Oral mucositis which results in severe pain is primarily due to cancer treatment but can also be related to immune-deficiency caused by infections and systemic inflammatory diseases. “The vast majority of patients undergoing radiation therapy with or without high-dose chemotherapy for head and neck cancer will develop oral mucositis in degrees ranging from minor erythema of the oral mucosa to large debilitating and painful ulcers.” A pilot study investigated the location of anesthetic effect and duration of pain relief after a single dose administration of a 25 mg bupivacaine lozenge to reduce pain in the oral cavity and pharynx in patients with head and neck cancer (HNC) and oral mucositis. The lozenge was compounded and included a sweetener and licorice powder to mask the taste. There was a significant reduction in pain in both the oral cavity and pharynx immediately after the lozenge was completely dissolved in the mouth. The mean time for maximal pain reduction after the lozenge was dissolved was 42 minutes. There was still a significant reduction in mean pain in the oral cavity after 180 minutes. “Results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC.”
A prospective, randomized, placebo-controlled, double-blinded trial concluded that misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.
Am J Gastroenterol 2000 Aug;95(8):1961-6
A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients.
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Seven patients with radiation proctitis completed an open pilot study to evaluate the effectiveness of short-chain fatty acid (SCFA) enemas. Four weeks of treatment resulted in clinical improvement in all patients and modest changes in endoscopic and pathological parameters.
Am J Gastroenterol. 1996 Sep;91(9):1814-6
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
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Oral Viscous Sucralfate Gel for Post-Procedural Treatment of Barrett’s Esophagus & Other Problems Solved with Topical Sucralfate Preparations
Barrett’s esophagus (BE) is an abnormal change in the cells of the lower portion of the esophagus, characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by columnar epithelium cells which are usually found lower in the gastrointestinal tract. Patients with BE have approximately an 0.5% risk of developing esophageal adenocarcinoma. In general, high-grade dysplasia and early stages of adenocarcinoma can be treated by endoscopic resection and/or endoscopic ablative therapy, whereas advanced stages (submucosal) generally require surgical treatment. Patients who undergo endoscopic resection and/or endoscopic ablative therapy might suffer from retrosternal discomfort and transient dysphagia, adverse effects that sometimes accompany these procedures. One of the common post-procedural treatments is oral sucralfate suspension or viscous gel, 1 gram four times daily for two weeks after the procedure. The rationale for this treatment is to enhance the wound-healing process in the esophageal tissues and to coat the wounded tissues with sucralfate, a cytoprotective agent.
Population studies suggest that gastroesophageal reflux disease (GERD) is increasing in prevalence, both in the U.S. and worldwide. The diagnosis of GERD is associated with a 10% to 15% risk of BE. Other risk factors associated with the development of BE include:
• Long-standing GERD
• Male gender
• Obesity
• Age over 50 years
Thirteen peer-reviewed articles have described the use of 5 mL of sucralfate suspension (200 mg/mL) 4 times a day for a period of 2 weeks after each endoscopic treatment of BE to ease the retrosternal discomfort and transient dysphagia that accompanies this procedure.
Randomized clinical trials (RCTs) have shown the benefit of topical sucralfate therapy for the treatment of:
• chronic venous leg ulcers
• burn wounds
• chronic radiation-induced proctitis (A sucralfate enema was chosen as a first-line treatment for this pathology by the Mucositis Study Group of Multinational Association of Supportive Care in Cancer in collaboration with the International Society of Oral Oncology).
RCTs have shown the benefit of sucralfate preparations to enhance wound-healing following:
• Hemorrhoidectomy
• Fistulotomy
• Tonsillectomy
However, less success has been noted for oral mucositis, radiotherapy-induced skin tissue damage and radiotherapy-induced esophagitis.
Pharmaceutics. 2018 Sep; 10(3): 159
Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview
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Int J Pharm Compd. 2019 Sep-Oct;23(5):376-381.
Oral Viscous Sucralfate Gel for Post-procedural Treatment of Barrett’s Esophagus
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Topical sucralfate may induce a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis.
Dig Dis Sci 1999 May;44(5):973-8
Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.
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Topical morphine is effective in relieving mucositis-associated pain following concomitant chemoradiotherapy in head and neck carcinoma. Three patients, who had been treated previously with oral morphine with no relief from esophagitis pain, swallowed from 2 to 10 mL of 0.1% morphine viscous gel three times a day, 5 to 60 minutes before eating. The gel covered esophageal surfaces and produced topical anesthesia. Benefit continued to increase over several days of use. In prior studies, relief of oral mucositis pain was obtained by a topical 0.1% morphine solution. The major advantages of topical morphine administration are simplicity, low incidence of side effects, and low cost.
J Pain Symptom Manage. 2005 Aug;30(2):107-9.
Chemoradiotherapy-induced esophagitis pain relieved by topical morphine: three cases.
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“Mucositis is a common adverse event related to many antineoplastic regimens… Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor channel blocker that can lead to decreased nocioception and inhibit the inflammatory cascade… Also, ketamine acts on a number of other pathways that may attenuate pain.”Ketamine mouthwash (20 mg/5 ml) administered using the “swish and spit” technique may be a viable treatment option in refractory mucositis pain.
J Palliat Med. 2009 Nov;12(11):989-91.
Ketamine mouthwash for mucositis pain.
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Systemic doxepin, a tricyclic antidepressant, has been used for pain management of patients with chronic pain. Practitioners at major US universities and in private practice assessed pain reduction after topical doxepin rinse in fifty-one patients with painful oral mucositis attributable solely to cancer therapy. A significant reduction of oral pain was recorded after doxepin was administered. At 5 minutes, on average, patients reported a 41% decrease in pain, and the median duration of pain reduction lasted for almost 2½ hours. Taste was acceptable and discomfort/burning with use was minimal. These findings are in contrast to typical complaints of taste and discomfort/burning associated with topical application of local anesthetics.
Anesth Analg 2006;103:465–70
Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy
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