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Tuberculosis Virus To Treat Bladder Cancer

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Availability Of Data And Materials

When BCG for Bladder Cancer Goes Rogue and How It Impacts TB Clinicians

The datasets supporting the conclusions of this article are available in the National Health Insurance Research Database, Taiwan .

Only citizens of the Republic of China who fulfill the requirements of conducting research projects are eligible to apply for the National Health Insurance Research Database . The use of NHIRD is limited to research purposes only. Applicants must follow the Computer-Processed Personal Data Protection Law and related regulations of National Health Insurance Administration and NHRI , and an agreement must be signed by the applicant and his/her supervisor upon application submission. All applications are reviewed for approval of data release.

What Is Bcg Treatment For Non

BCG is an intravesical immunotherapy using a bacteria of Mycobacterium bovis that has been reduced to cause less harm to the body. The bacteria is still kept viable so that it can actively work in the body to kill the cancer cells.

Intravesical is a way in which a medication is put into the bladder. Liquid drugs are put directly into the bladder through a catheter.

BCG is used as a therapy for and protection against bladder cancers that come back after a period of time in patients that have a more aggressive bladder cancer diagnosis. It is currently the most effective treatment.

History Of Usage Of Bcg

Tuberculosis was noted to have an antitumour effect at the start of the 20th century. It was Pearl, who in an autopsy series at the Johns Hopkins Hospital in 1929 reported a lower frequency of cancer in patients with tuberculosis. In the 1930s the use of BCG as a cancer therapy was first raised, but enthusiasm for this did not mount until the 1950s and 1960s. In 1969, Mathe et al produced a paper on the treatment of lymphoblastoid leukaemia with BCG, which produced promising results, but unfortunately others could not reproduce their results. This coupled with the development of successful modern chemotherapy and radiotherapy meant enthusiasm for BCG as a treatment waned. Further research carried out by Coe and Feldman rekindled interest in BCG with the demonstration of a strong delayed hypersensitivity reaction to BCG in the guinea pig bladder. This knowledge aided Morales et al who in 1976 carried out the first clinical trial with intravesical BCG. They were able to demonstrate a remarkable decrease in the rates of recurrence of superficial bladder cancer in nine patients. A randomised prospective trial by Lamm et al in 1980 confirmed these earlier observations. Since this time it has been shown that BCG when used has inferred benefit to those with superficial bladder cancer in terms of decreased recurrence rate and increased time to recurrence.

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Comparison Of Countries With Or Without Vaccination Policy

Table shows a summary of studies that compare countries with and without nation-wide vaccination policy. In particular, they evaluate incidence or mortality rates of COVID-19 in countries with current vaccine program for BCG versus countries that never have had BCG vaccination and/or countries that have stopped this vaccination .1). Most studies assess how BCG vaccinations can affect cases and/or mortality in the ongoing pandemic mainly using regression models. Although the data are collected from public resources in all of the studies, the conclusions are contradictory among various studies. As can be seen in Table , authors in six studies argued that the BCG vaccination policy may not be effective while seven studies indicated the BCG can reduce the severity of the disease.

Current Alternatives To Bcg

Treating Bladder Cancer With Tb Virus

Research on improving NMIBC therapy has mainly focused on rescue patients who do not respond to BCG therapy, since BCG is truly efficacious in the majority of patients for avoiding recurrence and progression episodes. The alternative treatment options include virus and other bacteria different from BCG as vehicles for specific tumor growth inhibition agents or immunostimulatory components, chemotherapeutic agents, new delivery options for current therapies, and systemic immunotherapies that have to be demonstrated to be efficacious in other types of cancers .

Current alternative research for nonmuscle invasive bladder cancer treatment.

Virus-Based Treatments

Bacteria-Based Treatments

Chemotherapeutic Treatments and Improved Delivery

Different strategies can improve the use of chemotherapy for treating NMIBC. The appearance of new agents, the combination of different chemotherapeutic agents, the use of hyperthermia for improving intravesical instillation, or other strategies have been considered for improving the treatment of intermediate- and high-risk NMIBC patients.

The efficacy of intravesical therapies can also be improved through delivery adaptations such as hyperthermia, electromotive drug administration or new devices.

Checkpoint Inhibitors in Nonmuscle-Invasive BC

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Researchers Eye Cancer Drug Bcg As Potential Covid

The frantic search for ways to stop, prevent and treat COVID-19 has put the spotlight on a decades-old drug originally developed for tuberculosis , but currently used to treat bladder cancer. The Bacillus Calmette-Guerin vaccine, one of the most widely administered vaccines in the world to prevent TB, is now being researched as a potential COVID-19 vaccine. While the research into BCG has generated headlines worldwide, it may take some time to determine whether the drug is safe and effective against the virus, an often-painstaking process for any potential treatment.

How Does Bcg Work Against Cancer

BCG stimulates the immune system to attack the bacteria found in the vaccine. In treating bladder cancer, BCG is injected through a catheter directly into the tumor. When the vaccine reaches cancer cells, it sends a wave of immune cells to attack the cancer. Some patients experience flu-like symptoms, including aches, fever and chills, for a couple of days after treatment.

BCG is a known immune stimulant that both generates an immune response related to a future exposure to the microbe responsible for tuberculous and also enhances the response an individual may develop when exposed later in life to other micro-organisms, says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® .

As with any new treatment or vaccine, it may take months, even years, before doctors know whether BCG is a safe and effective weapon against the disease. Dr. Markman recommends pumping the breaks on expectations BCG or any other drug will be developed in short order. The hope is that existing pharmaceutical agents with possible clinically relevant activity against the virus may provide some level of meaningful benefit for individuals with mild or more serious symptoms, Dr. Markman says.

If you are a cancer survivor or in active treatment and are concerned about how the COVID-19 situation may impact you or your care, please contact your care team.

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How Is Bcg Given

The combination of BCG and TURBT is the most effective treatment for high-risk non-muscle-invasive bladder cancer. BCG is given once a week for six weeks, starting 24 weeks after TURBT surgery. It is put directly into the bladder through a catheter. You may be asked to change position every 15 minutes so the vaccine washes over the entire bladder. This is usually done as a day procedure in hospital, and each treatment session takes up to two hours.

Your treatment team will outline some safety measures to follow afterwards at home. This is because BCG is a vaccine that contains live bacteria, which can harm healthy people.

Let your doctor know of any other medicines or complementary therapies you are using, as they may interfere with how well the bladder cancer responds to BCG. For example, the drug warfarin is known to interact with BCG.

Analysis Of Countries With Discontinued Vaccination

How Treating Cancer with Bacteria Works | Bacillus Calmette-Guérin

The mandatory BCG vaccination policy has been stopped in some countries where the incidence of TB declined. In Table , the incidence rates of COVID-10 in vaccinated and unvaccinated subpopulation of these countries were compared. Germany is a prominent example to examine the possible impact of the age of BCG vaccinations on COVID-19 susceptibility, as vaccination schemes were different before the unification of East and West Germany . In East Germany, BCG vaccination became mandatory in 1953. By contrast, this vaccination was much less common in West Germany and it was stopped completely between 1975 and 1977. As is shown in Table the relation between BCG and morbidity and/or mortality of coronavirus has been analyzed using Students t test approach and suggests it as an effective vaccination . An RD approach is used to study the correlation between BCG vaccine and COVID-19 severity in Sweden that stated this vaccination does not have any protective effect against infection . The benefit of a shift in BCG vaccinations policy was also taken to study the correlation between BCG vaccine and COVID-19 severity in Israel and Japan and two contradictions results have been reported .

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In Vitro Evidence Of Human Immune Responsiveness Shows The Improved Potential Of A Recombinant Bcg Strain For Bladder Cancer Treatment

  • 1Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil
  • 2Programa de Pós-Graduação Interunidades em Biotecnologia USP-I.Butantan-IPT, São Paulo, Brazil
  • 3Laboratório de Imunologia Aplicada, Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, Brazil
  • 4Institute of Genetic and Biomedical Research, National Research Council, Cagliari, Italy
  • 5Institute of Protein Biochemistry, National Research Council, Naples, Italy

What Happens During Treatment

A urinary catheter is inserted through your urethra and into your bladder. Then the BCG solution is injected into the catheter. The catheter is clamped off so the solution stays in your bladder. Some doctors may remove the catheter at this time.

You have to hold the medicine in your bladder. Youll be instructed to lie on your back and to roll from side to side to make sure the solution reaches your entire bladder.

After about two hours, the catheter is unclamped so the fluid can be drained. If the catheter was already removed, youll be asked to empty your bladder at this time.

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When You Go Home

Some hospitals allow you to go home with the medicine in your bladder if you live close by and are okay with the treatment. Your team will let you know if you can do this. You should follow the advice on what to do when you pass urine.

You need to drink lots of fluid after this treatment for 24 hours. It helps clear your system of the BCG.

You should not have sex for 24 hours after each treatment. During your course of treatment and for a week afterwards, you should wear a condom during sex.

Having bladder cancer and its treatment can be difficult to cope with. Tell your doctor or nurse about any problems or side effects that you have. The nurse will give you telephone numbers to call if you have any problems at home.

What To Expect During Bcg Treatment

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First, make sure you havent had any fluids for four hours before the treatment. Right before you go into the treatment room your doctor or nurse will have you empty your bladder.

Youll lie on your back, and the medical professional will insert a catheter into your urethra and into your bladder, likely using some local numbing, and use this tube to infuse the treatment.

Once the treatment is infused, your doctor or nurse will remove the catheter. Theyll have you lie on your back, each side, and your stomach for 15 minutes each. The BCG mycobacteria needs to touch the bladder cancer cells to activate the immune system. Youll then be free to go but will need to hold off on peeing for another hour.

Verywell / Alex Dos Diaz

For at least six hours after your infusion, youll need to disinfect your pee to ensure none of the mycobacteria spread to anyone else. Pour an equal amount of bleach into the toilet after you pee and let it sit for 15 minutes before flushing.

Also, people with a penis who undergo BCG treatment should avoid sex for 48 hours to ensure they dont pass the mycobacteria to their partners.

You will likely need multiple BCG treatments. They may be given weekly for a few weeks, then less often for months or years to prevent cancer from coming back.

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When Is Bcg Treatment Used

You may have BCG directly into your bladder after surgery to remove non-muscle-invasive bladder cancer. This type of surgery is called a transurethral resection of a bladder tumour .

This treatment helps prevent the cancer from coming back in the bladder lining. It also reduces the risk of the cancer becoming muscle-invasive. Doctors usually suggest this treatment if you have a high-risk bladder cancer, or sometimes if you have an intermediate-risk bladder cancer.

There is usually at least 2 weeks between the surgery to remove the cancer and the start of BCG treatment. This is to give your bladder enough time to heal from the surgery.

You usually have BCG treatment once a week for 6 weeks. This is sometimes called the induction course. You may be offered more BCG treatments. This is usually called maintenance treatment.

Treatment times vary. Your doctor will explain what is best for you.

Bcg And Safety At Home

  • For the first six hours after BCG treatment, sit down on the toilet when urinating to avoid splashing. Pour 2 cups of household bleach into the toilet bowl. Wait 15 minutes before flushing and wipe the toilet seat with bleach.
  • If you are wearing incontinence pads, take care when disposing of them. Pour bleach on the used pad, allow it to soak in, then place the pad in a plastic bag. Seal the bag and put it in your rubbish bin. You may be able to take it back to the hospital or treatment centre for disposal in a biohazard bin.
  • If any clothing is splashed with urine, wash separately in bleach and warm water.
  • For a few days after treatment, wash your hands extra well after going to the toilet, and wash or shower if your skin comes in contact with urine.
  • Speak to your doctor or nurse if you have any questions.

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Impact Of Bcg Revaccination On Safety

The rates of adverse reactions to the first and second doses of BCG vaccination were evaluated from the findings of a large population trial carried out in Brazilian children aged 7 to 14 years. Although reaction to the second dose was more frequent than first BCG vaccinations , it was not statistically significant. The author concluded that there is insufficient safety data, but based on results, the adverse reactions to the second dose of BCG are uncommon .

Recently in the phase 3 of a double-blind, active randomized trial, it has been done to determine the potential of BCG vaccine for protecting the adult patients from infections, particularly respiratory infections. Outcomes demonstrate that vaccination of BCG is safe and it can reduce the number of infections in elderly at-risk population. Moreover, people in the treatment group took longer to occur the first infection in comparison with the placebo arm . The researchers did not found any significant difference between two groups in terms of adverse effects. Consequently, they concluded that BCG vaccination was safe among adult patients. The vaccine may also protect the adults from COVID-19, but this has not been thoroughly tested so far .

Bcg Vaccination In Various Diseases

COVID Affected Treatment for Tuberculosis, Cancer

For around 100 years, the BCG vaccine with protective effects against TB has been the most popular vaccine used worldwide. This vaccine has heterologous protective effect against unrelated diseases. Experts propose two main types of immunological mechanisms of such effects. In the first type called heterologous immunity, memory cells of CD4 and CD8 can be stimulated in antigen-independent ways, for instants by cytokines activated by secondary infections . In the second type, vaccination of BCG causes histone modifications and epigenetic reprogramming of human monocytes. This process leads to a more active innate immune response known as trained immunity . Several important molecular aspects of trained innate immunity against COVID-19 have been discussed in .

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Sex After Bcg Treatment

Men should use a condom during sex for the first week after each BCG treatment. If you are a woman having the treatment, your partner should use a condom during this time. This protects your partner from any BCG that may be present in semen or vaginal fluid. Your doctor or specialist nurse can give you more information about this.

Doctors do not yet know how BCG may affect an unborn baby. They will recommend you do not become pregnant or make someone pregnant while having it. You should use effective contraception during treatment. Your doctor or specialist nurse can give you more information about this.

What To Know About Bcg For Bladder Cancer

Did you know May is Bladder Cancer Awareness Month? It’s a time to raise extra awareness and promote facts about this disease. Education and raising awareness about bladder cancer is an important part of moving closer to a cure.

If you or a loved one is diagnosed with bladder cancer it can be frightening. However, your doctor and medical team are there to help you.

Talk with your healthcare team about all the available forms of treatment. They will tell you about possible risks and the side effects of treatment on your quality of life.

Your options for treatment will depend on how much your cancer has grown. Your urologist will stage and grade your cancer and assess the best way to manage your care considering your risk. Treatment also depends on your general health and age. Visit our condition article to learn more about treatment options for bladder cancer.

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Mechanism Of Action Of Bcg

The mechanism of action of bacillus Calmette-Guérin therapy is incompletely understood. Some early studies purported that an immune response against BCG surface antigens cross-reacted with putative bladder tumor antigens, and this was proposed as the mechanism for the therapeutic effect of BCG however, multiple subsequent studies refute this claim.

The most likely mechanism of action of BCG immunotherapy involves a combination of its direct effect on tumor cells along with the patients immune response to the therapy. These effects are summarized by Kawai et al into three categories: infection of cancer cells, induction of immune response, and antitumor effects.

The infection of cancer cells is mediated by the glycoprotein fibronectin, which allows the internalization of BCG, breakdown of proteins, and cellular changes that trigger the immune system. This is similar to the immunologic reaction that occurs in patients with tuberculosis. This immune response comprises specific cellular changes including surface receptor changes and release of various cytokines. Interferon is considered to be an important part of this process and has been used in the past to determine appropriate response to treatment. The immune response crescendos to antitumor activity in which cells recognize the cancer cells, target them for destruction, and subsequently decrease cancer burden.

The overall response to BCG is limited if the patient is immunosuppressed.

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