SCLEROTHERAPY FOR LEG TELANGIECTASIA: A BLINDED COMPARATIVE TRIAL OF POLIDOCANOL AND HYPERTONIC SALINE
 McCoy S, Evans A, Spurrier N
Dermatol Surg 1999; 25:381-86

ABSTRACT AND COMMENTARY BY:
Robert A. Weiss, MD
Hunt Valley, Maryland

A total of 81 patients were treated by sclerotherapy using polidocanol on one leg and hypertonic saline on the other. An assessment was done after two months based on patient satisfaction, clinical findings on physical examination, and blinded photographic assessment by a non-treating physician. The sclerosants used were 1% polidocanol and 20% hypertonic saline derived by combining 2 ml of 30% saline with 1 cc of 1% lidocaine. No ulcers were reported, some "thrombosis" was noted mostly in the hypertonic saline group, and swelling and itching were reported rarely in the polidocanol group. As was expected, pain of injection was far greater in the hypertonic saline group. Hemosiderin staining incidence was 73% with polidocanol and 55% with hypertonic saline. No compression was used following treatment. Matting occurred between 31 and 36% at two months and was not statistically significant for either solution. A negative correlation was shown for patient satisfaction versus side effects.

COMMENTARY

Other studies have shown that detergent solutions lead to higher side effects of matting and staining. We published similar results in 1990.1 The unusually high incidence of side effects speaks to the importance of post sclerotherapy compression to reduce side effects and enhance results. The incidence of matting and pigmentation in this study is extraordinarily high but the use of compression can greatly reduce this.2

It is known that detergent solutions cause more inflammation, more endothelial damage, and greater red blood cell leakage with resultant higher incidence of side effects. Therefore, as previously reported, a higher incidence of post sclerotherapy pigmentation occurs with polidocanol 1% in treatment of telangiectasias. This would also be expected with 0.5% sodium tetradecyl sulfate. As Dr. Mitchel Goldman points out in his published commentary, a more accurate comparison for side effects and efficacy would have been with polidocanol 0.5% versus 20% hypertonic saline.

There are two significant findings in this study. One is that the dilution used for hypertonic saline with lidocaine seems to reduce the pain of injection. This pain reduction appears to be significant over undiluted hypertonic saline and the use of this substance can greatly reduce the practice of sclerotherapy as word travels about the great amount of pain. From our own experience, a pain incidence of 23.4% with hypertonic saline is enough to prevent 75% of patients from repeating the experience.

The second significant finding is that negative patient satisfaction is linked to the presence and appearance of hyperpigmentation and matting. It is clear that patients are quite dissatisfied when pigmentation replaces purple telangiectasias. This study is the first to quantify this. The importance of patient education that sclerotherapy is a delayed-gratification procedure is very important. Photographs to demonstrate the slight improvement during the first few weeks is also very important. Many patients who are initially dissatisfied will return within six months when the side effects have cleared. vdwei275

REFERENCES

1. Weiss RA, Weiss MA. Incidence of side effects in the treatment of telangiectasia by compression sclerotherapy: Hypertonic saline versus polidocanol. J Dermatol Surg Oncol 1990; 16:800-804.

2. Weiss RA, Sadick NS, Goldman MP, Weiss MA. Post sclerotherapy compression: Controlled comparative study of duration of compression and its effects on clinical outcome. Dermatol Surg 1999; 25(2):105-108.




RECURRENT VARICOSE VEINS: PATTERNS OF REFLUX AND CLINICAL SEVERITY
 Jiang P, van Rij M, Christie R, et al.
Cardiovasc Surg 1999; 7(3):332-39

ABSTRACT AND COMMENTARY BY:
Mr. Andrew W. Bradbury, MB, ChM FRCSE
Senior Lecturer & Consultant Vascular Surgeon
Royal Infirmary of Edinburgh
Edinburgh, Scotland

The authors used duplex scanning to determine the patterns of recurrent varicose veins in 264 limbs. They compared clinical features, including the type of initial surgery and severity of venous disease, with the distribution of reflux to determine whether specific patterns of varicose veins are associated with a greater severity of venous insufficiency. They attempted to present a classification of recurrence in the groin. All limbs had undergone previous saphenofemoral ligation. Recurrent saphenofemoral incompetence was present in 65%, long or short saphenous incompetence in 88%, perforator incompetence in 67%, and deep venous incompetence in 60%. Residual long saphenous veins were present in 43% and 74% of limbs with and without previous stripping of the long saphenous vein, respectively. They found that no particular reflux pattern in the groin was related to an increased incidence of ulceration. However, they found that ulceration was more frequent in patients with deep reflux and reflux below the knee. They conclude that the pattern of recurrence of varicose veins is highly variable and patients often present with multiple sites of incompetence. They recommend a full noninvasive workup, including duplex scanning.

COMMENTARY

Recurrent varicose veins remain a major clinical problem to the vascular surgeon. While there is no Level I evidence to prove that noninvasive duplex assessment of patients undergoing primary recurrent varicose vein surgery improves outcome, common experience strongly suggests that it does. The authors of the present study have analyzed in detail a large number of patients presenting to their clinic with symptomatic recurrent varicose veins and have related patterns of reflux to the severity of clinical disease. While any study examining recurrent varicose veins in this much detail is welcomed and undoubtedly provides useful information, there are two weaknesses to consider when evaluating the results.

First, it is clear that patients studied were preselected from a larger cohort of patients presenting with varicose veins. Thus, the authors studied "those judged to have disease warranting surgery in an environment of restricted resources and waiting lists." It would have been interesting to know their total recurrent varicose vein population between 1992 and 1996 as well as how the patterns of reflux varied between those who were and those who were not chosen for further assessment. This preselection may account for the high prevalence of chronic venous ulceration, deep venous thrombosis, multiple sites of superficial incompetence, and deep venous reflux in their patient cohort.

The second weakness of the paper is that the operative procedure was, in some cases (number not stated), determined from the description of the previous operation as recalled by the patient. In my experience, patients are less than reliable when recounting descriptions of their previous surgeries. Thus, this method of obtaining information may explain the large number of "remnant" long saphenous vein in patients who underwent stripping.

These points aside, however, this paper provides useful and detailed information on the patterns of reflux in patients presenting with recurrent varicose veins and stresses again how important it is to perform a thorough noninvasive assessment with duplex scanning. Failure to do this will undoubtedly lead to inadequate and incomplete surgery.

Finally, the authors provide a comprehensive duplex-defined classification of anatomical patterns of recurrence in the groin. There are several such classifications in the literature and the one described here is perhaps rather complex. Nevertheless it provides a framework in which to classify patients. vdbra257




ESTROGEN AND PROGESTERONE RECEPTORS IN NORMAL AND VARICOSE SAPHENOUS VEINS
 Mashiah A, Berman V, Thole HH, et al.
Cardiovasc Surg 1999; 7(3):312-331

ABSTRACT AND COMMENTARY BY:
Neil S. Sadick, MD, FACP
New York, New York

This report is concerned with identification of estrogen and progesterone receptors in normal and varicose vein segments. Varicose veins were obtained from 32 patients and the control normal vein segments were obtained from 29 normal individuals. Using anti-estrogen and anti-progesterone receptor antibodies, receptors to both hormones were detected in the nuclear regions of the intima and media in both female and male saphenous veins. Estrogen and progesterone receptors were found only in the nuclei in the vasa vasora in the adventitial region. Levels of estrogen receptors were lower in the non-varicose segments of varicose veins and these values were lower than in normal veins. Higher levels of estrogen receptors were present in varicose segments. Progesterone receptor levels were greater in non-varicose portions of varicose veins in females. The publication discusses the role of gender versus age as a predisposing factor to varicosities.

COMMENTARY

This study utilizes monoclonal antibodies and is therefore similar to our work in the same area.1 However, we looked at estrogen and progesterone receptors in areas of telangiectatic matting and class I telangiectasias. We did not find these receptors in the study subjects. The question arises whether or not hormones play a role in large varicose veins and not in smaller-diameter telangiectasias. The mechanisms of action of sex hormones in varicose veins and, for that matter, in telangiectasias may be somewhat different. These mechanisms are unknown at the present time. Further studies will be required to elaborate further on these intriguing findings. vcsad228

REFERENCE

1. Sadick NS, Niedt GW. A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities. J Dermatol Surg Oncol 1990; 16:620-23.




FROZEN ALLOGENIC HUMAN EPIDERMAL CULTURED SHEATHS FOR THE CURE OF COMPLICATED LEG ULCERS
 Bolivar-Flores YJ, Kuri-Harcuch W
Dermatol Surg 1999; 25:610-17

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

The authors treated ten consecutive patients with leg ulcers of various etiologies with frozen human allogenic epidermal cultures. Three patients had exposure of the Achilles or extensor tendon. The ulcers treated were as large as 160 cm2 with a duration of up to 20 years. Wounds were repaired by debridement to remove necrotic tissue. Thawed cultures were then applied biweekly from 2 to 15 times, depending on the size and complexity of the ulcer.

The authors noted that they could achieve healing in all of the ulcers. After the first few applications, granulation tissue formed. Time required for complete healing ranged from 1 to 31 weeks after the first application. The authors conclude that even with exposure of the tendon, it is possible to heal venous or diabetic ulcers with allogenic human epidermal cell cultures.

The only characterization of these ten patients was that five had diabetes mellitus and one suffered from rheumatoid arthritis. Five patients had acute ulcers, three of which were complicated by exposure of tendons. Five patients had a total of six chronic ulcers of more than one year's duration. Of these, all had been treated previously with split-thickness skin autografting without success.

In this well-illustrated article, the clinical course of each patient is reported in detail. Review of the case reports elucidates the careful followup and surgical techniques of the authors. Only two of the ten patients had ulcers of venous stasis etiology but, unfortunately, evaluation of the venous system was not reported in this study. This article is recommended for all students who treat chronic ulcers. Particularly impressive in these ten patients is the lack of recurrence over a two-year followup period. vdgol253




LEG ULCERS AND HYDROXYUREA:
41 CASES
 Sirieix M-E, Debure C, Baudot M, et al.
Arch Dermatol 1999; 135:818-20

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

In this study, 41 patients developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration was five years) for chronic myeloproliferative disorders. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80% of cases). The authors biopsied 11 patients. Histopathologic findings showed epidermal atrophy, dermal fibrosis, and scar tissue without evidence of vascular lesions. Clinical evaluation did not show evidence of arterial or venous pathology. (The type of venous and arterial examinations were not reported in this paper).

COMMENTARY

Enlargement of red blood cells as well as a decrease in their deformability occurs 24 hours after the start of hydroxyurea therapy. Red blood cells return to normal shape within a few weeks after chemotherapy is discontinued. The authors speculate that reduced red blood cell susceptibility to deformity may impair blood flow in the microcirculation and therefore hydroxyurea could induce cutaneous anoxia leading to cutaneous ulceration after minor trauma. This interesting observation and report provides credence to the microcirculation disorder hypothesis of leg ulceration. Curiously, white blood cell trapping was not observed in these patients.

Numerous studies have shown that pentoxifylline (Trental) aids in the healing of leg ulcerations. Although this may be due to increasing the deformability of red blood cells to allow oxygenation, many authors believe that the effects of pentoxifylline are more widespread and include, but are not limited to, the modification of various factors such as tumor necrosis factor. Perhaps the change in red blood cell deformability is more important than once thought. vdgol255




PATIENTS WITH CHRONIC LEG ULCERS SHOW DIMINISHED LEVELS OF VITAMIN A AND E, CAROTENES, AND ZINC
 Rojas AI, Phillips TJ
Dermatol Surg 1999; 25:601-04

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

The authors studied the levels of vitamins A, B1, B2, B6, B12 and E along with the trace elements of zinc, copper, iron sulfate, and carotene in fasting blood samples from 17 patients with chronic leg ulcers. They then compared this to data obtained from a nutritional survey of age-matched controls in the greater Boston area. They found significantly lower levels of vitamin A, zinc, and carotene in patients with chronic leg ulcers. In addition, significantly lower levels of vitamin E were noted in males with chronic leg ulcers.

This patient population was defined as leg ulcers which were unhealed for at least three months despite conventional treatment, including compression therapy, under the supervision of the physician. Mean duration of the ulcer was 60 months (range 4 to 312 months). A total of 14 patients had venous ulcerations, two had arterial ulcerations and one had mixed venous/arterial ulcerations. Photoplethysmography and duplex ultrasound studies confirmed the diagnosis of venous disease. Patients with other diseases known to alter serum trace elements or other nutritional parameters such as diabetes mellitus, chronic renal or liver failure, active alcoholism, malabsorption syndrome, malignancy, chronic inflammatory disease, or chronic infectious disease were excluded.

COMMENTARY

Multiple studies have shown impaired wound healing associated with deficiencies in vitamin A, C, B1, and E. A zinc deficiency has also been shown to impair wound healing. Past studies have shown that 50% of elderly patients consume less than two-thirds of the recommended daily allowance of the above-named vitamins. Therefore, it is not surprising that elderly patients, by and large, have a decreased healing ability. It is interesting, however, that there is a significant difference in the nutritional status between patients with chronic leg ulcers and the age-matched controls.

The authors' results suggest that a nutritional deficiency or an increased consumption of nutritional stores may delay wound healing in their Bostonian patients with chronic wounds. They recommended that elderly patients with chronic wounds be evaluated for nutritional deficiencies and that their diets be supplemented with multivitamins containing vitamin A, vitamin E, and zinc. vdgol254




PREDICTORS OF WOUND HEALING
 Belo YM, Phillips TJ
J Clin Dermatol 1999; 2:39-43

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

This is a retrospective study of 27 patients with 30 venous ulcers seen at the Wound Healing Clinic at Boston University Medical Center between 1996 and 1998. Sequential weekly ulcer tracings were done to determine the healing rate of ulcerations. It was found that 47% of ulcers healed within 20 weeks of therapy.

The mean healing rate of the ulcers that eventually healed was 0.109 cm2 per week. This was compared with a mean healing rate in nonhealing ulcers of 0.032 cm2 per week. Ulcers that healed were of shorter duration before the treatment (mean 13 months) than ulcers that did not heal (mean 9 years). Ulcers that eventually healed were also of smaller area (3.27 cm2) versus nonhealing ulcers (16.15 cm2). The authors conclude that the healing rate observed during the first three weeks is helpful in evaluating ulcer prognosis and may help the physician decide which wounds might benefit from more aggressive therapy.

COMMENTARY

This interesting retrospective review is in accordance with almost all other published studies on the healing rate of venous leg ulcers. Other factors studied, such as gender, history of deep venous thrombosis, location of the leg ulcer, and the extent of surrounding sun exposure change prove to be negligible predictors of wound healing.

No other clinical information was provided on the 27 patients reviewed in this study except that all were treated with similar standardized compression therapy.




VENOUS INSUFFICIENCY FOUR YEARS AFTER AN EPISODE OF DEEP VENOUS THROMBOSIS: A CLINICAL AND PLETHYSMOGRAPHIC INVESTIGATION
 Nordstr–m M, Lindblad B, Akesson H, Bergqvist D, Kjellstr–m T.
Phlebology 1998; 13:53-58

COMMENTARY BY:
Csaba Dzsinich, MD
Budapest, Hungary

In this report, the authors are attempting to estimate the incidence and severity of the postthrombotic syndrome four years after an episode of deep venous thrombosis. Their study patients come from patients seen in the Malm– region. Their attempt to provide clear data regarding the late fate of limbs with venous thrombosis is commendable. Existing reports on this subject are conflicting in nature.

The patient records selected followed rules of randomization but reflect all of the inaccuracies of a retrospective study. During the year selected (1987), there were 366 patients recorded to have deep venous thrombosis which were confirmed by phlebography at the Malm– General Hospital. The authors were only able to make a proper followup on 87 of the 211 randomly selected. All of these patients were treated with anticoagulation for six weeks to three months and all were prescribed elastic stockings. From the group of 211, 70 patients were dead, 13 had to be excluded because of not being able to cooperate with the study, 6 for technical reasons, and one for other manifestations of venous disorders. The remaining patients either refused or could not participate in the study. This left 87 study patients who answered questionnaires and underwent clinical examination and strain-gauge plethysmography.

Although detailed clinical and numeric data were collected, it occurs to this reviewer that this group might not represent the whole group of patients with deep venous thrombosis. After all, only the patients who survived and were relatively fit were included in the final phases of the study. The fact that clinical diagnosis alone is unreliable was emphasized by this study and the authors advocate noninvasive strain-gauge plethysmography as an objective method of assessing the late results of the postthrombotic syndrome. A review of the report suggests that there was a low incidence of trauma and gynecologic events in this patient cohort and this suggests a selection bias in the material presented. On the other hand, the data recorded at the four-year followup in this group of patients appear to be accurate and informative. It is suggested that reflux as well as venous occlusion may increase venous pressure in the distal microcirculatory bed. On the other hand, it has been found that healthy volunteers without venous disorders may be found to have reflux in selected segments of the venous tree.

One remarkable finding in this report is the high incidence of pathological responses in the healthy limb contralateral to deep venous thrombosis. This suggests that a subclinical thrombotic event occurred in the contralateral limb at the time of the first investigation of deep venous thrombosis or perhaps during followup.

Ultimately, the value of this paper is the authors' attempt to give a scientific approach to this important but somewhat hazy aspect of medicine. ivdfdzs




CHANGES IN MICROCIRCULATION IN PATIENTS WITH ATROPHIE BLANCHE VISUALIZED BY LASER DOPPLER PERFUSION IMAGING AND TRANSCUTANEOUS OXYGEN MEASUREMENTS
 Maessen-Visch MB, Sommer A, De Paepe JA, Neumann HAM
Phlebology 1998; 13:45-49

COMMENTARY BY:
Prof. Bengt Fagrell
Stockholm, Sweden

The purpose of this paper was to quantify differences in skin microcirculation in atrophie blanche areas of patients with chronic venous insufficiency (CVI).

The study was designed as an open study with healthy controls as a reference group. Sixteen patients with CVI and large lesions of atrophie blanche and ten patients with CVI but without atrophie blanche were investigated together with ten healthy controls. The technique of laser Doppler perfusion imaging (LDPI) measurements were performed over the location of areas of atrophie blanche in both the patients and the healthy controls. Transcutaneous oxygen tension measurements (tcPO2) were also performed in the same areas. The results showed that resting blood perfusion was higher in atrophie blanche areas than in healthy controls. The "veno-arteriolar" response was also significantly increased in the atrophie blanche areas. On the other hand, there was a decrease in tcPO2 values in the atrophie blanche lesions and in the skin of CVI patients without atrophie blanche when compared to normal skin. The authors conclude that basic resting flux in atrophie blanche is increased compared with clinically normal skin and that of CVI patients. These was also a more marked decrease in flow in response to venous occlusion in atrophie blanche areas.

COMMENTARY

The explanation by the authors is that the increased perfusion values seen with the LDPI technique is caused by an increased number of dilated subpapillary vessels and that the tcPO2 values are decreased because of the markedly reduced number of nutritional capillaries in the atrophie blanche regions. As the authors point out, this is in accordance with previous findings by others. The reason for the decreased tcPO2 is thought to be caused by trapping of leukocytes. However, no one has actually shown that there is a trapping of leukocytes in the microcirculation of affected skin areas in patients with CVI. It has been shown that there is an accumulation of leukocytes in the lower leg of CVI patients but no one has shown that this trapping takes place in the microcirculation of the affected regions. We have studied the microcirculatory disturbances in the skin of patients with CVI for several decades and have not yet been able to observe microscopically any capillaries that have been plugged by leukocytes. The reason is rather obvious as the skin capillaries in these patients usually have a diameter from 10 up to 30 . Therefore, leukocytes will most certainly not be able to "plug" such capillaries.

The explanations for the changes in perfusion values seen in patients with CVI is also questionable. As far as I can tell, the authors did not take into consideration the "biological zero" values in the LDPI technique. It has been clearly shown in several recent studies that there is a component in the laser Doppler signal which, to a larger or smaller extent, is caused by a nonflow- dependent variable. In patients with venous insufficiency, this value can be rather substantial, at least when measured by the single-fiber laser Doppler technique. Consequently, the differences seen in laser Doppler signal between the three different study groups in this investigation could well be caused by changes in this nonflow-dependent parameter.

The authors also state that venous hypertension is produced by inflating a cuff around the limb in order to mimic the standing position. This may be true in some instances during rest. However, during active muscle contraction and walking venous pressures are substantially elevated. This was shown in several studies published during the 1960s. Thus, the hemodynamic consequences of standing or, as in this study, an induced venous pressure elevation of 70 to 80 mmHg, is far less than would be expected in patients with deep CVI during their active muscle contraction. In CVI patients, the venous pressure can go up to much higher than 100 mmHg. This has dramatic consequences for the skin microcirculation in patients with CVI.

In the future, it would be of great interest to see how the LDPI values are influenced by active muscle contraction in CVI patients. ivdffag1




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


The Role of Leukotriene B4 in Chronic Venous Insufficiency
Danese C, Cifone MG, Zavattaro E, et al.
Vasc Surg 1997; 31:29-33

 This study postulates an interaction between hypoxia-injured endothelial cells and activated polymorphonuclear (PMN) leukocytes to produce release of the pro-inflammatory agent, LTB4. The findings imply improved pharmacotherapy directed at blockage of the endothelial PMN interactions.


Hirudin Versus Heparin and the Low-Molecular-Weight Heparin: And the Winner is...
Editorial: Hull RD, Pineo GF, Raskob GE.
J Lab Clin Med 1998; 132:171-74

Concerning the use of low-molecular-weight heparin for venous thromboembolic disease, the authors state "the new standard of care is no longer unfractionated heparin in these clinical situations but is instead low-molecular-weight heparin therapy." They go on to say that "low-molecular-weight therapy cannot be used in patients with heparin-induced thrombocytopenia." Hirudin has recently been approved by the FDA and may prove to be the primary agent to be used in such a situation.


Venous Haemodynamics During Laparoscopic Surgery: A Cause for Concern
Scott DJA, Wyld L, Paige J, et al.
Min Invas Ther & Allied Technol 1997; 5/6:484-86

It is becoming well known that laparoscopic surgery affects venous hemodynamics and the deleterious effects can be reversed with calf compression devices.


The Incidence of Occult Malignant Diseases in Patients with Deep Venous Thrombosis of the Pelvis and Lower Limb
Fahrig C, Heidrihc H, Penninger C.
Int J Angiol 1998; 7:249-51

The authors believe that acute deep venous thrombosis may be a paraneoplastic entity and that patients older than 50 should be screened for the presence of tumor.


The Role of Season in the Incidence of Deep Vein Thrombosis (French)
Galle C, Wautrecht J.-C, Motte S, et al.

 Journal des Maladies Vasculaires (Paris) 1998; 23(2):99-101

This study found no correlation between season and development of deep venous thrombosis and may lay to rest the question raised by previous studies.


Lower Extremity Edema: Evaluation and Diagnosis
Terry M, O'Brien SP, Kerstein MD
Wounds 1998; 10(4):118-24

This article reviews clinical evaluation and diagnostic standards for assessing lower extremity edema.


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

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.


Physician Practices in the Community Hospital Setting
Bratzler DW, Raskob GE, Murray CK, et al.
Arch Intern Med 1998; 158:1909-12

Despite widely disseminated evidence-based recommendations, venous thromboembolism prophylaxis is underused.