Sunday, March 3, 2024

How To Stimulate Salivary Glands After Radiation

Quantification Of Amylase Protein

Tissue Engineering to Restore Salivary Function

The collected saliva samples from day 30 were evaluated for total amylase protein using the Bio-Rad Experion System . Samples were loaded into a primed Experion Chip and run using the Experion Software Protein260 Assay. Proteins of different molecular weights were visualized as bands in each sample. Analysis was done from bands located at or around the molecular weight of amylase . Percent total amylase was calculated using the Experion software and graphed for each treatment group.

Tips For Protecting Your Teeth

  • Have regular check-ups with a dentist or dental hygienist every 3 to 6 months.
  • Use fluoride products prescribed by your dentist.
  • Only have sugary and acidic foods and drinks at mealtimes.
  • Follow a mouth care routine agreed with your dentist or hygienist.
  • Check your mouth daily for ulcers, signs of tooth decay or red, white or dark patches. When you have a dry mouth, decay often happens at the top or bottom of the tooth near the gum line.
  • If you notice a change in your mouth or teeth, do not wait for your regular check-up. Go and see your dentist immediately.

Using fluoride

Your dentist or dental hygienist will advise you on how to brush your teeth and keep your gums healthy. They may also prescribe fluoride. This strengthens the hard, outer layer on your teeth and helps protect them from decay. It can alsohelp reduce tooth sensitivity.

You can get toothpastes, mouthwashes and artificial saliva products with added fluoride. The highest fluoride toothpastes are Colgate Duraphat® 2800ppm and Colgate Duraphat® 5000ppm. These have to be prescribed, soask your dentist or doctor.

Your dentist may also recommend:

  • wearing mouth guards containing fluoride overnight
  • having fluoride painted on your teeth once every three months.

Cutting down on sugary and acidic foods and drinks

Here are some tips that might help:

Brushing your teeth

Here are some tips on brushing your teeth:

Managing Problems With Swallowing

Having trouble swallowing is called dysphagia . Your healthcare team will work with you to help you manage dysphagia. This team includes your doctors, nurses, a swallowing specialist, and a clinical dietitian nutritionist.

Youll see a swallowing specialist before, during, and after your treatment. They will:

  • Explain how treatment can affect your swallowing.
  • Teach you exercises to stretch and strengthen the muscles involved in swallowing.
  • Look for any changes in your ability to swallow as you go through radiation therapy.
  • Help you keep your ability to swallow after your treatment is done to prevent long-term or late-onset changes.

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The National Institutes Of Health Consensus Conference

As two decades had passed since the abovementioned conference, in 2009 the NIH held a second conference to update the community regarding current strategies and future research directions related to oral complications of emerging cancer therapies. Part of this conference was to critically review the long-term consequences of head neck radiotherapy for salivary gland hypofunction and xerostomia. The consensus reported in this paper is a compilation of recommendations from the 2009 conference, updated to 2019, and more recent systematic reviews of the literature providing prevalence, impact on quality of life, and management strategies of salivary gland hypofunction and xerostomia induced by cancer therapies . Three key research questions were addressed:

Can radiation injury of salivary gland tissue be prevented?

  • If radiation injury of salivary gland tissue has occurred, what is then the most effective method to alleviate the resulting problems?

  • Can radiation damage of salivary gland tissue be restored?

  • Rebuilding The Salivary Gland After Radiation

    Xerostomia (Dry Mouth)

    by Christina Hueschen, University of California, San Francisco

    Patients who undergo radiation therapy for head and neck cancers often lose the ability to produce saliva because radiation destroys salivary glands that lie in the way of the tumor.

    The damage to humans’ glands is permanent, but another species has the ability to rebuild the organ within two weeks of an injury.

    In experiments in mice, when radiation destroys saliva-producing structures called acini, the animals’ stem cells divide and differentiate into acinar cells to rebuild the salivary gland.

    Noel Cruz-Pacheco, MS, a staff research associate in UC San Francisco’s Department of Cell and Tissue Biology, and his colleagues in the lab of Sarah Knox, PhD, want to know what triggers mouse salivary stem cells to repopulate acini.

    To watch the repopulation process, Cruz-Pacheco inserted a fluorescent marker into the genome of salivary stem cells, visually labeling them and their progeny. This strategy, called lineage tracing, allows scientists to follow along as generations of a cellular family grow and spread across a tissue.

    The resulting image shows a section of a healthy mouse salivary gland with acinar cells labeled in green. The same image has pink-labeled cells, which are ductal cells that channel saliva from the acinar cells into the mouse’s mouth.

    Cruz-Pacheco hopes that their research will one day enable the development of stem cell therapies for gland regeneration in human patients.

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    Why Was This Study Needed

    Every day in the UK, 31 people are diagnosed with a type of head and neck cancer. Radiotherapy, a common treatment, often causes dry mouth. This can lead to mouth discomfort, a change in taste, dental disease and problems speaking, chewing and swallowing.

    Several treatments are available. Chewing gum and sucking sweets or ice are thought to stimulate saliva production. Artificial saliva can be given as a lozenge, spray or gel. Drugs, such as pilocarpine, have been available to stimulate saliva production for many years but can cause side effects including sweating, blurred vision and nausea.

    This review aimed to systematically compare all available treatments for a dry mouth and reduced salivation after radiotherapy for head and neck cancer.

    Restoring The Flow Of Precious Saliva

    IRP Researchers Aim to Regenerate Damaged Salivary Glands

    By Melissa Glim

    Friday, March 18, 2022

    IRP researchers are working on ways to restore natural saliva production in patients whose salivary glands have been damaged by autoimmune illnesses or radiation treatment for cancer.

    Its easy to take our saliva for granted. Most people have so much of it that they think nothing of spitting it out into a trash can when they finish chewing a stick of gum. Perhaps only people who have lived without it truly understand the great gift that is a perpetually moist mouth.

    Persistent dry mouth causes lots of problems with quality of life, and people forget how important saliva is until they lose it, says IRP senior investigator Matthew Hoffman, B.D.S., Ph.D.

    In honor of World Oral Health Day on March 20, a celebration of scientific efforts to reduce the burden of oral disease, I talked with Dr. Hoffman about his labs efforts to understand the biology of salivary gland dysfunction and translate that knowledge into treatments that bring relief to the many people suffering from it.

    Genetic abnormalities, radiation therapy for cancer, and certain autoimmune diseases can cause the salivary glands to degrade or reduce their output, leading to chronic dry mouth, or xerostomia. The condition is not only uncomfortable, but it can make tasting, chewing, and swallowing food difficult. It can also increase bacterial growth in the mouth, which leads to dental disease and infections.


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    How Cancer And Radiation Therapy Can Affect Swallowing

    Depending on the tumors size and location, your radiation therapy may weaken the muscles and structures that help you swallow. It can also keep them from working as well as they did before you started radiation therapy. This can make it harder to eat and drink normally.

    Radiation therapy can cause:

    These symptoms usually start 1 to 2 weeks after you start radiation therapy. They may get worse during treatment. Most symptoms will start to get better about 2 to 4 weeks after you finish treatment.

    Radiation therapy can also cause permanent tissue scarring. The effects of this scarring depend on the area that was treated. Some effects of scarring are listed below.

    • The muscles attached to your jaw may tighten and make it hard to open your mouth and chew your food. This is called trismus.
    • Your salivary glands may not make enough saliva. This can make it hard to swallow because your mouth is too dry.
    • The muscles in your tongue and the back of your throat may not be able to move as well. This can make it harder to push food or liquids down your throat and open up your esophagus.
    • The muscles that help protect your airway when you swallow may get weaker. They may not be strong enough to keep foods or liquids from going down your airway.
    • Your esophagus may narrow. This can cause food to get stuck in the back of your throat.

    Assessing The Morphology Of Salivary Glands

    Neutron radiation therapy for salivary gland cancer

    In the 1980’s, computed tomography was commonly used to image salivary glands, which was effective to demonstrate duct calculi, diffuse sialectasis, and enlarged lymph nodes . To avoid radiation dose to patient, non-invasive imaging modalities such as magnetic resonance imaging and ultrasound imaging have been introduced. These two imaging modalities can visualize changes in terms of gland location, appearance and density as well as the salivary glands function in the case of MRI. Moreover, MRI and UI are prominent modalities in providing detailed image of soft tissue, which is another advantage over CT.

    Another imaging technique for ductal condition of main salivary gland assessment is sialography which employs the use of contrast injection and radiographic technology. It is useful to detect blockage of the salivary ducts. During the procedure, the patient is instructed to hold the catheter which is placed at the opening of salivary duct, through which the contrast agent is injected, followed by the imaging of the gland by x-ray. Recently, more advanced imaging using MRI has been introduced instead of x-ray to provide 3-dimensional images of the salivary glands in post-radiotherapy patients .

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    Potential Restoration Of Salivary Gland Function Following Radiation Injury

    Currently, there is no clinical treatment option for restoration of salivary gland function lost due to irradiation. However, promising approaches, such as gene therapy, stem cell transfer, and pharmacologic agents, are aimed at regaining function after radiotherapy.

    Gene Therapy

    Stem Cell Therapy

    Pharmacological Approaches to Restoration

    What Can I Do If I Have Dry Mouth

    If you have xerostomia, there are things you can do to help deal with your dry mouth and prevent cavities and periodontal disease. Try to follow these simple guidelines:

  • Use a cool mist humidifier at night in the bedroom to provide humidity, especially in winter months when the house is heated.
  • See your dentist every 3 months for cleaning and a dental health checkup.
  • Acupuncture may increase saliva production for people who still produce some saliva naturally.
  • Dry mouth can be a challenging side effect to deal with on a daily basis. Contact your care provider for help with managing this side effect.

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    Sore Mouth And Problems With Your Teeth

    The cells lining your mouth are sensitive to radiation. So radiotherapy is likely to make your mouth sore and you might have ulcers after a week or so. This is called oral mucositis.

    The soreness usually only lasts while you are having treatment and for a few weeks afterwards. Your doctor, nurse or radiographer can give you painkillers to help. Following a mouthwash routine from the start of radiotherapy will also help.

    You might need to have a fine feeding tube into your nose if your mouth is sore and stopping you from eating or drinking properly. The tube is called a nasogastric tube. Or you might have a tube put directly into your stomach through your skin. This tube is called a percutaneous endoscopic gastrostomy tube .

    Prevention Of Radiation Injury To Salivary Gland Tissue


    Radiation Techniques

    Intensity-modulated radiation therapy is an improvement over traditional radiotherapy that allows more accurate delivery of specific radiation dosage and dose distribution to the tumor, enabling better sparing of surrounding normal tissues and has the potential to minimize the severity of salivary gland hypofunction and xerostomia . After an initial decrease in saliva secretion 1â3âmonths after IMRT, salivary secretion from spared salivary glands has the potential to gradually recover over time .

    Flow rate of 2% citric acid-stimulated parotid and bilateral submandibular-sublingual saliva as a function of time after start of radiotherapy . Initial flow rates are set to 100% . Modified with permission from Elsevier .


    It has been reported that preradiation intraglandular administration of botulinum toxin into rat submandibular glands may reduce radiation injury at a glandular level . Also, bethanechol was more effective than a placebo in preventing radiation damage to salivary gland tissue .

    Surgical Transfer of the Submandibular Gland

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    Drugs For Preventing Dry Mouth And Problems With Saliva After Radiotherapy

    Review question

    To assess the effects of treatment with drugs in order to prevent damage to salivary glands following radiotherapy to the head and neck


    Problems with saliva production and salivary glands are a significant and mostly permanent side effect for people after radiotherapy treatment to the head and neck. When this occurs the condition is known as dry mouth or xerostomia. Dry mouth is not measurable and is a subjective or personal expression of how the mouth feels. It can have other causes and is a consequence of the production of less saliva or by the consistency of saliva. The rate of flow of saliva in an individual’s mouth however can be measured. People who have dry mouth have a reduced quality of life. They can experience issues with taste and general discomfort, difficulties chewing, swallowing and speaking as well as tooth decay, thrush and other infections of the mouth. A wide range of drugs that work in different ways have been used to try and prevent problems with salivary glands caused by radiotherapy. Unfortunately there is currently not enough evidence to show which drugs or which type of drugs are most effective.

    Study characteristics

    Drugs included were any prescribed to prevent salivary gland problems and given before or during radiotherapy. Information was collected from the end of radiotherapy except for that about adverse effects. Different techniques for giving radiation treatment that might reduce damage were not included.

    Pilocarpine Improves Dry Mouth Caused By Radiotherapy

    This is a plain English summary of an original research article

    Out of several treatments tested, the drug pilocarpine gave the most significant improvement in dry mouth following radiotherapy for head and neck cancer. Less dry mouth and increased salivary flow were twice as likely after taking pilocarpine than after a dummy pill.

    Dry mouth from radiotherapy impairs quality of life. Although people can try simple measures at home, such as sucking ice cubes, they may wish to discuss pilocarpine treatment with their GP. Side effects from this medication are usually short-lived but if they are troublesome other options are available, though not supported by such good evidence as pilocarpine.

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    Stimulated Salivary Flow Rates Are Restored In Mice Receiving Post Therapy Igf

    FVB mice exposed to a single radiation dose exhibit significant reductions in salivary function throughout the time course consistent with previously published studies in other animal models . In contrast, injection with IGF-1 on days 4-8 following radiation increased salivary flow rates to 72% of the untreated control on day 30 compared to irradiated FVB mice . Further increases in salivary flow rates on days 60 and 90 in irradiated mice injected with IGF-1 result in return to untreated flow rates . Administration of recombinant IGF-1 to unirradiated FVB mice on days 4-8 did not show significant changes in salivary flow rates at any of the time points evaluated indicating that IGF-1 does not affect glandular function in unstressed environments. These functional data suggest that post therapy IGF-1 can alter the response of salivary glands to radiation damage leading to restoration of function.

    Figure 2

    Animal Models Provide Mechanistic Insight Into Radiation

    Salivary glands – Anatomy and Physiology

    3.1. DNA Damage, Insufficient DNA Repair and Cell Cycle Arrest

    3.2. Reactive Oxygen Species Generation

    3.3. Dysregulated Calcium Signaling

    3.4. Generation of Inflammatory Responses

    3.5. Apoptosis, Autophagy and Cellular Senescence

    3.6. Neuronal and Vascular Changes

    3.7. Stem/Progenitor Cell Dysfunction

    3.8. Compensatory Proliferation

    3.9. Alterations in Cell Structure

    3.10. Fibrosis

    3.11. Immunomodulation

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    What Did This Study Do

    This systematic review included 20 randomised controlled trials, three from the UK. Trials compared treatments with each other or a placebo among 1,732 adults with a dry mouth after radiotherapy. Interventions replaced or aimed to stimulate saliva production. They included mouth gels, toothpaste, acupuncture, laser therapy, herbal compounds, artificial saliva and two drugs pilocarpine and cevimeline.

    The trials of drugs were of high quality so we can be confident in these results. However, the trials of non-drug treatments had a high risk of certain bias because the person and assessor knew which treatment they were having. They were also mostly small trials of between 20 and 38 participants, so conclusions from these should be treated with caution.

    Treatments That Cause Dry Mouth Or Saliva Changes

    Radiotherapy or chemoradiation to the head or neck can affect your salivary glands. This means that you may not make as much spit as before and so your mouth may become dry. Your salivary glands may gradually recover after treatment finishes, but your saliva may be thicker and sticky. Some people have a dry mouth permanently.

    If you feel you have too much saliva rather than too little, this may be a sign of swallowing difficulties.

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    What Did It Find

    • People taking a pilocarpine tablet were twice as likely to have an improvement in sensation of a dry mouth. Defined as 25mm or more on a visual analogue scale from 0 to 100mm. This level of improvement was reported by 63/140 people on pilocarpine compared to 36/140 people on placebo, .
    • There was also an improvement in salivary flow 60 minutes after taking oral pilocarpine for 89/129 people compared to 65/132 people on placebo, .
    • Acupuncture did not increase salivary flow rate . However, these trials were small with a total of 50 participants.
    • There was insufficient evidence on the effect of biotene gel, toothpaste, mouthcare systems, herbal medicine, humidifiers or laser therapy.

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