Bladder cancer (BC) is a serious disease that, if diagnosed too late, can lead to disability and death. According to the results of a survey conducted in January 2021 by the European Cancer Patients Coalition (ECPC) in 6 countries, every tenth respondent did not know about the existence of this pathology1. But in the structure of malignant tumors of the urinary tract, bladder cancer ranks 1st. 34% of Russians diagnosed with bladder cancer first consulted a doctor more than six months after the onset of symptoms1. In the early stages of the disease, treatment is most effective, which significantly increases survival. If symptoms appear, you should immediately consult a doctor who will conduct a thorough examination. Laboratory and instrumental research methods are used as diagnostic methods.
Doctor's examination for bladder cancer
Diagnosis of any disease begins with a survey. The doctor finds out the history of life and illness, finds out what worries the patient and evaluates existing risk factors (smoking, quantity and quality of fluid consumed, occupational hazards, etc.)2. Next, the patient is examined. If damage to the urinary system is suspected (blood in the urine, pain in the lower abdomen, urination problems), the following examination methods are used:
- Palpation of the bladder and kidney area through the anterior abdominal wall. This method allows you to assess the location, size of organs and pain in the palpation area;
- Bimanual (two-handed) rectal and vaginal palpation. With an invasive bladder tumor, a dense formation may be detected during palpation. In men with bladder cancer, rectal palpation2 is performed (through the anterior wall of the rectum). Vaginal palpation2 (through the posterior vaginal fornix) is used in women with bladder cancer. Already at the stage of interviewing and examining the patient, the doctor may suspect bladder cancer. In this case, additional laboratory and instrumental examination methods are prescribed to clarify the diagnosis.
Why get tested for HPV
Cervical cancer is a disease with a proven viral etiology. Its causative agent is the human papillomavirus (HPV), an infection transmitted primarily through sexual contact. However, the more specialists accumulate knowledge about the nature of this disease, the more myths and misconceptions accumulate among the population. Today we’ll try to figure out what to believe and what not – and at the same time answer the most frequently asked questions about HPV.
Human papillomavirus - what is it?
First of all, it's a virus. Like all other viruses, it penetrates the cell, declares itself the local ruler and sets up a factory from the cell to produce its beloved self. These viral copies penetrate neighboring cells and take control of them in the same way.
Researchers have now identified more than 150 different types of HPV. Some of them cause small, harmless papillomas on the skin, and about 40 varieties prefer the tissue of the genital organs.
HPV is a highly contagious virus, easily jumping from person to person during any form of sexual contact, including petting. Due to its high contagiousness, almost every sexually active woman will be diagnosed with HPV at least once in her life.
What will happen to me if I am diagnosed with HPV?
Since HPV prefers to “settle” in the cells of stratified squamous epithelium, which is constantly renewed and exfoliated, in most cases no disease develops.
But if something goes wrong, HPV manages to integrate into the genome of the host cell and says: “I’m in the house.” From this moment on, the immune system ceases to recognize HPV, and the development of the disease begins. Which one depends on the specific type of HPV.
Some viruses are considered low-oncogenic and cause the development of genital warts (anogenital warts) in the genital area. These growths can appear on the skin and mucous membranes of the genital organs in men and women, around the anus, on the rectal mucosa or on the cervix in women. The most common low-oncogenic types are HPV-6 and HPV-11.
Genital warts can look very ugly, sometimes even scary, but they are easy to remove with the help of medications (not on your own! There may be such a chemical burn that it doesn’t seem like much) or surgical methods (cryotreatment, radio waves, laser or electrosurgery).
Highly oncogenic types of HPV (at least 14 different types) slowly but surely “enslave” all layers of the epithelium and penetrate deeper. This process does not manifest any symptoms at all, develops very slowly, but almost inevitably leads to the development of cancer of the cervix, anus and rectum, vagina, penis, mouth and throat. The most dangerous and “evil” types are HPV-16 and HPV-18.
How is HPV infection treated?
Whether you like it or not, attempts to treat HPV infection with all sorts of magical immunotropic drugs, extracts of potatoes, broccoli and some kind of flies are a waste of money.
You can find hundreds of domestic publications and studies telling how amazingly these medicines “work”. The problem is one thing - no one can claim that the virus is defeated by the pill, and not by the body’s own work. In women under 30 years of age, spontaneous clearance of HPV occurs in most cases.
If the virus has entered the integrative phase (into the “house”) and the development of an HPV-associated disease has begun, treatment can only be surgical. If these are genital warts, they must be excised; if this is a precancerous lesion of the cervix (CIN - cervical epithelial neoplasia) - the entire area of the lesion (the doctor sees this place through a colposcope) must be removed.
What can I do to prevent the disease?
The principles of protection are the same as for other infections transmitted primarily through sexual contact. However, even constant and correct use of condoms does not exclude infection (HPV is highly contagious), although it significantly reduces the risk.
The onset of the disease caused by HPV is possible within 8–10 years from the onset of sexual activity, but in order to identify the initial signs of the disease, it is necessary not only to go to the gynecologist, but to undergo cervical screening: a cytological smear from the cervix from the age of 21 (not less than once every 3 years) and analysis for HPV of high carcinogenic risk from the age of 30 (at least every 5 years)1.
Debate has been going on for many years about at what age it is advisable to start HPV testing. In our country, they decided to add an HPV test to cytological screening from the age of 30, and in some countries, including the USA2, from the age of 25. But experts are unanimous on one thing: in young patients, HPV is detected in 90% of cases and leaves the body as quickly and easily as it is colonized. Therefore, there is no need to start testing too early - there will be a lot of unnecessary movements, tears and pointless attempts at treatment.
Does correct diagnosis guarantee protection against cancer?
It is important to understand: screening is good, but not ideal. Of course, the opportunity to catch cervical cancer in its pre-stages is a magical chance given to humanity by Georgios Papanicolaou, but there are many different “buts”.
The analysis must be taken well, transported carefully, colored correctly, viewed correctly - and at each of these stages, errors can, unfortunately, occur. In any case, the task of screening is to “catch” an already started disease at the stage of early, still precancerous, changes in order to cure it as quickly as possible.
But there is a second strategy - vaccine prevention, the task of which is to prevent infection at all. And we’ll talk about the possibilities of preventing HPV-associated diseases through vaccination next time.
Oksana Bogdashevskaya
Photo istockphoto.com
1 Benign and precancerous diseases of the cervix from the perspective of cancer prevention. Clinical recommendations (treatment protocol). Letter from the Ministry of Health of the Russian Federation dated November 2, 2017.
2 Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP): Interim clinical guidance for primary hrHPV testing 2015
Laboratory diagnosis of bladder cancer
The bladder is a hollow organ whose main function is to store urine. Therefore, enough information can be obtained already at the stage of laboratory urine testing.
Several methods of urine examination are used, which include:
- General urine analysis. This is a simple laboratory test that allows for initial screening for urinary tract diseases. With bladder cancer, blood is often found in the urine (hematuria)2. You can also evaluate the color of the urine, which changes to pink or red when there is enough blood2;
- Urine culture. It is a mandatory laboratory method to exclude urinary tract infections. This is an important step because urinary tract infections and bladder tumors often have similar symptoms3. For culture, a urine sample is placed in a laboratory dish. After 3-4 days, assess the presence of growth of pathogenic bacteria in the sample;
- Cytological examination of urine. For this test, a urine sample is examined under a microscope to look for cancerous or precancerous cells. You can also use rinsing water after cystoscopy as a sample. The method is not 100% informative3. The absence of cancer cells in a urine sample does not rule out the disease;
- Urine analysis for tumor markers. Tumor markers for bladder cancer are specific substances produced by tumor cells. The disadvantage of the analysis is that a positive result in the initial diagnosis does not mean 100% presence of bladder cancer4. This method is effectively used to detect recurrent bladder cancer in the early stages after treatment4.
What are immunoglobulin titers and how do they fall?
Immunoglobulin titers are a term used to determine the concentrations of protein molecules.
On days 4-5 after infection, IgA is detected in the blood.
But due to the fact that this period of the infectious process does not give a pronounced clinical picture, tests for them are carried out extremely rarely.
7-8 days after infection, plasma cells begin to synthesize IgM.
Proteins are produced in the primary/secondary period of syphilis, and are eliminated in the tertiary period.
Monitoring how their concentrations fall is very important for assessing the quality of treatment.
If over the course of 2-3 weeks their titers decrease slowly, we can talk about the microbiological ineffectiveness of the prescribed therapy.
Class G immunoglobulins appear 35-40 days after infection
After 55-60 days they can already be seen in routine screening tests.
When do immunoglobulins disappear from the blood during syphilis?
IgM are produced 3-4 years after confirmed clinical remission.
In some patients, the protein can be secreted throughout life, which does not guarantee 100% protection against re-infection.
Cystoscopy of the bladder
If bladder cancer is suspected, the doctor must perform a cystoscopy. The application of the method is based on examination of the mucous membrane of the bladder and the urethra (the tube connecting the bladder to the external environment). A cystoscope, a long, thin, flexible tube with a light and a small video camera at the end, is inserted into the bladder through the urethra. The doctor examines the entire inner lining and looks for pathologically altered areas.
Cystoscopy of the bladder in a man
Along with conventional cystoscopy, fluorescent cystoscopy (blue light cystoscopy)5 can be performed. For this test, a light-activated drug is injected into the bladder and taken up by cancer cells. The doctor then shines a blue light through the cystoscope. When exposed to blue light, any cells containing the drug will glow (fluoresce). This allows the doctor to see abnormal areas that might be missed when examined with normal white light. If an abnormal area is found during cystoscopy, a biopsy must be performed5. A biopsy is the removal of a small piece of tissue from an abnormal area. Tissue samples are tested for the presence of cancer cells.
Diagnosis of bladder cancer by white light cystoscopy (left) and fluorescence cystoscopy (right)
Decoding test indicators
In most cases, in order to decipher the results of a blood test for bladder cancer, special knowledge is not required at all, since the parameters indicated in the extract are clear enough for interpretation. Thus, damage to the body by syphilis can be marked in the following ways: a certain number of plus signs in the column (from 1 to 4), the inscription “positive” or “detected,” a black or more often red stamp “antibodies to syphilis detected.”
A negative reaction, indicating the absence of an infectious agent, is expressed as follows:
- a “-” sign next to the name of the hemological diagnostics;
- the inscription “not detected” or “negative”;
- blue stamp “no antibodies to syphilis detected.”
Sometimes a negative result is an indicator of the incubation period of syphilis (up to 3-8 weeks), as well as the primary period (up to 6-8 months). Therefore, to clarify the diagnosis, doctors prescribe other tests - RPGA, ELISA, RIBT, RV, RIF, etc.
Transurethral resection of bladder tumor (TURP)
This method is the gold standard in diagnosing bladder tumors and determining the extent of their spread6. A resectoscope, a thin rigid cystoscope with a wire loop at the end, is inserted into the bladder through the urethra. During a TOUR, the doctor removes the apparently altered area of the bladder, capturing the muscle layer.
Transurethral resection of bladder tumor
The removed areas are sent to the laboratory for histological examination of the samples for the presence of a tumor. The study shows whether there is invasion (penetration) of cancer into the muscular lining of the bladder. TURBT is also used as a treatment for early stage or superficial (non-invasive) bladder cancer to remove the tumor6.
Results of histological examination of material in patients with suspected bladder tumor. All patients with suspected bladder tumor underwent histological examination. In 42.1% of cases, a diagnostic biopsy was performed, in 55.2% of cases the material was obtained during surgery, in 2.6% - autopsy material.
Cancer can sometimes start in several areas of the bladder. Therefore, the doctor takes samples from different parts of the wall6. This approach is especially important if a bladder tumor is suspected but not visually detected.
Interpretation of immunoblot results for syphilis
A positive result indicates recent infection.
Repeated (+) when conducting a study after 1-1.5 months confirms the diagnosis of syphilis.
The detection of IgM in newborn infants indicates the presence of a syphilitic infection.
Since placental transfer of maternal IgM is impossible.
A negative result suggests 2 scenarios: there was no infection, the analysis was carried out before a pronounced reaction of the immune system.
In doubtful cases, another test is carried out after 7 days.
Immunoblot positivity criteria:
- (+): for M - 1 clear stripe, for G - 2 clear stripes;
- (-): for G, M - no stripes;
- (-/+): for G - 1 clear stripe, for M - 1 weak stripe.
Evaluation of TOUR results
Samples of the resected tissue are sent to a laboratory where they are examined. When detecting bladder cancer, it is important to evaluate two factors: the depth of tumor invasion and the degree of cancer differentiation2.
- Invasiveness: TUR reveals how deeply the cancer has grown into the bladder wall;
- Grade of differentiation (malignancy): A rating of tumor tissue based on the appearance of cancer cells under a microscope.
There are several degrees of tumor differentiation:
- Highly differentiated cancer. The tumor cells are more similar to normal bladder tissue. Such tumors slowly grow into neighboring organs and rarely metastasize. Patients usually have a good prognosis3.
- Poorly differentiated cancer. The tumor cells are very different from normal bladder tissue. This type of cancer is more aggressive, more likely to invade the bladder wall, metastasize, and is more difficult to treat3.
Determination of invasiveness and grade of malignancy are important factors for choosing appropriate therapy for bladder tumors.
Imaging methods in the diagnosis of bladder cancer
Imaging tests are used to determine whether cancer has spread to tissues and organs near the bladder, nearby lymph nodes, or distant organs. These studies include:
- Intravenous urography. A special dye is injected intravenously, which is removed from the bloodstream by the kidneys and ends up in the ureters and bladder. After the injection of the dye, an x-ray is taken, which shows well-defined organs of the urinary system. Intravenous urography is contraindicated in cases of allergy to the injected dye and renal failure2.
- Retrograde urography. A thin tube (catheter) is inserted through the urethra and dye is injected into the bladder. After the dye is injected, an x-ray is taken. This method is preferable for searching for urinary tract tumors in patients for whom intravenous urography is contraindicated.
- Ultrasound examination (ultrasound). This is the simplest and safest research method. Ultrasound allows you to determine the approximate size of the tumor, its location and spread beyond the bladder to nearby organs or tissues. The information value of the method is sharply reduced for tumors smaller than 5 mm3.
From left to right - pictures of the bladder using research methods: intravenous urography, retrograde urography, ultrasound
- Computed tomography (CT). A CT scan provides detailed information about the size, shape and position of any tumors in the urinary tract, including the bladder. This test also helps determine whether cancer has spread to the lymph nodes and other organs in the pelvis and abdomen. CT can detect tumors smaller than 5 mm.
- Magnetic resonance imaging (MRI). Compared to CT, this method requires more time to take images. But with MRI, the image of the pelvic organs is more contrasting3. Like a CT scan, an MRI shows a detailed image of the tumor and its spread to nearby tissues and organs.
From left to right - pictures of the bladder using research methods: CT and MRI
What is RMP?
RMP means a blood microreaction to the so-called cardiolipin antigen (bovine heart muscle extract), which is close in nature to the causative agent of syphilis. When a special antigen is introduced into a sample containing a patient’s biomaterial, a response is checked. If in the body of the person being examined, the immune system has formed antibodies (protective proteins) to the virus itself, then they will react to a similar reagent.
The pathogenic microorganism that causes syphilis in humans is Treponema pallidum. This single-celled bacterium is a spirochete (Greek for “curled hair”). Outwardly, it resembles an ultra-thin spirally twisted ribbon without any outgrowths. The microprecipitation reaction in laboratory diagnostic results can be called not only RMP, but also PRP or VDRL. During the procedure, blood is drawn from a vein.
This is what Treponema pallidum, the causative agent of syphilis, looks like
