Venous Interventions: From Lower-Limb Deep Vein Thrombosis to May-Thurner Syndrome and Budd-Chiari Syndrome

Over the past decade, there have been great innovations in the diagnosis of venous disorder since the introduction of dual-source computed tomography (DSCT) in 2006. It provides fast and reliable diagnosis of deep vein thrombosis (DVT) with the capability of full leveling of thrombus burden and allows early endovascular interventions with pharmacomechanical aspiration thrombectomy (PMAT) being performed aiming to reduce the post-thrombotic syndrome (PTS) and improve quality of life. The newly introduced ultrafast clot removal system, in patients who failed with PMAT, AngioJet, and EKOS, aids in rapid restoration of venous flow and decline of venous hypertension to mitigate the valve damage. Percutaneous transluminal angioplasty (PTA) and stenting yield high technical success rate of 93–96% and a promising short-term 1-year and 2-year patency of around 93% and 75–79%, respectively, for symptomatic May-Thurner syndrome (MTS). Based on the cumulative endovascular treatment experience in over 2000 cases in Xizou, China, some relevant precipitating factors are addressed, and a new classification of subtypes have been proposed to guide the proper selection of endovascular management of Budd-Chiari syndrome (BCS).


Lower-limb deep vein thrombosis (DVT) 1.1 Introduction and background
It has been estimated that approximately 200,000 to 250,000 cases of lowerlimb DVT occurred annually in the USA [1,2].Dated back as early as in 1860, German pathologist Rudolf Virchow initially depicted the gold rules of pathophysiology involved in DVT: the triad of (1) venous stasis, (2) endothelial damage, and (3) hypercoagulability.Venous stasis can be resulted from external compression, mainly incomplete contrast opacification of the deep venous system and a variety of artifacts that may mimic intraluminal clots [8][9][10].
In acute DVT, the hallmark features are the detection of filling defects (thrombi) with simulated "tram-tracking sign" appreciated between the venous lumen and the venous wall and the acute venous cutoff identified not at the valve region.The affected veins tend to get distended along with the increased thrombi burdens [3,9,10].In chronic DVT, the hallmark features are (1) clot retraction, (2) clot recanalization, (3) valve destructions, and (4) loss of normal venous pathway.In selective minor case, the affected veins may recanalize completely and appear essentially normal [10].

Magnetic resonance venography (MRV)
Over the past decade, there have been remarkable advances in the magnetic resonance (MR) imaging technology of deep venous system that prompt both noncontrast-enhanced and contrast-enhanced MRVs nearly as comparable as contrast venography in the diagnostic accuracy of DVT [11][12][13].As shown in 2007, one metaanalysis evaluated the diagnostic sensitivity and specificity of MRV in lower-limb DVT to be 92 and 95%, respectively [14].Aside from claustrophobia, the limitations of MRV include a lengthy procedure time, pregnancy, and patient with renal failure and with implanted metallic devices.

Computed tomographic venography (CTV)
CTV had been used for diagnosis of DVT at the single-slice CT era [14,15].Over the past decade with the emergence of dual-source computed tomography (DSCT) in 2006 by Siemens, tremendous advances in fundamental technology and clinical utility of CTV have been brought about.In our institution, since the availability of the second-generation DSCT (Somatom Definition Flash, Siemens) in September 2009, we were able to develop our own scanning protocol in CTV with superb imaging quality in the majority of the patients around 2013 (Table 1 and Figure 1).Proper opacification of deep venous system of lower limb, starting from the lower inferior vena cava (IVC) down to the mid-level of tibioperoneal veins, can be acquired as a routine (Figure 2).Except in some selective patients with idiopathic increase in below-knee peripheral vascular resistance (PVR) and in patients with advanced peripheral arterial obstructive disease (PAOD), both of which result in sluggish input arterial flow and thus suboptimal venous opacification at CTV.In patients suspected of coexisting PAOD, a CT arteriography can be performed in one set prior to proceeding of CTV (Figure 3).Approximately 80 ml of 370 mgI contrast medium is injected at rate of 4 ml/s, and the collimation is made at 64 × 0.6 mm to cover shortly above the aortic bifurcation down to the toes.The CTA is displayed in maximum intensity projection (MIP) and bone removal to facilitate visual reading.The tibioperoneal artery greater than 1.5 mm can be well delineated; however, in the lower calf where close alignment of the artery is adjacent to the bone cortex, loss of artery outline may be encountered due to equalization of post-processing threshold.
In a recent meta-analysis focused on the diagnosis of lower-limb DVT, the cumulative sensitivity and specificity are 96 and 95%, respectively [16].The limitations of CTV are patients with significant renal failure, with idiopathic increase in below-knee PVR, and with severe PAOD.

Indication for endovascular interventions in DVT 4.1 Introduction and background
Anticoagulation therapy has long been the first-line management in patients presented with acute DVT.In the 1980s, systemic thrombolysis using streptokinase demonstrated better resolution of thrombus than heparinization alone but carried an unacceptable risk of bleeding complication [17].It was until the late 1990s when intraluminal catheter-directed thrombolysis (CDT) was initiated as an adjuvant to treat those patients in whom heparin worked slowly and patient could not tolerate intractable swelling of the affected lower limb.The treatment safety and the clinical efficacy of CDT were validated in iliofemoral DVT by Bjarnason et al. in 1997 [18].Within the following years, after conducting a nationwide multicenter study, Mewissen et al. proposed that CDT was safe and effective and to be preferentially carried out in proximal iliofemoral and femoropopliteal DVT in patients presented with symptomatic venous obstruction [19].In 2006, the Society of Interventional Radiology published the guidelines for the treatment of lower extremity deep vein thrombosis [20].(1) In a clinical subset of patients objectively documented with iliofemoral DVT, early debulking of thrombus burden can help mitigate post-thrombotic syndrome (PTS).( 2) In patients presented with severe symptoms of massive swelling and intractable pain, early intervention helps reduce mobility and prevent progression to venous gangrene (Table 2).As the thrombus ages, approximately 10 to 14 days after acute onset, CDT becomes less effective in terms of thrombus debulking.As indicated in the CaVenT study, the incidence of PTS reduced to 14.4%, and the 6-m venous patency rate was 65.9% in CDT vs. 47.4% in control, respectively (p = 0.012) [21].The long-term outcome of the ATTRACT study, a multicenter randomized controlled trial, was published in The New England Journal of Medicine in December 2017.The result showed no reduction of overall PTS at 2 years (48.0% vs. 47.4%), but a noteworthy difference of 6% declines in moderate-severe degree of PTS (24% vs. 18%, p = 0.04) [22].Given that primary endpoint was not achieved, however, in selective patients presented with profound DVT symptoms and lower risk of bleeding, the benefit of CDT in reducing moderate-severe PTS and earlier symptomatic relief [23,24] may gain reappraisal by clinicians and interventional radiologists.In addition, patients presented with significant venous steno-occlusive disease after CDT can be managed concomitantly with percutaneous transluminal angioplasty (PTA) or stent deployment to prevent recurrence of DVT [25].

Patient selection
In our institution, patients suspected of having DVT routinely received colorflow mapping and Doppler US and CTV.In advanced symptomatic patients presented with CT documentation of high-level (femoroiliac veins) or extensive involvement beyond popliteal and tibioperoneal veins but with lower risk of bleeding, CDT is conducted with pharmacomechanical thrombolysis with continued infusion of urokinase for 48-96 hours with an aim for early thrombus debulking and rapid symptomatic relief.While those presented with mild to moderate symptom and CTV documented popliteal and/or tibioperoneal DVTs, conventional anticoagulation is justified.

Access site of CDT
Typically, with the patient in prone position, the popliteal vein of the affected limb is accessed with US guidance.A 3-F micropuncture set (Cook Corporation, Indiana, USA) is used for a safe puncture and access into the popliteal vein as well as to prevent subsequent focal bleeding.The cannula is replaced with a 9-F introducing sheath for easy venous access.A 5-F pigtail catheter was inserted through the sheath, which is moved up and down a couple of times through the thrombosed segment in popliteofemoroiliac veins, accompanied with simultaneous infusion of 100,000-250,000 IU of urokinase, to assist macerating the thrombus burden for 15 min.An 8-F 60-cm-long multipurpose guiding catheter, attached with a 50-ml syringe, is used to aspirate the macerated thrombi (Figure 4).In the case presented with significant residual thrombi, a multi-slit infusion catheter of suitable length (Fountain infusion catheter, Merit, USA) was embedded into the distal-most segment and spared the proximalmost segment for sustained continual infusion of 500,000-1,000,000 IU of urokinase per 24 hours for up to 48-96 hours.The patient is kept in a ACU/ICU for close monitoring of general condition and bleeding.Concomitant intravenous infusion of heparin 20,000 IU per 24 hours to prevent new thrombus formation around the infusion catheter was also deemed necessary.Daily check of aPTT (<1.5 time of control level) and fibrinogen and platelet count was mandatory.The patient is sent back to DSA suite every 8-12 hours to check for the resolution of thrombi and repositioning of infusion catheter to facilitate further thrombus resolution toward the proximal end until satisfactory results are achieved.The infusion dose of urokinase can be adjusted depending on the bulk of residual thrombi.After successful CDT, the patient is put on anticoagulation with warfarin for at least 6-12 months.

CDT with new devices by using pharmacomechanical catheter-directed thrombolysis
The consensus that the earlier the thrombi lysed, the less severe the PTS will be paves the way for a better quality of life and less daily limitation of physical activity.Speedy thrombus resolution to salvage valve damage and venous insufficiency sounds reasonable and practical.In recent years, an ultrasound-emitting thrombolytic infusion catheter (EKOS Corporation, Bothell, WA) and the AngioJet Rheolytic Catheter System (MEDRAD Interventional, Minneapolis, MN) have become available in our institution (Table 2).In terms of being high-cost treatment modalities, they both are reserved for those patients who failed to respond well with PMAT (Figures 5 and 6).

Percutaneous transluminal angioplasty and stenting
After successful PMAT is achieved, the whole affected proximal venous pathway should be documented with DSA for any residual steno-occlusive disorder.A 0.035″ hydrophilic guide wire (Terumo, Tokyo Japan) is negotiated, and a 4-F Teflon-coated catheter (Terumo, Tokyo Japan) is advanced through the lesion.A 0.035″ stiff hydrophilic guide wire (Terumo, Tokyo Japan) is exchanged.Sequential ballooning was conducted, with 3-mm, 5-mm, and 8-mm balloons until the balloon waist was completely gone, to accommodate a self-expandable stent of sufficient size and length, mainly the Wallstent (Boston Scientific, Massachusetts, USA).Postdeployment dilation is carried out with a balloon catheter of appropriate size to scaffold the venous fibrosis that frequently comes across with significant venous stenosis.Follow-up DSA is performed to document the technical success, which is graded as a residual stenosis of <30% [26,27] (Figure 7).Aspirin 100 mg and clopidogrel 75 mg are recommended for at least 3 months after stenting.

Introduction and anatomical background
MTS has two synonyms: Cockett syndrome and iliac vein compression syndrome.In 1983, Dr. Ernest Ferris for the first time proposed May-Thurner syndrome in memory of Dr. May and Dr. Thurner for their relevant contributions [28].The first description of a septum-like structure in the left common iliac vein (LCIV) was made in 32% (10 out of 32) of cadavers, in 1906 by an anatomist McMurrich, with which a congenital remnant was implicated as such [29].In 1943, Ehrich and Krumbhaar through anatomic dissection in 412 cadavers found that obstructive lesion in the left common iliac vein (LCIV) in 23.8 and 33.8% of the lesion occurred after the first decade.The lesions were regarded as acquired and not congenital.In 1957, May and Thurner, through autopsy in 430 cadavers, demonstrated that among 19% of cadavers, the overriding right common iliac artery (RCIA) compressed the LCIV against the spine [30].Other investigators also presented different incidence of spurs in the LCIV by different imaging tools: 14% by Negus et al. [31], 50% by Vollman et al. with vascular endoscopy [32], and 62% by Juhan et al. with contrast venography [33], respectively.

Pathophysiology of MTS
Long-lasting pulsatile injury elaborated by the overlying RCIA prompted projectile fibrotic spurs into the lumen of the LCIV, which in turn resulted in accumulation of elastin and collagen over the spurs and extensive intimal proliferation of venous wall.Three varieties of classic venous spurs had been addressed, especially associated with a lower bifurcation position of the abdominal aorta [29].Other theories had been implicated as possible causative factors, namely, compression by pregnant uterus [34] and by sigmoid colon associated with constipation [35].Currently, with availability of modernized cross-sectional imaging modalities, like intravascular ultrasound and optic coherence tomography, the venous spurs can be well depicted and precisely documented the severity of venous obstruction than contrast venography [36][37][38].Regardless of spurforming mechanism [36], congenital or acquired, in case predisposed to hypercoagulability, thrombosis of the LCIV then issues initially at the stenosed segment and propagates in antegrade and retrograde fashions.However, in chronic MTS, the patient may be asymptomatic for quite a certain period of time if sufficient venous collaterals have developed [39].

Clinical manifestation and staging
MTS has a strong tendency to affect young and middle-aged woman (mean age, 42 y/o), although it does affect man [40].In acute stage, the majority of patients frequently presented with sudden onset of pain and swelling of the left lower extremity due to the accompanying DVT.In chronic stage, the symptoms may be more or less vague to define but generally comprised of persistent edema, heaviness, lower calf and ankle skin pigmentation, venous claudication, and ulcer as well as varicose veins [41,42].Rarely, in some selective patients affected with phlegmasia alba dolens and phlegmasia rubra dolens, limb salvage may provide an extremely difficult challenge for the multidisciplinary team physicians.Based on the clinical and imaging findings, MTS is classified into three stages: Stage I, asymptomatic LCIV compression; Stage II, presence of intraluminal venous spurs; and Stage III, occurrence of DVT in the LCIV (Figure 8) [43,44].Failure to correct the underlying anatomic substrate of the LCIV, complication of MTS can include pulmonary embolism, chronic venous stasis, PTS, and iliac vein rupture [39].

Diagnostic imaging modalities of MTS
As mentioned in the imaging diagnosis of DVT, a variety of imaging tools can offer a figure of diagnostic sensitivity and specificity.Each has its own advantages, disadvantages, and limitations.Among them, US is the first-line followed by CTV, MRV, and contrast venography to objectively document the level of DVT and grade the severity of iliac vein obstruction.A stenosis of >50% in the LCIV is considered as hemodynamically significant.As the stenosis percentage of the LCIV may be periodically altered with the circulating blood volume and the body position [38,39], in suspicious case, a pressure gradient across the RCIV and LCIV of >2 mmHg at rest and > 3 mmHg with exercise aids in making a definite diagnosis.Over the past decade with the availability of second generation of DSCT scanner (Somatom Definition Flash, Siemens) in our institution, CTV has nearly replaced others and become the first-line imaging modality for MTS in terms of rapid dataset acquisition and precise leveling of steno-occlusion of the LCIV and the associated DVT [45][46][47].In conjunction with 3-D volume rendering technique at CTA, the compressed segment of the LCIV by the overlying RCIA can be appreciated more precisely than contrast venography.Of paramount importance is the precise depiction of floating thrombi in the lower segment of the IVC with CTV, which may prompt the strategy to implant a temporary IVC filter to prevent pulmonary embolism during endovascular procedure.

Endovascular treatment of MTS
The endovascular treatment of MTS by PTA and stenting has been reported in the literature to be minimally invasive, technically feasible, and safe and clinically effective.Isolated PTA is not effective, similar to the result in other large central veins.The access site is from the left popliteal or common femoral veins.

(b) CTV incidentally showed Stage II MTS half year age at workup for colon cancer. (c) CTV showed Stage III MTS with diffuse DVT from the upper left tibioperoneal vein to the common iliac vein. (d) Contrast venography showed minimal floating thrombin into the IVC (arrow). (e) A Teflon-coated 4-F catheter successfully navigated through the tight stenosis in the common iliac vein (arrow). ( f) After sequential PTAs, a minimal channel was reanalyzed in the LCIV. (g and h) After a 14 mm x 80 mm Wallstent deployment and thrombolysis with a multi-slit infusion catheter for 48 hours, successful recanalization was achieved. (i) At discharge (8 days after admission), the left leg limb was even smaller than the right leg.
Venous Interventions: From Lower-Limb Deep Vein Thrombosis to May-Thurner Syndrome and… DOI: http://dx.doi.org/10.5772/intechopen.85363deployed stent to decompress left iliac vein obstruction.After successful PMAT is achieved, as done exactly in the treatment of DVT section, a 0.035″ hydrophilic guide wire (Terumo, Tokyo Japan) is vigorously negotiated through the stenoocclusion in the LCIV, and a 4-F Teflon-coated catheter (Terumo, Tokyo Japan) is advanced in to the lower IVC.A 0.035″ stiff hydrophilic guide wire (Terumo, Tokyo Japan) is exchanged.Sequential ballooning was conducted, with 3-mm, 5-mm, and 8-mm balloons until the balloon waist is completely gone, to accommodate a self-expandable stent of sufficient size and length.Wallstents (Boston Scientific, Massachusetts, USA) of 12-14 mm in diameter and 80-120 mm in length are used to span the lesion.During the deployment, the Wallstent is initially deployed in the lower IVC, after which the whole unit is pulled down to retain a distal landing zone in IVC of approximately 1-1.5 cm and spans over the entire steno-occlusive segment with a proximal landing zone of >2 cm.Postdeployment dilation is carried out with a balloon catheter of appropriate size to scaffold the venous spurs and fibrosis that frequently accompany MTS.Follow-up DSA is performed to document the technical success, which is graded as a residual stenosis of <30% (Figures 9-11) [26,27].Aspirin 100 mg and clopidogrel 75 mg are recommended for at least 3 months after stenting.Kaplan-Meier life table analysis is used to calculate the primary and secondary patency rate in the follow-up periods.Repeat PTA/stenting as indicated is relevant to maintain the long-term patency.

Technical success and treatment outcome of MTS
As reported in the literature, the technical success rates ranged between 93 and 96% [42][43][44]47].With repeat PTA/stenting, the midterm patency rates were promising and ranged between 95 and 100% [47,48].Although the prevalence of overall PTS did not decline with the adjunct use of PMAT, however, the reduction of moderate to severe degree of PTS was noteworthy.As to the long-term patency, it reserves meticulous monitoring.

Budd-Chiari syndrome
Budd-Chiari syndrome (BCS) occurs when obstruction of the hepatic venules anywhere along the inferior vena cava (IVC) to the right atrium junction can lead to portal hypertension.BCS can be life-threatening.The prevalence of BCS has different geographic variances.In Western countries, the prevalence of BCS is rare, occurring in about 1 in every 2.5 million people, whereas in some Asian countries, such as China, India, and Nepal, BCS is a common disease.For instance, in China's Yellow River and Huaihe River region, 6.8-12 people per 100,000 people suffer from BCS; and more than 20,000 BCS have been documented in China [49].Differences in obstruction sites can also be seen between Western and Asian populations.In the West, hepatic vein occlusion is more common, and venous congestion involving the IVC is less documented.However, in Asia, the diaphragm-type Budd-Chiari syndrome accounts for as high as 70% of all cases.Geographical variance, obstruction location, and pathological and anatomical differences have led to significant differences in clinical symptoms, treatments, and prognosis of BCS in the East and West.The development of modern imaging has enabled observing the hepatic vein, portal vein, inferior vena cava, and azygous vein in vivo, which revealed discordances in comparison to traditional liver biopsy and autopsy findings as described in the previous literature.Therefore, it is necessary to revisit BCS.

Etiology
BCS is considered primary or secondary based on the origin of the hepatic venous outflow obstruction.When the hepatic vein outflow tract is compressed or infiltrated, it is regarded as secondary BCS.Some examples include a primary or metastatic tumor of the liver, leiomyomas of the inferior vena cava, and tumor thrombus.So far, the most common etiology of primary BCS in Western countries is thrombosis, and 25-46% of patients are in prethrombotic or hypercoagulable states.Therefore, primary BCS is predisposed by prethrombotic conditions [50].However, in China, the etiology of BCS is different.The current research shows that in China, the primary thrombotic disease is not a common cause of BCS.Studies have demonstrated that (1) patients with inferior vena cava obstruction have elevated blood vascular endothelial growth factor (VEGF) [51], (2) there is higher groundwater iodine concentration in high-prevalence areas [52], (3) BCS patients have higher blood and urine iodine concentrations [53], (4) people living in rural areas have a higher prevalence, (5) restenosis can occur despite balloon venoplasty of the hepatic vein and inferior vena cava [54], and (6) membranous reformation can occur despite surgery.
Statistical analysis of 2406 patients found that the proportion of hepatic vein occlusion in adolescents under 30 years of age was significantly higher than in patients over 30 years of age [55,56].The proportion of inferior vena cava obstruction increases with increasing age in patients aged 30-79 years old.In 256 BCS patients in the 60-69 age group, 222 cases have inferior vena cava obstruction, and 34 cases have hepatic vein obstruction (7.2%);only 1 case of 34 cases of BCS in 70-79 years old was hepatic vein obstruction type (2.9%).

Iodine and vascular endothelial proliferation
Guo et al. found that in the groundwater iodine concentration of drinking water in 128 patients with inferior vena cava obstruction in Heze, Shandong Province, 98.44% of the 128 patients had iodine content of 150 μg/l or more, of which 150-300 μg/l accounted for 27.35% and 300 μg/l accounted for 71.09%.This result indicates that an area with high groundwater iodine concentration is at high risk of developing BCS [52].Further studies by Zhuang et al. found that blood iodine levels in 233 BCS patients were also higher than that in the healthy population [53] (see Table 3).
The results showed that the serum iodine concentration of BCS patients was more than five times higher than that of the control group.On this basis, we tested the urine iodine of BCS patients and found that the urinary iodine of BCS patients was also higher than the average population.Li et al. carried out in vitro research on the culture of umbilical vein endothelial cells and fibroblasts using different concentrations of iodide culture medium.It was found that at iodine concentration of 300-500 μg/l, the proliferation of vascular endothelial cells and hyperplasia of fibroblasts can be induced.It is speculated that high iodine concentration can lead to vascular endothelial cell proliferation [57,58].Our study of the inferior vena cava septum revealed that the vascular endothelium of the inferior vena cava gradually thickened and merged into a septum.The structure of the septum was fibrous connective tissue in the middle, and the upper and lower layers were vascular endothelium (Figure 12).However, the mechanism of how vascular endothelial cells migrate to form inferior vena cava septum is still unclear.

Vascular endothelial growth factor (VEGF)
In studies using enzyme-linked immunosorbent essay of 40    Venous Interventions: From Lower-Limb Deep Vein Thrombosis to May-Thurner Syndrome and… DOI: http://dx.doi.org/10.5772/intechopen.85363cava obstruction have serum VEGF concentration four times higher than that of the control group.These findings hint that the formation of the IVC septum may be related to inferior vena cava endothelial damage and repair [51] (see Table 4).

Abnormal bone marrow hyperplasia and gene mutation
A significant advance in myeloproliferative neoplasm research was the discovery of the Janus kinase 2 (JAK2) V617F mutation in 2005.This mutation was detected in 90% of patients with polycythemia vera and 50% of patients with essential thrombocytopenia and primary myelofibrosis.JAK2 is a member of the Janus family of tyrosine kinases.A retrospective analysis by Kiladjian showed that the detection of the JAK2 V617F mutation was the first diagnostic step in the diagnosis of BCS basic research [59].
In China, Wang collected 65 cases of BCS blood samples from October 2009 to July 2010.EDTA-K2 anticoagulation treatment, DNA extraction, primer design, the establishment of allele-specific polymerase chain reaction system, and comparison of point mutations at nine sites between the study group and control group were performed.After allele-specific PCR, there were nine positive mutations in the study group JAK2 V617F with a mutation rate of 13.85% (9/65).The control group did not have this point mutation.The mutation rate of JAK2 V617F was significantly lower than that of BCS patients in Western countries.The results show that differences exist in the pathogenesis of Chinese BCS compared with that of Western countries [60].

Acquired condition
Many acquired conditions can provoke the occurrence of BCS.Acquired prethrombotic lesions such as Behcet's disease, antiphospholipid syndrome, hyperhomocysteinemia, and paroxysmal nocturnal hemoglobinuria (PNH) promote BCS development.Behcet's disease, paroxysmal nocturnal hemoglobinuria, and oral contraceptives accounted for less than 1% of the study population.

Clinical manifestation and diagnosis
The clinical manifestations of portal hypertension caused by venous obstruction and posthepatitic cirrhosis and drug-induced (Gynura segetum) hepatitis are very similar, which often lead to misdiagnosis.For patients developing abdominal distension, hepatosplenomegaly, massive and refractory ascites, gastrointestinal bleeding, and hypersplenism leading to symptoms of white blood cells and thrombocytopenia, but without past medical history of hepatitis, chronic alcoholism, nor a history of taking Gynura segetum, hepatic venous occlusion should be considered.The clinical manifestations of inferior vena cava occlusion have characteristic signs including swelling, hyperpigmentation, varicose veins, and long-term unhealed ulcers of bilateral lower extremities.In addition, bulging varicose veins above the skins of the chest and abdomen wall, longitudinal varicose veins, and the lower back varicose veins are also indicative of inferior vena cava occlusion (Figure 13a-f  manifestations of inferior vena cava obstruction include fatigue, exercise-induced asthma, irregular menstruation in women, habitual abortion, and primary infertility.

Imaging diagnosis
The diagnosis of BCS is based on the manifestations of hepatic venous outflow obstruction.This obstruction can be accurately displayed by noninvasive imaging such as Doppler ultrasound, CT, or magnetic resonance imaging (MRI).Doppler ultrasound is considered to be the preferred initial technique, with the ability to directly show the obstruction and reverse blood flow of the hepatic vein and inferior vena cava.The formation of collateral branches between hepatic veins is an indirect sign of hepatic vein obstruction.Ultrasound has a high sensitivity and specificity for the diagnosis of BCS.
CT scan and MRI are effective methods for diagnosing obstruction of the hepatic vein outflow tract.MR angiography is superior to CT, ultrasound, and angiography in demonstrating anatomic structures of the hepatic veins, accessory hepatic veins (AHV), inferior vena cava, azygous veins, and superficial veins of the abdominal wall (Figure 14a).Magnetic resonance angiography can directly display the hepatic veins, the inferior vena cava septum and its thickness, length of segmental occlusion of the inferior vena cava and hepatic vein, location and size of thrombus, as well as the location, orientation, thickness, and number of collateral circulations.Although it is not as effective as Doppler ultrasound in recording the intrahepatic collateral branches, it is unique in showing the extrahepatic collateral and collateral circulations in the abdominal cavity and the abdominal wall (Figure 14b).MRI and CT can effectively show areas of liver parenchyma with reduced perfusion or necrosis.Magnetic resonance angiography not only makes the diagnosis of BCS more reliable but also facilitates the planning of treatment strategies.BCS can be precisely diagnosed by magnetic resonance angiography alone [61]; traditional percutaneous biopsy diagnosis of BCS may no longer be necessary [50].
Angiography is still the golden standard for the diagnosis of BCS.It complements ultrasound, CT, and MRI to provide comprehensive imaging diagnosis of BCS.At present, angiography is no longer used exclusively for diagnosis but also as a means of evaluating the efficacy of interventional therapy.

Definition of a membrane and segmental obstruction
Inferior vena cava and hepatic venous septum formation is a unique pathological feature of BCS.Segmental obstruction can coexist in the inferior vena cava and hepatic vein in some circumstances, making pathological differentiation of the septum and segmentation difficult sometimes.Thus, proper differentiation of the septum and segmentation not only contribute to unified diagnostic criteria and straightforward description of multiple imaging inspection techniques but also promote subtyping BCS.Furthermore, it has significant clinical value for interventional therapy.Therefore, it is necessary to define the inferior vena cava and hepatic venous septum and segmental obstruction.
In January 2016, we organized interventional radiology, pathology, and imaging diagnostic experts to analyze and discuss ultrasound, CT, MRI, and DSA images of more than 1000 patients with BCS and proposed the following viewpoints: inferior vena cava and hepatic vein "septum" and "segmentation" are defined by its thickness, 5 mm or less as a membrane, 10 mm or more as a segment, and 6-9 mm as a transitional zone where the two differentiations can coexist [62].

Classification and subtype
Because the method of interventional therapy is utterly different from surgical treatment, the classification used for surgery is not suitable for interventional therapy.Imaging diagnosis of hepatic vein and inferior vena cava obstruction has become a routine.After summarizing and reviewing the clinical experience of 10,000 cases of interventional therapy in China, the conditions for the establishment of BCS interventional classification have matured.Interventional classification will promote and standardize the behavior and procedures of BCS imaging diagnosis and interventional therapy.It has an objective, realistic, and long-term clinical significance.
In 2010, more than 10 experts in the Chinese Interventional Radiology Group engaged in developing an expert consensus guideline on interventional therapy of BCS.BCS is classified into three main types, namely, hepatic vein obstruction type, inferior vena cava obstruction type, and mixed type [63,64], which are still widely used today.Because of the vast differences in the extent, number, and thrombosis of hepatic veins and the inferior vena cava between individuals, it is necessary to subtype BCS.
In January 2016, experts from the Intracavitary Catheterization Committee of the Chinese Medical Association and experts of interventional radiology, vascular surgery, pathology, and imaging diagnostics discussed to further divide the 3 major types of BCS into 10 subtypes (Table 5, Figures 15-24).For the first time, the hepatic vein and inferior vena cava obstruction combined with thrombosis were included in the subtype, before which none of the previous classifications have done so.

Subtyping of BCS as a guideline for endovascular therapy
Endovascular therapies for BCS include percutaneous balloon dilatation, stent implantation, thrombolysis, transjugular intrahepatic portosystemic shunt (TIPS), and hepatic vein reconstruction [65].Approximately 98% of BCS patients benefit from interventional therapy.The difficulty of BCS intervention varies individually, depending on the procedures performed.Interventional treatment of inferior vena cava septum with a small opening is fairly simple.After completion of inferior vena cava angiography, dilation with a balloon of suitable diameter and length can be done straightforward.However, interventions involving inferior vena cava segmental occlusion, thrombosis formation, occlusion end with the formation of collateral branches, or diffuse hepatic vein occlusion can take the operators hours or even days to complete the procedure.The new subtyping system provides a clear guideline for the preparation of preoperative treatment plannings and selection of equipment including medications and tools for thrombolysis, as well as the proper selection of percutaneous puncture routes and endovascular treatment methods (Table 6).

Anatomical occlusion versus functional occlusion
According to our data analysis of more than 2400 cases, the incidence of obstruction of the left hepatic vein in patients with BCS is higher than 95%.Due to the small volume and smaller venous return of the left hepatic lobe, the outcome of occlusion of the left hepatic vein is minimal since collateral branches can form between the left hepatic vein, right hepatic vein, and left inferior diaphragmatic vein.Due to the presence of the collateral branches, even if the left hepatic vein and the middle hepatic vein are occluded, venous return can be entirely compensated by the venous return of the right hepatic vein or accessory hepatic vein.Therefore, we

Hepatic vein occlusion combined with thrombosis. (a) MRI showing the right hepatic vein occlusion with thrombosis (white arrow). (b) DSA showing hepatic venous occlusion with thrombosis (black arrow).
Venous Interventions: From Lower-Limb Deep Vein Thrombosis to May-Thurner Syndrome and… DOI: http://dx.doi.org/10.5772/intechopen.85363still subtype cases with obstruction of the left hepatic vein and middle hepatic vein as isolated inferior vena cava obstruction type.

Accessory hepatic veins
In addition to the three hepatic veins, there are scattered small hepatic veins, collectively called the accessory hepatic vein (AHV) or the short hepatic veins, that drain directly into the IVC.After conducting anatomic researches, Liu et al. find that there are two primary sources of AHV: one is from the caudate lobar vein and the other from the right posterior hepatic vein.However, since most of the AHV are too small and are not the central draining vein of the liver, they are often neglected [65].However, in patients with BCS, when hepatic vein occlusion occurs, AHV is     the main channel for venous return.Gai performed an ultrasound investigation on 244 BCS patients and found 191 (78.3%) cases presented with AHV.Among the 244 BCS patients, 209 had hepatic caudate lobar veins with an average diameter of (7.88 ± 2.78) mm, and 147 had a right inferior hepatic vein with an average diameter of (9.50 ± 3.11) mm [66].During expansion of the AHV lumen, collateral branches between the hepatic vein and the accessory hepatic vein can fully compensate the hepatic venous return (see Figure 21c).In cases accompanied with IVC obstruction, the degree of IVC obstruction aggravates the expansion of AHV lumen.The accessory hepatic vein can also get obstructed.When the diameter of the AHV reaches 6 mm, it has sufficient compensatory capacity.Therefore, the interventional treatment of the obstructed accessory hepatic vein above 6 mm is equivalent to the treatment of the hepatic vein.In short, the accessory hepatic vein is of equal value to the hepatic vein in the diagnosis and treatment of BCS [67].

Inferior vena cava septum and position of hepatic vein opening
The location of the inferior vena cava septum is generally above the hepatic vein opening, often causing hepatic venous blood flow obstruction.As the number of BCS cases increases, we find cases with the left hepatic vein and middle hepatic vein locating above the inferior vena cava septum.Dr. Zhang of the Chinese Department of Vascular Surgery also found a case (Figure 25) with the hepatic vein opening directly above the inferior vena cava septum while providing surgical resection of inferior vena cava septum.Although the numbers of this kind of cases are exceptionally few, the consideration on redefining BCS may be raised.

Azygos veins and its collateral branches
When hepatic vein becomes obstructed, the establishment of collateral branches between the intrahepatic veins is simple, but it is difficult for collateral branches to develop outside of the liver.This can result in portal hypertension with poor prognosis.In contrast, the establishment of the collateral branches after the inferior vena cava obstruction is relatively easy and extensive (see Figure 26).The azygous vein is the most crucial collateral branch when inferior vena cava obstruction occurs.The azygous vein can expand to a diameter of 2 cm (Figure 21) and compensate for the venous return of the inferior vena cava, and the patient usually can survive longer.Therefore, the severity of clinical symptoms of BCS is closely related to the compensatory capacity of the collateral circulation.

Closed collateral branch
After significant obstruction of the inferior vena cava, the superficial and deep vein begins to form collateral and communicating branches.In some cases, one or more collateral branches can appear above the site of inferior vena cava obstruction, with the diameter of reaching 2-3 mm.It can appear as single or multiple saclike structures, which are difficult to detect on preoperative ultrasound, CT, and MRV.However, DSA can easily show the obstruction and collateral branches which play a vital blood flow compensation.During endovascular treatment, the existence of this collateral branch poses a potential risk.Since the collateral branches cannot be wholly identified under fluoroscopy, they may be ruptured during balloon dilatation, resulting in fatal intra-abdominal or intrathoracic bleeding.Thus, it is essential to be aware of this situation to ensure the safety of endovascular therapy.

Conclusion
With the adjunct use of PMAT incorporated in percutaneous CDT technology dedicated to the sophisticated endovascular management of DVT and DVT-related syndrome, the prevalence of PTS of moderate to severe degree and the intractable pain associated with advanced venous hypertension can be improved substantially.However, a randomized controlled study, comparing the adjunct use of PMAT or not, is demanded to offer convincing evidence.In conjunction with PTA and stenting after successful PMAT, symptomatic MTS can be well managed in terms of high technical success rate and midterm patency rate with acceptable minor complications.Along with the appreciations of newly identified pathophysiology and the creation of a new classification of subtypes, the selection of optimal mode of endovascular interventions in BCS may be solidly anticipated.

Literature search methods
The key references used in this manuscript are primary obtained using PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) and the textbooks "Abrams' Angiography: Interventional Radiology Third Edition" and "Venous Interventional Radiology With Clinical Perspectives 2nd Edition," as listed in References section.Some co-authors' references and new concepts are acquired from the recent Chinese radiology professional committee discussions.
© 2019 The Author(s).Licensee IntechOpen.This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Figure 1 .
Figure 1.(a-d) CTV depicted optimal opacification of venous structure from bifurcation of IVC to the lower level of popliteal veins.

Figure 3 .
Figure 3.CT arteriography at the same set as CTV showed high-grade imaging quality as well as identification of two discrete obstructions in the right iliac and superficial femoral arteries.Collateral arteries were also clearly depicted.

Figure 4 . 8 Figure 5 .
Figure 4. Relatively fresh and subacute thrombi were aspirated by PMAT from the left iliofemoral veins in a 32-year-old female taking oral contraceptive pills for dysmenorrhea.

Figure 6 .
Figure 6.A 31-year-old obese male with hypertension suffered from gunshot wound over the abdomen and complicated with diffuse right leg iliofemoral DVT.(a and c) Diffuse DVT in the right iliofemoropopliteal veins due to immobilization.(b and d) After AngioJet, good blood flow regained.

Figure 7 .
Figure 7.A 48-year-old male developed chronic DVT in the left iliofemoral veins as a complication of dwelling perm catheter and successfully managed with PTA and two overlapping 8 m and 10 cm Wallstents.At 8-year follow-up, the stents remained patent.(a) Contrast venography revealed long-segment stenosis of the left iliofemoral veins and venous collaterals.(b) Balloon waist at predilation with an 8-mm balloon catheter.(c) Immediately after stenting, good flow is restored and minimal venous collaterals visualized.

Figure 8 .
Figure 8. Classification of MTS into three clinical stages.(a) CTV showed Stage I MTS 9 (arrow) incidentally while imaging of DVT.(b) CTV showed Stage II MTS presented with venous spur.(c and d) CTV showed Stage III MTS presented with DVT (black arrow).

Figure 9 .
Figure 9.A 70-year-old male with Stage III MTS successfully treated with PTA and stenting.(a) CT topography showed remarkable swelling of the entire left lower extremity.(b)CTV incidentally showed Stage II MTS half year age at workup for colon cancer.(c) CTV showed Stage III MTS with diffuse DVT from the upper left tibioperoneal vein to the common iliac vein.(d) Contrast venography showed minimal floating thrombin into the IVC (arrow).(e) A Teflon-coated 4-F catheter successfully navigated through the tight stenosis in the common iliac vein (arrow).( f) After sequential PTAs, a minimal channel was reanalyzed in the LCIV.(g and h)After a 14 mm x 80 mm Wallstent deployment and thrombolysis with a multi-slit infusion catheter for 48 hours, successful recanalization was achieved.(i) At discharge (8 days after admission), the left leg limb was even smaller than the right leg.

Figure 10 .
Figure 10.A 65-year-old schizophrenic female suffered from subacute Stage III MTS, successfully recanalized with PMAT and Wallstent deployment.(a-e)CTV showed excellent depiction of massive DVT spanning from the lower IVC down to the left tibioperoneal vein.( f and g) Venography demonstrated floating thrombi in the lower IVC (arrow), and an Optease caval filter was implanted to prevent pulmonary embolism.(h-j) Subacute thrombi were removed with aspiration thrombectomy.(k and l) After aspiration thrombectomy, venography revealed minimal residual thrombi and long-segment tight steno-occlusion of left iliofemoral veins and venous collateral.(m and n)After sequential PTAs and Wallstent deployment, the venous flow was restored, and at 2.5-year follow-up, the stent remained patent.

Figure 11 .
Figure 11.A 41-year-old with MTS Stage III presented in acute stage was successfully managed with PMAT, PTA, and stenting.(a-c) CTV depicted extensive DVT in the left femoroiliac veins.(b) Pre-treatment photo showed swelling of the left leg and cellulitis.(e) Posttreatment photo showed disappearance of swelling and healing of cellulitis at 1-month follow-up.( f and g) Venography showed extensive DVT above the left femoral vein and relatively fresh thrombi obtained by PMAT.(h and i) After PTA and stenting in the LCIV, good patency was depicted, and minimal residual thrombi were treated with warfarin.

Figure 12 .
Figure 12.Thickening of the vascular endothelium above the inferior vena cava septum (a).Lateral migration of thickened vascular endothelium cells and fibrous connective tissue forming the septum (b).

Figure 13 .
Figure 13.Clinical manifestations.(a) Swelling of the lower extremities.(b) Varicose veins of the lower extremities.(c) Pigmentation of the lower extremities.(d) Ulcers of bilateral lower extremities.(e) Thoracic and abdominal wall varices.( f) Lumbar dorsal varices.

Figure 15 .
Figure 15.Hepatic vein/hepatic venous membranous obstruction.(a) An ultrasound showing the septum at the left hepatic vein opening (arrow).(b) MRV showing the venous septum in the IVC (arrow).(c) DSA showing membranous venous occlusion in the right hepatic vein (arrow).(d) DSA showing membranous obstruction of the accessory hepatic vein (arrow).

Figure 16 .
Figure 16.Hepatic venous segmental obstruction.(a) An ultrasound showing the segmental obstruction (black arrow) of the right hepatic vein.(b) DSA showing segmental occlusion of the middle hepatic vein along with membranous obstruction (white arrow) of parahepatic venous structures.

Figure 19 .
Figure 19.Inferior vena cava membranous obstruction with a tiny perforation.(a) Color-flow mapping showing membranous obstruction (black arrow) of the inferior vena cava.(b) MRI showing membranous obstruction (black arrow) of the inferior vena cava.(c) DSA showing membranous obstruction of the inferior vena cava with a tiny perforation (black arrow).

Figure 17 .
Figure 17.Extensive hepatic vein occlusion.(a) An ultrasound showing the right hepatic venous occlusion of the liver with hyperechoic texture.The right hepatic vein is faintly depicted (black arrow), and the left hepatic vein is small in caliber.(b) MR showing hepatosplenomegaly.Hepatic veins are few and small in calibers.(c) Enhanced CT showing hepatomegaly and heterogeneous parenchymal enhancements.(d) DSA showing the disappearance of the main trunk of the hepatic vein and small reticular-shaped collateral vessels.

Figure 18 .
Figure 18.Hepatic vein occlusion combined with thrombosis.(a) MRI showing the right hepatic vein occlusion with thrombosis (white arrow).(b) DSA showing hepatic venous occlusion with thrombosis (black arrow).

Figure 20 .
Figure 20.Inferior vena cava membranous obstruction.(a) An ultrasound showing the vena cava septum as an echoic texture (white arrow).(b) MRV showing hypointense inferior vena cava septum (white arrow) right above the hepatic vein opening.(c) DSA showing membranous occlusion (black arrow) of the inferior vena cava.

Figure 21 .
Figure 21.Inferior vena cava segmental obstruction.(a) An ultrasound showing segmental occlusion (white arrows) of the inferior vena cava.(b) MRV showing a long segmental occlusion (black arrows) of the inferior vena cava.(c) DSA showing a long segmental occlusion (black arrows) of the inferior vena cava.(d) DSA projected in a lateral view showing an ultra-long segmental occlusion (black arrows) of the inferior vena cava.

Figure 22 .
Figure 22.Inferior vena cava obstruction with massive thrombosis.(a) Gadolinium-enhanced MRI demonstrating massive thrombi of various ages (black arrows and white arrow) in the IVC below the level of obstruction.(b) DSA showing membranous obstruction in the IVC along with bulky thrombi (asterisk).

Figure 23 .
Figure 23.Hepatic vein and inferior vena cava occlusion.(a) MRI showing right hepatic venous membranous obstruction (white arrowhead) with segmental occlusion (black and white arrows) of the inferior vena cava.(b) DSA showing membranous occlusions of the right hepatic vein (black arrow) and inferior vena cava (white arrow).

Figure 24 .
Figure 24.Hepatic vein and inferior vena cava occlusions with thrombosis.(a) DSA showing right hepatic vein occlusion (black arrow) and IVC segmental occlusion with massive thrombosis (white arrow).(b) MRI showing occlusions of the hepatic vein (black arrows) and IVC with massive thrombi of various ages (asterisk).

Figure 25 .
Figure 25.MRV showing that the middle hepatic venous opening (hatched arrow) is above the inferior vena cava obstruction.

Table 3 .
Serum iodine levels in patients with BCS in different types and in the control group.

Table 4 .
VEGF concentration value t-test result.

Table 6 .
Selection of endovascular treatment methods based on the subtypes of BCS.