Gastroenterology Associates of Central Georgia Macon, GA
Akshay Ranabhotu, BS1, Anjali Patel, BS1, Nicholas Habibian, BA2, Ali Keshavarzian, MD, MACG3, Emma Bjornstad, 1, Shahriar Sedghi, MD4 1Gastroenterology Associates of Central Georgia, Macon, GA; 2Tulane University School of Medicine, New Orleans, LA; 3Chicago, IL; 4Mercer University School of Medicine, Macon, GA
Introduction: Anal fissures are a common anorectal disorder caused by a tear in the anoderm below the dentate line. Crohn's disease, trauma, and passage of hard stools are associated with formation of fissures. Hypertonia (spasm of the internal sphincter) and formation of fibrotic tissue are implicated in the pathophysiology of anal fissure. Treatment options include fiber, NSAIDs, stool softeners, and topical relaxants, including nitroglycerin and diltiazem creams. While topical relaxants have demonstrated efficacy for acute anal fissures, only sub-optimal effects have been documented for resolution of chronic anal fissures over 6 week duration, especially among lesions containing fibrotic tissue, furthering hyperplasia/hypertrophy in anal papillae. Lateral sphincterotomy demonstrates a 96% success rate, but stool-leakage is reported as high as 30 percent. Since scar tissue formation and fibroblast proliferation are implicated in the pathogenesis of chronic anal fissures, we propose the use of an anti-mitotic agent, Paclitaxel, in the treatment of chronic anal fissures via inhibition of smooth muscle cell (SMC) and fibroblast proliferation. Such mechanisms stunt the cell cycle in the mitotic phase, inhibiting SMC, fibroblast proliferation and cell motility. Paclitaxel has been successfully used in coronary drug eluting stents (2.5-7.5 mg), balloon dilators for esophageal and colonic strictures (26-155 mg), and vascular (2 μg/mm2) and urological strictures.
Methods: Patients with chronic anal fissures (n=8, 3 males, 5 females) unresponsive to concurrent conservative approaches (including one patient with Crohn’s disease and two others with previous failed lateral sphincterotomy) were treated with additional compounded topically applied Paclitaxel gel (5mg/gm) for 3-8 weeks. Presence of fissures was confirmed in all patients prior to treatment via sigmoidoscopy. Rectal pain and bleeding were retrospectively assessed following Paclitaxel regimen using a standardized questionnaire.
Results: Significant reduction in pain scores were recorded following treatment (p< 0.001) (Table 1), and rectal bleeding was completely resolved in 7/8 patients. Further, four patients consented to a follow-up speculum exam, of which 3/4 demonstrated complete fissure resolution (Fig. 1), and 1/4 had partial reduction in fissure size.
Discussion: Data from this pilot study suggests that Paclitaxel may have a role in treatment of chronic anal fissures and warrants future investigation utilizing controlled studies.
Figure: Figure 1: Endoscopic image (1A) and rectal examination (1B) in a patient with failed lateral sphincterotomy. Endoscopic image (2A) and rectal examination (2B) in a patient with Crohn's anal fissure unresponsive to biological therapy.
Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.
Disclosures:
Akshay Ranabhotu indicated no relevant financial relationships.
Anjali Patel indicated no relevant financial relationships.
Nicholas Habibian indicated no relevant financial relationships.
Ali Keshavarzian indicated no relevant financial relationships.
Emma Bjornstad indicated no relevant financial relationships.
Shahriar Sedghi indicated no relevant financial relationships.
Akshay Ranabhotu, BS1, Anjali Patel, BS1, Nicholas Habibian, BA2, Ali Keshavarzian, MD, MACG3, Emma Bjornstad, 1, Shahriar Sedghi, MD4. P1952 - Topical Paclitaxel Therapy for Treatment of Chronic Anal Fissures: A Pilot Study, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.