AKT2 expression in histopathologic grading and recurrence of meningiomas

Background

AKT2 (protein kinase B), an important protein in PI3K signaling pathway, is overexpressed in a variety of malignant tumors. However, in patients with meningiomas, the potential correlation between AKT2 and clinical outcome remains unknown.

Methods

The expression of AKT2 and Ki-67 in meningioma tissues were evaluated immunohistochemically in 94 patients with meningiomas. The correlation of AKT2 immunoreactivity with clinicopathological features and the prognostic value of AKT2 in patients were also analyzed.

Results

In this study, we examined the expression of AKT2 in meningiomas and unveiled its possible relationship with the clinical outcome. Immunohistochemical analysis revealed high AKT2 expression in 46 patients (46/94, 48.9%) and low AKT2 expression in the remaining 48 patients (48/94, 51.1%). There was a positive correlation between AKT2 and Ki-67 immunoreactivity (r = 0.35, P = 0.01). Clinicopathological evaluation suggested that AKT2 expression was associated with pathological grade and recurrence (P < 0.05). Univariate and Cox analysis indicated a significant correlation between high levels of AKT2 immunoreactivity and high rates of tumor recurrence (P < 0.05).

Conclusions

We conclude that AKT2 may play an important role in the development of meningioma. High AKT2 labeling index indicates higher grade of meningioma, and therefore AKT2 may be a useful molecular marker for predicting the prognosis of meningioma.     

Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years

BACKGROUND: Both pentostatin and cladribine have efficacy in hairy cell leukemia (HCL), but it is not known which agent achieves better results. METHODS: We reviewed a series of 219 patients with HCL, with median follow-up from diagnosis of 12.5 years (range 1.0 -34.6 yrs), treated with either pentostatin (n = 185) or cladribine (n = 34), to compare these agents and assess the potential for cure. RESULTS: Overall response to pentostatin was 96% with a complete response (CR) in 81% and a median disease-free survival (DFS) of 15 years. Response to first-line cladribine was 100% with a CR in 82% and DFS of 11+ years. The relapse rates at 5 years and 10 years were 24% and 42%, respectively, with pentostatin, and 33% and 48% with cladribine. Survival at 10 years was respectively 96% and 100%. CR rates decreased with each sequential relapse through 69% to 45% (P < or = 0.001). Patients achieving CR after first-line treatment had a significantly longer DFS (P = 0.00007) than those achieving a partial response; a similar result was seen after second-line therapy (P = 0.00001). DFS also declined with sequential treatment (P = 0.00005). CONCLUSION: We have shown equivalent efficacies for both agents in the treatment of HCL, with DFS showing no plateau. True cure in HCL remains elusive, but the addition of monoclonal antibodies may be beneficial. Our results suggest that achieving CR should remain the main goal of treatment.     

Survival in breast cancer after nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants: A prospective trial with 13 years median follow-up in 216 patients

Aim

Validation of the oncological safety of nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants (NSM) and of the outcome in patients with locoregional recurrences (LRRs) after this procedure.

Methods

Two-hundred and sixteen patients, mean age of 52.8 (29–81) years with primary unilateral breast cancer, not suitable for partial mastectomy because of large (>3 cm) or multifocal carcinoma, underwent NSM, a single procedure lasting about 1 h 30 min, between December 1988 and September 1994. Lymph node metastases were found in 40.3% of the patients, and 47 patients received radiotherapy (RT) postoperatively. All patients were monitored for at least 11.6 years or as long as they lived. Median follow-up was 13 years. The end-points were locoregional recurrence (LRR) or distant metastases (DM) as first events, disease-free survival (DFS) and overall survival (OS).

Results

Specificity at frozen section from sub-areolar tissues was 98.5%. LRR occurred in 52 patients and DM in 44 patients. DFS was 51.3% and OS was 76.4%. The frequency of LRR was 8.5% among irradiated and 28.4% among non-irradiated patients (p = 0.025). These results compare well with results after conventional mastectomy in other trials. All patients were monitored for at least 6 years after the occurrence of LRR, finding 5 years freedom from further LRR or DM of 60% and OS of 82%.

Conclusions

NSM is an oncologically safe procedure and could be offered to most patients with breast cancer unsuitable for sector resection only. RT effectively lowers the frequency of LRR. The occurrence of LRR after this operation does not significantly affect OS.     

Serum tumor markers in colorectal cancer staging,grading, and follow-up

Early diagnosis of colorectal cancer, a frequent neoplasia in industrialized countries, permits curative surgery. In this study we assessed the clinical role of serum tumor markers determination in diagnosing, staging, and grading colorectal cancer; the role of carcinoembryonic antigen (CEA), CA 19-9, tissue polypeptide antigen (TPA) and CA 72-4 in colorectal cancer follow-up was also assessed. In 114 patients with colorectal cancer, the oncofetal antigen CEA was compared with the membrane-associated glycoproteins CA 19-9, CA 242, and CA 72-4 and with the cytokeratins TPA, tissue polypeptide-specific antigen (TPS) and tissue polypeptide monoclonal antigen (TPM). Overall, the most sensitive indices were TPA and TPS (67% and 70%, respectively). Tumor stage influenced the levels of CEA, CA 19-9, and TPA, but not those of TPS, while tumor grade influenced CEA and TPS, but not CA 72-4, TPA, and TPM. TPA was the most sensitive index in identifying early or well-differentiated colorectal cancers. The sensitivity was enhanced when this marker was determined in combination with CEA, in diagnosing both advanced and early colorectal tumors. Seventy-seven patients were followed up after therapy for at least 18 months. CEA was the most sensitive index of recurrence (58%); however, this sensitivity is too low to consider tumor markers useful in colorectal cancer follow-up. © 1996 Wiley-Liss, Inc.     

Clinical and prognostic features of adult patients with gangliogliomas

Background

Gangliogliomas (GGs) represent <1% of primary brain tumors in adults. Little is known regarding prognostic features, clinical characteristics, or the impact of treatment on patient outcomes.

Methods

Our neuro-oncology longitudinal database was screened for patients with GG from 1992 to 2012. Sixty-seven patients (age >18 y) were identified.

Results

Sixty-two patients presented with low-grade GG and 5 with anaplastic GG. The median age at diagnosis was 29 years. With a median follow-up of 4.7 years after the initial diagnosis, 23 patients had progressive disease. Range of time to progression was 0.2–20 years. Nine patients with low-grade GG progressed to a malignant tumor. The median overall survival (OS) for all patients was not reached. The 2-, 5-, and 10-year OS for patients with low-grade GG were 100%, 88% (95% confidence interval [CI]: 73%, 95%), and 84% (95% CI: 67%, 93%), respectively.Factors identified by univariate analysis that were significantly associated with OS were age, KPS, extent of resection (EOR), and grade. Factors on univariate analysis that were significantly associated with progression-free survival were grade and EOR. On multicovariate Cox regression, lower tumor grade and younger age were significant factors for longer OS. EOR is a significant factor for progression-free survival.

Conclusions

While GG has excellent prognosis, malignant histologic grade, older age, and diagnosis with biopsy could indicate worse prognosis. The late nature and high rate of progression emphasize the importance of long-term follow-up. The role of chemotherapy and radiation therapy for incompletely resected low-grade GG remains unclear.     

Prognostic Factors of Papillary, Follicular and Medullary Carcinomas of the Thyroid Gland: Retrospective multivariate analysis of 216 patients with a median follow-up of 11 years

Various prognostic factors have been tested in multivariate analyses of 216 patients with papillary, follicular or medullary thyroid carcinomas without initial distant metastases. The median follow-up time was 11 years. The patient's sex was not found to be a significant predictor. Age at diagnosis seemed to be an important predictor for papillary as well as for follicular carcinomas, but when deaths in intercurrent disease were estimated, marked cellular atypia and tumour invasion beyond the thyroid capsule proved to be more important predictors. For medullary carcinomas tumour invasion beyond the thyroid capsule was the only significant predictor.     

Nasopharyngeal cancer with neck recurrence at 8 years and a lung metastasis at 15 years after the first definitive radiotherapy: a case report

We report a patient with nasopharyngeal cancer with long-term follow-up of more than 16 years after the first course of radiotherapy in 1981. He developed a lung metastasis in 1996 after having a second course of radiotherapy for neck recurrence in 1989. The patient was a 42-year-old man with a nasopharyngeal tumor and a fixed upper neck metastasis (T1N1M0), which was treated with definitive radiotherapy. He manifested regional recurrence, at the margin of the radiation portal, with an 8 year disease-free interval, which was treated successfully by definitive re-irradiation. He developed a solitary lung metastasis, which was treated by video-assisted thoracoscopic lung resection, 7 years disease-free after the second course of radiotherapy. For 20 months after the removal of the lung metastasis he has been generally well without any signs of recurrence of sequelae. This case indicates the efficacy of definitive re-irradiation for regional recurrence and the necessity for long-term observation after radiation therapy for nasopharyngeal cancer.      

Prognostic value of static cytometry in transitional cell carcinoma of the bladder: recurrence rate and survival in a group of patients at 10 years follow-up

Many studies have indicated that nuclear DNA content evaluation can be used to predict biological behavior of transitional cell carcinoma (TCC) of the bladder. Some authors also indicated that static cytometry is more useful in DNA content analysis than flow cytometry. The aim of the present study was to evaluate the prognostic significance of DNA ploidy in TCC of the bladder, performed by using static cytometry with an image analyzer, and monitoring patients at 10 years follow-up. Thirty-one consecutive patients underwent transurethral or open surgery for bladder tumors, and neoplastic tissue samples taken from each patient were imprinted on glass slides and sent for histopathological and DNA content evaluation. DNA ploidy evaluation was performed using a CAS 200 image analyzer. Nuclear DNA content evaluation was compared to patient follow-up on recurrence, progression or survival performed 10 years after surgery. Pathological evaluation demonstrated the presence of superficial TCC in 23 patients, while 8 had an invasive bladder tumor. Twenty-nine tumor samples were adequate for DNA content measurement, with 13 showing diploid DNA content and 16 with aneuploid DNA content. At 10 years follow-up, all patients with aneuploid DNA content demonstrated a lower survival time (p=0.049) and higher recurrence rate (p=0.0346). A log-rank test demonstrated that stage, grade and nuclear DNA content are the most useful prognostic parameters for predicting the biological behavior of TCC of the bladder. These results confirm that static cytometry is a good and reliable method to evaluate DNA tumor content and considered a useful prognostic parameter for predicting recurrence rate, disease progression or survival in patients affected by bladder tumors.     

Clinical Characteristics and Surgical Management of Patients with Temporal Lobe Gangliogliomas

OBJECTIVE To review the clinical features and surgical treatment for patients with temporal lobe gangliogliomas. METHODS Patients with temporal lobe gangliogliomas who underwent resection of temporal lobe tumors, confirmed by surgical pathology, seen between September 1998 and November 2004 at the West China hospital, were selected. Medical records were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, extent of surgery, and pathologic diagnosis. The follow-up periods varied from 12 to 60 months (mean 30 months). RESULTS Eighteen patients were identified, including 14 males and 4 females. Age at operation ranged from 4 years to 34 years (mean 17.6 years). All patients underwent at least one surgical procedure. Fifteen tumors were classified as WHO Grade I lesions, and 3 as WHO Grade II lesions. None of patients experienced a tumor recurrence. Among the patients, 85% had complete and sustained seizure relief. CONCLUSION Complex partial seizures and auras were the common presenting symptom of these patients. The follow-up suggested good relief from the seizures after surgery and a low risk for tumor recurrence and malignant progression.     

Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma: a comparison of preoperative and intraoperative tumor localization with histopathologic findings

BACKGROUND: The objective of this study was to appraise the detection of metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using radioguided surgery (RGS) and to compare the results with external imaging modalities, surgical palpation, and histopathologic findings. METHODS: Twenty-five patients with recurrent MTC underwent preoperative scintigraphic imaging with 500 megabecquerels (MBq) of technetium 99m(V)-dimercaptosuccinic acid [(99m)Tc(V)-DMSA] and 222 MBq of indium 111 ((111)In)-pentetreotide. The radiopharmaceutical that showed the greatest preoperative tumor uptake was selected for intraoperative RGS. Surgery was performed 24 hours after the administration of (111)In-pentetreotide or 4 hours after the injection of (99m)Tc(V)-DMSA. Furthermore, three male patients underwent surgery who suffered from recurrent pheochromocytoma (injection of 180 MBq iodine 123-labeled metaiodobenzylguanidine [(123)I-MIBG] 4--5 hours before surgery). RESULTS: Overall, lesion detection sensitivities in patients with MTC for computed tomography, (111)In-pentetreotide, and (99m)Tc(V)-DMSA were 32%, 34%, and 65%, respectively. Surgical palpation identified lymph node metastases of recurrent MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were adjudged false positive with respect to MTC metastases. Both surgical palpation and RGS localized all paravertebral subdiaphragmatic lesions (size > or = 2 cm) of recurrent pheochromocytoma seen in the preoperative MIBG scan. CONCLUSIONS: RGS was capable of localizing more and smaller metastases of MTC compared with conventional imaging modalities and surgical palpation. However, the relatively high radioligand accumulation in the kidneys ((111)In-pentetreotide) and the dense hepatic and biliary signals using MIBG limited their use for intraoperative detection of tumors in the area of the adrenal gland.     

Local hyperthermia in combination with definitive radiotherapy: increased tumor clearance, reduced recurrence rate in extended follow-up

Fifty-nine patients with superficial malignancies appropriate for treatment with definitive radiotherapy and technically suitable for application of local microwave hyperthermia were available for at least 6 months follow-up. Thirty-one of these patients presented with two lesions, only one of which was heated, the other serving as internal control. The responses of the lesions which were heated were compared with those receiving only radiation. The heated lesions responded more quickly, reconfirming observations previously made. However, at subsequent 6 months, 1 year, 18 months and 2 years follow-ups, tumor clearance was shown to be significantly more complete as compared with the internal controls. At 6 months follow-up complete response with combined therapy was observed in 27 of 31 lesions (87%) in contrast to complete response in 12 of 31 (39%) lesions treated with radiotherapy alone. At one year combined modality treatment produced complete response in 19 of 19 lesions (100%) while radiotherapy alone yielded complete response in 10 of 19 lesions (53%). At 18 months, 8 of 9 lesions (89%) treated with combined therapy remained controlled, 1 having recurred. Seven of 9 (78%) treated by radiotherapy alone were controlled, 2 having recurred. At 2 years, 6 patients were available for follow-up and 6 of 6 (100%) of lesions treated with combined modality remained controlled. Among those treated by radiotherapy alone, 5 of 6 (83%) remained controlled, while 1 recurred. The rate of tumor recurrence among the heated lesions was significantly lower than was found among the controls. The recurrence rate among the controls was similar to that expected in a similar group of patients treated with definitive radiotherapy. Therefore, in addition to its established capability to shrink tumors, hyperthermia in combination with radiotherapy has been shown to increase the rate of overall tumor clearance and reduce recurrences compared with that obtained from radiotherapy alone.     

Long-term complications and post-treatment follow-up of patients with Wilms' tumor

An increasing number of children with Wilms' tumor can expect to be cured, reflecting the undisputed progress made in the treatment of children with this renal cancer. However, it does underscore the need to screen survivors for late effects of cancer therapy. Some of the late effects, such as those following radiation therapy, should be expected after a considerable latent period. Others, such as those occurring after the administration of certain chemotherapeutics agents, are commonly immediate, usually transient, but occasionally permanent. Although children seem to tolerate acute toxicities of therapy better than do adults, the growing child may be more vulnerable to the delayed adverse sequelae of cancer therapy, such as effects on growth, fertility, and neuropsychological function. This article reviews many of the late effects seen in survivors of Wilms' tumor and the way in which these effects relate to the different therapeutical modalities used (surgery, chemotherapy, and radiation).     

The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma.

Six patients with intradermal metastases of malignant melanoma were treated with intralesional bacile Calmette-Guérin (BCG). Four patients showed a good response with regression of injected, and in some cases, uninjected lesions, whereas two developed metastatic viscereal disease and died. Three of the six patients had complete regression of all lesions, and one exhibited complete regression of untreated lesions. All remain free of disease. The fourth patient had complete regression of injected and of some untreated lesions, but developed widespread dissemination and died. Preliminary experiments suggest the presence of a blocking factor in his sera which abrogates the lymphocyte stimulation in response to melanoma antigens. Three of four responders (i.e. those patients in whom treated lesions decreased in size by more than 50% for more than 1 month) showed a dramatic increase in lymphocyte stimulation to melanoma antigens. All responders (four out of four) had a marked increase to phytohemagglutinin (PHA), whereas non responders had no increase in lymphocyte stimulation either to melanoma antigens or PHA. Two of four responders showed inhibition of leukocyte migration to melanoma antigens before BCG, and two of four responders were positive after BCG. Of the nonresponders, one was positive and one negative before BCG; this remained the same after. There was a marked increase in active rosette forming cells in all responders and in one of the two nonresponders. Histopathologic studies at 3 hours, 6 hours, 24 hours, 14 days, and 4 weeks after BCG showed a definite sequence of events occurred, progressing from 1) inflammatory cell response at the periphery of the lesion, disruption of melanogenesis, extensive dumping of pigment from melanoma cells, proceeding to actual cell death at 24 hours, to 2) macrophages containing melanin and granulomas replacing tumor by 2 weeks. These studies suggest that BCG activates both specific and nonspecific immune responses. Thus, in vitro parameters of cellular immunity, including migration inhibitory factor production and inhibition of leukocyte migration, are affected by intralesional BCG, and some, particularly the lymphocyte stimulation and rosette test, seem to correlate with the clinical response of the patients.     

Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study

We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma‐free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by next‐generation sequencing before and after operation. Whole‐exome sequencing was used to detect the DNA of HCC and adjacent tissues. In total, 47 gene mutations were identified in the ctDNA of the 41 patients analyzed before surgery. ctDNA was detected in 63.4% and 46% of the patient plasma pre‐ and postoperation, respectively. The preoperative ctDNA positivity rate was significantly lower in the nonrecurrence group than in the recurrence group. With a median follow‐up of 17.7 months, nine patients (22%) experienced tumor recurrence. ctDNA positivity at two time‐points was associated with significantly shorter recurrence‐free survival (RFS). Tumors with NRAS, NEF2L2, and MET mutations had significantly shorter times to recurrence than those without mutations and showed high recurrence prediction performance by machine learning. Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in preoperative ctDNA was a strong independent predictor of RFS. ctDNA is a real‐time monitoring indicator that can accurately reflect tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of RFS in individuals with HCC.     

肿瘤浸润淋巴细胞输注预防乳腺癌复发

目的　探讨肿瘤浸润淋巴细胞输注预防乳腺癌复发的疗效。方法　从乳腺癌组织及淋巴结中提纯 TIL细胞 ,将其扩增达到一定数量 (>1.0× 10 9个 )后输入乳腺癌患者 ,并进行外周血中的 T细胞亚群及 TIL杀伤活性测定。结果　输注 TIL细胞后 ,机体细胞免疫功能增强 ,TIL最高杀伤率达 78.0 % ,2 6例输注者无 1例复发。结论　乳腺癌患者自身 TIL细胞输注 ,对预防乳腺癌复发有一定的积极作用     

Clinicopathologic factors of the recurrent tumor predict outcome in patients with ipsilateral breast tumor recurrence

BACKGROUND:

The role of clinicopathologic characteristics of the recurrent tumor in determining survival in a cohort of patients with ipsilateral breast tumor recurrence (IBTR) was investigated.

METHODS:

Among 6020 women with pT1‐T2, pN0‐1, M0 treated with breast‐conserving surgery from 1989 to 1999, 269 developed isolated IBTR. Ten‐year Kaplan‐Meier breast cancer‐specific survival (BCSS) and overall survival (OS), calculated from date of IBTR, were analyzed according to clinicopathologic characteristics.

RESULTS:

Factors that were associated with diminished OS and BCSS on univariate analysis were: time to IBTR ≤48 months, lymphovascular invasion positive status, estrogen receptor (ER) negative status, high grade, clinical IBTR detection, biopsy alone, and close/positive margins (all P < .05). On multivariate analysis, time to IBTR ≤48 months (hazard ratio [HR], 1.87, P = .012), lymphovascular invasion positive status (HR, 2.46; P < .001), ER negative status (HR, 2.08; P = .013), high‐grade recurrent disease (HR, 1.88; P = .013), and close/positive margins after surgery for IBTR (HR, 1.94; P = .013) retained significance for prediction of diminished OS. When stratified according to number of adverse prognostic features, 10‐year OS was 70.4% in patients with 1 factor, 35.8% with 2 factors, and 19.9% with 3 or more factors (P < .001).

CONCLUSIONS:

Time to recurrence ≤48 months, lymphovascular invasion positive status, ER negative status, high‐grade histology, and close/positive margins in association with the recurrent tumor are independent prognostic factors for survival after IBTR. The presence of 2 or more of these features at recurrence is significantly associated with poor OS. These criteria can be used to prognosticate and guide clinical decisions after recurrence. Cancer 2011. © 2010 American Cancer Society.     

Supratentorial extraventricular ependymal neoplasms: a clinicopathologic study of 32 patients

BACKGROUND: Published research on the clinicopathologic features of extraventricular ependymal neoplasms of the cerebral hemispheres has been scant. METHODS: Thirty-two archival cases were studied to investigate the prognostic impact of clinicopathologic parameters including flow cytometry, the proliferation (Ki-67) labeling index, and p53 expression. RESULTS: Among these 32 cases were 2 subependymomas, 19 ependymomas, and 11 anaplastic ependymomas. No significant gender predilection was observed, and 45% of patients were in their second or third decade of life. The left cerebral hemisphere was 1.5 times more commonly involved. On available imaging studies, lesions were often cystic, with or without a mural nodule. Tumors expressed glial fibrillary acidic protein (87%), S-100 protein (77%), cytokeratin (43%), and epithelial membrane antigen (17%). Ki-67 proliferation index paralleled tumor grade. Immunoreactivity for p53 protein was observed in the 2 cases of subependymoma, in 10 of 11 anaplastic ependymomas, and in 6 of 17 ependymomas. Flow cytometry performed in 27 tumors revealed diploidy in 20 cases and aneuploidy in 4 cases (3 anaplastic and 1 classic ependymomas), with S-phase fraction ranging from 0.2-9.7. Eleven subjects were additionally treated with radiotherapy, and 3 with chemotherapy. Follow up was available in 25 (78%) patients. CONCLUSIONS: The results of the current study suggest that there is no significant relation between histopathology, Ki-67 proliferation index, p53 immunolabeling, tumor ploidy, and biologic behavior.     

Undifferentiated sarcoma of the kidney: a tumor of childhood with histopathologic and clinical characteristics distinct from Wilms' tumor.

The pathological and clinical features of 123 patients with Wilms' tumor diagnosed between 1961 and 1977 were analyzed. A subgroup of nine patients with distinctive histology characterized by the presence of exclusively sarcomatous elements was identified. These patients were indistinguishable clinically from the other patients with Wilms' tumor and were treated as Wilms' tumor. The rate of recurrence in this group of sarcomatous Wilms' tumor was very high (7/9) and long-term disease-free survival correspondingly low )3/9 free of disease from 15 months to nine years) when compared to the patients with classical Wilms' tumor (50% recurrence rate and 71% currently free of disease). In addition, patients with metastases (seven of seven patients with recurrence had skeletal involvement as contrasted to one of 50 patients with metastatic classical Wilms' tumor). We conclude that the "sarcomatous Wilms' tumor" represents a distinct clinicopathological entity identifiable morphologically at diagnosis, best described as renal sarcoma and that in the future optimal treatment of this disease may vary somewhat from the treatment of classical Wilms' tumor.