Cardiac substructures exposure in left-sided breast cancer radiotherapy: Is the mean heart dose a reliable predictor of cardiac toxicity?

PURPOSE: This study aimed to assess radiation dose distribution to cardiac subvolumes in left-sided breast cancer radiotherapy (LBCRT) and to clarify whether the mean heart dose (MHD) reliably reflects cardiac substructures exposure. MATERIALS AND METHODS: Fifty women referred for adjuvant LBCRT were prospectively evaluated. All patients received 3D-conformal hypofractionated radiotherapy (40Gy delivered in 15 fractions of 2.67Gy±boost of 13.35Gy). Cardiac substructures were contoured using the F. Duane's cardiac atlas. Dose distribution to cardiac chambers, left main (LM), left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA)) was assessed. Dosimetric associations were analysed. RESULTS: The mean MHD was 3.08Gy (EQD2=3.67Gy). The mean Dmean/Dmax LAD was 11.45Gy (EQD2=13.64Gy)/29.5Gy (EQD2=35.15Gy). Low doses were delivered to LM, LCx, and RCA (Dmean≤1.3Gy). The left ventricle (LV) was the most exposed cardiac chamber with Dmean/Dmax of 4.78Gy/37Gy. The strongest correlation with MHD was found for Dmean LAD (r=0.81). For every 1Gy increase in MHD, Dmean LAD rose by 3.4Gy. However, the proportion of variance in Dmean LAD predictable from MHD was moderate (R2=0.65). For all other cardiac substructures, R2 values were<0.7. CONCLUSION: Our study showed high exposure of LAD and LV in LBCRT. With poor predictive value, MHD may underestimate doses to cardiac substructures. For optimal heart sparing radiotherapy, we recommend to consider LV and LAD as separate organ at risk.

The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome.

Metazoan genomes contain large numbers of genes that participate in responses to environmental stressors. We surveyed the sea urchin Strongylocentrotus purpuratus genome for homologs of gene families thought to protect against chemical stressors; these genes collectively comprise the 'chemical defensome.' Chemical defense genes include cytochromes P450 and other oxidases, various conjugating enzymes, ATP-dependent efflux transporters, oxidative detoxification proteins, and transcription factors that regulate these genes. Together such genes account for more than 400 genes in the sea urchin genome. The transcription factors include homologs of the aryl hydrocarbon receptor, hypoxia-inducible factor, nuclear factor erythroid-derived 2, heat shock factor, and nuclear hormone receptors, which regulate stress-response genes in vertebrates. Some defense gene families, including the ABCC, the UGT, and the CYP families, have undergone expansion in the urchin relative to other deuterostome genomes, whereas the stress sensor gene families do not show such expansion. More than half of the defense genes are expressed during embryonic or larval life stages, indicating their importance during development. This genome-wide survey of chemical defense genes in the sea urchin reveals evolutionary conservation of this network combined with lineage-specific diversification that together suggest the importance of these chemical stress sensing and response mechanisms in early deuterostomes. These results should facilitate future studies on the evolution of chemical defense gene networks and the role of these networks in protecting embryos from chemical stress during development.

The role of fine needle aspiration cytology and imprint cytology in cervical lymphadenopathy.

OBJECTIVE: To determine the diagnostic accuracy of cervical lymphadenopathy by fine needle aspiration (FNAC) and imprint cytology (IC). METHODS: This study included 94 patients with cervical lymphadenopathy. This study was carried out in the Departments of General Surgery and Pathology, King Fahad Hospital, Hofuf, Kingdom of Saudi Arabia, from June 2001 through to July 2002. They were subjected to clinical examination and FNAC of one of the enlarged lymph nodes. This was followed by IC and histological examination of this lymph node after its excision. RESULTS: Clinical examination was correct in 78% of the cases. The overall accuracy of fine needle aspiration was 93%. It was accurate on all cases of reactive hyperplasia, 93% of tuberculosis lymphadenitis, 90% in Hodgkin's lymphoma, 86% in non-Hodgkin's lymphoma, and 91% of metastasis lymphadenopathy. On the other hand, the overall accuracy of IC was higher than that of fine needle aspiration, being 97%. It diagnosed all cases of reactive hyperplasia and non-Hodgkin's lymphoma, 97% in tuberculosis lymphadenitis, 90% in Hodgkin's lymphoma and 95% in metastasis lymphadenopathy. CONCLUSION: These techniques proved to be reliable, rapid, and inexpensive procedures in diagnosis of lymphadenopathy. They can differentiate well between inflammatory and neoplastic lesions, in cases of lymphoma, cytological diagnosis should be followed by histological diagnosis for accurate classification and grading.