Servier – Phlebolymphology

XXIII. Keynote lectures

Chronic pelvic vein disease 2019 update: what do we know? what we do not know?
Mark Meissner (US)
Pelvic venous disorders in women can present as chronic pelvic pain, lower extremity and vulvar varicosities, lower extremity swelling and pain, and left-flank pain and hematuria. Multiple evidence gaps exist regarding chronic pelvic disease with the consequence that nonvascular specialists rarely consider the diagnosis. Mark Meissner started his lecture by pointing out that the term “pelvic congestion syndrome” is nonsense and it should be abandoned in favor of “chronic pelvic venous disorders.” Indeed, he highlighted that the term “syndrome” is imprecise, misleading, and could result in inappropriate treatment and poor treatment outcomes. Pelvic venous disorders can include four different clinical presentations: chronic pelvic pain (pain, dyspareunia, dysuria); pelvic varices (gluteal, perineal, vulvar); renal symptoms (flank, pain, hematuria); and leg symptoms (pain, swelling). Two patterns of primary reflux (ovarian and internal iliac reflux) and two patterns of obstruction (iliac vein or left renal vein) can be distinguished. The obstruction patterns can determine, in turn, a secondary reflux either in the internal iliac vein or in the ovarian vein. All of the symptoms seem to be related to distension of the abdominal and pelvic venous reservoir. All reflux and obstruction can occur according to two patterns: uncompensated (no outflow from the distal reservoir) or compensated (collateral outflow from the distal reservoir). However, these mechanisms can all coexist, so patients can manifest similar symptoms with concordant mechanisms or similar symptoms with discordant mechanisms. Therefore, four interconnected systems (left renal vein, ovarian veins, internal iliac veins, and great saphenous veins) and two abdominal-pelvic reservoirs (renal hilum and pelvis) should be considered. Symptoms are usually related to reservoir distension and different patterns of reflux or obstruction can produce identical reservoir distension and symptoms. In uncompensated reflux or obstruction, pressure is transmitted to the distal reservoir. In compensated reflux or obstruction, pressure is decompressed via the collaterals.

Pelvic venous embolization is now recognized as the procedure of choice in the treatment of pelvic venous disorders. However, despite the efficacy of pelvic venous embolization, data from literature¹ suggests that 6% to 31.8% of patients do not get substantial relief from the procedure. Potential explanations for an inadequate response to treatment include patient variability, procedural variability, and inadequate outcome measures. Relevant patient factors may include a differential response of individual symptoms to treatment, underlying psychosocial issues, as coexisting depression or anxiety, and issues related to the processing of chronic pain. Regarding the latter, the role of altered pain processing in pelvic venous disorders is underappreciated and poorly understood. There are at least some data suggesting that substantial differences may occur in central pain processing among patients with chronic pain syndromes.²

Mark Meissner concluded his presentation by mentioning recent scientific efforts related to this topic. Indeed, the Society of Interventional Radiology Foundation funded a Research Consensus Panel in 2018 to prioritize a research agenda to address the gaps related to pelvic venous disorders.³ A panel of experts, representing several societies of physicians involved in the care of pelvic venous disorders, identified, as the most important research topics, the development of a consensus on the clinical and imaging criteria for pelvic venous disorders, a CEAP-like discriminative tool to categorize patients with pelvic venous disorders, quality of life tools to measure the health burden in women affected by pelvic venous disorders and its change after treatment with disease-specific outcome measures.

References
1. Champaneria R, Shah L, Moss J, et al. The relationship between pelvic vein incompetence and chronic pelvic pain in women: systematic reviews of diagnosis and treatment effectiveness. Health Technol Assess. 2016;20(5):1-108.
2. Brawn J, Morotti M, Zondervan KT, Becker CM, Vincent K. Central changes associated with chronic pelvic pain and endometriosis. Hum Reprod Update. 2014;20:737-747.
3. Khilnani NM, Meissner MH, Learman LA, et al. Research priorities in pelvic venous disorders in women: recommendations from a multidisciplinary research consensus panel. J Vasc Interv Radiol. 2019;30(6):781-789.

From understanding chronic venous ulceration to effective treatment
Alfred Obermayer (Austria)
Intractable venous leg ulcers are still common, painful, quality of life reducing, expensive and cause amputations despite lots of research, studies, recommendations, and guidelines. Alfred Obermayer asked why all “venous ulcers” without exception are located below the knee. The answer is because of gravidity and hydrostatic pressure. Due to gravity, everything on earth is pulled or pushed down. Hydrostatic pressure in healthy skin does not strain the microcirculation of the skin. Contrary, hydrostatic pressure in insufficient veins may strain superficial side branches of the capillaries and interstitium of the skin. The thoracoabdominal pump is central to venous return. Obese people have chronic venous insufficiency despite competent valves. Dependency syndrome can cause “hydrostatic ulcers.” An ulcer is a symptom of gravidity and consequently strategies against gravidity are required.

Alfred Obermayer presented his study on active bed rest as an accompanying therapy for the successful surgical treatment of venous leg ulcers. A venous ulcer is defined as an open skin lesion of the leg or foot that occurs in an area affected by venous hypertension and shows little or no tendency to spontaneous heal. He compared the results from the ESHAR and EVRA studies with his own results, showing that the ulcers included in his study were bigger, deeper, and more chronic, and patients with ankle-brachial pressure index <0.85 were not excluded. In addition, Alfred Obermayer discussed his work on lateral fasciectomy sparing the superficial peroneal nerve with a simultaneous mesh graft in nonhealing lateral leg ulcers of diverse vascular origin. Surgery of the ulcer includes debridement, shaving, fasciectomy, and mesh grafts. Data in the literature has shown that “single-shot surgery” is also effective in mixed ulcers. Venous ulcers are complicated by direct causes, such as locoregional venous hypertension, and aggravating risk factors, such as obesity, edema, contact sensitization, diabetes, cerebrovascular insufficiency, chronic peripheral arterial disease. Arterial revascularization in mixed ulcers does not reduce local venous hypertension, but abolition of the responsible incompetent reflux routes does reduce the venous hypertension. Alfred Obermayer finished his lecture by recommending experienced patient-tailored therapy for chronic venous ulceration.

“Thrombosis” after sclerotherapy: is it the same as a “classical” venous thrombosis?
Kurosh Parsi (Australia)
Kurosh Parsi discussed the question of whether thrombosis after sclerotherapy was the same as a “classic” venous thrombosis. “Thrombi” postsclerotherapy can be divided into four types: (i) sclerothrombus, which is a fibrin thrombus formed as a direct effect of sclerosant on blood; (ii) sclerocoagulum, a semiliquid material that contains fibrin thrombi, hemolyzed blood, and other sclerosant by-products; (iii) venous thrombosis (true venous thrombosis); and (iv) venous sclerosis, a fibrosis of superficial or deep veins. Sclerothrombi are the only direct effect of sclerosants. Coagulation studies have shown that low concentration detergent sclerosants activate platelets and induce the release of procoagulant microparticles, soluble P-selectin, and serotonin (sodium tetradecyl sulfate). Detergent sclerosants are biologically active at low, sublytic concentrations. Detergent sclerosants are surfactants that are amphiphilic compounds with a hydrophilic (polar) head and a hydrophobic (nonpolar) hydrocarbon tail. Surfactants have a similar structure to phospholipid molecules. Low-concentration detergent sclerosants activate platelets and consequently coagulation. Activated endothelial cells are responsible for angiogenesis and matting, activated mast cells are responsible for vasodilatation and matting, and activated leucocytes are responsible for inflammation and phlebitis. High sclerosant concentrations (>0.15%) reduce lysed platelets (both sodium tetradecyl sulfate and polidocanol), reduce fibrinogen (sodium tetradecyl sulfate), reduce clotting factors (sodium tetradecyl sulfate), and inhibit clot formation (both sodium tetradecyl sulfate and polidocanol, with a stronger effect with sodium tetradecyl sulfate). Low sclerosant concentrations (0.075% to 0.1%) increase platelet activation and increase clot formation.

Parsi concluded by stating that a low final concentration of sclerosant has procoagulant activity via inflammation and thrombosis with the formation of sclerothrombus (acute closure) and later recanalization or fibrosis (permanent closure). A high final concentration of sclerosant has anticoagulant activity via inflammation, but no thrombosis with nonthrombotic occlusion and formation of sclerocoagulum or fibrosis (permanent closure).