Hemorrhoidal disease is the most prevalent pathology of the anorectal region in adult populations worldwide [1, 12] and is associated with major medical and socioeconomic issues. Exacerbations have a significant effect on patients’ quality of life and result in lost work days. Approximately 20% of patients will require surgical treatment and rehabilitation, which further increases recovery time and lost work days [12].
Current understanding of the pathogenesis of HD is based on two main pathologic factors. The first relates to the occurrence of pathologic arterial inflow through the branches of the superior rectal artery to the internal hemorrhoidal plexus and, as a consequence, the occurrence of an imbalance between arterial inflow and venous outflow from the cavernous tissue of the internal hemorrhoidal plexus, resulting in an abnormal dilation of the cavernous tissue [13]. Until recently, the mechanism of blood flow regulation in the hemorrhoidal plexus was not clear, as the increase in arterial inflow could not explain fully the development of prolapsed internal hemorrhoids.
A study by Aigner et al. [14] showed the presence of perivascular nerve fibers and smooth muscle sphincters regulating vascular diameter and, thus, the blood flow velocity. The decrease in the arterial lumen diameter leads to a temporary reduction in arterial inflow, which facilitates the venous outflow and cyclical drainage of the hemorrhoidal plexus. Failure of the autonomic regulation of submucosal anorectal vessels triggers a vicious circle with progressive dilation of blood vessels and impairment of venous outflow. As a result, the progressive hyperplasia of the cavernous tissue develops [14].
The second pathologic factor is related to the development of degenerative processes in the connective tissue of the hemorrhoidal plexus [15, 16]. The progressive destruction of the ligament of Parks and the muscle of Treitz leads to the mobility of internal hemorrhoids and their shift in the anal canal. The physiologic relaxation of the internal anal sphincter allows venous outflow during a bowel movement through the expanding “hemorrhoidal cushions”. The impairment of internal regulation of blood flow and the concomitant replacement of smooth muscle tissue by connective tissue are likely to be the key factors in the pathogenesis of HD [14, 17, 18].
It is widely believed that one of the risk factors for hemorrhoids is constipation and prolonged straining. The straining required to evacuate a solid fecal bolus may cause an increase in intra-abdominal pressure and lead to increased blood flow to the internal hemorrhoidal plexus and, consequently, to impaired venous outflow, which results in dilation of the hemorrhoidal plexus [15]. The evacuation of a solid fecal bolus is also thought to favor the shift of the hemorrhoidal cushion. However, recent studies have questioned the importance of constipation in the development of HD [1, 15, 19]. In particular, no significant relationship has been found between HD and constipation, and there have also been reports that diarrhea can act as a risk factor for HD development [5].
At present, general principles for both the prevention and conservative treatment of patients with HD include modification of dietary regimen and increase in fiber intake, which helps to avoid straining during defecation. Studies by Alonso-Coello et al. [20] have shown that the consumption of dietary fiber reduces clinical manifestations of HD by 50%. At the same time, in patients with grade III and IV hemorrhoids who have prolapsed hemorrhoids, the intake of fiber is not effective [21].
The administration of venoactive agents was first described in the treatment of chronic venous insufficiency (CVI). In Russia, MPFF (Detralex) has been in use for more than 20 years. As a result of micronization of the drug to particles of less than 2 μm and the synergism of action of the diosmin and hesperidin active components, drug absorption from the gastrointestinal tract is twice as fast as the regular form. In clinical practice, MPFF is therefore one of the most popular phlebotrophic drugs. It is also one of the most well-studied agents in this group with extensive data in the literature on the pharmacology of MPFF in clinical settings over the last three decades of clinical development and therapeutic use.
The pharmacological properties of MPFF have been demonstrated [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]:
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At the microcirculatory level with an effect on venous inflammatory processes leading to endothelial protection and a reduced inflammatory cascade from the early stages of venous inflammation to later stages involving skin changes
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On venous tone with a decrease in venous distensibility and an increase in elastic modulus and venous emptying with an optimal dose/effect ratio obtained at a 1000 mg daily dose
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On microcirculatory permeability by reinforcing capillary resistance, decreasing capillary permeability, and improving microlymphatic drainage
A meta-analysis of 14 randomized trials of flavonoid agents in patients with HD has shown beneficial effects on the clinical symptoms and signs of the disease, reducing the risk of bleeding by 67%, pain by 65%, itching by 35%, and relapse of HD by 47% [37]. Some researchers have also reported that MPFF can reduce discomfort, pain, and rates of secondary bleeding after hemorrhoidectomy [8, 38,39,40,41].
Topical treatment with various drugs is also prescribed for HD, and the main goal of such therapy is to reduce HD symptoms rather than to cure the disease itself. Traditionally, topical treatment includes administration of suppositories and ointments, which contain various active ingredients, such as local anesthetics, corticosteroids, antibiotics, and anti-inflammatories.
Despite the lack of sufficient data to confirm the efficacy of diet and lifestyle modifications in the treatment of HD, many physicians include these recommendations as part of the conservative treatment of HD and as a preventive measure. The recommendations usually include an increase in dietary fiber and fluid intake, and regulating stools in order to avoid straining during prolonged defecation [17, 42]. However, recommendations for conservative treatment should be based on the current understanding of the pathogenesis of HD. It is, therefore, important to consider not the presence or absence of constipation or diarrhea in a patient, but whether these syndromes change the synchronous mechanism of defecation, physiologic relaxation of the anal sphincter, and venous drainage of the hemorrhoidal plexus, and, as such, impair the pattern of blood flow in the hemorrhoidal plexus [14].
In the observational part of our study, 705 (36.1%) patients reported a change in stool type, and 873 (44.7%) indicated a prolongation of defecation time of more than 6 min. Taking the above into account, conservative treatment should be targeted at recovering motor function of the colon and restoring blood flow in the hemorrhoidal plexus, preferably with the use of systemic phlebotropic therapy.
The aim of our study was not to compare the effectiveness of conservative treatment using phlebotonics and the effectiveness of various methods of invasive or minimally invasive treatment of HD. Our population-based study aimed to obtain information on the effect of phlebotropic therapy on the evolution of clinical manifestations in patients with different degrees of internal hemorrhoids. HD symptoms affected patients from grade I disease, providing considerable rationale for the prescription of phlebotropic drugs, such as MPFF, to address the underlying cause, and dietary therapy and topical treatments to relieve symptoms. Conservative treatment with MPFF was shown to be effective for all grades of HD in patients who underwent minimally invasive and invasive treatment and in those who did not. For the entire follow-up period, MPFF treatment was effective in 1489 (76.3%) patients. In 463 (23.7%) patients, treatment was combined with minimally invasive or invasive treatment: minimally invasive treatment was performed in 395 (20.2%) patients with grade I–III HD, and invasive treatment in 68 (3.5%) patients with grade IV HD.
Of particular interest is the finding that after the 30-day course of conservative treatment, 995 (51.0%) patients were free of any clinical HD manifestations.
On the basis of the findings of the current study, conservative treatment of HD with the phlebotropic agent MPFF is effective for all grades of the disease. However, some patients with grade I–III HD will in addition require minimally invasive treatment, and some grade IV will require invasive treatment. At the same time, the combination of conservative treatment including MPFF with surgical treatment creates favorable conditions for a smooth postoperative period.