Treatment of patients with pelvic venous disorders is a “controversial topic,” Kathleen Gibson (Lake Washington Vascular Surgeons, Bellevue, USA) said at the Charing Cross Symposium (CX; 24–27 April, London, UK), as there is “no consensus on the best mode of treatment and no long-term outcome data” on the subject. To meet this global lack of guidelines and evidence-based clinical data, the International Pelvic Venous Work Group (IPVWG) launched last year with the aim of developing standardised classification systems and tools for clinical research and treatment of pelvic venous disorders. The group is supported by the American College of Phlebology (ACP) Foundation and the Society of Interventional Radiology Foundation (SIRF), and involves a multidisciplinary range of representatives from venous, phlebological, radiological, surgical and gynaecological societies and institutions.
Embolisation as a treatment for chronic pelvic pain is widely in use in the venous community, with two systematic reviews of case series and trials showing a link between embolisation and improved outcomes in affected women. However, as Neil Khilnani (Weill Cornell Medical College of Cornell University, New York, USA) maintained in a pelvic vein session at CX, “There is evidence that supports that patients do get better, but the evidence is weak.” Khilnani, who initiated the IPVWG, stated the group is “taking on the responsibility of accumulating evidence relatively rapidly”.
He told Venous News, “There are clear evidence gaps in taking care of patients with pelvic venous disorders, and as a group, we have embarked on a process to address those evidence gaps that exist within that area.”
Undermining the findings of the systematic reviews and, in general, trials or case series of pelvic venous disorders, is the heterogeneity of outcome measures, treatments techniques and diagnostic criteria. Mark Meissner (University of Washington, Seattle, USA) commented during the same session at CX, “The current state we are in is this alphabet soup of pelvic venous disease. We have this group of syndromes—Nutcracker, pelvic congestion, May-Thurner—none of which make a lot of sense.” The poorly defined and overlapping nature of the syndromes, along with gaps in knowledge about the pathophysiology underlying the syndromes, leads to “a number of errors” in diagnosis and subsequently causes poor treatment outcomes, Meissner argued. In the following presentation, Melvin Rosenblatt (St Vincent’s Medical Center, Bridgeport, USA) echoed this sentiment, saying, “There is enough overlap between these syndromes to cause confusion,” and as “we do not have a good definition … the reality is we have to get rid of this concept of syndrome.” Meissner similarly suggested disposing of the syndromes, in order to introduce “a new paradigm” in the area.
Not enough is known, however , about the pathophysiology or aetiology of the syndromes, and previous literature has been mainly focused on finding and treating venous reflux as the cause of pelvic venous disorder symptoms. Gibson and Khilnani both point out that venous obstruction has emerged as a component involved in the disorders. “We are talking about both reflux and obstruction,” Gibson said to Venous News, “and although there are groups that have been working in these areas that think what they are doing is the right thing in terms of treatment and diagnosis, when they present their data, their outcome measures are all vastly different because there is no standardisation. So, you cannot perform a meta-analysis in a really good way to know whether we are helping people or not.”
Developing standardised tools and measures
In 2017, the SIRF funded a multidisciplinary Research Consensus Panel that convened in October of last year in Washington DC, USA, to identify research questions and prioritise tools needed to perform clinical trials with high evidence-graded data results.
“It was clear that we need to have the proper tools before we embark on outcomes research in this area,” Khilnani said. “There is no point in doing research if we are not going to be able to define our patients very clearly,” Khilnani explained, pointing to the lack of disease criteria and discriminative tools for pelvic venous disorders. He added that validated endpoints were also a central discussion point during the consensus panel, with a lot of priority placed on a quality of life assessment tool to track patient improvement or deterioration in response to treatment. “We wanted to include the patient’ s voice, and also make the tool FDA acceptable”, to allow tool use in device and drug labelling studies.
Following a vote, the consensus panel selected five “top issues” to prioritise. These included a series of consensus multidisciplinary meetings to develop diagnostic criteria for pelvic venous disease, as well as a discriminative tool, a quality of life tool, a clinical scoring tool and finally a meeting to develop guidelines for evaluating and treating patients with symptoms related to the disease.
There currently are “very few guidelines in the gynaecologic community that affirms the disease even exists”, Khilnani said, “let alone gives us guidance in terms of what to do.” Nor is there much guidance given in the Venous Disease Guidelines, Khilnani pointed out, offering only a 2B recommendation for treatment of reflux for pelvic pain. No recommendations are given for obstruction or pelvic-origin varicose veins.
Currently in progress, however, is the work to develop discriminative tools. Two classification systems have been submitted by Rosenblatt and Meissner, who presented their respective tool proposals at CX. Meissner suggests a tool operating on distinctions in six categories of clinical presentations:
0. No clinical manifestations of venous disease
1. Non-cyclic chronic pelvic pain of venous origin
2. Pelvic origin lower extremity varices
3. Lower extremity oedema of pelvic venous origin
4. Venous claudication
5. Chronic left flank pain of venous origin with or without haematuria
a. Left flank pain
“This is the tool I personally favour , in that it is very cohesive with CEAP,” Meissner explained, adding that further designation of aetiology, anatomy and pathophysiology would be included in the classification. In Meissner’s examples of what the proposed classification would look like, a case of post-thrombotic venous claudication could be described as C4ESALCIV,LEIVPO. Aligning with CEAP, C here indicates clinical category (as described above), E indicates primary or secondary aetiology, A refers to anatomy—in this example, involvement of both the left common and external iliac veins, and the P distinguishes between reflux or obstruction in pathophysiology. A strength of this system, Meissner maintained, is the wide-spread familiarity with CEAP among vascular surgeons, which could mean uptake of a pelvic-specific version should prove easier than the introduction of a novel system.
Rosenblatt in contrast proposed a discriminative instrument that departs from the CEAP structure, relying on a three parameter classification: Pathology (P), symptom location (S) and varicosity location (V). Similar to CEAP, use of subscript defines variables within these categories, but the classification system is “very different” to Meissner’s, Rosenblatt said. With five variables of pathology and symptoms respectively, and four variables of varicosities, the tool emphasises location of problem areas for the patient. Rosenblatt explained, “the reality is, these are the parameters that will govern what I will do for the patient.” In addition to the numeric values of the three parameters, subscripts can provide information on the character of the symptoms as well as localisations such as right, left, or bilateral. Showing a few examples, Rosenblatt argued the tool produces classifications that are “simpler in terms of their configuration” compared to Meissner’s pelvic-specific CEAP examples. A patient with left gonadal vein reflux, pelvic pain and pelvic varicosities would in Rosenblatt’s proposed instrument be defined as P1,LS1V1. “The more letters you add, the more subscript you add, the more complicated it becomes,” he told his audience at CX, “and we want this tool to be accepted not only by vascular communities, but by the community at large— particularly the gynaecologic community that sees these patients primarily.”
A face-to-face meeting of the IPVWG scheduled for July 2018 is set to host a discussion to develop a consensus on a final discriminative tool to move forward with, and begin to introduce it internationally.
Meanwhile, Khilnani reported that a seed grant has been awarded by the SIR to work on developing a quality of life or patient-reported outcome tool, a project led by Khilnani along with Gibson, Meissner and gynaecologist Lee Learman (Florida Atlantic University, Boca Raton, USA). Khilnani maintained that establishing diagnostic criteria (disease definition) as well as treatment and reporting standards remain “on the horizon”.
“We started out with the idea that we needed to improve guidelines”, and to do so the group set out to initiate randomised clinical trials. However, “as we started out we realised that a lot of preliminary work was needed; we saw other venous trials, like ATTRACT, come out that were criticised because the outcome measures had flaws. So we decided to make sure we got the horse in front of the cart, not to proceed in doing randomised studies but rather to initiate our analysis instead on what tools we needed to be able to do those studies.”
Khilnani emphasised the project’s aim to “fast-track” development of its proposed instruments, with hopes that publications and implementation of the new tools will quickly follow the decision-making meetings like the one taking place in July. The original goal of the initiative, to provide robust clinical evidence for comprehensive guidelines in the field, thus remains visible at the end of the conscientious and methodical path to standardisation that the IPVWG has taken on.