Endophlebectomy of the common femoral vein and endovascular iliac vein recanalization for chronic iliofemoral venous occlusion

Endophlebectomy of the common femoral vein and endovascular iliac vein recanalization for chronic iliofemoral venous occlusion Mert Dumantepe, Selim Aydin, Murat Ökten, and Hasan Karabulut, Istanbul, Turkey

ABSTRACT Background: Chronic post-thrombotic occlusion of the iliofemoral veins causes significant morbidity, which can be alleviated if venous drainage is restored. We report our technique of surgical endophlebectomy and patchplasty of the common femoral vein (CFV) in conjunction with iliac vein stenting to restore venous flow from the infrainguinal venous system to the vena cava. Methods: There were 157 patients who underwent CFV endophlebectomy combined with iliocaval recanalization. Questionnaires were completed both preoperatively and postoperatively to allow comparison. These included the Clinical, Etiology, Anatomy, and Pathophysiology clinical classification; the Venous Clinical Severity Score; the Villalta scale; the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms; and the 36-Item Short Form Health Survey quality of life questionnaire. Results: Mean follow-up duration was 14.4 6 2.9 months (range, 10-29 months). The mean preoperative Venous Clinical Severity Score was 15.3 6 2.2, and this fell to 6.1 6 1.8 after treatment (P < .001). The mean preoperative Villalta score dropped from 12.7 6 2.6 to 6.3 6 1.4 (P < .001). The quality of life and symptom severity scores were improved after 3 months by 17.2 points for quality of life (P < .001) and 20.5 points for symptom severity (P < .001). Primary patency was 81% (124/153) and secondary patency was 89.5% (137/153) at 12 months. Wound complications related to groin incision and lymphatic fistulas were observed in 22.8% (35/153) and 28.7% (44/153), respectively. Conclusions: The hybrid operation of CFV endophlebectomy in conjunction with iliac vein recanalization should be considered a safe and effective treatment option in patients with severe post-thrombotic syndrome and iliofemoral venoocclusive disease. (J Vasc Surg: Venous and Lym Dis 2019;-:1-11.) Keywords: Deep venous thrombosis; Post-thrombotic syndrome; Endophlebectomy; Iliac vein stenting; Quality of life

Chronic venous occlusion of the common femoral vein (CFV) and iliocaval venous segment is associated with severe and continuous post-thrombotic morbidity.1,2 Chronic stenosis or occlusion of the iliac veins can be successfully treated with balloon angioplasty and stenting in most cases.3,4 However, chronic occlusion of the CFV, which may be concomitant with iliac veno-occlusive disease, presents an added challenge. After balloon angioplasty, partial obstruction or stenosis of the CFV can persist, leading to inadequate drainage of the femoral and profunda femoris venous systems, thereby cancelling the benefit of iliac vein recanalization and risking rethrombosis. Stent implantation below the inguinal

From the Department of Cardiovascular Surgery, Acibadem University School of Medicine. Author conflict of interest: none. Correspondence: Mert Dumantepe, Barbaros Mah. Gül Sokak, Agaoglu Starland Sitesi, E-2 Blok, D:43, Batı Atas¸ehir, 34662 Istanbul, Turkey (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvsv.2019.11.008

ligament with venous Wallstents (Boston Scientific, Marlborough, Mass) has been reported with poor patency rates and high stent-related complications. Furthermore, stenting below the inguinal ligament with newgeneration nitinol stents has reasonable and accepted patency in venous reconstruction in contrast to arterial interventions. On the other hand, if CFV stents diminish venous flow from the deep femoral vein, postthrombotic symptoms will worsen. It has been recommended that iliac vein stenting could be combined with surgical removal of the obstructive element from the CFV, its side branches, and especially the profunda femoral vein orifice, which is termed endophlebectomy.5,6 The advantage of endophlebectomy in conjunction with iliac vein stenting is the provision of adequate inflow into the stents by securing flow from all major side branches of the CFV, which should reduce the risk of rethrombosis. We describe patients with severe post-thrombotic syndrome (PTS) who underwent a hybrid procedure of CFV endophlebectomy in conjunction with iliocaval recanalization, restoring unhindered venous flow from the infrainguinal veins to the vena cava. This study evaluated the efficacy, safety, and impact on quality of life of this hybrid venous recanalization procedure. 1

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METHODS Between April 2014 and November 2017, there were 157 patients suffering from severe post-thrombotic iliofemoral obstruction who underwent endophlebectomy and intraoperative endoluminal iliofemoral/caval recanalization in Acibadem University School of Medicine, Department of Cardiovascular Surgery. PTS was described by clinical findings. PTS symptoms had to be present in combination with post-thrombotic trabeculations extending from the iliac or caval veins into the CFV over the ostium of the femoral and deep femoral vein. To evaluate these symptoms, the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, the Venous Clinical Severity Score (VCSS), and the Villalta score have been used. The severity and extension of post-thrombotic changes were determined through Doppler ultrasound (DUS) examination and magnetic resonance venography (MRV). Patients were observed for a minimum of 12 months postoperatively from enrollment in the study. Treatment success was defined as the patency rate, reduced venous claudication, disappearance of abdominal or pelvic collaterals, and ulcer healing rate. Written informed consent was obtained from the patient or from the patient’s family after the aims and the risks of the treatment were fully explained. The Institutional Committee of Ethics in Research approved this clinical research project. Quality of life. The Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) questionnaires were completed preoperatively and readministered postoperatively. The VEINES-QOL/Sym questionnaires are composed of 25 items; 10 items assess symptoms, 9 items are related to limitations in daily activities, 1 item assesses changes during previous years, and 5 items evaluate the psychological impact of deep venous thrombosis (DVT). All items are measured on a 2- to 7-point Likert scale of frequency, severity, or agreement. Two scales are calculated from the completed questionnaire: the VEINESQOL score, which measures the overall quality of life of venous occlusive disease patients; and the VEINES-Sym score, which measures symptom severity.7 Inclusion criteria. Enrolled patients were older than 18 years with a life expectancy of at least 1 year and presented with a history of extensive iliofemoral DVT for at least 12 months. Patients had a Villalta score higher than 12 and had failed to respond to at least 6 months of conservative therapy. The degree of stenosis induced by chronic endoluminal changes of previous DVT is difficult if not almost impossible to quantify. Therefore, symptoms that can be attributed to venous obstruction and that adversely affect the patient’s quality of life, in the presence of chronic

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ARTICLE HIGHLIGHTS d

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Type of Research: Single-center, retrospective cohort study Key Findings: Endophlebectomy of the common femoral vein with endovascular recanalization of iliac veins was performed in 157 patients. Primary patency was 81% and secondary patency was 89.5% at 12 months. A reduction of venous claudication after successful treatment was found in 92.1% of patients. The mean postoperative Venous Clinical Severity Score and Villalta score were significantly improved (P < .001). Patients showed a significant increase in Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms scores. Take Home Message: This retrospective singlecenter study evaluated the feasibility, efficacy, safety, and impact on quality of life of a hybrid approach for venous recanalization of 157 patients with extensive chronic iliofemoral deep venous thrombosis. The authors suggest that the combination of endophlebectomy, iliac vein stenting, and arteriovenous fistula creation for patients with severe post-thrombotic syndrome is feasible, effective, and safe.

endoluminal changes of previous DVT on either duplex ultrasound or venography, were defined as our criteria for endophlebectomy. Significant venous disease was defined as CEAP class C4 to C6; the presence of venous claudication or chronic pain; post-thrombotic occlusion, trabeculations, fibrosis, and synechiae in the external iliac vein and femoral or deep femoral vein seen on DUS and MRV; or significant deterioration in quality of life, especially due to severe venous claudication or nonhealing venous ulcers. Exclusion criteria. Exclusion criteria were unwillingness to receive or contraindications to prolonged anticoagulation treatment and recent DVT within 1 year.8 Endophlebectomy was contraindicated in patients with a major risk factor for long general anesthesia time, such as low cardiac output, low ejection fraction, <1 year of life expectancy due to cancer, and impaired renal function or allergy to contrast media. Venous claudication. Venous claudication was described as a persistent pain and discomfort in the thigh or calf that presented during the treadmill test and worsened with exercise time. Exercise was performed on a RAM model 870 treadmill (Medisoft, Sorinnes, Belgium). Preoperatively, patients were asked to walk at a set speed of 3.5 km/h and 10% inclination for 1 minute. The postexercise ankle-brachial pressure index (ABPI) was then measured with sphygmomanometers and DUS (Logiq S8 XDClear; GE Healthcare,

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Fig 1. Intraoperative images of endophlebectomy. A, Silastic vessel loops are seen controlling the major and minor side branches of the common femoral vein (CFV). B, After endophlebectomy, most of the fibrotic tissue is removed. C, Patch closure of the venotomy is performed with a bovine pericardial patch. D, An arteriovenous fistula (AVF) is created between the common femoral artery and CFV by use of a ring-reinforced 6-mm polytetrafluoroethylene (PTFE) graft in a loop configuration.

Wauwatosa, Wisc). Patients were asked to walk for a maximum time of 10 minutes (approximately 600 meters) at a speed of 3.5 km/h and 10% inclination after 15 minutes of repose. Venous claudication was recorded as the claudication distance of the affected limb. Patients were required to have normal ABPIs at rest and during walking on the treadmill to confirm a diagnosis of venous claudication. All patients had a full complement of infra-aortic pulses, and there was no clinical evidence of peripheral vascular disease based on resting and postexercise ABPIs (>1.0). The treadmill exercise test was completed preoperatively and readministered postoperatively to all patients for end point analysis. In addition, all patients underwent echocardiography for evaluation of cardiac function and were assessed with DUS for any peripheral artery disease before the operation and creation of an arteriovenous fistula (AVF).

Operative technique. After the standardized diagnostic workup, the surgical procedure took place in a hybrid operating suite under general anesthesia. Access was obtained by ipsilateral ultrasound-guided puncture of the midthigh femoral vein or popliteal vein. Intravascular ultrasound was not used in this study. On occasion, retrograde cannulation through the jugular veins or contralateral femoral vein access was necessary to perform the intervention. We performed recanalization of the iliac vein segment in the supine position and under general anesthesia because venous dilation and stenting are painful and may take some time. A hydrophilic coated guidewire and chronic total occlusion catheter were used to recanalize the entire obstructed venous tract. The iliac venous system and, if necessary, inferior vena cava were sequentially recanalized with balloon dilation.

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Fig 2. A, Venography shows a diseased external iliac vein and a totally occluded left common iliac vein. Multiple collateral veins cross the midline. B, Crossing and balloon angioplasty of the common iliac vein. C, Stenting of left common iliac and external iliac veins after endophlebectomy. D, Completion venography demonstrating unobstructed venous drainage from the common femoral vein (CFV) into the vena cava.

If the lower extremity venous inflow was inadequate, endophlebectomy including bovine pericardial patch reconstruction of the CFV was performed. All endophlebectomies were unilateral; simultaneous bilateral endophlebectomies were not performed in this cohort of patients. Complete dissection of the CFV and meticulous preservation of all the side branches are essential for obtaining sufficient venous inflow to the stented iliac segment. The great saphenous vein, femoral vein, profunda vein, and CFV were dissected and looped with Silastic tapes (Fig 1, A). Patients were anticoagulated with 100 IU/kg of unfractionated heparin. After the venotomy was performed, the dense synechiae and endoluminal fibrous tissue were excised (Fig 1, B). The aim of adequate endophlebectomy is to remove all intraluminal synechiae and post-thrombotic trabeculations. Because of chronic recanalization, these trabeculae may have many free septa and surfaces lined with endothelium and may tightly adhere to the venous wall. The

obstructive element is usually made up of collagen, which is unlike atheroma, and it is difficult to find clearly defined planes unless all the synechiae are excised. The Watson Cheyne dissector typically works well, although in some areas, because of the extension of collagen in some venous branches, excision with Potts scissors is required. The release of the Silastic loops or clamps from the profunda vein or other branches helps to show that sufficient venous flow of branches is achieved. The fibrotic material of chronic endoluminal scar tissue can be lifted en masse from the venous wall and removed from the CFV as much as possible. Patch closure of the venotomy was performed with bovine pericardial patch material (Fig 1, C); in addition, an AVF can then be created between the common femoral artery and CFV by use of a ring-reinforced 6mm polytetrafluoroethylene (PTFE) graft. The fistula was given a loop shape to simplify later percutaneous plug occlusion, and this guarantees a high flow rate in

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the first months with improved hemodynamic performance9 (Fig 1, D). After excision of the obstruction within the CFV, the next phase of the procedure is carried out angiographically. The chronic occlusion was visualized by multiplane venography (Fig 2, A), and balloon angioplasty of the iliofemoral tract was then performed with noncompliant balloon sizes of 12 to 18 mm (12- to 14-mm Armada [Abbott, North Chicago, Ill]; 16- to 18-mm Boston Scientific; Fig 2, B). Venous Wallstents (Boston Scientific) were placed after sequential dilation of the affected areas of the iliac veins (Fig 2, C). In general, 14- to 18-mm Wallstents can be used for the common iliac vein and 12- to 14-mm stents for the external iliac vein. Common iliac or inferior vena cava stents were placed initially, followed by stenting of the external iliac vein. Completion venography was performed after venoplasty and stenting, which demonstrated clear and unobstructed venous drainage into the inferior vena cava (Fig 2, D). The intraoperative heparin was not reversed, and therapeutic anticoagulation was continued. Postoperative care. Patients received an intermittent pneumatic compression stocking until completely mobilized after successful recanalization. Ogawa et al10 demonstrated the significant contribution of this pneumatic compression. Oral anticoagulation was not stopped before surgery and was continued after the operation if the patient was already receiving oral anticoagulation. In all others, low-molecular-weight heparin was started twice daily directly after the intervention for 1 week; warfarin and clopidogrel were started the next day if no active bleeding was present, aiming at an international normalized ratio of 3 to 3.5. Clopidogrel was discontinued at 12 weeks postoperatively. Anticoagulation was continued for at least 6 months with warfarin or rivaroxaban (Xarelto; Bayer Pharma, Whippany, NJ). Patients were scheduled for a second hospital admission for permanent AVF closure if no stenoses were found on duplex ultrasound examination 6 to 8 weeks after endophlebectomy. During this procedure, the AVF was temporarily closed by balloon occlusion through a contralateral transfemoral approach. If stent flow was deemed sufficient, the AVF was permanently closed with an Amplatzer vascular plug (St. Jude Medical, St. Paul, Minn). During the follow-up examinations after 1 week, 4 weeks, 3 months, and 6 months and annually, DUS was performed to evaluate the patency of the recanalization. There are no effective and validated diagnostic tests currently available to quantify hemodynamic parameters associated with calculation of sufficient stent flow. We measured the flow velocity at the inflow and outflow site of the stented segment with DUS and washout time of contrast media. There are no agreed on criteria of sufficient stent flow, and therefore the

decision to close the fistula was based on the judgment of the surgeon at the time of the procedure. Statistical analysis. Statistical analysis was performed with GraphPad InStat software (version 3 for Mac; version 11.5; GraphPad Software Inc, La Jolla, Calif). Descriptive statistics were used to present the mean 6 standard deviation or median (range) for continuous variables and the counts (percentages) for categorical variables. The t-test was used to analyze changes in clinical scores. Patency rates were estimated by use of Kaplan-Meier survival analyses based on the total number of legs that received endophlebectomy in conjunction with iliac vein recanalization. P # .05 was used to demonstrate statistical significance. Quality of life data analysis started with paired t-tests and Wilcoxon signed rank tests. Next, repeated measures analysis of variance was done by both an analysis from baseline to 3 months for the larger group of patients and a longitudinal analysis from baseline to 1 year for a subset of the group with 1-year results on follow-up.

RESULTS Patient characteristics. A total of 157 patients were treated by endophlebectomy with endoluminal recanalization of the iliofemoral/venacaval segments. Endovascular iliac recanalization was unsuccessful in four patients in our cohort, and these patients underwent a Palma-Dale cross-femoral bypass procedure. Two vascular surgeons were involved in all procedures during the study period. The baseline characteristics are reported in Table I. Mean age was 37.9 6 15.3 years (range, 21-73 years), and 89 were female. Mean body mass index was 26 6 3.5 kg/m2 (range, 19-34 kg/m2); 115 patients had a single episode of DVT (73.2%) and 42 patients had recurrent DVT (26.8%) in the medical history. No patients were included in our study who had prior iliofemoral venous stenting that had been unsuccessful. Twelve patients (7.6%) who had previously undergone an invasive or thrombolytic procedure were included in the study, but all had inadequate recanalization and total or subtotal occlusion in the iliac veins and CFV as shown with DUS and MRV. Median time between the first DVT and operation was 36.5 months (range, 14 months-31 years). Forty-nine patients (31.2%) suffered from venous ulceration (CEAP C6). The left leg was affected in 61.1% (96/157), and both legs were involved in 14% (22/157). Mean procedure time was 235 6 78 minutes (range, 143-426 minutes). The mean length of stay was 6.3 6 3.1 days (range, 5-19 days). We treated the iliac veins unilaterally in 85.3% (134) of patients; furthermore, in 9.5% of patients (15/157), the vena cava was treated simultaneously by venous stent and balloon angioplasty. In 135 patients (88.2%), an adjunctive AVF was performed after venous reconstruction. New-generation selfexpandable nitinol stents (sinus-Venous [OptiMed,

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Table I. Patients’ baseline characteristics (N ¼ 157) Age, years Sex ratio, F:M BMI, kg/m2

37.9 6 15.3 (21-73) 89:67 26 6 3.5 (19-34)

Thrombophilia

69 of 157

Single DVT

115 (73.2)

Recurrent DVT Interval between DVT and treatment, months

42 (26.8) 36.5 (14 months-31 years)

Left-sided DVT

96 (61.1)

Right-sided DVT

61 (38.9)

Bilateral DVT

22 (13.7)

History of pulmonary embolism

22 (14)

Highest CEAP class C4a

27 (17)

C4b

25 (16)

C5

55 (35)

C6

50 (31.8)

VCSS

15.3 6 2.2

Villalta score

12.7 6 2.6

Venous claudication

139 (89)

BMI, Body mass index; CEAP, Clinical, Etiology, Anatomy, and Pathophysiology; DVT, deep venous thrombosis; VCSS, Venous Clinical Severity Score. Continuous data are presented as mean 6 standard deviation (range). Categorical data are given as count (percentage).

Ettlingen, Germany] and Abre [Medtronic, Santa Rosa, Calif]) were used in 5.8% (9/153) of patients. Clinical assessment, patency rates, and reinterventions. Mean follow-up duration was 15.4 6 4.9 months (range, 11-33 months); 136 (88.8%) patients were followed up for 12 months or more and form the basis of the follow-up data beyond the operative period. Reduced venous claudication after successful treatment was seen in 92.1%. Patency rates were assessed after 3 and 6 months and annually on the basis of DUS findings. Primary patency was 81% (124/153) and secondary patency was 89.5% (137/153) at 12 months. Fig 3 shows further details of the patency rate. Only three patients were lost to follow-up and did not complete the surveys, although 98% of patients successfully completed the quality of life questionnaires. At 3 to 6 months after the procedure, 89.7% (44/49) of patients who had venous ulcers were healed. Compared with baseline, all clinical outcome measurements improved at 3 months and after endophlebectomy and iliac recanalization. The mean VCSS preoperatively was 15.3 6 2.2, which fell to 6.1 6 1.8 postoperatively (P < .001). The Villalta score dropped from 12.7 6 2.6 preoperatively to 6.3 6 1.4 postoperatively (P < .001). Patients showed a significant increase in both VEINES-QOL and VEINES-Sym scores. Scores

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improved 17.2 points for quality of life (P < .001) and 20.5 points for symptom severity (P < .001) after 3 months and 19.3 points for quality of life (P ¼ .004) and 22.1 points for symptom severity (P ¼ .003) after 12 months (Table II). The AVF provided high flow through the venous and lymphatic systems, and this increased pressure sometimes caused venous hypertension or edema and swelling of the leg. Almost 20% of the patients reported this temporary pressure overload and swelling until the AVF was closed. All complaints related to this disappeared after percutaneous closure with the Amplatzer vascular plug at 3 months, and this had an impact on all venous scoring systems. The 36-Item Short Form Health Survey quality of life questionnaire showed statistically significant change in three of the eight domains: physical function (13.5 at 3 months [P < .001] and 15.8 at 12 months [P ¼ .012]), bodily pain (11.3 at 3 months [P < .001] and 15.1 at 12 months [P ¼ .015]), and general health (10.7 at 3 months [P ¼ .010] and 13.4 at 12 months [P ¼ .013]; Table III). Reintervention due to early occlusion or stenosis within the first month of venous reconstruction was necessary in 18.3% (28/153) of all cases. Reinterventions were performed with balloon angioplasty and catheter-directed thrombolysis in 14 patients and balloon angioplasty with pharmacomechanical thrombectomy in 8 patients. Surgical thrombectomy was performed in only 3.9% (6/153) of the patients. In six patients, reintervention included extension of the stented tract into the previously treated part of the vein as a result of shortening of the Wallstent and restenosis of the CFV. This was performed with the same Wallstents as had been used for primary stenting. There was only one case of stent fracture; 19% (29/153) of all patients showed a mild stent tapering (not needing reintervention) with <20% of diameter narrowing in the 6-month follow-up. The most common factors in the reintervention group were stent shortening, thrombophilia, and Behçet disease. There were eight thromboses in the reconstructed veins after closure of the AVF at the third month in our cohort of patients. Five patients had stent thrombosis and three patients experienced thrombosis of the endophlebectomy. Four of these patients who came to us with recurrent thrombosis have factor V Leiden mutation. Complications. There were no deaths or pulmonary emboli after the procedure. Because of the increased thrombogenic surface of the CFV after endophlebectomy, our international normalized ratio goal in patients undergoing surgical endophlebectomy is 3.0 to 3.5. Minor bleeding complications occurred in 8.4% (13/153) of all cases without the need for blood transfusion or surgery. In six (3.9%) patients, major bleeding complications (mostly hematoma or bleeding at the surgical site and

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Fig 3. Kaplan-Meier analyses of primary, assisted primary, and secondary patency of the patients treated by endophlebectomy and endovascular recanalization of the iliocaval tract.

one gastrointestinal bleed) had to be treated, and those patients received only blood transfusions. We did not observe early rethrombosis because extended anticoagulation of at least 1 year is used in most patients. Other than reocclusion and CFV stenosis, the most frequent complications were related to the groin incision. Wound complications and lymphatic fistulas could be seen in 22.8% (35/153) and 28.7% (44/153), respectively (Table IV). Thirty-eight patients developed a prolonged lymphatic leak after surgery, which was managed by negative pressure wound therapy and wound dressings; 19 patients needed surgical wound revisions. The femoral

AVF graft and bovine pericardial patch had to be removed because of persistent infection in four patients in whom the AVF was already occluded.

DISCUSSION Iliofemoral venous occlusive disease is the major cause for development of venous hypertension and PTS. Whereas endovascular recanalization has become the method of choice for restoring patency to the iliac venous system, infrainguinal obstruction of the CFV remains a problem.4,5 In cases with post-thrombotic occlusion extending below the inguinal ligament, venous

Table II. Overall Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/ Sym) scores (disease specific) and results of paired t-test analysis at baseline (T0), after 3 months (T3), and after 1 year (T12)

VEINES-QOL No. VEINES-Sym No.

T0

T3

P valuea (trend)

P valueb (group)

T12

P valuec (trend)

P valued (group)

49.4 (18.5)

66.6 (22.1)

<.001

.008

68.7 (23.4)

.004

.078

153

153

152

136

135

47.7 (21.3)

68.2 (23.6)

<.001

69.6 (25.5)

.003

153

151

150

136

135

.128

Values are reported as mean (standard deviation). a P value of paired t-test (T0-T3). b P value of group difference in trends (T0-T3) by repeated measures analysis of variance. c P value of paired t-test (T0-T12). d P value of group difference in trends (T0-T12) by repeated measures analysis of variance.

.035

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Table III. Overall 36-Item Short Form Health Survey (SF-36) quality of life scores (generic) and results of paired t-test analysis at baseline (T0), after 3 months (T3), and after 1 year (T12) T0

T3

P valuea (trend)

P valueb (group)

T12

P valuec (trend)

59.6 (17.1)

73.1 (18.2)

<.001

.275

75.4 (18.9)

.073

.835

61.1 (27.5)

P valued (group)

.012

.713

.110

.648

.015

.237

.013

.673

.656

.644

.364

.671

.514

.218

.621

.174

SF-36 Physical functioning No. Roledphysical No. Bodily pain No. General health No. Vitality No. Social functioning No. Roledemotional No. Mental health No.

153

153

53.7 (26.5)

58.1 (28.3)

153

153

55.4 (22.9)

66.7 (23.5)

153

151

56.8 (20.1)

67.5 (21.4)

153

152

53.3 (20.9)

57.1 (22.5)

153

151

66.2 (24.8)

70.5 (25.3)

153

150

69.6 (25.1)

73.8 (26.6)

153

152

69.4 (19.2)

72.6 (18.5)

153

151

98 98 <.001

.184

70.5 (22.6)

.010

.442

70.2 (20.9)

98 98 .193

.071

58.6 (21.4)

.146

.487

73.9 (27.2)

98 98 .169

.056

75.7 (24.3)

.152

.032

73.7 (21.1)

98 98

Values are reported as mean (standard deviation). Bold values are considered statistically significant. a P value of paired t-test (T0-T3). b P value of group difference in trends (T0-T3) by repeated measures analysis of variance. c P value of paired t-test (T0-T12). d P value of group difference in trends (T0-T12) by repeated measures analysis of variance.

inflow may be inadequate and adversely influence results of iliac vein stenting.11 Furthermore, the problem with extending stents below the inguinal ligament is that it is possible to extend the stents only into one of the branches, either the femoral vein or the deep femoral vein. Despite the increased risk of occlusion, many DVT patients need stenting into the CFV to adequately treat areas of residual stenosis that, if left untreated, might lead to recurrent thrombosis.12 Endophlebectomy in this scenario becomes an attractive option, either with or without iliac vein stenting, to provide outflow to the profunda vein, which otherwise is “axially transformed” in chronic iliofemoral DVT.13,14 Endophlebectomy was first described in 1964 by Manabe15 in the inferior vena cava for Budd-Chiari syndrome. Hybrid techniques were developed by Garg et al,16 and further experience was reported by Comerota et al17 and Grommes et al.18 Neglén et al19 described the method of endovascular recanalization of the iliofemoral venous occlusion and published the largest study to date on the technique in 2006 (n ¼ 982 patients and 464 with PTS). In a majority of patients, they used Wallstents. Mortality was 0%; the primary patency rate was 57% in PTS patients after 72 months, and the secondary patency rate was 86%. They have demonstrated a significant improvement in the patients’ quality of life.

Because the iliofemoral venous segment is the only venous outflow from the leg, it is understandable that obstruction of this segment causes severe postthrombotic morbidity. Puggioni et al5 described endophlebectomy of 23 vein segments in 13 patients in 2004. They focused on the occlusive component of PTS, as indications were either to enhance inflow into reconstructed CFV segments to allow valve repair or to increase lower extremity venous outflow. They reported a primary patency rate of 77% after a median of 8 months. Last, de Wolf et al20 reported endophlebectomy of the CFV in conjunction with PTA and stenting in 70 patients. Median follow-up was 1 year. Primary and secondary patency rates at 12 months were 51% and 83%, respectively. The Villalta score had decreased 7 points at 1-year follow-up; 60% of loss of primary patency was due to CFV stenosis or occlusion. Other complications related to groin incision included wound infection (29%) and lymphatic leak (39%), similar to our study. According to this study, endophlebectomy combined with iliac vein recanalization resulted in noteworthy improvement in the clinical signs and symptoms of PTS in patients clinically followed up to 12 months. The existing literature on endophlebectomy combined with iliac vein stenting is limited; in most series, it was performed for milder venous disease (CEAP C3 or lower), and 46% to 94% of patients in these series did not have

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Table IV. Complications (n ¼ 153 patients) Reocclusion

28 (18.3)

Pulmonary embolism

0 (0)

Stenosis distal to stents

31 (21)

Wound infection

35 (22.8)

Lymphatic leak

44 (28.7)

Minor bleeding

13 (8.4)

Major bleeding

6 (3.9)

Paresthesia

8 (5.2)

Heparin-induced thrombocytopenia

2 (1.3)

Bladder infection

3 (1.9)

Mild stent tapering (not needing reintervention)

29 (19)

Stent kinking

14 (9.1)

Residual stent compression

4 (2.6)

Proximal stent placed too distally

2 (1.3)

Stent fracture Mortality

1 (0.6) 0 (0)

Values are reported as number (%).

any ulcers.6,9 However, endophlebectomy has been recommended for healing of venous ulcers in patients with C4 and above disease in the Society for Vascular Surgery guidelines for venous ulcer management.21 Wound complications (infection, lymphorrhea, and hematoma) are the most common complications in our series and in previously published literature. Therefore, this type of hybrid operation should be considered only in patients who are impaired in their daily life, patients with CEAP C4 disease and above, and particularly patients who have acute or chronic venous leg ulcers. To our knowledge, no effective and validated diagnostic tests are currently available to quantify hemodynamic parameters to determine whether there is an indication for an endophlebectomy. Adequate venous inflow from the lower extremity plays a significant role in patency and clinical improvement. Previous literature findings show lower patency rates and subsequently deterioration of clinical outcome whenever inflow is inadequate.22 However, precise measurement of inflow and outflow at the level of the CFV is presently not possible. Therefore, inclusion or exclusion criteria for endophlebectomy combined with iliac vein recanalization are usually based on signs of post-thrombotic scar tissue through the CFV confluence identified on DUS, MRV, or venography with or without intravascular ultrasound.23 These parameters include location and extension of post-thrombotic trabeculations, percentage of luminal narrowing, and number and extent of collateral veins. Consequently, the decision to perform endophlebectomy was based on the surgeon’s judgment with consideration of these diagnostic findings and postthrombotic changes. Therefore, this is one of the limitations of this operation as others in less experienced

clinics may have difficulty in deciding which patients are suitable for intervention. After removal of the obstructive element from the CFV and restoration of the flow with this hybrid procedure combined with proper anticoagulation, there was still a highly thrombogenic surface at the level of endophlebectomy caused by both surgical damage to the vessel wall and the stent material. This is why we often prefer endophlebectomy combined with an AVF to enhance flow to the treated area and to reduce the risk of rethrombosis.5,6,20 Although AVF is required to ensure adequate flow into the stented iliac tract, additional support of the remodeling process in the endophlebectomy space allows endothelial coverage of the stents to prevent postprocedural thrombosis.9,24 We frequently prefer a loop-shaped AVF with a 6-mm ring-reinforced PTFE graft that is anastomosed between the common femoral artery and CFV. We learned that native fistulas are too small usually or, when created with a diameter >5 to 6 mm, need to be closed surgically before 8 weeks because of persistent lymphedema and swelling of the leg. The major benefit of using a loop-shaped PTFE graft is that it guarantees a high flow rate in the first months and that it can be percutaneously closed with an Amplatzer vascular occluder plug. The long-term effects of femoral AVF are still unknown. Potential complications might be intimal hyperplasia due to shear stress and cardiac overload.25 Therefore, all patients were scheduled for endovascular plug closure of the AVF 6 weeks to 3 months after the intervention. Temporary balloon occlusion of the AVF was performed for venous outflow assessment of the leg. After contralateral transfemoral access, a long sheath was positioned in the CFA; thereafter, the AVF loop was catheterized and a 6-mm noncompliant balloon was placed inside the AVF. Angiography was performed through the balloon catheter lumen after balloon occlusion; if the venous flow was deemed sufficient, the AVF was closed with an Amplatzer plug. Regarding the literature, adequate venous flow was described as an arbitrary cutoff of contrast material washout of 4 seconds. When flow was presumed insufficient, the AVF was not closed.26 No patients were believed to have inadequate flow through the reconstruction at the time of AVF test occlusion in our cohort. There is currently no published data on the appropriate time for closing the AVF, but some centers perform this procedure between 6 and 8 weeks, which is shorter than in our protocol. In our study group, the AVF is mostly closed at the 3-month time point. We believe that the remodeling process in the endophlebectomy space and adequate endothelial coverage of the stents are complete at the third month. Compared with clinical outcome measurements after endophlebectomy and iliac recanalization, the mean VCSS and Villalta score dropped significantly in the postoperative period (P < .001). Furthermore, patients

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Dumantepe et al

Journal of Vascular Surgery: Venous and Lymphatic Disorders ---

showed a notable improvement in VEINES-QOL/Sym scores. Improvements in the bodily pain and physical functioning scores might be elucidated by the nature of DVT, whereby venous outflow is occluded and leads to increased venous pressure in the lower limbs, which causes pain, swelling, heaviness, skin changes, and venous ulcers. When the venous obstruction is treated, these symptoms will disappear, and quality of life scores eventually increase.27 According to our results and practices, a wound healing disorder related to the groin incision has to be seen as one of the most compelling parts of this treatment as the patency of the venous recanalization is markedly decreased in case of wound complications. On the other hand, wound complications have an important effect on the postoperative quality of life assessments, specifically in patients who suffered chronic DVT with venous leg ulcers. Obesity (body mass index >30 kg/m2), sustained lymphatic leak and lymphorrhea after endophlebectomy, female sex, and repeated procedures have higher risks of wound complications according to our singlecenter experience. We believe that the use of negative vacuum therapy is necessary for preventing wound complications. Oral or intravenous intake of antibiotics and a low-protein diet were required in all of the patients for the first 7 days of treatment. Furthermore, for alleviation of lymphatic leak, we recommend BioGlue surgical adhesive (CryoLife, Kennesaw, Ga) for closing microlymphatic vessels. Finally, the relevance of the increased lymphatic outflow from the leg has not yet been assessed. A change in lymphatic drainage of the legs in patients suffering from PTS could be demonstrated by the use of isotopic lymphography.28 Preoperative lymph drainage therapy might also influence outcome. Further investigation should focus on this issue. Limitations of this study are that data were collected retrospectively and not all patients completed 2 years of follow-up. Furthermore, a learning curve of this hybrid treatment may affect our patients’ outcome and also represents an early and midterm experience. However, the procedure and follow-up were standardized, and patency rates and clinical scores were both collected.

CONCLUSIONS Endovenous recanalization of post-thrombotic veins with sequential balloon angioplasty and venous stenting is rapidly gaining in popularity. However, in the case of femoral involvement, sufficient venous inflow from the CFV into the iliac veins is required. CFV endophlebectomy combined with iliocaval endovascular recanalization is safe and effective for treatment of patients with chronic extensive iliofemoral veno-occlusive disease. Unhindered venous flow from the CFV to the iliac veins and vena cava, resulting in better quality of life, reduced postthrombotic morbidity.

2019

AUTHOR CONTRIBUTIONS Conception and design: MD, SA, MÖ, HK Analysis and interpretation: MD, SA, MÖ, HK Data collection: MD, SA, MÖ, HK Writing the article: MD, SA, MÖ, HK Critical revision of the article: MD, SA, MÖ, HK Final approval of the article: MD, SA, MÖ, HK Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: MD

REFERENCES 1. Delis KT, Bountouroglou D, Mansfield AO. Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg 2004;239:118-26. 2. Akesson H, Brudin L, Dahlstrom JA, Eklöf B, Ohlin P, Plate G. Venous function assessed during a 5-year period after acute ilio-femoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990;4:43-8. 3. Neglen P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007;46:979-90. 4. Kolbel T, Lindh M, Akesson M, Wassèlius J, Gottsäter A, Ivancev K. Chronic iliac vein occlusion: midterm results of endovascular recanalization. J Endovasc Ther 2009;16:483-91. 5. Puggioni A, Kistner RL, Eklof B, Lurie F. Surgical disobliteration of postthrombotic deep veinsdendophlebectomydis feasible. J Vasc Surg 2004;39:1048-52. 6. Vogel D, Comerota AJ, Al-Jabouri M, Assi ZI. Common femoral endovenectomy with iliocaval endoluminal recanalization improves symptoms and quality of life in patients with postthrombotic iliofemoral obstruction. J Vasc Surg 2012;55:129-35. 7. Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patientreported measure of symptoms and quality of life. J Vasc Surg 2003;37:410-9. 8. Templeton JY III. Endovenectomy for the relief of obstruction of the superior vena cava. Am J Surg 1962;104:70-6. 9. Kurstjens RL, de Graaf R, Barbati ME, de Wolf MA, van Laanen JH, Wittens CH, et al. Arteriovenous fistula geometry in hybrid recanalisation of post-thrombotic venous obstruction. Phlebology 2015;30(Suppl):42-9. 10. Ogawa T, Hoshino S, Midorikawa H, Sato K. Intermittent pneumatic compression of the foot and calf improves the outcome of catheter-directed thrombolysis using low-dose urokinase in patients with acute proximal venous thrombosis of the leg. J Vasc Surg 2005;42:940-4. 11. Neglén P, Raju S. In-stent recurrent stenosis in stents placed in the lower extremity venous outflow tract. J Vasc Surg 2004;39:181-7. 12. Raju S, Darcey R, Neglén P. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg 2010;51: 401-8. 13. Hartung O, Otero A, Boufi M, De Caridi G, Barthelemy P, Juhan C, et al. Mid-term results of endovascular treatment for symptomatic chronic nonmalignant iliocaval venous occlusive disease. J Vasc Surg 2005;42:1138-44. 14. de Graaf R, Arnoldussen C, Wittens CH. Stenting for chronic venous obstructions a new era. Phlebology 2013;28(Suppl 1): 117-22.

Journal of Vascular Surgery: Venous and Lymphatic Disorders Volume

-,

Number

Dumantepe et al

11

-

15. Manabe H. Endovenectomy for the surgical treatment of Budd-Chiari syndrome. Jpn Circ J 1964;28:183-6. 16. Garg N, Gloviczki P, Karimi KM, Duncan AA, Bjarnason H, Kalra M, et al. Factors affecting outcome of open and hybrid reconstructions for nonmalignant obstruction of iliofemoral veins and inferior vena cava. J Vasc Surg 2011;53:383-93. 17. Comerota AJ, Grewal NK, Thakur S, Assi Z. Endovenectomy of the common femoral vein and intraoperative iliac vein recanalization for chronic iliofemoral venous occlusion. J Vasc Surg 2010;52:243-7. 18. Grommes J, Gombert A, Barbati ME, von Trotha KT, Schleimer K, Jalaie H. Deep veins: hybrid procedure for treatment of iliofemoral obstruction. Zentralbl Chir 2017;142: 487-91. 19. Neglén P, Berry MA, Raju S. Endovascular surgery in the treatment of chronic primary and post-thrombotic iliac vein obstruction. Eur J Vasc Endovasc Surg 2000;20:560-71. 20. de Wolf MA, Jalaie H, van Laanen JH, Kurstjens RL, Mensinck MJ, de Geus MJ, et al. Endophlebectomy of the common femoral vein and arteriovenous fistula creation as adjuncts to venous stenting for post-thrombotic syndrome. Br J Surg 2017;104:718-25. 21. O’Donnell TF Jr, Passman MA, Marston WA, Ennis WJ, Dalsing M, Kistner RL, et al. Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg 2014;60(Suppl):3S-59S.

22. Neglen P, Tackett TP Jr, Raju S. Venous stenting across the inguinal ligament. J Vasc Surg 2008;48:1255-61. 23. Arnoldussen CW, Toonder I, Wittens CH. A novel scoring system for lower-extremity venous pathology analysed using magnetic resonance venography and duplex ultrasound. Phlebology 2012;27:163-70. 24. Rosales A, Sandbaek G, Jorgensen JJ. Stenting for chronic post-thrombotic vena cava and iliofemoral venous occlusions: mid-term patency and clinical outcome. Eur J Vasc Endovasc Surg 2010;40:234-40. 25. Hammes M. Hemodynamic and biologic determinates of arteriovenous fistula outcomes in renal failure patients. Biomed Res Int 2015;2015:171674. 26. van Vuuren TM, Kurstjens RL, de Wolf MA, van Laanen JH, Wittens CH, de Graaf R. Stent extension into a single inflow vessel is a valuable option after endophlebectomy. Phlebology 2018;33:610-7. 27. Catarinella F, Nieman F, de Wolf M, Wittens C. Short-term follow-up of quality-of-life in interventionally treated patients with post-thrombotic syndrome after deep venous occlusion. Phlebology 2014;29(Suppl):104-11. 28. Partsch H, Mostbeck A. Involvement of the lymphatic system in post-thrombotic syndrome. Wien Med Wochenschr 1994;144:210-3.

Submitted Nov 28, 2018; accepted Nov 25, 2019.