PRESIDENTIAL ADDRESSFrom the American Venous Forum
Improving management of chronic venousdisorders: Exploration, description, andunderstanding—parallels in the worlds of theRenaissance and the American Venous Forum
Frank Thomas Padberg, Jr, MD, Newark and East Orange, NJ
The American Venous Forum (AVF) facilitates com-munication between surgical and medical specialists,bridges various geographic and cultural environments, andprovides a platform for exchange of both clinical and basicresearch for the worldwide community.
● Exploring the inter-relationship between disease sever-ity and prognosis promises to improve our conception andunderstanding of venous problems.
● Exploration of innovative surgical and minimally inva-sive therapy offers to decrease pain and promises equivalentor better outcome for both refluxive and embolic venousdisorders.
● Exploration of new compounds has resulted in theintroduction of new and effective oral anticoagulants foracute venous thrombosis.
● Descriptions of clinical findings using the internation-ally utilized CEAP classification, its derivative scoring sys-tems, and other functional assessments, now offer a com-mon language and framework for communications onchronic venous disorders.
● Understanding derives from exploration and descrip-tion, and will inevitably improve with technologicalinnovation.
From the Division of Vascular Surgery, New Jersey Medical School, Uni-versity of Medicine and Dentistry of New Jersey; and Section of VascularSurgery, Veterans Affairs New Jersey Health Care System; and President,American Venous Forum 2003-2004.
Competition of interest: none.Correspondence: Frank Padberg, Jr, MD, University of Medicine & Den-
tistry of New Jersey, New Jersey Medical School, Surgery, Doctors OfficeCenter, 90 Bergan Street, Suite 7200, Newark, NJ 07103(e-mail: [email protected])
With organized review and prospective observation,these tools lead us to a better understanding of the diseaseprocess and its effects. However, much remains to belearned, as new knowledge often brings more questionsthan answers. Ultimately, the role of the AVF is to identifyvalue, based upon good evidence for interventions thatmake a difference to the patient, to improve the manage-ment of patients with these diseases.
PERSONAL REFLECTIONS
Let me briefly digress to recognize that all of you, byencouragement and critique, have stimulated and encour-aged my interest in the problems associated with medicalscience and venous disease, in particular. As is often thecase, various individuals have contributed specific legacies.First, it is indeed fortunate that both of my parents couldattend this year’s annual meeting. They imbued values ofhonesty and persistence, a desire to make a contribution by“doing it right” in whatever I chose to do, and apparently,bequeathed healthy genes. At an age similar to that of myson Tom, my dad invited me to attend an American Collegeof Surgeons Meeting where he was presiding and his pro-gram director, Professor Loyal Davis from NorthwesternUniversity, was the featured guest speaker. I don’t remem-ber much of what Dr Davis had to say but was dulyimpressed that Dad and Dr Davis had “gotten it right” ornone of us would have been there. Subsequently, I haveenjoyed a professional relationship with two former presi-dents of this organization associated with Northwestern,Drs Bergan and Yao. Mom, who graduated with an ad-vanced degree in music from the same institution, encour-aged my meager musical abilities and in the process, devel-oped the instinct to revise or practice until a job gets doneright—even though there is never enough time. My sisterKristen has always offered a mirthful beacon of respite fromthe too busy, too serious, world of academic vascular sur-gery and will make up for my lack of participation with the
AVF tennis enthusiasts.
355
surg
JOURNAL OF VASCULAR SURGERYFebruary 2005356 Padberg
In no small measure, it is certain that I would not bestanding here today were it not for the loving and unselfishsupport tendered by my wife Sharon. Thank you, Sharon,for all of your sacrifices in looking after us and especially fornurturing Tom III, who provided another chance for bothof us to participate in the activities of a modern childhood!
As a surgical intern, newly migrated from the southwest(Arkansas) to the urbane Boston environment of NewEngland, I encountered a classical scholar who was thenchief resident of the Harvard Surgical Service, former Pres-ident T.F. O’Donnell. I suspect Tom was more impressedwith my transportation than me, but he left an indelibleimpression of self-confidence supported by an instantlywell-referenced encyclopedic knowledge of vascular topics.It was real honor to have our recent work on venoushemodynamics included in his presidential musings.
Al Persson, who arrived in Boston later than I, providedsincere friendship and professional guidance during myinitial consideration of a career in vascular surgery. He wasresponsible for sponsoring my first exposures to the na-tional vascular society meeting and a vascular-specific post-graduate symposium similar to the one that preceded thismeeting. In part deriving from participation in these pro-grams, I came to know Bob Hobson, who gave me respon-sibility for the vascular service at University Hospital,Newark, and who continues to provide an accomplishedprofessional example.
A key feature of the academic section at New JerseyMedical School was an emphasis on detailed knowledge ofclinical data as well as its source and the quality of theinformation. A master of persuasion, Bob is particularlyadept at rallying his troops to make things work, especiallywhen the odds seem to militate against success. While he
Fig 1. The American Venous Forum, founded in 198research for the worldwide community of physicians and
encouraged us in our calf pump therapy trial, we returned
the favor by contributing to major trials in which he servedas principal investigator (the Veterans Administration trialfor asymptomatic carotid stenosis, the Asymptomatic Ca-rotid Atherosclerosis Study [ACAS], and the Carotid Re-vascularization Endarterectomy Stenting Trial, [CREST]).Our entire clinical group (Pappas, Lal, Araki, Cerveira) hasregularly contributed to this meeting.
Sincere thanks to Bob Kistner, Bob Rutherford, and BoEklof for providing solid advice, experienced clinical obser-vation, and the power of leadership by example. As the AVFleadership makes the transition from its founders into ournew generation, we intend to ensure that the quest toexplore, describe, and understand chronic venous diseasehas a promising future.
THE MISSION OF THE AMERICAN VENOUSFORUM
“The mission of the American Venous Forum is to im-prove the care of patients with venous and lymphatic disordersby providing a forum dedicated to the clinical practice andeducation and to the exchange of information concerningbasic and clinical research pertaining to the venous and lym-phatic systems.” How have we, the members of the AVFsucceeded in accomplishing our goals (Fig 1)?
The annual meeting of the AVF is considered by manyto be the most important meeting of the year for thoseinterested in the management of patients with venousdisorders.1,2 Numerous unsolicited suggestions, full atten-dance despite good weather, and comments on the evalu-ation forms have reinforced the educational value of thepostgraduate course. The plenary sessions continue to offerexchange of information in both basic and clinical science.The modest size of our organization and the structure of
vides a platform for the exchange of clinical and basiceons interested in the management of venous diseases.
8, pro
the meeting facilitate collegial interaction and frequent,
land
JOURNAL OF VASCULAR SURGERYVolume 41, Number 2 Padberg 357
informal opportunities for information exchange. Ourguest lecturers (Table) represent a virtual Who’s Who ofthose making significant contributions to the general ve-nous knowledge base. The same can be said of the group ofsurgeons (Table) who have preceded me on this podium.The annual attendance by many of these individuals atteststo the value of this enclave for the serious study of venousand lymphatic diseases.
The influence of the programs sponsored by the AVF inthe United States and, indeed, throughout the world hasbeen enormous. Witness the existence of the EuropeanVenous Forum and proposals for other freestanding soci-eties devoted to venous diseases now occurring throughoutthe civilized world. The concept of a forum specifically forthe presentation of material on venous topics alone waspioneered by a venous forum attached to the British RoyalSociety of Medicine.3
Observing the productive response to this forum andthe several European-American Venous Symposia, a num-ber of prominent surgeons in the United States (ourfounders)4,5 petitioned the Society for Vascular Surgeryand the then joint council for support of a similar forum tobe attached to the larger society and to meet on an annualbasis. Fortunately (in retrospect), the joint council re-sponded with the recommendation that a new organizationbe established for this purpose.
“Naissance of the American Forum” was the subject ofthe first AVF Presidential Address by John Bergan, whichdiscussed the organization of our then fledgling society.The term naissance means new birth, and implies a nationalorigin; the more familiar term, renaissance, refers to amultinational or cultural rebirth. Both concepts are encom-passed by the role of the AVF. I am grateful to our archivistfor the opportunity to preview the discs summarizing theconception, founding, and realization of the maturing or-ganization we now proudly call the AVF, and hope thateach of you enjoy the enormous effort which has culmi-
Table I. Guest lecturers and presidents of the American V
Guest Lecture
19891990 Hugo Partsch, Austria1991 Jack Hirsch, Canada1992 G.W.Schmid-Schonbein, Un1993 Olav Thulesius, Sweden1994 Andrew Nicolaedes, United1995 Phillip D Coleridge-Smith, U1996 Ermengildo A Enrici, Argent1997 Prof Kevin G Burnand, Unit1998 David Bergquist, Sweden1999 David Robinson, United Sta2000 Prof Sir Norman Browse, Un2001 Prof Vaughn Ruckley, Scotla2002 Prof Alfred Bollinger, Switze2003 Prof Claudio Allegra, Italia2004 Prof Eberhard Rabe, Deutch
nated in its collection.5
The inclusion of all of North and South America wasmodeled after the broad envelope exemplified by the Amer-ican College of Surgeons. In 2003, a South Americansession was featured from the abstract submissions; in2004, an international session. In addition to reporting theresults of several randomized clinical trials at the Society forVascular Surgery, AVF members have been prominentlyinvolved in several educational symposia at other meetings,including the Congress of the International Union forPhlebology and the American College of Surgeons.
The Handbook of Venous Disorders: Guidelines of theAmerican Venous Forum6 has collated experience fromthese meetings and is now in its second edition. A layman’sversion is available to the public on the AVF Website,venous-info.com.7 A thrombosis risk assessment tool isdistributed for personal digital assistants at the annualmeeting. The CEAP classification for venous diseases,which was developed at a consensus conference sponsoredby the AVF but is clearly an internationally based docu-ment, has been adopted as the language of venous diseaseworldwide.8,9 The outcomes committee has developed in-struments for assessment of severity and disability, whichare becoming more widely used.10 Another AVF commit-tee has again solicited an internationally based group toconsider revision of CEAP; its final report was prepared atthis meeting and published in the Journal of VascularSurgery (2004;40:1248-52).
Despite these accomplishments, we must still ask if wehave met the first goal—to improve the care of patients withvenous and lymphatic disorders (Fig 1). Have we convinc-ingly demonstrated which interventions make a difference?Do we know which interventions to recommend? When?Which anti-thrombotic is best?11 Although there are excel-lent, long-term observational data on vena cava filters, onlyone randomized trial was identified in a recent systematicreview of the topic.11,12 We can estimate the prevalence ofthromboembolism from air travel, but cannot state that our
s Forum
Presidents
John J. BerganNorman M. RichLazar J. Greenfield
tates Micheal HumeGeorge Johnson, Jr
om James A. DeWeeseKingdom Robert W. Hobson II
Robert L. Kistnerngdom James S.T. Yao
D. Eugene StrandnessThomas F. O’Donnell
Kingdom David S. SumnerAnthony J. ComerotaGregory L. MonetaPeter GloviczkiFrank T. Padberg, Jr
enou
rs
ited S
Kingdnitedinaed Ki
tesitedndrland
recommendations have made a difference.13 We can mea-
Basle
JOURNAL OF VASCULAR SURGERYFebruary 2005358 Padberg
sure the adverse effects of chronic venous disease on qualityof life, but cannot yet determine which interventions aremost effective in ameliorating this disability.14
As with so many other advances, CEAP has also offerednew challenges. Where do we classify the morbidly obeseindividual with no anatomic evidence of venous disease? Dothey have a different form of chronic venous hyperten-sion?15 What is the relationship between symptoms andclassifications of venous disease?14,16,17 Although severalstudies have confirmed that the clinical classes correlatewith increasing severity, the relative risk of progression ispoorly understood. Is edema a precursor of lipodermato-sclerosis? How commonly does lipodermatosclerosis leadto ulceration?18 What is the role of the sensory abnormalityassociated with chronic venous insufficiency (CVI)?19 Doesit confer a higher risk of recurrence? Of occurrence?
Is our knowledge incomplete? Can we make it better?Will exploration, description, and understanding produceimproved management of chronic venous disorders? Likeany lawyer asking pointed questions in the pursuit of cross-examination, we know the answer to these latterquestions—and it is yes.
KNOWLEDGE AND VEINS: THE RENAISSANCEAND THE AVF
The geographic, cultural, and scientific world haschanged much since the 15th and 16th centuries, but theexploration of the human form, description of the veins(and arteries), and an understanding of their function,
Fig 2. Mid-15th century: the world as known to Europsecond century, but now the information was widelyworld-view, Sebastian Münster, Geographia Universalis,
bears a remarkable parallel to the status of venous knowl-
edge today. We have explored the territory, identified theanatomic components, and agreed upon the means todescribe the disease process. Greater understanding comeseach year, and new generations of investigators continue totranslate these findings into patient benefit.
Exploration. The discovery and exploration of theNew World coincided with important developments in theidentification and description of the anatomic parts that,when pieced together with scientific understanding, wouldconstitute the critical physiologic concept of circulation ofthe blood—knowledge that fostered improved manage-ment of innumerable conditions. Concurrently, a renais-sance was taking place in philosophy (characterized by anemphasis on the power of reason), art (characterized by anemphasis on realistic rendition of the human form), andcommunication (characterized by printing with movabletype).
Before the exploration and discovery of America, theworld was a Eurocentric universe.20 The three continentsof Europe, Asia, and Africa retained the geography con-ceived in the second century work of Claudius Ptolemy, asillustrated in Fig 2. Modern 15th century technology, awoodblock with moveable type, was used to print this mapon a press and it appeared in the Geographica Universalisand Cosmographia of S. Munster.20 Southern Africa, itsseaward passage into the Southern Hemisphere, Australia,Antarctica, and North and South America were still un-known. Mid-15th century Europeans knew nothing of thelatter four continents, nor could they describe California or
as little changed from that described by Ptolemy in theminated as a result of the printing press. Ptolemaic. Private Collection.
eans wdisse
Hawaii (Fig 2).
JOURNAL OF VASCULAR SURGERYVolume 41, Number 2 Padberg 359
Fig 3. A, 1543—the height of the renaissance. The vein figure is attributed to the author himself; Andreas Vesalius,Book III, De Humani Corporis Fabrica, Basle. Private Collection. B, Die Nüw Welt (The New World) is a
contemporary illustration of the two newly discovered continents; S Münster, Geographia Universalis, Basle.
JOURNAL OF VASCULAR SURGERYFebruary 2005360 Padberg
Likewise, medical knowledge derived from Ptolemy’sauthoritative second century contemporary, Galen of Per-gamun. Based largely on the influence conferred by centu-ries of reliance in his works, students and doctors at the turnof the 15th century believed that the arteries, veins, andnerves were all vessels distributing different “spirits” to thebody. Blood was manufactured in the liver and distributedby a process of ebb and flow along these hollow arteries andveins. The animal spirit resided in the brain and was respon-sible for animation through the nerves. The vital spirit orheat was carried as air and blood in the arteries afterbeginning in the trachea, which at that time carried thename Aspera Arteria for “rough artery.” Galen had real-ized that the arteries had to carry blood but postulated thatboth blood and spirit were present in the smooth arteries.The veins, which carried the blood to the body, wereconsidered more important than the arteries because therewere more of them and they were larger; they were usuallydepicted in front of the artery.21,22
Description. The generation that matured in the yearsfollowing the discovery of the New World was primed toquestion authoritative knowledge. Relevant to our state ofunderstanding today, physicians and, particularly, surgeonsbegan asking important questions about Galenic dogmapassed down from previous centuries.
Based upon direct personal experience, Andreas Vesa-lius (1514-1564) explored and described the anatomy ofthe body and reasoned that the authority of these ancienttexts should not be regarded above the actual findingsobserved in human dissection. His detailed text De Hu-mani Corporis Fabrica Libri Septem (Seven Books on theStructure of the Human Body), published in 1543, wasremarkable for its integration of accurate, artistically ren-dered illustrations coordinated with definitive text.21,23
This venerable text embodied the Renaissance values ofreason, artistry, and the new technology of printing. As anexample, the vein figure (Fig 3) lacks a surrounding enve-lope of skin but conveyed structure from the images of theveins themselves. However, both the arterial and venousfigures inaccurately depict the great vessels. The vein figuredemonstrated cephalic venous drainage to the externaljugular and equivalent-length innominate veins in the up-per midline. The vein figure (depicted in Fig 3) and itsaccompanying arterial figure (not illustrated) were attrib-uted to the author himself (Fig 3).
Detailed musculoskeletal anatomic illustrations, nowhighly prized for their intrinsic artistic value, were attrib-uted to the studio of the Renaissance artist Titian. A con-temporary surgeon, Ambroise Paré (1510-1590), appliedpractical knowledge gained from personal treatment ofwounds and rapidly achieved fame for improved healingwith markedly less pain. In addition to advocating ligatureof bleeding vessels, he described varicose vein removal andwas aware of the value of compression bandaging. Reputedas authorities in surgery, Vesalius and Paré consulted to-gether on the management of a fatal jousting injury to King
Henry II of France.24
Both individuals brought the same Renaissance spirit tothe advancement of medicine that Christofor Columbusbrought to the geophysical world. The geographic frame-work of the world was forever altered by the explorationand description of a new world that lay between Europeand Asia (Fig 3)! The contemporary illustration depicts thetwo new continents (Die Nüw Welt) that had been ex-plored and described only 50 years previously. The dis-torted outlines depicted were the first widely circulatedimages of the New World and suggested the savage natureof its inhabitants (“cannabali”) in the area that is nowBrazil. Efforts to find a Northwest Passage to the Orientwould continue for decades, fueled by a mistaken descrip-tion of the Chesapeake as a northwest sea.
In conjunction with the accompanying maps of Africa,Asia, and the world, these illustrations reflected Magellan’sexploration of 1522, which proved that the globe could becircumnavigated in the southern latitudes. Two continentswere still undiscovered, however. The map reflected priordescriptions from Marco Polo and depicted the crudeknowledge derived from explorations contemporaneouswith Paré and Vesalius.
The advances of these scientists were achieved by theapplication of empiric observation and public discourserefuting the discrepancies of established ancient authority.Despite these enormous contributions, the concept of an“ebb and flow” was still the explanation for blood distribu-tion in the publications of both of these eminent authori-ties.21-23 We live in a world similar to theirs, wherein wehave now developed a new language for reporting (CEAP),and available diagnostic tools (duplex scanning and pleth-ysmography) have allowed for noninvasive dissection of theanatomic and physiologic abnormalities of venous insuffi-ciency and thrombosis, respectively. Like the explorers ofthe 16th century, we expect that some observations willlead to inaccurate conclusions and others will provide thekeys to critical new concepts.
Understanding the meaning and import of an observa-tion may require the fresh insight of a new generation.Then as now, we continue to rely on authority when newhypotheses are either absent or ridiculed. At the close of the16th century, the professor of anatomy and surgery atPadua was a second-generation student of Vesalius. Hiero-nymus Fabricius Aquapendente (1533-1620) was creditedwith the description of valves in the lower extremity veins(Fig 4). Although described in lectures as early as 1587,publication of these findings in De Venarum Ostiolis (Onthe Valves of the Veins) was delayed for almost twodecades.25 Like his predecessor Vesalius, he made an im-portant discovery but did not complete the critical connec-tion to understanding. He surmised that the valve pre-vented retrograde venous flow, but he continued toadvance this explanation in the framework of the ebb andflow of the spirits that Galen had described in the secondcentury.
Meanwhile, Mercator’s world map (Fig 4) providedoutlines of what appear to be the sixth and seventh conti-
nents; however, this reflected a common but misleading
JOURNAL OF VASCULAR SURGERYVolume 41, Number 2 Padberg 361
Fig 4. A, 1587—the close of the 16th century. H Fabricius initially described the structure of venous valves DeVenarum Ostiolis (On the Valves of the Veins) in 1587. From Franklin KJ. Facsimile edition with introduction,translation, and notes of De Venarum Ostioli (On the Valves of the Veins) 1603 of Heironymus Fabricius ofAquapendente. Springfield (IL): Chas C. Thomas; 1933. Reprinted with permission. B, The contemporary double-hemisphere world map is a reduced version of the original published by Gerhard and Rumold Mercator in The Atlas,
Geneva, 1587 (G. A. Magini, MD, Venice, 1596). Private Collection.
ction
JOURNAL OF VASCULAR SURGERYFebruary 2005362 Padberg
practice of early cartographers who filled geographic spaceswith illustrations, typescript, and other postulated areas notyet physically explored.26 The breadth of the North Amer-ican continent is overestimated, but the concept of aNorthwest Passage had been dismissed by now.
Because we often become comfortable with existingknowledge, we risk failure if we don’t recognize that someof these illustrative descriptions are hypothetical. Widelyheld beliefs often lead to delayed appreciation of actual factfrom direct observation, which were problems for both theearly cartographers, Columbus, and our next anatomistfrom Padua, William Harvey.
Deduction and understanding. It is up to us, thenext generation of the AVF, to further utilize newly devel-oped tools, such as magnetic resonance and computed
Fig 5. A, 1628: along with other observations, the controf the blood. William Harvey, De Motu Cordis, FrankfortSanguinis in Animalibus (Movement of the Heart antranslation with reproductions from the 1928 TercentSpringfield (IL): Chas C. Thomas; 1930. Reprinted wpermanent colonization of the new world and perpetuatFamous Parts of the World, London, 1626. Private Colle
tomography, to complete the description of the anatomy
and venous pathophysiology and to develop and use newinstruments to measure the severity of disease from theperspectives of both the treating physician and the patient.
It is our responsibility and opportunity to make theconnection between anatomic findings, to make the criticaldeductions derived from newly developed diagnostic andevaluative instruments, and to explain the physiologic con-nections. Sixteenth century physicians deduced physiologyfrom macroscopic observations; microscopic anatomy pro-vided understanding to the next generation. Newly devel-oped molecular and functional advances now offer similaropportunity to 21st century matriculants.
It was the third academic generation, in the person ofEnglishman William Harvey, who synthesized the radicalnew concept of circulation of blood in Exercitatio Ana-
venous flow by valves leads to the concept of a circulationm Harvey W. Exercitatio Anatomica De Motu Cordis etod in Animals), Frankfort, 1628. A modern EnglishEdition as presented by Chauncey D. Leake. 2nd ed.ermission. B, A contemporaneous world-view reflectstographic misconceptions. Speed, A Prospect of the most.
ol of. Frod Bloenialith pes car
tomicae de Motu Cordis et Sanguinalis in Animalibus (On
JOURNAL OF VASCULAR SURGERYVolume 41, Number 2 Padberg 363
the Movement of the Heart and Blood in Animals) in 1628(Fig 5).27 His conclusion was built on the foundation of histeachers. He too matriculated in the anatomic theatre atPadua, as had Fabricius and Vesalius before him.
Harvey’s hypothesis was developed while he conducteda lucrative medical practice in London, which included tworoyal clients. One of the several arguments supporting theconcept was the observation that the venous valve pre-vented reflux of blood against gravity or pressure. Anyasthenic individual can demonstrate this by examining thedistended superficial veins on their forearm; in modernvenous surgery this is illustrated by the strip test for com-petence after reconstruction of the venous valve. Otherevidence cited in support of this concept of a circulation wasto regard the heart as a pump and not just a muscle, theabsence of air in the arteries, and an estimate of the outputfrom the cardiac chamber.
He postulated that an individual with a 60 cm3 capacityof the cardiac chamber and a rate of 65 beats per minutewould greatly exceed any volume that could be accommo-dated by the ebb and flow theory. Harvey advanced theseassertions without the knowledge of capillary structure.Despite logical and compelling reason, this seminal work,De Motu Cordis, was only slowly accepted. Contemporarywith Harvey, his countryman John Speed published thisworld-view (Fig 5) in 1626.28
Permanent colonization of North America was repre-sented by the founding of Jamestown, Virginia in 1607 andPlymouth Colony, Massachusetts Bay, in 1620. New Am-sterdam was founded the same year, Boston in 1630, andWilliamsburg in 1633. The subsequent development ofthese cities and the cultivation of tobacco in Virginia pre-saged the future role of the new continent in the worldorder. The map (Fig 5) illustrated 6 continents, continuedto overestimate the breadth of the North American conti-nent, and portrayed California as an island; the latter erro-neous concept was finally rectified 75 years later.
It was another 35 years after De Motu Cordis before thecapillary circulation was visualized, a description of whichoccurred after the development of a functional microscope.It was Marcello Malphighi (1626-1694) who confirmedthe existence of a pulmonary capillary circulation in1661.24 Despite the accumulating evidence, it took manymore years before the practical aspects of this discoverysupplanted the Galenic theories of the spirits. In the geo-graphic realm, it would be well over 100 years before theexploration and description of the Sandwich Islands(Hawaii) in 1778, Australia in 1788, and Antarctica in1820. Even today, with the rapidity of electronic commu-nication, it may often require a generation for new knowl-edge to be widely assimilated into clinical practice.29,30
Improving management. Eventually, Harvey’s viewswere accepted and are now common knowledge among ourschoolchildren. The geophysical world is now visualized ona grand scale from space; however, we have yet to unravelthe complex circulatory dynamics of the venous system.Physiologic assessment of obstruction to venous flow re-
mains a major challenge; it remains difficult to define and
accurately diagnose obstruction. The relationship betweensymptoms, physical findings, and objective abnormalities,such as reflux and chronic thrombosis, has not alwayscorrelated closely.14,16,17 The advantage of using a com-prehensive classification that requires noninvasive data (ie,basic CEAP) is the elimination of the inaccuracies inherentin decisions based solely on clinical appearance.31 Perhapsnew hypotheses will arise from technological innovation,and new clinical trials will be generated to confirm them.
Major trials contributing new practice algorithms arecertain to raise new questions, just as old beliefs will bedifficult to jettison. New anticoagulants are poised to rev-olutionize the management of long-term therapy, just asthe beneficial effects of Coumadin therapy have been sol-idly entrenched with multicenter, randomized prospectivetrials. The benefits of physical training to ameliorate theadverse effects of CVI on calf pump function were sug-gested by a small, randomized, single-center trial.32 Thevalue of perforator ligation has been assessed by a Dutchtrial that suggested this modality had limited effects on theoutcomes measured.33
Accurate diagnostic classification with CEAP has raisedinteresting new questions in familiar populations. Numer-ous studies have confirmed that severe complications fromCVI increase with age.16-18 Morbidly obese patients fre-quently develop severe, resistant, lower-extremity symp-toms typical of CVI, but 62% have normal duplex exami-nations; it is doubtful that this would all be due to occultproximal venous occlusion.15 The response reported aftersuccessful weight loss supports the concept that it is amanifestation of a relative abdominal hypertension.
There is very little information on the probability ofprogression from edema to pigmentation or induration;similarly, there is little information on the likelihood that anindividual will progress from these more advanced states toulceration. Heit et al,18 in their 25-year population-basedstudy in Olmstead County, reported that 6.5% of patientswith a first-time, clinically defined diagnosis of “venousstasis” progressed to ulceration in 5 years. The incidence ofulceration in limbs with a post-thrombotic etiology is sim-ilar and ranges from 3% to 15%.
In re-evaluating our own group of patients with severeCVI, we identified a sensory neuropathy localized to thegaiter distribution rather unlike the diffuse stocking distri-bution seen with diabetes mellitus.19 Each of these devel-opments has influenced the recommendations for manage-ment of chronic venous disorders and offered guidance forthe direction of future investigation.
MISSION IMPOSSIBLE OR MISSIONACCOMPLISHED?
The current call for increasing reliance on evidence-based practice is again driven by reason. Reliance on au-thority or expert opinion is a much easier path. However, asdemonstrated by our medieval forebears, the sovereignknowledge base rapidly becomes stagnant and immutable ifit is allowed to reign without periodic reassessment. The
development of a new paradigm requires evidence that new
JOURNAL OF VASCULAR SURGERYFebruary 2005364 Padberg
therapies improve patient outcome. Thus, an emphasis onevidence-based practice has inevitably led to a call for areassessment of the methods for reporting and investigat-ing our experience. Although the exploration of new tech-niques and methods are essential to integrate potentialadvances into patient care, an accurate description of theresults are essential to understanding their benefit. It re-mains a major challenge to effect meaningful change, how-ever, even when based on good evidence.29,30
The prospective, randomized, controlled trial (RCT) isconsidered the best design for the reduction of investigatorand random bias in subject allocation.34 The critical differ-ence between an RCT and a historically controlled trial isthe acquisition of an unbiased control group.35 Well-conducted trials have advanced the therapy of venousthromboembolism at an astounding rate during the 20thcentury. From Sevitt and Gallagher’s36 demonstration ofthe benefit of anticoagulation for pulmonary embolism, themanagement of both prophylaxis and treatment has beensteadily refined.11 The arrival in the near future of new oralanticoagulant agents will make this therapy safer, morewidely applicable, and more patient friendly.
Defining the role of surgical management for venousproblems has proven more problematic.37,38 New proce-dures are now characterized by a less-invasive methodol-ogy, exemplified by the increasing range of endovascularoptions. Because most manifestations of chronic venousdisorders are not life threatening, a reasonable point ofclinical equipoise between interventions for venous prob-lems may be easier to establish than for other more invasiveprocedures. Thus, it remains important to ethically designtrials that will establish the relative risks and benefits ofinvasive therapies and to recruit individuals to participate inthem.38
Although the RCT is the best method for determiningcause and effect or evaluating differences from an interven-tion, these trials are lengthy and expensive.34,35 To reduceincomplete data reporting, most journals, including theJournal of Vascular Surgery, now expect RCT reports toadhere to the Consolidated Standards of Reporting Trials(CONSORT) statement.39 However, subtle bias still existswith this methodology, including publication bias or thetendency to print research that is positive and reports astrong effect; language bias (the positive results are morelikely to appear in English); and time-lag bias, in whichnegative results are less likely to be rapidly published.40 Insituations where randomization is not ideal or reasonable,observational studies or registries may be the best means ofcollecting data for analysis.
A recently collated hierarchy for levels of evidence insurgical trials addresses some of these special situations. Forexample, level 1C is assigned to decisions with an “all ornone” outcome where the alternative treatment to surgicalintervention is likely to result in death (ie, ruptured aneu-rysm or perforated viscus).37 Although pulmonary embo-lism has a lethal implication, its mortal potential is substan-tially less frequent than the incidence of venous thrombosis;
thus, to retain power while avoiding inordinately large
recruitment, most anticoagulant trials assess pulmonaryembolus as a component of an a priori endpoint of venousthromboembolism.
Exploration and description of CVI has been greatlyenhanced by use of CEAP. Availability and reliability ofduplex analysis combined with noninvasive plethysmogra-phy offers new methodology for description of the ana-tomic and physiologic abnormalities associated withCVI.8,9 Severity scores offer a method to record the physi-cian’s assessment of the disease process, and new psycho-metric instruments analyze the patients’ perspective withquestionnaires reflecting impact on their quality of life.10,14
Generic questionnaires provide information about outsideinfluences on the patients’ perception of their disability;disease specific questionnaires assess the effect of the diseaseon the individual’s quality of life.
New imaging modalities such as computed tomogra-phy and magnetic resonance venography are just beginningto be explored, and others will inevitably appear in the nearfuture. Molecular techniques offer to elucidate factors invaricose disease, wound healing, and pharmacotherapy. It ishoped that combining these methods will increase under-standing of venous insufficiency and offer new directionsfor improving patient care in venous and lymphatic dis-eases.
By continuing to forge ahead with exploration of newchallenges, we modify our descriptions as new knowledge isacquired. Understanding the balance of the risks and ben-efits of new therapies leads to improvement in the care ofpatients with venous and lymphatic diseases. By providing acongenial venue for professional exchange on a high aca-demic plane, the format of the AVF provides an importantopportunity to facilitate behavioral change in the form ofpromoting, adopting, and disseminating value-based ad-vances in the management of venous disorders. Thus, thebroadly brushed mission of our organization is integrallyrelated to advancing the treatment of chronic venous dis-orders. It has truly been a pleasure to serve as your presidentthis year, and I look forward to a long and continuedrelationship with this growing organization. Thank you.
Special thanks to Lois Densky-Wolff, Special Collec-tions Librarian of the UMDNJ, George F. Smith Library,for help with the illustrations.
REFERENCES
1. Moneta GL. There really is a pony in there. J Vasc Surg 2003;36:873-6.2. Gloviczki P. Presidential address: venous surgery—from stepchild to
equal partner. J Vasc Surg 2003;38:871-8.3. Hume Michael. A venous renaissance. J Vasc Surg 1992;15;671-73.4. Rich, NM. Venous disease, injury, and politics. Surgery 1993;113:120-
122.5. Archives of the American Venous Forum, a CD available from the AVF,
PMB #311, 203 Washington St., Salem, MA 01970.6. Gloviczki P, Yao JST, editors. Handbook of venous disorders: guide-
lines of the American Venous Forum, 2nd edition. Arnold, New York;2001.
7. Gloviczki P, Yao JST. Abridged chapters of the Handbook of venousdisorders: guidelines of the American Venous Forum, 2nd edition
JOURNAL OF VASCULAR SURGERYVolume 41, Number 2 Padberg 365
8. Porter JM, Moneta GL. Reporting standards in venous disease: anupdate. International Consensus Committee on Chronic Venous Dis-ease. J Vasc Surg 1995;21:635-45.
9. Ad Hoc Committee of the American Venous Forum. Classification andgrading of chronic venous disease in the lower limbs: a consensusstatement. In: Gloviczki P, Yao JST, editors. Handbook of venousdisorders: guidelines of the American Venous Forum, 2nd ed. London:Arnold; 2001. p. 521-5.
12. Girard P, Stern PB, Parent F. Medical literature and vena cava filters: sofar so weak. Chest 2002:122; 963-7.
13. Ansell JE. Air travel and venous thromboembolism—is the evidence in?N Engl J Med 2001:345;828-9.
14. Kurz X, Lamping DL, Kahn SR, Baccaglini U, Succarelli F SpreadficoG, et al. Do varicose veins affect quality of life: results of an internationalpopulation-based study. J Vasc Surg 2001:34;641-8.
15. Padberg FT Jr, Cerveira JJ, Lal BK, Pappas PJ, Varma S, Hobson RW II.Does severe venous insufficiency have a different etiology in the mor-bidly obese? Is it venous? J Vasc Surg 2003:37:79-85.
16. Bradbury AW, Evans CJ, Allan PL, Lee AJ, Ruckley CV, Fowkes GW.What are the symptoms of varicose veins? The Edinburgh Vein Studycross sectional population survey. Brit Med J 1999:381(7180):353-6.
17. Rabe E, Pannier-Fischer F, Bromen K, Schuldt K, Stang A, Poncar CH,et al. Bonner Venenstudie der Deutschen Gesellschaft für Phlebologie:Epedemiologische Untersuchung zur Frage der Häufigkeit und Aus-prägun von chronischen Venenkrankenheiten in der städtischen undländlichen Wohnbevölkerung. Phlebologie 2003:32:1-14.
18. Heit JA, Rooke TW, Silverstein MD, Mohr DW, Lohse CM, PettersonTM, et al. Trends in the incidence of venous stasis syndrome and venousulcer: a 25-year population based study. J Vasc Surg 2001:33:1022-7.
19. Padberg FT Jr, Maniker A, Carmel G, Pappas PJ, Silva MJ, Hobson RWII. Sensory impairment a feature of chronic venous insufficiency. J VascSurg 1999:30;836-43.
20. Munster S. Geographica Universalis, Basle, Switzerland, 1552.21. Richandson WF in collaboration with Carman JB. Introductory re-
marks in “On the fabric of the human body: book III the veins andarteries. By Andreas Vesalius”, a translation of De Humani CorporisFabrica Libri Septem. Novato, CA: Norman Publishing; 2002.
22. Paré A. The collected works of Ambroise Paré (translated out of theLatin by Thomas Johnson, London, first English edition, 1634). PoundRidge, NY: Milford House Inc; 1968.
23. Vesalius A. De Humani Corporis Fabrica Libri Septem (Seven Books on
the Structure of the Human Body) (1543) Basel.
24. Rutkow IM. Surgery: An illustrated history. St Louis: Mosby-YearBook; 1993.
25. Franklin KJ. Facsimile edition with introduction, translation, and notesof De Venarum Ostioli (On the Valves of the Veins) 1603 of Hierony-mus Fabricius of Aquapendente. Springfield, IL: Chas C Thomas;1933.
26. Magini GA. Geographiae Universae tum veteris tum novae absolutissi-mum opus. Venice, 1596.
27. Harvey W. Exercitatio Anatomica De Motu Cordis et Sanguinis inAnimalibus, Frankfort, 1628. A modern English translation with repro-ducions from the 1928 Tercentenial Edition as presented by ChaunceyD Leake, 2nd edition. Springfield, Ill: Charles C Thomas; 1930.
28. Speed J. A prospect of the most famous parts of the world, London,1626.
29. Doust J, DelMar C. Why do doctors use treatments that do not work?BMJ 2004;328:474-5.
30. Haines A, Jones R. Implementing findings of research. BMJ 1994;308:1488-92.
31. Widmer LK. Peripheral venous disorders: prevalence and socio-medicalimportance: observations in 4529 apparently healthy persons. Basle IIIStudy. Bern: Hans Huber; 1978.
32. Padberg FT Jr, Johnston MV, Sisto SA. Structured exercise improvescalf muscle pump function in chronic venous insufficiency (CVI): arandomized trial. J Vasc Surg 2004;39:79-87.
33. Wittens CHA, vanGent BW, Hop WCJ, Sybrandy JEM. The DutchSubfascial Endoscopic Perforating Vein Surgery (SEPS) Trial: a ran-domized multicenter trial comparing ambulatory compression therapyversus surgery in patients with venous leg ulcers. Society for VascularSurgery, Abstract #18, 2003.
34. Evidence-Based Medicine Working Group. Evidence-based medicine: anew approach to teaching the practice of medicine. JAMA 1992:268:2420-5.
35. Sacks H, Chalmers TC, Smith H. Randomized versus historical controlsfor clinical trials. Am J Med 1982;72:233-40.
36. Sevitt S, Gallagher N. Venous thrombus and pulmonary embolism: Aclinico-pathological study in injured and burned patients. Br J Surg1961:48:475-89.
37. Jonathan Meakins. Innovation in surgery: the rules of evidence. Am JSurg 2002:183;399-405.
39. Moher D, Schulz KF, Altman D; CONSORT Group (ConsolidatedStandards of Reporting Trials). The CONSORT statement: revisedrecommendations for improving the quality of reports of parallel-grouprandomized trials. JAMA 2001; 285:1987-91.
40. Jadad AR, Rennie D. The randomized controlled trial gets a middle-
