Ways to Improve the Surgical Treatment of Patients with Varicose Disease of the Lower Extremities

Description

This dissertation study is devoted to improving the outcomes of surgical treatment of patients with varicose disease of the lower extremities (VDLE) of CEAP clinical classes C2–C5. The author developed a comprehensive surgical technique that includes the use of an ultrasonic scalpel at the crossectomy stage, short invagination stripping, miniphlebectomy, and intraoperative flow reduction, and carried out a molecular genetic study of polymorphic variants of hemostasis system genes (FII-G20210A, FV-G1691A, FXII-C46T, FGB-G455A) in patients with VDLE. Based on the data obtained, a personalized algorithm for the prevention of venous thromboembolic complications was proposed. The work was carried out in Novosibirsk; the materials were presented at Russian and international conferences, and the proposed techniques have been introduced into the practice of medical institutions of the city.

Table of contents

• LIST OF ABBREVIATIONS.
• INTRODUCTION.
• CHAPTER 1. CURRENT CONCEPTS OF VARICOSE DISEASE OF THE LOWER EXTREMITIES (LITERATURE REVIEW).
• 1.1. Etiopathogenesis and diagnosis of varicose disease of the lower extremities.
• 1.2. Technologies of surgical treatment of patients with varicose disease of the lower extremities.
• 1.3. Venous thromboembolic complications and hereditary thrombophilias.
• CHAPTER 2. MATERIALS AND METHODS.
• 2.1. General characteristics of patients.
• 2.2. Examination methods.
• 2.2.1. Clinical assessment of patients' condition and treatment outcomes.
• 2.2.2. Duplex angioscanning.
• 2.2.3. Molecular genetic study.
• 2.2.4. Quality of life assessment.
• 2.3. Statistical methods of data processing.
• CHAPTER 3. COMBINED APPLICATION OF MODERN SURGICAL TREATMENT TECHNOLOGIES IN PATIENTS WITH VARICOSE DISEASE OF THE LOWER EXTREMITIES.
• 3.1. Technique of the surgical intervention.
• 3.2. Results of surgical treatment.
• CHAPTER 4. THROMBOPHILIC STATES IN PATIENTS WITH VARICOSE DISEASE OF THE LOWER EXTREMITIES.
• 4.1. Analysis of the results of the molecular genetic study.
• 4.2. Prevention of venous thromboembolic complications taking into account the molecular genetic study data.

Introduction

Relevance of the topic. Varicose disease of the lower extremities (VDLE) is unanimously recognized as the most common pathology of the peripheral vessels and constitutes a major socioeconomic problem. According to foreign and Russian researchers, VDLE is detected in 40–50 % of the population. The annual increase in new cases of VDLE in the population of industrially developed countries reaches 2.6 % among women and 1.9 % among men. Moreover, whereas this pathology was previously regarded as a problem primarily of the older age group (over 50 years), the first signs of venous reflux are currently detected in 10–15 % of schoolchildren aged 12–13 [Savelyev V. S. et al., 2001; Kiriyenko A. I., Grigoryan R. A., Zolotukhin I. A., 2008; Gloviczki P. et al., 2009; Cossio J. A., 1995].
The greatest consequences for society are associated with severe forms of VDLE — chronic venous insufficiency (CVI) and venous trophic ulcer. CVI of the lower extremities in the stage of trophic disorders occurs in 2 % of the population of developed countries, which approximately corresponds to the prevalence of diabetes mellitus. Lower extremity ulcers are found in every fifth patient with CVI. After the age of 65, the frequency of venous trophic ulcers increases threefold or more, reaching 36 %. In the Russian Federation, venous trophic ulcers occur in no fewer than 2.5–3 million people [Bogachev V. Yu., 2008; Shevchenko Yu. L., Stoyko Yu. M., Zamyatin M. N., 2008; Gloviczki P. et al., 2009; Perrin M., Kern P., Ramelet A.-A., 2008].
The outcomes of treatment of patients with VDLE, as well as its consequences, cannot be considered satisfactory. At present there is no single method of radical treatment of patients with VDLE that meets all requirements, and the search for ways to improve it remains relevant. At the same time, an active surgical approach employing modern techniques interrupts the development of CVI and subsequently of venous trophic ulcer. In deciding in favor of one technique or another, many factors must be taken into account. The proposed treatment option should be attractive to the patient (well known, safe, cosmetic, with numerous advantages over other techniques), maximally comfortable, and accompanied by a long-lasting therapeutic effect [Krylov A. Yu., Shulutko A. M., Khmyrova S. E., 2008; Shevela A. I., Egorov V. A., Novikova Ya. V., 2008; Zolotukhin I. A., 2008; Shevchenko Yu. L. et al., 2005; Perrin M., Kern P., Ramelet A.-A., 2008; Merchant R. F. et al., 2005].
The Babcock phlebectomy method has over time undergone modification owing to evident shortcomings in its classical application. It is currently performed as short stripping, with removal of the vein in a retrograde direction by the invagination method, using flexible metal or plastic probes. The technique has advantages when the diameter of the removed vein exceeds 10–15 mm. The advantages of the method include the simplicity of its use and its low cost [Zolotukhin I. A., Karavayeva P. A., Bogachev V. Yu., 2006; Morrison C., Dalsing M., 2003; Villavicencio L., 2002].
The appearance of alternatives to stripping for obliteration of the great saphenous vein (GSV) has always aroused interest among surgeons and patients. Currently, cryostripping, endovenous laser coagulation, and radiofrequency obliteration of the GSV lead the ranking of the most gentle, effective, and popular techniques. Despite the absence of long-term results (more than 10 years), these techniques demonstrate high effectiveness. With radiofrequency obliteration, effectiveness reaches 80–90 % over a long period [Merchant R., Pichot O., 2005; Lurie F., Creton D., Eklof B. et al., 2003].
The effectiveness of endovenous laser obliteration is 80–97 %, accompanied by minimal complications not exceeding 3–10 % [Agus G., Mancini S., Magi G., 2006; Pannier F., Rabe E., 2006; Myers K., Jolley D., 2009]. Unfortunately, the use of these techniques for the treatment of patients with VDLE in widespread practice is limited, as it requires special expensive equipment. A significant increase in postoperative complications and recurrences is also noted when the diameter of the altered GSV exceeds 10 mm [Shevela A. I., Egorov V. A., Novikova Ya. V., 2008; Sokolov A. L., Lyadov K. V., Lutsenko M. M., 2009; Perrin M., 2004].
Sclerotherapy, by contrast, as an exception requires no special technologies. The emergence of modern sclerosing agents, foam-form sclerotherapy, echo-sclerotherapy, and microsclerotherapy has made it possible in many countries to provide up to 90 % of phlebological care by means of these techniques. The effectiveness of echo-sclerotherapy with foam sclerosants reaches 88–98 %. The recurrence rate of VDLE in this case is 2–24 %. Their main advantages today are the low cost compared with any surgical intervention and outpatient performance [Chumakov A. A., Byrykhin N. I., Serebryansky Yu. B., 2007].
Minimization of operative trauma is a steady trend in phlebological surgery. It reached its limit in the removal of varicose dilated tributaries of the GSV and the small saphenous vein (SSV) by Muller's miniphlebectomy method [Tsukanov Yu. T., Tsukanov A. Yu., 2005; Stoyko Yu. M., Lyadov K. V., Yermakov N. A., 2005; Villavicencio L., 2002].
In most cases, surgical interventions are supplemented by crossectomy, the adequate performance of which largely determines the risk of a true recurrence of the disease. Moreover, it is at this stage that the most dangerous complications, including iatrogenic ones, may occur: pronounced bleeding, injury to or ligation of the deep femoral veins [Savelyev V. S., Kiriyenko A. I., Zolotukhin I. A., 2007]. In order to optimize this stage, various modifications of crossectomy are often used, including those involving various equipment [Shevela A. I., Egorov V. A., Novikova Ya. V., 2009].
Dissatisfaction is caused by the frequency of recurrence of varicose disease of the lower extremities (RVDLE) after surgical treatment. The frequency of RVDLE requiring repeat surgical intervention ranges from 20 to 80 % and significantly increases with the length of time after the first operation. Using duplex scanning, RVDLE is found in 43–76 % of patients after 2 years. Within 5 years, clinically detected RVDLE is found in 50 % of previously operated patients [Bogachev V. Yu., 2008; Gavrilenko A. V., Vakhratyan P. E., 2008; Zolotukhin I. A., Andriyashkin A. V., Kiriyenko A. I., 2007; Gloviczki P. et al., 2009].
The emergence of new surgical technologies and the high level of modern anesthesiology steadily lead to a decrease in postoperative mortality and a reduction in the number of specific postoperative complications. Against this background, thromboses in the inferior vena cava system and pulmonary embolism are becoming the dominant postoperative complications [Savelyev V. S. et al., 2001; Belentsov S. M., Ektova M. V., Popov A. N., 2006; Kapustin S. I., 2007].
According to various authors, the frequency of postoperative thromboses is 20–59 %. More than 70 % of deep vein thrombosis of the lower extremities is asymptomatic. Fatal pulmonary embolism is often the first and only manifestation of venous thrombosis and ranks third in the overall structure of causes of sudden death. An important place in the pathogenesis of venous thrombosis is assigned to the phenomenon of thrombophilia, or an increased individual propensity to thrombosis. Interest in the study of hereditary thrombophilia increased with the discovery of mutations in the genes of coagulation factors II and V, which are considered the most common causes of genetic predisposition to venous thrombosis. The risk of postoperative venous thromboembolic complications (VTEC) is primarily associated with Factor V Leiden, the G20210A mutation of the prothrombin gene, and elevated FVIII levels [Barkagan Z. S., 2002; Shevela A. I., Egorov V. A., Novikova Ya. V., 2008; Kapustin S. I., 2007; Papayan L. P., 2004; Martin J. et al., 2001; Couto E., 2005; Gonzalez-Porras J. R., 2006].
To date, the question of the necessity of anticoagulant therapy in patients with VDLE for the prevention of postoperative thrombosis continues to be debated. On the one hand, the presence of varicose veins is a risk factor for deep vein thrombosis in operations on other organs; on the other hand, venous operations in patients with the uncomplicated form of VDLE are classified as low risk, which does not require the use of heparins [Asamov R. E., Boboev K. T., Tulakov R. P., 2009; Belentsov S. M., Ektova M. V., Popov A. N., 2006; Novikova Ya. V., Egorov V. A., Livshits G. I., 2008].
All this determines the relevance of the study and defines the aim and objectives of the present work.
Aim of the study. To improve the results of surgical treatment of patients with varicose disease of the lower extremities by optimizing operative techniques and preventing venous thromboembolic complications.
Objectives of the study:
1. To develop a comprehensive technique of surgical treatment of patients with VDLE of clinical classes C2–C5 (CEAP).
2. To compare the results of surgical treatment of patients with VDLE of clinical classes C2–C5 (CEAP) performed by the developed technique with traditional methods of surgical treatment.
3. To study the frequency of occurrence of polymorphic variants of the prothrombin genes FII-G20210A, FV-G1691A, FXII-C46T, and fibrinogen FGB-G455A in patients with VDLE.
4. To develop an algorithm of preventive measures against VTEC in the surgical treatment of patients with VDLE based on molecular genetic testing data.
Scientific novelty of the study. For the first time, a technique of combined application of modern surgical treatment methods in patients with VDLE has been developed.
For the first time, the frequency of occurrence of polymorphic variants of hemostasis system genes FII-G20210A, FV-G1691A, FXII-C46T, and FGB-G455A in patients with VDLE has been studied, and an individual approach to the prevention of VTEC has been developed on the basis of molecular genetic study data.
The effectiveness of the developed comprehensive surgical treatment method and personalized prevention of VTEC in patients with VDLE of clinical classes C2–C5 (CEAP) has been demonstrated.
Practical significance. A comprehensive approach to the application of modern surgical techniques in the treatment of patients with VDLE of clinical classes C2–C5 (CEAP) has been developed and introduced.
The use of an ultrasonic scalpel at the crossectomy stage, short invagination stripping, miniphlebectomy, and intraoperative flow reduction shortens the duration of the operation, reduces the number of postoperative complications, and shortens the period of disability.
The use of molecular genetic testing before surgery in patients with VDLE of clinical classes C2–C5 (CEAP) identifies patients at high risk of VTEC.
Statements submitted for defense:
1. The application of a comprehensive method of surgical intervention in patients with VDLE reduces the operative time, the number of postoperative complications, and the duration of disability.
2. 50 % of patients with VDLE are carriers of various polymorphic variants of hemostasis system genes. Molecular genetic testing makes it possible to identify the group of patients at high risk of developing VTEC.
3. A personalized approach to the prevention of VTEC in patients with VDLE of clinical classes C2–C5 (CEAP), based on molecular genetic testing data, reduces the risk of venous thrombosis in the early and late postoperative periods.
Approval of the dissertation materials. The main provisions of the dissertation were reported at the research-to-practice conference "Fundamental Sciences for Medicine. New Materials and Methods for Medicine" of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk, 2008); the Far Eastern Angiological Forum (Khabarovsk, 2008); the International Research-to-Practice Conference "Genomics and Proteomics" (Novosibirsk, 2009); the XXI International Conference of the Russian Society of Angiologists and Vascular Surgeons (Samara, 2009); the XXVI World Congress of Phlebologists (Monaco, 2009); and the All-Russian Conference "Post-Thrombotic Disease" (Omsk, 2009).
Implementation of the research results. The proposed treatment and examination techniques are used in the practical work of the surgical department of the Central Clinical Hospital of the Siberian Branch of the Russian Academy of Sciences, the cardiovascular surgery department of Municipal Healthcare Institution City Hospital No. 12, and the clinical department of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences — the surgical department of the multidisciplinary medical and diagnostic center "Center for New Medical Technologies in Akademgorodok" (Novosibirsk).
Personal contribution of the author. All the material presented in the dissertation was processed and analyzed personally by the author. The author took direct part in the surgical treatment of 67 % of the patients.
Scope and structure of the dissertation. The dissertation is set out on 109 printed pages. It consists of an introduction, five chapters, a conclusion, findings, practical recommendations, and a bibliography containing 86 domestic and 63 foreign sources. The dissertation is illustrated with 2 tables and 32 figures.

Questions and answers

What is the aim of the study?

The aim of the study is to improve the results of surgical treatment of patients with varicose disease of the lower extremities by optimizing operative techniques and preventing venous thromboembolic complications.

What genetic markers were studied in this work?

The study examined the frequency of polymorphic variants of the prothrombin gene FII-G20210A, Factor V FV-G1691A (Leiden), Factor XII FXII-C46T, and fibrinogen FGB-G455A in patients with varicose disease of the lower extremities.

What elements make up the developed comprehensive surgical technique?

The technique includes the use of an ultrasonic scalpel at the crossectomy stage, short invagination stripping, miniphlebectomy, and intraoperative flow reduction.

What are the advantages of the proposed approach?

According to the author, the comprehensive method reduces operative time, decreases the number of postoperative complications, and shortens the period of disability, while personalized prevention of venous thromboembolic complications based on molecular genetic testing reduces the risk of venous thrombosis.

Where were the research results implemented?

The proposed treatment and examination techniques are used in the surgical department of the Central Clinical Hospital of the Siberian Branch of the Russian Academy of Sciences, the cardiovascular surgery department of City Hospital No. 12, and the clinical department of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk).