Conservative treatment of haemorrhoids.

1. INTRODUCTION Hemorrhoids are vascular cushions underlying the distal rectal mucosa and contributing for approximately 15-20% of the resting anal pressure with a complete closure of the anal canal. They can become pathological (hemorrhoidal disease, HD) being the most common cause of painless rectal bleeding during defecation with or without prolapsing anal tissue1 . In this case the blood is bright red, not mixed with faeces but instead coated on their outer surface, or dropping after bowel movement. HD is generally classified by its location in internal (originated above the dentate line and covered by anal mucosa) and external (originated below the dentate line and covered by anoderm). Internal hemorrhoids are commonly graded based on the degree of prolapse, according to Goligher's classification2 . Its treatment must be tailored both to the severity of disease and patient's expectation: conservative treatment, including dietary and lifestyle modifications, is effective in managing the majority of patients complaining of early stages of the disease. Surgery is required only for the most advanced stages, when non-operative approaches have failed, or complications have occurred. External hemorrhoids require no specific treatment unless become acutely thrombosed or causes severe patient discomfort3 . According to a recent Consensus Statement, excisional hemorrhoidectomy is the gold standard technique for III and IV degree HD, but surgery should be used as last resort because medical treatment can relief symptoms in the majority of cases, also if it cannot cure the underlying prolapse4,5 . 2. DIETARY AND LIFESTYLE MODIFICATIONS Patients with HD of any degree could benefit from an appropriate dietary and lifestyle modifications that often lead to an improvement in defecation reducing straining and symptoms. A high-fibre diet and adequate water intake is the first medical advice to all patients with HD6 . Fiber has well-known beneficial effects on human bowel regularity, increasing fecal weight and reducing colonic transit time. Sielezneff et al. demonstrated that dietary imbalance (increased fat, alcohol and pepper intake) together with smoking, low water intake and constipation were more frequently observed in patients with HD than in healthy volunteers7 . A systematic review and meta-analysis stated that oral fiber supplementation reduce the risk of persisting symptoms and bleeding for HD by approximately 50% (RR 0.50, 95% CI 0.28-0.89), but does not improve the other symptoms such as prolapse, pain, and itching8 . Recently, the traditional definition of dietary fiber (polysaccharides and lignin, resistant to digestion by human digestive enzymes) has been expanded to oligosaccharides, such as inulin, and resistant starches9 . Using the energy guideline of 2000 kcal/day for women and 2600 kcal/day for men, the recommended daily dietary fiber intake is 28 g/day for adult women and 36 g/day for adult men10 . Moreover, the addition of fiber supplements as calcium polycarbophil, methylcellulose, and psyllium_ that have had FDA approval for laxation_may play an important role in helping to achieve adequate ifber intakes11 . These products are safe and low-cost. Of course, increasing the intake of fluid is mandatory for their mechanism of action. According to Garg et al.12,13 the "TONE method" (T, three minutes at defecation; O, once-daily defecation frequency; N, no straining and no mobile phone or newspaper in the toilet; and E, enough fiber) can correct the three well-known causes of HD or rather increased straining, prolonged defecation-time, and frequent bowel-motions, the so-called "deranged defecation habits (DDH)", reducing the progression of HD and further episodes of bleeding. Potential negative effects of fiber include reduced absorption of vitamins, minerals, protein, and calories. It is unlikely that healthy adults who consume fiber in amounts within the recommended ranges will have problems with nutrient absorption, but high-fiber intakes may not be appropriate for children and the elderly people. Moreover, with the ingestion of a large amount of high fiber, a large proportion of the dietary intake will be unabsorbed and the subsequent bulky faecal material can be difficult to evacuate in a patient with pre-existing evacuatory problems14 . The empiric and widely diffuse opinion about the role of spicy foods on the onset and deterioration of HD symptoms is not supported by epidemiological studies, and it has been confrimed by a randomized controlled trial based on the blind assumption of a moderate dosage of chili pepper in patients with symptomatic III degree HD15 . Lastly, regardless of fiber intake, is also important to adopt the correct position during defecation 16 . According to Sikirov D. sitting position requires more straining if compared with the squatting position17 . 3. MEDICAL TREATMENT Medical treatment consists of phlebotonics and topical agents. Their main goal is the control of the symptoms rather than cure HD. Most phlebotonics are extracted from plants (i.e. flavonoids), such as oxerutin, diosmin, hesperidin, coumarin, rutosides and quercetin, whereas others are synthetic compounds (i.e. calcium dobesilate). Regarding oral preparation, hesperidin in combination with diosmin (Dalfon®, Servier, Neuilly-Sur-Seine, France) is the most widespread. All these drugs act as scavengers of hydroxyl radicals, improving venous tone as well as stabilizing capillary permeability and increasing lymphatic drainage. A meta-analysis including 14 trials and 1514 patients found that the use of lfavonoids decrease the risk of worsening or persisting symptoms by 58% showing an apparent reduction of bleeding, persistent pain, itching and recurrence 18 . A Cochrane review of 24 randomized controlled trials and 2344 patient concluded that phlebotonics show a statistically significant beneficial effect in comparison with a control group for pruritus (p=0.02), bleeding (p=0.0002), post- haemorrhoidectomy bleeding (p=0.004), discharge and leakage (p=0.0008) and overall symptoms improvement (p< 0.00001). However, there was no statistically significant effect in pain and post-haemorrhoidectomy pain scores 19 . Both the abovementioned Cochrane review and meta-analysis underline the limitations in methodological quality and the heterogeneity of the included trials, so the real efficacy of phlebotonics is still on debate. Another common medical prescription in patients with acute and thrombosed HD is Mesoglycan (PRISMA®, Mediolanum Farmaceutici, Milan, Italy) derived from a group of glycosaminoglycans as amino hexose polysaccharides contained in mucoproteins, glycoproteins, and blood group substances that have demonstrated proifbr.nolytic activity20 . After two old studies regarding its use in acute HD21,22 recently Gallo et al. demonstrated the efficacy of mesoglycan in reducing postoperative thrombosis and pain at 7-10 days after an open diathermy excisional hemorrhoidectomy, permitting a faster return to normal activities23 . Topical therapy is an alternative treatment for the acute symptoms of HD. A large number of creams and suppositories are avalaible, although the evidence supporting their efficacy is weak. The primary objective of these approaches is to control symptoms by exerting a local anesthetic effect which eliminates burning and itching associated with hemorrhoidal prolapse. These medications are often multicomponents drugs containing local anesthetics, corticosteroids, antibiotics and antiinflammatories. They have no effect on bleeding, even if frequently used for this specific indication24 with the risk of causing allergic reactions or dermatitis in the long-run25,26 . CONCLUSIONS Conservative treatment plays an important role in the management of symptoms from HD being the treatment of choice in the early stages of the disease. Nevertheless, it should be considered a bridge to surgery for more advanced stages. Dietary and lifestyle modifications to achieve regular defecation and soft stool as well as the use of topical medications or phlebotonics, particularly during the acute phase or in the post-hemorrhoidectomy period can also be beneficial. Very few randomized controlled trials have been carried out and up to date we cannot know the real validity of these drugs27 . Moreover, in many trials funding by the pharmaceutical industry can bias results and this leaves doubts about the real benefit of all types of drugs in the treatment of early stages of HD.