Physician, patient and family attitudes regarding information on prognosis: a Brazilian survey.

BACKGROUND: Communication between physicians and patients is a fundamental aspect of cancer care, yet most physicians' perceptions are often inconsistent with the patients' stated preferences while prognostic information is the most misunderstood. PATIENTS AND METHODS: Members of the Brazilian Society of Oncology Physicians (n=609) were identified and asked to complete a mailed questionnaire. Outpatients (n=150) and their family members (n=150), oncologists and fellows (n=55) from a public healthcare hospital and a tertiary cancer hospital in Sao Paulo were also personally invited to participate. RESULTS: A total of 202 physicians, 150 outpatients and 150 family members were participated. The majority of patients (92%) believe they should know about their terminal stage compared with 79.2% of physicians and 74.7% of families (P=0.0003). Cancer patients were most likely to support disclosure of diagnosis and terminality (P=0.001), to consider that this disclosure was not stressful (P<0.0001) and that this knowledge would improve their quality of life (P<0.0001). CONCLUSIONS: Cancer patients seen in these centers in Southeastern Brazil prefer to know the truth about their poor prognosis more than their physicians and families think. Further studies with larger samples of patients and physicians are necessary to show if our results are representative of all Brazilian situations.

Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001.

BACKGROUND: To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols. METHODS: Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery. RESULTS: 5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors. CONCLUSION: Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.

DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy.

The aim of the present study was to evaluate DNA damage (micronucleus) in cytokinesis-blocked lymphocytes and exfoliated buccal mucosa cells from children with malignant tumours and under chemotherapy. Micronucleated cells (MNCs) were assessed from children before and during chemotherapy. A total of 21 healthy children (controls), matched for gender and age, were used as control. The results pointed out higher frequencies of micronucleated lymphocytes in children with malignant tumour before any therapy when compared to healthy probands. Furthermore an increase of micronucleated lymphocytes during chemotherapy was detected when compared to the data obtained before chemotherapy. No statistically significant increases of MNCs were noticed in buccal mucosa cells at any of the timepoints evaluated. Taken together, these data indicate that the presence of malignant tumours may increase the frequency of DNA damage in circulating lymphocytes, these cells being more sensitive for detecting chromosome aberrations caused by anti-cancer drugs.

A new treatment protocol for childhood non-Hodgkin's lymphoma: preliminary evaluation.

Between November 1986 and July 1988, 21 consecutively diagnosed children with nonlocalized abdominal lymphoma (Murphy's stage III and IV without CNS disease) were eligible for treatment with a multidrug chemotherapy schedule. The induction phase was the same for all (fractionated cyclophosphamide, intermedian-dose methotrexate [Mtx], vincristine [Vcr], and prednisone). After that the children were randomized to repeat the same scheme or intercalate teniposide (VM26) plus cytarabine (AraC) with the induction-phase scheme. All of them were treated for only 6 months. The protocol approved to be very effective with 85% remission in all the children and 94% survival in patients surviving the induction phase. The toxicity was acceptable, also considering the characteristics of our population (malnourished children). The group VM26 and AraC had few hospital admissions in spite of the small number of children because they received VM26 and AraC as outpatients. The sale purpose of the present study is to report that with a few simple procedures such as hydration, alkalinization, and drug fractionation, the chemotherapy schemes used can bring about a dramatic improvement in short-term survival.

Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).

Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

The role of radiology in the diagnosis and follow-up of Langerhans cell histiocytosis.

Diagnostic imaging plays a major role in the management of patients with Langerhans cell histiocytosis. Plain radiography depicts most lesions. Nuclear scintigraphy may detect additional areas of bone involvement, but its routine use is controversial. Ultrasonography may be used to evaluate the abdomen for evidence of solid organ involvement. CT and MR imaging are often of great value in clarifying and delineating findings seen on plain radiographs and other imaging modalities. Ultimately, the choice of imaging study depends on the patient's clinical presentation and the body part affected.

Electrophysiological correlates among the radial nerve, the caudate and the entopeduncular nuclei in cats.

The entopeduncular nucleus (EPN), as the medial part of the globus pallidum, has been considered the efferent structure of the striatum. Based on this, we decided to study its possible somatosensory projections and the electrophysiological relationship with the caudate nucleus (CN). Radial nerve stimulation produced evoked responses (ER) in CN and EPN. The ERs recorded in EPN are of shorter latencies (11 msec) than those in CN (23 msec). Electrical stimulation of CN elicited ERs in EPN. These ERs are bigger when the stimulation sites coincide with the regions of CN where somatic stimulation also elicited ERs. The same regions of CN yielding ERs by somatic stimulation respond to EPN stimulation. The ERs recorded in EPN by radial nerve stimulation diminished when the CN was stimulated 7 msec after the radial nerve, while other intervals were less effective. The results show that the radial nerve probably has direct ipsi and contralateral projections to the EPN and a bidirectional connection between EPN and CN. We suggest a feedback response of EPN to CN stimulation, an arrangement which would be the functional basis for the central motor regulation.

Effects of general anesthesia, neodecortication and spreading depression upon somatic evoked responses in caudate and entopeduncular nuclei, and their electrophysiological correlates in cats.

The electrophysiological relationship among an afferent somatic input (radial nerve), the caudate and the entopeduncular nuclei was studied in intact animals under chloralose anesthesia and in decorticated ones. The results confirm the hypothesis that the cerebral cortex is not essential to record somatic evoked responses in both nuclei, nor for the reciprocal responses in these nuclei when one of them is stimulated, suggesting the existence of direct somatic projections to these nuclei from the subcortical structures. On the other hand, the spreading depression by microinjection of KCl 3M into the CN does not modify the ERs in EPN, but the spreading depression in EPN does modify the CN response. Thus, the somatic projection to EPN seems to course directly from the thalamus or the reticular formation but not through the CN. The results suggest a reciprocal influence of the outflow structure (EPN) upon the higher level (CN), in which the inferior structure is modifying the excitability of the higher one.

Fetal rhabdomyomatous nephroblastoma. Report of a case with unusual clinical behavior.

The authors report a case of fetal rhabdomyomatous nephroblastoma that presented pulmonary metastases at diagnosis, a feature infrequently observed in this type of tumor.

Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group.

PURPOSE: Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal tumour. Only a few homogeneously treated CCSK cohorts have been reported. This study aims to describe clinical characteristics and survival of CCSK patients treated according to recent International Society of Pediatric Oncology (SIOP) protocols. PATIENTS AND METHODS: We analysed the prospectively collected data of patients with a histologically verified CCSK, entered onto SIOP 93-01/2001 trials. RESULTS: A total of 191 CCSK patients (64% male) were analysed, with a median age at diagnosis of 2.6 years. Stage distribution for stages I, II, III and IV was 42%, 23%, 28% and 7%, respectively. Pre-operative chemotherapy was administered to 169/191 patients. All patients underwent total nephrectomy and 189/191 patients received post-operative chemotherapy. Radiotherapy was applied in 2/80 stage I, 33/44 stage II, 44/54 stage III and 6/13 stage IV patients. Five year event-free survival (EFS) and overall survival (OS) were 79% (95% confidence interval (CI): 73-85%) and 86% (95% CI: 80-92%) respectively. Stage IV disease and young age were significant adverse prognostic factors for event-free survival. Factors such as gender, tumour volume and type of initial treatment were not found to be prognostic for EFS and OS. CONCLUSION: In this largest SIOP cohort described so far, overall outcome of CCSK is reasonable, although treatment of young and advanced-stage disease patients is challenging. As further intensification of treatment is hampered by direct and late toxicity, future directions should include the development of targeted therapy based on specific molecular aberrations of CCSK.

Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset.

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets.

Report of the second international symposium on molecular epidemiology in childhood leukaemia and embryonal tumours, Rio de Janeiro, Brazil.

The recent International Symposium on Molecular epidemiology in Embryonal Tumours and Paediatric Leukaemia was held on 4-6 March 2008 in Rio de Janeiro, Brazil. It proved a very productive meeting in which studies relating to genetics, therapeutical trials, identification of risk factors in acute leukaemia neuroblastoma and Wilms' tumours were presented. Over 120 participants gathered for three days of fruitful discussions, including representatives of paediatrics, haematology, laboratory, epidemiology and pathology. Debates were held about strategies of applications of important biomarkers for clinical trials. Highlights of each of the scientific presentations are summarized below.

Single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Preliminary results of a clinical trial. The Brazilian Wilms' Tumor Study Group.

A clinical trial was conducted by the Brazilian Wilms' Tumor (WT) Study Group to compare the single-dose (60 micrograms/kg x 1 day) administration of dactinomycin (AMD) with the standard fractionated dose (15 micrograms/kg/d x 5 days) used in the US National WT Study. Except for the AMD administration, treatment for all patients followed that of the latter study. Patients were randomized to receive either of the two AMD regimens in the schedules most appropriate for their stage and histologic condition. One hundred seventy-six children with WT entered the study until December 1988. No significant differences in overall or relapse-free survival distributions were observed between treatment arms using data for all patients or data stratified by disease stage. Two-year survival rates were 83.0% and 85.3% for patients receiving the fractionated and single doses of AMD, respectively. Survival distributions could also be compared once patients with protocol violations were excluded. The overall 2-year survival rates were 89.7% and 88.6% and the relapse-free 2-year survival rates were 78.2% and 76.1% for the fractionated and single AMD doses, respectively. Altered liver function was seen in three patients who received fractionated dose and in four patients who received the single AMD dose. Acute toxicity was observed in only one patient of the fractionated-dose group and in zero of the patients of the single-dose group. At the closing date, patients assigned to the simplified AMD regimen had accumulated 1840 days less of hospital stay than those treated by the standard regimen.

A randomized clinical trial of single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Results after extended follow-up. Brazilian Wilms' Tumor Study Group.

BACKGROUND: To verify the adequacy of a simplified chemotherapeutic regimen for the treatment of Wilms' tumor (WT), the authors conducted a clinical trial to compare the standard fractionated dose (15 mcg/kg x 5 days) of dactinomycin (AMD) with a single dose (60 mcg/kg x 1 day) administration of the drug. METHODS: From October 1986 to December 1988, 176 WT patients were enrolled in a randomized, multicentric clinical trial conducted by the Brazilian WT Study Group in 38 institutions from 8 states. Patients were randomly assigned to treatment arm A (standard 5-day fractionated AMD administration) or arm B (single high dose AMD administration) in the schedules most appropriate for their stage and histology. Except for the differences in AMD administration, patients were managed by the Third U.S. National WT Study protocol. The endpoints of interest were relapse free and overall survival. Complete follow-up information was obtained until December 1992. RESULTS: After a median follow-up of 47 months, there were no significant differences in survival distributions between treatment arms, using data for all patients or data stratified by disease stage. Relapse free and overall 4-year rates were similar in both groups: 67% and 72%, respectively, in arm A, and 67% and 75%, respectively, in arm B (P = 0.839 and 0.710, respectively). Patients assigned to the simplified arm had cumulatively 1921 fewer hospital days as compared with those receiving the fractionated dose. Hepatic toxicity was observed in only one patient assigned to the divided dose regimen and in none of the single dose group. CONCLUSIONS: WT can be treated using a single dose regimen for AMD administration, thus minimizing the inconvenience for the children and their parents and reducing considerably health care delivery costs.

Management of synchronous bilateral Wilms tumor: Brazilian Wilms Tumor Study Group experience with 14 cases. Brazilian Wilms Tumor Cooperative Group, Sao Paulo, Brazil.

The Brazilian Wilms Tumor Study Group has registered 16 cases of synchronous bilateral Wilms tumor since 1986, of which 14 were available for analysis. Most patients were treated according to a prospective trial in which bilateral renal preservation was emphasized. Overall survival was 79% (11 of 14 cases), and both kidneys were preserved in 57% (8 of 14) of the patients with synchronous disease. Of the 14 patients 5 had undergone at least 3 surgical procedures. In 10 cases in which pathological reports were available for review residual disease was documented in 5 but none had relapse.

Experience with six children with fetal rhabdomyomatous nephroblastoma: review of the clinical, biologic, and pathologic features.

BACKGROUND: Fetal rhabdomyomatous nephroblastoma (FRN) is a rare variant of Wilms tumor. MATERIALS AND RESULTS: One hundred and thirty two children with kidney tumors were seen at our hospital from 1985 to 1993. Among them were 6 (4.5%) who had FRNs. Five were boys aged 8 months to 3 years; the girl was 17 months old. Three of the four with unilateral disease had tumors so large that they were considered unresectable at diagnosis. Five received pre-operative chemotherapy and three also received pre-operative radiation therapy. None of the tumors responded. Both patients with bilateral tumors died of progressive disease. Three of the four patients with unilateral disease followed for at least one year are alive for 1 to 10 years after diagnosis. CONCLUSIONS: FRN should be in the differential diagnosis of huge kidney tumors in children, and preoperative therapies escalated with caution since FRN is not responsive to treatment used for classic Wilms tumor.

Catching up with history: treatment of Wilms' tumor in a developing country.

Despite the tremendous progress that pediatric oncology has achieved in the treatment of Wilms' tumor over the last several decades, survival rates in our institution before 1970 did not exceed 8%. In order to correct the problem standardized therapy was instituted in 1970 through a multimodal oncological team. Results using the new approach were reviewed in 1979 (50 patients) and showed an overall 34% 2-year survival rate. Although encouraging, these results were still far below the ones reported in the literature. This prompted us to use a vigorous professional and lay educational program in the city. Treatment methods were replaced by those advocated by the Second National Wilms' Tumor Study. A second evaluation period initiated in 1979 and extended through 1984 (35 patients) yielded an overall 83% survival rate. A retrospective study of the two periods by univariate and multivariate survival analysis revealed that, although much of the improvement in survival could be attributed to a shift in stage distribution towards earlier disease, the admission period itself had an important additional explanatory effect with respect to survival. This was probably due to the improvement in treatment protocols used in the latter period. Age was a prognostic variable only for patients admitted during the 1979-1984 period.

[The propedeutic course given at the School of Medicine and the academic performance of the students that passed it]. / Consideraciones sobre el Curso Propedéutico que se dicta en la Facultad de Medicina y sobre el rendimiento académico de los estudiantes que lo aprobaron.

A report of the results of the Propedeutic Course in the Medical School of the University of Panama is informed. This course was established by the Academic Council, at the request of the Medical School, to diminish the registration form 280 to 180 students, taking into account the low academic performance of the students with the lowest grades in the Admission Process. The study showed that the correlation indices of the students in the Propedeutic Course and in the first regular semester was low. The study also showed that the number of students from the Propedeutic Course who repeated or were separated from the school, was higher than those from the regular semester.

Association of malignancy and Langerhans' cell histiocytosis: report of three cases.

Among 44 children with Langerhans' cell histiocytosis (LCH) seen at the Pediatric Department of the A.C. Camargo Hospital, São Paulo, Brazil, three developed malignancy, two before and one after the diagnosis of LCH. Malignancy could be attributed to treatment in one of the three children. Whether the cancer in the other two children represents a chance association of the two processes or is treatment-related, is unknown.