Oral mucositis, an inflammation of the oral mucosa, often occurs in association with cancer treatments, particularly radiation and chemotherapy. It manifests as severe pain, redness, and swelling in the patient's mouth, potentially impacting the success of cancer therapy. To date, no existing medication has effectively prevented the development of mucositis. Recent research suggests that antibacterial dual light therapy may be an effective method to manage the symptoms of this condition.

Traditional approaches to treating oral mucositis include preventive measures such as maintaining good oral hygiene and using ice therapy during chemotherapy. If bacterial infection is present, the use of antibiotics may be considered by the physician. Corticosteroids are also a treatment option to alleviate pain and the inflammatory response associated with mucositis. However, corticosteroid use poses risks, as it can suppress the immune system, making cancer patients more susceptible to infections.

Ongoing research explores novel methods for preventing and treating oral mucositis. Mitochondria-stimulating red light therapy has proven to be very effective in treating oral mucositis, particularly as a preventive measure. Although light therapy is estimated to be the most effective treatment modality, its widespread implementation faces challenges such as availability and practical issues.

The latest studies investigate antibacterial treatments to preventively address oral mucosal ulcers originating from mucositis, aiming to mitigate the adverse effects of aggressive cancer treatments.

In the bachelor's thesis from the Faculty of Medicine at the University of Helsinki titled "Oral Mucositis – Antibacterial Dual Light in the Treatment of Oral Mucositis," medical student Jessica Hentilä explores the effects of antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) on mucositis ulcers as local treatments.

Hentilä's research evaluates the efficacy of dual light therapy against Streptococcus Oralis – a common bacterium in the oral microbiome. The study indicates that antibacterial dual light, a combination of aPDT and aBL, not only effectively targets streptococcal infections found in mucositis-induced ulcers but provides red light therapy simultaneously.

According to Dr. Tommi Pätilä, the thesis advisor of Hentilä’s project and specialist in pediatric heart and organ transplantation surgery, the reduction of oral bacterial load in the mouth promotes mucosal wound healing, concurrently reducing the risk of local and systemic infection complications common in cancer patients. This is an important addition to the conventionally applied red light therapy.

Oral Health Improves Quality of Life

Oral mucositis is a prevalent side effect in cancer patients undergoing chemotherapy, radiation therapy, or combined chemo-radiation therapy. Its pathophysiology stems from the ability of cancer treatments to inhibit rapidly dividing cells, present not only in cancer tissues but also in the oral mucosa.

Clinically, oral mucositis induces an inflammatory reaction in the oral mucosa, leading to swelling, redness, and painful ulcers. These mucosal variations create an entry point for oral bacteria, exacerbating mucositis-related inflammation or potentially spreading to other parts of the body, explains Dr. Matti Mauramo, a dentist and specialist in pathology.

Mauramo emphasizes that maintaining good oral hygiene is crucial for overall well-being. For cancer patients, oral health preservation is especially vital, as a clean mouth reduces the inflammatory burden caused by bacteria, worsening mucositis. Cancer patients must maintain good chewing ability and a diverse, high-calorie diet during intensive cancer treatments to avoid malnutrition and the development of a general weakness known as cachexia.

Professor Tuomas Waltimo from the University of Basel notes that while mucositis can occur in any part of the digestive tract, its manifestation on the oral mucosa poses specific challenges for cancer patients. Severe cases may hinder oral nutrition intake, leading to premature discontinuation of cancer treatments and compromising overall prognosis.

Waltimo, currently practicing as a private dentist at a Finnish clinic providing specialized dental care for patients undergoing cancer treatments, acknowledges the improvement in managing the side effects of cancer treatments compared to the early 2000s. Throughout his two-decade-long career as a researcher, Waltimo closely observed the development of cancer treatment pathways, particularly the increasing understanding of the role of oral infections in treatment outcomes.

In the early 2000s, according to Waltimo, the importance of oral health in the context of general healthcare was not systematically recognized as it is today in many European countries. However, the situation has improved, with dental care becoming a standard practice before initiating stem cell transplantation treatments in countries like Switzerland.

Simultaneously, patients’ prognoses have improved, and, most importantly, the quality of life for many patients has improved as the management and prevention of side effects of cancer treatments have become more efficient.

A Healthy Mouth Guards Against Serious Infections

Professor Waltimo highlights that alongside mucosal inflammation, cancer treatments often induce dry mouth, exposing cancer patients to various other oral diseases as well, such as tooth decay, gingivitis, and challenging periodontal and peri-implant diseases.

Oral infections are detrimental to overall health, causing a low-grade inflammatory state and potentially affecting the entire body. Oral infections are particularly harmful to cancer patients due to an increased risk of bacteremia – a bacterial infection that occurs when bacteria entering the bloodstream trigger the body's defense reaction. In severe cases, bacteremia can lead to life-threatening sepsis.

Waltimo emphasizes that good oral care can prevent infection complications, which cancer patients are more susceptible to, given their increased risk of diseases. Maintaining oral health is crucial for cancer patients, as the mouth is the primary source of routine bacterial seeding in the body. Mucous membranes, teeth, and gums must be kept in impeccable condition through daily effective oral hygiene.

According to Dr. Matti Mauramo, Lumoral's antibacterial treatment can influence the inflammatory process and induce an anti-inflammatory effect. Additionally, antibacterial dual light therapy can complement traditional bactericidal treatments.

Professor Tuomas Waltimo suggests that Lumoral's antibacterial dual light therapy could potentially serve as a preventive measure to support the oral health of cancer patients before the initiation of cancer treatments.

Preliminary observations suggest that Lumoral's antibacterial dual light therapy might be an important tool in the armory for oral mucositis treatment. Confirmation studies shall be set up to further investigate the effectiveness of the novel approach. A new doctoral dissertation study will commence at the University of Helsinki in spring to delve into this topic, adds Tuomas Waltimo.

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World Cancer Day is observed on February 4th every year. It is a day dedicated to raising awareness about cancer, promoting its prevention, detection, and treatment, as well as advocating for improved access to cancer care for all people globally. The day also serves as a reminder of the importance of early detection and education about cancer risk factors.

Sources:

Brown TJ, Gupta A. Management of Cancer Therapy-Associated Oral Mucositis. JCO Oncol Pract. 2020 Mar;16(3):103-109. doi: 10.1200/JOP.19.00652. Epub 2020 Feb 3. PMID: 32048926.

Al-Rudayni AHM, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of Oral Cryotherapy in the Prevention of Oral Mucositis Associated with Cancer Chemotherapy: Systematic Review with Meta-Analysis and Trial Sequential Analysis. Curr Oncol. 2021 Jul 29;28(4):2852-2867. doi: 10.3390/curroncol28040250. PMID: 34436016; PMCID: PMC8395421.

Hentilä, Jessica. "Oral Mucositis – Antibacterial Dual Light in the Treatment of Oral Mucositis." Bachelor of Medicine, University of Helsinki, Faculty of Medicine, October 22, 2023.

Gholami L, Shahabi S, Jazaeri M, Hadilou M, Fekrazad R. Clinical applications of antimicrobial photodynamic therapy in dentistry. Front Microbiol. 2023 Jan 5;13:1020995. doi: 10.3389/fmicb.2022.1020995. PMID: 36687594; PMCID: PMC9850114.

Jessica Hentilä, a student at the Faculty of Medicine, University of Helsinki, conducted in-depth research on oral mucositis and its treatment. Oral mucositis is an inflammatory condition of the oral mucosa that arises from cancer treatments such as chemotherapy and radiation therapy, commonly affecting cancer patients as a side effect.

The symptoms of oral mucositis include swelling, redness, and painful ulcers on the oral mucosa, leading to difficulties in eating, interruptions in treatments, and even severe consequences such as sepsis and death. Traditional prevention and symptomatic treatment are commonly employed, but Hentilä's research suggests that antibacterial dual-light therapy provides a new and effective approach to managing oral mucositis.

Hentilä's bachelor's thesis, titled "Oral Mucositis – Antibacterial Dual-Light Therapy in the Treatment of Oral Mucositis," focused specifically on the use of antibacterial light in treating oral mucositis. The research explored antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL), as well as their combination – known as dual-light therapy. 

The study investigated the efficacy of dual-light therapy against Streptococcus Oralis (S. Oralis), a type of bacteria present in the oral microbiome. The results indicated that dual-light therapy could eliminate all bacterial colonies, regardless of the relative light energies of aPDT and aBL.

Addressing Side Effects of Cancer Treatments

In Finland, one in three individuals develops cancer during their lifetime, making the study of treatment side effects, particularly oral mucositis, crucial. According to the research, oral mucositis adversely affects many cancer patients, impacting their overall quality of life. Traditional treatments, such as ice therapy and maintaining oral hygiene with traditional means, may not always provide sufficient benefits, necessitating the exploration of new therapeutic approaches.

The study emphasizes that maintaining oral hygiene remains a crucial aspect of oral mucositis treatment, and light therapy devices could play a permanent role in oral healthcare. While reducing the significance of oral mucositis in the long term is an overarching goal, research on antibacterial dual-light therapy devices offers promising prospects for the advancement of oral healthcare.

Source:

Hentilä, Jessica. "Oral Mucositis – Antibacterial Dual-Light Therapy in the Treatment of Oral Mucositis." Bachelor of Medicine, Faculty of Medicine, University of Helsinki, October 22, 2023."

Scientists have discovered a significant link between poor oral health and systemic diseases, including specific cancers. This connection is centered around so-called oral dysbiosis, a condition where imbalanced oral bacteria can lead to a range of health issues. It also emphasizes the crucial role of oral hygiene in promoting overall health.

The oral cavity houses more than 700 types of bacteria. While some bacterial species are beneficial for dental and overall health, in some cases, they can play a role in the development of serious systemic illnesses.

Studies show that maintaining a balanced microbial ecosystem in the mouth is crucial for oral health and it has a significant impact on how the body responds to various diseases. Dysbiosis, or an imbalanced oral microbiome, or ecosystem, can lead to various health issues ranging from common dental problems like cavities and gum disease to severe conditions such as heart disease, Alzheimer’s disease, and diabetes. [1, 2]

Recent studies have revealed that oral dysbiosis may even be involved in the development of life-threatening digestive cancers. Digestive cancers include cancers located in the esophagus, stomach, liver, pancreas, colon, and rectum. Their incidence and related mortality are increasing worldwide, with the majority of new cases of digestive cancers (63%) and related deaths (65%) occurring in Asia, followed by Europe and North America. [3].  

Scientists believe that many digestive cancer forms are influenced by various environmental factors that can be potentially changed. These include tobacco smoking, diet, alcohol consumption, and obesity. Some recent evidence also suggests a role of the human oral microbiota in the development of digestive cancers. Fusobacterium nucleatum is one bacteria species found commonly in the mouth, which is a key member of colorectal cancer-associated bacteria. However, many other oral pathogens can play a role in the development of cancer as well. [4,5]

Exposing the oral bacteria-pancreatic cancer link

One study published in the British Journal of Cancer (BJC) reported that Trepenoma denticola (Td), the bacteria responsible for periodontitis, may cause pancreatic cancer [6,7]. Pancreatic cancer is one of the deadliest forms of cancer caused by the abnormal and uncontrolled growth of cells in the pancreas – a large gland that is part of the digestive system. Around half of all new cases are diagnosed in people aged 75 or over. [8]

–  The Treponema bacterium can enter the bloodstream through inflamed gums and spread to other parts of the body. If left untreated and undiagnosed, periodontal disease contributes to the development and spread of cancer and cancer deaths – not only from oral cancer, but especially pancreatic cancer, explains Timo Sorsa, Professor of Oral and Maxillofacial Diseases at the University of Helsinki, findings of the study.

Professor Sorsa points out that Treponema bacterium shares a specific enzyme with some cancer types in the gut. This enzyme is called Treponema denticola chymotrypsin-like proteinase – or dentilisin – and it is usually found in the mouth, where it is known to contribute to severe gum disease (periodontitis). However, this same enzyme has also been observed in malignant and life-threatening tumors. [6,7].

In the oral cavity, dentilisin not only contributes to gum disease but also triggers other enzymes that promote cancer. These enzymes are called matrix metalloproteinases (MMPs), and they break down the material between cells and cell membranes, making it easier for cancer to invade healthy tissue. This connection raises concerns about potential health issues related to dentilisin in the oral cavity, Prof. Sorsa stresses.

The BJC study from 2017 was the first to show that virulence factors from gum disease bacteria could spread from the mouth to other parts of the body and take part in central mechanisms of cancer-related tissue destruction.

Since then, supplementary research has supported the study’s findings.  One report released in the International Journal of Cancer – also by Prof. Sorsa’s team – examined registry data for over 10 years on over 68,000 adults in Finland who had made a primary dental healthcare visit. This revealed that periodontitis was associated with a 33% increased risk for overall cancer mortality. The mortality risk associated with gum disease among individuals with pancreatic cancer was far higher, with a more than twofold increased risk, the study shows [7].

From fast diagnosis to a quick onset of treatment 

The links revealed so far between oral bacteria and cancer developments have inspired Prof. Sorsa’s team to search ways to help prevent cancerous developments. One potential solution is to detect gum infections in their initial stages through early diagnosis. By quickly identifying gum disease with a chair-side aMMP-8 rapid test, researchers believe that we might be able to prevent certain cancers because it allows for faster treatment of the underlying issue: gum inflammation. The test makes invisible visible, points out Prof. Sorsa. [9,10]

– Out of all MMP enzymes, especially active MMP-8 enzyme has been found to be elevated in patients suffering from gum disease leading to periodontal connective tissue destruction, Prof. Sorsa explains his team’s findings.

Periodontitis, or severe gingivitis, is a common disease that is estimated to affect as many as half of the global population – often without any symptoms at all. Early detection of these diseases is important because it allows for intervention and treatment before irreversible damage occurs. Traditional methods like check-ups and X-rays might, however, miss early signs of these diseases since they often show symptoms in later stages. Using biomarkers like aMMP-8, clinicians can spot subtle inflammation and tissue damage, allowing them to start treatment before the disease becomes visible.

–The aMMP-8 rapid test can measure and assess active periodontal adhesive tissue loss and the risk of its progression within five minutes in the dental chair non-invasively. The test complements the diagnosis, follow-up, and maintenance treatment of periodontitis and peri-implantitis, explains Prof. Sorsa. 

Advanced approaches for treating oral diseases

Periodontal and peri-implant diseases are conditions that affect the supporting structures of teeth and dental implants and can lead to tooth loss if left untreated. Gum infections can develop for various reasons. One key factor is the buildup of bacterial plaque, also known as biofilm, on the surfaces of teeth due to inadequate oral hygiene. [9]  

When discussing new treatment options and prevention of periodontitis, Prof. Sorsa emphasizes modern antibacterial methods for better oral hygiene and efficient plaque removal in periodontitis treatment and prevention. Also, research reveals that antibacterial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections – even ones that do not respond well to antibiotics [12].

Lumoral treatment is the first aPDT treatment device designed for home use. It has been developed by Finnish scientists as a drug-free alternative for treating and preventing severe gum disease.

– Poor oral health is linked to over 200 chronic diseases. Lumoral is a product that enhances oral hygiene when used regularly at home, and research suggests that it can also enhance the effectiveness of professional dental care. What's more, it may reduce the need for conventional medications like antibiotics and chlorhexidine in the treatment of gum disease, according to Tommi Pätilä, a cardiac and organ transplant surgeon at the New Children's Hospital in Helsinki.

– Based on a light-activated antibacterial effect, Lumoral slows down plaque formation and significantly reduces the burden of harmful bacteria in the mouth, Pätilä explains further.

The product is suitable for patients of all ages, but it is particularly recommended for those with a history of problems with common oral diseases, tooth decay, and gum disease [9].

The crucial role of oral hygiene in cancer care

Brushing and flossing on a regular basis is key to maintaining a healthy mouth by removing dental plaque from the surfaces of teeth and interdental spaces. However, it is not always enough. Good oral hygiene requires adequate motor and mental skills. On the other hand, even when brushing teeth perfectly, studies show that even the most effective electric toothbrush only removes about 65% of harmful oral bacteria from the mouth [13].

– The key to overall well-being is good oral hygiene. For cancer patients, this is all the more important because they must maintain a high-calorie diet in order to fight the disease, notes Prof.  Dr. Tuomas Waltimo from the University of Basel.

Prof. Waltimo also acts as a private dentist at a clinic that offers dental services to patients with special dental needs, for example patients undergoing cancer treatments. He reminds that cancer treatments often bring along side-effects that can require special attention. Mucositis, as one example, can lead to generalised infection and even be life-threatening.

Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract. It can occur anywhere along the gastrointestinal (GI) tract, but oral mucositis refers to the inflammation and ulceration that occurs specifically in the mouth. Maintaining good oral hygiene habits is a prerequisite for treating oral mucositis. Lumoral supports regular mechanical dental hygiene, helps achieve gum health, and prevents inflammation when regular dental hygiene is insufficient. 

– Good oral hygiene is of paramount importance also in the management of oral mucositis. Initial findings suggest Lumoral treatment might help prevent and potentially treat oral mucositis, but this hypothesis requires further scientific research to confirm. We are, therefore, starting a new PhD study examining the topic at the University of Helsinki, Prof. Waltimo says.

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November is Stomach Cancer Awareness Month, and the goals of stomach cancer awareness primarily include: Raising public awareness and supporting educational efforts about stomach cancer, including risk factors, prevention, and early detection.

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References:

1.   Maier, T. Oral Microbiome in Health and Disease: Maintaining a Healthy, Balanced Ecosystem and Reversing Dysbiosis. Microorganisms 2023, 11, 1453. https://doi.org/10.3390/microorganisms11061453
2.   Silva DNdA, Casarin M, Monajemzadeh S, Bezerra BdB, Lux R and Pirih FQ (2022) The Microbiome in Periodontitis and Diabetes. Front. Oral. Health 3:859209. doi: 10.3389/froh.2022.859209
3.     https://dceg.cancer.gov/news-events/news/2020/global-burden-gastro
4.   Pignatelli, P.; Nuccio, F.; Piattelli, A.; Curia, M.C. The Role of Fusobacterium nucleatum in Oral and Colorectal Carcinogenesis. Microorganisms 2023, 11, 2358. https://doi.org/10.3390/microorganisms11092358
5.   Reitano E, de'Angelis N, Gavriilidis P, Gaiani F, Memeo R, Inchingolo R, Bianchi G, de'Angelis GL, Carra MC. Oral Bacterial Microbiota in Digestive Cancer Patients: A Systematic Review. Microorganisms. 2021 Dec 14;9(12):2585. doi: 10.3390/microorganisms9122585. PMID: 34946186; PMCID: PMC8707512.
6.   Nieminen, M., Listyarifah, D., Hagström, J. et al. Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation. Br J Cancer 118, 428–434 (2018). https://doi.org/10.1038/bjc.2017.409
7.   Heikkilä, P., But, A., Sorsa, T. and Haukka, J. (2018), Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults in 10-year follow-up. Int. J. Cancer, 142: 2244-2253. https://doi.org/10.1002/ijc.31254
8.     https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/pancreatic-cancer/
9.   Pakarinen, S.; Saarela, R.K.T.; Välimaa, H.; Heikkinen, A.M.; Kankuri, E.; Noponen, M.; Alapulli, H.; Tervahartiala, T.; Räisänen, I.T.; Sorsa, T.; Pätilä, T. Home-Applied Dual-Light Photodynamic Therapy in the Treatment of Stable Chronic Periodontitis (HOPE-CP)—Three-Month Interim Results. Dent. J. 2022, 10, 206. http://hdl.handle.net/10138/350606
10. Sorsa T, Gursoy UK, Nwhator S, Hernandez M, Tervahartiala T, Leppilahti J, Gursoy M, Könönen E, Emingil G, Pussinen PJ, Mäntylä P. Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontol 2000. 2016 Feb;70(1):142-63. doi: 10.1111/prd.12101. PMID: 26662488.
11. Sorsa T, Nwhator SO, Sakellari D, Grigoriadis A, Umeizudike KA, Brandt E, Keskin M, Tervahartiala T, Pärnänen P, Gupta S, Mohindra R, Bostanci N, Buduneli N, Räisänen IT. aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases. Front Oral Health. 2022 Jun 10;3:897115. doi: 10.3389/froh.2022.897115. PMID: 35757444; PMCID: PMC9226345.
12. Liu Y, Qin R, Zaat SAJ, Breukink E, Heger M. Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections. J Clin Transl Res. 2015 Dec 1;1(3):140-167. PMID: 30873451; PMCID: PMC6410618.
13. 1 Neha Aggarwal, Sunil Gupta, Rashu Grover, Gunmeen Sadana, and Karan Bansal; Plaque Removal Efficacy of Different Toothbrushes: A Comparative Study, Int J Clin Pediatr Dent. 2019 Sep-Oct; 12(5): 385–390.  doi: 10.5005/jp-journals-10005-1669