The Usefulness of Pre-Radiofrequency Ablation SUVmax in 18F-FDG PET/CT to Predict the Risk of a Local Recurrence of Malignant Lung Tumors after Lung Radiofrequency Ablation

The aim of the present study was to assess the diagnostic usefulness of Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the prediction of local recurrence of malignant lung tumors by analyzing the pre-radiofrequency ablation (RFA) maximal standardized uptake value (SUVmax). We performed a historical cohort study of consecutive malignant lung tumors treated by RFA from January 2007 to May 2008 at Okayama University Hospital. We selected only lung tumors examined by PET/CT within 90 days before RFA and divided them (10 primary and 29 metastatic) into 3 groups according to their tertiles of SUVmax. We calculated recurrence odds ratios in the medium group and the high group compared to the low group using multivariate logistic analysis. After we examined the relationship between SUVmax and recurrence in a crude model, we adjusted for some factors. Tumors with higher SUVmax showed higher recurrence odds ratios (medium group;1.84, high group;4.14, respectively). The tumor size also increased the recurrence odds ratio (2.67);we thought this was mainly due to selection bias because we excluded tumors less than 10mm in diameter. This study demonstrated the pre-RFA SUVmax in PET/CT may be a prognostic factor for local recurrence of malignant lung tumors

Radiotherapy for choroidal hemangioma

PURPOSE: Circumscribed choroidal hemangioma is an uncommon, benign vascular tumor that typically appears in the posterior pole of the eye. Visual acuity loss typically results from its exudation, followed by serous retinal detachment. The purpose of the study was to evaluate the efficacy and the safety of external beam irradiation in treating circumscribed choroidal hemangioma. METHODS: We treated 4 eyes of 4 patients with circumscribed choroidal hemangioma with external beam irradiation at Okayama University Hospital from 2002 to 2009. A total absorbed dose of 20 Gy (beam energy, 4, 10 MV) was applied to each of the 4 patients. Each patient received a single 2-Gy daily fraction for five consecutive days in a week, for two consecutive weeks. RESULTS: In all cases, the retinal detachment showed complete resolution within 8 to 48 days after treatment. A decrease in tumor thickness was observed in all cases except one in which the follow-up period was rather short (3.7 months). The visual acuity improved in all 4 eyes. No eyes showed deterioration of visual acuity. During follow-up periods of 3.7 months to 58.5 months, there were no signs of radiation-induced cataract, retinopathy or optic neuropathy

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Jurkat Cells Using Bio-phantoms

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis

Correlation of <i>UGT1A1</i> Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101)

The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy

β-Secretase Inhibitor Potency Is Decreased by Aberrant β-Cleavage Location of the “Swedish Mutant” Amyloid Precursor Protein

The amyloid-β (Aβ) peptide, widely known as the causative molecule of Alzheimer disease (AD), is generated by the sequential cleavage of amyloid precursor protein (APP) by the aspartyl proteases BACE1/β-secretase and presenilin/γ-secretase. Inhibition of BACE1, therefore, is a promising strategy for preventing the progression of AD. However, β-secretase inhibitors (BSIs) exhibit unexpectedly low potency in cells expressing “Swedish mutant” APP (APPswe) and in the transgenic mouse Tg2576, an AD model overexpressing APPswe. The Swedish mutation dramatically accelerates β-cleavage of APP and hence the generation of Aβ; this acceleration has been assumed to underlie the poor inhibitory activity of BSI against APPswe processing. Here, we studied the mechanism by which the Swedish mutation causes this BSI potency decrease. Surprisingly, decreased BSI potency was not observed in an in vitro assay using purified BACE1 and substrates, indicating that the accelerated β-cleavage resulting from the Swedish mutation is not its underlying cause. By focusing on differences between the cell-based and in vitro assays, we have demonstrated here that the potency decrease is caused by the aberrant subcellular localization of APPswe processing and not by accelerated β-cleavage or the accumulation of the C-terminal fragment of β-cleaved APP. Because most patients with sporadic AD express wild type APP, our findings suggest that the wild type mouse is superior to the Tg2576 mouse as a model for determining the effective dose of BSI for AD patients. This work provides novel insights into the potency decrease of BSI and valuable suggestions for its development as a disease-modifying agent