Sarah Onida

Nutcracker Syndrome: An Update on Current Diagnostic Criteria and Management Guidelines

BACKGROUND Nutcracker syndrome (NCS) describes left renal vein compression between the superior mesenteric artery and the aorta. Although uncommon, it is an important diagnosis due to the important morbidity associated with it, including the risk of chronic kidney disease from long-term left renal vein (LRV) hypertension and the risk of LRV thrombosis. METHODS This article reviews the literature on NCS, particularly with respect to the diagnostic accuracy of different imaging modalities and the success rates, complications, and long-term follow-up data associated with various surgical interventions. RESULTS AND DISCUSSION The diagnosis of this condition is based on a stepwise work-up with history and clinical examination, followed by Doppler ultrasonography, computed tomography, magnetic resonance imaging, intravascular ultrasound (IVUS) and phlebography with measurement of the renocaval pressure gradient. Management is determined by symptom severity; often symptom resolution occurs following a conservative approach. However, in some cases, surgical management is required, particularly when conservative management is unsuccessful. When it comes to the surgical management of NCS three main pathways exist: open surgery, laparoscopic surgery and endovascular approaches, with the latter 2 becoming increasingly popular due to their minimal invasiveness. Additionally, cases involving the use of robotic surgery in the management of NCS have been reported. CONCLUSION Despite the rarity of NCS, its recognition and management are important. This article has explored the evidence basis for conservative, medical and surgical options.

Phlebectomies: to delay or not to delay?

Varicose veins are a common disease, with a reported prevalence of 20–40%. – 3 Their treatment represents one of the most common elective surgical procedures in vascular surgery. Numerous advances have been made in this field, moving away from surgical ligation of the saphenofemoral junction and stripping, towards less invasive options, including ultrasound-guided foam sclerotherapy, radiofrequency ablation (RFA) and endovenous laser ablation (EVLA). Although these methods all address the truncal incompetence with similar technical success rates, residual superficial varicosities may remain postoperatively and their treatment is still a matter of debate. There are two schools of thought with regard to treating varicosities in those patients undergoing truncal vein ablation. The first suggests simultaneous truncal treatment and phlebectomy as a single procedure. The second advises delayed phlebectomy after monitoring for varicosity regression. If still present, these can be addressed with ambulatory phlebectomies or foam sclerotherapy. Advocates of the first option suggest that immediate treatment of surface varicosities is advantageous in that it ensures patients are treated in a single session and reduces the varicosity reservoir. However, this may increase operative time, and could be over-treating patients whose varicosities may regress. Those in favour of delayed phlebectomies claim that this treatment is shorter, saving operative time. However, a variable number of patients do come back with troublesome residual varicosities, which require secondary procedures. The evidence of the timing for phlebectomy is at best confusing. Carradice et al.’s 2009 study showed that while there was no sustained difference in quality-of-life measures between delayed and simultaneous phlebectomy in the context of EVLA treatment, 66% of patients in the truncal ablation only group required secondary interventions. Monahan et al. suggested that after RFA, 13% of patients had spontaneous varicosity regression and 41% of patients did not require further treatment, suggesting that monitoring for regression is the best option. This appears confusing and contradictory, but both EVLA and RFA truncal ablation have been shown to save 30–40% of patients from having needless phlebectomies. However, Doganci et al.’s comparison of laser wavelengths utilized a delayed approach but 100% of subjects required further intervention. Part of the issue is that the literature is very heterogeneous, making comparisons between studies challenging. Variations exist in the reporting standards for surgical vs. EVLA/RFA or foam sclerotherapy both in terms of vein classification, as well as length to follow-up, objective assessments and questionnaires. Studies looking at specifically immediate vs. delayed phlebectomies are few in number. Most randomized studies into catheter type or modality to date have used standardized delayed or simultaneous phlebectomies across their study groups, with no clear definition of the trigger to varicosity treatment. This makes comparison difficult. Furthermore, there are a number variables that confound the picture. Patient factors such as age, body habits and mobility will influence the result of any intervention on the venous system. Patient preference and expectations, as well as operator experience, may have an effect on patient and operator satisfaction. Pain levels experienced have been assessed in only one study, which showed no statistical difference in pain or return to normal activities. Finally the anatomy of the venous system and its preoperative haemodynamic state will also influence the outcome of any intervention, as will the condition of the patient and the venous calf pump. These factors need to be considered when considering treatment options, with the appreciation that any alteration in the venous tree will lead to haemodynamic changes. Ultimately, the aim of procedures for residual venous disease are to provide the maximum symptomatic relief for as long as possible. An ideal treatment would be minimally invasive, safe, effective from a functional and cosmetic point of view, have low recurrence rates and be cost-effective. However, the goal of ambulatory minimally invasive treatment should not preclude the full management of the disease. Venous disease affects a large proportion of our population. Despite advances in the field, the evidence behind treatment is still unclear; this is particularly true of tributary vein treatment at the

Genetics in chronic venous disease

Chronic venous disease is highly prevalent in the Western world, with varicose veins being the most common form of clinical manifestation. With recent developments in sequencing technology, clinicians and geneticists alike are embarking on a journey to identify and unravel the genetic candidates of chronic venous disease. There is now currently substantial evidence to suggest the presence of genetic influences in the aetiology and pathology of venous disease. Despite this, the precise nature and profile of the genes involved in chronic venous disease remain a poorly understood entity. Moreover, it is strikingly apparent that the majority of venous genetic studies conducted over the past decade do not adhere to fundamental research principles. The emergence of high-throughput genotyping platforms permits a more systematic search for inherited components of venous disease. Pursuing a genome-wide frontier has the potential to reveal novel critical metabolic pathways and explain the genetic susceptibility of chronic venous disease. An expedited knowledge of the genetic factors in the aetiology of venous disease may translate into better prevention or treatment, which would benefit patients suffering from its clinical sequelae. Researchers should be urged to foster collaborative links and design a genome-wide case-control association study as an international consortium to provide a statistically robust paradigm in the field of chronic venous disease genetics. This will carry promise for clinically relevant progress and represent a first step towards better understanding of the genetics of chronic venous disease aetiology.

A systematic review and meta-analysis on the role of varicosity treatment in the context of truncal vein ablation

Background With the advent of endovenous truncal ablation under local anaesthetic for the treatment of varicose veins, the fate of varicosed tributaries has become controversial, with centres offering different timings of treatment, if offered at all. This study aims to review the literature assessing delayed and simultaneous varicosity treatment during truncal ablation. Methods Randomised trials and cohort studies concerning varicosity treatment timing were identified through a systematic literature search. Requirements for further treatment, quality of life and rate of venous thrombotic events were assessed for meta-analysis. Results Four studies were identified assessing need for further varicosity procedure, with no significant difference seen between simultaneous or delayed treatment (p = 0.339). Two studies assessed quality of life, with simultaneous treatment providing significantly improved outcomes at six weeks (p = 0.029) but not at 12 weeks (p = 0.283). Studies examining venous thrombotic events showed no difference in venous thromboembolism rate between simultaneous or delayed treatment approaches (p = 0.078). Conclusion The evidence base regarding timing of varicosity treatment is sparse; however, it does show that simultaneous treatment of varicosities leads to early gains in quality of life, with a non-significant trend for fewer further procedures but more venous thrombotic events.

Long-haul travel and venous thrombosis: What is the evidence?:

Travel is a booming business thanks to globalisation, the rise of commercial aviation and significant reductions in fare prices. In 2015, 3.5 billion passengers were carried on scheduled flights, a 6.8% increase on the previous year. However, increased travel mobility is not entirely without risk. Venous thromboembolism (VTE), first linked to travel in the 1950s, is of particular concern. Growing public and media interest in this preventable and potentially fatal condition has prompted airlines, healthcare professionals and advisory bodies to offer advice on ‘traveller’s thrombosis’. The National Institute for Health and Care Excellence (NICE) advises compression stockings for all moderate or high-risk long-haul travellers, and consideration of low-molecular weight heparin (LMWH) in high-risk travellers. ‘General measures’ such as leg exercises and avoiding dehydration or excessive alcohol intake feature amongst advice given by patient websites and airline carriers. However, is this guidance evidence based? This is debatable. Several issues exist regarding VTE, travel and available evidence, raising questions including: ‘What travel-related factors determine an increased VTE risk?’, ‘Who is most likely to be affected by this risk?’ and ‘How should the risk be mitigated?’ At a more fundamental level, ‘How long is long-haul?’ Studies addressing these questions are heterogeneous and therefore difficult to compare and draw conclusions from. One area of consensus is that a travellers’ background VTE risk plays an important role in determining their travel-related risk. A 2008 international consensus statement grouped subjects into low, medium and high risk for traveller’s thrombosis; highrisk subjects included those with a personal history of VTE, malignant disease or recent major surgery. Evidence indicates that subjects at low to medium risk of VTE have a 0–2% risk of developing thrombosis associated with long-haul air travel; this increases to 5% for individuals at high risk, such as those with a history of DVT or hypercoagulable states including factor V Leiden mutation and obesity. Unfortunately, the inter-study consensus largely ends there. Studies employ various definitions of longhaul travel, ranging from journeys longer than 4 h to 7 h, up to 10–12 h. Furthermore, VTE assessment differs both in modality and timing. Two of the largest studies employed very different assessments. Researchers in the LONFLIT study performed systematic duplex ultrasound scanning (DUS) for all participants within 24 h of their flight. Conversely, the New Zealand Air Traveller’s Thrombosis Study considered subjects at risk for three months after travel and performed DUS only if they became D-dimer positive or symptomatic during this period. This may have led to an underestimation of DVT, as, although this assay is sensitive in suspected DVT, it may be less reliable in prediction of travel-related VTE. This is illustrated in the LONFLIT studies where there was no significant difference in the D-dimer level of those with ultrasound-detected VTE and those without. Lastly, many studies have significant dropout rates and insufficient subjects to accurately calculate risk. Due to the low incidence of DVT in the general population, studies require large numbers of travellers to confirm a significantly increased risk above controls. Evidence exists that VTE risk is not confined to air travel. Results from a large case-control study revealed a 2-fold increased VTE risk for all modes of travel including train, bus, car and plane, suggesting that immobility is an important contributing factor. However, in specific individuals, air travel increases VTE risk above simple immobility. One study compared participant’s blood results after an 8-h flight, an 8-h movie marathon and 8 h of normal activity. Markers of coagulation activation, specifically thrombin–antithrombin complexes, were raised in individuals after air travel but not in the other situations, particularly if using oral contraceptives or factor V Leiden mutation positive. This provides further evidence that specific patient risk factors convey an increased risk in travel.

What is pathological May–Thurner syndrome?

With the advent of endovascular therapy and the increasing recognition of this entity, it is time to evaluate what truly is a May–Thurner syndrome (MTS). As early as 1851, Virchow noted a striking five-fold left-sided preponderance for lower extremity deep venous thrombosis (DVT). It was not until the seminal cadaveric study by May and Thurner in 1957 that comprehensive description of the anatomy underlying this peculiarity was provided; namely, the compression of the left common iliac vein (LCIV) by the overlying right common iliac artery (Figure 1). The authors postulated that venous ‘spurs’ arose through a combination of chronic mechanical compression and endothelial disruption from adjacent arterial pulsations. Thus, by fulfilling two elements of Virchow’s triad, this entity represents an anatomical substrate for DVT. MTS, or iliac vein compression, now encompasses a wider spectrum of pathology; rarer variants have been described, including compression of the right common iliac vein by the right common iliac artery. Clinical manifestation may be acute, with venous spur development and left lower limb DVT (disease classification stages II and III, respectively), or chronic, including unilateral limb swelling, venous claudication, varicose veins, and ulceration. However, this anatomical anomaly may represent a subclinical phenomenon (stage I disease); evidence of LCIV obstruction has been identified in up to 30% of cadavers. Furthermore, in a review of 50 computed tomography (CT) scans performed in patients with abdominal pain, surprisingly, a quarter had at least 50% and two-thirds at least 25% LCIV compression. The often silent nature of the lesion precludes accurate assessment of its true prevalence. Additionally, it may be overlooked in the investigation of left iliofemoral DVT and so under-diagnosed as an aetiological factor. A parallel may be drawn to the presence of isolated perforator disease in patients with superficial venous insufficiency; the clinical significance of treating these vessels is debated. Nonetheless, MTS is clearly clinically relevant in both acute and chronic presentations. Iliac vein ‘spurs’ have been reported on intra-operative phlebography in 49% of patients presenting with left iliofemoral DVT; in a population of patients with left lower limb chronic venous disease (CVD), 14.8% had evidence of MTS. Therefore, when does MTS become pathological rather than simply a silent anatomical variant? May and Thurner believed this syndrome to be an acquired phenomenon present in cadavers but absent in embryonic development. This is an important question to address, as this syndrome is most frequently observed in healthy individuals, in the second to fourth decades, where it can translate into a source of significant morbidity and, potentially, mortality. Regrettably, there is a paucity of high-level evidence upon which to base guidelines regarding the diagnosis of MTS. Studies are small, often retrospective, and employ a variety of imaging modalities. There is also little consensus regarding intervention in individuals with MTS who have not developed DVT or regarding the optimal management of CVD in this context. Clinical presentations suggestive of MTS include left lower extremity DVT in the absence of differential causes of iliofemoral thrombosis and, more indolently, signs and symptoms of CVD not responding to conventional management. A retrospective study found that over 50% of patients with venous ulceration not responding to compression therapy or surgical intervention aiming to correct superficial reflux had evidence of iliac vein narrowing. The bedrock of diagnosis remains within a plethora of imaging modalities including, duplex ultrasound (DUS), conventional venography, magnetic resonance venography (MRV), computed tomography venography (CTV) and intravascular ultrasound (IVUS). The first is often employed initially to assess lower limb venous anatomy; however, due to its limitations

CHIVA, ASVAL and related techniques – Concepts and evidence

Chronic venous disease (CVD) is a highly prevalent condition with significant effects on patients’ quality of life. Despite this, the underlying pathophysiology of venous disease still remains unclear. Two schools of thought exist, explaining the development and propagation of venous disease as an “ascending” and “descending” process, respectively. The descending theory, stating that CVD is secondary to proximal disease (e.g. saphenofemoral/saphenous incompetence), is the most widely accepted when planning treatment aiming to remove or destroy the junction or truncal veins. The ascending theory, describing the disease process as developing in the lower most part of the leg and propagating cranially, aims to re-route the venous circulation via minimally invasive interventions. Classically, superficial venous insufficiency has been treated with the removal of the incompetent trunk, via open surgery or, increasingly, with endovenous interventions. Minimally invasive treatment modalities aiming to preserve the saphenous trunk, such as CHIVA and ASVAL, may also play an important role in the treatment of the patient with varicose veins.

Guidelines on venous ulceration: A mess

Of the many presentations across the clinical spectrum of chronic venous disease, venous leg ulceration can be considered amongst the most important. Despite a prevalence of 1% in the general population, it accounts for an annual expenditure of 1–2% of the national health budget, equating to over

To compress or not to compress: The eternal question of the place of compression after endovenous procedures.

2.5 billion in the US and £300–£600 million in the UK. Importantly, with prevalence increasing to 4% in the elderly and significant negative effects on quality of life due to disability, social isolation and psychosocial burden, venous leg ulceration will continue to present an important challenge, particularly in light of the expected increase in prevalence in the next decade dictated by an ageing and increasingly obese population. Prevention and intensive management are key in this condition; to this end, numerous guidelines have been developed endorsed by a number of professional bodies and healthcare organisations. Clinical guidelines provide evidence-based frameworks for healthcare professionals and patients. Recognised benefits include health outcome improvement, establishing standards for care in clinical decision making and reducing expenditure by promoting costeffective interventions. Despite regulatory body and editorial scrutiny, guideline recommendations may be influenced by subjective notions, such as the experience of the writing committee and analysis of data that are lacking, misleading, or subject to misinterpretation. In a chronic, highly prevalent, historical and expensive condition such as venous leg ulceration, general consensus between guideline recommendations is to be expected. However, is this actually the case? Hippocrates (460–377 B.C.) was the first to provide advice, or guidance, on venous leg ulceration. Since then, numerous guidelines have been published from all over the world, particularly from the United States and Europe. This is a testament to the importance and relevance of venous ulceration; despite the attention, there is large heterogeneity on numerous fronts. The largest factor determining this heterogeneity lies in the definition of levels of evidence and levels of recommendation. Although ‘‘systematic’’ assessment of the literature is performed by all guidelines, its appraisal differs quite importantly. Grading systems employed include those from the European Society of Cardiology, the American College of Chest Physicians and the Agency for Health Care Policy and Research evidence criteria, to provide some examples; furthermore, guideline development groups have devised their own criteria for the assessment of levels of evidence and grades of recommendation. This difference in grading systems results in similar recommendations being classified as high/medium/or low depending on how the literature has been interpreted by the different guideline committee groups. Translating this to clinical practice can result in variations in the level of care provided depending on which guideline (or evidence) is followed. Another factor determining heterogeneity is structure, which does not always reflect the multidisciplinary nature key to venous leg ulcer guideline development. Venous leg ulceration is in the remit of vascular surgeons, phlebologists, angiologists, dermatologists, physicians, primary care physicians and nurses. Although guidelines are accessible to all healthcare professionals, it is to be expected that, depending on the overseeing body, guidelines may present information relevant to a specific category of healthcare professionals, leading to heterogeneity in the topics addressed and the need to refer to different guidelines to gain a comprehensive picture of a specific condition. This is particularly apparent in guidance relating to diagnosis and management, with ‘‘secondary careoriented’’ guidelines concentrating on duplex ultrasound and the evidence for intervening on the superficial and/or deep venous systems, and ‘‘primary care’’-oriented guidelines highlighting details on compression modalities and criteria for referral to specialist units. Interestingly, certain themes are recurring between different guidelines. Taking a detailed history and performing a comprehensive physical examination are universally discussed. Ankle brachial pressure index (ABPI) measurement for both diagnostic and

Compression therapy for uncomplicated varicose veins – Too little for too much?

The management of varicose vein disease has witnessed a dramatic transformation over the past decade. Surgery for this common condition, long considered the ‘gold-standard’ treatment, has gradually been replaced by endothermal ablation and ultrasoundguided foam sclerotherapy (UGFS). These minimally invasive techniques have allowed a more rapid improvement in patients’ quality of life and return to normal activities. The focus on enhancing patients’ experience even further has led to the introduction of newer, non-thermal, non-tumescent (NTNT) technologies. These completely obviate the need for uncomfortable thermal ablation and tumescent infiltration with possibly a similar level of efficacy as radiofrequency ablation (RFA) and endovenous laser ablation (EVLA) in the short term. The next potential area where a substantial difference in the management of varicose veins can be made is the use of compression therapy following endovenous ablation. It is widely believed that compression reduces post-operative swelling, haematoma formation and pain following surgery for varicose veins, but no irrefutable evidence exists. Edwards et al. surveyed the members of the Vascular Society of Great Britain and Ireland and found that 75% used either elastic or non-elastic bandages post-operatively, with 77% changing to compression stockings afterwards. There was a high variability with respect to the length of time the bandages and stockings were worn for. Another questionnaire survey of the members of the same society demonstrated that following endothermal ablation, 87% of responders stated that they used compression stockings and 60% used bandages. Similar numbers used compression stockings and bandages after foam sclerotherapy. Once again, however, there was marked inconsistency in the length of time these were prescribed for. Bakker et al. carried out a randomised controlled trial looking at the use of compression stockings for two days compared to seven days following EVLA of the great saphenous vein (GSV). At one week, the physical function, vitality and pain score was significantly better in the seven-day compression group. By 6 weeks though, there were no major differences between the two groups. Elderman et al. also looked at the effect of compression stockings post-EVLA of the GSV. Patients were randomised to receiving either compression stockings or no stockings. Those in the no compression group had significantly worse pain scores up to seven days and used analgesia more frequently than the group randomised to compression. These two studies appear to indicate a benefit in the short term of compression therapy in patients undergoing EVLA, but are limited by the considerable dropouts in both studies (40 patients of the original 109 approached in the Bakker et al. study and 32 patients from Elderman et al. trial). The role of compression therapy followingUGFS has also been investigated. Hamel-Desnos et al.conducted a randomised study looking at the use of compression stockings post-foam sclerotherapy. Class 2 compression stockings (pressure exerted: 15–20mmHg) were used. No significant differences were found in the pain scores, inflammation, ecchymosis, induration, pigmentation or matting at 14 and 28 days. Compliance was an issue with only 40% of patients wearing compression stockings everyday. Due to the relatively small sample size (60 patients in total), the study may not have been powered sufficiently to enable detection of a significant difference between the groups. O’Hare et al. evaluated the use of compression bandaging for 1 and 5 days in patients having UGFS followed by TED stockings for two weeks. At the six-week point, no significant differences were noted in the