Mucositis

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Mucositis is a painful inflammation and ulceration of the mucous membranes lining the gastrointestinal tract, usually as a detrimental effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal tract (GI), but oral mucositis refers to certain inflammation and ulceration occurring in the mouth. Oral mucositis is a common and often debilitating complication of cancer treatment.

Oral and gastrointestinal (GI) mucositis affects almost all patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT), 80% of patients with head and neck malignancy receive radiotherapy, and various patients receiving chemotherapy. Alimentary tract mucositis increases mortality and morbidity and contributes to increased health care costs.

For most cancer treatments, about 5-15% of patients experience mucositis. However, with 5-fluorouracil (5-FU), up to 40% get mucositis, and 10-15% get 3-4 levels of oral mucositis. Irinotecan is associated with severe GI mucositis in more than 20% of patients. Seventy-five to eighty percent of bone marrow transplant recipients experience mucositis, in which oral mucositis is the most common and most debilitating, especially when the melfalan is used. In grade 3 oral mucositis, patients can not eat solid foods, and in grade 4, patients can not consume fluids as well.

Radiotherapy to the head and neck or to the pelvis or stomach is associated with oral mucositis of grade 3 and grade 4 or GI, respectively, often exceeding 50% of patients. Among patients undergoing head and neck radiotherapy, pain and decreased oral function may persist after the conclusion of therapy. The fractional radiation dose increases the risk of mucositis becoming & gt; 70% of patients in most trials. Oral mucositis is very deep and prolonged among HSCT recipients who receive total body irradiation.

Video Mucositis

Signs and symptoms

Cancer patients undergoing chemotherapy usually become symptoms four to five days after starting treatment, peaking around the 10th day, and then slowly improving for several weeks. Radiotherapy-associated mucosa usually appears at the end of the second week of treatment and may last six to eight weeks.

As a result of cell death as a reaction to chemotherapy or radio therapy, the mucosal layer of the mouth becomes thin, can peel and then become red, inflamed and ulcerated. The ulcer may be covered by a yellowish white fibrin clot called a pseudomembrane. Peripheral erythema is usually present. Ulcer can range from 0.5 cm to more than 4 cm. Oral mucositis can be very painful. The degree of pain is usually associated with a degree of tissue damage. Pain is often described as a burning sensation accompanied by flushing. Because of the pain, the patient may have difficulty speaking, eating, or even opening his mouth.

Dysgeusia, or a change in taste perception, is common, especially for those who receive concurrent radiation therapy to the neck and mouth areas. The "feeling of blindness", or the taste of a changed appetite, is a temporary condition that occurs because of the effects on the taste buds that are mostly on the tongue. Sometimes, only partial taste recovery occurs. Common complaints are foods that are too sweet or too bitter or the taste of metal is continuous.

Complications

Injury or ulceration can be infected by viruses, bacteria or fungi. Pain and loss of taste perception make it more difficult to eat, leading to weight loss. Ulcers may act as sites for local infections and incoming portals for oral flora which, in some cases, can cause septicemia (especially in immunosuppressive patients). Therefore, oral mucositis may be a dose-limiting condition, interfere with optimal patient cancer care plans and consequently decrease their chances for survival.

Maps Mucositis

Pathophysiology

The pathophysiology of mucositis is complex and multifactorial. Currently, the five-phase Sonis model is an accepted explanation for the process. 5 stages are:

1. Initiation phase. Free radicals are produced because of DNA damage caused by chemotherapy or radiotherapy.
2. Main damage response. Chemotherapy, radiotherapy and free radicals all contribute to the activation of transcription factors, such as NF-? B. This results in increased regulation of pro-inflammatory cytokines, ceramides, nitric oxide and metalloproteinase matrices. The consequence of this is the destruction of the mucosa, caused by epithelial depletion due to tissue injury and cell death.
3. Signal amplification. Positive or negative feedback loops involving multiple molecules in the previous phase may worsen or prolong a tissue injury. For example, TNF proinflammatory cytokines? can give positive feedback on NF-K? thus inducing the production of pro-inflammatory cytokines.
4. Ulceration. Bacteria colonize ulcers and their cell wall products infiltrate submucosa. This leads to tissue macrophage activation, leading to further production of pro-inflammatory cytokines. In addition, bacterial mediated immunity through Toll-like receptors indirectly forms genotoxic damage induced by chemotherapy in the gastrointestinal tract.
5. Healing. Signaling of the extracellular matrix of submucosa results in epithelial proliferation and differentiation, and thus epithelial thickening. Local oral flora is restored.

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Diagnosis

The diagnosis is based on the patient's symptoms and the appearance of the mouth tissue after chemotherapy, bone marrow transplant or radiotherapy. Wounds such as red sores or ulcers throughout the mouth are sufficient to diagnose mucositis.

The severity of oral mucositis can be evaluated using several different assessment tools. The two most commonly used are the Oral Toxicity Scores of the World Health Organization (WHO) and the National Cancer General Toxicity Criteria (NCI-CTC) for Oral Mucosa. While the NCI system has separate scores for appearance (erythema and ulceration) and function (pain and ability to eat solid, fluid, or non-mouth foods), WHO scores combine both elements into a single score that assesses the severity of the condition from 0 ( no oral mucositis) up to 4 (swallowing is not possible so the patient needs additional nutrition). Another scale developed in 1999, the Mucositis Oral Measurement Scale (OMAS) has been shown to be highly reproducible between observers, responsive over time, and accurate in recording symptoms associated with mucositis. The OMAS provides an objective assessment of oral mucositis based on appearance and redness and ulceration assessments in different areas of the mouth.

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Prevention

The 2015 Cochrane systematic review rate of prevention of oral mucositis induced by chemotherapy concluded that oral cryotherapy leads to a substantial reduction in the incidence of oral mucositis all severity in adults receiving 5-FU treatment for solid cancer. The evidence also suggests reduction of oral mucositis in adults receiving high-dose melophalan-based cancer treatment prior to hematopoietic stem cell transplantation, although there is uncertainty about the size of the reduction in this regard. No evidence was found for the use of these precautions in children. Oral cryotherapy involves placing iced chips in the mouth, which cools the tissues of the mouth and causes vasoconstriction. This reduces blood flow to the area and, therefore, also limits the amount of chemotherapy drugs delivered to the tissues.

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Treatment

Treatment of mucositis is mainly supportive. Oral hygiene is the mainstay of care; patients are encouraged to clean their mouths every four hours and at bedtime, more often if the mucositis becomes worse.

The water-soluble jelly can be used to lubricate the mouth. Salt saliva can soothe pain and keep food particles in order to avoid infection. Patients are also encouraged to drink plenty of fluids, at least three liters a day, and avoid alcohol. Citrus fruits, alcohol, and hot foods are all known to aggravate mucositis lesions. Medication gargle can be used such as Chlorhexidine gluconate and Lidocaine thick for pain relief. However, care should be taken as high doses of my thick lidocaine cause adverse effects. A study reported that lidocaine has potential toxicity; when tested in patients with oral mucositis undergoing bone marrow transplantation, a lidocaine anesthetic mouthwash was found to be systemically absorbed.

Palifermin is a human KGF (keratinocyte growth factor) that has been shown to increase the proliferation of epithelial cells, differentiation, and migration. Experimental therapy has been reported, including the use of cytokines and other inflammatory modifiers (eg, IL-1, IL-11, TGF-beta3), amino acid supplementation (eg glutamine), vitamins, colony-stimulating factors, cryotherapy, and laser therapy.

Relieve the symptoms of oral mucositis pain can be given by barrier protective agents such as concentrated oral gel products (eg Gelclair). Caphosol is a mouthwash that has been shown to prevent and treat oral mucositis caused by high-dose radiation and chemotherapy. MuGard is an FDA mucoadhesive oral protective device developed by Access Pharmaceuticals, Inc., designed to form a protective layer of hydrogel over the oral mucosa while patients undergo chemotherapy and/or radiotherapy cancer treatment to the head and neck. In addition, MuGard's efficacy for the prevention or treatment of mucositis has been tested by prospective, randomized clinical trials in which 43% of head and neck cancer patients who used MuGard prophylactically never received oral mucositis. NeutraSal is an FDA-frozen calcium phosphate cleanser that has been shown in an open label, an observational registry test to prevent and reduce the severity of oral mucositis caused by high-dose radiation and chemotherapy. In the trial, 56% of radiotherapy patients reported 0 (WHO score) or no mucositis, which was significantly lower than historical levels. Other super saturated calcium phosphate levels on the market and cleared by the FDA are SalivaMAX based in the US. The Mayo Clinic has been testing doxepin antidepressants in mouthwash to help treat the symptoms.

In 2011, the FDA cleansed oral episil fluid for management and eliminates the pain of oral lesions with a variety of etiologies, including oral mucositis/stomatitis that may be caused by chemotherapy or radiation therapy. The transformative mechanism of action of episodes creates a lipid membrane that is mechanically bound to the oral mucosa to coat and alleviate inflammation and ulceration, and injure painful lesions. In a multicenter, randomized, double-blind, single-dose study involving 38 head and neck cancer patients with oral mucositis (WHO grade 2-3) who underwent radiation therapy, clinically episodes showed rapid acute relief that lasted up to 8 hours. Episil oral fluid is marketed in the US by Cangene.

In a 2012 randomized controlled pilot study involving pediatric patients, topical application of honey was found to reduce recovery time compared to benzocaine gel in grade 2 and 3 chemotherapy-induced chemotherapy-induced mucositis chemotherapy to a statistically significant level. In grade 3 oral mucositis, honey is as effective as a mixture of honey, olive oil and propolis, while both treatments are found to reduce recovery time compared to benzocaine control.

Clinical studies are under way in oral mucositis. A recent 2-phase exploratory trial in oral mucositis reported that dusquetide, a unique innate immune modulator with mechanisms that potentially overcome each of the pathophysiology phases of OM, was able to reduce the duration of severe oral mucositis, as well as reduce the incidence of infection. Dusquetide is being developed by Soligenix, Inc.

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See also

• Stomatitis

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References

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Common sources

• Mucositis Resource Center Study Group MOCALIS MASCC/ISOO. Medical journal articles, guidelines, recommendations, and slides and videos from conference presentations.
• Oral British Mucositis in Cancer Group. Guidance and support for oral care in cancer and palliative care. Educational materials, events, articles, and resources.

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External links

Source of the article : Wikipedia