Let’s discuss about Wilms Tumor. You may wonder what causes this rare disease, how it is diagnosed and treated, and the chances of recovery. You may also want to know about the latest research and emerging therapies for this condition.
This blog post will answer some of these questions and provide helpful information about Wilms and other childhood kidney tumors. We will also share some tips and resources to help you cope with this challenging situation.
Wilms Tumor: An Introduction
Wilms tumor is a type of kidney cancer mainly affecting children under five. It is also known as nephroblastoma, a tumor of immature kidney cells. It is the most common cancer of the kidneys in children and the fourth most common childhood cancer overall.
Wilms tumor can affect one or both kidneys. It can also spread to other body parts, such as the lungs, liver, bone, brain, or nearby lymph nodes. The symptoms of Wilms tumor may include:
- A lump or swelling in the abdomen
- Abdominal pain
- Fever
- Nausea and vomiting
- Constipation
- Loss of appetite
- High blood pressure
- Shortness of breath
- Blood in the urine
The exact cause of Wilms tumor is unknown, but it is believed to be related to errors in the DNA of kidney cells that allow them to grow and divide uncontrollably, forming a tumor. These errors may be inherited from one or both parents or occur randomly during fetal development.
Some children with Wilms tumor have specific genetic syndromes, congenital disabilities, or environmental exposures that increase their risk of developing this disease. These include:
- WAGR syndrome: A condition that affects the eyes (aniridia), genitals (ambiguous genitalia), kidneys (Wilms tumor), and mental development (intellectual disability).
- Denys-Drash syndrome: A condition that affects the kidneys (Wilms tumor and kidney failure), genitals (ambiguous genitalia), and blood (low blood platelets).
- Beckwith-Wiedemann syndrome: A condition that causes overgrowth of particular body parts (large tongue, large organs, significant birth weight), low blood sugar, umbilical hernia, and increased risk of tumors (Wilms tumor and others).
- Hemihypertrophy: A condition that causes one side of the body or a part of the body to be larger than the other.
- Familial Wilms tumor: A rare form of Wilms tumor that runs in families.
What are the symptoms of Wilms tumor?
The symptoms of Wilms tumor may vary depending on the size and location of the tumor, whether it has spread to other organs, and whether it affects the function of the kidneys. Some common symptoms are:
- A lump or swelling in the abdomen that can be felt or seen
- Stomach ache that could be acute or dull
- Fever that may come and go
- Nausea and vomiting that can get worse in the morning
- Constipation that may be caused by pressure on the intestines
- Loss of appetite and weight loss that may lead to malnutrition
- High blood pressure may cause headaches, dizziness, or blurred vision
- Shortness of breath that may be caused by fluid in the lungs or pressure on the chest
- Blood in the urine that may make it look pink or red
Some children with Wilms tumor may not have any symptoms until the tumor is enormous or has spread to other body parts. Therefore, seeing a doctor if your child has any of these signs or symptoms is important.
What are the causes of Wilms tumor?
The causes of Wilms tumor are not fully understood, but they are thought to involve genetic factors that affect how kidney cells grow and develop. Usually, kidney cells follow a program that tells them when to divide, mature, and die. This program is controlled by genes that act like switches that turn on or off certain functions.
In some children with Wilms tumor, these genes are mutated or missing, which disrupts the standard program of kidney cell development. This allows some immature kidney cells to escape from their usual location and form a nephrogenic rest mass. These cells may remain dormant or start overgrowing and forming a tumor.
Some children inherit these genetic changes from one or both parents, while others acquire them randomly during fetal development or after birth. Some of the genes that are known to be involved in Wilms tumor are:
- WT1: A gene that regulates the development of the kidneys, genitals, and other organs. Mutations or deletions of this gene can cause Wilms tumor, WAGR syndrome, and Denys-Drash syndrome.
- WT2: A gene located on the same chromosome as WT1 but has a different function. It plays a role in the control of metabolism and growth. Duplications or overexpression of this gene can cause Wilms tumor and Beckwith-Wiedemann syndrome.
- WTX is a gene located on the X chromosome that regulates cell growth and survival. Mutations or deletions of this gene can cause Wilms tumor, especially in boys.
- CTNNB1: A gene that encodes a protein called beta-catenin, which is involved in cell signaling and adhesion. Mutations or overexpression of this gene can cause Wilms tumor and other cancers.
- TP53: A gene that encodes a protein called p53 is involved in DNA repair and cell cycle regulation. Mutations or deletions of this gene can cause Wilms tumor and other cancers.
What are the Wilms tumor risk factors?
Whatever raises the likelihood of contracting an illness is considered a risk factor. Having a risk factor does not mean that a person will get the disease, and not having a risk factor does not mean that a person will not. Some risk factors for Wilms tumor are:
- Age: Wilms tumor is most common in children younger than five and rare in children older than 10.
- Race: Wilms tumor is more common in African-American children than white children.
- Family history: Wilms tumor can run in families, mainly if it affects both kidneys or occurs at an early age.
- Genetic syndromes: Wilms tumor can be associated with specific genetic syndromes, such as WAGR syndrome, Denys-Drash syndrome, Beckwith-Wiedemann syndrome, hemihypertrophy, etc.
- Birth defects: Wilms tumor can be associated with specific congenital disabilities, such as aniridia (absence of the iris), cryptorchidism (undescended testicles), hypospadias (abnormal opening of the urethra), and others.
- Environmental exposures: Wilms tumor may be linked to certain chemicals or radiation exposure before or after birth.
How is Wilms tumor diagnosed?
A combination of physical examination, blood tests, urine tests, imaging tests, and biopsy diagnoses Wilms tumor. These tests are used to:
- Confirm the presence of a kidney tumor
- Determine the type and stage of the tumor
- Assess the function of the kidneys and other organs
- Plan the best treatment option
Some of the tests that are used to diagnose Wilms tumor are:
- Physical examination: The doctor will check for signs and symptoms of Wilms tumor, such as a lump or swelling in the abdomen, high blood pressure, blood in the urine, etc. The doctor will also look for signs of genetic syndromes or congenital disabilities that may be associated with Wilms tumor.
- Blood tests: The doctor will take a sample of blood to check for low blood counts (anemia), high blood calcium (hypercalcemia), high blood urea nitrogen (BUN) or creatinine (indicating kidney damage), high levels of lactate dehydrogenase (LDH) or alpha-fetoprotein (AFP) (indicating tumor activity), and other abnormalities.
- Urine tests: The doctor will take a urine sample to check for blood, protein, bacteria, or other substances that may indicate kidney problems or infection.
- Imaging tests: The doctor will use one or more imaging tests to create pictures of the kidneys and other organs. These tests may include ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, chest x-ray, bone scan, positron emission tomography (PET) scan, or others. These tests can show the tumor’s size, shape, location, and extent and whether it has spread to other parts of the body.
- Biopsy: The doctor will take a small piece of tissue from the tumor using a needle or surgery. The tissue will be examined under a microscope to confirm the diagnosis of Wilms tumor and determine its subtype and grade.
What are the Wilms tumor treatment options?
The treatment options for Wilms tumor depend on several factors, such as:
- The stage and subtype of the tumor
- The child’s age and general health
- The kidneys’ and other organs’ operations
- The preference of the child and family
The main treatment options for Wilms tumor are:
Surgery
Surgery is the primary treatment for most cases of Wilms Surgery is the primary treatment for most cases of Wilms tumor. Surgery aims to remove the tumor and as much of the affected kidney as possible while preserving the function of the remaining kidney. There are two types of surgery for Wilms tumor:
- Nephrectomy: Surgery to remove part or all of a kidney. There are two types of nephrectomy:
- Partial nephrectomy: Surgery to remove only the part of the kidney that contains the tumor. This is done when the tumor is small and confined to one area of the kidney and when the other kidney is not working well or is missing.
- Radical nephrectomy: Surgery to remove the entire kidney and some surrounding tissue, such as the adrenal gland, lymph nodes, and blood vessels. This is done when the tumor is large or has spread to nearby structures.
- Bilateral nephrectomy: Surgery to remove both kidneys. This is done when the Wilms tumor or other diseases affect both kidneys. After this surgery, the child will need dialysis (a machine that filters the blood) or a kidney transplant (a surgery that replaces a diseased kidney with a healthy one from a donor).
Surgery may be done before or after chemotherapy, depending on the stage and subtype of the tumor. Sometimes, surgery may not be possible or advisable, such as when the tumor has spread to vital organs or blood vessels or when the child has specific genetic syndromes that increase the risk of complications.
Chemotherapy
Chemotherapy is using drugs to kill cancer cells or stop them from growing. Chemotherapy is usually given by mouth or through a vein (intravenous). Chemotherapy may be given before surgery (neoadjuvant) to shrink the tumor and make it easier to remove or after surgery (adjuvant) to kill any remaining cancer cells and prevent recurrence.
The type and dose of chemotherapy depend on the stage and subtype of the tumor, as well as the response and side effects of the treatment. Some of the drugs that are used for Wilms tumor are:
- Dactinomycin: A drug that blocks the growth of cancer cells by interfering with their DNA.
- Doxorubicin: A drug that damages the DNA of cancer cells and prevents them from dividing.
- Vincristine: A drug that stops cancer cells from forming new microtubules needed for cell division.
- Cyclophosphamide: A drug that damages the DNA of cancer cells and makes them more sensitive to radiation therapy.
- Etoposide: A drug that blocks an enzyme that helps repair DNA damage in cancer cells.
- Irinotecan: A drug that blocks an enzyme that helps cancer cells survive DNA damage.
Chemotherapy may cause side effects, such as nausea, vomiting, hair loss, mouth sores, low blood counts, infection, bleeding, fatigue, kidney damage, heart damage, and nerve damage. The doctor will monitor the child closely and prescribe medications or other treatments to prevent or relieve these side effects.
Radiation therapy
Radiation therapy uses high-energy beams, such as X-rays or gamma rays, to kill or stop cancer cells from growing. Radiation therapy may be given externally (from a machine outside the body) or internally (from radioactive materials placed inside the body near the tumor).
Radiation therapy may be used for Wilms tumor in certain situations, such as:
- When the tumor has spread to nearby lymph nodes or other organs
- When there is a residual tumor after surgery
- If there is a significant chance of recurrence,
- When there is an unfavorable histology (anaplastic) or stage (IV or V) of the tumor
The dose and duration of radiation therapy depend on the location and extent of the tumor, as well as the response and side effects of the treatment. Radiation therapy may cause side effects, such as skin irritation, nausea, vomiting, diarrhea, bladder irritation, kidney damage, growth problems, infertility, secondary cancers, etc. The doctor will try to minimize these side effects by using precise techniques and shielding healthy tissues.
What are the emerging Wilms tumor treatment options?
The treatment of Wilms tumor has improved significantly over the years, thanks to advances in surgery, chemotherapy, radiation therapy, and targeted therapy. However, there is still room for improvement, especially for children with high-risk or relapsed disease. Therefore, researchers constantly look for new and better ways to treat Wilms tumor.
Some of the emerging treatment options for Wilms tumor are:
- Immunotherapy: A treatment that uses the body’s immune system to fight cancer. Immunotherapy may work by stimulating the immune system to recognize and attack cancer cells or by giving the immune system artificial antibodies or cells that can target specific molecules in cancer cells. Some of the immunotherapy approaches that are being studied for Wilms tumor are:
- Monoclonal antibodies: Man-made antibodies that can bind to specific molecules on cancer cells and either kill them directly or mark them for destruction by the immune system. Some of the monoclonal antibodies that are being studied for Wilms tumor are:
- GD2: An antibody that targets a molecule called GD2 found on some Wilms tumor cells.
- CD171: An antibody that targets a molecule called CD171 found on some Wilms tumor cells.
- CAR T-cell therapy: A type of immunotherapy that uses genetically modified T cells (white blood cells) that can recognize and kill cancer cells. The T cells are taken from the patient’s blood, modified in the laboratory to express a receptor (called CAR) that can bind to a specific molecule on cancer cells, and then infused back into the patient. Some of the CAR T-cell therapies that are being studied for Wilms tumor are:
- GD2-CAR T cells: T cells that express a CAR that can bind to GD2 on Wilms tumor cells.
- CD19-CAR T cells: T cells that express a CAR that can bind to CD19 on Wilms tumor cells.
- Monoclonal antibodies: Man-made antibodies that can bind to specific molecules on cancer cells and either kill them directly or mark them for destruction by the immune system. Some of the monoclonal antibodies that are being studied for Wilms tumor are:
- Gene therapy: A type of treatment that uses genes to treat or prevent disease. Gene therapy may work by replacing a faulty or missing gene with a normal one or introducing a new gene that can help fight cancer. Some of the gene therapy approaches that are being studied for Wilms tumor are:
- WT1 gene therapy: A type of gene therapy that uses a virus to deliver a typical copy of the WT1 gene to Wilms tumor cells. The WT1 gene is mutated or deleted in some cases of Wilms tumor, which affects the development and function of kidney cells. By restoring the WT1 gene, the gene therapy may help stop or slow down the growth of Wilms tumor cells.
- p53 gene therapy: A type of gene therapy that uses a virus to deliver a regular copy of the p53 gene to Wilms tumor cells. The p53 gene is mutated or deleted in some Wilms tumor cases, which affects kidney cells’ ability to repair DNA damage and undergo programmed cell death. By restoring the p53 gene, the gene therapy may help trigger apoptosis (cell death) in Wilms tumor cells.
What are the future directions of Wilms tumor research?
The future directions of Wilms tumor research aim to improve this disease’s understanding, diagnosis, prevention, and treatment. Several of the topics of interest include:
- Biomarkers: Molecules or characteristics that can be measured or observed in biological samples (such as blood, urine, or tissue) and can provide information about a disease or its response to treatment. Biomarkers may help identify children at risk of developing Wilms tumor, predict how they will respond to different therapies, monitor their disease status and progression, and detect early signs of recurrence or resistance.
- Genomics: The study of the complete set of genes (genome) and their interactions in an organism. Genomics may help reveal the genetic causes and mechanisms of Wilms tumor development and progression, identify new targets for diagnosis and treatment, and classify tumors into subtypes based on their molecular features.
- Proteomics: The study of the complete set of proteins (proteome) and their interactions in an organism. Proteomics may help identify the proteins involved in Wilms tumor development and progression, discover new biomarkers and targets for diagnosis and treatment, and understand how. Proteomics may help identify the proteins involved in Wilms tumor development and progression, discover new biomarkers and targets for diagnosis and treatment, and understand how different treatments affect the protein networks in Wilms tumor cells.
- Metabolomics studies the complete metabolites (small molecules produced or consumed by biochemical reactions) and their interactions in an organism. Metabolomics may help identify the altered metabolic pathways in Wilms tumor cells, find new biomarkers and targets for diagnosis and treatment, and monitor the effects of treatments on the metabolic profile of Wilms tumor cells.
- Epigenetics: The study of the changes in gene expression or activity that are not caused by changes in the DNA sequence but by other factors such as chemical modifications, environmental influences, or interactions with other genes. Epigenetics may help explain how Wilms tumor cells acquire or lose specific characteristics, such as stemness, differentiation, or aggressiveness, and how treatments or lifestyle factors can influence these characteristics.
- Immunology: The study of the immune system and its role in health and disease. Immunology may help understand how the immune system recognizes and responds to Wilms tumor cells, how Wilms tumor cells evade or suppress the immune system, and how the immune system can be stimulated or modified to fight Wilms tumor more effectively.
Conclusion
Wilms tumor is a rare but severe type of kidney cancer that affects children. It can cause various symptoms and complications and spread to other body parts. The treatment of Wilms tumor depends on many factors, such as the tumor’s stage and subtype, the child’s age and health, and the family’s preference. Surgery, chemotherapy, radiation therapy, and targeted therapy are the main modes of treatment. The prognosis of Wilms tumor is generally good, but some children may have a higher risk of recurrence or resistance to treatment. Therefore, following up with regular check-ups and tests is essential to monitor the disease status and detect any signs of relapse or side effects.
Wilms tumor research constantly evolves and improves our knowledge and understanding of this disease. New and better ways to diagnose, prevent, and treat Wilms tumor are being developed and tested in clinical trials. These trials offer hope and opportunities for children with Wilms tumor who may not benefit from standard treatments or have relapsed after treatment. By participating in these trials, children with Wilms tumor can contribute to advancing science and medicine, improving their outcomes and quality of life.
This blog post has given you some helpful information about Wilms tumor and other childhood kidney tumors. We also hope it has inspired you to learn more about this disease and the available treatment options. Remember that you are not alone in this journey and that many people and resources can help you and your child. We wish you all the best for your child’s health and recovery.
