VD402R

TELANGIECTASIAS: NOT ONLY A COSMETIC PROBLEM
Marshall M.
Perfusion 1996; 9:285-87

ABSTRACT AND COMMENTARY BY:
Matthias Widmer, M.D.
Liestal, Switzerland

The goal of this study was to show how duplex scanning can document variations in the deep venous system in men and women with or without varicosis but with telangiectasias. Measurement of the diameter of the common femoral vein during a Valsalva test and the diameter of the greater saphenous vein close to the junction gives an absolute value. There is an obvious difference between men (1.57/1.58 R/L) and women (1.35/1.37 R/L). There is no significant variation in relation to age (15-77 years).

The diameter of the greater saphenous vein for normal men was 0.82 compared to 0.72 for normal women. Telangiectasias are a common complaint of women. Therefore, the same measurement was done for 30 women with telangiectasias who had no sign of chronic venous insufficiency (97%). Forty percent had a positive Valsalva test for more than two seconds. The average diameter of the common femoral vein in women with telangiectasias was 1.56 cm. When compared to the control group with 1.34 cm, the difference was 16% (p < 0.05). The value for females with branch varicosities was 1.41 cm and 1.53 cm if the greater saphenous vein showed varicosities.

In a small number of limbs, each with 11 patients, the measurements were done before and six months after treatment with either sclerotherapy and compression or with compression only. In the group with sclerotherapy, the diameter diminished from 1.49 cm to 1.42 cm, but with compression alone, the diameter increased from 1.45 cm to 1.54 cm.

In summary, telangiectasias, especially those of the thigh, correlate with an increase in the diameter of the common femoral vein. The author concludes that this indicates progression of the venous pathophysiology and that short-term results of sclerotherapy show evidence of prevention of progression of this pathology.

COMMENTARY

The first part of the paper shows an anatomic fact that vessels of men are larger than those of women. It is important to know the absolute value but there is no information concerning the height and weight of the patients. Also, the Valsalva test is not exactly reproducible. Even the patient age is a concern. Analyzing the data, the average diameter of 1.56 cm in the group of 30 females with telangiectasias has an age-dependent variability (< 30 years 1.46 cm., 30-40 years 1.63 cm, and > 40 years 1.56 cm). In the group of 11 patients with telangiectasias, the average value of 1.56 cm contrasts with 1.49 cm in the normals. That means a difference of 0.7 cm between these groups. This fact is important for interpretation of the data and should be explained by the author.

It is interesting that the average diameter of the common femoral vein is greater in patients with telangiectasias than in those with varicosities of branches or of the greater saphenous vein. There are no details or explanation for this phenomenon in the study. Another important question remains. Which is first: the telangiectasias which influence the deep vein system or dilatation of the deep system which leads to telangiectasias? Documentation in a small number of patients that sclerotherapy can diminish the diameter of the deep vein system suggests the first hypothesis is true. A clinical fact is that 97% of patients with telangiectasias have a chronic venous insufficiency, grade I. The fact that 40% have a positive Valsalva test greater than two seconds is surprising but suggests that changes in the deep system lead to telangiectasias. Further investigation with long-term duplex studies for all categories of varicosis should be done to document changes of femoral vein diameter before and after operative or conservative treatments. 5965b

MANEUVER TO FACILITATE AMBULATORY PHLEBECTOMY
Olivencia JA
Dermatol Surg 1996; 22:654-55

ABSTRACT AND COMMENTARY BY:
Mitchel P. Goldman, M.D.
La Jolla, California

In the course of phlebectomy, varicose veins often break under traction. When this happens, many stab incisions are needed and veins must be extracted piecemeal. This article describes a traction maneuver that facilitates vein extraction, allowing longer vein segments without breaking the vein and thereby decreasing the number of "micro-incisions" needed.

COMMENTARY

This short, well-illustrated caveat provides the reader with three additional techniques for facilitating removal of varicose veins under local anesthesia with the ambulatory phlebectomy procedure. Essentially, these maneuvers have been previously published along with many others.1 Although it is debatable whether the extraction of varicose vein segments should be performed with multiple minute stab incisions or with fewer incisions, certainly the greater the amount of vein which can be removed, the greater the patient's satisfaction with the procedure. One should strive to leave as few disrupted segments within the skin as possible. When varicose vein segments are left under the skin, they will be resorbed through an inflammatory reaction which is disturbing to the patient since it causes warmth, erythema, and nodularity. 5966b

REFERENCE

1. Ricci S, Georgiev M, Goldman MP (eds). Ambulatory Phlebectomy: A Practical Guide for Treatment Varicose Veins, 1995.

THIRD-GENERATION ORAL CONTRACEPTIVES AND RISK OF VENOUS THROMBOLIC DISORDER: AN INTERNATIONAL CASE-CONTROLLED STUDY
Spitzer WO, Lewis MA, Heinemann LAJ
Br Med J 1996; 312:83-88

THIRD-GENERATION ORAL CONTRACEPTIVES AND RISK OF MYOCARDIAL INFARCTION: AN INTERNATIONAL CASE-CONTROLLED STUDY
Lewis MA, Spitzer WO, Heinemann LAJ, et al.
Br Med J 1996; 312:88-90

ABSTRACT AND COMMENTARY BY:
Richard E. Blackwell, PhD, MD
Professor of Obstetrics & Gynecology
Reproductive Biology & Endocrinology
University of Alabama at Birmingham
Birmingham, Alabama

The combination oral contraceptive pill was introduced in 1960 and is currently used by 13.8 million women in the United States and 60 million women worldwide. The first oral contraceptive agent approved by the FDA (Enovid) contained 150 mcg of mestranol and 10 mg of norethynodrel. The side-effects associated with Enovid and other high-dose estrogen pills resulted in the introduction of formulations containing less than 50 mcg of estrogen in 1973. Currently, 82% of prescriptions (1988) are written for these low-dose compounds.

The majority of these agents contain between 20 and 35 mcg of ethinyl estradiol and between 0.5 and 1.0 mg. of norethindrone or norgestrel. Norgestrel is considered to be the most androgenic progestogen. Norgestimate, a progestogen recently approved for use in the United States, has been shown to have less androgenic side-effects than the other derivatives of 19-nortestosterone. It was thought that this feature might be important as many of the side-effects of steroid contraceptive agents were assigned to the androgenic activity of progestogen. However, it appears that most of these effects are mediated by estrogen. Subsequently, two third-generation progestogens were introduced in the United States and European markets (desogestrel and gestodene) which have similar clinical profiles to norgestimate.

COMMENTARY

In 1995, the German Federal Institute for Drug and Medical Devices restricted the distribution of third-generation oral contraceptive agents containing desogestrel or gestodene. They suggested that these drugs not be prescribed for women under the age of 30 who were taking birth control pills for the first time or those who had any risk of possible blood clots. Epidemiologic studies were distributed at the institute prior to publication which suggested that blood clots occurred roughly twice as often among women who took third-generation oral contraceptives as those who had used second-type pills. They emphasized that the clots were very rare, and did not recommend discontinuation of the third-generation pills if the women were currently experiencing no difficulty.

Subsequently, the Transnational Research Group on Oral Contraceptives and the Health of Young Women published two papers in the British Medical Journal . One indicated the possibility of death from thrombovenous embolism for women using second-generation products to be approximately 20 million users per year, and the second indicated that this number was approximately 14 million users per year with nonusers having a rate of 5 million per year. Their studies also indicated that with an odds ratio of 0.45 and a wide confidence interval, third-generation oral contraceptives were associated with an increased risk of myocardial infarction or with no difference when compared to second-generation products.

The emboli study was a match case-controlled design and involved ten centers in Germany and the United Kingdom. There were 471 women (ages 16-44) who had venous thromboembolism with 1,772 controls unaffected by venous thromboembolism (three controls per case) matched with corresponding cases per age and per hospital or community setting. The outcome measurements include odds ratio, ratios derived with stratified analysis, and unconditional logistic regressions to adjust for potential compounding variables.

The myocardial infarction study was a match case-controlled design involving 16 centers in Austria, France, Germany, Switzerland, and the United Kingdom. There were 153 women (ages 16-44) with a myocardial event with 498 controls unaffected by myocardial infarction (three controls per case) matched with corresponding cases per age and per hospital or community setting within four months of the index infarction. The mean outcome measurements include odds ratio, ratios derived with stratified analysis, and unconditional logistic regressions to adjust for potential compounding variables.

Regarding emboli the authors conclude, "increased risk of venous thromboembolism alone is equivalent to the increase of death from cancer and heart disease if a woman smoked ten cigarettes a year. Our data justifies clinical prudence but allows doctors and women seeking contraception to exercise informed choice."

With regard to myocardial infarction, the authors state, "our findings on the potential benefits of third-generation oral contraceptives with respect to the risk of myocardial infarction against a backdrop of potential harm with respect to the risk of thromboembolism shows that all known risks and benefits should be evaluated simultaneously when decisions about such products are taken. Both generations of oral contraceptives can be recommended on the basis of judicious clinical advice by the doctor and the informed choice of the women using contraception."

Further, one of the principal investigators in these studies was quoted in OB/GYN News (August 1, 1996) as saying, "I stand here as an epidemiologist and tell you that an odds ratio of 1.5 in an uncommon disease like venous thromboembolism is trivial, has no public health importance, and no clinical significance. In drug safety and public health, relative risks are often misleading. Threefold and twofold increases in uncommon diseases are favorites of the press but the absolute rate differences are what is essential. Oral contraceptives constitute the singlemost important public health invention in the history of womankind since the conquest of communicable diseases. All second- and third-generation oral contraceptives currently on the market are safe and effective. Certainly much safer than pregnancy itself." 5967b

PATHOPHYSIOLOGY OF CHRONIC VENOUS INSUFFICIENCY
Bauersachs J, Fleming I, Busse R.
Phlebology 1996; 11:16-22

ABSTRACT AND COMMENTARY BY:
Peter J. Pappas, M.D.
Assistant Professor of Surgery
UMDNJ - New Jersey Medical School
Newark, New Jersey

This article summarizes the accepted theories and facts regarding the pathophysiology of chronic venous insufficiency. The authors review the macrocirculatory mechanisms of venous return to the heart and how valvular incompetence and outflow obstruction leads to venous hypertension. Post capillary venular activation, cellular adhesion molecule alterations, leukocyte and protein extravasation are all reviewed. The article concludes with a brief overview of nitric oxide and its possible role in venous insufficiency.

COMMENTARY

This review article is an attempt to superficially summarize the information known regarding the pathophysiology of chronic venous insufficiency and to speculate on the possible role of nitric oxide. My objection relates to the degree to which the authors explained various concepts and theories. There was no attempt to alert the reader as to which facts are universally accepted and which are controversial.

As such, the reader is slightly misled. For example in the section entitled "Plasma Protein Extravasation" the authors state, "since these [interendothelial] pores are not immediately closed, there is enhanced and prolonged extravasation of plasma proteins." Although it has been reported that the interendothelial gap junctions are widened in patients with active ulcers, it is not known how long they remain open and if this is the main mechanism of protein extravasation. The authors go on to state, "the outflow of fibrinogen together with a decreased fibrinolytic activity is thought to be responsible for the interstitial deposition of fibrin in the legs of patients with CVI (chronic venous insufficiency)." Although Burnand and Browse hypothesized that fibrin was the major constituent of perivascular cuffs, it is now clearly known that the cuff is made of collagen types I and III, tenascin, laminin, fibronectin, vitronectin, and very little fibrin. These proteins are the fabric of the extracellular matrix. Their formation into a cuff suggests that they may be the scaffolding upon which endothelial cells migrate and elongate. The cuff clearly has nothing to do with fibrinogen extravasation.

The major flaw with this review article relates to the issue of nitric oxide, an exciting molecule with enormous effects on the microcirculation. Nitric oxide affects leukocyte attachment and endothelial cell signalling. In their abstract, the authors state that they wanted to focus on the role of alterations in nitric oxide production by the vascular endothelium. However, there have been no studies to date that have attempted to investigate the role of nitric oxide in the pathogenesis of chronic venous insufficiency. As such, any statements regarding nitric oxide and venous insufficiency are purely speculative.

In conclusion, I found this article to be too superficial and slightly misleading. It is a good general introduction on the topic of chronic venous insufficiency but the areas of controversy are not clearly stated for the reader. Furthermore, the role of nitric oxide in CVI has not been investigated and is speculative at this time. If the reader is interested in an in-depth review of microcirculatory dysfunction and CVI, I recommend the following article: Leu AJ, Leu HJ, Franzec UK, Bollinger A. Microvascular changes in chronic venous insufficiency: A review. Cardiovasc Surg 1995; 3:237-45. 5968b

SUBFASCIAL ENDOSCOPIC SURGERY OF PERFORATING VEINS: SEPS (Chirurgie Sub-Fasciale Des Veines Perforantes: CSVP)
Bergan JJ, Ballard JL, Sparks S, Murray JS
Phl�bologie 1996; 49:467-72

ABSTRACT AND COMMENTARY BY:
Dr. med. Reinhard H. Fischer
St. Gallen, Switzerland

This article, which was requested by the guest editors of the journal, Phl�bologie , consists of three parts. In the first, the pathophysiology of perforating veins and the rationale for their interruption is described. The authors state that chronic venous insufficiency (pigmentation, lipodermatosclerosis, and ulceration) are related to venous hypertension. In this situation, incompetent perforator valves play a key role and gravitational reflux and muscle pump forces are additive. Division of the incompetent perforating veins, therefore, improves the situation of chronic venous insufficiency.

In the second section of this article, the work on subfascial endoscopic perforator vein surgery (SEPS) done by phlebologic surgeons in German-speaking countries of Europe is described and appreciated. Hauer was the first to develop special instruments for this purpose. He showed that from a small incision in the proximal medial leg, the 24 cm. and Cockett perforating veins could be visualized and divided, usually in the course of a standard stripping procedure. Attention is called to the fact that earlier phlebologists such as Arnoldi and Linton had advocated the division of perforating veins by open surgery. They simultaneously advised division of the superficial and deep fascia to relieve the pressures in the deep muscular compartment. These operations often healed venous ulcers but the endoscopic technique allows this to be done with minimal invasion.

In the third part of this article, the authors report their own 31 cases observed from the summer of 1993 to the summer of 1995. In 16 of the 31, the objective of the SEPS was to prevent recurrent ulcer. In these 16, severe lipodermatosclerosis definitely improved following the operation. In another 15 patients, the objective was to heal an existing ulcer. Thirteen of these had a history of ulceration of greater than five years. In 7 of the 13, the ulcer healed within four weeks, and in four more, the ulcer healed within eight weeks of surgery. One ulcer healed after six months, and in another, a femoral vein stent for May-Thurner syndrome and excision of the ulcer bed was necessary. The operation was done on an outpatient basis in 13 of the 31 cases, and low-molecular-weight heparin was given as prophylaxis against thrombosis and embolism in cases with a previous history of deep venous thrombosis.

Two cases illustrate the benefit of the method particularly well. In one, an 82-year-old, wheelchair-bound woman had a prior stripping procedure of the greater saphenous vein and skin grafting for an ulcer 8 x 12 cm. in size. The initial graft did take but subsequently sloughed, and the ulcer remained unhealed. An ambulatory endoscopic division of incompetent perforating veins was done under general anesthesia and within 16 weeks, the ulcer was healed and has remained healed since that time. In another case, a diabetic, 45-year-old man on permanent coumarin anticoagulant therapy and with symptomatic coronary artery disease, presented with a history of multiply recurrent deep venous thrombosis and a long-standing inframalleolar ulceration 2 cm. in diameter. After pursuing conservative ambulatory treatment, the ulcer remained painful and unhealed. At operation, stripping of the greater saphenous vein, phlebectomy of varicose clusters, and endoscopic division of incompetent perforating veins allowed the ulcer to become pain free immediately and healing was complete within 14 days.

These two cases illustrate the general experience of the authors that the subfascial perforator vein operation, with or without stripping of the incompetent superficial veins is an efficient adjuvant in surgical treatment of venous ulcers. It is apparent that this is less invasive than the former Linton and other operations which have been advocated.

COMMENTARY

It is a fact that almost all physicians seek professional information within their own country and in their own language from their own colleagues. However, for the best possible advanced treatment, there should be an exchange between international experts in addition. This holds particularly true in the new and highly specialized field of endoscopic subfascial vein surgery. This article is an example of such beneficial international exchange across language barriers. At present, it is of special value that the American authors should present limited numbers of cases observed very closely with available hemodynamic data.1 In contrast, German-speaking physicians in Europe tend to publish large numbers of cases in the form of consensus documents and are slower to publish.2

This paper confirms the experience of the authors and others which document the fact that the SEPS is a worthwhile adjuvant in venous surgery.3,4 Two aspects of the paper strike us on the other side of the Atlantic. First, in contrast to Europe, in the United States, the SEPS can be done on a large scale on an ambulatory basis. Second, anticoagulant prophylaxis against thromboembolism is used when SEPS is done even though in the United States, such prophylaxis is not usual in varicose vein surgery. The question arises does that mean that the United States surgeons consider that the addition of SEPS to a stripping operation increases the risk for thromboembolic complications? 5794b

REFERENCES

1. Bergan JJ, Murray J, Greason K. Subfascial endoscopic perforator vein surgery (SEPS): A preliminary report. Ann Vasc Surg 1996;10:211-19.

2. Fischer R, Schwahn-Schreiber C, Sattler C. Ergebnisse der konsensuskonferenz �ber die subfasziale endoskopie der Vv, perforantes des medialen unterschenkels. Phlebologie (in press).

3. Gloviczki P, et al. Surgical technique and preliminary results of endoscopic subfascial division of perforating veins. J Vasc Surg 1996; 23:517.

4. Gloviczki P, Bergan JJ, Menawat SS, et al. Safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery (SEPS): A preliminary report from the North American Registry. Presented to 50th Annual Meeting, Society of Vascular Surgery, June 1996, Chicago, Illinois. Submitted to J Vasc Surg.

THE LONG-TERM CLINICAL COURSE OF ACUTE DEEP VENOUS THROMBOSIS
Prandoni P, Lensing AWA, Cogo A, et al.
Ann Intern Med 1996; 125:1-7

ABSTRACT AND COMMENTARY BY:
Lois A. Killewich, M.D., Ph.D.
Assistant Professor of Surgery
University of Maryland School of Medicine
Baltimore, Maryland

This article describes a long-term, prospective cohort study in which 355 patients with a first episode of symptomatic deep venous thrombosis documented by contrast venography were followed for up to eight years to assess the risk of development of recurrent venous thromboembolism, the postthrombotic syndrome, and death.

At the time of enrollment, demographic information, a medical history, and risk factors for venous thromboembolism (VTE) were recorded. Each patient underwent contrast venography and the majority were then treated with high-dose intravenous heparin or subcutaneous low-molecular-weight heparin followed by three months of oral warfarin. Patients with cancer, hypercoagulable states, isolated calf thromboses, or contraindications to anticoagulation had modifications of this treatment strategy, although the modifications were not specified in the paper. All patients were instructed to wear compression stockings for at least two years.

Patients returned for followup visits at three months, six months, and every six months thereafter for a maximum of eight years. Interviews and physical examinations were performed to determine whether patients had developed recurrent thromboembolism or postthrombotic syndrome. In cases where the patient was thought to have experienced a recurrent embolic episode, venography was repeated.

Seventy-eight patients suffered one or more episodes of recurrent thromboembolism. These included 63 episodes of deep venous thrombosis (DVT) and 15 episodes of pulmonary emboli (PE), nine of which were fatal. The majority of these episodes occurred during the first two years of followup. By eight years, the cumulative incidence was 3.03%. The presence of cancer or documented hypercoagulable state increased the risk of recurrent VTE while surgery and trauma or fracture were associated with a lower risk.

Eight-four patients developed manifestations of the postthrombotic syndrome and at eight years of followup, the cumulative incidence was 29.1%. Thirty percent were considered "severe," meaning that significant symptoms (pain, cramps, heaviness, pruritus, paresthesias) and signs (edema, induration, hyperpigmentation, and ulceration) were present. The incidence of the postthrombotic syndrome increased most rapidly during the first year following the initial episode of venous thromboembolism and thereafter, increased gradually over the first five years.

A total of 90 patients (approximately 30% of the study group) died during followup, most commonly of malignancy.

COMMENTARY

The risk of symptomatic, recurrent VTE diagnosed in this group of patients was surprisingly high (30.3% at eight years of followup). However, this study may have underestimated the true incidence since only patients with symptoms of recurrent disease were reevaluated with contrast venography. If all patients had undergone diagnostic testing, such as duplex ultrasound, to screen for the presence of recurrent VTE, the incidence may have been much higher. Although the clinical significance of these asymptomatic thrombotic episodes is not fully known, most physicians would institute anticoagulant therapy after diagnosis. Therefore, this work could be criticized since many episodes may have gone undiagnosed.

The high incidence of recurrent VTE noted in this study may be related to the high incidence of cancer and documented hypercoagulable states (almost 30%) in the study population since these disease states are known to be associated with increased risk of venous thromboembolism. The literature supports the use of life-long anticoagulation in patients with known hypercoagulable states after a first episode of VTE. The authors of this study could also be criticized for not employing this strategy in these patients. Moreover, some clinicians have suggested that either chronic anticoagulation or vena caval filters should be employed in patients with VTE and known malignancy for similar reasons.1

The incidence of the postthrombotic syndrome reported in this study was lower than in previous studies.2 The authors suggest that this lower incidence may have been related to the use of compression stockings but this has not been substantiated by previous work.3 One possible explanation would be that these patients had less extensive initial thrombosis and thus developed less extensive valvular incompetence. However, since no information is provided regarding either the extent of initial thrombosis or the development of valvular incompetence, no conclusions can be drawn.

A final issue with this study is that approximately 30% of the participants died during the study period, primarily due to malignancy. These patients may have behaved differently with regard to the development of recurrent VTE or the postthrombotic syndrome than those who survived to the end, again calling into question the overall conclusions.

In summary, this is an important but flawed study that contributes to our overall knowledge of venous disease. It also also leaves many unanswered questions and points to the need for ongoing research in this important area. 5969b

REFERENCES

1. Hirsh J, Prins MH, Samama M. Approach to the thrombophilic patient. In: Colman RW, Hirsh J, Marder VJ, Salzman EW (eds). Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed. Philadelphia, Lippincott 1994; pp 1543-61.

2. Strandness DE Jr, Langlois Y, Cramer M, et al. Long-term sequelae of acute venous thrombosis. JAMA 1983; 250:1289-95.

3. Killewich L, Martin R, Cramer M, et al. An objective assessment of the physiologic changes in the postthrombotic syndrome. Arch Surg 1985; 120:424-30.

MINI ABSTRACTS
John J. Bergan, M.D.
Items of Interest Which Have Crossed the Editor's Desk
(Provided for reference purposes and general interest)

Endoscopic Subfascial Division of Incompetent Perforating Calf Veins
Paraskeva PA, Cheshire N, Stansby G, Darzi AW
Br J Surg 1996; 83:1105-06

This one-page article explores the technique of covering the subfascial endoscope with an endotracheal tube and then blowing up the tracheal cuff balloon to create additional space within which to work on perforating veins. This idea makes the Storz instrument much easier to use.