Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

The therapy regimen of high‐grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high‐grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT‐PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up‐regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlatedto response to chemotherapy. Other results include correlationof IFITM2, IFITM3, and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials. © 2009 UICC     

Cancer of the kidney invading the vena cava and heart. Results after 11 years of treatment

Between October, 1973, and October, 1983, 18 patients with cancer of the kidney or adrenal gland that had invaded the vena cava, and in 11 cases had reached the heart, were operated on by seven surgical teams. The surgical excision in all patients was performed with extracorporeal circulation, circulatory arrest and deep hypothermia. No deaths occurred. If there are no detectable metastases before operation, the 5 year survival rate is 75% as compared to 6 months with medical treatment. This clinical situation is not uncommon, as 3% to 10% of cancers of the kidney invade the inferior vena cava and 40% of them reach the heart. The possibility of curing the cancers with minimal operative risk should prompt a systematic search for venous invasion with any cancer of the kidney.     

Vitamin A and acute respiratory infections.

By questionnaire we studied the occurrence of acute respiratory infections (ARI) in 1961 children between 0 and 5 years old from a total of 3225 families in Cikutra, Bandung. In 38.7% of them 200.000 IU vitamin A supplement had been given at least once during the preceding year. Mild or moderate ARI occurred in 54.7% of the children during the previous month and in 87.9% during the previous year; severe ARI occurred in 5.5% during the previous month and in 16.8% during the previous year. Surprisingly slightly more ARI occurred in children with vitamin A supplementation. However, vitamin A had been distributed more to low income than high income families, and in the latter group significantly less children suffered from ARI (p less than 0.05; 44% versus 54 a 56%).     

Frizzled A, a novel angiogenic factor: promises for cardiac repair.

OBJECTIVE: Frizzled A is a very recent protein expressed in the cardiovascular hood by cardiomyocytes and by endothelial cells. This protein plays key roles in vitro in vascular cell proliferation and is able to induce an in vivo angiogenic response. Regarding these properties, we assess the hypothesis that Frizzled A could act in the healing process after myocardial infarction. METHODS: To investigate the role of Frizzled A, we established a transgenic mouse line overexpressing the protein and developed a model of myocardial infarction by coronary artery ligation. RESULTS: The incidence of cardiac rupture after myocardial infarction was reduced in transgenic mice (6.5 versus 26.4% in controls, n=165; P<0.01). Infarct sizes were smaller in transgenic mice (18% of left ventricle circumference versus 28.1% in control at day 30; P<0.001; n=6) and the cardiac function was improved (3800 +/- 370 versus 2800 +/- 840 mmHg/s dp/dtmax in controls, -2800 +/- 440 versus -1800 +/- 211 dp/dtmin in controls at day 15; P<0.001; n=6). Early leukocyte infiltration had decreased in transgenic mice during the first week (103 +/- 59 versus 730 +/- 463 cells/mm2 in controls at day 7; P<0.001; n=6) and the apoptotic index was decreased by 50% at day 7. Capillary density in the scar was higher in transgenic mice (290 +/- 103 versus 104 +/- 43 vessels/mm2 in control at day 15; P<0.001) and vessels were more muscularized and mean lumen area was 3-fold higher (952 +/- 902 versus 313 +/- 350 microm2 in control; P<0.001). CONCLUSION: Overexpression of Frizzled A reduced the infarct size, improved cardiac recovery, modified inflammatory response and amplified angiogenesis. For these reasons, this protein would be of interest for cardiac surgeons using angiogenic therapy (as gene or protein injection) in ischemic heart diseases in non-revascularizable patients.     

Long-term evaluation of direct repair of traumatic isthmic aortic transection

Direct repair of traumatic aortic isthmic transection eliminates the late complications of prosthetic graft repair. This study evaluates the long-term fate of direct aortic repair to which little attention has been paid. Among 32 patients operated upon from 1965 to 1987, 27 (84%) underwent direct repair. The tear was circumferential in 15 patients and partial in 12. Multiple traumatic lesions were present in 26 patients, including intracranial injury in 19. Partial cardiopulmonary bypass was used in 15 patients and simple aortic cross-clamping in 12. No paraplegia was observed. There were 4 deaths from associated lesions among the 14 patients operated upon for acute traumatic isthmic transection and no deaths in the others. Among the 23 survivors, 4 were lost to follow-up; the other 19 patients have excellent clinical results. Intravenous digital aortic angiography performed in 14 patients at a mean delay of 5 years 3 months showed excellent aortic reconstruction in all cases. Technically more demanding and faster than a graft interposition, direct repair is recommended as the procedure of choice in the surgical treatment of traumatic isthmic transection, particularly in young patients, the group most at risk from this lesion.     

Patterns of Incident Reporting Across Clinical Sites in a Regionally Expanding Academic Radiation Oncology Department

PurposeWe evaluated patterns of event reporting across five clinical locations within an academic radiation oncology department, with the goal of better understanding variability across sites.Methods and MaterialsWe analyzed 1,351 events reported to a departmental incident learning system over 1 calendar year across the five locations with respect to volume of events, event type, process map location of origin and detection, and event reporter.ResultsWe found marked variability in reporting patterns, including reporting rate, event type, event severity, event location of origin and detection within the departmental process map, and discipline of event reporters. These differences relate both to variability in process and workflow (reflected by frequency of specific workflow events at each site) and in reporting culture (reflected by volume or rate of event reporting, and discipline of event reporter).ConclusionsThese data highlight the variability in reporting culture even within a single department, and therefore the need to tailor and individualize safety and quality programs to the unique clinical site, with the long-term goal of achieving a common culture of safety while supporting unique processes at individual locations. This work also raises concern about extrapolating single-institution incident learning system results without understanding the unique workflow and culture of clinical sites.     

Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children.

OBJECTIVE: To assess the safety of live, attenuated influenza vaccine (LAIV) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children. METHODS: Twenty-five non-HIV and 24 HIV-infected children (CDC Class N or A1,2) were enrolled into this double blind, placebo-controlled study. Children were randomized within each HIV status group to one of two dosing regimens: Regimen 1, Dose 1 = LAIV, Dose 2 = placebo, Dose 3 = LAIV; or Regimen 2, Dose 1 = placebo, Dose 2 = LAIV, Dose 3 = LAIV. Study doses were separated by 28 to 35 days. Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded. Blood HIV RNA concentrations, CD4 counts and CD4% were measured throughout the study on HIV-infected children. Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose. Influenza isolates were assessed for retention of the temperature-sensitive phenotype. Serum influenza HAI antibodies were measured before and after each LAIV vaccination. RESULTS: No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group, nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV. Overall none of the HIV-infected children experienced a significant LAIV-related serious adverse event or influenza-like illness, making the one sided 95% CI of such a serious event occurring after LAIV 0 to 12%. No significant changes in geometric mean HIV RNA concentrations, CD4 counts or CD4% or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV. All recovered influenza isolates retained the temperature-sensitive phenotype. After two doses of LAIV, 83% of the non-HIV-infected and 77% of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains. CONCLUSION: If relatively healthy HIV-infected children become exposed to LAIV inadvertently, then serious adverse outcomes would not be expected to occur frequently.