Thurner syndrome or common skeletal vein compression syndrome mainly refers to the long-term compression of the left common iliac vein at its confluence with the inferior vena cava by the right iliac artery that crosses anteriorly and the mechanical effect of its pulsation, resulting in changes such as intimal hypertrophy, intraluminal adhesions, luminal narrowing or occlusion of the left common iliac vein, which in turn causes obstruction of iliac venous return. The pelvic and lower limb venous return obstruction produces a series of clinical symptoms syndrome.
1.Etiology of COCKETT syndrome
1.1 Anatomical factors
The basis of the iliac vein compression syndrome is the special anatomical relationship between the right common iliac artery and the left common iliac vein. The right common iliac vein is almost straight and continuous with the inferior vena cava, while the left common iliac vein is transverse to the right from the left side of the pelvis and joins the inferior vena cava at almost right angles before passing through the lumbosacral vertebrae. The right common iliac artery crosses the left common iliac vein in front of the left common iliac vein and then extends to the lower right side of the pelvis. Nearly 3/3
The right common iliac artery crosses the left common iliac vein at the level of the confluence of the common iliac veins bilaterally in nearly 3/4 of individuals, and at a mildly superior level in 1/5 of individuals, with a few below this point[1,2] .
The left common iliac artery is located anterior to the physiologically anterior lumbar body and posterior to the right common iliac artery, so it is compressed anteriorly and posteriorly and by the pelvic rim. When the body is upright and the lumbosacral region is highly anteriorly inclined, the physiological pronation increases, making the compression more pronounced, and when the body is in a sitting position, the compression is relieved or disappears [ 3 ]. In addition, the left internal iliac artery can also ride in front of the left common or external iliac vein, and the right internal and external iliac arteries can also ride in front of the vein of the same name, and can cause different degrees and types of compression. This anatomical feature creates an important potential disadvantage to iliac vein blood return [ 4, 5 ]. The long-term pulsation of the compressed artery stimulates the production of chronic damage to the intima of the left iliac vein, which eventually leads to pathological changes such as hypertrophy hyperplasia fibrosis of the intima of the vein.
1.2 Structural abnormalities of the vena cava
The presence of abnormal structures in the lumen of the left common iliac vein has been classified by Pinsolle et al [6] into five structural states: (1) ridges, tiny structures that protrude vertically into the lumen in a sagittal position at the junction of the two common iliac veins in a triangular shape; (2) flaps, structures resembling a bird’s nest at the lateral border of the common iliac vein; (3) adhesions, fusion of the anterior and posterior walls of the vein of a certain length and width; (4) bridges, long strip-like structures that divide the lumen into two to three different calibers and spatial orientations; (5) bridges, long strip-like structures that divide the lumen into two to three different calibers and spatial orientations. ～(4) bridges, long strips of structure that divide the lumen into two to three parts of different caliber and spatial orientation; (5) bands, septum-like structures that result in a sieve-like porous change in the lumen [ 7 ]. There are currently two explanations for the production of intraventricular adhesive structures, congenital and acquired.
1.2.1 The basis for considering the lesion as a congenital factor is that, firstly, this abnormal structure in the lumen of the vein is histologically distinct from similar adhesive structures in neoplastic or inflammatory tissues; secondly, embryologically, the right common iliac vein originates exclusively from the right major iliac vein and the left common iliac vein from the fusion of the bilateral major sacral veins, and often forms two or more ducts, and the abnormal structure in the vein The abnormal structures within the veins originate from the incomplete degeneration of these ducts during development [ 8 ].
1.2.2 In terms of the origin of the abnormal structures in the iliac veins, it is currently preferred to be due to the repeated stimulation of the vein wall, i.e., due to the close contact between the right common iliac artery, the lumbosacral spine and the left common iliac vein and the compression and stimulation of the artery by long-term pulsation, which causes chronic injury to the vein lining resulting in intimal hyperplasia, fibrosis and other tissue reactions. The basis for this is: (1) the position of this anatomical structure is fairly constant,
(2) the presence of dense fibrous tissue between the artery and vein; ( 3) the replacement of the normal intimal and mesenteric tissue in the lumen by a neat connective tissue covered with a layer of normal endothelial cells, a structure significantly different from the mechanized thrombus[9] .
1.3 Other factors Other factors are also mostly anatomically related, such as pelvic hematoma compression after blunt trauma [10 ], pelvic adiposity, abdominal cavity, pelvic tumor compression, smooth muscle sarcoma of the hypoplastic abdominal aorta compressing the left common iliac vein, lumbar macromuscular abscess compression due to sigmoid diverticulitis, bladder disease, ectopic kidney, and synovial fluid cyst of the ilium [11 ] can lead to left common iliac vein compression syndrome.
2. Evolution of Cockett’s syndrome
Cockett’s syndrome evolves in 3 phases. In the first phase, the compression alone (continuous arterial pulsation) causes damage to the venous lumen. In the second stage, the first stage changes plus damage to the left common skeletal vein, including the formation of intravenous adhesive bands, requiring surgical treatment to remove the obstruction. In the third stage, skeletal-femoral vein thrombosis.
3.Clinical manifestations of Cockett syndrome
The main clinical manifestation is mild sunken edema of the affected limb, which is progressively aggravated and forms a series of syndromes such as varicose veins of the lower limb, sclerosis, pigmentation, skin soft tissue bruising dystrophy, chronic ulcer, venous claudication and even deep vein thrombosis of the lower limb. There are four types: (1) Asymptomatic: This syndrome may be caused by adhesions near the distal sacral and arterial compression of the left common iliac vein, and is often asymptomatic, often found during angiography for other diseases. (2) Lower limb edema: This type mainly presents with lower limb edema, capillary dilation and varicose veins. (3) Iliofemoral vein thrombosis: The final stage of Cockett syndrome will evolve into iliofemoral vein thrombosis. This is characterized by a sharp increase in swelling of the lower extremities with distension, increased skin temperature of the extremities, and compensatory dilation of the superficial veins of the lower abdomen and thighs. Zhao Jun et al [12] found that the incidence of venous thrombosis is greatly increased when iliac vein stenosis is equal to or greater than 50% of the normal vein diameter. When the triggers of thrombosis appear, such as surgery, especially orthopedic surgery, gynecological pelvic surgery after various factors caused by bed rest and reduced activity of lower limbs, will induce thrombosis. (4) Varicocele type:It is mainly caused by the reflux of the iliac spermatic vein. In fact, varicocele is one of the side branches formed compensatively because of the poor reflux of the left common iliac vein. In fact, varicocele is one of the side branches of the left common iliac vein compensated for by poor reflux. ponthieu [13] et al. suggested that idiopathic left spermatic varicocele is not always caused by renal spermatic reflux, but can also be caused by skeletal spermatic reflux. bomalask [14] et al. reported a case of varicocele due to cockett syndrome.
4. Diagnosis of Cockett syndrome
COCKETT syndrome can cause serious complications such as pulmonary embolism [15] and cerebral infarction [16]. It is noteworthy that COCKETT syndrome without lower extremity symptoms can also cause pulmonary infarction [17]. Therefore, the early diagnosis of COCKETT syndrome is particularly important, and imaging is preferred.
4.1 Lower extremity deep vein cascade imaging: it can show the deep venous reflux of the lower extremity throughout the whole process, and observe whether the common iliac vein and inferior vena cava are patent, which is one of the most reliable methods to detect iliac vein compression syndrome, and most patients with COCKETT syndrome can be clearly diagnosed by cascade venography.
(1) Direct imaging: ①The transverse diameter of the compressed segment is widened and the contrast density is limited to varying degrees, the left common iliac vein is significantly widened at the site of convergence into the inferior vena cava and gradually thins distally, showing a trumpet shape with thick proximal and thin distal ends. The distal external iliac vein and femoral vein are significantly dilated. ③Limited filling defect, which may be manifested as one or more punctate or block defects. (iv) Venous occlusion is mostly seen in the common iliac vein, but if secondary to thrombosis, it may manifest as a longer segment of occlusion up to the external iliac vein. ⑤ Angulation of the compressed segment of the vein, which shows a downward displacement of the left common iliac vein by stretching and local angulation.
(2) Indirect imaging: ① Formation of collateral circulation. Usually, the iliac veins on both sides communicate with each other through rich anastomosing branches in the pelvis, such as the anterior sacral plexus and uterine plexus, and most of these anastomosing branches are branches of the internal iliac vein. These anastomotic branches are mostly branches of the internal iliac vein. When the common iliac vein is pressurized and affects the venous return, the above-mentioned anastomotic branches gradually expand and thicken, playing an important compensatory role. (2) Delayed emptying of the contrast medium. During the imaging process, a delayed emptying of the contrast medium in the lateral branch vein can be seen, suggesting poor iliac venous reflux. If the patient has a typical clinical presentation and the left common iliac vein is only widened or normal in the transverse diameter on orthogonal imaging, stenosis of the left common iliac vein or left external iliac vein is often found on lateral imaging [18].
4.2 Intravenous manometry is one of the most reliable methods to detect Cockett’s syndrome [19]. Compression of the left common iliac vein can cause obstruction of blood return, resulting in increased pressure distal to the compressed vein. The pressure gradient between the proximal and distal parts of the compressed iliac vein is greater than 2 mmHg at rest, and the distal venous pressure rises more than 3 mmHg during exercise
This is a pathological condition requiring treatment [20]. Surgical treatment is required when the venous pressure rise in the affected limb during exercise is greater than three times the venous pressure rise in the healthy side. The venous system is a low-flow, low-pressure system, with a typical pressure of 2 cmH2O (
0.196 kPa) is sufficient to reflect the hemodynamic characteristics of a narrowed or compressed vein [19], and a catheter pressure gradient greater than 2 cmH2O ( 0.196 kPa) in the distal and proximal left common iliac vein during cannulation retrograde venography is of clinical significance [21].
4.3 Intravascular ultrasonography ( IVUS) IVUS
Can differentiate iliac vein compression syndromes with different types of adherent structures.
It can show the echogenically enhanced vessel wall in the compressed iliac vein, distinguish the lumen of the iliac vein divided into multiple ducts by intra-luminal strong echogenic structures, and show changes in deep vein thrombosis, such as adhesions and mechanized thrombi. The ability to measure the size of the venous vessels is useful in the diagnosis, classification and prediction of complications of iliac vein compression syndrome, and in the design of endovascular stents and treatment of iliac vein compression syndrome [22].
4.4 Color Doppler ultrasound, MRI and CT examinations These examinations can show the extent of venous thrombosis, the anatomical location of the vascular system such as the relationship between veins and arteries, the relationship between arterial veins and lumbosacral vertebrae and surrounding soft tissues, and the condition of collateral vessels, and they can detect pelvic tumors or some other causes of foreign compression, providing an important basis for a definitive diagnosis. However, the disadvantage is that treatment cannot be performed at the same time.
4.5 Air volume tracing (APG) is the best screening index for iliofemoral vein compression syndrome. In patients with this syndrome, the maximum venous flow in the lower extremities is normal at rest and decreases after activity compared to normal, while the duration of venous filling is shortened and venous pressure increases after activity compared to normal. This method has a high rate of false positives [23] and low sensitivity in the diagnosis of iliac vein compression syndrome [24].
5, Treatment
5.1 Conservative treatment Iliac vein compression syndrome is a mechanical obstruction and has no particular effect on general treatment [25]. Early symptoms are mild and mostly treated conservatively, such as elevating the affected limb and wearing circulatory decompression compression stockings to relieve symptoms. Patients are prone to secondary thrombosis due to altered hemodynamics caused by the presence of abnormal fibrous structures in the iliac vein lumen. Therefore, prophylactic oral anticoagulants can be administered. In patients with secondary thrombosis in the iliac veins, anticoagulation and thrombolysis are often not effective. Because there is often more collateral circulation established around the iliac vessels in the lesioned segment, it is difficult for drugs to enter the thrombus. Therefore, it is difficult to recanalize or dissolve the thrombus by drugs in this segment.
5.2 Surgical treatment The purpose of surgery is to relieve the compression of the iliac vein and restore normal venous return to the affected limb. dale [26] considered that only severe symptoms and the patient’s voluntary acceptance of surgery are indications for surgery. rigas [27] et al. reported that the pressure gradient difference between the distal and proximal ends of the compressed segment of the left common iliac vein was greater than 0.196kpa (2cmH2O), suggesting that severe venous compression is an indication for surgery. There is no significant correlation between the pressure difference measured in practice and the severity of clinical manifestations, mainly due to the opening of a large number of collateral vessels in the pelvis, which alleviates the pressure difference, while the lying position and calm state reduces blood return even more and is not conducive to the generation of pressure difference. It has been reported in the literature that the probability of secondary thrombosis will be greatly increased when venography shows more than 50% narrowing of the iliac vein lumen, with indications for surgery. In COCKETT syndrome, the lesioned segment of the iliac vein is compressed by both the artery located anteriorly and the lumbosacral spine located posteriorly, as well as by the lumen created by the abnormal fibrous structures within the lumen. stenosis. Therefore, it is often difficult to obtain good results with simple adhesiolysis or procedures to correct luminal stenosis. In addition, because the anatomical site of the vena cava is deep in the artery, it is under long-term compression with different degrees of inflammation and adhesions in the surrounding tissues and abundant collateral circulation. This makes the surgery difficult. In order to minimize the collateral damage during surgery and avoid the lesion area, palma surgery (bilateral suprapubic vein crossover between femoral veins) is mainly performed. Most of the graft material for the transfer vessels is taken from the saphenous vein or artificial vessels of the contralateral limb. The human venous system is a low-flow, low-pressure system, and vascular grafts are more prone to thrombosis than arteries. Artificial blood vessels lack the antithrombotic function of human vascular endothelial cells and are more likely to form thrombosis than arteries. The main complication of the Palma procedure is early graft thrombosis, and in order to reduce the incidence of this complication and improve graft patency, a temporary arteriovenous fistula (palma-dale procedure) is added distal to the graft intraoperatively to accelerate intravascular blood flow while emphasizing surgical technique and intraoperative and postoperative anticoagulation. Stanse [28] stated that arteriovenous fistulas maintain graft patency primarily due to increased blood flow through the graft rather than increased venous pressure. Therefore, a smaller diameter fistula can maintain graft patency and avoid swelling of the affected limb due to increased venous pressure in the lower extremity. Whenever possible, the fistula material should be made of autologous saphenous vein with a diameter of 2-3 mm,
At 8 weeks postoperatively, the tube can be ligated after the surface of the artificial vessel has been endothelialized. Some patients with COCKETT syndrome have chronic venous hypertension in the lower extremities due to venous stenosis of the iliac veins and venous reflux disorders in the left lower extremity, resulting in swelling of the limbs and superficial varicose veins due to incomplete closure of the femoral vein valves. These symptoms are often difficult to improve after surgery, so the corresponding valve repair surgery is often taken after surgery to restore the valve function, and high saphenous vein ligation and stripping is performed.
5.3 Interventional treatment (balloon dilation, stent implantation) is a new modality developed in recent years to treat COCKETT syndrome. It has become the treatment of choice for the disease because it acts directly on the diseased segment to support the lumen of the vein from being compressed by the artery and lumbosacral bone, and at the same time dilates the lumen to relieve the stenosis caused by the abnormal structures in the lumen, which is less invasive, faster recovery, less complications, and simpler to perform. The main tissue composition of the abnormal structures in the lumen of the diseased iliac veins is collagen fibers and fibroblasts, so their physical properties lack elasticity and extensibility, which makes the lumen expansion more difficult during the intervention and the dilated walls are easily retracted [29], so stenting angioplasty is feasible. For acute lower extremity deep vein thrombosis, catheter-mediated thrombolysis followed by or followed by percutaneous balloon dilatation angioplasty and in-stent support is considered the most effective treatment for acute iliofemoral vein thrombosis. Catheter-mediated thrombolysis is usually more effective within 3 weeks after the onset of thrombosis.