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Hyperbaric Oxygen Therapy For Radionecrosis

Medical information reviewed by: ANDREI BOGDAN, MD, Orthopedics-traumatology doctor
i.php?p=2. Oxigenoterapia hiperbarica in

Discover the hyperbaric medicine center opened in our clinic. Centrokinetic has the top-performing hyperbaric chamber in Bucharest, with multiple medical and anti-aging uses. The Baroks chamber has 5 seats, and operates at a constant pressure of 2.5 atmospheres, being fully automated and having protocols for each condition, and can be used individually for each patient. 

Hyperbaric oxygen therapy - benefits

Patients who use the clinic's hyperbaric therapy services benefit from:

  • The only medically accredited hyperbaric therapy chamber in Bucharest, which operates at 2.5 atmospheres (those for aesthetic use go to 1 atmosphere and have no medical benefits).
  • A safe medical procedure, without irradiation, without pain, without other side effects. 
  • The specialized medical team consists of recovery doctors, orthopedists, rheumatologists, neurologists, and neurosurgeons, meaning a multidisciplinary team specialized in all diseases that can be treated with hyperbaric therapy. 
  • Premium conditions at a fair price. Our clinic is recognized for the conditions offered and for the care of each patient. But we do not need to pay exorbitant prices to have access to quality medical services. At Centrokinetic you can find an affordable and fair price. But note that we do not have a contract with the National Health Insurance House (we do not offer state reimbursed services)

Centrokinetic is keeping contact with prestigious clinics and universities in Belgium, the Netherlands, France, and Greece to constantly update treatments to provide patients with the best medical solutions.

What is soft tissue radionecrosis?

Soft tissue radionecrosis refers to the delayed effects of radiation therapy, i.e long-term damage to the irradiated anatomical area. Radiation can damage capillary beds and arterioles that lead to relative tissue hypoxia, leading to characteristic fibrosis, and these tissue changes can develop over time, away from initial radiation exposure. Soft tissue radionecrosis can develop between 6 months and a few years after exposure. Capillaries can regress through the process of angiogenesis, but in tissue damaged by hypoxic radiation, new capillaries tend to grow disorganized, leading to telangiectasias. This abnormal neovascularization results in improper tissue perfusion that can subsequently cause tissue necrosis and skin ulceration. Only minor trauma or surgical procedures can lead to tissue rupture and ulceration. Radiation can damage superficial and deep tissues. Radionecrosis of the spine and brain can be particularly problematic to treat. The radiation exposure dose is usually over 5000 cGy (Cents-gray) but can be done with up to 3000 cGy.


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Etiology

Soft tissue radionecrosis can occur in any organ or tissue that has received substantial radiation exposure, a medical conduit commonly used to treat cancer. The initial radiation damage (acute phase) in the tissue is in the DNA, and if the damage is severe enough, the cells will not be able to recover. This will lead to cell death. If these are cancer cells, this is the desired effect of the radiation, but when normal tissue that is in the field of ionizing radiation is damaged, then unwanted changes can occur in the tissue. 

Initially, there is edema and inflammation in the tissue due to radiation, which leads to clinical erythema. After the radiation-induced erythema, the tissue may develop hypoxia, and fibrous tissue appears. 

These changes in fibrotic tissue are a precursor to the development of delayed effects of radiation therapy. Damaged tissue has a lack of normal capillaries and arterioles, growing stroma, which gives the tissue the fibrotic appearance and texture. Such tissue is hypoxic due to the more distant distance of oxygen diffusion from red blood cells that pass through fewer capillaries. Not only the normal capillary beds are missing, but the capillaries present are often disorganized and do not provide adequate tissue perfusion for normal oxygenation. Proliferative endarteritis and fibrosis result in ruptured tissue, either spontaneously or often in combination with trauma and/or infection.

Epidemiology

In the United States, there are more than 1.2 million cases of invasive cancer diagnosed annually and about half of these patients will receive radiation therapy to relieve symptoms or treat the disease. About 3% to 5% of patients who have had radiation therapy for cancer will develop delayed effects of radiation therapy, such as soft tissue radionecrosis or problems with wound healing. The risk of developing this problem depends on the amount of radiation delivered, the type of ionizing radiation, and the tissue that has been radiated.

Pathophysiology

The dose of radiation exposure is usually over 5000 cGy, sometimes at least 3000 cGy. The biological effect of radiation is DNA damage, lipid peroxidation, and protein denaturation. Cells exposed to radiation will either die or malfunction and then undergo cell repair. 

The cells that are most affected by radiation are the cells that divide faster, which are found in the dermis, mucosa, and vascular tissue. Endothelial cells are especially prone to damage, which leads to fibrotic changes and the lack of cells that function normally in radiation-damaged tissue. Cellular sensitivity to radiation starts from the most sensitive tumor cells, reaching endothelial cells, fibroblasts, muscles, and then nerves.

The acute clinical phase occurs in the first 6 months after radiation therapy, which is often fractionally dosed. This phase may not involve gross tissue changes but may cause dose-dependent changes. These changes can be manifested clinically by hair loss, erythema, skin diseases, and skin ulcers. Lung tissue can develop radiation-induced pneumonitis, which usually occurs 2 to 3 months after radiation therapy and is considered a subacute phenomenon. Clinically pneumonitis behaves like chronic bronchitis. It can resolve gradually or progress to a chronic problem such as pulmonary fibrosis. If radiation therapy is applied to the spinal cord, then demyelination may occur and, clinically, this condition is known as Lhermitte. Most of the time this symptom will resolve without treatment, but sometimes the symptoms can persist for more than 6 months and will become a chronic condition. These delayed effects of radiation therapy are usually seen more than 6 months after radiation therapy but may occur 5 or more years later. The delayed effects of radiation therapy are dependent on the tissue that has been irradiated.

The pathology behind soft tissue damage follows the principle that cells that have a faster rate of rotation or divide at a higher rate are more sensitive to radiation and are more damaged than cells that don’t undergo division. 

Endothelial cells in the arterioles and capillary beds are particularly sensitive to radiation compared to stromal cells. This results in an obliterative endarteritis that causes hypoxia in the tissue and fibrotic changes characteristic of radiation-damaged tissue stroma.

Arterioles may try to grow again, but this proliferative endarteritis results in disorganized growth of vascular tissue and often does not provide adequate oxygenation of the tissue to maintain normal function. The relatively hypoxic and fibrotic tissue is now susceptible to rupture resulting in trauma or infection. The resulting chronic wounds are very difficult to treat, and further surgery and grafting can be problematic due to a lack of tissue vascularity.

Historic 

It is important to have a history about when radiotherapy was given, what type of ionizing radiation was used, and what was the dose of radiation that the tissue received. Also, when the patient has a problematic wound, it is important to consider other factors that can cause poor wound healing, for example, malnutrition, macro-vascular disease, tobacco use, diabetes, age, and repeated tissue trauma. For example, a lesion in the pelvic area may not heal simply by treating the tissue, but also by previous radiation therapy. It is also important what surgical procedures have been performed on the problematic wound.

The acute effects of radiation on soft tissues in the development of erythema, tissue edema, skin pigmentation changes, hair loss, and mucosal ulceration should be studied. The acute effects of radiation therapy are usually self-limiting and are treated with supportive care and the use of antibiotics if the infection develops due to infected skin ulcers. 

Usually, the damaged radiated tissue will recover in about a month with reduced inflammation, edema, and repair of damaged endothelial cells. If the arterioles do not recover, then this precipitates the formation of a hypoxic environment with fibrotic changes that can become permanent and can lead to delayed effects of radiation therapy. Delayed effects can cause wounds that are difficult to heal, and the tissue develops progressive endarteritis and an obliterative process of the arterioles that decreases blood supply to the tissue, and the hypoxic environment causes the typical fibrotic change. Clinically, the damaged skin tissue has a contracted appearance, a woody appearance, and a waxy appearance. Telangiectasias are commonly observed on the surface and it is common for this skin to ulcerate with minor or spontaneous trauma. 

Assessment

When evaluating a problematic wound in previously radiated tissue, it is important to determine if the problem is due to soft tissue radionecrosis and not some other cause. Usually, the accumulated radiation dose was over 3000 cGy and more frequently 5000 cGy. For example, a squamous cell carcinoma of the skin previously treated with 1000 cGy would be very unlikely to develop a future skin ulcer from the delayed effects of radiation therapy. More likely, in this scenario, the skin ulcer may be a recurrence of skin cancer and a biopsy should be done.

Macrovascular condition, if wounds appear to the extremities, can be assessed using the heart rate, brachial index of the ankle, arterial Doppler, and angiography. Transcutaneous oxygen measurement (TCOM) can also be done to assess tissue oxygenation, and the TCOM must be greater than 40 mm Hg PaO2 to predict a good chance of wound healing.

Wound cultures or bacterial cultures on tissue biopsy may help target antimicrobial therapy and treatments adapted to secondary infections, which are common in soft tissue radionecrosis. It is often difficult to determine whether tissue necrosis results from delayed effects of radiation or side infections. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic due to its pathogenicity and antimicrobial resistance. Therapy should be adapted based on antimicrobial sensitivity.

Recurrence of cancer or secondary cancers should always be considered and there should be a low rate of suspicion for performing a biopsy. Radiation therapy causes DNA damage and can cause cellular mutations and carcinogenesis.

Not all soft tissue radionecrosis is easily identified by clinical examination. For example, cystitis or hemorrhagic proctitis may be a delayed effect of radiation therapy for pelvic cancers. Evaluation of cystitis and hemorrhagic proctitis will often require cystoscopy or colonoscopy for further diagnosis and treatment. A biopsy may be done during these procedures to confirm the diagnosis and to help look for recurrent cancer or secondary cancer. Often, the diagnosis can be confirmed by CT examination or MRI scan. Spinal cord demyelination in determining the delayed effects of radiation therapy and electrical pain in the lower extremity with the extension of the spine may be characteristic of radionecrosis of the soft tissues of the spine.

What are the effects of oxygen therapy on the body?

  • Decreases inflammation
  • Increases the body's oxygen saturation by 20-30%
  • Increases the body's immunity
  • Increases blood circulation and stimulates the formation of new capillaries
  • Decreases toxins in the body
  • Stimulates the production of new blood cells
  • Increases healing rate

Treatment 

Conventional therapies for incurable wounds and bleeding problems, as seen in soft tissue radionecrosis, are unsatisfactory and often unsuccessful in controlling symptoms. Because the tissue lacks adequate vascularity to provide oxygen and nutrients for the tissue to heal, surgery has a higher failure rate and can contribute to further tissue damage and decomposition. Tissue damaged by radiation is also more prone to complications such as infection, especially after surgery.

Hyperbaric oxygen therapy is useful in treating soft tissue radionecrosis by improving oxygenation of damaged tissue during 30 to 40 sessions, usually, 2 to 3 absolute atmospheres (ATA) for 90 to 110 minutes, which will stimulate angiogenesis. . The new capillary beds and the granulation tissue that is formed have a better blood supply and a lasting improvement of the tissue through improved oxygenation. This tissue improvement is clinically manifested in chronic wound healing, more elastic and less fibrotic texture of the tissue, and conditions such as xerostomia (dry mouth due to lack of saliva production) are treated with hyperbaric oxygen therapy. The most common areas with soft tissue radionecrosis treated with hyperbaric oxygen therapy are the head and neck, breast, or thoracic wall.

i.php?p=10. Terapia hiperbara in necroza

Hyperbaric oxygen therapy generally has a response rate of about 80%, with an improvement in the patient's symptoms of soft tissue radionecrosis, but the tissue never recovers to what is considered normal tissue. Clinically, what is seen is an improvement in fibro-atrophic tissue changes. For example, improvement in granulation of the injured tissue, reduction or resolution of bleeding in the affected tissue, improvement in osteocyte function, and improvement in neurological symptoms.

Hyperbaric oxygen therapy is useful in treating soft tissue radionecrosis through improved oxygenation of the tissue during treatment, and after 20-30 sessions, angiogenesis is stimulated with the formation of new capillary beds and granulation tissue, which bring a higher blood supply for healing. wounds. 

Typically, hyperbaric oxygen therapy is done at 2 to 3 ATA, for 90 to 110 minutes. A pressure of 2.4 ATA is often chosen for treatment, for the maximum benefit of hyperbaric oxygen therapy, but minimizes the risk of seizures caused by excess oxygen. Approximately 20 sessions are needed to begin seeing clinical evidence for improved angiogenesis and improved symptoms of soft tissue radionecrosis. This improvement of the tissue is clinically manifested by a greater elasticity of the fibrotic tissue, the improved granulation of the wound bed. It may take 30 to 40 or more sessions to see the benefits of hyperbaric oxygen therapy.

Not only the clinical parameters can be monitored in response to therapy, but improvement in transcutaneous oxygen measurement and fluent angiography may be sought. 

The risk of hyperbaric oxygen therapy includes hypoglycemia in diabetic patients, especially if they are taking insulin and/or hypoglycemic agents, ear barotrauma, pneumothorax, and seizures of oxygen toxicity, and rarely, pulmonary toxicity with oxygen. 

Cancer patients who have had a history of bleomycin chemotherapy have an increased risk of pulmonary fibrosis, even if the chemotherapy was given remotely. This has been a relative contraindication, but some doctors will treat the patient if the benefits outweigh the risks. A patient who is actively receiving cis-platinum has a high risk of bladder toxicity if he also receives hyperbaric oxygen therapy and this is a contraindication. Also, a relative contraindication is if the patient had a history of spontaneous pneumothorax with underlying lung conditions with air cushions.

There are especially anecdotal cases and prospective studies on the benefit of treating cerebral radionecrosis, which is very difficult to treat with standard steroid therapy and surgery. Further studies are needed in this area to make consensus statements on the best therapy and how hyperbaric oxygen therapy should be used. 

Theoretically, the use of hyperbaric oxygen therapy should be beneficial for angiogenesis and repair of brain radionecrotic tissue.

Differential diagnosis

The differential diagnosis of soft tissue radionecrosis should take into account other causes of tissue necrosis. Necrotizing infections, especially Staphylococcus and Streptococcus infections, can cause tissue necrosis and should be excluded from the assessment of wound infectious disease and deep tissue culture. 

Superficial wound cultures are often inadequate and have the negative effect of detecting microorganisms that can colonize the wound. Ulcerations in arterial insufficiency and tissue necrosis caused by macrovascular insufficiency should be considered especially in a patient with risk factors such as smoking, hypertension, and diabetes. Sometimes, soft tissue radionecrosis presents as a tissue that is at risk of bleeding in proliferative arthritis. 

Hemorrhagic cystitis is a complication of pelvic radiation, and the delayed effects can be very difficult to treat and often lead to further bladder damage that occurs after cauterization treatments. Proctitis is also a delayed soft tissue radionecrosis that can lead to significant rectal bleeding. Such bleeding problems can be severe enough to require repeated blood transfusion and have significant morbidity. 

It is always important when the patient encounters such a situation, the specialist to ensure that there is no recurrence of cancer or a secondary carcinoma or a precancerous adenomatous polyp that causes bleeding, to make all the necessary tests.

Cystoscopy or colonoscopy with biopsy is often needed to rule out cancer and to confirm the diagnosis of soft tissue radionecrosis as the cause of the patient's symptoms. 

Surgical oncology

Common forms of soft tissue radionecrosis are central nervous system (CNS) radionecrosis (cerebral and spinal cord), radiation-induced cystitis where hemorrhage results, radiation-induced proctitis, vaginal radionecrosis, and laryngeal radionecrosis. The morbidity for these patients is substantial, with 50% of patients having complications if future surgery is required on the radiation field. Annually, there are between 6,000 and 30,000 patients who develop this condition in the United States. Radiation-induced cystitis with bleeding can be ameliorated in approximately 80% of patients, a significant reduction in hematuria being observed.

The beneficial effects of hyperbaric oxygen therapy are sustained effects due to the major angiogenesis that takes place in the tissue, along with the supply of oxygenated blood and improved granulation of the injured tissue. Hyperbaric oxygen therapy is most beneficial when used in combination with good surgical technique, as demonstrated by Dr. Marx's extensive studies on osteoradionecrosis of the mandible and the development of the Marx protocol. 

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Related issues

The risk of hyperbaric oxygen therapy techniques includes hypoglycemia in diabetic patients, especially if taking insulin and / or hypoglycemic agents, ear barotrauma, pneumothorax and seizures of toxicity and rarely pulmonary toxicity with oxygen. Cancer patients who have had a history of bleomycin chemotherapy have an increased risk of pulmonary fibrosis, even if the chemotherapy was given remotely. This was a relative contraindication, but some doctors will treat the patient if the benefit outweighs the risk. Due to the hyperbaric environment of the oxygen chamber, there is always the risk of fire, which is why a series of strict protocols are followed to prevent the devices from causing accidents. 

Hyperbaric oxygen therapy is the only treatment that is available to treat the lack of normal microvascularity characteristic of soft tissue radionecrosis. Hyperbaric oxygen therapy supports capillary regeneration by increasing vascular epidermal growth factor (VEGF) and supports more normal fibroblast activity that requires adequate tissue oxygenation. 

The synthesis of collagen that is essential for tissue regeneration is dependent on oxygen and the energy produced by mitochondria through oxidative phosphorylation that forms ATP also comes from the presence of oxygen. Hyperbaric oxygen also has effects on the improved function of neutrophil's ability to kill bacteria and makes neutrophils less adherent to endothelial cells, helping to reduce tissue edema. 

Improving results 

The patient with soft tissue radionecrosis must be treated with a multidisciplinary approach with hyperbaric oxygen therapy, and not as an isolated treatment. It is recommended to apply hyperbaric oxygen therapy in combination with appropriate surgical debridement, promptly, with antimicrobial therapy for infection, adequate nutrition, oncological considerations and consideration of plastic surgery options for treating the wound.

The affected patient must receive good wound care with the proper use of dressings to control wound moisture and bacterial growth. Cases can become very complex and not all therapy options are reasonable.

Hyperbaric oxygen therapy is often added as an adjunct especially if the tissue is fibrotic or has continuous progressive necrosis. At this point in therapy, a necrotizing infection present in soft tissue radionecrosis can be treated. It is often beneficial to perform repeated selective debridement of the wound while using hyperbaric oxygen therapy. It is especially useful to have a selective debridement about once a week after the hyperbaric oxygen treatment because the viable tissue still has a healthy color, and the necrotic tissue will stand out well, making selective debridement easier. Negative pressure therapy can be started once the tissue no longer has active tissue necrosis.

Once a healthy bed of granulation tissue has formed, treatment options are either to allow the wound to heal or to consider grafting the skin or closing the flap obtained after surgery. At this stage of the process, a plastic surgeon may help in the treatment and may even use extra treatment with hyperbaric oxygen to efficiently weld the tissues.

Fluorescent angiography is used in conjunction with the evaluation of hyperbaric oxygen therapy to produce neovascularization without the need for further treatment. Hyperbaric oxygen therapy is not limited to an arbitrary number of sessions, but sometimes more than 40 sessions are needed to achieve the desired level of healing.

IN CASE YOU HAVEN'T ALREADY HEARD ABOUT US

Centrokinetic is the place where you will find clear answers and solutions for your motricity problems. The clinic is dedicated to osteoarticular diseases and is divided into the following specialized departments:

  • Orthopedics , a department composed of an extremely experienced team of orthopedic doctors, led by Dr. Andrei Ioan Bogdan, primary care physician in orthopedics-traumatology, with surgical activity at Medlife Orthopedic Hospital, specialized in sports traumatology and ankle and foot surgery. .
  • Pediatric orthopedics , where children's sports conditions are treated (ligament and meniscus injuries), spinal deformities (scoliosis, kyphosis, hyperlordosis) and those of the feet (hallux valgus, hallux rigidus, equine larynx, flat valgus, hollow foot).
  • Neurology , which has an ultra-performing department, where consultations, electroencephalograms (EEG) and electromyography (EMG) are performed. 
  • Medical recovery  for adults and  children , department specialized in the recovery of performance athletes, in spinal disorders, in the recovery of children with neurological and traumatic diseases. Our experience is extremely rich, treating over 5000 performance athletes.
  • Medical imaging , the clinic being equipped with ultrasound and MRI, high-performance devices dedicated to musculoskeletal disorders, and complemented by an experienced team of radiologists: Dr. Sorin Ghiea and Dr. Cosmin Pantu, specialized in musculoskeletal imaging.

Find the latest news by following the Facebook and YouTube accounts of the Centrokinetic clinic.  

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