Gastroenterology/Proctology

Anal Fissure

Chronic anal fissures can be simply and effectively treated medically without the risk of incontinence associated with sphincterotomy. The American Gastroenterological Association (AGA) has noted: “In most cases, an initial trial of conservative care alone is appropriate, particularly for acute fissures. The timing and choice of additional treatment depend on the chronicity of the fissure, the severity of its symptoms, and the rate and completeness of its response to conservative care. Although lateral internal sphincterotomy (LIS) is the procedure of choice for anal fissures that do not resolve with conservative care or that are simply too painful for conservative care, in a minority of patients, LIS is associated with minor, but sometimes permanent, defects in continence.

Topical therapy is directed at reversibly decreasing resting anal pressure, with a goal of allowing fissure healing without permanent sphincter damage. Several preparations have been used, including compounded nitroglycerin ointment 0.2% (glyceryl trinitrate; GTN). Studies have shown healing rates of 25-50%. Side effects, particularly headache with higher doses of nitroglycerin ointment such as found in the commercially available 2% product, have been reported, but only infrequently require cessation of therapy with the less concentrated preparations.

An Italian position statement aimed to identify the best treatment option for anal fissures by drawing on evidence-based medicine and the expert advice of 6 colorectal surgeons with extensive experience in this field. Altomare et al. noted that use of 0.4% glyceryl trinitrate in standardized fashion seems to have the best results despite a higher percentage of headache, while the use of botulinum toxin had inconsistent results. Nonresponding patients should undergo lateral internal sphincterotomy.

Because a long interval of time between first symptoms and treatment negatively affects fissure healing and increases recurrence rate, treatment for anal fissure should be initiated early.
Tech Coloproctol. 2011 Jun;15(2):135-41. Epub 2011 May 3.
The management of patients with primary chronic anal fissure: a position paper.
Altomare DF, Binda GA, Canuti S, Landolfi V, Trompetto M, Villani RD.
Click here to access the PubMed abstract of this article.

Can J Surg. 2006 Feb;49(1):41-5.
Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin.
Click here to access the PubMed abstract of this article.

Gastroenterology 2003;124:233–234
American Gastroenterological Association medical position statement: Diagnosis and care of patients with anal fissure, This document presents the official recommendations of the American Gastroenterological Association (AGA) on Anal Fissures. It was approved by the Clinical Practice Committee on May 19, 2002 and by the AGA Governing Board on July 27, 2002.
Click here to access the abstract of this article.

 


Sodium Butyrate Enemas for Treatment of Acute Radiation-induced Proctitis in Patients with Prostate Cancer and the Impact on Late Proctitis

To evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis, 31 patients were treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. 23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference was found between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and two of these patients from grade II toxicity as well. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity.

Strahlenther Onkol. 2008 Dec;184(12):686-92. Epub 2008 Dec 24.
Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis. A prospective evaluation.
Hille A, Herrmann MK, Kertesz T, Christiansen H, Hermann RM, Pradier O, Schmidberger H, Hess CF.
Click here to access the PubMed abstract of this article.

 


Short Chain Fatty Acid Enemas for Short-Term Treatment of Chronic Radiation Proctitis

Radiation proctitis is a common complication of abdominal and pelvic radiotherapy. Short chain fatty acids are the main energy source of colonocytes and their use may be impaired in chronic radiation proctitis. A prospective, randomized, double-blind trial compared short chain fatty acid enemas with placebo in 19 patients with chronic radiation proctitis. Short chain fatty acid enemas contained 60 mM sodium acetate, 30 mM sodium propionate, and 40 mM sodium butyrate. The treatment period lasted five weeks and patients were followed up for six months. After five weeks, short chain fatty acid-treated patients showed a significant decrease in the number of days with rectal bleeding from the previous week and an improvement of endoscopic score. Hemoglobin values were also significantly higher in short chain fatty acid-treated patients. Although short chain fatty acid-treated patients did not get worse in the next six months, placebo-treated ones gradually improved, and at the end of six months, differences between the two groups were no longer observed. The study concluded that short chain fatty acid enemas can accelerate the process of healing in chronic radiation proctitis, but treatment has to be continuous if a complete and sustained clinical, endoscopic, and histologic response is to be obtained.

Dis Colon Rectum. 1999 Jun;42(6):788-95; discussion 795-6.
Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial.
Pinto A, Fidalgo P, Cravo M, Midões J, Chaves P, Rosa J, dos Anjos Brito M, Leitão CN.
Click here to access the PubMed abstract of this article.

Am J Gastroenterol. 1996 Sep;91(9):1814-6.
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
al-Sabbagh R, Sinicrope FA, Sellin JH, Shen Y, Roubein L.
Click here to access the PubMed abstract of this article.

 


Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.

Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. A double-blind, double-dummy, randomized, multicentre study compared the therapeutic efficacy, tolerability and safety, and patient’s preference of budesonide foam vs. budesonide enema. Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) received 2mg/25mL budesonide foam and placebo enema (n=265), or 2mg/100mL budesonide enema and placebo foam (n=268) for 4 weeks. Clinical remission rates were 60% for budesonide foam and 66% for budesonide enema. Both formulations were safe and no drug-related serious adverse events were observed.

Budesonide enemas can be compounded in a “patient-friendly” more concentrated volume such as 2 mg/60 ml.

Aliment Pharmacol Ther. 2006 Jan 15;23(2):303-12.
Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.
Gross V, Bar-Meir S, Lavy A, Mickisch O, Tulassay Z, Pronai L, Kupcinskas L, Kiudelis G, Pokrotnieks J, Kovács A, Faszczyk M, Razbadauskas A, Margus B, Stolte M, Müller R, Greinwald R; International Budesonide Foam Study Group.
Click here to access the PubMed abstract of this article.

 


Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.

Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether a 2 mg budesonide enema administered twice daily could increase the remission rate in comparison with the once daily standard regimen, and whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect.

149 patients with active distal UC were treated in a controlled, double-blind multicenter study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse.

The remission rates at 4 weeks were 33% for daily and 41% for b.i.d. regimens and correspondingly 51% and 54% at 8 weeks. The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% (P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS).

This study concluded that budesonide enema 2 mg daily appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.

Scand J Gastroenterol. 2002 Jun;37(6):705-10.
Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.
Lindgren S, Löfberg R, Bergholm L, Hellblom M, Carling L, Ung KA, Schiöler R, Unge P, Wallin C, Ström M, Persson T, Suhr OB.
Click here to access the PubMed abstract of this article.

 


Oral Naloxone to Prevent or Reverse Opioid-Induced Constipation

Opioid analgesics are the cornerstone of pain management for moderate-to-severe cancer pain and, increasingly, chronic non-cancer pain. The use of opioids is commonly associated with dose-limiting constipation that seriously impacts patients’ quality of life. Agents currently used to manage opioid-induced constipation (OIC), such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective. A novel approach for selectively and locally antagonizing the gastrointestinal effects of opioids involves the coadministration of a mu-opioid receptor antagonist with negligible systemic availability, such as oral naloxone. Combination therapy with prolonged-release (PR) oxycodone plus PR naloxone has been shown to provide effective analgesia while preventing or reducing constipation. This novel strategy has the potential to significantly improve the quality of life of patients suffering from chronic pain, affording patients the benefit of full analgesia, without the burden of OIC.

Pharmacology. 2009;83(1):10-7.
Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach
Click here to access the PubMed abstract of this article.

In a controlled trial involving 202 patients with chronic pain under stable oral prolonged-release (PR) oxycodone therapy (40, 60 or 80mg/day), patients were randomized to receive PR oral naloxone (10, 20, 40mg/day) or placebo. No loss of analgesic efficacy with naloxone was observed; mean pain intensity scores were comparable for placebo and all doses of naloxone and remained unchanged during treatment. Naloxone 20 mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo. The 2:1 oxycodone/naloxone ratio was identified as the most suitable. The conclusion: co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.

Eur J Pain. 2009 Jan;13(1):56-64
A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.
Click here to access the PubMed abstract of this article.

A small double-blind, randomized, placebo-controlled study of 9 patients evaluated the effects on constipation and analgesia of low doses of oral naloxone (4 mg, 2 mg, or placebo) given three times daily in patients taking stable doses of opioids with complaints of constipation. All the patients who received oral naloxone had some improvement in their bowel frequency. Two patients experienced partial reversal of analgesia, and one patient had complete reversal of analgesia. Patients using high doses of opioids appeared to be the most vulnerable to reversal of analgesia by oral naloxone.

J Pain Symptom Manage. 2002 Jan;23(1):48-53
Low-dose oral naloxone reverses opioid-induced constipation and analgesia.
Click here to access the PubMed abstract of this article.

To prevent systemic opioid withdrawal symptoms, therapy should be started with low doses and patients carefully monitored during titration.4
Oral naloxone, particularly when formulated as an extended release preparation, may provide an option for relief of opioid-induced constipation in patients who desire to avoid subcutaneous injections of methylnaltrexone.

Pain 2000 Jan;84(1):105-9.
Oral naloxone reverses opioid-associated constipation.
Click here to access the PubMed abstract of this article.

 


 

Glyceryl Trinitrate Suppository For Anal Fissure: Safety and Efficacy

A double-blind placebo-controlled clinical trial concluded that use of glyceryl trinitrate 0.2% suppositories represents a new, promising, and effective treatment for chronic anal fissure.

Dis Colon Rectum. 2008 May 10. [Epub ahead of print]
Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.
Click here to access the PubMed abstract of this article.

 


 

Topical Amitriptyline/Ketamine for Analgesia in Refractory Proctodynia
Idiopathic proctodynia, an enigmatic pain syndrome affecting the perianal region, can be persistent, relatively refractory to treatment, and associated with considerable psychological distress. Lehman and Sciallis of the Department of Dermatology, Mayo Clinic, presented the case of a patient with a long history of severe proctodynia that had been resistant to a range of topical and systemic treatments. With the use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% cream, the patient’s pain resolved rapidly, leading to a substantially improved quality of life.

J Drugs Dermatol. 2008 Sep;7(9):887-9.
Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia.
Click here to access the PubMed abstract of this article.

 


 

Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. Low-dose naltrexone (LDN) therapy appears effective and safe in subjects with active Crohn’s disease.
Am J Gastroenterol 2007;102:1-9
Low-dose naltrexone therapy improves active Crohn’s disease.
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS.
Click here to access the PubMed abstract of this article.

 


 

Topical Metronidazole 10% Decreases Posthemorrhoidectomy Pain and Improves Healing

Oral metronidazole has been demonstrated to decrease postoperative pain after open diathermy hemorrhoidectomy. A prospective, randomized trial at the Georgia Colon and Rectal Surgical Clinic in Atlanta, Georgia investigated the efficacy of topical metronidazole 10% vs. placebo, applied to the surgical site, in reducing postoperative pain and promoting wound healing after Harmonic Scalpel hemorrhoidectomy. In the metronidazole group, postoperative edema was ranked significantly lower and overall wound healing ranked significantly better than in controls. The study concluded that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort on postop days 7 and 14. Postoperative edema is reduced and overall healing is improved, compared with placebo.

Dis Colon Rectum 2004 May;47(5):711-6
Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing.
Click here to access the PubMed abstract of this article.

A separate double-blind, randomized trial evaluated the effect of topical metronidazole 10% versus placebo, applied to surgical site, in reducing postoperative and post-defecation pain after hemorrhoidectomy. Findings indicated that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort.
Dis Colon Rectum. 2008 Feb;51(2):235-8. Epub 2008 Jan 4
Topical Metronidazole can Reduce Pain after Surgery and Pain on Defecation in Postoperative Hemorrhoidectomy.
Click here to access the PubMed abstract of this article.


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