The investigation of prostatic calcifications using µ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4.

Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences.Four pathological calcification samples were characterised with micro-particle induced x-ray emission (µ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2-5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific factors in the patient's individual treatment. These factors include the number, size, composition and spatial distribution of calcifications in the prostate as well as the distribution of brachytherapy seeds.

Modelling the blast environment and relating this to clinical injury: experience from the 7/7 inquest.

This paper addresses the computational modelling of a series of specific blast-related incidents and the relationships of clinical and engineering interpretations. The Royal Centre for Defence Medicine and the Defence Science and Technology Laboratory were tasked in 2010 by the UK Ministry of Defence to assist the Coroner's inquests into the 7 July 2005 London bombings. A three phase approach was taken. The first phase included an engineering expert in blast effects on structures reviewing photographs of the damaged carriages and bus to give a view on the likely physical effects on people close to the explosions. The second phase was a clinical review of the evidence by military clinicians to assess blast injury in the casualties. The third phase was to model the blast environment by structural dynamics experts to assess likely blast loading on victims to evaluate the potential blast loading on individuals. This loading information was then assessed by physiology experts. Once all teams (engineering, clinical and modelling/physiological) had separately arrived at their conclusions, the information streams were integrated to arrive at a consensus. The aim of this paper is to describe the methodology used as a potential model for others to consider if faced with a similar investigation, and to show the benefit of the transition of military knowledge to a civilian environment.

Benign pigmented nevi in children. Prevalence and associated factors: the West Midlands, United Kingdom Mole Study.

BACKGROUND AND METHODS: Prevalence of benign melanocytic nevi (moles) has been shown to be a major predictor of malignant melanoma. In this study the prevalence of moles in a group of 2140 children, aged 4 to 11 years, was determined. A standard questionnaire was completed by the parents of each child and included information on environmental and life-style factors. Examination data for each child were linked to the data obtained from the questionnaire. RESULTS: Prevalence increases rapidly throughout childhood and studies of children may indicate which factors contribute to mole development. Boys had more moles than girls, as did white children when compared with other ethnic groups. Prevalence of moles increased with age in children of both sexes. Among whites, skin color had little influence on mole prevalence. The following characteristics, however, were associated with an increased prevalence of moles: a propensity to burn rather than tan, a history of sunburn, a tendency to freckle, and a life-style involving increased sun exposure. A striking positive association between prevalence of moles and number of foreign holidays in a hot climate was observed. This association was independent of a history of sunburn. CONCLUSIONS: The study supports the hypothesis that environmental factors influence the prevalence of moles in childhood.

Subsequent primary cancers in relation to treatment of ovarian cancer.

The incidence of subsequent primary cancers was assessed in relation to treatment for a cohort of 7,203 patients from the Birmingham and West Midlands Cancer Registry diagnosed between 1957 and 1976. The total of 213 cancers observed one or more years after treatment for ovarian cancer (mean follow-up = 6.5 person-years) represented a significant excess (observed (O) = 213, expected (E) = 140.07, relative risk (RR) = 1.5, 95% CI 1.3-1.7, P less than 0.001). Among patients whose treatment included chemotherapy (CT), with or without radiotherapy (RT), the risk of acute and non-lymphocytic leukaemia (A + NLL) was significantly increased (O = 5, E = 0.18, RR = 27.8, 95% CI 9.0-64.8, P less than 0.001). The relative risks of A + NLL following RT without CT (RR = 4.5) and after other treatments (RR = 2.9) were not significantly in excess of 1.0. Significant excesses of subsequent cancers were observed at several sites: breast (RR = 1.7, 95% CI 1.3-2.2), lung (RR = 2.0, 95% CI 1.3-3.4), colon and rectum (RR = 1.6, 95% CI 1.1-2.3), urinary system (RR = 1.9, 95% CI 0.9-3.7), nervous system (RR = 3.3, 95% CI 1.2-7.3) and connective tissue (RR = 6.7, 95% CI 1.8-17.1) but the relationship with type of treatment was not so clearly defined as that for leukaemia. Although the treatment groups were broad and based on routinely collected data, they can enhance the use of cohort analyses for exploratory and monitoring purposes.

Hodgkin's disease: subsequent primary cancers in relation to treatment.

A consecutive series of 2,999 patients, diagnosed with Hodgkin's disease (HD) between 1950 and 1979, was assembled from the records of the Birmingham and West Midlands Cancer Registry and followed to the end of 1984. Cohort analyses of subsequent primary cancers among 1,976 patients, surviving one or more years (mean follow-up 6.7 person-years), were carried out in relation to overall treatment by radiotherapy (RT), chemotherapy (CT) or both modalities (CT + RT). Over all sites a 50% increase in risk, relative to the West Midlands population, was found [observed (O) = 65; relative risk (RR) = 1.5; P less than 0.01]. Among patients treated by CT (with or without RT) a significant increase in acute and non-lymphocytic leukaemias was found (O = 6; RR = 30.0; P less than 0.001). The excess risk was of the order of 1 per 1000 patient-years and the cumulative risk was 1.2%. Among solid tumours increased risks, which might be attributable to RT, occurred in the lung (O = 15; RR = 1.6; P less than 0.05), breast (O = 9; RR = 2.2; P less than 0.05) and bone (O = 2; RR = 20.0; P less than 0.01). The excess of skin cancers (O = 13; RR = 2.9; P less than 0.01) occurred mainly within 10 years of treatment with CT. The follow-up period is still insufficient to determine the long-term effect on the incidence of solid tumours with long latent periods from multiple-agent CT which became more frequently used in the early 1970s. A sub-set of these data was analysed over all treatments and the results were contributed to an international study co-ordinated by the International Agency for Research on Cancer, Lyon.

Studies of two novel sulfasalazine analogs, ipsalazide and balsalazide.

Sulfasalazine appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid in the colon, but its use can be limited by side effects. Ipsalazide and balsalazide are novel sulfasalazine analogs designed to release 5-aminosalicylic acid and a nontoxic carrier molecule in the gastrointestinal tract. They have a low oral toxicity following single or repeat administration to mouse, rat, and ferret, and balsalazide is not mutagenic in the Ames test. Ipsalazide and balsalazide are split in rat and man, and the urinary and fecal excretion pattern of the 5-aminosalicylic acid released is similar to that of sulfasalazine; the carrier molecules are absorbed to a lesser extent than the sulfapyridine derived from sulfasalazine. These two analogs deserve therapeutic trial.

Bifluranol, a novel fluorinated bibenzyl anti-androgen, its chemistry and disposition in different animal species.

The synthesis of bifluranol, a new fluorinated bibenzyl anti-androgen, and of 3H-labelled bifluranol is described. The absorption, distribution and excretion of bifluranol has been studied in mouse, rat, ferret and dog; it is readily absorbed following oral administration, but blood concentrations of the drug are low due to hepatic uptake and biliary excretion. Enterohepatic re-circulation occurs, but the drug is excreted primarily in the faeces and only small amounts appear in urine. This pattern of disposition and excretion is similar to that reported elsewhere for the bibenzyl, hexoestrol, and for the stilbene, diethylstilboestrol.

The metabolism of bifluranol by rat, dog and ferret.

The synthesis of monohydroxy- and dihydroxy-bifluranol, and of glucuronide and sulphate conjugates of bifluranol are described. Bifluranol administered orally to rats, ferrets and dogs at a dosage of 50 to 200 microgram kg-1 is mostly excreted in the faeces as unchanged bifluranol and bifluranol monosulphate, disulphate and monoglucuronide. The bifluranol is well absorbed and is mostly excreted in the bile, as six different conjugates, including a glucuronide sulphate found in all 3 species, and a glucuronide phosphate found only in ferret and dog bile. Hydroxylation of the aromatic rings occurs in the rat, to an extent of about 8% of the dose, but was not detected in ferret or dog.