Dose reconstruction from PET images in carbon ion therapy: a deconvolution approach.

Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the [Formula: see text]-decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively.

Experimental validation of the FLUKA Monte Carlo code for dose and [Formula: see text]-emitter predictions of radioactive ion beams.

In the context of hadrontherapy, whilst ions are capable of effectively destroying radio resistant, deep seated tumors, their treatment localization must be well assessed to ensure the sparing of surrounding healthy tissue and treatment effectiveness. Thus, range verification techniques, such as online positron-emission-tomography (PET) imaging, hold great potential in clinical practice, providing information on the in vivo beam range and consequent tumor targeting. Furthermore, [Formula: see text] emitting radioactive ions can be an asset in online PET imaging, depending on their half-life, compared to their stable counterparts. It is expected that using these radioactive ions the signal obtained by a PET apparatus during beam delivery will be greatly increased, and exhibit a better correlation to the Bragg Peak. To this end, FLUKA Monte Carlo particle transport and interaction code was used to evaluate, in terms of annihilation events at rest and dose, the figure of merit in using [Formula: see text] emitter, radioactive ion beams (RI [Formula: see text]). For this purpose, the simulation results were compared with experimental data obtained with an openPET prototype in various online PET acquisitions at the Heavy Ion Medical Accelerator in Chiba (HIMAC), in collaboration with colleagues from the National Institute of Radiological Sciences' (NIRS) Imaging Physics Team. The dosimetry performance evaluation with FLUKA benefits from its recent developments in fragmentation production models. The present work estimated that irradiations with RI [Formula: see text], produced via projectile fragmentation and their signal acquisition with state-of-the-art PET scanner, lead to nearly a factor of two more accurate definition of the signals' peak position. In addition to its more advantageous distribution shape, it was observed at least an order magnitude higher signal acquired from 11C and 15O irradiations, with respect to their stable counterparts.

Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002-2009: a population-based cohort study.

BACKGROUND: The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. METHODS: This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. RESULTS: We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient-days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008-2009 and 2002-2003 respectively). CONCLUSIONS: In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.

Correlation between physiological assessment and outcome after liver transplantation.

BACKGROUND: Critical shortages of organ donors for transplantation require appropriate utilization of this scarce resource. The purpose of this study was to assess whether use of physiological parameters of preliver transplant recipients is helpful in determining eventual outcome. METHODS: Between October 1989 and June 1999, 215 liver transplants were performed on 199 patients at the Vancouver Hospital nad Health Sciences Centre. Thirty-one patients undergoing transplantation between May 1993 and June 1994 were retrospectively evaluated to obtain a minimum 5-year follow-up. Variables examined included pretransplant activation status (status 1, at home; status 2, hospitalized; status 3, admitted to intensive care; status 4, mechanical ventilation), simplified acute physiological score (SAPS), Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II, and APACHE III scores at the time of transplantation. The scores were correlated to posttransplant mortality and functional outcome. RESULTS: The 5-year mortality for status 1 patients was 14.3% versus 30% for patients listed as status 2 or greater (P = not significant). There were no significant differences in any of the physiological scoring assessments with regard to posttransplant mortality or functional assessment. Of the surviving patients, 18 of 22 who were employed, in school, or active at home pretransplant returned to their pretransplant activity. CONCLUSIONS: Detailed physiological scoring systems are no more accurate in predicting outcome after liver transplant than current listing status parameters.

Assessment of immunologic status of liver transplant recipients by peripheral blood mononuclear cells in response to stimulation by donor alloantigen.

OBJECTIVE: To determine whether there is a role for assessing peripheral blood mononuclear cell (PBMC) cytokine patterns as a means of measuring the immunologic and clinical status of liver transplant recipients. SUMMARY BACKGROUND DATA: The role of assessing cytokine patterns in the prediction of clinical graft rejection or acceptance remains unclear. The purpose of this study was to examine the cytokine profiles of PBMC stimulated in vitro with donor alloantigen and to correlate prospectively the data with clinical assessment of graft status in orthotopic liver transplant (OLT) recipients. METHODS: PBMCs from OLT recipients were examined for proliferation and cytokine mRNA expression after stimulation by donor alloantigen, third-party alloantigen, or phytohemagglutinin (PHA). mRNA extracted from PBMC was amplified by reverse transcriptase-polymerase chain reaction with oligospecific primer pairs for interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta. Results were prospectively correlated with each patient's allograft status. RESULTS: Increased IL-4 and TGF-beta and decreased IL-2, IFNgamma, and TNF-alpha mRNA expression by PBMCs in response to donor alloantigen stimulation predicted immunologic graft stability over a minimum 60-day interval compared with mRNA expression of PBMCs from patients with established rejection or those who experienced a rejection episode within a 30-day period (p < 0.05). Stimulation of recipient PBMCs with third-party alloantigens or PHA yielded similar but less specific results. PBMC proliferation to varying antigenic stimulation did not correlate with clinical graft status, nor did cytokine production by unstimulated PBMC. CONCLUSIONS: Prospective assessment of cytokine expression by PBMC from OLT recipients in response to stimulation by donor alloantigen is helpful for predicting the clinical status of the allograft and may be useful in the development of more precise immunologic monitoring protocols.

Selecting candidates for liver transplantation: a medical ethics perspective on the microallocation of a scarce and rationed resource.

Liver transplantation has evolved over the past 35 years from an experimental procedure with high perioperative mortality to an accepted form of treatment with an approximate 85% one-year and 80% three-year patient survival rate. Following the success and acceptance of transplantation in the treatment of end-stage liver disease, there has been a progressive increase in the number of patients seeking a limited supply of donor organs. The ethical focus, on a microallocation level, has therefore changed from that of the 1960s, when the question was whether the procedure should be offered at all, to that of the 1990s and beyond, when the focus is on the proper allocation of a scarce, life-saving resource. The ethical issues concerning fair allocation surrounding liver transplantation are explored, from both the referring physician's perspective and the perspective of the transplant physician. In particular, the contrasting viewpoints of bioethicists Nicholas Rescher and James Childress, with respect to nonmedical and social criteria in the selection of patients for scarce, life-saving therapies are explored. Lastly, some alternative ethical models for patients selection are reviewed.

Workload and cost-benefit of hospital pharmacy residents.

The workload performed by three hospital pharmacy residents during typical clinical rotations was quantified then subjected to cost-benefit analysis. Daily activities and interventions were recorded on standardized forms for a four-week period. The cost of a resident to provide direct patient care services was compared to that of a staff pharmacist. In addition, the balance of the residents' salary and partial salaries of any pharmacists spending time with the residents were included in the cost analysis. The interventions were analyzed for their impact on patient care and potential cost avoidance by an external review committee. Collectively, more than 660 hours were recorded. Fifty-two percent of hospital time was spent on education-related activities and 32 percent on the provision of clinical services. Thirty interventions were submitted to a review panel of three physicians. Of the 90 evaluations, 76 percent were considered to have a positive impact on patient care, 22 percent no effect, and two percent a potentially detrimental effect. In one case, reviewers thought that hospitalization could have been prolonged had the intervention not occurred. Cost-benefit analysis yielded a ratio of 1.4 to 1 in favour of the residents. While the major benefit of a residency program is the perceived long-term benefit to the profession and patients, this study suggests that even during their residency year, hospital pharmacy residents provide cost-beneficial clinical services.

[A case of severe juvenile pulmonary tuberculosis associated with malnutrition in special reference to nutritional assessment].

We reported a case who had suffered from severe pulmonary tuberculosis in association with severe malnutrition. A 19-year-old man was admitted complaining of high fever, productive cough and body weight loss. Before admission, he worked as a cook for long hours a day and had meals irregularly. On admission, he was cachexic. Coarse crackles were auscultated on the both lung field, and the liver was enlarged. Chest X-ray revealed multiple ringed and mottled shadows mainly in bilateral upper and middle lung field. Laboratory examination revealed inflammatory reaction defined by an increase of white blood cells, accelerated erythrocyte sedimentation rate and positive CRP, impairment of liver function and cell-mediated immunity, hypoxemia and restrictive lung dysfunction. Ziehl-Neelsen stain of sputum showed a large number of acid fast bacilli. The assessment of his nutritional status showed decrease in anthropometric measurements, visceral proteins and the Fischer ratio, which suggested that he was in the status of protein-calorie malnutrition in association with amino acid imbalance. He was treated with nutritional therapy in addition to antituberculous drugs, which improved his clinical symptoms, laboratory data and nutritional assessment. These results suggested the importance of nutritional assessment and nutritional therapy based on it.