Use of an allogeneic biosubstrate in the treatment of wounds after open haemorrhoidectomy

The dissertation is devoted to improving the effectiveness of treatment of postoperative wounds in patients who have undergone open haemorrhoidectomy by means of local application of an allogeneic biosubstrate — a preparation based on embryonic tissues. The study covers the clinical, cytological, microbiological, morphological and hormonal aspects of the course of the wound process, as well as the issues of medical and vocational rehabilitation of patients.

The author investigated the features of wound healing in the anal canal and perineum against the background of permanent bacterial contamination and carried out a comparative assessment of traditional methods of wound treatment and the proposed method using an allogeneic biosubstrate. The data obtained indicate a shortening of wound healing times and a reduction in the frequency of inflammatory postoperative complications without a negative effect on the hormonal status of the patients.

Relevance of the topic.

The treatment of postoperative wounds after operations on the distal rectum and perineum is one of the most challenging problems in coloproctology [49,50,67,70,71,87,118,120,145,163]. Even relatively limited surgical interventions result in a fairly prolonged loss of working capacity [49,50,67,70,71]. Operations performed on the anal canal and pararectal tissues take place against a background of permanent bacterial contamination of postoperative wounds [107, 140, 146, 152, 155, 158, 165]. This factor is the principal cause of delayed repair processes in this category of patients [4,50,67,70,71,158].

Haemorrhoids are among the most common proctological diseases. According to data from different authors [10,14], their prevalence reaches 130–145 cases per 1,000 adult population, while their share in the structure of coloproctological diseases ranges from 34 to 41%. The clinical picture of haemorrhoids is well known and includes bleeding, prolapse of haemorrhoidal nodes, pruritus and pain [25,37]. In Russia, the most widespread method of treatment is surgical intervention — haemorrhoidectomy, performed in 75% of hospitalised patients, with an annual frequency reaching 480 thousand operations [14].

Over many decades, colorectal surgeons have proposed ever new schemes for the treatment of postoperative wounds [8,25,50,70,117,145,148]; however, this problem has not lost its relevance to the present day [49,50,67,70,71,87,118,120,145,163].

Therefore, one of the pressing issues in the treatment of patients operated on for haemorrhoids, as the most common disease, is the drug therapy of postoperative wounds. Despite the wide arsenal of modern pharmaceutical preparations, physical methods of wound management and various forms of their application, the terms of complete recovery remain quite long. The main objective of drug therapy in the postoperative period is to shorten the duration of repair and epithelialisation of the wound with the formation of a postoperative scar. Drug therapy in the postoperative period, in addition to combating infection, is aimed at stimulating regenerative processes in the wound and, as a rule, includes irrigation with antiseptic solutions and the application of ointment dressings on a water-soluble base.

It is well known that, despite the wide arsenal of drugs with various mechanisms of action, classical methods of treating wounds and wound infection in some cases do not yield the desired result. This is determined, first of all, by the long healing times of perineal and anal canal wounds. At present, the widespread and not always substantiated and rational use of antibiotics and hormones, due to their mutagenic action, has led to an increased incidence of purulent-inflammatory diseases caused by resistant flora and to the appearance of dysbacterioses, which have become an independent clinical problem. A total allergisation of the population and a decrease in immunity are taking place. In practical medicine, biologically active substances lacking allergenic and immunosuppressive properties have come into wide use. Embryonic tissues (ET) may serve as a source of such preparations.

At present, embryonic tissue transplantation (ETT) is used in various diseases: insulin-dependent diabetes mellitus, central nervous system pathology (Parkinson's disease, Alzheimer's disease), diseases of the haematopoietic and circulatory organs [61,72,79,121,130,137]. A certain, still modest, positive experience has been accumulated in the transplantation of hepatocytes in chronic hepatitis (CH) and liver cirrhosis (LC) [80,154,157]. The unique properties of embryonic tissue are determined by:

- the presence of a large number of stem (blast) cells containing biologically active compounds, such as growth factors, cytokines, tissue hormones, oligonucleotides, stage-specific proteins and peptides, including fetoproteins, antioxidants and scavengers of reactive oxygen species, adaptogens, anti-inflammatory bacteriostatic compounds stimulating immunocompetent cells, etc.;

- reduced antigenic activity and the absence of an immune rejection response, since in the first and second trimestres of germ layer differentiation, class 1 and class 2 major histocompatibility proteins are not yet expressed.

Thus, in tissue therapy with the use of embryonic tissue (allogeneic biosubstrate), the mechanisms of non-specific modulation of regeneration, repair, proliferation and differentiation are activated. At present, stem cells (including embryonic and foetal cells) are being studied by scientists worldwide. At the same time, the literature contains no reliable data on the use of an allogeneic biosubstrate in the treatment of perineal and anal canal wounds that convincingly demonstrate the advantages of existing methods of patient treatment aimed at accelerating repair processes and shortening the terms of treatment after open haemorrhoidectomy; the mechanism of action of the allogeneic biosubstrate on the course and phases of the wound process, on the level of bacterial contamination of the wound, on the hormonal status, and on the terms of medical and social rehabilitation of operated patients has not been studied.

Aim of the study: To improve the results of surgical treatment of patients with chronic haemorrhoids.

Objectives of the study:

1. To evaluate clinical data and determine the frequency of inflammatory postoperative complications in patients after open haemorrhoidectomy with local application of an allogeneic biosubstrate.

2. To identify the cytological features of the wound process by studying impression smears from the wound surface of the anal canal with the use of an allogeneic biosubstrate in haemorrhoid patients in the postoperative period.

3. To assess the background microflora in haemorrhoid patients and analyse its changes at different times after surgical intervention with and without the use of an allogeneic biosubstrate.

4. To study the morphological features of the wound process after the use of an allogeneic biosubstrate in patients after open haemorrhoidectomy.

5. To determine the concentration of hormones in the blood of patients before and after surgery with the use of an allogeneic biosubstrate.

6. To carry out a comparative assessment of wound healing times and indicators of social and medical rehabilitation of patients who underwent open haemorrhoidectomy with the use of preparations containing an allogeneic biosubstrate and without such use.

Scientific novelty. For the first time, the features of the clinical course of the wound process have been studied against the background of the use of an allogeneic biosubstrate in patients after open haemorrhoidectomy. Under the conditions of exposure to an allogeneic biosubstrate, the cytological picture at different phases of the wound process, changes in the level of bacterial contamination, the hormonal status at different times of the postoperative period, and the pathomorphological picture of the wound process have been evaluated.

Practical significance of the work

According to clinical, cytological and morphological studies, the use of an allogeneic biosubstrate in the postoperative period after open haemorrhoidectomy made it possible, through stimulation of repair processes and reduction of bacterial contamination of postoperative wounds, to shorten the various phases of the wound process, accelerate repair processes and thereby shorten the healing time of postoperative wounds. The study conducted with the use of an allogeneic biosubstrate after open haemorrhoidectomy established that the use of an allogeneic biosubstrate reduces wound healing times from 35.5±2.9 days (in the control group) to 25.1±1.2 days (in the main group). The study of hormonal status showed that the use of an allogeneic biosubstrate has no adverse effect on the overall hormonal background of the patient. Thus, the results obtained indicate the expediency of using an allogeneic biosubstrate in the treatment of patients who have undergone open haemorrhoidectomy. Local application of an allogeneic biosubstrate reduced the number of inflammatory postoperative complications. The reduction of rehabilitation times in operated patients makes it possible to recommend it for introduction into the practice of surgical and coloproctological hospitals.

Main propositions of the dissertation submitted for defence:

1. The use of an allogeneic biosubstrate in the postoperative period after open haemorrhoidectomy accelerates repair processes and shortens wound healing times.

2. In studying the severity of the pain syndrome in patients in the postoperative period, it was found that the use of an allogeneic biosubstrate reduces the intensity of the pain syndrome on the first day and leads to its disappearance by day 10.

3. The use of an allogeneic biosubstrate has no adverse effect on the macro-organism. According to the data obtained, the allogeneic biosubstrate does not affect the overall hormonal status of operated patients.

4. According to clinical, cytological and morphological studies, the use of an allogeneic biosubstrate, by reducing bacterial contamination of postoperative wounds and promoting the early appearance of macrophages, fibroblasts and collagen fibres, made it possible to shorten the phases of the wound process, accelerate repair processes and thereby reduce wound healing times from 35.5±2.9 days (in the control group) to 25.1±1.2 days (in the main group) (chi-square with Bonferroni correction (p<0.001)). A reduction of inflammatory postoperative complications from 9.9% (in the control group) to 3.3% (in the main group) was observed.

Implementation of research results into practice. The method of using an allogeneic biosubstrate in the treatment of wounds after open haemorrhoidectomy is applied in the clinical practice of the State Scientific Centre of Coloproctology of the Ministry of Health of the Russian Federation; the results of the study have been implemented in the clinical practice of the coloproctology department in Chelyabinsk.

Approbation of the work. The main propositions and conclusions of the dissertation were reported at a scientific and practical conference at the State Scientific Centre of Coloproctology on 21 March 2006.

The dissertation was approbated at a joint conference of the Federal State Institution "State Scientific Centre of Coloproctology of Roszdrav", 1st and 2nd Clinical Departments of the SSC of Coloproctology, on 21 June 2007. Positive reviews from reviewers were received.

Publications. Three scientific works have been published on the topic of the dissertation, including one in the central press.

Structure and scope of the dissertation. The dissertation is written in Russian and presented on 139 typewritten pages. It consists of an introduction, 5 chapters including a literature review, research methods and research results, a conclusion, conclusions, practical recommendations and a list of references. The work contains 68