2. Kistner RL. Classification of chronic venous disease. Vascular Surgery 1997; 3:217-18.
3. Almgren B, Eriksson I. Valvular incompetence in superficial, deep, and perforator veins of limbs with varicose veins. Acta Chir Scand 1990; 1:69-74.
4. Perrin M, Bayon JM, Hiltbrand B, Nicolini P. Deep venous insufficiency and recurrent varicose veins after surgery of superficial venous insufficiency. J Maladies Vasculaires 1997; 22:343-47.
5. Kistner RL. Definitive diagnosis and definitive treatment in chronic venous disease: A concept whose time has come. J Vasc Surg 1996; 24:703-10.
6. Perrin M, Nicolini P. Reconstructive surgery in chronic venous disease of the lower limbs. Rev Med Suisse Romande 1997; 117:113-16.
7. Sottiurai VS. Surgical correction of recurrent venous ulcer. J Cardiovasc Surg (Torino) 1991; 332:104-09.
8. Walsh JC, Bergan JJ, Beeman S, Comer TP. Femoral venous reflux abolished by greater saphenous vein stripping. Ann Vasc Surg 1994; 8:566-70.
9. Padberg FT, Pappas PJ, Araki CT, Back IL, Hobson RW. Hemodynamic and clinical improvement after superficial vein ablation in primary combined venous insufficiency with ulceration. J Vasc Surg 1996; 24:711-18.
10. Sales CM, Bilof ML, Petrillo KA, Luka NL. Correction of lower extremity deep
venous incompetence by ablation of superficial varicosities. Ann Vasc Surg 1996;
10:186-189.
A total of 946 patients with clinically suspected deep vein thrombosis were tested.
The use of ultrasound and D-dimer testing allowed treatment decisions to be made
which reduced the number of repeat ultrasound examinations and in 598 patients receiving testing who did not receive anticoagulation, only one thromboembolic episode occurred.
HAEMODYNAMIC PATHOPHYSIOLOGY OF VENOUS INSUFFICIENCY OF THE LOWER LIMBS
Franceschi C.
ActualitÈs Vasculaires Int 1997; 47:17-27
ABSTRACT AND COMMENTARY BY:
Attilio Cavezzi, MD
San Benedetto del Tronto (AP), Italy
Dr. Franceschi has summarized his thoughts on the pathophysiology of venous insufficiency
in a lengthy article. The original may of great interest to readers of the Venous Digest
.
Dr. Franceschi feels that lower extremity venous dysfunction is mainly caused by
anatomic or functional blockage. Actual blockage may be caused by deep venous thrombosis,
obliteration of vessels by sclerotherapy, or extrinsic compression such as in the
Cockett syndrome. Functional obstruction is exemplified by venous drainage mechanism
dysfunction. This includes valvular incompetence or muscle pump failure. Valve
incompetence proximal to the muscle pump allows normal systolic blood flow but produces
diastolic reflux. Valve incompetence distal to the muscle pump may produce bidirectional
flow without venous disease if the muscle pump is efficient. Venous shunts react
differently, depending on posture. For example, during ambulation, venous flow is
toward the heart during systole and back into the deep veins through the incompetent
saphenous vein during diastole. This may exhaust the muscle valve pump and dilate
superficial incompetent veins. Each of the venous shunts has two pathways, one deep
and one superficial. These are interconnected. Segmental deep reflux may occur near
entry of incompetent superficial veins such as common femoral vein reflux in cases
of incompetence of the saphenofemoral junction or popliteal reflux above an incompetent
saphenopopliteal junction.
The concept of reentry of blood from varicose veins into the deep venous system is
of great importance. The normal function of perforating veins is to aspirate superficial
blood into the deep venous system. Pathologic reflux, that is diastolic flow from
deep to superficial veins, occurs in perforating veins proximal to a normally functioning
venous pump. In cases of primary varicose veins, many of the perforating veins perform
a predominant aspirating function even if dilated. This is also true when the perforating vein is under a trophic lesion caused by primary, not postthrombotic
disease. Even the smallest varicosities and telangiectasias are mainly a sign of
incorrect drainage of blood in major veins. They are either a sign of blocked drainage
of superficial subcutaneous venules or an overloading of venous capillaries.
Dr. Franceschi goes on to say that large varicose veins do not give rise to dystrophic
changes such as ulceration if there is good reentry into the deep venous system at
some distance from the perimalleolar region where there is an abnormal lack of normal
venous drainage and a maximum gravity-induced overload. He further stresses the importance
of avoiding the elimination of draining pathways, whether are diseased or normal.
He feels it is necessary to disconnect pathologic veins but preserve drainage pathways and direct flow towards more efficient reentry perforators.
COMMENTARY
Commenting on an article like this is difficult, especially for one who does not
totally agree with Dr. Franceschi's CHIVA technique. On the other hand, this reviewer
appreciates most of the CHIVA diagnostic approaches and premises.
The hemodynamic models which have been proposed by careful research and the use of
color Doppler has helped us to understand why saphenous disease is mainly a result
of reflux. One thing should be said regarding CHIVA treatment. If the function
of the muscle valve pump is important in the pathogenesis of venous insufficiency, then the
CHIVA method is clearly muscle valve pump dependent. The question arises whether
in time the muscle valve pump will be compromised, thus threatening the hemodynamic
correction achieved by the CHIVA operation.
One interesting concept supported by color duplex scanning is that deep venous incompetence
may be caused by superficial venous incompetence. The common femoral and popliteal
veins are affected by reflux in the adjacent saphenous junctions. Saphenous incompetence is capable of overloading the deep venous system with its own private recirculation.
Regarding the hemodynamics of perforating veins, it does appear that venous trophic
disorders are a sign of superficial microvascular hydrostatic hypertension.
The conclusions reached in this article are characterized by recognition of the hereditary/constitutional
nature of venous insufficiency and therefore of our own ignorance in the origins
of varicose veins. The article highlights the importance of hemodynamic investigation before any treatment. It may be the role of the echo-color Doppler
to bring specialists together to share and perfect their experiences.
Many more points are made by Dr. Franceschi but space limitations have allowed only
a discussion of the principal concepts. vdbercav
PERICAPILLARY FIBRIN CUFFS IN VENOUS DISEASE: A REAPPRAISAL
Van de Scheur M, Falanga M
Dermatol Surg 1997; 23:955-59
ABSTRACT AND COMMENTARY BY:
H.A.M. Neumann, MD
Department of Dermatology
University Hospital Maastricht
Maastrict, The Netherlands
In this review, the authors focus on the complex pathogenesis of venous disease with
special attention to the role of fibrin cuffs. Browse and Burnand postulated that
venous ulceration is due to pericapillary fibrin cuffs which act as barriers to
the diffusion of oxygen and nutrients. The barrier function of these cuffs is highly debated
since the cuffs tend to be discontinuous around dermal capillaries and the extent
of fibrin deposition may not be related to the relative degree of venous insufficiency. The fibrinogen molecule has a trinodular structure. Three types of chains exist.
Higher order of cross-linked chains occurs through the formation of gamma chains.
Perhaps this structure contributes to the resistance of fibrinolysis of the fibrin
cuffs.
It has been suggested that patients with venous disease lack an "escape route" from
the conversion of fibrinogen to cross-linked fibrin. Fibrin may contribute to the
inflammatory process in lipodermatosclerosis. In addition to the fibrin cuff hypothesis, white cell trapping is gaining importance in the pathogenesis of venous disease.
Recently, Falanga and Eaglstein proposed an alternative hypothesis. They hypothesized
that not only fibrin but macromolecules leak into the dermis and "trap" growth factors
which renders them unavailable for the homeostasis of tissue integrity and the repair process. Fibrin itself may be the most important factor but it acts as a marker
for decompensation of the venous system and especially for the larger problem of
macromolecular leakage.
COMMENTARY
This review summarizes many of the ideas concerning the pathogenesis of venous disease.
The fibrin cuff theory was one of the first recent hypotheses to be published (1982).1 Important to this is the knowledge that reflux in the veins results in alterations
of the microcirculation. All skin changes, including leg ulcers, are the result
of failing microcirculation. Particularly relevant to this discussion is microangiopathy, a prominent feature in chronic venous insufficiency (CVI).2 Bollinger, et al. combined the techniques of intracavital capillaroscopy and fluorescein
angiography with videodensitometry.3 The results are suggestive of a diffusion-limited transport in those areas of the
skin which have a decreased capillary density. Microthrombosis will occur, probably
in relation to white cell trapping, which results in diminishing capillary density.
In the fibrin cuff therapy, it was proposed that the high venous pressure in chronic
venous insufficiency caused leakage of large molecules through capillaries into the
pericapillary fibrin cuff. It has been shown that the cuff consists of fibrin and
not fibrinogen.4 This cuff should act as an oxygen-diffusion barrier. In addition, a significant
increase in the collage IV layer in or around the capillaries has been found. Over
time, however, significant doubts arose about the role of fibrin as a diffusion barrier.5 Neumann, et al. suggested that fibrin may function as a matrix for the formation
of collagen.6
In a prospective, comparative, human model study, 16 patients with chronic venous
insufficiency, six patients with porphyria cutanea tarda without venous disease,
four with ecthyma ulcers, and ten healthy volunteers were examined. Transcutaneous
oxygen readings were significantly lower in venous patients than in all other groups. Fibrin
cuffs were found in 8 of 16 venous patients, in all patients with porphyria cutanea
tarda, and in three of four patients with ecthyma ulcers. Based on these results,
it was concluded that fibrin cuffs alone do not act as a barrier for oxygen transport.7 Fibrin deposits are more an indicator of microcirculatory disturbances than as
the cause of low TcPO2.
A human model mimicking venous insufficiency in patients with Klinefelter syndrome
was described. These patients lacked objective hemodynamic signs of chronic venous
insufficiency but all had skin alterations typical of CVI such as lipodermatosclerosis
and atrophie blanche. Plasminogen activator inhibitor 1 (PAI-1) was significantly
increased in these patients.8 As fibrinolysis is disturbed in tissue in CVI, it is very possible that white cell
trapping combined with local disturbances in fibrinolysis is the final cause for
the most significant and serious skin changes noted in chronic venous insufficiency:
lipodermatosclerosis, atrophie blanche, and leg ulceration.
The final mechanism leading to non-healing venous leg ulcers is still unknown. We
can only hypothesize, on information from the literature that dilated capillaries
develop under the high venous pressure in venous disease. This ambulant high venous
pressure (venous hypertension) leads to low flow. White cell trapping will occur as non-immunological
binding to the capillary endothelium. White cell trapping causes occlusions in the
microcirculation which leads to microthrombosis. As the capillaries occlude, the capillary density diminishes. This leads to low tissue oxygen levels.
Leakage of macromolecules leads to cuffs with fibrin as a marker but also other macroglobulins
such as a-2 macroglobulin are a part of these cuffs. a-2 macroglobulin binds growth factors such as TGF-þ. Therefore, fibrin cuffs, which
are only the indicators of a seriously disturbed microcirculation, attracted our
attention to the pathway of low tissue oxygen tension and also to trapping of growth
factors. This could explain why chronic venous insufficiency leads to leg ulcers and why
they do not heal spontaneously. More studies are needed concerning these fascinating
fibrin cuffs. vdneu034
REFERENCES
1. Browse NL, Burnand KG. The cause of venous ulceration. Lancet 1982; 2:243-45.
2. Leu AJ, Yanar A, Pfister G, et al. Mikroangiopathie bei chronischer ven–serum
insuffizienz. Dtsch Med Wschr 1991; 116:447-53.
3. Bollinger A, J”ger K, Geser A et al. Transcapillary and interstitial diffusion
of Na-fluorescein in chronic venous insufficiency with atrophy. Int J Microcirc
Clin Exp 1982; 1:5-17.
4. Brakman M, Faber WR, Kerckhaert JAM et al. Immunofluorescence studies of atrophie
blanche with antibodies against fibrinogen, fibrin, plasminogen activator inhibitor,
factor VIII-related antigen, and collagen type IV. VASA 1992; 21:143-48.
5. Michel CC. Oxygen diffusion in edematous tissue and through pericapillary cuffs.
Phlebology 1990; 5:223-30.
6. Neumann HAM, van den Broeck MJTB. Increased collagen IV layer in the basal membrane
area of the capillaries in severe chronic venous insufficiency. VASA 1991; 20:26-29.
7. Neumann HAM, van den Broek MJTB, Boersma IH, Veraart JCJM. Transcutaneous oxygen
tension in patients with and without pericapillary fibrin cuffs in chronic venous
insufficiency, porphyria cutanea tarda, and non-venous leg ulcers. VASA 1996; 25:127-33.
8. Veraart JCJM, Hamulyak K, Neumann HAM, Engelen J. Increased plasma activity of
plasminogen activator inhibitor 1 (PAI-1) in two patients with Klinefelter syndrome
complicated by leg ulcers. Br J Dermatol 1994; 130:641-44.
THANKS TO THE 1998 CONTRIBUTORS
In 1998, the Venous Digest continued its commitment to improve the treatment of venous disease. Our success
is dependent upon the excellent abstracting of articles and commentary provided by
the following individuals. This is truly an international Who's Who of physicians interested in diagnosis and management of venous disorders. The Editorial
Office extends many thanks to them for their good work. vd.contr
Allegra, Claudio, Rome, Italy
Andreozzi, Giuseppe, Padua, Italy
Ascher, Enrico, Brooklyn, New York
Ballard, Jeffrey, Loma Linda, California
Bass, Arie, Zerifin, Israel
Bergqvist, David, Uppsala, Sweden
Bl”ttler, Werner, Z¸rich, Switzerland
Bradbury, Andrew, Edinburgh, Scotland
Bundens, Warner, San Diego, California
Burnand, Kevin, London, United Kingdom
Cairols, Marc, Barcelona, Spain
Caprini, Joseph, Evanston, Illinois
Charlesworth, Peter, Auckland, New Zealand
Conrad, Peter, Sydney, Australia
Cordts, Paul, Tripler, Hawaii
D'Addato, Massimo, Bologna, Italy
DeBarros Jr., Newton, Sao Paulo, Brazil
DePalma, Ralph, Reno, Nevada
Eklof, Bo, Honolulu, Hawaii
Fagrell, Bengt, Stockholm, Sweden
Fischer, Reinhard, St. Gallen, Switzerland
Fronek, Arnost, La Jolla, California
Goldman, Mitchel, La Jolla, California
Gradman, Wayne, Los Angeles, California
Green, David, Bethesda, Maryland
Green, David, Chicago, Illinois
Guex, J.-Jerome, Nice, France
Hingorani, Anil, Brooklyn, New York
Hoffmann, Ulrich, Z¸rich, Switzerland
Hoshino, Shunichi, Fukushima, Japan
Hunter, Glenn, Galveston, Texas
Kerstein, Morris, Philadelphia, Pennsylvania
Killewich, Lois, Baltimore, Maryland
Labropoulos, Nicos, Maywood, Illinois
Lalka, Stephen, Indianapolis, Indiana
Linde, N., St. Gallen, Switzerland
Mackiewicz, Zygmunt, Bydgoszcz, Poland
McIntyre, W. Burley, Loma Linda, California
Murray, Jay, San Diego, California
Myers, Kenneth, Richmond, Australia
Nachbur, Bernard, Berne, Switzerland
Norgren, Lars, Lund, Sweden
Olivencia, Jose, Des Moines, Iowa
Ouvry, Paul, Toulouse, France
Ouvry, Pierre, Toulouse, France
Padberg, Frank, Jr., East Orange, New Jersey
Partsch, Hugo, Vienna, Austria
Perrin, Michel, Decines, France
Pfeifer, John, Troy, Michigan
Rooke, Thomas, Rochester, Minnesota
Ruckley, C. Vaughan, Edinburgh, Scotland
Sales, Clifford, Belleville, New Jersey
Sanders, Richard, Denver, Colorado
Sapio, Nicola, Berne, Switzerland
Schmid-Sch–nbein, Geert, La Jolla, California
Schoevaerdts, Jean-Claude, Godinne, Belgium
Sobel, Michael, Richmond, Virginia
Somjen, George, Melbourne, Australia
Sottiurai, Vikrum, New Orleans, Louisiana
Stemmer, Robert, Illkirch, France
Struckmann, Jan, Charlottenlund, Denmark
Sykes, Mellick, San Antonio, Texas
Takase, Shinya, Fukushima, Japan
Vandendriesse, Marianne, Gent, Belgium
Villavicencio, J. Leonel, Bethesda, Maryland
Widmer, Matthias, Berne, Switzerland
A UNIFYING CONCEPT OF PRIMARY VENOUS INSUFFICIENCY
Bergan JJ
Dermatol Surg 1998; 24:425-28
ABSTRACT AND COMMENTARY BY:
Lois Killewich, MD
Assistant Professor of Surgery
University of Maryland Medical Center
Baltimore, Maryland
Dr. Bergan has written a concise, useful monograph on primary venous insufficiency,
a disease process in which valvular incompetence develops in lower extremity veins
without an antecedent episode of deep venous thrombosis. Valvular incompetence produces
incomplete emptying of lower extremity veins with resultant dilatation and varicosity
formation. Dr. Bergan begins by establishing the concept that varicose veins, reticular
varicosities, and telangiectasias all represent different manifestations of this disease. He then discusses its underlying etiology, indications for intervention,
and treatment options.
The development of primary venous insufficiency is influenced by heredity, hormones
(particularly high progesterone levels), gravitational forces, and the calf muscle
pump. This explains why varicosities develop during pregnancy and why deep venous
incompetence can be translated into superficial and perforator incompetence through the
pumping action of the calf muscles. The indications for intervention include pain,
heaviness, fatigue, bleeding, thrombophlebitis, and ulceration. Ambulatory phlebectomy
aimed at correcting the abnormal hydrostatic and hemodynamic forces remains the mainstay
of surgical therapy.
COMMENTARY
Several of the concepts discussed in this paper deserve attention. The importance
of the calf muscle pump in promoting the development of varicosities cannot be underestimated.
When deep veins become incompetent, the volume of blood within their lumens increases. This results in increased pressure in the superficial veins which dilate,
become incompetent, and increase pressure in the superficial veins. Since no further
outlet for the increased volume and pressure exists, these vessels not only become
incompetent but also dilate and become varicose. By increasing pressure in the deep
and perforating veins each time contraction occurs, the calf muscle pump promotes
this cascade. Interruption of the pressure (i.e., correcting incompetence in deep
veins) can restore competence to superficial veins and provide at least partial relief.
Furthermore, physicians need to understand the relationship between symptoms such
as leg aching and the various types of varicosities. Therapy cannot be initiated
if the physician does not make this connection. Dr. Bergan makes the point that
"...neither the patient nor the physician may understand that these symptoms [of venous insufficiency]
arise from telangiectatic blemishes just as easily as from venous varicosities."
He states further that "...85% [of these patients] will be relieved of them by appropriate therapy." Primary care physicians, surgeons, and dermatologists should
be aware of these relationships since they are most likely to conduct the initial
evaluation.
A final point for those of us who treat venous insufficiency surgically is the importance
of assessing the saphenofemoral and saphenopopliteal junction and performing excision
(rather than simple ligation) if either are found to be incompetent. Dr. Bergan cites many studies which demonstrate a high rate of recurrence if saphenous incompetence
is ignored when ambulatory phlebectomy is performed. He also reminds us that it
is unnecessary to remove the saphenous vein below the knee and that this results
in a high incidence of saphenous nerve injury.
This paper provides useful information for the primary care physician and the practicing
dermatologist or vascular surgeon. For those of us whose classical education is incomplete,
Dr. Bergan could assist us by providing a definition of "atrophie blanche." vdkil288
Venous Disorders of the Legs: Principles & Practice
L. L. Tretbar
Springer-Verlag, London, 1998
139 pages with color plates
It is a refreshingly welcome experience to see a single-authored medical textbook.
In this case, the author's personality comes through directly. His approach is
straightforward and, as he says in the preface, he "speaks in ordinary English."
The author himself is quite authoritative. He has a 30-year experience in America after one
year spent in the Middlesex University Hospital in London. The Hospital is now the
site of the most elegant clinical and basic science research on venous disorders.
Dr. Tretbar's personality also comes through in his execution of many of the drawings
in the book and, as it turns out, he is a good artist as well as a good surgeon.
As straightforward as the author himself is the organization of the volume. It
contains sections on anatomy of leg veins, venous function, modern evaluation, and venous
testing as well as sections on therapy. This reviewer found the history of medical
and surgical treatments of varicose veins to be amusing and enlightening. Therapy
by sclerotherapy as well as surgery is well covered and there are separate chapters on
complications of chronic venous insufficiency and venous thromboembolic disease.
It is important that Tretbar emphasizes that what used to be called the postphlebitic
leg is now referred to as chronic venous insufficiency which implies that there is surgical
treatment available.
Tretbar has been concerned mainly with treatment of varicose veins and it is in these
sections that his work is most valuable. This is in contrast with the chapter on
venous thromboembolic disease which, in other texts, occupies much more space and
emphasis. It is junior surgeons often assigned the treatment of patients with venous disorders.
As they are assigned responsibility, this book can be recommended to them. It is
here that the anatomy and pathophysiology are well explained. Treatment based on
that knowledge is also explained thoroughly.
Thus, this volume provides an introduction to the diagnosis and treatment of the most
common venous disorders and hopefully will stimulate younger surgeons to accept the
veins as part of their practice of vascular surgery. This book is recommended for
the use of general surgeons, dermatologists interested in venous disease, and vascular
surgeons who, in their fellowship, are interested in expanding their work to the
other side of the vascular system. It is an attactive, well-designed, well-executed
volume which fulfills its promise of describing principles and practice. book-015
A NOVEL CULTURING AND GRAFTING SYSTEM FOR THE TREATMENT OF LEG ULCERS
Villeneuve P, Hafner J, Prenosil JB, Elsner P, Burg G.
Br J Dermatol 1998; 138:849-51
COMMENTARY BY:
Prof. Ricardo Gesto
Madrid, Spain
Autologous tissue cultures and allogenic keratinocytes have been used for years to
cover chronic skin defects of venous and diabetic foot ulcers. The clinical results
of these studies have been heterogeneous. It is difficult to establish the usefulness of a technique with no data from controlled trials. The objective of this project
was to develop an efficient system of culturing and grafting that was more rapid
and easier to achieve than that described by Green et al. (Proc Nat Acad Sci USA
1979; 76:5665-68).
The culture system is a combination of two commercially available products. A Petriperm
culture vessel was aseptically placed in a Petri dish. The bottom of the Petriperm
disk was made of a fine Teflon film. This film was nonreactive, non-adhesive, flexible, permeable to gas, and transparent. The human epidermal cells were separated,
processed, and cultured as described by Green with some modifications.The technique
was used in a 61-year-old female who had suffered a superficial trauma which left
her with a wound on the anterior surface of the right tibia. The ankle/arm index and
oscillogram were normal and there were no clinical signs of venous disease. The
Doppler did not show reflux of the deep and superficial venous systems. Local dressings
and skin grafts had failed. The wound was finally treated with four epidermal grafts
over a 12-week period using this method, showing good progress and eventual closure
of the wound.
Culture of epidermal grafts requires trained personnel, an adequate medium, and a
constant supply of fibroblasts. This method allows grafts to be obtained with less
effort at a reasonable cost and could be used in other skin alterations such as vitiligo.
COMMENTARY
The authors describe obtaining skin graft cultures, modifying Green's method. This
appears to be simpler with an adequate cost/benefit balance. As stated in the article,
the usefulness of a technology must be confirmed through data based on controlled
clinical trials. In this case, the clinical experience is based on a single case
in a patient with no vascular disease and in whom a good result was obtained after
other treatment forms had failed. The method needs to be compared in prospective
clinical trials in order to be validated.
In general, patients with chronic ulcers of the lower extremities suffer from vascular
disease responsible for the lesion. Therefore, it is imperative that treatment of
these ulcers includes treatment of the underlying disease. Subsequently, treatment
of the ulcer with the usual means (topical treatment or free skin grafts over large
defects) offers no particular problems.
In any case, the new method seems to be a valid alternative treatment for chronic
ulcers as it permits treatment of wounds with a variety of cell types simultaneously.
However, this new method needs to be validated by comparative trials with other
therapy. ivdfges
MINI ABSTRACTS
John J. Bergan, M.D.
Items of Interest Which Have Crossed the Editor's Desk
(Provided for reference purposes and general interest)
D-dimer Testing as an Adjunct to Ultrasonography in Patients with Clinically Suspected
Deep Vein Thrombosis: Prospective Cohort Study
Bernardi E, Prandoni P, Lensing AWA, et al.
Br Med J 1998; 317:1037-40