Adaptive Mechanisms and Correction of Lympho- and Hemodynamics in Complex Conservative Therapy of Lymphedema of the Upper and Lower Extremities (A Clinico-Pathophysiological Study)

The dissertation is devoted to a clinico-pathophysiological investigation of adaptive mechanisms of the lymphatic system and correction of lympho- and hemodynamics in complex conservative therapy of lymphedema of the upper and lower extremities. A diagnostic algorithm for the evaluation of adaptive capabilities of the lymphatic system has been developed and substantiated, encompassing lymphoscintigraphy, ultrasonic vessel investigation, assessment of prothrombotic factors, dynamics of blood coagulation indicators, and quality of life assessment. The influence of complex staged physical therapy, including intermittent pneumocompression and basic treatment, on the pathophysiological mechanisms of correction of lymphatic edemas of varying localization and severity has been investigated. It has been established that edema reduction is in inverse dependence on the degree of severity of the pathological process, which allows the formulation of individual programs of conservative treatment.

Relevance of the Study. From a physiological standpoint, the lymphatic system has remained one of the most poorly studied systems of the body for many centuries. No less enigmatic are the mechanisms of pathogenesis of diseases of the lymphatic system. Among them, the most widespread form has remained and remains lymphedema of the extremity or the edematous syndrome.

According to M. Feld [139], in the world, "lymphatic elephantiasis" affects no fewer than 100 million people. The majority of them live in the countries of Africa and Asia. This form of elephantiasis is considered endemic, developing as a result of the bite of a special species of mosquito — Mansonia. This form of extremity and external genital elephantiasis is not observed in countries with a temperate climate. According to other data [46], lymphedema affects 10% of the world's population.

The significance of the problem of treatment and rehabilitation of patients with various forms of chronic lymphatic edema is determined by the following circumstances. On the one hand — the prevalence of the disease — lymphatic edemas occupy up to 9% in the overall structure of vascular pathology [1, 3]. On the other hand, one must take into account the diversity and multifaceted nature of an entire complex of medical and social measures [54, 95].

The number of patients with lymphedema is steadily increasing both in our country and abroad [1, 3, 95]. At the same time, the number of patients with both primary lymphedema and secondary form is growing, mainly due to patients with oncological pathology who have undergone radical surgical or surgical-radiation treatment of malignant neoplasms [50]. The number of patients with secondary form lymphedema of the upper extremity, or postmastectomy lymphedema (GTEL), has increased. According to various data, lymphatic edema of the upper extremity occurs after radical mastectomy in 10–46.1% of cases, and when combined with radiation therapy — in 58.9–87.5%, with 15.0–17.1% of cases presenting lymphedema of severe degree [50].

Lymphedema of the extremities represents an actual medical and social problem [1, 3, 95]. Since lymphatic edemas arise in early and mature age, this leads to a reduction in work capacity, deterioration of quality of life, and psychological maladaptation [127, 139]. Elephantiasis of the external genital organs of men occupies second place and is often combined with lymphedema of the lower extremities [46]. Being a progressive disease, lymphedema often leads to early disability. "Independent" return to work without special therapeutic measures is possible, perhaps, for no more than 53.2% of patients [1, 3, 46, 95]. Often the disease cannot be completely cured. For this reason, patients require lifelong treatment and psychosocial rehabilitation [95].

Analyzing the world experience in searching for a one-time solution to the problem of treating lymphatic edemas by operative means [1, 3, 8, 24, 61, 74], it is necessary to note that all attempts to overcome this problem solely through the creation of new and the improvement of old techniques did not yield the desired result. This is explained by the fact that the pathological process in lymphatic edema involves not a single organ, but an entire system performing an important role in maintaining tissue homeostasis.

Disruption of the function of the lymphatic system entails a whole series of serious pathophysiological changes in tissues, which ultimately lead to irreversible, fibrosclerotic changes and chronic erysipelas [3, 61, 95]. The distinctive features of approaches to the diagnosis and treatment of lymphatic edemas lie in the unique structure of the lymphatic system, which sharply complicates and limits the range of conducted studies [15, 95].

In recent years, the problem of rehabilitation of such patients has been brought to one of the forefront positions [33, 62, 86]. For decades, the emphasis in our country was placed on operative treatment methods. Meanwhile, in many developed countries, conservative methods of treating lymphedema of the extremities, and in particular, physical therapy effects, were used in the overwhelming majority [55, 127, 139, 192].

The role of conservative therapy in the overall structure of treatment of lymphatic edemas was unjustifiably underestimated until recently, which could not but affect the long-term results. Skeptical attitude toward conservative treatment during the vigorous development of microsurgical methods was replaced by a differentiated selection of patients for the use of therapeutic measures, and an understanding of the significance of this direction in lymphedema treatment [86].

A radical method for treating lymphedema does not exist at the present time [3, 95]. Further development of clinical lymphology sets before researchers tasks, the most important of which are methods for studying the lymphatic bed, as well as the development and implementation into clinical practice of new methods of operative and conservative treatment.

Thus, the above allows us to consider further development and improvement of a model of conservative physical therapy for lymphedema of the extremities as timely, serves as a justification for the relevance of the chosen topic, and predetermines the goal and objectives of the study. Its development should lead to substantial functional and cosmetic improvements of the extremity, accelerate the terms of rehabilitation, reduce or eliminate patient disability, avoid the onset of lymphedema complications, avoid surgical treatment methods and their associated potential complications.

On this basis, the goal of the present study was to investigate the adaptive capabilities of the lymphatic system using a modern therapeutic-diagnostic complex depending on the degree of its involvement in the pathological process.

To achieve the stated goal, the following tasks were assumed:

1. To analyze contemporary views on the etiopathogenesis of lymphatic edemas of the extremities.

2. To evaluate the validity and algorithm of the modern diagnostic complex in pathology of the lymphatic system.

3. To study the pathophysiological mechanisms of correction of lymphatic edemas of the extremities depending on the degree of development of the pathological process.

Scientific Novelty:

A diagnostic algorithm for the evaluation of adaptive capabilities of the lymphatic system has been proposed, consisting of lymphoscintigraphy, ultrasonic vessel investigation, data on prothrombotic factors, dynamics of blood coagulation indicators, as well as quality of life assessment. It has been established that the pathophysiological mechanisms of correction of lymphatic edemas of the extremities are determined by the localization, degree of development, and qualitative characteristics of the edema. Edema reduction under the influence of intermittent pneumocompression and basic therapy is in inverse dependence on the degree of severity — the more severe the pathological process, the greater the fluid loss.

Practical Significance:

The role and significance of special research methods — lymphoscintigraphy, plethysmography, ultrasonic Dopplerography, duplex scanning — in the diagnosis of adaptive capabilities of the lymphatic system at different localizations and degrees of severity of lymphatic edemas have been determined, with the aim of creating individual programs of conservative therapy. The dynamics of quality of life depending on the severity and localization of the pathological process have been calculated. A diagnostic algorithm for lymphedema has been developed. Optimal schemes of complex therapeutic treatment and the sequence of execution of its individual stages have been formulated.

Propositions for Defense: 1. Lymphedema is a progressive, complex, systemic disease with a complex of pathophysiological mechanisms. The links of pathogenesis are reduced to the formation of a high-protein edema caused by a decrease in the transport capacity of lymphatic vessels and proteolysis in tissues. The disease develops as a result of the interaction of polyetiological and polypathogenetic factors of congenital, constitutional, and acquired nature, leading to disorders of tissue protein metabolism and causing permanently progressive development of coarse-fibrous connective tissue.

2. The diagnostic algorithm for the evaluation of adaptive capabilities of the lymphatic system is based on lymphoscintigraphy, which is the leading method of diagnosis of lymphatic edemas, showing changes in skin reverse outflow, radioisotope outflow through lymphatic vessels, as well as radioisotope outflow/accumulation in lymph nodes after conservative physical therapy. The state of valvular structures upon ultrasonic investigation allows an assessment of the degree of their insufficiency. Evaluation of prothrombotic factors, dynamics of blood coagulation indicators are related to the pressure and content of lymph in vessels and the intercellular space, tissue hypoxia, inflammatory reactions, and rheology of blood and lymph. Quality of life assessment has diagnostic and medical-social significance.

3. The pathophysiological mechanisms of correction of lymphatic edemas of the extremities are determined by the localization, degree of development, and qualitative characteristics of the edema. Contemporary complex staged physical therapy of lymphedema of the extremities, to achieve an optimal result, should follow the following principles — complexity, sequence, mandatory nature, and low pressure during manual lymphatic drainage. Intermittent pneumocompression in addition to basic treatment ensures further edema reduction, which is in inverse dependence on the degree of severity — the more severe the pathological process, the greater the fluid loss.

Author's Contribution to the Conducted Study: The author's personal contribution to the conducted study consists of carrying out an analytical review of domestic and foreign literature on the studied problem, as well as in the composition of the research program (contribution share 85%). Maps for the processing of blood parameters, complex psychological testing protocols, and mathematical measurement of extremity volume have been developed (personal contribution 100%). The author directly participated in the examination of the subjects of the study groups, in the collection of material and compilation of the database, and also fully performed the statistical study of the obtained material within the framework of descriptive statistics and multifactor statistical processing. Overall, the author's contribution to the study exceeded 90%.

Validation of the Work and Implementation of the Obtained Results. The main results of the research were reported at the 1st Congress of Lymphologists of Russia (Moscow, Russia, May 2003), at the V Congress of Lymphologists of Russia (Saint Petersburg, Russia, May 2005), at the VI Conference of the Association of Phlebologists of Russia (Moscow, Russia, May 2006), at the V International Annual Conference "Problems of Diagnosis and Treatment of Breast Cancer" (Saint Petersburg, Russia, June 2008), and at the XXI International Congress of Lymphology (Shanghai, China, June 2007).

The main theoretical and practical results of the study have been implemented:

- in the educational process and scientific research at the departments of normal physiology, physical therapy, physical medicine, and medical control of SPbGPMU and at the Central Phlebology Clinic.

Based on the dissertation materials, 11 scientific works have been published. Of these, 1 was published in publications recommended by the VAK. The dissertation is presented across 135 pages of typed text and contains 27 figures and 27 tables.

The work contains references to 105 domestic and 98 foreign literary sources.