Treatment and Prognosis Wilms Tumor ADULT kidney tumors

The prognosis of adults with WT is poor compared with children who have a 85% chance of cure. This success in pediatric WT represents a paradigm shift to multimodal treatment. Historically in the 1980's, most series of adult cases had reported long-term survival of about 25%. Before the report of Arrigo et al. of 27 patients reported to NWTSG 1979-87 with an overall survival at 3 years of 67%, it was believed that this high cure rate can not be achieved in adults. What is Wilms Tumor? you can read in Wilms Tumor ADULT kidney tumors

This series includes six stages I, five stage II, four stage III, eleven stage IV, one patient with stage V-four patients with anaplastic histology. In this series, 26 patients underwent nephrectomy, 25 received chemotherapy and 20 received radiation treatment. This led to recommendations that patients with stage I disease and favorable histology should be treated with surgery followed by 6 months of postoperative chemotherapy with actinomycin-D and vincristine without postoperative radiotherapy, and for stage II, III and IV / FH vincristine, actinomycin-D and doxorubicin for 15 months with 2000 cGy radiation to the tumor bed, from 1200 to 1500 cGy to the lungs, liver 2000 cGy and 3,000 cGy to other sites where appropriate in patients with metastatic at diagnosis. Kattan et al. reported the French experience in 22 adult patients 1973-92.

His series included four stage I, eight stage II, three stage III and seven patients with stage IV. All patients underwent nephrectomy followed by adjuvant treatment modality in only seven patients (radiotherapy and chemotherapy in one in six) and combined modality in 15 patients. The chemotherapeutic agents most often used actinomycin-D, vincristine and doxorubicin. Two of the seven (29%) and 07/15 (47%) patients were free of disease after first-line treatment. salvage chemotherapy had to be given in 13 patients. After a mean of 100 months, 12/22 patients (55%) were alive, including ten who were free of disease (45%). We recommend aggressive treatment, including the three-drug regimen (actinomycin-D + vincristine + doxorubicin), regardless of the stage, and irradiation starting phase II. Terenziani et al. reviewed the Italian experience with 17 adult patients between 1983-2001 who were treated with an Italian protocol and were followed for an average of 131 months.

This included eight patients with stage II, four patients with stage III and five patients with stage IV and included a patient with anaplasia. Sixteen patients undergoing nephrectomy patients, fifteen received chemotherapy (ten with both drugs and five with three drugs) and seven patients received radiation. The 5-year survival free of disease was 45% with an overall survival of 62%. Reinhard et al. reviewed the German experience, which included 30 adult patients in the SIOP 93-01 study. Ten patients (33%) had metastatic disease at presentation. There was a predominance of the upper stage (Stage I, 8 stage II, 7, stage III, 15 patients), histology revealed an intermediate risk in 23 high-risk patients and in 2 patients. Twenty-six patients underwent radical nephrectomy and primary of the other four patients received neoadjuvant chemotherapy before surgery. Nineteen patients received chemotherapy and 11 intermediate risk patients received chemotherapy with high risk according to the protocol. Intermediate-risk chemotherapy includes vincristine, doxorubicin, actinomycin-D ± 18 to 27 weeks, and high-risk scheme etoposide, carboplatin, ifosfamide and doxorubicin for 34 weeks. Four-teen patients received radiotherapy 15 to 35 Gy and three patients received radiation to sites of metastasis. Complete remission was obtained in 24 patients (80%) with event-free survival of 57% and overall survival of 83% with an average observation time of 4 years.

These four modern contemporary series have tended to rest the skepticism with regard to multimodal treatment of PT in adults. Multimodal approach tailored risk similar treatment to pediatric protocols WEIGHT is the current standard of care. In contrast to the pediatric population, where opinion differs as to whether the nephrectomy should be done primarily or after neoadjuvant therapy, there is a consensus view that primary surgery is recommended for adult WT because of the difficulty to establish this rare diagnosis before the operation. Only in cases of primarily inoperable patients the diagnosis is established by biopsy and neoadjuvant therapy in place to try to tumor regression and improve operations. In the absence of bilateral disease, which is rare in adults, primary surgery should include a radical nephrectomy with lymph node sampling.

Despite a complete resection of all viable tumor is the effort desirable surgical can endanger vital organs is not advisable, since the local control can be achieved by adjuvant treatment. Because of the rarity of the disease, there is no established treatment guideline in WT adult. The treatment should preferably be conducted in a tertiary hospital with expertise in this disease. On the basis of the recommendations in the literature, including the series of four cases cited above, current and previous experience NWTSG trial in the pediatric population suggest the following:

1. Based on test data and previous multinational experience NWTSG, radiotherapy can be avoided in patients with stage I and stage II patients with favorable histology, when treated with a combination chemotherapy regimen such as vincristine and actinomycin-D. Radiation should be used in the adjuvant treatment of stage III and IV after surgery. Radiation probably also be given to sites of metastasis.
2. Chemotherapy should be used in the adjuvant treatment at all stages in patients with adequate organ function and functional status. Stage I can be treated with a regimen of two drugs for 18 weeks. Chemotherapy for Stage II must be adapted to the risk based on histology and can vary from two to four drug regimens in 18 to 24 weeks. Chemotherapy for Stage III and IV also has to be adapted to the risk based on histology and requires three or four-drug regimens 18 to 24 weeks. The chemotherapy regimens used should be based on existing pediatric experience. In the recently closed NWTS-5 study, the two-drug regimen was vincristine and actinomycin-D for 18 weeks, the three-drug regimen was vincristine, actinomycin-D and doxorubicin for 24 weeks, and was the four-drug regimen doxorubicin vincristine, cyclophosphamide and etoposide for 24 weeks.
3. Patients with bilateral tumors (stage V) should be given primary chemotherapy for about 6-8 weeks, followed by bilateral partial nephrectomy nephrons in an attempt to preserve normal kidney tissue. Additional chemotherapy and radiotherapy may be needed after surgery. In an earlier series of Byrd et al. , Was observed that adults are at risk of relapse over a longer period of time compared with children. This has not been supported by more recent series. Recurrent disease in children has been successfully treated with radiation, multiagent salvage chemotherapy regimens (etoposide, carboplatin and ifosfamide), 129 or high-dose chemotherapy with stem cell support 130 which leads to long-term remissions (30-60%).

Wilms Tumor ADULT kidney tumors

WT (Wilms Tumor) is the most common renal tumor in children. It affects about 1 in 8,000 children with no significant sex predilection, and about 450 new cases reported each year in the United States. Ninety-eight percent of cases occur in children under 10 years and less than 300 cases of TW adults have been reported in the literature. It tends to occur with almost the same incidence throughout the world, suggesting the absence of an environmental factor. However, the incidence in the United States is highest among African Americans and lowest in Asians, suggesting a possible genetic redisposition.

Its true incidence in adults is difficult to determine since it is included with renal cell carcinoma in the epidemiological reports, and varying diagnostic criteria used in case reports. Currently, most experts use the following criteria to define adult WT (I) primary renal neoplasm, (ii) blastematous primitive spindle or round cell component, (iii) formation of the tubular structure or glomeruloid abortion or embryonic, (iv) any area of the tumor diagnosis of CRC, (v) a graphic confirmation of the histology, and (vi) age> 15 years. Approximately 1.2% of pediatric weights have a family background; however, this has not been reported in adults.

Pathology
In contrast to childhood turbines, which are often multicentric and bilateral, most adult cases are unincentric WEIGHT with multicentric and bilateral disease in 7 and 5% of patients, respectively. Horseshoe kidneys are associated with twice the incidence of WT. The macroscopic and microscopic appearance of WT adult it tends to resemble a pediatric weight. WT gross appearance is variable and reflects the proportion of stromal components and nonstromal. WT generally is pale gray or cream and has a soft, however, the predominant stromal tumors can be white and firm. cyst formation may be important in certain cases.

WEIGHT contains variable proportions of undifferentiated blast cells and differentiated cells of epithelial and stromal lineage. Blast cells are undifferentiated, small, active mitosis, rounded or oval, and densely populated, with little cytoplasm. Can occur in several distinctive growth patterns within individual tumors, including diffuse, nodular, serpentine, and basaloid. WT epithelial component may appear as rosette-shaped primitive tubules and occasional glomeruloid structures.

heterologous epithelial differentiation squamous epithelial components, mucinous, or hair can be detected. The stromal component may have great diversity, but is usually composed of spindle cells with a myxoid background. heterologous elements including skeletal muscle, cartilage, bone, fat and neural tissue may be present. WT histological diversity is a hallmark. Characteristically, it has a triphasic pattern with components called blast, epithelial and stromal. Chemotherapy can alter the morphology by inducing the maturation of the elements blast, epithelial and stromal that leads to a disproportionate reduction of actively proliferating cells compared with the sample prechemotherapy. WEIGHT Metastatic may comprise a single element or a combination of what is present in the primary tumor. WT-1 antigen is usually identified in the blast and epithelial elements, but not in differentiated epithelial and stromal components.

nuclear anaplasia associated with an adverse outcome has been recognized in 5% of pediatric cases and the increase in prevalence with age and in certain populations (eg African Americans). Anaplasia requires the presence of multipolar mitotic figures, marked nuclear enlargement (three times higher than that of anaplastic nuclei) and nuclear hyperchromasia. The prognostic significance is deeper in the diffuse anaplasia compared with focal anaplasia. Large blast cells have also been identified as an adverse prognostic factor.

Nephrogenic rests are abnormally persistent foci of embryonic kidney tissue are capable of becoming WT. The presence of diffuse or multifocal nephrogenic rests is
defined as nephroblastomatosis. There are two variants of nephrogenic rests perilobular called nephrogenic rests (PLNR) and intralobar nephrogenic rests (ILNR). Can be seen in 25-45% of WT were pediatric and adult patients seen in WT as well as in several ectopic sites outside the kidney.

Pediatric weight has been associated with a number of known syndromes and genetic mutations. WAGR (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) and Denys-Drash syndrome (gonadal dysgenesis, nephropathy early onset) syndromes associated with deletion or mutations of the WT1 gene (11p13), a gene critical for development renal and gonadal. The Beckwith-Wiedemann syndrome (hemihypertrophy, macroglossia, omphalocele, and organomegaly) is associated with loss of imprinting of WT2 (11p15). Due to lack of enough cases, genetics and syndromic associations have not been well elucidated in adults.

Clinical Presentation
The most common clinical presentation of an adult WT flank pain, hematuria, abdominal mass or constitutional symptoms. Hypertension, which commonly occurs in pediatric WT has not been commonly reported in WT adult. While Kilton had described the 42% of patients have symptoms for more than a year before diagnosis, which has not been seen in other adult series. The tumors are often quite large on initial presentation. The varicocele may indicate an obstruction of the spermatic vein tumor thrombus secondary to renal vein or inferior vena cava. Acquired von Willebrand disease has been associated with pediatric WT proof is justified in adult patients with clinical bleeding tendency. CT scan of the chest and abdomen should be done before surgery to evaluate the metastasis and extrarenal WT. intravascular extension involving the renal vein and inferior vena cava can be seen. The most common sites of metastasis of WT are lung, lymph nodes and liver. The bone metastasis is rare and a bone scan or skeletal survey is warranted only in the presence of symptoms.

The classification system used by the Children's Oncology Group (COG), Société International d'Oncology Paeditrique / International Society of Pediatric Oncology (SIOP) and the National Wilms Tumor Study Group (NWTSG) has been accepted by most WEIGHT authorities’ adults in the staging of WT. The staging is based on both radiological and surgical pathology. WT's forecast is worse in adults than children, possibly due to a constellation of factors, including frequent advanced stage disease at presentation, increased incidence of nuclear anaplasia, increased incidence of recurrence, poorer tolerance of aggressive treatment, and poorer response to treatment.
to be continued in Treatment and Prognosis Wilms Tumor ADULT kidney tumors