Nephroblastoma

Summarize

1. General

OVERVIEW: Nephroblastoma, also known as Wilms tumor, is an embryonal malignant tumor of the abdomen and the most common renal malignancy in children.
Prevalence: Commonly seen in children under 15 years of age, especially 3-4 year olds.
Presentation: Asymptomatic abdominal mass, abdominal pain, abdominal distension, hematuria, hypertension, and in a few patients, fever, anorexia, and weight loss.
Treatment: The main treatment is a combination of chemotherapy, surgery and radiotherapy.
Prognosis: Overall survival rate of Nephroblastoma is more than 85%.

2. Definition of disease

Nephroblastoma is an embryonal malignant tumor of the abdomen. It accounts for about 6% of all childhood cancers and is the most common malignant tumor of the kidney in children.
Most nephroblastomas are unilateral, meaning they affect only one kidney. However, in a few cases, there are bilateral tumors, meaning both kidneys are affected. In rare cases, a patient will develop a unilateral tumor first, which later develops into a bilateral tumor.

3. Epidemiology

Nephroblastoma is most common in children under the age of 15, especially those aged 3-4 years. 98% of patients are younger than 10 years of age at the time of diagnosis, and 75% are younger than 5 years of age. The incidence of nephroblastoma in the United States is 7.1 cases per 100,000 people, with a slightly lower incidence in Asian populations. The average age of diagnosis for unilateral nephroblastoma is 44 months, and the average age of diagnosis for bilateral nephroblastoma is 31 months. There were slightly more women than men with unilateral nephroblastoma (male to female ratio of 0.92:1.00), while 62.5% of patients with bilateral nephroblastoma were women.

4. Types of diseases

(1) Pathohistologic typing
Pathohistologically, nephroblastoma includes three different types of components: primitive renal germ, epithelium and mesenchymal tissue. According to the proportion of different types of components, nephroblastoma can be divided into the following six subtypes:
● Germ-dominant type: >65% germ component in nephroblastoma. Germ cells are small, tightly arranged, with round and oval nuclei, coarse nuclear chromatin, small nucleoli, many nuclear schizonts, little cytoplasm, and basophilic. According to the arrangement of germs, they are divided into four types: diffuse germ type, serpentine germ type, nodular or organoid germ type, and basal cell-like germ type.
● Epithelial-dominant type: the epithelial component of the tumor is >65%, which includes glandular lumens, glandular ducts, chrysanthemum-shaped masses, and glomeruloid-like structures composed of epithelial cell clusters of different different degrees of differentiation, and heterogeneous epithelium such as mucus cells, squamous cells, and neuronal cells in rare cases; according to the differentiation degree of the epithelial component, the tumors are classified into differentiated and undifferentiated types. SIOP emphasizes that the epithelial type should not contain more than 10% germinal tissue, otherwise it is a mixed type.
● Mixed type: the tumor consists of a mixture of 3 or 2 of the above tissue forms, with no component greater than 65%.
● Regressive type: for nephroblastoma that has undergone preoperative chemotherapy, when necrotic regression occurs in more than 2/3 of the entire tumor tissue it is regressive; if the necrotic tissue is less than 2/3, it is classified according to the residual predominant tumor tissue components and labeled with the content (e.g., germ, epithelial, and mesenchymal components); if the tumor cells are completely necrotic and there are no diagnostic tumor cells, it is the completely necrotic type, indicating sensitivity to chemotherapy and a Prognosis is good.
● Mesenchymal type: about 5% to 8% of nephroblastoma develop mesenchymal degeneration, and the characteristics of mesenchymal degeneration include: the nucleus of tumor cells is obviously enlarged, with a diameter larger than three times that of adjacent similar cells; the chromatin of cell nucleus is obviously increased, and the nucleus is deeply stained; and the appearance of nuclear schizophrenia with atypical or obvious polyploidy is seen. According to the number of interstitial lesions, they can be divided into:
● Focal interstitial lesions: fewer than 10% of cells per high power field of view interstitial lesions, regionally confined, limited to the renal parenchyma (those appearing in the vascular interstitium should be excluded), with a favorable prognosis.
● Diffuse interstitial lesions: interstitial cells are multifocal, the boundary between interstitial cells and surrounding non-interstitial tissues is indistinct, beyond the tumor periphery; interstitial cells may invade intra- or extra-renal vessels, renal sinusoids, extra-renal periphery, and metastatic foci. The prognosis is poor.
In addition, there are some special types of nephroblastoma:
● Teratoma-like nephroblastoma: nephroblastoma variant, the tumor tissue contains not only renal germ, epithelial and mesenchymal components, but also heterologous components fat, cartilage, muscle, squamous epithelium, etc., and its heterologous components >50% of the tumor components.
● Cystic partially differentiated nephroblastoma: it is a multicystic renal tumor, the wall of the capsule is covered with flat, cuboidal epithelium, and the fibrous intervals contain different amounts of renal germ, epithelial tubules or glomerular structures and mesenchymal tissue components at different stages of differentiation, and skeletal muscle, cartilage, and mucus-like mesenchymal stroma are also seen, and the prognosis is good.
● Fetal rhabdomyosarcoma-type nephroblastoma: a mesenchymal-dominated special type, 30% are bilateral, the tumor section is tough and resembles uterine tumor leiomyoma. Microscopically: the tumor is long spindle-shaped, mostly well-differentiated fetal rhabdomyosarcoma, with visible myotome texture, containing islands of primitive renal germ or primitive tubular components. The prognosis of the child is good.
(2) Disease staging
At present, the international common clinical staging of nephroblastoma mainly includes the American Children's Oncology Research Cooperative Group (COG) in North America and the International Cooperative Group for the Study of Pediatric Oncology (SIOP) in Europe, and the current domestic staging system mainly refers to the COG staging system.
COG staging
Stage I: the tumor is confined to the kidney, complete resection is possible, the renal peritoneum is intact, there is no rupture or biopsy of the tumor before operation, the renal sinus vessels are not invaded, the margins are negative, and the lymph nodes are negative.
Stage II: complete resection is possible, negative margins, local invasion of the tumor (renal peritoneum, renal sinus), renal sinus vascular invasion, negative margins, if the hemangioma is embolized and can be resected along with the tumorous kidney it is considered as stage II.
Stage III: abdominopelvic lymph node involvement, tumor penetration through the peritoneal surface or peritoneal implantation, visual or microscopic residue, tumor invasion of important organs, visual inability to complete resection, preoperative or intraoperative rupture of the tumor, preoperative biopsy, and resection of the tumor in pieces.
Stage IV: hematogenous metastasis (lung, liver, bone, brain), extra-abdominal pelvic lymph node metastasis.
Stage V: bilateral nephroblastoma.
SIOP staging
Stage I: the tumor is confined to the kidney or perinephric fibrous pseudoepithelium, does not invade the perinephric membrane, and can be completely resected with negative margins; tumor tissue may protrude into the renal pelvic system, but the surrounding tubular wall is not involved; renal sinus vasculature is not involved; intranasal vasculature may be involved; percutaneous puncture biopsy; perinephric fat/renal sinus may appear necrotic.
Stage II: Tumor extends beyond the renal or perirenal fibrous pseudocapsule and invades perirenal fat; complete resection is possible with negative margins; tumor invades renal sinus vessels and lymphatics; complete resection is possible; tumor invades adjacent organs or the inferior vena cava but can be completely resected; percutaneous biopsy is possible.
Stage III: tumor cannot be completely resected, with residual margins (visual or microscopic residual); abdominal lymph node involvement; preoperative tumor rupture; tumor invasion of peritoneal tissues; peritoneal implantation metastasis; tumor embolus residuals in blood vessels or ureteral margins, resected in chunks; preoperative biopsy surgery; if lymph nodes or margins are necrotic after chemotherapy, it is recognized as stage III.
Stage IV: hematogenous metastasis (lung, liver, bone, brain), extra-abdominal pelvic lymph node metastasis.
Stage V: bilateral nephroblastoma.
(3) Disease risk grouping
At present, the international risk grouping mainly refers to the grouping methods of the U.S. Children's Oncology Research Cooperative Group (COG) and the Children's Oncology Research International Cooperative Group (SIOP). Since the treatment modalities recommended by COG and SIOP are different, and both treatment modalities are common in China, the grouping method is usually chosen according to the patient's initial treatment modality.
● COG grouping
COG recommends direct surgery, after which patients are categorized into those with a good prognosis (FH) and those with a poor prognosis (UFH) according to the type of pathology:
● Favourable prognosis type (FH): nephroblastoma that does not contain mesenchymal lesions.
● Poor prognosis type (UFH): focal and diffuse mesenchymal nephroblastoma.
● SIOP subgroup
The SIOP subgroups recommend preoperative chemotherapy and postoperative classification into different risk groups according to the type of pathology:
● Low-risk group: mesenchymal nephroma, partially cystic differentiated nephroblastoma and completely necrotic nephroblastoma;
● Intermediate risk group: mesenchymal-dominant, epithelial-dominant, mixed, degenerative and focal mesenchymal;
● High-risk group: germinal-predominant, diffuse mesenchymal, clear cell sarcoma and malignant rhabdomyosarcoma.

Dpidemiological

not have

Etiolog & Risk factors

1. General

Nephroblastoma develops from kidney cells that have not developed and differentiated to maturity, and the exact cause is unknown. Most cases of nephroblastoma are not hereditary. The tumor develops due to a genetic variation that causes the cells to grow and proliferate abnormally, forming a tumor. The genetic variant that causes nephroblastoma is not fully understood.

2. Underlying causes

During fetal development, there may be some undifferentiated kidney cells called "nephrogenic surplus". Usually, these cells mature by the age of 3-4 years. However, in a small number of children, these cells may proliferate abnormally and develop into nephroblastoma.
The exact cause of nephroblastoma remains unclear and most cases are not hereditary. About 1/3 of patients with nephroblastoma are known to have mutations in the genes WT1, CTNNB1, and WTX.

3. Vulnerability factors

:: Beckwith-Wiedemann syndrome:: This genetic disorder is caused by an abnormality in the genes that control growth and development and can cause overgrowth in various parts of the body. Most children with Beckwith-Wiedemann syndrome will be diagnosed with nephroblastoma by age 10.
● Denys-Drash syndrome: a genitourinary abnormality caused by a genetic abnormality whose patients have a 90% chance of developing a nephroblastoma.
● Frasier syndrome: a genitourinary abnormality caused by a genetic abnormality.
● Isolated lateralized hyperplasia: a developmental abnormality that manifests as an abnormal enlargement of one side of the body or part of the body.
● Family history of nephroblastoma: if a child has a parent or sibling with nephroblastoma, that child is at a higher risk of developing the disease.
● Absence of iris: The iris is the colored part of the eye, and absence of the iris is often caused by a genetic abnormality.
● Urinary abnormalities: such as cryptorchidism or hypospadias, which often accompany nephroblastoma.
● 11p deletion syndrome (WAGR syndrome): an abnormality of the genetic material (chromosomes) that may lead to nephroblastoma, absence of irises, genitourinary abnormalities, and mental retardation.
It is important to note that susceptibility factors and the disease cannot be equated. It is not a certainty that you will develop nephroblastoma with all of the above risk factors, and it is possible to develop nephroblastoma without any of the above susceptibility factors.

Classification & Stage

not have

Clinical manifestations

1. General

Initial symptoms of nephroblastoma are not obvious, commonly showing symptoms of abdominal mass, abdominal pain, abdominal distension, hematuria, hypertension, and in a few patients, fever, anorexia, and weight loss.

2. Typical symptoms

The most common symptom of nephroblastoma is an unintentionally detected abdominal mass. About 40% of patients present with abdominal pain, and about 18% present with hematuria with the naked eye and 24% with microscopic hematuria (blood in the urine is not visible to the naked eye, but blood cells can be seen under the microscope on urinalysis). Hypertension manifests itself in about 25% of patients. It may be accompanied by fever, anorexia, and weight loss in 10% of patients; patients with lung metastases may present with respiratory symptoms, and liver metastases may cause epigastric pain.

3. Accompanying symptoms

It may cause obstruction of the inferior vena cava, which may manifest as varicose veins of the abdominal wall or varicose veins of the spermatic cord. In some rare cases it can cause pulmonary embolism.

Clinical Department

1. General

The primary diagnosis of nephroblastoma is based on history, physical examination, imaging and/or histopathology.

2. Departments attended

Urology, Surgical Oncology

Examination & Diagnosis

related checkup

(1) Abdominal imaging examination
● Abdominal ultrasound: used to initially determine the location of the tumor, its size, its relationship with the surrounding tissues, and whether there is a tumor thrombus in the blood vessels.
● Abdominal enhanced CT (contrast agent is prohibited in the presence of renal insufficiency) or magnetic resonance imaging (MRI): about 4% of patients with nephroblastoma are accompanied by tumor thrombus in the inferior vena cava or atrium, and 11% of patients are accompanied by tumor thrombus in the renal veins, and pulmonary embolism is very rare but often fatal; therefore, preoperative enhanced CT and MRI can not only determine the origin of renal tumors, determine whether it is a unilateral tumor or bilateral tumors, and observe whether there is tumor metastasis in the abdominal organs, but also determine whether there are tumor metastases in the abdominal organs, but also determine whether there are tumor metastases in the abdominal organs. the presence of tumor metastases in the abdominal organs, but also to identify vena cava tumor embolism and detect possible inferior vena cava or atrial tumor embolism, renal vein tumor embolism, and pulmonary embolism.
● Chest CT: used to check for tumor metastasis in the lungs and to determine the status of metastatic lesions within the lungs.
● PET-CT: usually used for multiple metastases or recurrence, not recommended as a routine test.
● Interstitial nephroblastoma requires head MRI and whole-body bone scanning.
(2) Laboratory tests
Routine blood, urine and biochemical tests, including liver and kidney function, electrolytes and lactate dehydrogenase.
There is no specific tumor marker for nephroblastoma, but there are some indicators that can help typing or differential diagnosis. For example, alpha-fetoprotein (AFP) level can be used to identify teratoma-type nephroblastoma, and neuron-specific enolase (NSE) can be used to identify tumor rupture and renal neuroblastoma.
(3) Biopsy
According to the US Children's Oncology Research Collaborative Group (COG), preoperative puncture biopsy of stage I or II nephroblastoma will elevate the stage of the tumor, so routine puncture biopsy is not recommended, and direct surgical resection can be performed.
The International Collaborative Group for the Study of Pediatric Oncology (SIOP) recommends preoperative chemotherapy and does not recommend puncture biopsy as a routine procedure, although it is believed that puncture biopsy does not affect tumor stage.
Therefore, for nephroblastoma, puncture biopsy is not a routine operation and is only used for some lesions that are difficult to determine clinically.
(4) Bone marrow cytology
It is used for the diagnosis of mesenchymal nephroblastoma.

4. Differential diagnosis

(1) Clear cell sarcoma
Clear cell sarcoma is diagnosed at an average age of about 3 years and is easily confused with nephroblastoma. However, there is no renal embryonic, epithelial and mesenchymal tissues in clear cell sarcoma, and clear cell sarcoma cells express waveform protein and cyclin D1, but epithelial markers, WT1, CD99, etc., are negative, so it can be differentiated from nephroblastoma accordingly.
(2) Renal malignant rhabdomyosarcoma
Renal malignant rhabdomyosarcoma is most common in children under 2 years of age, and it is easy to be confused with nephroblastoma because of the presence of embryonic kidney-like tissue in the tumor. However, renal malignant rhabdomyosarcoma has no epithelioid and mesenchymal tissues and the expression of INI1 is negative in immunohistochemistry, and there is an intermediate filamentous structure in the cytoplasm of the cells as seen in the electron microscope, which can be differentiated from nephroblastoma.
(3) Neuroblastoma
Neuroblastoma can sometimes be confused with nephroblastoma. However, there are no nephroblasts, epithelial and mesenchymal tissues in neuroblastoma tissues, and the tumor cells only express TH, PGP9.5, chromogranin A (CgA), synaptophysin, etc., and do not express WT1, CK, myoplasmic protein and WT1, so it can be differentiated from nephroblastoma accordingly.
(4) Congenital mesodermal nephroma (CMN)
A small amount of residual tubules and glomeruli can be seen in congenital mesangial lobe nephroma, which may sometimes be confused with nephroblastoma. However, there is no renal embryonic or epithelial tissue component in congenital mesodermal lobe nephroma. Meanwhile, congenital mesodermal nephroma expresses junctional proteins, actin, and fibronectin, but is negative for epithelial markers, and its cell type has a characteristic t(12;15)(p13,q25) translocation, which can be differentiated from nephroblastoma accordingly.
(5) Renal teratoma
Renal teratoma can occur at all ages, with characteristic renal embryonic, epithelial and mesenchymal tissue components, and its mesenchymal components and glomeruloid structure are similar to that of nephroblastoma, which is sometimes difficult to distinguish. However, renal teratomas do not have consistent primitive renal germ components and lack embryonic tubular or glomerular structures, and WT1 is negatively expressed, so they can be distinguished from nephroblastomas accordingly.

Clinical Management

1. General

At present, in the world, the treatment of nephroblastoma is mainly divided into two major treatment options: in North America, the American Children's Oncology Research Collaborative Group (COG) protocol is mostly used, which recommends direct surgical treatment, and further treatment is taken according to the postoperative pathology and staging; in Europe, the International Collaborative Group for the Study of Children's Oncology (SIOP) protocol is mainly used, which recommends preoperative chemotherapy, and surgical resection after the tumor has shrunk. Treatment is based on different risk levels. According to the current study, there is no significant difference in the 5-year survival rate between these two treatments. The Recommendations for the Diagnosis and Treatment of Nephroblastoma in Children, issued by the Pediatric Tumor Committee of the Chinese Cancer Society (CCCG) in 2016, are mainly based on the protocol of COG. Currently in China, the protocols of COG and SIOP are equally commonly applied, and the attending physician usually chooses the appropriate initial and subsequent treatment plan according to the hospital situation and the patient's condition.
(1) COG/CCCG program
COG/CCCG recommends direct surgical resection, but preoperative chemotherapy is recommended for some special types of nephroblastoma, such as: isolated renal nephroblastoma, inferior vena cava thrombus above the level of the hepatic vein, tumor invasion of the surrounding organs (except the spleen, pancreas, colon, and adrenal glands), inoperable nephroblastoma, diffuse lung metastasis, and bilateral nephroblastoma. Further therapeutic measures, such as chemotherapy regimens and radiotherapy, are taken after surgery based on staging and pathologic typing; bilateral nephroblastoma is treated with the highest unilateral staging.
If direct surgery is considered at the time of initial consultation, the patients should be treated according to COG standards after surgery, taking into account the staging, pathology, and heterozygous deletion of chromosome 1p/16q.
(2) SIOP program
After clinical diagnosis of nephroblastoma, preoperative chemotherapy can be carried out according to the staging (SIOP believes that puncture biopsy will not improve the staging, but not as a routine means of examination), with 4 weeks/6 weeks evaluation. Postoperatively, further treatment options are based on staging and pathologic typing; the highest unilateral staging is used for bilateral nephroblastoma treatment. In the SIOP protocol, surgical sampling biopsy follows chemotherapy, so the histological type monitored in the case is post-chemotherapy, and should be strictly classified according to the histological criteria for the subtypes of nephroblastoma recommended by the SIOP, and also combined with staging, to perform risk grouping and target individualized treatment.

2. Surgery

(1) Radical resection of unilateral nephroblastoma (for most unilateral lesions)
Unilateral radical nephroblastoma resection can be performed for most unilateral tumors. In order to obtain a good surgical field, radical resection of unilateral nephroblastoma is usually performed through a transverse abdominal incision, which must be large enough to avoid excessive intraoperative compression of the tumor, and may be performed as a combined thoraco-abdominal incision if necessary.
(2) Unilateral nephroblastoma with preserved renal unit tumor stripping (NSS)
At present, unilateral nephroblastoma with preserved renal unit tumor stripping is still controversial. If unilateral preserved renal unit tumor stripping is considered, comprehensive consideration is needed, and the cases should be limited to stage I as much as possible, the tumor is located in one pole of the kidney, and it has not infringed on the collecting system, and it is necessary to appropriately excise more peritumoral renal tissues in the surgical resection, to ensure the margins of the cuts are negative and to avoid the residuals.
(3) Bilateral nephroblastoma with preserved renal unit tumor stripping (NSS)
Whether COG or SIOP, bilateral nephroblastoma is recommended to undergo bilateral preserved renal unit tumor stripping, with routine preoperative chemotherapy, and evaluation of bilateral kidneys after chemotherapy, and preserved renal unit tumor stripping can be performed in stages. Depending on the size and extent of the tumor, enucleation or tumor plus partial nephrectomy may be chosen; if both tumors are small, one-stage resection is feasible. It is also feasible to perform nephrectomy on one side and tumor debulking with preservation of renal unit on the other side.

3. Chemotherapy and radiotherapy

The U.S. Children's Oncology Research Collaborative Group (COG) recommends chemotherapy after surgery based on the pathology and staging decision, and the Society for the Study of International Oncology in Children (SIOP) recommends preoperative chemotherapy and surgical resection of the tumor after it has shrunk, depending on the level of risk. Commonly used chemotherapy regimens are:
● AV regimen: vincristine + gentamicin
● AVD regimen: vincristine + gentamicin + doxorubicin (cumulative dose of doxorubicin 150 mg/m²)
● VDACE regimen: vincristine + gentamicin + doxorubicin + cyclophosphamide + etoposide (cumulative dose of doxorubicin 195 mg/m²)
● VDCBE regimen: vincristine + doxorubicin + carboplatin + cyclophosphamide + etoposide
● VDCBEI regimen: vincristine + doxorubicin + cyclophosphamide + etoposide + etoricoxib (cumulative dose of doxorubicin 225 mg/m²)
Both COG and SIOP recommend radiotherapy within two weeks of surgery. Radiotherapy is generally delivered in low-dose fractions of 10-20 Gy.
(1) Principles of COG radiotherapy

(2) SIOP radiotherapy principles

4. Other treatments

Kidney transplantation: In patients with bilateral kidney tumors, a kidney transplant may sometimes be needed due to problems with kidney function. Usually, kidney transplantation is waited for 1-2 years before it is performed, both to complete the treatment and to confirm that there are no signs of recurrence.

Prognosis

1. General

Overall, the prognosis for nephroblastoma is excellent, with an overall survival rate of more than 85%. No significant difference between COG and SIOP treatment regimens in terms of 5-year patient survival has been found.
According to a retrospective summary conducted by the Chinese Pediatric Tumor Board in 2015, the 5-year event-free survival rate was 81.2% for the COG good-prognosis type and 8.9% for the poor-prognosis type. Among the COG prognostic good type, the 5-year event-free survival rates for stages I to V were 91.7%, 78.0%, 78.3%, 77.2%, and 50.4%, respectively.
Meanwhile, for patients who needed to receive radiotherapy according to the treatment plan, radiotherapy could significantly improve the event-free survival rate of patients.
Factors affecting prognosis are:
● Tumor risk grouping: the lower the grouping, the better the prognosis
● The stage of the tumor at diagnosis: usually the earlier the stage, the better the prognosis
● Whether the tumor has a heterozygous deletion of chromosome 1p/16q: if such a deletion is present, the prognosis will be relatively unsatisfactory.
● Age of the patient at diagnosis: younger patients usually have a better prognosis.

2. Complications and treatment side effects

(1) Surgical complications
The main complications of nephroblastoma surgery include: intestinal obstruction (5.1%), bleeding and infection (1.9%), and vascular injury (1.5%). The chances of complications are mainly related to the size of the tumor, its relationship with the surrounding tissues, and the surgeon's technique.
Meanwhile, bilateral nephroblastoma that undergoes tumor debulking with preservation of the renal unit may develop transient renal insufficiency, urinary fistulae, urinary tract infections, and intussusception in the postoperative period.
(2) Drug cardiotoxicity
Anthracycline chemotherapeutic drugs are cardiotoxic. The patient's ECG needs to be checked before each course of therapy with anthracyclines. If a risk of serious arrhythmia or cardiac insufficiency is identified, coadministration of dexpanthenol may be considered. Once cardiac insufficiency is detected, anthracyclines should be disabled and cardiology consultation should be invited to assist in treatment.
(3) Drug hepatotoxicity
Some chemotherapeutic drugs are toxic to the liver and are clinically manifested by elevated aminotransferases (ALT). If the simple aminotransferase elevation does not exceed 10 times the normal limit before treatment, then no adjustment can be made to the treatment; if the elevation of aminotransferase exceeds 10 times the normal limit, then chemotherapy should be delayed for 1 week and liver function should be reviewed; if the elevation of aminotransferase persistently exceeds 10 times the normal limit, then the cause of the liver impairment should be actively searched for and treated, and treatment can be continued under close observation. Simple transaminase elevation during the treatment period, unless it is clearly non-treatment-related elevation, should be observed only and no adjustment of treatment is needed.
(4) Anemia
Anemia can usually be relieved by transfusion of red blood cells. Transfusions are mandatory for hematocrits below 60 g/L.
(5) Thrombocytopenia
Platelets should be transfused when the platelet count is less than 20×109 /L. When there are obvious bleeding symptoms or infections, the indications for transfusion can be appropriately relaxed.
(6) Neutrophil deficiency
Granulocyte colony-stimulating factor (commonly known as leukocyte boosting injection) may be used if it is anticipated that the patient may develop a prolonged granulocyte deficiency.
(7) Hemorrhagic cystitis
Certain chemotherapeutic agents, such as cyclophosphamide and isocyclophosphamide, when administered intravenously in high doses and in the absence of effective prophylaxis, may lead to hemorrhagic cystitis, which manifests itself as bladder irritation, oliguria, hematuria, and proteinuria, due to bladder irritation by its metabolite acrolein. However, the incidence of hemorrhagic cystitis is low when cyclophosphamide is applied at routine doses. During high-dose intravenous infusion of cyclophosphamide and isocyclophosphamide, hydration, bladder protection, and other symptomatic treatments may be administered.
(8) Nephrotoxicity
Certain chemotherapeutic drugs, such as carboplatin and cisplatin, may cause nephrotoxicity, which is mainly manifested as renal tubular injury. Acute damage usually occurs 10-15 days after drug administration, with increased blood urea nitrogen (BUN) and creatinine (Cr) and decreased creatinine clearance, which is mostly reversible. However, repeated high-dose therapy may result in persistent mild to moderate renal damage. There is no effective means of prevention other than hydration.
(9) Neurotoxicity
Certain chemotherapeutic agents, such as vincristine and vinblastine, may cause peripheral neurologic symptoms, such as finger and neurotoxicity, the severity of which is related to the cumulative amount. There may be numbness of the toes, sluggishness or loss of tendon reflexes, peripheral neuritis, abdominal pain, constipation, paralytic intestinal obstruction occasionally, motor, sensory, and cerebral nerves may also be ruptured and produce corresponding symptoms, but they are usually reversible and are better tolerated by children than by adults.
(10) Hearing impairment
Platinum-based chemotherapeutic agents may have an effect on the patient's hearing, causing hearing loss. Therefore, each time before chemotherapy with this type of drug, it is necessary to conduct a hearing examination to understand the patient's hearing.

3. Recurrence

The recurrence rate of nephroblastoma is not high, but it does occur, usually within 2 years of the end of treatment.

Follow-up & Review

After patients finish treatment, regular review follow-up is required to monitor recurrence and long-term effects.

Within 2 years after surgery, review is done once every 3 months, every 6 months between the 2nd and 5th years, and once a year is recommended after 5 years.
Blood tests, biochemistry, abdominal ultrasound, chest radiograph or chest CT (alternately) should be checked at the time of review. If suspicious lesions are found at the review, further examination by localized enhanced CT or enhanced MRI is recommended.

Routine

(1) Rest and exercise
Patients need to be guaranteed a sleep schedule. Regular and quality sleep is helpful for physical recovery and immunity. A suitable sleeping environment (usually dimly lit, quiet and at a suitable temperature) may be helpful in improving the quality of sleep.
If the patient's physical condition permits, simple activities can be encouraged and assisted. Moderate exercise is helpful in preventing muscle atrophy, enhancing physical strength and endurance, and promoting appetite.
(2) Diet
It is recommended to provide patients with a nutritious and balanced diet, guaranteeing the intake of high-quality proteins (e.g. meat, eggs, milk, poultry, fish and shrimp, soybeans and soybean products, quinoa, etc.), as well as more grains and cereals, vegetables and fruits to ensure the intake of other nutrients. Patients during treatment will have reduced immunity and should avoid expired, spoiled, unclean and potentially food-safe foods. If the tumor or treatment affects kidney function (to be determined by relevant test results), it may be necessary to restrict the intake of certain trace elements (such as potassium and phosphorus). Specific dietary advice can be obtained from the dietitian at your hospital.

4. Special considerations

All consultation and treatment records of the patient should be kept for future review and medical consultation as reference.
Meanwhile, if a patient has a unilateral kidney removed during treatment, the postoperative period will generally have little effect on daily life if there are no complications, and the patient can eat and live normally. It is just that in the future life, we should pay attention to avoid the use of drugs with relatively high nephrotoxicity or treatments that may have the risk of kidney damage, and try to preserve the function of the kidney as much as possible.

5. Daily disease monitoring

Post-operative complications, chemotherapy-induced side effects (e.g., hair loss, fatigue, vomiting, etc.), recurrence of tumor metastasis, growth and development problems, and other issues need to be addressed. Consult your doctor when there is fever, worsening of symptoms, new symptoms, and treatment-induced side effects.

6. Prevention

Since the exact cause of nephroblastoma is not known, there is no method of prevention. However, certain diseases are known to be associated with an increased risk of hepatoblastoma (see "Predisposing Factors"). Therefore, if a child has such a condition, he or she should be screened for the tumor.

Cutting-edge Therapeutic & Clinical Research

not have

References

1. National Health and Health Commission of the People's Republic of China. Pediatric nephroblastoma diagnosis and treatment standard (2019 edition). 2019.
2.Pediatric Tumor Specialized Committee of the Chinese Anti-Cancer Association. Recommendations for diagnosis and treatment of pediatric nephroblastoma (CCCG-WT-2016). Chinese Journal of Pediatrics. 2017, 52(2): 90-94.
3.Beijing Children's Hospital Group Pathology Collaborative Group. Consensus on pathologic diagnosis of pediatric nephroblastoma. Chinese Journal of Pathology. 2017, 46(3): 149-154.
4.Xu H, Ding J, Yi W. Pediatric Nephrology. People's Health Publishing House. 2018.
5. https://www.cancer.gov/types/kidney/hp/wilms-treatment-pdq#_1
6. https://www.cancer.net/cancer-types/wilms-tumor-childhood/ introduction
7. https://www.cancer.org/cancer/wilms-tumor.html
8. Szychot et al. Wilms' tumor: biology, diagnosis and treatment. Transl Pediatr. 2014. 3(1): 12-24.
9.Treger et al. The genetic changes of Wilms tumour. Nature Reviews Nephrology. 2019. 15: 240-251.