ABSTRACT
OBJECTIVE: Passive scattering proton beam (PSPB) radiotherapy for accelerated partial-breast irradiation (APBI) provides superior dosimetry for APBI three-dimensional conformal photon radiotherapy (3DCRT). Here we examine the potential incremental benefit of intensity-modulated proton radiotherapy (IMPT) for APBI and compare its dosimetry with PSPB and 3DCRT. METHODS: Two theoretical IMPT plans, TANGENT_PAIR and TANGENT_ENFACE, were created for 11 patients previously treated with 3DCRT APBI and were compared with PSPB and 3DCRT plans for the same CT data sets. The impact of range, motion and set-up uncertainties as well as scanned spot mismatching between fields of IMPT plans was evaluated. RESULTS: IMPT plans for APBI were significantly better regarding breast skin sparing (p<0.005) and other normal tissue sparing than 3DCRT plans (p<0.01) with comparable target coverage (p=ns). IMPT plans were statistically better than PSPB plans regarding breast skin (p<0.002) and non-target breast (p<0.007) in higher dose regions but worse or comparable in lower dose regions. IMPT plans using TANGENT_ENFACE were superior to that using TANGENT_PAIR in terms of target coverage (p<0.003) and normal tissue sparing (p<0.05) in low-dose regions. IMPT uncertainties were demonstrated for multiple causes. Qualitative comparison of dose-volume histogram confidence intervals for IMPT suggests that numeric gains may be offset by IMPT uncertainties. CONCLUSION: Using current clinical dosimetry, PSPB provides excellent dosimetry compared with 3DCRT with fewer uncertainties compared with IMPT. ADVANCES IN KNOWLEDGE: As currently delivered in the clinic, PSPB planning for APBI provides as good or better dosimetry than IMPT with less uncertainty.
Subject(s)
Breast Neoplasms/radiotherapy , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated , Female , Humans , Photons/therapeutic use , Proton Therapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
Morphological changes of hepatocyte death have so far only been described on cells in culture or in tissue sections. Using a high-resolution and high-magnification multiphoton microscopic system, we recorded in living mice serial changes of acetaminophen (APAP)-induced hepatocyte necrosis in relevance to metabolism of a fluorogenic bile solute. Initial changes of hepatocyte injury included basal membrane disruption and loss of mitochondrial membrane potential. An overwhelming event of rupture at adjacent apical membrane resulting in flooding of bile into these hepatocytes might ensue. Belbs formed on basal membrane and then dislodged into the sinusoid circulation. Transmission electron microscopy disclosed a necrotic hepatocyte depicting well the changes after apical membrane rupture and bile flooding. Administration of the antidote N-acetylcysteine dramatically reduced the occurrence of apical membrane rupture. The present results demonstrated a hidden but critical step of apical membrane rupture leading to irreversible APAP-induced hepatocyte injury.
Subject(s)
Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Bile Canaliculi/drug effects , Cell Membrane/drug effects , Liver/drug effects , Necrosis/chemically induced , Acetylcysteine/pharmacology , Acetylcysteine/toxicity , Animals , Antidotes/pharmacology , Bile Canaliculi/physiopathology , Cell Membrane/ultrastructure , Liver/cytology , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Microscopy, Fluorescence, MultiphotonABSTRACT
A multiple tracer dilution method measuring total body water, extracellular water, plasma volume, and red cell volume was used to study body composition. Healthy Chinese subjects were compared to a group of Chinese patients with various newly diagnosed gastrointestinal disorders scheduled for elective operation. Compositional data obtained from these groups showed no significant differences in compartmentalization, suggesting absence of major changes during the early stages of certain gastrointestinal diseases. In addition, healthy Chinese subjects were compared to a group of healthy Americans previously evaluated by similar dilutional methods. In males, body weight (kg) differed considerably (Chinese = 62.1 +/- 2.0 versus American = 72.5 +/- 4.1, p less than 0.02) and could be explained by alterations in body fat (Chinese = 12.4 +/- 1.3 versus American = 19.2 +/- 2.2, p less than 0.02) and extracellular water (Chinese = 14.4 +/- 0.5 versus American = 16.8 +/- 0.8, p less than 0.02). Functional tissue ("body cell mass") was similar in the 2 groups which suggested that Chinese have comparable body composition without an additional fat burden. The multiple tracer technique using deuterium oxide, sodium bromide, Evans dye, and Cr51 for body compositional assessment is accurate but expensive and laborious. Therefore, equally precise but more economical bedside methods are needed for routine compositional analysis.
