By Monique Swiecichowski, BSN,RN,CCRC Alverno College Picture from Microsoft Clipart Click on arrow to move back a slide Click on arrow to move forward a slide Click on underlined arrow to return to beginning slide Click on house to return to topic page TOPICS Click on desired topic to go directly to content Word Role over underlined words for definitions or explanations V Click on V to see video depiction on YouTube. Sound is recommended. Exiting out of or minimizing YouTube video will return you to the slide you were on. *** Hint: ‘finger pointing hand’ must be visible when clicking for commands to work Objectives Identify the five biological phases of mucositis Identify at least three risk factors contributing to mucositis in cancer patients Be able to assess those cancer patients at risk for and with mucositis Identify at least three preventative measures and/or interventions of mucositis Identify at least four implications of mucositis to the cancer patient Case study Mr. M is a 72 year old African American man with newly diagnosed Stage III squamous cell carcinoma of the hypopharnyx. His treatment plan includes concurrent radiation and cisplatin. He states that he has not been to a doctor in ‘years’ and admits to smoking half a pack of cigarettes and drinking 3 beers a day. He has never been to the dentist. You note that he has a history of not showing for his appointments. Is Mr. M at risk for mucositis? What are his risk factors? What interventions might you offer Mr. M? If Mr. M experiences mucositis what are the five biological phases that will occur? You will be assessing Mr. M frequently, what will you be assessing and how might you consider documenting it? Why is it important to minimize Mr. M’s mucositis? TOPICS REVIEW PATHOBIOLOGY CAUSES and RISK FACTORS GENETICS ASSESS and DOCUMENT IMPLICATIONS INTERVENTIONS REFERENCES REVIEW layers of the oral mucosa ---Oral epithelium Stratified squamous cells ---Basement membrane------Lamina propia ------submucosa Loose connective tissue under epithelium containing capillaries and gland ducts Minor salivary glands, striated muscle, fat, fibroblasts, endothelial cells, nerves, and inflammatory cells Muscle or bone REVIEW Acute Inflammation Activation of macrophages, dendritic call, histocytes and mastocytes residing in endothelium Release of inflammatory mediators -Vasodilatation (rubor) -Heat (calor) -Permeability of blood vessels=exudation of plasma proteins/fluid into tissues (edema or tumor) -Sensitivity to pain (dolor) -Loss of function (functio laesa) necrotic loss of tissue=exposing lower layers=Ulcerative inflammation REVIEW affects of stress Cancer as a stressor Immune cells (monocytes and lymphocytes) Cytokines (cross the blood-brain barrier) Corticosteroid releasing factor Stress hormone activation (catecholamines, corticosteroids, growth hormone, glucagon, and renin) Neuroendocrinological pathways: (sympathetic nervous system, renin angiotensin system, hypothalamic pituitary axis) Acute phase response Acute phase proteins (inflammatory mediators) Black, 2002; Porth, 2009 REVIEW Definition Mucositis: refers to the inflammation of any mucosal membrane Stomatitis or oral mucositis: describes any inflammatory condition of oral tissue Not an inflammatory disorder PATHOBIOLOGY Historical belief of mucositis in cancer patients cytotoxic treatments kills rapidly dividing cells; cancerous and normal Current belief of mucositis in cancer patients series of simultaneous events beginning in the epithelium or submucosa and progressing to other tissue layers Working model of mucositis=5 phases I. Initiation II. Upregulation III. Signaling and Amplification IV. Ulceration V. Healing Sonis et al., 2004 Phase I: Initiation Chemotherapy (CT) or radiation (RT) exposure: Begins day 1 of treatment Begins in the submucosal endothelium Radiation will stimulate nuclear factor-kappaB NF-kB RT or CT causes direct damage to DNA resulting in cell death RT and CT generate reactive oxygen species (ROS) that damage lipids, DNA, connective tissue and cell membranes [stress response] Sonis et al., 2004; Sonis, 2007 Diagram used with permission by John Wiley and Sons Chemotherapy will stimulate Ceramide synthase Phase II: Upregulation days 1-3 Occurs in the epithelium and submucosa Multiple pathways resulting in damage NF-kB regulates the pro-inflammatory cytokines-that lead to an inflammatory response And promotes apoptosis direct damage to DNA by ROS Diagram used with permission by John Wiley and Sons Sonis et al., 2004; Sonis, 2007 Phase II: Upregulation (cont’d) Additional pathways resulting in damage Do you remember the previous Initiation Phase? Click for a reminder. fibronectin breakup leads to increased macrophages, and tissue damage or eventual apoptosis Damaged cell membranes stimulate sphingomyelinase Ceramide pathway signals cells to enter apoptosis (V1 ) Diagram used with permission by John Wiley and Sons Sonis et al., 2004; Sonis, 2007 V1: Alberts et al, 2002 Excessive apoptosis and/or decreased clearance of apoptotic cells induce secretion of other pro-inflammatory cytokines Gupta, 2006 Phase III: Signaling and Amplification Day 4-8 Pro-inflammatory cytokines= positive feedback loops re-initiating the damage response pathways Mucosal surface still appears clinically normal Do you remember the Initiation previous Phases? Upregulation Click for a reminder. NF-kB activates cyclooxygenase-2 (Cox-2) and produces prostaglandins resulting in inflammatory mediation and angiogenesis (V2) PROCESS (cont’d) TNF-Alpha activates NF- kB which activates more TNF **RT induced FEEDBACK LOOP** MMP degrades the extracellular matrix (ECM); ECM begins to swell with fluid (inflammatory response) Diagram used with permission by John Wiley and Sons Sonis et al., 2004; Sonis, 2007 V2: Alberts et al., 2009 Tumor Necrosis Factor (TNF)-alpha stimulates apoptosis and sphingomelinase **Chemo induced FEEDBACK LOOP** Phase IV: Ulceration Day 8-12 Cell death, reduced epithelial regeneration, and apoptosis thin the epithelium Characterized by inflammation and ulceration Do you remember I. Initiation theUpregulation previous II. Phases? Click& III. Signaling for a amplification reminder. Breakdown of mucosa=ulcers Bacteria penetrate the submucosa and stimulate macrophages to produce and release additional pro-inflammatory cytokines. Pro-inflammatory cytokines Diagram used with permission by John Wiley and Sons Sonis et al., 2004; Sonis, 2007 V3: http://www.youtube.com/watch?v=CmbWE3jLUgM V4: http://www.youtube.com/watch?v=uNG-jZxvhcg Stimulate inflammatory responses. Bacteria and debris are removed and factors are released to promote proliferation V3/ V4 Do you -Initiation remember -Upregulation the previous -Signaling phases? Click &amplification for a -Ulceration reminder. Phase V: Healing Day 12-21 Downregulation of the inflammatory response Signaling from extracellular matrix = epithelial proliferation and differentiation Epithelial cells multiply and migrate to close the ulcers Submucosal cells regenerate Increased risk of future injury with subsequent therapy Wound repair V5 V5: Alberts, 2009 Sonis et al., 2004; Sonis, 2007 Testing your knowledge Click on the letter box in each section below that corresponds to the correct phase of mucositis listed at the bottom. A B A B C D C D E F E F Pre treatment Phase I A.Upregulation A B C A B C A B C A B C D E F D E F D E F D E F Phase II B. Healing Phase III C. Signaling and Amplification F. Normal Diagram used with permission by Sonis, 2007 Phase IV D. Initiation Phase V E. Ulceration Now let’s apply it! Remember Mr. M? He is a 72 year old African American man with newly diagnosed Stage III squamous cell carcinoma of the hypopharnyx. His treatment plan includes concurrent radiation and cisplatin. Click on the right answer. Mr. M began his chemotherapy and radiation today. You True False don’t need to worry because it is too early for any pathobiological process to have begun. On Day 3 of Mr. M’s treatment, you suspect that there will be multiple damage response pathways resulting in damage. On Day 6, due to all the activity of TNF-alpha and the feedback loops in Phase III, you anticipate Mr. M will have sign of mucositis. When you see Mr. M on day 11 he might complain of a sore mouth. When you assess him chances are there might be signs of biological phase IV mucositis. If Mr. M develops mucositis, once it resolves. You expect that he will not be a risk with further therapy. True False True False True False True False RISK FACTORS #1 Causative risk is the cancer therapy being administered RADIATION-to the head and neck Conventional external beam (once a day) Hyperfractionated (twice a day) CHEMOTHERAPY- of any cancer type Thymide synthetase inhibitors: methotrexate Topoisomerase II inhibitors: Etoposide, irinotecan Pyrmidine analogs: cytarabine, 5-FU Alkylating agents: busulfan, melphalan, cytoxan, cisplatin Purine analogs: 6-MP Intercalating drugs: idarubicin, doxorubicin, daunorubicin Pictures from Microsoft Clipart BOTH or COMBINED MODALITIES-to the head and neck Chemosensitizer Niscola et al., 2007; Sonis, 2004 RISK FACTORS (cont’d) #2 Patient-related variables AGE Younger age is associated with more severe mucositis 3 higher basal cell proliferation rate4 greater epidermal growth factor receptors Older age may be at risk due to other factors Decreases salivary flow & increased prevalence of gingivitis poor oral health at baseline 2 Very old age (>70 year old) has also been associated with increased mucositis Diminished organ function 5 chronic inflammation process=elevated proinflammatory cytokines 1 Oxidative stress of aging=NF-kB activation 1 Elevated NF-kB=programmed cell death 1 1.Csiszar ,2008; 2. Niscola et al.,2007; 3.Sonis , 1998; 4. Treister & Woo, 2010; 5.Zalcberg , Kerr, Seymour, & Palmer, 1998 RISK FACTORS (cont’d) #2 Patient-related variables SALIVARY FUNCTION xerostomia predicts mucositis hyposalivation can be caused by anxiety/stress, medications, alcohol, depression, endocrine disorders, nerve damage from surgery, oxygen, dehydration, tobacco Obstructive nasal disease ORAL HEALTH Poor baseline oral status exacerbates mucositis ill-fitting prostheses or faulty restorations Pre-existing oral infections (viral or fungal) Dental disease Barasch & Peterson, 2003 RISK FACTORS GENETICS May explain why patients of the same age, treatment regimens, and equivalent oral health status vary in the incidence of mucositis Microsoft ClipArt deficiencies of enzymes due to polymorphisms = greater risk of mucositis variations in the metabolism of chemotherapy= different rates of mucositis variations in apoptotic activity = variations in risk Example: • psoriasis patients lack apoptosis of the skin; when treated for cancer= lower incidence of mucositis • Addison’s disease patients have excess apoptosis; cancer treatments= higher incidence of mucositis Sonis,2007 Mice with deficiency in the acidic sphingomyelase gene= increased resistance to mucositis Sonis et al., 2004 Testing your knowledge What are the risk actors associated with mucositis? Across 2. conventional external beam or hyperfractionated 4. young or old 5. ill-fitting dentures, gingivitis, caries, broken teeth 6. may cause variations in drug metabolizing enzymes and deficiencies in metabolizing enzymes Down 1. radiation with chemotherapy (chemosensitizer) 3. caused by medications, alcohol, tobacco, nerve damage from surgery, dehydration 7. antimetabolites, antitumor antibiotics, alkylating agents CLICK WHEN READY TO SEE ANSWERS Now let’s apply it! Mr. M’s treatment plan includes concurrent radiation and cisplatin. He states that he has never been to a dentist and admits to smoking half a pack of cigarettes and drinking 3 beers a day. Since his last visit he has established a primary care physician, was found to have hypertension and depression, and was placed on corresponding medications. What are Mr. M’s risk factors? (Click on the right answer) The radiation and cisplatin will put Mr. M at risk. True False Genetics will play a role in mucositis. True False Mr. M likely has excellent oral health so is not a risk for mucositis. True False Mr. M is too old to be at risk. True False True False Mr. M does not evidence any behaviors to be concerned about xerostomia. ASSESSMENT I. Pretreatment-stratify risk based on: treatment plan level of xerostomia list of prescribed and over-the-counter medications baseline oral hygiene II. Each visit: during treatment Examine the lips, tongue, and oral mucosa (after removing dental appliances): Color, moisture, integrity, cleanliness *Adequate illumination; halogen light sources provide consistent intensity and color Sonis et al., 2004 Assess for changes: in taste, voice, ability to swallow Examine the saliva: for amount and quality Assess oral pain (0-10 scale) Document all of the above Polovich , Whitford, & Olsen , 2009 Microsoft ClipArt DOCUMENTATION A wide variety of scales have been developed focusing on symptomatic and functional outcomes: World Health Organization (WHO)-Oral Mucositis Grade 0 1 2 3 4 Normal Oral soreness, erythema Ulcers but able to eat solids Oral ulcers and able to take liquids only Oral alimentatio n impossible 5 N/A Microsoft ClipArt National Cancer Institute Common Toxicity Criteria (NCI-CTC)-Oral Mucositis Grade 0 1 2 3 4 5 Clinical (version 3.0) Normal Erythema Patchy ulcerations or pseudomembranes Confluent ulcerations or pseudomembranes; bleeding with minor trauma Issue necrosis; significant spontaneous bleeding; lifethreatening consequences Death Functional (version 3.0) No symptoms Minimal symptoms, normal diet; minimal respiratory symptoms but not interfering with function Symptomatic but can eat and swallow modified diet; respiratory symptoms interfering with unction but not interfering with ADL Symptomatic and unable to adequately aliment or hydrate orally; respiratory symptoms interfering with ADL Symptoms associated with life-threatening consequences Death Asymptomatic or mild symptoms; intervention not indicated Moderate pain; no interfering with oral intake; modified diet indicated Severe pain; interfering with oral intake Lifethreatening consequences; urgent intervention indicated Death Version 4.0 DOCUMENTATION (cont’d) Another all inclusive Oral Assessment Guide 1 Ratings Category 2 3 Voice Normal Deeper or raspy Difficulty talking or painful Swallow Normal swallow Some pain on swallow Unable to swallow Lips Smooth and pink and moist Dry and cracked Ulcerated or bleeding Tongue Pink and moist and papillae present Coated or loss of papillae with a shiny appearance with or without redness Blistered or cracked Saliva Watery Thick or ropy Absent Mucous Membranes Pink and moist Reddened or coated (increased whiteness) without ulceration Ulcerations with or without bleeding Gingiva Pink and stippled and firm Edematous with or without redness Spontaneous bleeding or bleeding with pressure Clean and no debris Plaque or debris in localized areas (between teeth if present) Plaque or debris generalized along gum line or denture-bearing area Teeth or dentures or denture-bearing area Modified from the Oral Assessment Guide with permission by J. Eilers RN,MSN, UNIVERSITY OF NEBRASKA MEDICAL CENTER, 83 Rev 2-84, 5-84, 4-85, 11-85, 4-86 jeilers@nebraskamed.com Click here to see original Oral Assessment Guide with pictures The key is for all caregivers to consistently use an accepted grading scale throughout all patient’s treatments. Microsoft ClipArt ASSESSMENT AND DOCUMENTATION Let’s focus on the NCI-CTC version 3.0 Grade Clinical (version 3.0) Functional (version 3.0) 0 Normal No symptoms 1 Erythema Minimal symptoms, normal diet; minimal respiratory symptoms but not interfering with function 2 3 Patchy ulcerations or pseudomembranes Confluent ulcerations or Symptomatic but can eat and swallow modified diet; respiratory symptoms interfering with unction but not interfering with ADL Symptomatic and unable to adequately aliment or hydrate orally; respiratory symptoms interfering with ADL pseudomembrane- bleeding with minor trauma 4 5 Issue necrosis; significant spontaneous bleeding; lifethreatening consequences Death Symptoms associated with lifethreatening consequence Death Microsoft ClipArt This Changes scale is in thetaste most and used voice, in documenting amount and quality the assessment of saliva,of a oral pain.patient’s As well lips, as vital tongue signsand for oral signsmucosa. of infection and But what else should be assessed dehydration. and documented? (Click to find out.) ASSESSMENT AND DOCUMENTATION Grade 0 Grade 1 Normal/No symptoms Erythema/minimal symptoms, normal diet Grade 2 Patchy ulcerations or pseudomembranes/ symptomatic but can eat and swallow modified diet G 0 from Microsoft ClipArt/ G1-4 photos used with permission from EUSA Pharma @ www.caphosol.com/patients/oral-mucosiis/index.php Grade 3 Confluent ulcerations or pseudomembranes (contiguous patches > 1.5 cm in diameter)/Symptomatic and unable to adequately ailment or hydrate orally ASSESSMENT AND DOCUMENTATION (cont’d) Grade 4 Grade 5 DEATH (indirectly from mucositis: sepsis and other treatment related side effects) Tissues necrosis; significant spontaneous bleeding/symptoms associated with life-threatening consequences Testing your knowledge Grade 3 Pseudomembranes; bleeding with minor trauma Grade 0 Not mucositisHairy tongue: decreased salivary flow causes debris that is normally washed away by saliva builds up in the oral cavity. Grade 4 Tissue necrosis and spontaneous bleeding; life-threatening especially for bone marrow transplant patients and other immunosupressed patients Click on the picture of a: 1. Grade 0 mucositis 2. Grade 1 mucositis 3. Grade 2 mucositis 4. Grade 3 mucositis 5. Grade 4 mucositis Images reprinted with permission from Medscape.com, 2011. Available at: http//emedicine.medscape.com/article/1079570-overview Grade 2 or 3 Depending on extent and intake ability Grade 2 Can eat a modified diet Grade 1 Erythema: Eating a normal diet Now let’s apply it! Mr. M comes in and you assess him. He states that his mouth is sore. When asked about what he is eating he admits that he is not eating his usual fried chicken dinners due to pain but is able to eat the mashed potatoes, grits and apple sauce. He admits that they don’t taste the same. You notice that his voice is a bit raspy. When you check his oral mucosa you find this: Furthermore, you note that his lips are without erythema or lesions, his saliva is thick, there is food at his gum line, it takes a lot of effort for him to swallow, and when asked his pain level he ranks it at a 4/10. You would document: level of xerostomia ? oral hygiene?, taste ?, voice?, color of oral mucosa ? You would also indicate the grade of mucositis so as to gage his mucositis compared to past assessments and to aid in future assessments. Using the NCI-CTC Oral Mucosa Scale. What grade would you assess his mucositis to be? Oops this is not normal! Try again. 0 There is erythema, but there is more, Try again. 1 YES!! There is patchy pseudomembranes and symptoms: soreness, and soft diet 2 photo used with permission from EUSA Pharma @ www.caphosol.com/patients/oral-mucosiis/index.php Try again. He could bleed with trauma, but he is able to eat 3 No, not yet. The tissue is not necrotic and his symptoms are not lifethreatening 4 5 He is still alive!!! WHY IS IT IMPORTANT? AFFECTS PATIENT OUTCOMES Decreases the efficacy of RT, chemotherapy, and chemo/RT Studies have shown: -treatment breaks in RT were predictive of local recurrence and overall survival in locally advanced head and neck patients. -treatment breaks were associated with higher rates of first relapse, rate of failure in the chest, and rate of failure in the brain for limited small-cell lung cancer patients -chemotherapy dose reductions in breast cancer patients result in a higher recurrence rate Studies indicate this is due to: -Tumor growth during the breaks -a dose-response threshold; increases in the dose are needed for tumor control Rosenthal, 2007 IMPLICATIONS PAIN “…reported as the most distressing symptom by patients receiving treatment for head and neck cancer...” Harris (2006, p.252) Domino affect: PAIN Reduced oral intake If severe enough requires opiods Keefe et al., 2007 Weight Loss/Malnutrition Fatigue Death IMPLICATIONS (cont’d) INFECTION Ulceration Compromise of mucosal barrier Local invasion of colonizing microorganisms Local infection: Streptococcal/candida/reactivation of HSV-1 Systemic infection: sepsis, bacteremia, and systemic fungal infection IMPLICATIONS (cont’d) ECONOMIC IMPACT Ulceration Local infection Systemic infection IV antibiotics Reduced oral intake Pain IV opiods ?Hospitalization? Malnutrition/dehydration TPN/feeding tube ECONOMIC IMPACT •Study of 75 patients treated for head and neck cancer 78% of opiods prescribed were for pain of the mouth and throat 51% had a feeding tube placed 30% were hospitalized due to mucositis (length of stay= 4.9 days) Average cost for a 5-day hospitalization=$23,000 Isitt et al., 2007 •Study of bone marrow transplant patients in US, Canada, and Europe + correlation between severity of mucositis, # days of injectable narcotics, TPN, and injectable antibiotics Hospital costs were $43,000 higher for patients with ulcerations than those without Papas et al., 2003 IMPLICATIONS (cont’d) NUTRITION/HYDRATION Mucositis Oral intake Malnutrition/dehydration DECREASED QUALITY OF LIFE NON-COMPLIANCE to THERAPY may not show for treatments may not take oral chemotherapeutics Testing your knowledge Which of the following implications of severe mucositis could affect our patient Mr. M? (Click on the best answer.) Severe mucositis would not affect M. M’s quality of life. True False True False True False Severe mucositis would not have any nutritional implications. True False Severe mucositis could place significant financial burden on Mr. M. True False Treatment breaks due to toxicity might affect his cancer outcomes and compliance to therapy. Infections are a very real issue with severe mucositis. INTERVENTIONS Before therapy begins Evidenced-based Comprehensive oral/dental consult Oral cleaning Removal of excess plaque Treatment of all dental caries Extraction of teeth with poor prognosis Check prosthesis fit Consider a fluoride tray Bhatt et al., 2010; Bensinger, 2008 Microsoft clipart Patient education Mouth care Floss once a day Brush w/soft-bristle toothbrush for 90 seconds 3 times a day Use fluoride toothpaste Rinse w/bland (non-alcohol based) rinse Keep lips lubricated Harris, 2006 Recommended intake Drink 1-3 liters of fluid a day Maintain nutrition; emphasize intake of high protein foods Eat non-acidic fruits (banana, mango, melon, peach) Avoid Smoking Rough hard foods Acidic foods (grapefruit, lemon, orange, tomatoes) Alcohol Alcohol-containing and highly flavored oral products Microsoft clipart Strohl & Camp-Sorrell , 2006 INTERVENTIONS: cont’d During therapy Evidenced-based Nursing interventions Microsoft clipart Likely to be effective Cryotherapy: ice chips 30 minutes prior and during melphalan and bolus 5-FU (agents with short half-life); local vasoconstriction Normal saline (with or without baking soda) mouthwash: 30 ml swish 30 seconds and spit after meals and bedtime; removes debris without compromising healing Eaton, 2009; Besinger, 2008 Effectiveness not established Raw honey: 20ml honey applied 15 min before and 15 min after radiation & 6 hrs later; active enzymes have antimicrobial properties Eaton, 2009; Khanal et al, 2010; Rashad et al, 2008 Fluoride chewing gum: chew 5 pieces x 20 minutes each every day; increases salivary flow Eaton, 2009 Patient Education Change tooth brush q month or with each chemo cycle (Plt <50K and WBC <1,000 use moistened gauze sponge) Rinse w/saline mouthwash after meals and a bedtime Salt/sodium bicarbonate: 1 part salt/1-2 parts baking soda mix ½-1 tsp dry mix in 1 cup water Use fluoride mouth rinse, tray, or toothpaste daily Re-enforce what to avoid and recommendations for intake NOTIFY PROVIDER WITH ANY SIGNS AND SYMPTOMS Polovich, Whitford & Olsen, 2009 Per NCCN Guidelines: “Adequate patient education and communication between the patient and all members of the cancer care team are critical, particularly since nursing staff…interact with the patient more frequently than the physician” Besinger, (2008, p. 17). Microsoft clipart INTERVENTIONS During therapy Prevention/reduce severity Likely to be effective (medical interventions) Palifermin- IV bolus (for high dose chemotherapy/Bone Marrow Transplant) Mid-line radiation blocks and conformal radiotherapy(CRT) or (3D) CRT Benzydamine- mouhwash for head and neck radiation patients (In the NCCN guidelines but not available in the US) Gelclair (EKR Therapeutics, Inc)-mix product w/2-3 T water, swish for 1 minute and spit, 3x a day. Recommended to not eat or drink or 1 hour after use. (Approved as a medical device for oral mucositis; Not a NCCN recommended treatment and conflicting ONS recommendations) Eaton, 2009 & Polovich, Whitford & Olsen, 2009 Low-level laser therapy (LLLT); not generally used due to cost Bensinger, 2008 INTERVENTIONS During therapy Prevention Unlikely to be effective Oral aloe vera Pilocarpine Oral povidone-iodine Iseganan Misopostol Topical vitamin E Flurbiprofen tooth patch G-CSF IM Immunoglobulin Wobe-mugos E Amifostine for mucositis has not been determined Eaton, 2009 & Bensinger, 2008 Prevention Not recommended for Practice GM-CSF mouthwash Sucralfate Antimicrobial lozenges Hydrogen peroxide Chlorhexidine INTERVENTIONS Review (click on box to review) Oral cleaning Removal of excess plaque Treatment of cavities DENTAL CARE Pull teeth as needed Check fit of dentures and partials EDUCATION NURSING Cryotherapy Mouth rinses INTERVENTIONS Honey? Mouth care Recommended intake PATIENT Food, behaviors, and products EDUCATION to avoid Palifermin MEDICAL CRT or 3D-CRT LLLT INTERVENTIONS Gelclair? Pain Management Nociceptive pain: -mediated by C fibers relieved w/opioids Other strategies-Cox-2 inhibitors, NSAIDS, gabapentin Harris, 2006 Microsoft clipart Incidental pain: -caused by movement and contact -mediated by A-8 fibers Only effective treatment is “functional exclusion of the anatomic parts” Niscola et al. (2007, p.226) Temporary relief strategies Magic mouthwash: 15ml swish and spit QID (however, little evidence to support) Eaton, 2009 Various lidocaine/xylocaine rinses (not recommended due to compromise of the gag reflex and possibility of incidental injury when numb) Besinger, 2008 Xerostomia Management Frequent fluid intake Artificial saliva (i.e. Biotene, Oasis) Sucrose-free lemon drops Caphosol mouthwash (EUSA Pharma, Inc): prescription ‘supersaturated’ (with calcium and phosphate ions) mouthwash Not listed in current ONS or NCCN guidelines Eaton, 2009 & Strohl, 2006 Microsoft clipart Testing your knowledge Which of the following is the most important nursing intervention for a patient at high risk for mucositis? Click on the correct response. Indeed, this is very important as therapy will affect salivary function and it’s role in mucosal protection. But what else? Xerostomia management Right, patients at significant risk, such as head and neck cancer patients should be assessed and treated by a dental professional prior to initiating cancer therapy. What else? Dental exam Yes, oral hygiene is extremely important before and during therapy. What else? Re-enforce oral hygiene Although there are non-prescriptive therapies that nurses can offer such as cryotherapy, normal saline mouthwash, pushing fluids is there anything that encompasses more? YES!!!!! Patients and families need to understand the importance of oral hygiene , ways to reduce their risk of xerostomia and mucositis, s/s oral inflammation, and the importance of notifying providers of s/s Very important for quality of life and although nursing is important for assessing pain at onset most treatments involve prescribe medications. Anything else? Patient education Preventative therapies Pain management Now let’s apply it! Let’s review. Mr. M is your 72 year old patient with head and neck cancer. His treatment included concurrent radiation and cisplatin. At treatment onset, he admitted to smoking half a pack of cigarettes and drinking 3 beers a day. He had never been to the dentist. During treatment he was placed on hypertensive and antidepressant medications. You assessed him with a Grade 2 mucositis. What have been your interventions? YES NO YES NO Activated the preventative measures of normal Saline mouthwash, honey, cryotherapy and GM-CSF mouthwash? YES NO Xerostomia management including oral fluids, oral moisturizers, and sugar free lemon drops? YES NO Pain assessment and management such as topical swish and spit medications? YES Assisted Mr. M in making a dental appointment? Educated Mr. M on oral hygiene, foods to avoid and those to try, tobacco cessation, alcohol avoidance? NO Microsoft clipart Thank you for viewing this tutorial For questions or comments: swiecime@alverno.edu • Alberts, Bray, Hopkin, Johnson, Lewis, Raff, Roberts, Walter, (2009). Essential cell biology, 3rd edition: angiogenesis. from http://www.youtube.com/watch?v=7YgwJeVEgvU • Alberts, Johnson, Lewis, Raff, Roberts, Walters, 2002. Molecular biology of the cell, 4th edition: apoptosis. From http://www.youtube.com/watch?v=witLM--V2v8 • Alberts, Johnson, Lewis, Raff, Roberts, Walters, 2002. Molecular biology of the cell, 4th edition: wound healing. From http://www.youtube.com/watch?v=pn2TOGqHMrI • Barasch, A., & Peterson, D. (2003). Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions. Oral Oncology 39, 91-100. • Bensinger, W., Schubert, M., Ang, K., Brizel, D., Brown, E., Eilers, J., Elting, L., Mittal, B., Schattner, M., Spielberger, R., Treister, N., & Troti, A. (2008). NCCN task force report: prevention and management of mucositis in cancer care. Journal of the National Comprehensive Cancer Network 6 [supplement 1]. • Bhatt, V., Vendrell, N., Nau, K., Crumb, D., & Roy, V. (2010). Implementation of a standardized protocol for prevention and management of oral mucositis in patients undergoing hematopoietic cell transplantation. Journal of Pharmacy Practice, 16, 195-204. • Black, P. (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain, Behavior, and Immunity, 16, (6):622-53. • Chung, Y., Lee, M., & Pui, N., (2009). Epigenetic therapy using the histone deacetylase inhibitor for increasing therapeutic gain in oral cancer: prevention of radiation-induced oral mucositis and inhibition of chemical- induced carcinogenesis. Carcinogenesis 30 (8), 1387-1397. • Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (2003)and 4.0 (2010). DCD, NIH, NCI, DHHS. http://ctep.cancer.gov. • Csiszar, A., Wang, M., Lakata, E., & Ungvari (2008). Inflammation and endothelial dysfunction during aging: role o f NF-kB. Journal of Applied Physiology 105: 1333-1341. • Eaton, L. & Tipton, J. (Eds.) (2009). Putting Evidence into Practice-Improving Oncology Patient Outcomes. Pittsburgh, Pennsylvania: ONS • Gupta, S., Agrawal, A., Agrawal, S., Gollapudi, H, & Gollapudi, S. (2006) . A paradox of immunodeficiency in human aging: lessons learned from apoptosis. Immunity and Aging. 3 (5). doi:10.1186/1742-4933-3-5. • Harris, D. (2006). Cancer treatment-induced mucositis pain: strategies for assessment and management. Therapeutics and Clinical Risk Management 2(3), 251-258. • Isitt, J., Murphy, A., Beaumont, J., Garden, A., Gwede, C., Trotti, A., Meredith, R., Epstein, J., Brizel, D., Bellm, L., Wells, N., & Cella, D. (2007). Oral Mucositis-related morbidity and resource utilization in a prospective study of head and neck cancer patients. The Journal of Supportive Oncology 5 (4) [supplement 2], 54-55. • Keefe, D., Schubert, M., Elting, L., Sonis, S., Epstein, J., Raber-Durlacher, J., Migliorati, C., McGuire, D., Hutchins, R., & Peterson, D. (2007). Updated clinical practice guidelines for prevention and treatment of mucositis. Cancer 109(5), 820-831. • Khanal, B., Baliga, N., Uppal, N. (2010). Effect of topical honey on limitation of radiation-induced oral mucositis: an intervention study. International Journal of Oral & Maxillofocal Surgery 39 (12), 1181-1185. • Niscola, P., Romani, Cupelli, L., Scaramucci, L., Tendas, A., Dentamaro, T., Amadori, S., & de Fabritiis, P. (2007). Mucositis in patients with hematologic malignancies: an overview. Haemtologica 92, (2), 222-231. doi:10.3324/haematol.10232 • Papas, A., Clark, R., Martuscelli, G., O’Loughlin, K., Johansen, E., Miller, K. (2003). A prospective, randomized trial or the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplantation. 00, 1-8. Doi:10.1038/sj.bm.1703870 • Polovich, M. Whitford, J., Olsen, M. (Eds.) (2009). Chemotherapy and Biotherapy Guidelines and recommendations for Practice. (3rd ed.). Pittsburgh, Pennsylvania: ONS, 163-182. • Porth, C. & Matfin, G. (2009) Pathophysiology: concepts of altered health states. Philadelphia, PA: Lippincot Williams & Wilkins. • Rashad, U., Al-Gezawy, S., El-Gezawy, E., Azzaz, A. (2009). Honey as topical prophylaxis against radiotherapy-induced mucositis in head and neck cancer. The Journal of Laryngology & Otology, 123(2), 223-228. • Rosenthal, D. (2007). Consequences of mucositis-induced treatment breaks and dose reductions on head and neck cancer treatment outcomes. The Journal of Supportive Oncology 5,(9) [supplement 4],23-31. • Sonis, S. (2004). Oral mucositis in cancer therapy. The Journal of Supportive Oncology, 3(3), 3-8. • Sonis, S., Elting, L., Keefe, D., Peterson, D., Schubert, M., Hauer-Jensen, M., Bekele, N.B., Raber-Durlacher, J., Donnelly, J.P., & Rubenstein, E. (2004). Perspectives on cancer therapy-induced mucosal injury. Cancer Supplement 100(9), 1995-2025. • Sonis, S. (2007). Pathobiology of oral mucositis: novel insights and opportunities. The Journal of Supportive Oncology 5(9, supplement 4), 3-11. • Sonis, S. (1998) Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatoxicity. Oral Oncology 34, 39-43. • Strohl, R., & Camp-Sorrell, D., (2006). Stomatitis/xerostomia. In Camp-Sorrell, D., & Hawkins, R. (Eds.) Clinical Manual for the Oncology Advanced Practice Nurse.. (2nd ed.), 73-77. Pittsburgh, Pennsylvania: ONS • Treister, N. & Woo, S-B. Chemotherapy-induced oral mucositis. http://emedicine.medscape.com/article/1079570 • World Health Organization (1979). WHO handbook for reporting the results of cancer treatment. http://whqlibdoc.who.int/publications/9241700483.pdf • Zalcberg, J., Kerr, D., Seymour, L., & Palmer, M.(1998) Haematological and non-haematological toxicity after 5-fluorouracil and leucovorin in patients with advanced colorectal cancer is significantly associated with gender, increasing age and cycle number. European Journal of Cancer 34, (12), 1871-1875.