Time series analysis of injuries

We used time series models in the exploratory and confirmatory analysis of selected fatal injuries in the United States from 1972 to 1983. We built autoregressive integrated moving average (ARIMA) models for monthly, weekly, and daily series of deaths and used these models to generate hypotheses. These deaths resulted from six causes of injuries: motor vehicles, suicides, homicides, falls, drownings, and residential fires. For each cause of injury, we estimated calendar effects on the monthly death counts. We confirmed the significant effect of vehicle miles travelled on motor vehicle fatalities with a transfer function model. Finally, we applied intervention analysis to deaths due to motor vehicles.     

Updates on Gallbladder Cancer Management

Purpose of Review

We will review the current standard of care management for metastatic gallbladder cancer (GBC), recommendations for resection of incidentally or non-incidentally diagnosed GBC, and developments in preoperative risk stratification and adjuvant chemotherapy.

Recent Findings

Gemcitabine-cisplatin is the standard of care therapy for advanced-stage disease. Patients with incidentally diagnosed GBC should undergo re-resection for T1b, T2, or T3 disease. The presence of residual disease is associated with decreased survival. Diagnostic laparoscopy should be used in select patients to avoid unnecessary laparotomy. Major hepatectomy and common bile duct excision should only be performed in select cases. Current standard of care for adjuvant therapy includes 6 months of oral capecitabine.

Summary

Gallbladder cancer continues to carry high mortality rates due to its aggressive course and early spread. Recent developments in preoperative risk stratification, surgical resection, and chemotherapy have greatly shaped management of this malignancy in the current era.

     

Radiation-mediated up-regulation of gene expression from replication-defective adenoviral vectors: implications for sodium iodide symporter gene therapy

PURPOSE: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)-mediated (131)I therapy with EBRT. EXPERIMENTAL DESIGN: Expression of reporter genes [NIS, green fluorescent protein (GFP), beta-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc. RESULTS: EBRT increased NIS, GFP, and beta-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin alpha(v)) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors. CONCLUSIONS: Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.     

Experimental bagassosis: role of infection

The pathological lesions of bagassosis have been reproduced in guinea pigs given bagasse fibers along with low doses of actinomycete spores. In the early stages, interstitial infiltration with lymphocytes and macrophages as seen in humans was noted. Later, small interstitial bagasse granulomas composed of foreign body giant cells, fibroblasts, and lymphocytes developed, some of which had a laminated appearance. Lymph node changes consistent with an immunological reaction were observed. Actinomycetes alone showed occasional areas of pneumonitis and bagasse alone small granulomas consisting of foreign body giant cells and bagasse fibers. Finally, the combined effect of dust and actinomycetes produced interstitial fibrosis composed of thick reticulin fibers and occasional collagen fibers, which persisted to the end of the experiment. Bagasse alone and actinomycetes alone produced only thin reticulin fibers. It has been suggested that bagassosis is due to the synergistic action of bagasse fibers and Micropolyspora faeni and that in the pathogenesis of the syndrome an immunological component may be involved.     

Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer.

PURPOSE: The present study was conducted to determine clinical relevance of surfactant protein A (SP-A) genetic aberrations in early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: To determine whether SP-A aberrations are lung cancer-specific and indicate smoking-related damage, tricolor fluorescence in situ hybridization with SP-A and PTEN probes was done on touch imprints from the lung tumors obtained prospectively from 28 patients with primary NSCLC. To further define the clinical relevance of SP-A aberrations, fluorescence in situ hybridization was done on both tumor cells and adjacent bronchial tissue cells from paraffin-embedded tissue blocks from 130 patients NSCLC for whom we had follow-up information. RESULTS: SP-A was deleted from 89% of cancer tissues and the deletion was related to the smoking status of patients (P < 0.001). PTEN was deleted from 16% in the cancer tissues and the deletion was not related to the smoking status of patients (P > 0.05). In the cells isolated from paraffin-embedded tissue blocks, SP-A was deleted from 87% of the carcinoma tissues and 32% of the adjacent normal-appearing bronchial tissues. SP-A deletions in tumors and adjacent normal-appearing bronchial tissues were associated with increases in the risk of disease relapse (P = 0.0035 and P < 0.001, respectively). SP-A deletions in the bronchial epithelium were the strongest prognostic indicators of disease-specific survival (P = 0.025). CONCLUSIONS: Deletions of the SP-A gene are specific genomic aberrations in bronchial epithelial cells adjacent to and within NSCLC, and are associated with tumor progression and a history of smoking. SP-A deletions might be a useful biomarker to identify poor prognoses in patients with NSCLC who might therefore benefit from adjuvant treatment.     

Assessment of S Values in Stylized and Voxel-Based Rat Models for Positron-Emitting Radionuclides

Purpose

Positron emission tomography (PET) is a powerful tool in small animal research, enabling noninvasive quantitative imaging of biochemical processes in living subjects. However, the dosimetric characteristics of small animal PET imaging are usually overlooked, although the radiation dose may be significant. The variations of anatomical characteristics between the various computational models may result in differences in the dosimetric outcome.

Methods

We used five different anatomical rat models (two stylized and three voxel based) to compare calculated absorbed fractions and S values for eight positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Y-86, and I-124) commonly used to label various probes for small animal PET imaging. The MCNPX radiation transport code was used for radiation dose calculations.

Results

For most source/target organ pairs, O-15 and Ga-68 produce the highest self-absorbed S values because of the high-energy and high-frequency of positron emissions, while Y-86 produces the highest cross-absorbed S values because of the high energy and high frequency of γ-rays emission. Anatomical models produced from different rat strains or modeling techniques exhibit different organ masses, volumes, and thus give rise to different S values and absorbed dose. The variations of absorbed fractions between models of the same type are less than those between models with different types. The calculated S values depend strongly on organ mass, and as such, different models produce similar S values for organs of comparable masses. In most source organs presenting with high cumulated activity, the absorbed dose is less affected by model difference compared with other organs.

Conclusions

The produced S values for common positron-emitting radionuclides can be exploited in the assessment of radiation dose to rats from different radiotracers used in small animal PET experiments. This work contributes to a better understanding of the influence of different computational models on small animal dosimetry.