Contents P Editorial 54 By Alberto CAGGIAITI (Rome, lial) EIB Focus on venous embryogenesis of the human 55 lower limbs Jean-Francois UHL (Paris, France) fl The venous system of the foot: anatomy, physiology, 64 and clinical aspects Stefano RICCI (Rome ttaly) Micronized Purified Flavonoid Fraction 7 in the treatment of pelvic pain associated with pelvic varicose veins Sergey G. GAVRILOY, Anatoly V. KARALKIN, Ekaterina P MOSKALENKO (Moscow, Russia) Ps Management of superficial vein thrombosis of the 82 © | lower limbs: update and current recommendations Jean-Luc GILLET Ualliev, France) VEINews 90 Comments on recent publications Bo EKLOF (Lund, Sweden), Jenry G. NINIA, (New York, USA), and Paolo PRANDON, (Padua, tal) Congress % Congress and conference calendar 53Fy Editorial Alberto CAGGIATTI Dear Readers, Jean Francois Uhl from Pars (France) undertakes the challenge of explaining venous embryogenesis of the lowerlimbs. In act, most referenced studies in phlebology lewis, Hochstatar, et) relate not io humans, but to other mammals, and even fo birds or tepiles. After an interesting review ofthe techniques of embryological studies, Dr Ul provides aa updated summary of current knowledge on the development of leg veins. Moreover, he illustrates the text with his original, magnificent, and time-consuming 3D reconstructions. Finally Dr UN desrbes the else relatorship between embryology and eincoly relevant vascular ‘malformations. In his paper Stefano Ricei fom Rome (aly) reviews curent knowledge on the anatomy of foo! veins. Starting from anatomy (and ulrasound anatomy), Dr Rici sheds light on the complex mechanisms of the venous foot pump and how this pump connects with the more proximal pumps of the anterior and posterior leg. Moreover he highlights the possible implications of functional abnormalities inthis “chain of pumps." paying particular attention fo the phlebolagis’s point of view. When should a dilated vein on the dorsum ofthe foot be considered varicose, and therefore, neated? And how should i be neated? What are the causes ond significance of corona phlebectatica? Do primary varicose veins ofthe fot exist? Sergey G. Gravilov and colleagues from Moscow (Russia) report on a selected group of 85 women with pelvic pain and lower mb varicose veins, reated with micronized purlied flavonoid fraction for 8 weeks. Pobic pain (selassessed using a visual analog scale) wos significantly reduced in all women during the period of adminishaton, Pelvic pain soon recurred in women with evidence of pelvic varices. In tum, pain was still reduced afer 14 weeks in women with only lag varicose veins, In conclusion, the authors suggest the need for long-tem administration of micronized poured flavonoid fraction in women with pelvic varices, especially n those “wishing fora future pregnaney or reluctant to undergo surgery” Jean-Lue Gillet fom Bourgoin-Jalieu (France) reviews he evidence, or lack thereo, fr the correct reaiment of superficial vein thrombosis. Once considered a benign disease or a common complication of varicose veins, superizial vein thrombosis is currently included among the venous thromboembolic diseases because of the frequent concunence of deep vein thrombosis and pulmonary embolism. Although long: term anticoagulant treatment was recently proposed, Dr Gillet points out that the guidelines assign such treaiment a low-grade recommendation, He concludes tha futher research is needed to define subgroups of patients with a higher incidence of deep vein thrombosis or pulmonary embolism, in whom long-term anticoagulation may be warranted. Bo Eklaf from Lund (Sweden) crtically analyzes an excellent poper by Malas etal on the effectiveness of surgery of superficial veins in ulcerated patien's. Curious, Malas et al report that “adding supericial vein ligation and stipping to compression did not improve the wound healing rat," whereas Dr Eklof considers that “ablation is suggested for ulcer healing due to weak evidence; while fr the prevention of recurrence, ablation is commended due to sronger evidence” More prospecive stdies are surely needed! JJemy G. Ninia from NY (USA) comments on an important atile by Asbevioh ef ol showing that cyclic. ‘morphological and functional changes occur in the leg veins of women, These consist of a significant increase in vein diameter and in valve closure fimes. Dr Ninia descnbes the relationship between these venous changes and cyclic hormonal variations Finally Paolo Prandoni from haly analyzes for Phlebolymphology readers the randomized study of Haig et al on residual rates of reflux and obstruction after catheter-directed thrombolysis. Dr Prandoni shows how the resul’s of this study and others ore stongly suggestive of the protective role of early restoration of vein patency in preventing posthrombotc syndrome. Enjoy reading this issue! Alberto Caggiati 54Phiebolymphology - Vol 22. No. 2. 2015 Focus on venous embryogenesis of the human lower limbs Jean-Francois UHL Descartes Universy Paris France Keywords: compulsrasisted anatomical dissection, embryogenesis; embryo 3D reconstruction; human embryology primitive veins vasculogenesis; venous system Phlebolymphology. 2015,22(2}55-63 Copyright © US SAS. lights zoned wurwephlebolymphologyorg Abstract Embryogenesis of the venous system is a complex phenomenon that is not fully understood. In spite of the studies done by Bom, Hochsttter, and Lewis, ‘we do not know the precise chain of events leading to vasculogenesis of the ‘venous network in humans. Yet, ths is an important topic in order to improve our anatomical knowledge, which is of the highest interest in clinical practice. A good knowledge of anatomy is mandatory to perform in-depth assessments of chronic venous disorders by ultrasound mapping. Understanding venous embryology is also crucial to investigate and treat congenital venous malformations. Further research projects, particularly using new techniques of 3D modeling combined with immunolabeling of the anatomical structures (computer-assisted anatomical dissection) will contebute precious data regarding the onset and maturation of the human embryo's vessels, as well as providing data on the relationship between veins and nerves. Introduction Today, human embryology is one of the main topics in biomedical research! Several 3D atlases of the human embryo have been produced using the Camegie embryo collection (National Museum of Health ond Medicine, Washington, D.C, USA) and the Kyoto collection (Congenital Anomaly Research Contes, Kyoto, Japan|? The Visual Human Embryo with digital serial sections of human embryos from the Carnegie embryo collection illustrates the major stages cf human embryonic development The Kyoto human embryo collection’ is an example of computerized 3D modeling of human embryos by MRI, presented according to the Carnegie stages. However, today, to our knowledge, there have been no studies describing the different steps of development and the procise human anatomy ofthe venous systom ofthe lower limbs, due to the lack of direct observation The im of this paper is to focus on the updated knowledge about venous embryogenesis of the lower limbs and to discuss the interest of a new research technique for 3D modeling of human embryos-computer-assisted anatomical 55Phlebolymphology - Vol 22. No.2. 2015 Venous Embryology Better knowledge in venous anatomy J 4 Improvement in CVD Diagnosis and diagnosis and mapping treatment of CVM| Figure 1. Usefulness of embryology and anatomy al nical rachce, which is ewcial for the ivesigation of CDs and Inanogement of CV Abbreviations: CVD, venous malfomations. hronic venous disease; CVM, congenital dissection (CAAD)! A better understanding of embryology, and therefore venous anatomy, is of the highest interest for the clinical practice in phlebology and vascular medicine (Figure 1) Historical References The Scandinavian method of Born’ was created in 1883 to build 3D reconstructions of embryos. Its based on the enlargement of serial anatomical slices, displayed on a tablet of colored wax. In 1893, Hochstetter also made huge progress on the embryogenesis of amniotes.® However, he most innovative results were shown by Lewis in 1906 in the rabbit? In addition, the works of Bokova (1970)® and Gilbert (1990)" are also noteworthy. Since then, several works on the Hox genes have brought about a revolution in our knowledge of limb organogenesis. Hox genes control the positional information, spatial orientation, morphogen gradients, and diflerentiation.® Molecular models and growth factors also condition the limb's development. Finally, vasculogenesis is alo tightly related to the skeleton formation. Development of the Human Embryo and Lower Limbs The human embryo development can be divided into three main stages: (i) embryogenesis occurs between postovulatory weeks 0 and 4; (i) organogenesis between postovulatory weeks 4 and 8 (Figure 2) and (ii) the fetal period between week 9 and birth. Jean-Francois UHL 56 Figure 2. Organogenesis period from postowlatory weeks 4 108. The lower limb buds fis! oppear ot Comegio stage 15 (33 days; embryo size, 8 mm). Copyrights Brady R Smith, Figure 2 recopitulates the Camegie stages of organo genesis, which is the main period of interest for the lower limb’s development, taking place between the 4th and the 8th postovulatory weeks (Camegie stages 13 to 23) Limb development is a complex phenomenon directed by Hox genes, as we have seen previously. Here, we will only consider the simple morphological point of view. The lower limb’s development steps are shown in Figure 3.The first bud of the lower limb appears a couple of days after the upper limb, around 33 days (embryo size, 8 mm; Camegie stage 15). At the beginning, itis reduced to a flat palette, which appears thicker at its extremity and along its caudal border at 6 weeks (embryo size, 15 mm). This is explained by the superficial migration of ectodermal cells, which increases IG < 6 8 » 2 6n@g a 6mm 12 15 17 19 25 re 3. Development of the lower limb buds during exgano-Focus on venous embryogenesis ofthe human lower limbs the density of vessels in those locations, particulary in the ‘marginal venous network The foes appear at stage 20 (50 doys; 18 mm) and the limb’s development ends at stage 23 (56 days; 30 mm). Classic “Basic” Knowledge about Venous Embryogenesis The early stages of development The “primitive veins” were desciibed by lewis fer observations made in the rabbit (Figure 4)° Lower limb buds appear toward the end of day 10 during rabbit ‘embryonic development. Stating on day 14, Lewis observed «@ concentration of the venous network at the caudal and distal aspect ofthe limb bud, which is called the marginal vein, This drains into a primitive fibular vein, then into an ischiatic and posterior cardinal vein (Camegie stage 1). On day 17, he observed that the fibular vein became the main vein, while the lateral marginal vein disappears (Camegie stage 2). At about 3 weeks of development (Camegie stage 3), he noticed the existence of an anastomotic branch originating from the sciatic vein and connecting to 4@ new vessel, the femoral vein. The latter forms the final deep venous system, while the sciatic vein disappears 1 2 Figure 4. The primitive veins af woek 5 ‘Note that the veins of the primitive limb are fed by the umbilical vein (containing oxygenated blood): the blood flux goes from the 00! o the extremity ofthe mb (black arrows). Therefore, the veins appear fst. The arteries then drain the blood back fom the limb fed onowsh Abbreviations: primitive marginal vein; 2, primitive fibular vein; 3, primitive axial vein; 4, primitive ischiatie vein, 5, primitive “anterior bial vein; Um, umbileal vein Theory of angio-guiding nerves Loter (after week 6), the arcangement of the venous network could be explained by the theory of the angio-guiding nerves proposed by Gill: the nerves appear at 6 weeks (embryo size, 18 mm; Camegie stage 19; Figure 5). the axons ond Schwann calls sacrote a vascular endothelial growth factor (VEGF). It hos a 2old role: () to attract the 97 Phiebolymphology - Vol 22. No. 2. 2015 Figure 5. Growth of the three angioguiding nerves at week 6 Abbreviations: 1, primitive marginal vein 2, primitive fibular vein; 3, primitive axial vein; 5, primitive anterior tibial vein: 6, Intorgemellar vein (vein of the sural nerve); A axial (sciatic) popliteal crossroad; Cav, caudal (smal sciatic Ce cranial (femoral) F femoral plexus purple, caudoploxus:s sural nerve vascular plexuses to the vicinity of the nerves; and (i) to induce their arterial, venous, or lymphatic specialization.” The ephrin fomily (82-84) plays an important role in the diferentation of primtve endothelial cell." Fetal period Aer postovulatory week 8, known as the fetal period, the venous plexuses along the three newes condense and mature (Figure 6) Figure 6. Venous sytem of weeks 7 10 8 Abbreviations 1, primitive marginal vein; 1b, SSV; 2, primtivo fibular vein; 3, pimilve exial voy 4 cranial extension ‘of the 58V thom caudal plexus), 5 priniive ontorior tibial vin, 6, intergemellar vein {vein of the sural nove), 7. higher part of the 85V {fom coudal plexus) 8, arch of the SSV (anastomosis botwoon arial and cavdal plexuses} A, axial nono {sia Cpoplioal cossoad {anastomosis bonveon axial and cranial plexuses) Cou, coudal nono (small sca, Cr cranial now fromoral F lomoral plexus, 5 sural nore, SSV, small saphonous Data limitations Data about the early stages ore from small mammals and need to be confirmed by direct observations inhuman embryos. Angio-guiding newes are just a hypothesis that is bosed on extensive anatomical observations in adults, but has not yet been confirmed in embryos.Phlebolymphology - Vol 22. No.2. 2015 Today's Hypotheses and Proposals for the Steps of Venous Embryogenesis Our knowledge is reduced to several hypotheses, which need to be confirmed by further direct obsorvations and 3D_ reconstructions of human embryos (Figures 7 and 8): + The lower limb bud first appears at 33 days (embryo size, 6 mm; Camogie stage 15). The vascular layout is then reduced to @ peripheral undifferentiated venous network, which is located subcutaneously ‘and secondary to central artery. Around week 5 (37 days; embryo size; 8 to 11 mm; Camegie stage 16), the primitive veins emerge. A thickening appears at the distal and caudal aspect of the bud due to the migration of endothelial cells, ‘and explains the location ofthe frst veins of the limb, Ansieging ‘geatapbences Figure 7 Summary of he organogenesis period of an embryo’s development (postowlatory weeks (POW) 4 to 8; Camegie stages 15 10 23). Ar wook 4 (Comegio stage 15) the roicular phase starts where the contal artery a) and superical venous plows ( develop. Al weok 5 (Camegie stage 16), the primitive veins {marginal [121 fbvlor 1 ond axa (4), umbilical vein (5, posteror cardinal vein (6), anterior tibial vein (7), and small saphenous vein (SSV 18}) appear ‘Ar weok 6 (Camogio stage 19) tho thrae angio-quiding nonos (axial lsioke af cranial femoral bl ond caudal (small sions aD oppear At woek 7 10 8 (Comegio stage 23), tho following appear marginal vein (1); fibular vein (3) cxial vein (4) umbrleal vein (5h, anterior tibial voin (7) small saphonous vein (8), posterior tibial voin (9 lomoropopleal axis (10) deep fomorl voin (11) ‘opigastic voi (12) cronial exonsion of the SSV (13) groot Sophonous vain (14) arch ofthe SV Note the direction of blood circulation coming fram the umbilical vein: from the root to the extremities of the veins (black arrows), and then circulated back by the arteries (red arrows) 58 Jean-Francois UHL Fetal period 1245 Ton Femeral voln Fgu,8. Summary oho fatal prod of dowlopmon (aor wook 8) The prime veins are colored in purple, Notice th he ft {oeks 910 15 commonly has a big axial vein whilo the lomoral ein is smaller ond ploxus shaped lator the axial vein becomes © small orcade along the scone nena, and the Temorol vein Becomes the moin tvnkof the thigh inthe major ofcoses ot birth commonly wt 2 coltoral canal Abbreviations: 3, fbulor veins, 4, arch of tho $SV; 5, groat Saphonovs vein; 7 anterior bial wens, 8, SSV, 9, posterior Mba 1G femoral vein II, axial vin; 12, opigashic vei 13, thigh secs ef S81 coe ene en 8 cat oy ypogosirc vein, 17 extemal tac vain, 18, inferior gluteal vin ce calojoal canal P pororating branches ofthe femoral vin POW, postowlotory woek sna oxi arcade along tho sciatic nero; 854 small sophonovs vain which ore located supericially and are called the marginal venous sinus. The oxygenated blood comes from the placenta by the umbilical vein joining the posterior cardinal vein Ir then reaches the root of the limb by the primitive ischiatic vein, feeds the primitive fibular vein, and finally, forms the lateral marginal vein located ot the caudal aspect of the bud. The distal part of the ‘marginal vein will fer the “primitive smal saphenous vein” the vary first vain present in the adult to appear in the embryo. At that time, the nerves do not exis. The blood goes back to the root ofthe primitive lim by the arteries (Figure 7, left). ‘Around week 6 (47 days; embryo size, 16 to 18 mm; Camogie stage 19), the three angio-guiding nerves ‘appear and quickly grow along the limb bud. ThisFocus on venous embryogenesis ofthe human lower limbs will initiate the development of the deep venous system and the great saphenous vein. In fact, due to the secretion of VEGF by the Schwann cells, the three angio-guiding nerves will tract the undifferentiated vascular plexuses and induce their maturation into veins, artaries, and lymphatics. These three angio: guiding nerves are: (i) axially, the sciatic nerve; (i) cronialy, the femoral nerve; and (ii) caudally, the small sciatic nerve. ‘Acound week 7 to 8, the three venous plexuses of the lower limb grow and mature along the three angio guiding nerves. Along the sciatic (axial) nerve, the primitive axial vein becomes a huge vein and joins the deep femoral vein upwards. At this time, this is the main venous trunk of the thigh, but it will ragrass to become a small arcade in the majorily of adults Along the femoral (cranial) nerve from the cranial ploxus, the great saphenous vein appears together with the femoral vein, which connects upward with the ischiatic vein to form the iliac vein. Downward, the anastomosis with the axial plexus will give bith to the popliteal crossroad. Along the caudal nerve {small sciatic), the caudal plexus forms the distal part cof the small saphenous vein (SSV) below the knee ‘and the cranial extension of the SSV at the thigh level. A possible anastomosis with the axial plexus will lead to $SV termination into the popliteal axis (saphenous popliteal junction or French “crosse"). Of note, around weeks 6 to 8, there is « medial rotation of the limb, where the cranial ospect of the limb becomes medial and the caudal aspect becomes lateral AY the end of the 12th wock, organogenesis is finished and the venous anatomy is similar to an adult. However, some remodeling of the venous ‘xis will occur, particularly at the femoral level. The coxial vein, which i @ large vein, will become « small carcade along the sciatic nerve, while the femoral vein commonly reduces to a thin network along the femoral nerve and will become the main venous axis of the thigh in 90% of the cases in adults Alter 12 weeks, remodeling of the subcutaneous pat of the supericial venous system (reticulum network) will lead to its definitive anatomy at birth. The venous vales appear and are closely related to the hemodynamic pattems of the anatomical ‘arrangement, and thus, the blood circulation. Phiebolymphology - Vol 22. No. 2. 2015 CAAD: A New Technique to Build 3D Models Depicting the Main Steps of Venous Embryogenesis CAAD was fist used by Yucel and Baskin to identity the penis newes.” Our laboratory then published several papers showing the benetit of CAD for the studies of the male and female uretra2* and intrapehic innervation? Wo recently dedicated the CAD technique to the 3D reconstruction of the embryo's limbs. Briefly the principle of this technique is to make thin horizontal slices of the limbs. Alter digitalzation and alignment of the slices, « different staining is used, in particular, proteins $-100 and D2-40 are stained to recognize the newves and vessels, respectivaly. ‘An example is shown in Figure 9 with the reconstruction of « big axial vein at the thigh 59 Figure 9. lnmune markers for nowes and vessels in 0 13.80k- old fous Panel A A 3D reconstructed limb showing a big axial vein along the sciatic nerve, while the femoral vein is reduced to a small plexus-shoped network located inside the femoral canal wilh is companions the femoral artory and femoral nerve. Slices of a 13-weekold fol stained for nerve-specific immune ‘markers (slice A with protein S-100; Panel 8) and vessel-specifc immune markers (sce B with D2-40; Panel C) using the CAD technique. Abbroviations: I, sciatic nerve; 2, femoral nene; 3, femoral vein; 4, femoral arty: a, axial vein; CADD, compulerassistod anatomical dissection; & fibula; F femur Tibia ‘The first results ofthese 3D reconstructed limbs were recently obtained from three embryos at postovulatory weeks 13 10 15* (discussed in the following section and illustrated in Figures 10 and 11), but its « work in progress as detailed data about the eaier stages are sill lacking,Clinical Applications of Embryogenesis Anatomical variations of the femoral vein Three types of anatomical variations of the femoral vein have been observed in 12% of adults (Figure 12)?" If the large primitive ‘axial vein’ of the embryo persists, then either an axiofemoral trunk (unitruncular layout, 3%) or axiofemoral vein (bitruncular layout, 9%) is found in adults. ‘Most commonly, a modal layout (88%) will be found in the adults anatomy: the primitive axial vein becomes hypotrophic and reduced to a small arcade. The main vein of the thigh is a femoral vein inside the femoral canal fac ies) EieieeFocus on venous embryogenesis ofthe human lower limbs Phiebolymphology - Vol 22. No. 2. 2015 Venous Embryogenesis in a Nutshell The primitive venous system of the lower limb appears between weeks 5 and 6 of the embiyo's development. The ‘marginal vein and the small saphenous vein appear superficially. They come from the primitive ischiatic vein, then the ‘axial system, and then from the primitive fibular vein, The second stage occurs between weeks 7 and 8, after the apparition of the nerves (end of week 6) by maturation of the three plexuses along the angio-guiding nerves; the femoral vein, the great saphenous vein, and the posterior fibial veins appear. The anastomosis between the three plexuses also forms the popliteal crossroad, the saphenous popliteal junction, and the Giacomini vein. Anatomy of the lateral network of the leg and fibular in adults, is @ remnant of the primitive marginal vein. Just like in the embryo, itis connected to the fibular veins by perforators in the adult A thin marginal venous network ofthe leg, commonly seen several fibular perforators as is nicely shown in Figure 13 of marginal vein and fibular perforators in an adul bone). Notice the alig ions (10, 14, 17 and 22 em dissection afer latex injection in the lo og (lateral view afar resection of tho fi ting the thin marginal nowork tothe fibular veins a! spec the apex of 1al network connected tothe fibular cied fo the anterior tibial perlorators; 2, lateral maxg 1e small saphenous vein, Abbreviations: 1, dorsal foo! nehwork co veins; 3, caleaneus perforator vein; 4, Achiloon vein jo 6Phlebolymphology - Vol 22. No.2. 2015 Conclusion Understanding embryogenesis is important mostly in terms of clinical applications: it improves our anatomical knowledge about the venous system and is particularly useful to perform a venous mapping for all CVD patients Embryology is also essential for the diagnosis and management of congenital vascular malformations (CVM) As explained in the Hamburg classification of CVM™ the severity of the malformations is related to the stage of the tembryo's development when they occur (i) before week 4, they provide severe “extratunculay” malformations; (i) between week 4 and 8, they are responsible forless severe “truncular’ malformations; and (i) after the organogenesis period (week 8), simple anatomical variations will occur Jean-Francois UHL Corresponding author Jean-Francois UHL, \Vesculer surgeon, member ofthe French Academy of Surgery Development, Imaging ond Anatomy Laboratory of Anatomy Resaorch Unit URDIA EA4465 Universi Pris Descartes UNESCO chair of digital Anctomy Emil jeanfrancoisubl@gmailcom 7. Bom G. Die paten modeler methode ‘ich Miko Ane 188322 584.599 REFERENCES 1. Popper MS Anlogentse 8 Hoch eage 2 17 Mulouyoma 5. Shin, Bach phogense de fb ssa: Enlongescie da Verenyems ‘nigcht Andon Dl Sensory debe clone lo cinge chien Sauper iy Cogenbou tents deere he pane of in Fencl adecne Sconces, Fea Tie leet ohsed Sree dironaten re ea ood eave ee Sine ZattB Antonue” ‘esl brncing the in Ca Etmiclaongugecca 0. Soon107009 968, 2. Yamada Nooshina F Hiose A tui Garry Yeo Yon tli “ropame A ftedo flake Engelnarn BV 3e9 208 18. Wang HU. Chen 2 Andean DL Detlopmaileratony a he hun Male Sacto and egiogeni tbe SD'mogng ord chal © eis F Development lhe ‘Marcon beac enbnon ces Chgces GS lel tind ct eniogos Aw nor Ge veins veld by on 2 od Sr The Huon Ember. Coat: tossi3 0 seco ght Call Ponsa 758 itech 2 10. Ketow Hooke M.Ctyton des. Yael Bein I Wntaton of 3. Ofahiy Mller = Developments vena pte paint nel ‘Srmmincatng benches meng he Spe toman bios een Pilialge Ssedtoan 8 SEeur pein Sees fares of epoca Nerden Sra Pos the pe ol 200870153 18 er 11 Sephan & Haman Pov mboyaooy Sel WA Unt) Washnge” 20. Krom | Droupy Abd eo The 4. The Viel Han Enbro Adigal Fae 98. proche cate ond nae ol he nr imoge dteban cf senclysctoned (tbe mel amen uth togeal in enya fon he Conegie 12. Toms Tele C Going models td mmunchisachomal sues Sa {Staci Nw Oteane tocar Tveratoe bb dewopen eligmurchitacrercl aus ibang Sats UmentyecihSdences ‘Development 2009136 7190 Ustsoossesssee Err 3AM hap antahonenenin. Caeser 1a Tobin Ch Rani honecbows and 2. Kat | Deugy 5 Abd Alama rns locos tar eel models URI Bart & Berns nnenatn of 5. Yamada Usabe C Nolasa Tt Erin devopnen Ca 191 60199 Teens oman val spa $3 fi Grohe ond mei stan of m eaotsenf hanenchabeloni m'nenlJoclopsen' rd er Sedona he lous Eur Ul Ae ere fey 1. karOun sk 5, Soaah ee ‘based on the human embryo specimens cal The farming limb skeleton serves as bezel one tne enon © Suignangconurfotmnbvacue 72. Abid 8 Bssede 1 ale 00825568. pulning regulon ol eg Conpurented oncom discion Bovlopent 2009 361268272 CUB a nagy Karbe N Holoion hain Spplecion in espa ctcton Se Btina ies Fe te 15, GileC Dapostspoplitshypohais $y Sup Bok hot 30123470170, SDrecontacon ot he ower ib’ Sr ernodesPhcboepa 1996510574 vevow sr men ee ng he 23. UNE Gilt, Chaim M. The compulerasssted anatomical dissection 16. UbLIF Gillot C Embryology and theee- ‘anatomical variations of the femoral vein. (Ril clave Sy foil Act Snead Tose Sap oi0sae SIaraTLSS, Phlebology. 2007;22:194-206. 24, Lee BB. New approaches to the treatment of congenial wear rnollomatons (GVM)-2 engl cone fxperance Eur / Vos Endovase Sur, 2050 84-197 62Focus on venous embryogenesis ofthe human lower limbs FURTHER READING: RECONSTRUCTION-TYPE BOR! eter K Rehonsiuktions mathodn Gralswald, Germany, 1922 Bom G. Uber die Notenchlen und den Thvenennasengang der Anpibion Mel lb 18762577 645. Bom G. Die Plsenmodeimahede, ‘Auch lr mikoshopche Anatom 1886,22:564 (1883) 4 Bom G. Nach inl di Plotenmodaliemathode.Z Wiss Mikes Tass s(eb35-055, Kastchonko N, Dis graphiche tlorng, Anal Ane 1887,2:426-435, Ker JG. The development of lpidoson potodaxa IL Develgpment ol he skin Sd ts ervaves. 1 Mirose Set oaaeale-a59, Phiebolymphology - Vol 22. No. 2. 2015 (lens WH The ute of guide planes pd plster of pai for recansucsons iro sl sections some pans on recondhuctn, Anat Rac 19159.719-720 he de Boer GR the Developme ofthe Vertebrate Stull Onord, UK: Carendon Press 1997, 63Phlebolymphology - Vol 22. No.2. 2015 The venous system of the foot: anatomy, physiology, and clinical aspects Stefano RICCI ‘Ambulotorio Febologico Rome, lly Keywords: cal foot plantar sole; venous return venous system Phlobolymphology. 2015;22(2)64.75 Copyright © US SAS. lights zoned wurwephlebolymphologyorg Abstract Venous return from the foot is worthy of interest for both research and clinical purposes. This review summarizes the available knowledge of venous rotuen from the foot with @ special focus on research and clinical implications. The anatomy and physiology of venous return are described with an emphasis on the diffeconces betwoen standing and walking and the interplay between the venous systems of both the foot and the calf. Selected conditions of clinical intorost are discussed and mechanistically interpreted, including the distinctive localization of log ulcers, the corona phlebecatica, the possible independence of dilatation of the veins of the foot from refluxing varices, and the arteriovenous fistulae of the foot. From this perspective, the practice of using a postoperative lower-log bandage is also discussed. Lilo attention has been devoted to the veins of the foot surgeons begin the saphenectomy where the foot ends and echographists do not extend their exploration distally to the malleolus. Even onatomists have been more interested in the ortories of the foot, rather than the veins, as demonstrated by the more detailed description of artries in anatomical tables. Finally experts in hemodynamics focus on the calf to explain the mechanism of the limb pump, leaving the blood in the foot “undrained” However, as shown in the present bibliography a few wel-conducted classic studies have clarified the anatomical and functional characteristics of venous circulation in the foot, although some areas of uncertainty stl exis ‘The main concepis conceming the anatomy and physiology of venous return from the foot will be revisited in this article, followed by observations of clinical interest and hypotheses for research and daily practice. ‘Anatomy In 1968, Kuster et al provided the most complete description of the veins of the foot! describing five systems: (i) the superficial veins of the sole (also known as 64Venous system ofthe foot Lojars’ venous plexus); (i) the deep veins of the sole; (i) the superficial dorsal plexus; (iv) the marginal veins and dorsal venous arch; and (.) the perforating system. i. The superficial veins of the sole (lejars’ venous plexus), once considered the most important impulse for venous retumn, is @ net of tiny veins with limited clinical intorest (Figure 1)? Figure 1. The sypericil vein network of he slo is made by a Eure 2 The appari vin netwolf the soe it made by Image courtesy of Ub ji. The deep veins of he sole are the most interesting from a functional point of view. © the deep plantar venous arch euns from the proximal end of the fist interosseous space to tho base of the fith metatarsal and accompanies the deep plantar arterial arch, which receives the deep metatarsal veins and surounding muscular veins (Figure 2)* The deep plantar venous arch measures =9 cm (range, 5 to 14 cm) according to Binns and Pho® and =48 mm according to Corley? with an average external diameter of 5 mmné In 8 out of 10 foot dissections, 2 deep plantar venous arches wore identified, which is ofen rafored to as boing doubled: A single, constant, and proximally oriented valve has been described The medial plantar vein is a thin ond short vein (5 em long according to Uhl et al? =12 cm according to Binns and Pho’ and =38 mm according to Corley’) that is usually doubled, with « fow proximally oriented valves: Itruns along the medial border of the sole from the medial end of the plantar arch to the medial malleolus to form the posterior tibial veins after the confluence with the lateral plantar vein. The medial plantar vein receives blood from the adjacent muscles, ie, the 65 Phlebolymphology - Vol 22. No. 2. 2015 Figure 2. Deep plantar veins projected over the foot bones. abductor hallucis, the flexor digitorum brevis, ond the plantar quadratus muscle. The lateral plantar vein (length between 80 mmé and 84 mm is curved, constantly doubled, and large (2 mm) with fusiform dilatations (resembling the gastrocnemius sinuses)! and it is located between the two muscle layers of the sole of the foot (ie, quadratus planiae and abductor allucis). Proximally directed valves are present in the lateral plantar vein. The lateral plantar artery lies between the two parts of this vein, which are interconnected an average of three times! The lateral plantar vein is in continuity with the lateral end of the plantar venous arch and runs back across the sole fo join the medial vein at the caleaneal confluent, forming the posterior tibial veins. It receives blood from the lateral marginal vein, the calcaneal veins, and the veins in the adjacent large plantar muscles. In the deep plantar system, doubled veins have been constantly observed with the comesponding arteries! The ves- sels are surrounded by connective fissue and this arrange- ‘ment facilitates venous compression by the artery, serving as a localized pumping action’ Furthermore, while performingPhlebolymphology - Vol 22. No.2. 2015 Stefano RICCI cadaveric dissections, Corley found a consistent presence of an evident secondary arch either located deep in the quadratus plantae or as part of a more complex network of deep interconnections® This could represent a potential blood reservoir explaining the interindividual diferences in venous outflow recorded during muscular activiy® ii, The supericial dorsal plexus may be clinically important because it is in continuity with the superficial veins of the leg and ankle and may be involved in varicose dilatation of the superficial veins. These veins are very superficial (limited to the fat layer), well visible (esthetically demanding), and contiguous with the cutaneous nerves (easily encountered during foot phlebectomies). iv The marginal veins and the dorsol arch are separated from the superficial dorsal plexus by a relatively strong connective fascia (coresponding to the fascia covering the great saphenous vein and the small saphenous vein all over the limb) thus, the superficial network of the dorsum runs separaiely over these veins in a distinct layer (Figure 3 and 4)*° The dorsal arch lies over the proximal ends of the metatarsal bones and is the origin of the marginal veins, receiving the dorsal metatarsal veins and several perforating veins. The medial marginal vein arises from the perforator of the first Figure 3. Marginal veins and their superficial n The marginal veins, connected anteriorly by vein (Panel A) ere the origin of Ihe heo ‘re similarly situated under the super twork of the dorsum of the loot super metatarsal interspace and is contiguous with the great saphenous vein. It receives several perforators from the plantar veins that are important from a functional point of view. The lateral marginal vein ends in the short saphenous vein, which receives important perforators from the deep plantar veins \._ The perforating system is the most distinctive system of the foot because these veins are valveless or contain valves oriented from deep to superficial veins. According to Uhl et al:* Figure 4. Suypericial network of clearly visible wih o duplex sca dorsum flongitudl © The perforator of the first metatarsal interspace generally has @ large diameter without valves and connects the dorsal venous arch with the deep plantar system, and as a consequence, it is the true starting point of all venous networks in the foot. It accompanies the dorsalis pedis artery. The network runs independently over an arch vein (hansversal), which is separated by the supericial fascia © The medial marginal perforators, which open into the medial marginal vein, diferentiate into plantar veins (i, malleolas, navicular, and cuneiform veins) and dorsal veins (ie, anterior tibial vein) © Consistently the lateral marginal perforators-the caleaneal and cuboidal veins-join the lateral marginal vein at the perimalleolar plexusVenous system ofthe foot Venomuscular Pumps The energy needed for venous blood to overcome the hydrostatic pressure, which is generated by the distance between the heart and the leg in standing subjects in a dynamic state, is created by multiple myofascial compariments that are separate yet integrated, act like ‘muscle pump units® and are known as the venomuscular pumps (VMP). The composition of VMPs includes the following": () the venous foot pump; (i) the distal and proximal calf pumps; (i) the thigh pump; and (i) the abdominal pump. The contraction ond relaxation of the skeletal muscles surrounding the veins impress volume and pressure variations to the venous blood, while the flow direction is conditioned by the valvular arrangements." The position ofeach deep venous vahulartractwilldetermine the pump output. A tract located inside the muscle creates very effective ejection systoms (gastrocnemius, soleus) At the soleus and gastrocnemius sites, the veins are numerous tand arranged in @ spiral shape due to the longitudinal excursion amplitude of the muscles between contraction and relaxation (volumetric pump). Exramuscular tracts are subjected to compression over tough sudaces, ie, bone or aponeuroses, by the close muscles; therefore, they have a lower, though sill satisfactory, efficiency (distal calf pump Cr peristaltic pump). Ths isthe case for the posterior deep compariment veins (posterior tibial veins and peroneal veins) and the anterior extemal compartment veins (anterior tibial veins), which have a rectilinear organization, as the containing muscles lean against the bones and have a limited shortening during contection? The supeticial venous network is only inditeclly affected by the VMPs through aspiration during muscle relaxation or diastole; here is an exception for he venous foot pump where the supericial veins may be directly filled, which is in contrast with the deep veins. Proximal calf muscle pump The most active pump of the lower limb is the one due to the sural and gastrocnemius muscles: these muscles are rich in venous sinuses that are strongly squeezed during the impulse phase of the step, when pressure exceeds 200 mm Hg and calf volume decreases by 80%? ‘When the calf muscles contrac, the pressure rsesin all veins of the lower limb, and the increase is three times greater in muscle than in supeicial veins. During muscle contraction (systole), the strong pressure gradient between the deep 67 Phlebolymphology - Vol 22. No. 2. 2015 calf veins and the popliteal vein causes a rapid flux of blood from the calf to the thigh (Figure 5). Venous pressure exceeds the intramuscular pressure in calf compartments in most of the stop phases, but competent venous valves prevent retrograde flow. On subsequent muscle relaxation (diastole), venous pressure falls below the pressure at rest. The fall is greater in the deep veins, less in the superficial veins, and negligible in the popliteal vein. In this phase, pporforator veins allow blood to flow from the superical to the deep veins, while competent valves prevent backllow from the popliteal to the deep calf veins A B Cc Muscle Distal calf Foot pump pump pump PASSIV: ACE Figure 5. Mechanism of action fr the distal colf pump. Panel A. Muscles (M) are unsheathed by common fascia (F) and veins within the same compartment. Contraction ofthe calf ‘muscles, as in plantar flexion of the ankle joint during walking bottom) expels blood into the proximal collecting vein. During relaxation (lop), the blood is drained fom the supericial veins {V1 info tho deep veins (DV) in addition to the arterial inflow; thereby, preparing for the subsequent ejection. V, venous vale. Rane! 8 Distal call pump: upon dorsiflexion of the ankle (passive ¢r active), the bulk of the colf muscle (M) descends within the fosil sheath (Fand expel blood in tho distal veins lke a piston. Panel ‘venous foo! pump: upon weight bearing, the tarso-metoiarsal joins are extended and the tarsal arch is atened Thus, the veins are stretched. causing them fo eject their content of blood. Image courtesy ofE Standen,Phlebolymphology - Vol 22. No.2. 2015 Distal calf “piston” pump In contrast with conventional descriptions, there are two pumping systems in the calf, a proximal (gastrocnemius/ soleus) and a distal systems The distal one is activated by dorsiflexion of the ankle (Figure 5), ie, when the calf muscles are stretched and their distal parts descend within the fascial sheath. This movement acts like a piston, which expels venous blood in a proximal direction. The pump mechanism has been documented by ultrasound Doppler measurements of venous blood flow‘ and is supported by compariment pressure measurements * Venous foot pump According to Browse et al” the force required to overcome the pressure of the blood column within the venous system of the lower legs exceeds that generated within the muscular compariments of the calf during motion. For Gardner and Fox’ the plantar venous plexus could overcome this Figure 6. Phlebogram ofthe lateral plantar veins with a dilated! middle portion that acts like a reservoic Panol A. Nonweight bearing. Panel B. Weight bearing, which empties the venous foot pump into the calf From reference 14: archer and Fox, (OS Press. 2001, © 2001 68 Stefano RICCI pressure. Located within the plantar surface of the foot, the plontar venous plexus is submitted to high-pressure compression during ambulation, possibly constituting a mechanism for driving the venous outflow from the leg (Figure 6° During the gait process, the plantar plexus is able to overcome the pressure of the blood column within the deep venous system of the call It squeezes a small volume (20 to 30 ml)” but the pumping mechanism is very effective; it works by voiding chambers distal to their axis and without a proximal valve, but closed distally in a cul de-sac formation (C. Franceschi, unpublished data) The venous foot pump, in fact, is activated by the compression caused by either body weight or plantar muscle contractions during each step. According to the anatomical disposition, the site of the pump may be identified in the lateral plantar veins, whose middle portion is dilated and acts os a reservoir with a volume of 20 to 30 ml (Figure 6)” The ratio of the diameter of the lateral plantar veins when compared with the diameter of the posterior tibial veins is L91:1, which creates a bellows: type elect to rapidly increase the velocity of flow within the posterior tibial veins. The distal part of the pump is a sort of “suction pole’ coming from the highly vascularized toes and the large metatarsal perforator vein that drains the superficial network of the medial marginal vein’ The posterior par, at the calcaneal confluent, comesponds to an “ejection pole,” which empties directly into the posterior fibial veins? During a walking exercise, the foot is in contact with the ground 60% of the time and remains off the ground 40% of the fime.® The foot architecture is designed so that ‘weight bearing takes place almost entirely on the ball of the foot, the heel, and the lateral part of the plantar surface of the foot. The medial part remains pressure free; thus, the plantar veins, which are located here, are protected from direct pressure, except in subjects with flat feet The pumping mechanism has been explained as follows. The plantar veins are connected like a bowstring between the base ofthe fourth metatarsal and the medial malleolus. Upon weight bearing, the tarso-metatarsal joints are extended and the tarsal arch is flattened. Thus, stretching makes the veins eject their content of blood. Successively, upon heel strike, weight bearing on the forefoot with dorsiflexion of the toes makes the muscles of the sole contract, resulting in compression of the pump in the musculotendinous plane (Figure 7):” There is no differenceVenous system ofthe foot Figure Z Anatomical structure ofthe foot pump. Abbreviations | posterior thal veins 2, antenor bial veins 3, grea! sophenous very 4, shar sophanous vai 5, malleler perforate vein 6, ‘vicular ven; 7, cuneiform perforatr ver: 8, perforate vein ofthe fst ‘metotenal interspace; 9, dessa perforate vei: 10, calcaneolpedorator sein: 1, dorsal vain ofthe hall: 12 itermetotarsal von: 13, medial ‘marginal vain 1, lateral marginal vein: A suction pole body ofthe ‘pump or resewoirC,ejacton pole athe caleanealconfvent Image courtesy of Gilat. between the venous volume elicited by weight bearing and by toe curls tis still not clear why both ofthese mechanisms produce the same effect or which mechanism is dominant; however these two different venous foot pumps would be active at slightly different points in the phase of the gait eycle and both are likely active during the stance phase Probably the muscle contraction pump is @ memory of the preplaniigrade phase in ontogenesis (ie, suspended or immersed le) in the absence of plantar support. Finally in the suspension phase, pump fling is alowed During normal walking, the three veinspumping systems (foot, proximal calf, and distal calf pumps) are synchronized to form a complete network both in series and in parallel, which promote venous retum. Even moderate muscular movements of the legs, while in a seated position, may activate the pumping mechanism, and significantly reduce mean distal vein pressure” Alhough synchronized with the calf pumps, the outflow from the foot plexus is independent of the proximal calf muscle contraction. This is possible because the proximal calf pump and the venous foot pump work “in parallel” ie, voiding their volumes separately into the main duct (popliteal vein) and not “in series” ie, emplying in the same longitudinal duct in succession, Ths arrangement allows for «an independent behavior ofthe two stronger pumps. 69 Phlebolymphology - Vol 22. No. 2. 2015 Venous foot pump voiding Considering the three main deep veins ofthe leg ie, anterior, posterior, and peroneal veins, which are all doubled, with frequent interduplication connections), during venous foot pump activity (weight bearing and flexion ofthe first toe) the prevalent flow is directed into the posterior tibial veins The posterior tibial vein is doubled with a deeper vein that is parallel to a more superficial vein, The more supericial vein originates from the medial plantar vein, whereas the deeper vein originates from the lateral plantar vein The peroneal vein is doubled and drains the lateral aspect of the foo! surrounding the calcaneal confluent and the ankle, passing upward and posteriorly through the calf, as well as passing posteriorly and medially o the fibula?! The peroneal veins may receive the soleus veins at midcall, creating an independent pump. The anterior tibial vein is doubled and drains the blood from the dorsum of the foot staring from the perlorator of the first metatarsal interspace and running up the anterior compartment, lateral to the tibia, and close to the interosseous membrane that connects the tia and fibula. At the knee, the junction of the tibia ond fibula, the vessels penetrate the interosseous membrane and enter the posterior compartment of the leg. Just below the knee, the four anterior and posterior tibial veins join with the two peroneal veins to become the large popliteal vein? Video phlebography investigations confimed that the preferential outlow of the pump isthe posterior tibial vein, which is in dieet continuity with the venous foot pump? The peroneal and anterior tibial veins shore the same akematve outlow paths as the saphenous vein (rough the malleolar perforators). Mechanical compression of the plantar venous plexus produced a mean peak velocity of 12371 cm/sec in the posterior tibial veins, 2926 cm/sec in the peroneal veins, and 24:14 em/sec in the antorir hbial veins Consequently, each volumetric pump is anatomically independent (athough with multiple connections) and connected in parallel with he final formation of he popliteal vein. However the venous foot pump has @ supplementary way of emptying through the saphenous vein, possibly by being fed from the medial marginal vein (ie, the dorsal perforator that communicates with the anterior tibial vein) and the malleolar perforator vein, which is connected to the calcaneal confluent?Phlebolymphology - Vol 22. No.2. 2015 This event is indiectly demonstrated by the studies of Standen et al that showed greater ambulatory pressure reduction in the dorsal foot vein (behaving like deep foot veins) than in the saphenous vein of the calf (mean, 25 mm Hg) during exercise” suggesting that a par of the ejected volume goes via the great saphenous vein. In another more recent study by Neglén and Raju, the drop in venous pressure in the dorsal foot is significantly more marked compared with both the popliteal vein and great saphenous vein at all levels (Figure 8%" The recovery fime is significantly increased in the long sophenous vein compared with the deep vein, and it is then further prolonged in the dorsal foot vein, proving that the three: veins hydraulically behave as separate compartments. ‘As the measurements are made distally to the calf pump, this indicates that the venous foot pump is the “engine” of the distal blood return. This may explain why signs and symptoms of chronic venous insufcieney occur with normal ambulatory venous pressures in he dorsal foot. The channel with the lower gradient will be favored in any occasion, depending on the muscular activity, temperature, position, overflow, and/or obstruction Stefano RICCI Gait Althe beginning of a step, the distal calf pump is activated. This process is inated by dorsiflexion ofthe foot as the leg is lied to take a step. The anterior compartment muscles contact, dosilect the foot, and emply its veins (ie, the anterior tibial veins). Dorsllexion passively stretches the Achilles tendon and empties blood from the lower portions ofthe peroneal and posterior tibial veins. As the foot strkes the ground, weight bearing activates the second phase: the above-described venous foot pumps. Plantar flexion initiates the third phase as the foot comes up on ils foes the muscles of the posterior compartments, particularly the gastrocnemius and soleus muscles, contract, and then temply the proximal venous reservoir Plantar flexion also tenses and shortens the Achilles tendon, which maintains pressure on the distal potion of the calf muscle pump.* More detail regarding dorifleion of the ankle (passive or active) is provided in Figure 9. The bulk ofthe calf muscle descends within the fascial sheath and expels blood in the distal veins lke a piston, which provides space to the blood coming from the venous foot pump (due to weight bearing), A Dorsal V B Deep V c csv Figure 8. lower log venous pressure tracings. Tho dorsal fot (Panel A), poplital (Panel 8. and great sophonous (Rane C) venous pressure tracings simultaneously corded 5 10.7 cm above the ankles during 10 toe stands in & patient with no rellux or obstucion. The night sa of curves sa: magniication of he lek set Abbreviations: GV, great saphenous vei V vein, 70Venous system ofthe foot Phlebolymphology - Vol 22. No. 2. 2015 Figure 9. Synchronization of the log pumps. Dorsiflexion, weight bearing, and plantar flexion lead to distal calf pump emptying (Panel A), foot emplying (Panel B). and upper calf empiying (Panel C) spectively which will prevalently feed the posterior tibial veins. The proximal calf pump and venous foot pump act “in series,” je, in succession on the same axis. If the deep veins are not emptied regularly the venous foot pump finds resistance to expel the blood in the deep veins; hereby, creating a favorable gradiant. The proximal pump, on the other hand, is song and can empl a high (although variable) volume of blood in the popliteal vein, even in the absence of a favorable gradient, and it works “in parallel” with the more. distal complexes (ie, the systems working separately on variable volumes at independent pressures The distal lag pump may become insufficient, i, unable to void the blood volume coming from the perforators during diastole, due to reflux or functional overlow (excess of volume} or an organic or functional obstruction (excess of pressure). In this instance, the venous foot pump will redirect the blood in the altemative direction, that is from the saphenous veins (marginal veins at the foo!) through the perforators, which are nomally vaheloss. ‘Many of he records by Pegum and Fagan were generated by cannulation of deep and supericial veins through {an incision at the first interosseous space and show that when the pressure in the deep veins rose to exceed the: superficial pressure, the supericial pressure also began to a "ise, although to a lesser extent This suggests that pressure in the deep veins of the sole was being transmitted to the superficial veins (dorsal venous arch) by the perforating veins along the pressure gradient. This finding is consistent with the deep layer ofthe supericial fascia ofthe foot, which alo suppor the dorsal venous arch against this pressure (similar to, but stronger than, the saphenous fascia) Blood from the lateral side of the foot and ankle is not drained in an upward direction by the saphenous veins, but downward through the intermetatarsal veins that feed the lateral plantar vein, ie, the venous foot pump “resenvoic” These veins are all interconnected by the rich net of vessels around the ankle joint. The high number of perforators in the foot and the absence of an oriented valwlar system are the most interesting aspects and the anatomical basis ofthe venous foot pump. They allow a rapid filing ofthe reservoir, draining of the deep and supericial network, and they make possible, in alternative outflow channels, the ejection of a volume of blood greater than could be achieved in a closed system* The saphenous veins of the distal calf are able to transfer the blood received from the venous foot pump in the deep veins via the valvular perforating veins during the diastole (relaxation) of surrounding muscles, when the gradient is favorable.Phlabolymphology - Vol 22. No. 2. 2015 Clinical Considerations Asa consequence ofthese observations, some clinical events could be related to the venous foot pump's work against ‘venous overload of the more proximal sections ofthe limb, 4s in most chronie venous insuficiency (CM) situations The pressure increase, due to the proximal obstacle (functional cr organic) on the main duct charges the collateral veins and activates shunts with @ subsequently possible dilatation, This mechanism may overcome the increased flow resistance and be fully compensatory. However, even if full compensation is achieved, the valvular system may become insufficient, thereby causing an inefficient action of the VMPs, and consequently, « functional obstuction, generating a short circuit Corona phlebectatica Corona phlebectatica has been described as @ fan: shaped cluster of smal, dilated veins radiating down from the soleus perforator area over the medial side ofthe ankle and foot corresponding to C, of the clinical, etiological, anatomical, pathophysiological (CEAP) classifcation (Figure 10)? The Society for Vascular Surgery and the ‘American Venous Forum consider it an early sign of advanced venous disease.” Figure 10, Coranaphlebecaca porgplontars in the absence ‘of venous insuliconcy. Inthe Phlebolymphological Guidelines ofthe talian College of Phlebology, the corona phlebectatica paraplantars (elso known as malleolar or ankle flares) is, by definition, due to the telangiectatic dilatation of intadermic veins at the medial (more frequent) and lateral sides of the foot. This is sometimes considered a sign of venous hypertension at «an advanced stage of CVI; however, it may also be present Stefano RICCI independently, ie, in the case of difuse telangiectasios, Esher definition or significance is uncertain. The dilatation of the superficial network of the skin of the foot could be explained os a hypertensive state due to an initially normal actvily of the venous foot pump associated with events leading to « slowing of the blood flow in the deep veins, such as for chronic hypomobilty (long periods of siting, obesity laziness), 10 the use of the wrong shoes, to age- related progressive inactivity, which is not necessarily in association with CV. The association with CM could be casual, or akemativel, the venous hypertension could enhance an already present tendency Skin lesions Venous ulcers lipodermatosclerosis, and pigmentations are typical skin manifestations of venous hypertension during M (Figure 11). Such signs typically appear in the medial supramalleclar area, regulary sparing the foot skin, with limited exceptions. An explanation may be that many patients with CVI have normal venous value pressure in the foot, as shown in 1986 by Stranden et al”? This lesion’s location is probably due to the relative shemodynamic weakness” of the supramalleclar area, containing perforators that act as reentry ways for superficial reflux, but missing a strong pumping mechanism, Figure 11 Supramalleolar uleer associated with Iipodemosclerosis and skin pigmentation.Venous system ofthe foot Indeed, the distal calf pump, generates a pressure that is much lower than the pumping energy of the venous foot pump (distally) and the sural-gastrocnemius pump (proximally) When submitted to reenty flow due to saphenous incompetence, hypertension may be aggravated by pressure peaks generated ot every step by the venous foot pump that radiates upward. Skin lesions could then be the result ofthe conflict between the venous overllow due to the relluxing volume reentering the distal calf perforators and the active “kicks” coming from below. Similar effects could take place when venous hypertension is due to impairment of the deep veins (postthrombotic syndrome). Postexercise pressure, percentage of pressure drop, and recovery mes are widely diferent in the deep veins, long saphenous veins, and dorsal foo! veins, indicating that the three veins hydraulically behave as separate compartments This may explain why signs and symptoms of chronic venous insuficiency occur with normal ambulatory venous pressures in the dorsal foot” Varices of the foot Yorices of the foot, alten present in patients with varicose veins, have a peculiar behavior (Figure 12). Although the most distal part of the leg undergoes the strongest hydrostatic pressure, usually hese varices appearlate in the progression of the disease, and interestingly, they often do not seem to be directly involved inthe reflux pathways, as if they were “suspended varices” Indeed, the most important reentry perforators are located more proximally the dilated veins ofthe foot are connected to foo! perforators and may sometimes, but not olvays, communicate with the reflux pathway, These varices might result from the action of the plantar pump “agains!” a system submitted to hypertension, particularly the deep veins, which are involved in the reenty of the relluxing volume. The song venous foot pump would empty into the more compliant superficial network, developing varicose dilatations of the foot which are connected with, but functionally unrelated to, the shunt circuit. Interestingly, dilatations of the foo! veins almost exclusively involve the superficial network, which is unprotected by the superficial fascio, and spares the saphenous-type veins (ia, the marginal veins), which are sheltered by the superficial fascia (Figure 4) and ore paiculary robust in the foot? Phlebolymphology - Vol 22. No. 2. 2015 (crear ogy sens) lee en satan Joon Figure 12 Varces of he calf ed by saphenous incompetence tg 12. Varios of the co led by jaerene P At the foot, varicose dilatation exists, which is separated from venous incompetence. Abbreviations: SV, grec saphenous vin; Fem, femoral vin, Is compression necessary for the foot? Postsurgery compression of the limb is mandatory especially when treatment is parlly based on phlebectomy cf varicosities (under local anesthesia). The compression by selective pads provides hemostasis and allows the patient to walk immediately after the procedure. It also improves venous retum and provides an analgesic effect. With 40yearsofexperiencein his practice,onecfthe authors observed that excluding the foo from the compression does rot result in distal swelling and congestion. Naturally, this is possible only in C, (of the CEAP classification) patients wih normal deep venous system, without edema, and who are actively walking (like most of our patient), and when the foot and distal mb are not involved in varices. Furthermore, the compression must be inelastic, which only acts during muscle activity and not at rest, and must involve the gastrocnemius area. Il works like a “Perthes test” Limited swelling may be present in the morning when rising from bed and disappears soon after the subject begins to walk Inelastic compression of the leg allows the patient to wear normal shoes, conceal the surgical procedure, wash the foo, and is more comfortable. Of he 183 phlebectomies (associated with or without great saphenous vein exclusion) performed from September 2010 to June 2011 at our insttuion, about half (90) of the feetPhlebolymphology - Vol 22. No.2. 2015 were not given compression and did nat show any notable inconveniences According to this concept, a similar “suspended compression’ may be used in cases of knee joint inflammatory swelling for decongesive and analgesic purposes, provided that the patient is able to actively walk. The same experience is made by athletes and sportsmen wearing compression sleeves in limited areas of the limb, Furthermore, a new stocking has been commercialized, which provides more compression at the upper calf than at the ankle, producing a “progressive” compression as opposed to the traditional “regressive” one” According to Gardner, “if function can be maintained, encircling bandages limited to the proximal limb cre permissible-as long they are not excessively tight~since the venomuscular pump are able to overcome resistances in excess of 150 mm Hg" Arteriovenous fistulae Yoshida et al suggests, using a potential method to identify, spontaneous arteriovenous fistulae, that arteriovenous fistulae occur between the plantar artery and the dorsal venous arch. These fistulae are activated when the foot is heated, eg, using a 38°C to 40°C footbath for 5 minutes, and can be visualized by duplex ultrasonography employing a 12 MHz transducer. Arteriovenous shunts (Sucquet-Hoyer canals) are present in the skin of toes, fingers, ears, and nose with themoregulating functions. In fact, during vasodilation induced by heat, even vigorous walking movements fail io reduce the mean venous pressure below O mm Hg. However, when in the comfort zone, far less actvily is required to effect such a reduction. Finally, when cool, even normal involuntary postural movements will reduce venous pressure to 50 mm Hg Stefano RICCI While arteriovenous fistulae have been reported as a potential contributor to the development of thigh and calf varices,?no information is vailable on the clinical relevance of arteriovenous fistulae of the feet. The hemodynamic role of these fistulae would be worthy of clarification, especially in the presence of varices of the lower leg or foot. Conclusion The pathophysiological and clinical conditions summarized here show that venous return from the foot is more than 4 gait-activated sponge and could be hemodynamically more important than has been previously considered. However the incomplete knowledge of the physiopathology of venous return from the foot univocally hinders defining the relationship between dysfunction and consequences. Some clinical aspects of venous pathology (eg, ulcer localization, corona phlebectatica, and venous dilatations) could be explained by a conflicting mechanism between the venous foot pump and the more proximal leg pumps, rather than @ generic venous pump insuficiency More thorough anatomy/physiology knowledge of the ‘venous system of the foot could even enhance new methods of compression treatment (ie, “progressive” stockings)? Corresponding author Stefano RIC, Ambulatorio Flabologico Rome, tly Email varcci@tscalit Pad of this paper has been published in Dermatol Surg (Ricci S, Moro |, Antoneli Incalzi 8. The foot venous systom: anatomy, physiology and relevance to clinical practice. Dematal Surg. 2014;40:225.233). m%Venous system ofthe foot REFERENCES Phlebolymphology - Vol 22. No. 2. 2015 10, u. 2 Kester G,llgren EF Hellinshoad WH ‘ncn ofthe vei ofthe foot Surg Gynecol Obster 1968;127 817-826. Leja Flas Vanes de la Plone do Pied Archives de Physolgie Ste se, 1290, UNL Beier C. Peveteu C. Gilt C le pong renee nar mca 4 bypasses plyielog.aucs in Frond Paidbclogie 200960818 Fegan G. Varicose Vain: Compretsion Thergpy london, UK: Heinemann Med. wer Binns M Pho RI. Anatomy of he venous foot pump! une 1988195403445, Coley G.The anatomy and physiology lhe venous foat pump. Ana! Ree doio.293a70378 Benringhefl A Drencthahn D. Anctomia Teth ed Munich, Gemany Eloier Gm 2004, Broderick By Coley G1, Quondarnaeo Been FE Senader], Olighin Venous emptying frm the fot Iluences cl weight bearing toe cus eleticl Stelation, passive compression and posture. Jp! Piel 2010;109:1045 "82 ci Phlabecoria dee vances du pied lip French] Phabologie 2000553225, 228 Gardner AVN, Fox RH, The stun of blood Yo the hect agit he force el gril Negus B lant! G, ed Phleboiggy 85 tondes, UK-Lbbey, 98687 FrnceschC Zombon! Peds Peneples ‘ol venous hemedynemies New Yo Ni Nova Setence Pushers 2009, Pies A. Gath M Santini Mh Morel F-Comamella A Uresonogeaphie anatomy ofthe deep veins a he lower lin Vase fch 200226201-21. rey rn 15 6, ” 8 w. 20, a 2. 2 Browse NR Burnand KG, Thomas ML Physelogy and fncional anatomy. Incfanald Fed, Dueoses ol he Voins Diagnosis and FectmentLondan, UR ler B Sloughon 19885369. Gardner AMIN, Fox H. The venous system imhealh and dsease Amsterdam the "Nethedands: [OS Pes 2001, SBN Sosioea3ae, ‘White WV Kae Ml, Cie Kicthen enous outflow af he lg: anatomy ond phnaloge mechani he oni fectova lenis Vse Sg, 1996.24. 219-824. Ludbrook The museulowenous pump slike hur lower lib, Arm Hao 996763564 Sur I, Coleridge Sth PC. La Pompe masclare dy pied importance Dhysclogique ef Clique ba French brlebologin 1993.46200-216, Murray MP Drought AB Kony 8C ‘Welkatg pate normal men, J Bone doin Sng 1964 40R335-960, Gorda AMIN, Fox RH. The retun of Dlzod the heort london UK: eh Ubbey, 1993.63.85, Stondan Dy lg vole changes then stag tv ocd onde acing Uhetice dc Egonomee 2000.43 421 8 Corley Gi, Broderick By, Nestor SM, et el The gnalomy ond physiology ol he enous fol pum Atal Ree 2010,298. 70.378 Sronden E,Ogreid FSeem E Venous pres grades in patents wah Shronie venous dicate Plebology. 198.4750, agli ju 5 Dilerences in pressures tbe poplical long saphencus and lao vr 1 oe ug 200022 894001 24, Pegum IM, Fegan WG. Anam of ‘nou lirn fom the fot, Catlovaue en 1967,1.241 248 25, Tibbs DI Various Vein and Related Diserders Oxford, UK: Ballarat Heinemann Ut 192-204-222, 26, Buckley CV, Evans Cl Allon PL Le Al Fewkat GR Chri vanovs nafiiangy dln end duplex consations. The Eenburgh Vein Sky of venaus dace inthe ganaral population Yse Sung 2003,36.520-525, 22. Glow ® Comerta Al Deling MC, ft The cave of pavers wih vricose ‘eins and auoctied cone venous ducosee dineel procice gudainas of the Society or Votulr Surgery and the ‘American Venous Forum, J ese Surg 2011'5325-485 28, Rice 5, Mow L Tilo Incl RA Foo! sparing poloperalve competion Bandage: posubleclemalve trdional bandage Plabology. 2013284750 29, Most G,Patsch H. Compression slacking wih e nega pressure (gradient hove o more pronounced hte on venous pump function thon (gorated elesie compression stockings Eur Jose Endovose Sug, 2011,82:261 266, Me 30, Yoshida Fa M. Shun! Row of ‘eaesovenovs flesh plata any Phiebology 201126:32°34 1. Hen JB Gover OH, The ialuenee of lemperalue upon venous pesiure in the foot Clin invest 195029855-661, 32. Hoimove H. Role of pracapily ‘oaenorenovs shuning ihe pathogenesis ofvaricve vis and fs herapeute mplcatons Surge. 1987, 101 515-522, 75Phlebolymphology - Vol 22. No.2. 2015 Micronized Purified Flavonoid Fraction in the treatment of pelvic pain associated with pelvic varicose veins Sergey G. GAVRILOV, Anatoly V. KARALKIN, Ekaterina P. MOSKALENKO Loninski Prospekt ‘Moscow, Russia Keywords: micronized purified flavonoid fracion, pele pain, pelvic varicose vein Phlebolymphology.2015;22(2)76-81 Copyright © US SAS. lights zoned wurwephlebolymphologyorg Abstract Aim: To evaluate the benefit of micronized purified flavonoid fraction (MPFF) in ‘women suffering from chronic pehic pain associated with pelvic varicose veins (PW) and possible gonadal varicose veins (GW) Methods: Consecutive women consuling for pelic pain lasting more than 6 months, whore a differential diagnosis of PW had been made and possible concomitant diseases ruled out, were included in the study. Selected patients received MPF treatment: 1000 mg a day for 8 weeks. Polic pain was self assessed weekly using 0 visual analogue scale (VAS) during the 8 weeks of MPF treatment and for 14 weeks after treatment was stopped. Imaging investigations using transvaginal ultrasound angioscan (USAS) and emission computer tomography (ECT) were repeated at 8 weeks, then at 6, 12, 36, and 60 months. Results: A total of 85 women aged 284.6 years, of which 65 were in the PW group and 20 in the PW+GW group, were enrolled in the study between 2000 and 2010. From weeks 2 to 4 of MPFF treatment, a reduction in pelvic pain was seen in either group. While a continuous pain decrease was reported by the PW Patients up to week 8 of treatment, there was no addiional pain reduction in the PW+GW group. Over the 14 weeks following MPFF treatment, pelvic pain intensity was increased back to the pretreatment level in the PW+GWV group, but ‘was eliminated in the PW group. In the latter group, the diameter of the PVVs did not significantly change over the long tem (up to 60 months) as illustrated by USAS, and pelvic venous congestion declined as shown by ECT, reflecting a stabilization of the disease course. Conclusion: In the present study, an B-weck MPFF treatment, 1000 mg up to 2000 mg per day, in women with isolated PWV, relieved them from their chronic pelvic pain in the short and long tem. In patients with combined PW and GW, MPFF did not eliminate pain. However, MPFF may be used in women who wish & future pregnancy or in those reluctant to undergo surgery. ECT of the pelvic veins 76MPFF and pehic pain is @ reliable method for monitoring the efficacy of treatment cor progression of the disease thanks to quantitative assessment of the degree of pelvic vein congestion. Introduction Millions of women may suffer from chronic pelvic pain at somo time in their life and the frequency may be as high as 39%! The association with pelvic varicose veins (PV) was first documented in 1949? Severe and chronic pelvic poin offen results from the presence of ovarian varicose veins and PW, reflecting chronic venous disorders in the polvic veins. the compression of the left ovarian vein, the left ronal vein, oF the common iliac vein may also cause pelvic varices and pain® Clinical practice has shown that only one-third of patients with PW need surgical treatment. The rest require conservative therapy, and the use of venoactive drugs has the most justification with regard to the pathogenesis and underpinnings of this pathology Research objective The aim of our research was to evaluate the benefit of «@ pharmacological treatment with micronized purified flavonoid fraction (MPFF)* in women suffering from chronic pelvic pain associated with PW and possible gonadal varicose veins (GW). ‘Registered os Daflon 500 mg, Alnor Ardium, Arvenum Capen Datolex Variton, Venta! Materials and methods Consecutive women consulting the Si. Spasokukotski Faculty Surgery Clinic for pelvic pain lasting greater than 6 months, where differential diagnosis of PW had been made and other possible causes had been ruled out, were included in the study. The diagnosis of PWV was made on linical presentation (pelvic pain, coital and postcoital poi, menstrual cycle disturbances, ond dysuria), and was confimed by imaging investigation on transvaginal ultrasound angioscan (USAS) and emission computer tomography (ECT) of the pelvic veins. Among the inclusion ctiteria was the absence of concomitant diseases. A bimanual pelvic examination by a urologist must reveal tendemess without induration or masses that could suspect another condition. An ultrasound investigation was systematically performed by a gynecologist to uncover 7 Phiebolymphology - Vol 22. No. 2. 2015 pathological causes, such as endometriosis, adhesions, intersitial cystitis, and initable bowel syndrome. Once selected, the participants were further divided into 2 groups depending on the findings at investigation: (i) those with isolated dilation of pelvic venous plexus without any deterioration of the vulwar or ovarian veins (PWV group and (i) the others with more extended pelvic vein damage, combining both PYY and GW (PW+GWV group). Both groups underwent @ consewative treatment with MPFE at least 1000 mg per day for 8 weeks, with the goal of assessing the extent of pelvic vein damage, such that a conservative treatment could be efficient. The primary end points were: ‘+ Reduction or even elimination of the chronic pelvic pain on a 10-cm visual analogue scale (VAS) during MPFF troatment ‘+ Reduction in or absence of blood deposits in the pelvic venous plexus on ECT, reflecting a diminution of the pelvic venous congestion that could be assessed by a cooffcient of palvic venous congestion (CPVC), during MPFF treatment. The long-term results (or secondary end points) were: ‘Reduction in pelvic pain on VAS. Reduction in pelvic vein diameter on transvaginal USAS. Diminution of the CPVC. ‘Amelioration of the associated symptoms (coital pain, dyspareunia, menstrual pain, and dysuria) Every week during the 8 wooks of MPFF treatment, and then during the 14.weck follow-up after treatment (uni ‘week 22), the patients soltassessed their pehic pain on YAS. Imaging investigations (ie, USAS, ECT) were repeated at diferent timas during the study: 8 weeks, then at 6, 12, 36, 48, and 60 months Results A total of 85 women were enclled in the study between 2000 and 2010. The age ranged from 18 to 43 years, with an average of 284.6 years. The clinical picture of the disease was characterized by the prosence of chronic pelvic pain in 100%, coital and postcaital pain in 72%, menstrual cycle disturbances in 42%, and dysuria in 34% of the enrolled women. A total of 65 women had PVV in isolation, and 20 prosented with both GV and PW.Phlebolymphology - Vol 22. No.2. 2015 During MPFF treatment (baseline to week 8) Pelvic pain measurement on VAS We noticed that the starting MPFF dose of 1000 mg/day ralieved most of the women, right from the first month in both groups (58 women; 50 in the PVV group and 8 in the PW+GW group), but was insulficient to relieve the 27 remaining patients from their pelvic pain. In “nonrespondent” women (15 in the PYV group and 12 in the PW+GWV group), we had to increase the MPFF dosage up to 2000 mg/day after 1 month From weeks 2 to 4 of treatment, a reduction in pelvic pain was seen in either group (PV and PW+GV) at the dosage of MPF 1000 mg/day. From weeks 5 to 8 of MPFF treaiment, the dose increase archieved a continuous pelvic pain decrease in the PW group. There was no additional pain reduction in the PW+GW group despite the dose increase (Figure 1). 3 Pweaw —Pw 8 7 Ze Ss Ba gs e, 1 ST Te Wook curing MPF treatment Figure 1 Assessment of pelvic venous pain. B.weok MPFF aaiment in patien isolated PW ond wi th pele vein dilation in associated PWV and GW. Abbrev Pelvic venous congestion on ECT In the 65 PWV patients who were all relieved from pelvic pain with MPFF treatment (with VAS=1) as evidenced in Figure 1, the comparison of ECG imaging at baseline and at week 8 of treatment showed a decline in the level of labeled erythrocytes in the venous plexus of the pelvis (Figure 2), together with a drop in the CPVC from L6#04 at baseline to 1L.0+0.02 at week 8 (P<0.05). In contrast, patients presenting with PW+GWV did not report a complete elimination of pelvic pain alter 8 weeks of MPFF treaiment, even though they felt an improvement. This was confirmed by an absence of any significant changes on 78 Sergey G. GAVRILOY, Anatoly V. KARALKIN, Ekaterina P MOSKA ECT of he pelvic ains a! baseline (Panel A) and afer an 8-week trealment (Panel 8) in a patient with pebic vein dilation ated PW. Deposit of labeled en venous plexus is indicatod by the arrowsMPFF and pehic pain ECG imaging, A surgery of ovarian veins was proposed to these women and was accepted by 12 of the 20 women. —Pweew — Pw ° 8 7 Bo Bs Ba 23 e, 1 OT Wook ost MPF westment Figure 3, Assessment of pelvic venous pain. Polvic venous pain was measured using a 10-cm VAS in the 114 weols following MPFF ectmen in patients with poli voin dilation in isolated PWV and with associated PWV and GW. Abbreviations: GW, gonadal vancase veins: MPFE micronized punted flvoncid action; PW, peli varicose eins: VAS visual analog scale Pw ea Month post-MPFF teatrent @ Figure 4, Assessment of pelvic venous pain. Pelvic venous pain was measured using a 10-cm VAS in the long tom (with @ mean of three 3-month MPFF reaiments/year) in 57 women with pekic vein cllation in isolated PW only Abbeviaton: MPF, micronized punted favanoid facton: PW, pebic varicose veins VAS, vival analog scale Phiebolymphology - Vol 22. No. 2. 2015 After MPFF treatment (week 9 to week 22) Patients in the PW group who sel-ossessed their pain during the 14 weeks following MPFF treatment (week 9 to week 22) were almost relieved of their pelvic pain in the long term. Conta those who belonged to the group with more extended PWV (PW/+GWV group! reported an increase in pelvic pain that reached the pre-MPFF treatment level within the 10 weeks that followed the treatment (Figure 3). Long-term readministration of MPFF Over the 60 months of observation of patients with PWV in isolation (PW group), additional courses of MPFF therapy were undertaken using the previously recommended dose and duration. A total of 8 patients were excluded for the long-term observation due to concomitant pathology that occured in the meantime: 4 women developed endometriosis; 2, vulvar varicose veins; 1, an adhesive process; and 1, acute cysilis, Of he 57 PWV women who followed several, long-term treatment courses, 7 took MPFF for preventive purposes and the others only when the symptoms reoccurred (pelvic pain, dyspareunia, coital and postcotal pain, etc). Table | summarizes the number of MPFF.reatment courses undertaken by 57 PYV women at the different times of the study. Of note, the number of courses per year usually did not exceed 3, and the duration of administration ranged from 2 to 3.2 months. Long-term pelvic pain measurement Over a 60-month period, pehic pain scores in PY patients were maintained around 1 em according to the VAS assessment, with an increase at 36 and 48 months, corresponding to noncompliance with MPFF treatment in some pation's. The PYV +GWV group of patients remained with @ high level of pelvic pain similar to that before MPFE treatment despite drop in pain from VAS 8 cm to VAS 4-em after @ 2-month MPFF treatment (1000 mg/day) ‘was seen. The patients! flow diagram is summarized in Figure 5. sania a | ae | noe Number of courses 2.2405 27203 24402 2.2404 [Duration of MPFF Jocministation in months 2 2 32204 26203 23204 Table |. Number of courses and duration of MPFF treatment in 57 patients with pelvic vein clilation in isolated PW over a 60-month obsomation period Ablreviatons: MPFF miconized puried flavonoid fraction; PWV, pac wacose veins 79Phlebolymphology - Vol 22. No.2. 2015 ws. ge Sergey G. GAVRILOY, Anatoly V. KARALKIN, Ekaterina P MOSKALENKO Eom v ‘85 woman wih pee pain 20.women with Pew ns 50 PW pis wth dacoaad pain a PYVIGW pie 12 PWGW pis wih sed ain continued pain To) Pvc (ECT) (Sel) and dio [65 PWV ps wih pain ‘ore mainained at Pain (VAS) Pvc (ECT) 20PW+GWY pe with incomplete goin ‘decrease ASS) no CPVC dp 2OPW+GWY pe with pain score 57 PW wih low VAS Figure 5. Patients flow-diagram. CPV, coeficien' of us micronized purified flavanoid fra aperten See gion 1 adhesive process versie 20 PWsGVV wath high VAS score congestion; ECT, emission computer tomography; GVV, gonadal varicose vein; Mi, jon: pts, patients; PVV, pelvic varicose vein; VAS, visual analogue scale; W, week 80MPFF and pehic pain Pelvic venous congestion on ECT In PVV patients who were al lieved from pehie pain and congestion of the pelvis with MPFF treatment (Figure 1 and Figure 2), the comparison of ECT imaging at baseline, and at 6, 12, 36, and 60 months showed results similar to 8 Study time in months (mo) ee Baseline 1620.40 mo 112020" 12mo 102030" 36 me 12008" 160 me 132010 Table I Results of ECT in 57 patients with pelvic dilation in isolated PVV assessed using the CPVC. baseline "0.05 compared wi Abbreviations: CPVC, coeiciant of poic vein congestion: ECT, emission computer tomography: PVV, poic varicose veins Pelvic vein diameter (mm) ST) Baseline 3.22040 ire anor _| re wow | re asioor | Table fl Resulls of tranvaginal USAS in 57 pationts with pekic dilation in isolated PVV using the diameter of the pelvic vein NS compared wi Abbreviations: PWV, pec varicose wens; USAS ulhazound angioscon. Phiebolymphology - Vol 22. No. 2. 2015 ‘weeks post MPFF treatment the level of labeled erythrocytes in the venous plexus of the pebis declined (Table I) and the CPVC remained at a low level (1.3401) even at the 60-month follow-up. Pelvic vein diameter on transvaginal USAS The diameter of PVV did not significantly change over the long term, reflecting a stabilization of the disease course wih MPFF treatment (Table i) Side effects Over @ 60:month follow-up period with iterative MPFF treatments, no side effects were noted, except a few manifestations of gastric dyspepsia, which disappeared after a short time (2 to 3 days) when the drug was withdrawn and did not recut Conclusion In the present study, an 8.woek MPFF treatment, 1000 or 2000 mg per day, in women with isolated PVV, relieved them from their chronic pelvic pain. In the long term (up to 60 months), itoratve MPFF trealments of an overage of three 3-month courses helped to eliminate pelvic pain in these PVV patients. In patients with combined PVV and GW, MPFF treatment failed to eliminate pelvic pain. However, MPEF may be used in women who wish a future pregnancy or in those reluctant to undergo surgery, ECT of the pebic veins is a reliable method of monitoring the efficacy of treatment or progression of the disease thanks to quantitative assessment of the degree of pelvic vein congestion, Corresponding author Sergey G. GAVRIOV, Leninski Prospebs, Moscow, Russia \ Emait gawlofeg@malns 1 gnodio EA, Due R Sain St ol Pie 3 cangeston syndrome: dhognoss ond tetment Semin Inert Race 200825361368. 2. Toor HC Vanior congestion and perenne econo ed Lorcon in the lam oped ‘nem AJ Ob! Gycal ihans7. 290, REFERENCES Tw Fe Hohn D, Seago Pic 4 {nguiton specter caso pelvic panto operate ren ol dogross End management Obstet Gyracl Sug Sows s82°300. Simsok M, Boro E,Taskin ©. lets of metonized pused lovoned hacton (Dati) on pelvic pain in women with leparscepitaly diagnosed pee congestion setome: a randomized {Gousver tal Cin Exp Obst! Gynecol S007 3496-98Phlebolymphology - Vol 22. No.2. 2015 Management of superticial vein thrombosis of the lower limbs: update and current recommendations Jean-Luc GILLET Vascular Medicine and Phlebology: BourgoinJalieu, France Keywords: supericial vein thrombosis; anicoagulant deep vein thrombosis: pulmonary ‘embolism; recommendation Phlebolymphology. 2015;22(2}82-89 Copyright © US SAS. lights zoned wurwephlebolymphologyorg Abstract Initially, supericial vein thrombosis (SVT) was considered a benign disease or a common complication of varicose veins. Recent studies have shown the potential severity of SVT and defined is place within the venous thromboembolic (VTE) diseases, along with deep vein thrombosis (DVT) and pulmonary embolism (PE) ‘A concomitant DVT was identified in 25% to 30% of patients at presentation and a PE in 4% to 7% of patients. Subsequent VIE were reported in 3 to 20% of patients, depending on the follow-up duration. Until recently, numerous anticoagulant strategies have been tested, with no clearly demonstrated clinical benefit. However, the recent CALISTO study (Comparison of Avixira in lower Uimb Superficial vein ThrombOsis with placebo) validated an anticoagulant therapy protocol based on fondaparinux, 25 mg daily for 45 days, resulting in updated recommendations for the management of SVT. This aricle will present an update con the management of lowerleg SVT and the current recommendations and guidelines. Briefly all patients with SVT should have a bilateral duplex scan to confirm the diagnosis of SVT, determine the precise location and extent of the SVT, and diagnose or rule out the presence of a DVT. For patients with symptomatic SVT at least 5 cm in length, it is recommended to prescribe a prophylactic dose of fondaparinux or lowmolecularweight heparin for 45 days over no anticoagulation (Grade 28), and when the cost of treatment with fondaparinux is acceptable, itis recommended to use fondaparinux 2.5 mg daily vs low- molecularweight heparin (Grade 2C). However, the recommendations and guidelines have assigned these treatments with a low grade, and questions remain about SVT management. Some risk factors for subsequently developing a VIE have been identified, but further research is needed to define subgroups of patients with a higher incidence of a VIE after an SVT. Introduction Superticial vein thrombosis (SVT) has been considered a benign disease or common complication of varicose veins; however, recent studies have shown 82‘Management of supericial venous thrombosis their potential severly and defined their place within the venous thromboembolic (VTE) diseases, along with deep vein thrombosis (DVT) and pulmonary embolism (PE) Anticoagulant therapy is widely used today instead of nonsteroidal ant-inflammatory drugs (NSAID), which were commonly used until the last decade. A recent study has, for the first time, validated © therapeutic protocol: However, questions remain conceming SVT management: (i) is anticoagulant therapy required to treat all patients with SVT of the lower limbs?; (i) should prophylactic or therapeutic doses be used?; ii) what is the recommended treaiment duration?; (iv) should the management be the samo for SVT occurring in varicose veins and non-varicose veins?; (v) can the risk factors of VIE complications after SVT be prodicted?; and (vi) is surgery stl indicated for the management of an acute SVT? This article will present the rationale behind the update for the management of SVFs of the legs and the curent recommendations and guidelines. Incidence of superficial vein thrombosis of the lower limbs SVT is considered a common disease, but the actual incidence in the adult population remains unknown. ‘A recent study, conducted in France? showed that the annual diagnosis rate was 0.6%. It was higher in women and increased with advancing age regardless of gender Surprisingly the annual diagnosis rate of SVT was lower than expected and lower than the annual diagnosis rate (of DVT (about half that of DVT). According to another French study, which was conducted with comparable methods, the annual incidence of @ lower limb DVT and PE was 124% and 0.6%, respectively? Superficial vein thrombosis with concomitant deep vein thrombosis at presentation The POST (Prospective Observational Superficial Thrombophlebits) and OPTIMEV studies (OPTimisation de Hnterogatoire dans lévaluation du risque throMbo- Embolique Veineux), two large obsenational and epidemiological. studies, recently published essential dota on SVE A total of 844 pationts with SVT of the lags were analyzed in the POST study and a DVT or PE was. identified in 25% of patients with SVT at presentation and «@ proximal DVT was diagnosed in 9.7% of the pationts. We 83 Phiebolymphology - Vol 22. No. 2. 2015, ‘must emphasize that DVT was not contiguous with SVT in 419% of patients with DVT. A total of 788 patients with SVT ‘were enrolled in the OPTMEV study where an SVT was associated with a DVT at inclusion in 29% of patients, with distal DVT occurring in 59.5% of these patients (128/215; the exact location of DVT was missing in 12 patients) These data confirm previous studies showing that DVT was associated with SVT in 23% to 36% of patients and show coherence among the diffrent studies (Table i)24"° Lutter et al? 1991 53 / 186 (28.5%) Barrellies” 1993 38 / 105 (36%) Morgensen et al! 1993 10/14 (227%) Bilancini ond Luechi? 1999 25 / 106 (236%) ite et t® 2001 32/ 100 (32%) . 210 / 844 (249%) Decousus et alé 2010 10 7 Baa 24 JGolancud et ol* 2011 227 1 788 (28%) Froppé et ol? 2014 42/1 (246%) Table | Supestcial vein thrombosis with concomitant deep vein thrombosis at presentation. “Abbreviations: DVT deep vein thombosis PE, pulmonary embolism: SV ‘upertcial vin tromboss, Superficial vein thrombosis associated with pulmonary embolism at presentation ‘At inclusion, symptomatic PE was diagnosed in 3.9% and 69% of patients in the POST and OPTIMEY studies, respectively. However, SVT with PE, but without DVI, accounted for only 22% of all SVIs with DVT or PE. These data corroborate findings from previous studies (Table W279 In practice, a duplex scanning examination is mandatory in patients with SVT to confirm the diagnosis (Figure 1), determine the precise location and extent of the SVT, and diagnose or rule out the presence of a DVT.Phlebolymphology - Vol 22. No.2. 2015 Dele eo a ry Luter at al® 1991 8/186 (4%) Berrelier? 1993, 14 / 108 (133%) Bilencini ond Luechi? 1999 2/106 (19%) Gillet et al 2001 3/100 (3%) Decousus etal 2010 33/844 (39%) JGolenaud et al 2011 54/788 (69%) 8/171 (47%) Frappe ot al? 2014 Tablet Superficial vein thrombosis wih concom embolism a! presentation. pulmonary Abbreviations FE; pulmonary emboli SV sypeial vein thrombosis Recommendation Clinical examinations may underestimate the real extent of SVIs and do not provide information on the status of the deep venous system. Therefore, it is mandatory to perfor an extensive color duplex ultrasound scan of both the superficial and deep venous system. 84 Jean-Lue GILET Outcome and venous thromboembolic recurrence In the literature, the rate of thromboembolic recurrence ranges from 3% to 20% depending on the duration of the follow-up. In a personal study! we reported the occurrence of symptomatic VIEs in 16.4% of patients with isolated SVT, with « mean follow-up of 14.5 months. The VTE events induded DVT (31%), PE (6%), another SVT in a diferent saphenous system (37.5%), and a recurrent SVT in the same saphenous systom (25%) In the POST study 8.3% of patients with an isolated SVT at inclusion developed at least 1 symptomatic VIE event at 3 months (symptomatic DVT, 2.8%; symptomatic PE, 0.5%; symptomatic extension of SVI, 33%; and symptomatic recurrence of SVT, 19%). In the OPTIMEY study.’ 3% of Patients with on isolated SVT and 5.4% of patients with an SVT associated with DVT at presentation, developed a VIE at 3 months; the rate of VIEs was 12.5% at the year follow-up. In the study by Dewar and Panpher!* a symptomatic DVT occurred in 4% of the patients with an isolated SVT at a 6-month follow-up. These epidemiological findings show the potential severity of SVE They should no longer be considered a benign condition. Consequently their place has now been clearly defined within the VIE diseases. Risk factors for developing a thromboembolic event ‘A multivariate analysis of the POST study identified male sex, history of DVT or PE, previous cancer, and no varicose veins as risk factors for a symptomatic VTE at 3 months, including recurrence or extension of the SVT. In the STENOX study (Superficial Thrombophlebits treated by ENOXoparin)" history of a VIE (DVT or PE), male sex, and severe chronic venous insufficiency were identified as independent predictive factors for a. VIE at 3 months. Only severe chronic venous insufficiency was an independent predictive factor for DVI or PE. In a pooled analysis of the POST and OPTIMEV studies! Golanaud et al showed that male sex, cancer, personal history of VIE, and saphenofemoral or saphenopopliteal involvement significantly increased the risk of a subsequent VIE or DVI/ PE in 0 univariate analysis. In multivariate analyses, only male sex significantly increased the risk of a subsequent VIE or @ DVI/PE recurrence. For cancer and a personal history of VIE, the adjusted hazard ratios were only slightly‘Management of supericial venous thrombosis below the level of statistical significance (P=0.06 for both) suggesting that, for these factors, the study merely lacked sufficient statistical power. ln the STEFLUX study (Superlcial Thromboembolism FLUXum}” having a body mass index (BM) between 25 and 30 kg/m? and a composite of a previous SVT and/or VTE and/or family history of VIE were identilied 4s significant independent rsk factors for a VIE event (composite of symptomatic and asymptomatic DVI, PE, and SVT recurrence or extension) Vein status Vericose vein status has been reported to influence the ‘isk of exhibiting DVT at presentation. In the POST* and OPTIMEV studies. SVIs occurring in a non-varicose vein (NW-SVT) were more often associated with a concomitant DVT or PE than SVs occurring in « varicose vein (W-SVT} Similar findings were reported by Gorty et al At tho 3-month followup in the OPTIMEY study, isolated NW-SVT was not associated with a higher risk of adverse outcomes (ie, death, VIE recurrence, and bleeding). Isolated NW

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