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Hemorrhoids pp 49-72 | Cite as

Medical Therapy of Hemorrhoidal Disease

  • Franco Scaldaferri
  • Fabio Ingravalle
  • Tiziano Zinicola
  • Grainne Holleran
  • Antonio Gasbarrini
Reference work entry
Part of the Coloproctology book series (COLOPROCT, volume 2)

Abstract

Hemorrhoids can occur normally as part of the vasculature of the anal canal, however; in some patients they can also be the source of a number of bothersome perianal problems. These problems encompass a condition referred to as hemorrhoidal disease. The cardinal features of this condition include anal pruritus, prolapse, bleeding, and pain in the case of thrombosis. Symptomatic hemorrhoids have a prevalence ranging from 4.4% in the general population, to 36.4% in the population attending general practitioners (Johanson and Sonnenberg, Gastroenterology 98:380–386, 1990), and are known to have an increased prevalence during pregnancy and postpartum (Johanson and Sonnenberg, Gastroenterology 98:380–386, 1990).

Medical treatment of hemorrhoidal disease include the treatment of the associated disorders like constipation and the active treatment of hemorrhoidal disease.

The therapy for hemorrhoidal associated constipation is discussed in Sect. 2. Briefly, constipation is a common and sometimes disabling condition worldwide, above all among patients presenting hemorrhoids. A variety of traditional and novel treatment options are nowadays available. Fiber has been indiscriminately recommended for the treatment of constipation. As a matter of fact, an increase in the amount of dietary fiber is an almost universal recommendation in the primary care management of constipation and more in general in the management of hemorrhoids. Insoluble fibers appear to have the greatest impact on stool frequency and output. Traditional laxatives are effective at inducing bowel movements, but data for their role in long-term management and on efficacy on constipation-associated abdominal symptoms are limited. Long-term studies are available for polyethylene glycol (Macrogol), confirming sustained efficacy. The critical importance of the enteric microbiota to intestinal and, especially, colonic function, together with some limited clinical evidence to suggest some changes in the flora in the constipated subject provide a rationale for the use of probiotics and prebiotics in constipation. However, with the exception of the constipated IBS subject, clinical trial data on these agents in constipation, per se, is very scanty. Large-scale, high-quality, trials are indicated and are clearly feasible given the prevalence of the complaint. When patients fail to respond to standard therapy, the colonic secretagogue lubiprostone, or the 5-HT4 agonist prucalopride, or linaclotide, a GC-C receptor agonist, are available as the next step in management. In controlled trials in chronic constipation, these drugs were shown to significantly improve constipation and its associated symptoms, and both seem to have a favorable safety record, although a high incidence of nausea was reported with lubiprostone. Among the new therapeutic agents Plecanatide, another GC-C agonist, has been proven to be effective in the treatment of constipation, although its long-term risks and benefits remain to be determined. The accessibility of multiple drugs with different mechanisms of action will continue to benefit patients suffering from chronic constipation as well as the hemorrhoids-associated one. The treatment of constipation has become easier with the exciting development of new medications and effective biofeedback therapy over the past decade. Other therapies on the horizon should further improve health care providers’ ability to effectively treat symptoms of hemorrhoids and its complications.

The active therapy for hemorrhoidal disease is discussed in Sect. 3. Briefly, conservative approaches are recommended in particular for low-grade internal hemorrhoids and nonthrombosed external hemorrhoids (grade I hemorrhoids), which can generally be effectively treated with dietary and lifestyle modifications. The main goal of medical treatment is to control hemorrhoidal symptoms. Several drugs are available in various forms including tablet, suppository, cream, and wipes. Oral therapy is based on flavonoids, mesoglycan, calcium dobesilate, and herbal extracts. Local therapy is based on corticosteroids, analgesics, vasoconstrictors, and barrier cream including several active ingredients such as sodium hyaluronate, aloe vera, and other herbal extracts. Flavonoids are a heterogeneous class of drugs with venotonic properties, capable of increasing vascular tone, reducing venous capacity, decreasing capillary permeability, and facilitating lymphatic drainage in addition to having anti-inflammatory effects. Mesoglycan is a set of glycosaminoglycans of venous vascular diseases due to its fibrinolytic effect. Calcium dobesilate is a venotonic drug, which is capable of controlling symptoms of a hemorrhoidal attack, reducing microvascular permeability, decreasing platelet aggregation, and having antioxidant properties. Oral supplementation with herbal extracts as Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, and Hamamelis virginiana may help control hemorrhoidal symptoms. Pharmacological mechanisms of action are very similar to those of the flavonoid drug class, by improving circulation and reducing inflammation. Several dietary factors including a low-fiber diet, spicy or fatty foods, coffee, alcohol, and others may be implicated in the pathogenesis of hemorrhoidal disease, but reported data in most cases is inconsistent or conflicting. Increasing dietary fiber intake and oral fluids are both recommended to manage hemorrhoidal disease and reduce the likelihood of recurrence. Spicy food is one of the most important dietary risk factors for hemorrhoidal crisis. Alcohol is another possible risk factor for hemorrhoidal disease, and although reliable data in the literature is sparse, patients should still avoid alcohol consumption during a hemorrhoidal crisis. Smoking is not associated with an increased risk of hemorrhoid. Local anesthetics reduce hemorrhoidal symptoms by exerting a local anesthetic effect, which eliminates the burning and itching associated with hemorrhoidal prolapse. They have less of an effect on bleeding, although they are frequently used for this indication. Antispasmodic agents, glyceryl trinitrate (GTN), and nifedipine are used to relieve symptoms associated with anal sphincter spasm and high resting anal canal pressures. Topical GTN treatment has also resulted in a decrease rectal bleeding, an improvement of anal pain, throbbing, itching, and irritation. Nifedipine ointment has good efficacy particularly in the treatment of acute thrombosed external hemorrhoids and chronic anal fissures. Phenylephrine is a vasoconstrictor which provides temporary relief of acute symptoms of hemorrhoids, such as bleeding and pain on defecation. Anti-inflammatory topical therapy is based on hydrocortisone acetate or 5-aminosalicylic acid (5-ASA), both with similar anti-inflammatory effects, and suppository forms are more useful than cream to treat internal hemorrhoids. Several botanical extracts have been shown to improve hemorrhoidal symptoms. Aloe vera is one of the most commonly used extracts for treating acute and chronic wounds. The gel of aloe vera reduces the pain, swelling and itching of burns, and skin irritation. Topical therapy with herbal extracts, such as Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, and Hamamelis virginiana, may also help control hemorrhoidal symptoms, these are often prescribed in clinical practice due to their effectiveness and the very few reported side effects.

References

  1. Abcarian H, Alexander-Williams J, Christiansen J et al (1994) Benign anorectal disease: definition, characterization, and analysis of treatment. Am J Gastroenterol 89(Suppl 8):S182–S193PubMedGoogle Scholar
  2. Aggrawal K, Satija N, Dasgupta G, Dasgupta P, Nain P, Sahu AR (2014) Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: a randomized, controlled, open-label multicentre study. J Ayurveda Integr Med 5(2):117–124CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ait-Belgnaoui A, Han W, Lamine F et al (2006) Lactobacillus farciminis treatment suppresses stress-induced visceral hypersensitivity: a possible action through interaction with epithelial cells cytoskeleton contraction. Gut 55:1090–1094CrossRefPubMedPubMedCentralGoogle Scholar
  4. Alesiani D, Pichichero E, Canuti L, Cicconi R, Karou D, D’Arcangelo G, Canini A (2007) Identification of phenolic compounds from medicinal and melliferous plants and their cytotoxic activity in cancer cells. Caryologia 60:90–95CrossRefGoogle Scholar
  5. Allain H, Ramelet AA, Polard E, Bentué-Ferrer D (2004) Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids. Drug Saf 27(9):649–660CrossRefPubMedGoogle Scholar
  6. Alonso-Coello P, Mills E, Heels-Ansdell D, López-Yarto M, Zhou Q, Johanson JF, Guyatt G (2006) Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis. Am J Gastroenterol 101(1):181–188CrossRefPubMedGoogle Scholar
  7. American College of Gastroenterology Chronic Constipation Task Force (2005) An evidence-based approach to the management of chronic constipation in North America. Am J Gastroenterol 100(Suppl 1):S1CrossRefGoogle Scholar
  8. Andreozzi GM (2007) Effectiveness of mesoglycan in patients with previous deep venous thrombosis and chronic venous insufficiency. Minerva Cardioangiol 55(6):741–753PubMedGoogle Scholar
  9. Bennett WG, Cerda JJ (1996) Dietary fiber: fact and fiction. Dig Dis 14:43–58CrossRefPubMedGoogle Scholar
  10. Berthet P, Farine JC, Barras JP (1999) Calcium dobesilate: pharmacological profile related to its use in diabetic retinopathy. Int J Clin Pract 53(8):631–636PubMedGoogle Scholar
  11. Bharucha AE, Pemberton JH, Locke GR 3rd (2013) American Gastroenterological Association technical review on constipation. Gastroenterology 144:218CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bryant AP, Busby RW, Bartolini WP, Cordero EA, Hannig G, Kessler MM et al (2010) Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci 86(19–20):760–765CrossRefPubMedGoogle Scholar
  13. Bueno L, de Ponti F, Fried M et al (2007) Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity. Neurogastroenterol Motil 19(Suppl 1):89–119CrossRefPubMedGoogle Scholar
  14. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM et al (2010) Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol 649(1–3):328–335CrossRefPubMedGoogle Scholar
  15. Chiang CP, Jao SW, Lee SP, Chen PC, Chung CC, Lee SL, Nieh S, Yin SJ (2012) Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer. Alcohol 46(1):37–49CrossRefPubMedGoogle Scholar
  16. Chmielewska A, Szajewska H (2010) Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol 16:69–75PubMedPubMedCentralGoogle Scholar
  17. Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ (2007) Cumulative incidence of chronic constipation: a population-based study 1988–2003. Aliment Pharmacol Ther 26(11–12):1521–1528CrossRefPubMedGoogle Scholar
  18. Cinca R, Chera D, Gruss HJ, Halphen M (2013) Randomised clinical trial: macrogol/PEG 3350+electrolytes versus prucalopride in the treatment of chronic constipation – a comparison in a controlled environment. Aliment Pharmacol Ther 37:876CrossRefPubMedGoogle Scholar
  19. Clinical Practice Committee, American Gastroenterological Association (2004) American Gastroenterological Association medical position statement: diagnosis and treatment of hemorrhoids. Gastroenterology 126(5):1461–1462CrossRefGoogle Scholar
  20. Cummings JH (1984) Constipation, dietary fiber and the control of large bowel function. Postgrad Med J 60:811–819CrossRefPubMedPubMedCentralGoogle Scholar
  21. Dat AD, Poon F, Pham KB, Doust J (2012) Aloe Vera for treating acute and chronic wounds. Cochrane Database Syst Rev 2:CD008762Google Scholar
  22. di Visconte MS, Nicolì F, Del Giudice R, Mis TC (2017) Effect of a mixture of diosmin, coumarin glycosides, and triterpenes on bleeding, thrombosis, and pain after stapled anopexy: a prospective, randomized, placebo-controlled clinical trial. Int J Color Dis 32(3):425–431CrossRefGoogle Scholar
  23. Ebrahimi N, Vohra S, Gedeon C, Akoury H, Bernstein P, Pairaudeau N, Cormier J, Dontigny L, Arsenault MY, Fortin C, Goyet M, Lafortune C, Lalande J, Beauchamp C, Engel F, Fortin A, Taddio A, Einarson T, Koren G (2011) The fetal safety of hydrocortisone-pramoxine (Proctofoam-HC) for the treatment of hemorrhoids in late pregnancy. J Obstet Gynaecol Can 33(2):153–158CrossRefPubMedGoogle Scholar
  24. Facino RM, Carini M, Stefani R, Aldini G, Saibene L (1995) Elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch Pharm (Weinheim) 328:720–724CrossRefGoogle Scholar
  25. FDA (2012) FDA approves Linzess to treat certain cases of irritable bowel syndrome and constipation. https://www.drugs.com/newdrugs/fda-approves-linzess-certain-cases-irritable-bowel-syndrome-constipation-3469.html
  26. Giannini I, Amato A, Basso L, Tricomi N, Marranci M, Pecorella G, Tafuri S, Pennisi D, Altomare DF (2015) Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol 19(6):339–345CrossRefPubMedGoogle Scholar
  27. Gionchetti P, Campieri M, Belluzzi A, Brignola C, Miglioli M, Barbara L (1992) 5-ASA suppositories in hemorrhoidal disease. Can J Gastroenterol 6:18–20CrossRefGoogle Scholar
  28. Gohil KJ, Patel JA, Gajjar AK (2010) Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci 72(5):546–556CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gupta PJ (2008) Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. A prospective, randomized, placebo-controlled, double blind, crossover trial. Arq Gastroenterol 45(2):124–127CrossRefPubMedGoogle Scholar
  30. Gurel E, Ustunova S, Ergin B, Tan N, Caner M, Tortum O, Demirci-Tansel C (2013) Herbal haemorrhoidal cream for haemorrhoids. Chin J Physiol 56(5):253–262CrossRefPubMedGoogle Scholar
  31. Hernández-Bernal F, Valenzuela-Silva CM, Quintero-Tabío L, Castellanos-Sierra G, Monterrey-Cao D, Aguilera-Barreto A, López-Saura P, THERESA-2 Group of Investigators (2013) Recombinant streptokinase suppositories in the treatment of acute haemorrhoidal disease. Multicentre randomized double-blind placebo-controlled trial (THERESA-2). Color Dis 15(11):1423–1428CrossRefGoogle Scholar
  32. Hernández-Bernal F, Castellanos-Sierra G, Valenzuela-Silva CM, Catasús-Álvarez KM, Valle-Cabrera R, Aguilera-Barreto A, López-Saura PA, THERESA-3 Group of Investigators (2014) Recombinant streptokinase vs phenylephrine-based suppositories in acute hemorrhoids, randomized, controlled trial (THERESA-3). World J Gastroenterol 20(6):1594–1601CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hernández-Bernal F, Castellanos-Sierra G, Valenzuela-Silva CM, Catasús-Álvarez KM, Martínez-Serrano O, Lazo-Diago OC, Bermúdez-Badell CH, Causa-García JR, Domínguez-Suárez JE, THERESA-4 (Treatment of HEmorrhoids with REcombinant Streptokinase Application) Group of Investigators (2015) Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids: a randomized controlled trial. World J Gastroenterol 21(23):7305–7312CrossRefPubMedPubMedCentralGoogle Scholar
  34. Herold A, Dietrich J, Aitchison R (2012) Intra-anal iferanserin 10 mg BID for hemorrhoid disease: a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther 34:329–340CrossRefPubMedGoogle Scholar
  35. Higashikawa F, Noda M, Awaya T et al (2010) Improvement of constipation and liver function by plant-derived lactic acid bacteria: a double-blind, randomized trial. Nutrition 26:367–374CrossRefPubMedGoogle Scholar
  36. Jabri M-A et al (2017) Role of laxative and antioxidant properties of Malva sylvestris leaves in constipation treatment. Biomed Pharmacother 89:29–35CrossRefPubMedGoogle Scholar
  37. Jancic-Stojanović B, Malenović A, Marković S, Ivanović D, Medenica M (2010) Optimization and validation of an RP-HPLC method for analysis of hydrocortisone acetate and lidocaine in suppositories. J AOAC Int 93(1):102–107PubMedGoogle Scholar
  38. Johanson JF (2002) Nonsurgical treatment of hemorrhoids. J Gastrointest Surg 6(3):290–294CrossRefPubMedGoogle Scholar
  39. Johanson JF, Rimm A (1992) Optimal nonsurgical treatment of hemorrhhoids: a comparative analysis of infrared coagulation, rubber band ligation, and injection sclerotherapy. Am J Gastroenterol 87:1600–1606PubMedPubMedCentralGoogle Scholar
  40. Johanson JF, Sonnenberg A (1990) The prevalence of hemorrhoids and chronic constipation. An epidemiologic study. Gastroenterology 98:380–386CrossRefPubMedGoogle Scholar
  41. Johanson JF, Ueno R (2007) Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther 25:1351CrossRefPubMedGoogle Scholar
  42. Joksimovic N, Spasovski G, Joksimovic V, Andreevski V, Zuccari C, Omini CF (2012) Efficacy and tolerability of hyaluronic acid, tea tree oil and methyl-sulfonyl-methane in a new gel medical device for treatment of haemorrhoids in a double-blind, placebo-controlled clinical trial. Updat Surg 64:195–201CrossRefGoogle Scholar
  43. Jones MP, Talley NJ, Nuyts G et al (2002) Lack of objective evidence of efficacy of laxatives in chronic constipation. Dig Dis Sci 47:2222–2230CrossRefPubMedGoogle Scholar
  44. Karawya MS, Balbaa SI, Afifi MSA (1971) Investigation of the carbohydrate contents of certain mucilaginous plants. Planta Med 20:14–23CrossRefPubMedGoogle Scholar
  45. Kenny KA, Dkelly JM (2001) Dietary fiber for constipation in older adults: a systematic review. Clin Effect Nurs 5:120–128CrossRefGoogle Scholar
  46. Koliani-Pace J, Lacy BE (2017) Update on the management of chronic constipation. Curr Treat Options Gastroenterol.  https://doi.org/10.1007/s11938-017-0118-2
  47. Korting HC, Schäfer-Korting M, Hart H, Laux P, Schmid M (1993) Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose. Eur J Clin Pharmacol 44(4):315–318CrossRefPubMedGoogle Scholar
  48. Lang L (2008) The Food and Drug Administration approves lubiprostone for irritable bowel syndrome with constipation. Gastroenterology 135:7CrossRefPubMedGoogle Scholar
  49. Lee J-H, Kim H-E, Kang J-H, Shin J-Y, Song Y-M (2014) Factors associated with hemorrhoids in Korean adults: Korean National Health and nutrition examination survey. Korean J Fam Med 35:227–236CrossRefPubMedPubMedCentralGoogle Scholar
  50. Lembo A, Camilleri M (2003) Chronic constipation. N Engl J Med 349:1360–1368CrossRefPubMedGoogle Scholar
  51. Lohsiriwat V (2012) Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol 18(17):2009–2017CrossRefPubMedPubMedCentralGoogle Scholar
  52. Lohsiriwat V (2015) Treatment of hemorrhoids: a coloproctologist’s view. World J Gastroenterol 21(31):9245–9252CrossRefPubMedPubMedCentralGoogle Scholar
  53. Lyseng-Williamson KA, Perry CM (2003) Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 63(1):71–100CrossRefPubMedGoogle Scholar
  54. MacKay D (2001) Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 6(2):126–140PubMedGoogle Scholar
  55. Marsicano LJ, Pérez M, Urquiola G (1995) Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids. G E N 49(4):296–302PubMedGoogle Scholar
  56. Menteş BB, Görgül A, Tatlicioğlu E, Ayoğlu F, Unal S (2001) Efficacy of calcium dobesilate in treating acute attacks of hemorrhoidal disease. Dis Colon Rectum 44(10):1489–1495CrossRefPubMedGoogle Scholar
  57. Mosavat SH, Ghahramani L, Sobhani Z, Haghighi ER, Heydari M (2015) Topical Allium ampeloprasum subsp Iranicum (leek) extract cream in patients with symptomatic hemorrhoids: a pilot randomized and controlled clinical trial. J Evid Based Complementary Altern Med 20(2):132–136CrossRefPubMedGoogle Scholar
  58. Peery AF, Sandler RS, Galanko JA, Bresalier RS, Figueiredo JC, Ahnen DJ, Barry EL, Baron JA (2015) Risk factors for hemorrhoids on screening colonoscopy. PLoS One 10(9):e0139100CrossRefPubMedPubMedCentralGoogle Scholar
  59. Perera N, Liolitsa D, Iype S, Croxford A, Yassin M, Lang P, Ukaegbu O, van Issum C (2012) Phlebotonics for haemorrhoids. Cochrane Database Syst Rev 8:CD004322Google Scholar
  60. Perrotti P, Antropoli C, Molino D, De Stefano G, Antropoli M (2001) Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum 44(3):405–409CrossRefPubMedGoogle Scholar
  61. Perrotti P, Bove A, Antropoli C, Molino D, Antropoli M, Balzano A, De Stefano G, Attena F (2002) Topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study. Dis Colon Rectum 45(11):1468–1475CrossRefPubMedGoogle Scholar
  62. Perrotti P, Dominici P, Grossi E, Antropoli C, Giannotti G, Cusato M, Regazzi M, Cerutti R (2009) Pharmacokinetics of anorectal nifedipine and lidocaine (lignocaine) ointment following haemorrhoidectomy: an open-label, single-dose, phase IV clinical study. Clin Drug Investig 29(4):243–256CrossRefPubMedGoogle Scholar
  63. Perrotti P, Dominici P, Grossi E, Cerutti R, Antropoli C (2010) Topical nifedipine with lidocaine ointment versus active control for pain after hemorrhoidectomy: results of a multicentre, prospective, randomized, double-blind study. Can J Surg 53(1):17–24PubMedPubMedCentralGoogle Scholar
  64. Petticrew M, Rodgers M, Booth A (2001) Effectiveness of laxatives in adults. Qual Health Care 10:268–273CrossRefPubMedPubMedCentralGoogle Scholar
  65. Pigot F, Siproudhis L, Allaert FA (2005) Risk factors associated with hemorrhoidal symptoms in specialized consultation. Gastroenterol Clin Biol 29(12):1270–1274CrossRefPubMedGoogle Scholar
  66. Pourrat H, Texier O, Barthomeuf C (1990) Identification and assay of anthocyanin pigments in Malva sylvestris L. Pharm Acta Helv 65:93–96Google Scholar
  67. Punchard NA, Greenfield ASM, Thompson RPH (1992) Mechanism of action of 5-arninosalicylic acid. Mediat Inflamm 1:151–165CrossRefGoogle Scholar
  68. Quigley EM (2007) Bacteria: a new player in gastrointestinal motility disorders – infections, bacterial overgrowth and pro-biotics. Gastroenterol Clin N Am 36:735–748CrossRefGoogle Scholar
  69. Quigley EM (2011) The enteric microbiota in the pathogenesis and management of constipation. Best Pract Res Clin Gastroenterol 25(1):119–126.  https://doi.org/10.1016/jbpg.2011.01.003CrossRefPubMedGoogle Scholar
  70. Quigley EM, Vandeplassche L, Kerstens R, Ausma J (2009) Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation–a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 29:315CrossRefPubMedGoogle Scholar
  71. Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, Shi K, MacDougall JE, Shao JZ, Eng P, Fox SM, Schneier HA, Kurtz CB, Johnston JM (2012) A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 107(11):1714–24; quiz p.1725CrossRefPubMedPubMedCentralGoogle Scholar
  72. Rousseaux C, Thuru X, Gelot A et al (2007) Lactobacillus acidophilus modulates intestinal pain and induces opioid and canna-binoid receptors. Nat Med 13:35–37CrossRefPubMedGoogle Scholar
  73. Ryoo S, Song YS, Seo MS, Oh HK, Choe EK, Park KJ (2011) Effect of electronic toilet system (bidet) on anorectal pressure in normal healthy volunteers: influence of different types of water stream and temperature. J Korean Med Sci 26(1):71–77CrossRefPubMedGoogle Scholar
  74. Sanchez C, Chinn BT (2011) Hemorrhoids. Clin Colon Rectal Surg 24(1):5–13CrossRefPubMedPubMedCentralGoogle Scholar
  75. Scondotto G, De Fabritiis A, Guastarobba A, Amato AC, Filippini M (1984) Use of a minor fibrinolytic drug (mesoglycan) in phlebitis. Minerva Med 75(28–29):1733–1738PubMedGoogle Scholar
  76. Shafik A (1993) Role of warm-water bath in anorectal conditions. The “thermosphincteric reflex”. J Clin Gastroenterol 16(4):304–308CrossRefPubMedGoogle Scholar
  77. Sneider EB, Maykel JA (2010) Diagnosis and management of symptomatic hemorrhoids. Surg Clin North Am 90(1):17–32CrossRefPubMedGoogle Scholar
  78. Spiller RC (1994) Pharmacology of dietary fiber. Pharmacol Ther 62:407–427CrossRefPubMedGoogle Scholar
  79. Staroselsky A, Nava-Ocampo AA, Vohra S, Koren G (2008) Hemorrhoids in pregnancy. Can Fam Physician 54(2):189–190PubMedPubMedCentralGoogle Scholar
  80. Sugimoto T, Tsunoda A, Kano N, Kashiwagura Y, Hirose K, Sasaki T (2013) A randomized, prospective, double-blind, placebo-controlled trial of the effect of diltiazem gel on pain after hemorrhoidectomy. World J Surg 37(10):2454–2457CrossRefPubMedGoogle Scholar
  81. Tejerina T, Ruiz E (1998) Calcium dobesilate: pharmacology and future approaches. Gen Pharmacol 31(3):357–360CrossRefPubMedGoogle Scholar
  82. The GRADE Working Group (2004) Grading quality of evidence and strength of recommendations. BMJ 328:1490–1494CrossRefGoogle Scholar
  83. Tjandra JJ, Tan JJ, Lim JF, Murray-Green C, Kennedy ML, Lubowski DZ (2007) Rectogesic® (glyceryl trinitrate 0.2%) ointment relieves symptoms of haemorrhoids associated with high resting anal canal pressures. Color Dis 9(5):457–463CrossRefGoogle Scholar
  84. Tomoda M, Gonda R, Shimizu N, Yamada H (1989) Plant mucilages. XLII. An anti-complementary mucilage from the leaves of Malva sylvestris var. mauritiana. Chem Pharm Bull (Tokyo) 37(11):3029–3032CrossRefGoogle Scholar
  85. Tramonte SM, Brand MB, Mulrow CD et al (1997) The treatment of chronic constipation in adults: assystematic review. J Gen Intern Med 12:15–24CrossRefPubMedPubMedCentralGoogle Scholar
  86. Tufano A, Arturo C, Cimino E, Di Minno MN, Di Capua M, Cerbone AM, Di Minno G (2010) Mesoglycan: clinical evidences for use in vascular diseases. Int J Vasc Med 2010:390643PubMedPubMedCentralGoogle Scholar
  87. Yiannakou Y, Piessevaux H, Bouchoucha M et al (2015) A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. Am J Gastroenterol 110:741CrossRefPubMedPubMedCentralGoogle Scholar
  88. Zimmermann J, Schlegelmilch R, Mazur D, Seiler D, Vens-Cappell B (2007) Proof of systemic safety of a lidocaine ointment in the treatment of patients with anorectal pain. Arzneimittelforschung 57(1):12–19PubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Franco Scaldaferri
    • 1
  • Fabio Ingravalle
    • 1
  • Tiziano Zinicola
    • 1
  • Grainne Holleran
    • 1
  • Antonio Gasbarrini
    • 1
  1. 1.Polo Apparato Digerente e Sistema Endocrino MetabolicoFondazione Policlinico A. Gemelli, Università Cattolica del Sacro Cuore – Policlinico “A. Gemelli”RomeItaly

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