damage. The SVS guidelines, with a GRADE 1B recommendation, promote traditional high ligation of the SSV but in the body of their document provide no evidence supporting this nor do they make any comparison of the minimally invasive modalities with ligation and stripping.

12. Perforator Vein Incompetence
Subfascial perforator ligation (Linton procedure) in areas of often compromised, inflamed skin and subcutaneous tissue was fraught with incision complications
Advent of endoscopic perforating vein surgery has been associated with a substantial decrease in incisional complications
Meta-analysis of SEPS versus historic Linton procedure data reveals OR of wound infections of 0.06 (95% CI )
North American SEPS registry (C5-C6 disease): Wound healing rates were 88% at 1-year with a median healing time of 54 days; recurrence was 28% at 2 years
Nelzen et al. (2000): SEPS performed in a cohort in which 89% received concomitant saphenous surgery revealed 87% ulcer healing and recurrence of 8 and 18% at 3 and 5 years, respectively
SVS guidelines still recommend the use of SEPS in C5-C6 disease
Finally, regarding perforator vein incompetence, the historic Linton procedure was fraught with wound complications following surgery given the compromised skin in these patients. The advent of SEPS was welcome given its ability to successfully treat perforator insufficiency at a fraction of the wound complications. Wound healing rates from the North American SEPS registry were impressive at 88% at 1 year with a median healing time of 54 days. The recurrence rate however, was 28%. Prospective data collected by Nelzen and others combining SEPS with concomitant saphenous surgery revealed an 87% ulcer healing and recurrence of only 18% at 5 years. The SVS guidelines still recommend treatment of perforators with >500ms reflux, diameter >3.5mm associated with C5-C6 disease. They recommend SEPS as the procedure of choice, a weak recommendation, although at that time there was limited data and few published studies on the closure rates and ulcer healing rates associated with perforator vein ablation. The next set of guidelines may reflect changing practice with a new recommendation depending on published outcomes.

13. Conclusions
We’ve come a long way since high ligation and stripping is no longer the gold standard for treating great saphenous vein reflux*
Larger randomized-controlled trials comparing long-term (>5 years) occlusion and recurrence rates, adverse effects, cost and QoL of all modalities are still warranted
However, surgical intervention still has an enduring role:
Endovenous ablation is technically impossible or relatively contraindicated:
Significant tortuosity of GSV or its branches
GSV >15mm or aneurysmal SFJ
Acute thrombosis of the GSV
Chronic thrombophlebitis of the GSV
Large varicosities immediately under the skin
Hepatic dysfunction limiting anesthetic use
Role in recurrence where endoluminal or sclerotherapy options are not feasible
Small saphenous vein
Perforating veins as a primary therapy or failed ablation/sclerotherapy
Adjunctive phlebectomy during endovenous ablation therapies
Capital costs
Physician comfort with newer procedures
Remains the reliable treatment standard in countries where ablation/sclerotherapy are not widely available
In summary, the history of treating saphenous vein reflux has undergone significant change over the past 125 years. Larger, randomized controlled trials need to be performed to assess occlusion and recurrence rates, cost and quality of life at greater than 5 year follow-up given all of the possible modalities for treating saphenous vein disease. So what is the role of surgery in 2016? Based on the most recent clinical practice guidelines, it is indispensible for treating GSV reflux in patients who are contraindicated to endovenous thermal ablation or have anatomy that make it technically impossible: large GSVs >15mm, aneurysmal SFJ, acute thrombosis of the GSV, chronic GSV thrombophlebitis, large varicosities under the skin and significant tortuosity of the GSV precluding catheter advancement to the SFJ. Further, it is recommended for treatment of recurrent varicose veins, small saphenous vein reflux and perforator vein reflux associated with C5-C6 disease, however these recommendations may change. Thank you for the opportunity to discuss this interesting topic today.
*For now

14. References
Gloviczki P, et al. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011 May;53(5 Suppl):2S-48S.
Howard A, Howard D, Davies A (2009). Surgical treatment of the incompetent great saphenous vein. In Gloviczki P (Ed.) Handbook of Venous Disorders: Guidelines of the American Venous Forum (3rd Edition). London (Hodder Arnold).
Coughlin PA, Berridge DC. Is there a continuing role for traditional surgery? Phlebology. 2015 Nov;30(2 Suppl):29-35. 
Dwerryhouse S, et al. Stripping the long saphenous vein reduces the rate of reoperation for recurrent varicose veins: five-year results of a randomized trial. J Vasc Surg. 1999 Apr;29(4):
Gauw SA, et al. Five-year follow-up of a randomized, controlled trial comparing saphenofemoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anesthesia. J Vasc Surg. 2016 Feb;63(2):420-8.
Rass K, et al. Same Site Recurrence is More Frequent After Endovenous Laser Ablation Compared with High Ligation and Stripping of the Great Saphenous Vein: 5 year Results of a Randomized Clinical Trial (RELACS Study). Eur J Vasc Endovasc Surg. 2015 Nov;50(5):
van der Velden SK, et al. Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins. Br J Surg. 2015 Sep;102(10):
Biemans AA, et al. Comparing endovenous laser ablation, foam sclerotherapy, and conventional surgery for great saphenous varicose veins. J Vasc Surg. 2013 Sep;58(3):
Nesbitt C, et al. Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus open surgery for great saphenous vein varices. Cochrane Database Syst Rev. 2014 Jul 30;7:CD
Rigby KA, et al. Surgery versus sclerotherapy for the treatment of varicose veins. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD
Luebke T, Brunkwall J. Meta-analysis of subfascial endoscopic perforator vein surgery (SEPS) for chronic venous insufficiency. Phlebology. 2009 Feb; 24(1): 8-16.
Perrin M. Recurrent varices after surgery (REVAS), a consensus document. REVAS group. Cardiovasc Surg. 2000 Jun;8(4):
Rasmussen L, et al. Randomized clinical trial comparing endovenous laser ablation and stripping of the great saphenous vein with clinical and duplex outcome after 5 years. J Vasc Surg. 2013 Aug;58(2):421-6.

15. Great Saphenous Vein Incompetence
SVS recommended techniques to reduce complications and recurrence:
GSV high ligation and inversion stripping from the groin to the knee (not the ankle)
Post-operative compression bandages reduce hematoma formation
Invagination/inversion stripping techniques have reduced rates of hematoma formation
Oversewing the saphenous vein stump with non-absorbable suture to prevent endothelial exposure reduces neovascularization
Ligation of GSV tributaries to their second branch reduces recurrence
Performance of segmental stripping techniques (CHIVAS or ASVAL) is limited to select patients with varicose veins by surgeons familiar in these techniques