Management of uveal melanoma: a consensus-based provincial clinical practice guideline.

INTRODUCTION: Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are highly related to the size of the tumour, timely and accurate diagnosis can increase the chance for cure. METHODS: A consensus-based guideline was developed to inform practitioners. PubMed was searched for publications related to this topic. Reference lists of key publications were hand-searched. The National Guidelines Clearinghouse and individual guideline organizations were searched for relevant guidelines. Consensus discussions by a group of content experts from medical, radiation, and surgical oncology were used to formulate the recommendations. RESULTS: Eighty-four publications, including five existing guidelines, formed the evidence base. SUMMARY: Key recommendations highlight that, for uveal melanoma and its indeterminate melanocytic lesions in the uveal tract, management is complex and requires experienced specialists with training in ophthalmologic oncology. Staging examinations include serum and radiologic investigations. Large lesions are still most often treated with enucleation, and yet radiotherapy is the most common treatment for tumours that qualify. Adjuvant therapy has yet to demonstrate efficacy in reducing the risk of metastasis, and no systemic therapy clearly improves outcomes in metastatic disease. Where available, enrolment in clinical trials is encouraged for patients with metastatic disease. Highly selected patients might benefit from surgical resection of liver metastases.

Longitudinal evaluation of the metabolic response of a tumor xenograft model to single fraction radiation therapy using magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy (MRS) was used to evaluate the metabolic profile of human glioblastoma multiform brain tumors grown as xenografts in nude mice before, and at multiple time points after single fraction radiation therapy. Tumors were grown over the thigh in 16 mice in this study, of which 5 served as untreated controls and 11 had their tumors treated to 800 cGy with 200 kVp x-rays. Spectra were acquired within 24 h pre-treatment, and then at 3, 7 and 14 d post-treatment using a 9.4 T animal magnetic resonance (MR) system. For the untreated control tumors, spectra (1-2 per mouse) were acquired at different stages of tumor growth. Spectra were obtained with the PRESS pulse sequence using a 3  ×  3 × 3 mm(3) voxel. Analysis was performed with the LCModel software platform. Six metabolites were profiled for this analysis: alanine (Ala), myo-inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine and glutamate (Glu + Gln), and total choline (glycerophosphocholine + phosphocholine) (GPC + PCh). For the treated cohort, most metabolite/water concentration ratios were found to decrease in the short term at 3 and 7 d post-treatment, followed by an increase at 14 d post-treatment toward pre-treatment values. The lowest concentrations were observed at 7 d post-treatment, with magnitudes (relative to pre-treatment concentration ratios) of: 0.42  ±  24.6% (Ala), 0.43  ±  15.3% (Ins), 0.68  ±  27.9% (Tau), 0.52  ±  14.6% (GPC+PCh), 0.49  ±  21.0% (Cr + PCr) and 0.78  ±  24.5% (Glu + Gln). Control animals did not demonstrate any significant correlation between tumor volume and metabolite concentration, indicating that the observed kinetics were the result of the therapeutic intervention. We have demonstrated the feasibility of using MRS to follow multiple metabolic markers over time for the purpose of evaluating therapeutic response of tumors to radiation therapy. This study provides supporting evidence that metabolite/water concentration ratios have the potential to be used as biomarkers for the assessment of the response to therapy.

Full range determination of ²²²Rn at the watershed scale by liquid scintillation counting.

(222)Rn has been increasingly used to identify groundwater contribution to surface water. Particular attention has been paid to analytical protocols and counting parameters used for liquid alpha scintillation measurements over a range of activities covering river and groundwater domains. Direct measurements and Rn-extraction protocols are optimized, and scintillometer efficiency is calibrated using international standards over the 0.5-35 Bq/L range. The interval of activities was performed in surface water and groundwater from a small Canadian watershed.

Sci-Fri PM: Delivery - 09: Response of a tumor xenograft model to radiation therapy using magnetic resonance spectroscopy.

9.4T 1 H magnetic resonance spectroscopy (MRS) was utilized to track the response of mouse xenograft glioblastoma multiform (GBM) brain tumors to single fraction radiation therapy. Six metabolites were analyzed with LCModel: alanine (Ala), myo-inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine and glutamate (Glu + Gln), and total choline (glycerophosphocholine + phosphocholine) (GPC + PCh). 11 mice received 800 cGy of 200 kVp x-rays, 5 were untreated controls. PRESS spectra (27 µL volumes) were acquired at multiple time points for treated and control animals. In treated animals, all metabolite : water ratios decreased 3 days post-treatment, with further decreases at day 7, and then increases at day 14 relative to the 7 day mark. Concentrations on day 7 relative to pre-treatment were as follows: 0.42 (Ala), 0.43 (Ins), 0.68 (Tau), 0.52 (GPC+PCh), 0.49 (Cr + PCr) and 0.78 (Glu + Gln). Metabolite ratios did not correlate with tumor volume in control animals, suggesting a real therapeutic response was observed. Our 1 H MRS data suggests that perturbations in the metabolic signature of GBM cancers occur in response to irradiation. Such changes in the metabolite : water concentration ratios could potentially be exploited for the improvement of radiotherapy.

Positive and negative dimensions of weight control motivation.

This study examined weight control motivation among patients (N=5460 females and 547 males) who sought weight loss treatment with family physicians. An eight-item measure assessed the frequency of thoughts and feelings related to weight control "outcome" (e.g. expected physical and psychological benefits) and "process" (e.g. resentment and doubt). Factor analysis supported the existence of two factors, labeled Positive and Negative motivation. Positive motivation was high (average frequency of thoughts about benefits was 'every day') and stable throughout treatment, while Negative motivation declined rapidly and then stabilized. The determinants of changes in the Positive and Negative dimensions during treatment were examined within 3 time frames: first month, months 2-6, and 6-12. Maintenance of high scores on Positive motivation was associated with higher BMI and more disturbed eating habits. Early reductions in Negative motivation were greater for those starting treatment with higher weight and more disturbed eating habits, but less depression and stress, while later reductions in Negative motivation were predicted by improvements in eating habits, weight, stress and perfectionism. Clinicians treating obesity should be sensitive to fluctuations in both motivational dimensions, as they are likely to play a central role in determining long-term behavior and weight change.

Sci-Sat AM(1): Imaging-01: Tumour and normal tissue T2 and ADC distributions for a mouse model at 9.4T.

Magnetic resonance (MR) measurements of relaxation times and diffusion coefficient in tissue have been demonstrated to be sensitive to biological changes induced by radiation therapy. We are currently using mouse models of human glioblastoma multiforme (GBM) to study tumour response to ionizing radiation by MRI at 9.4T. Utilizing conventional imaging techniques coupled with quantitative measurements of transverse relaxation time (T2) and apparent diffusion coefficient (ADC), we monitor changes during tumour growth and subsequent changes after single-fraction radiotherapy. In addition to tumour parameters, we have measured T2 and ADC in other structures that appear in the same transverse slices as tumour tissue. Here we report the measured distributions of T2 and ADC in tumour and in normal tissues that are likely to be encountered during MR imaging of tumour xenografts in mice, including liver, kidney, fat, skeletal muscle, spinal cord, and brain. Quantitative knowledge of these distributions in normal tissue is important in optimizing the sequences used for imaging of these tissues, and in optimizing continued measurements of T2 and ADC changes. Knowledge of parameter distributions in tumour is important because recent studies have suggested that the T2 and ADC responses after therapy may be the result of large shifts in smaller isolated pockets of tumour, rather than more moderate shifts in T2 and ADC over the whole tumour volume. These distributions provide a baseline measurement of typical distributions in advance of radiation therapy.

Early treatment response as a predictor of ongoing weight loss in obesity treatment.

OBJECTIVES: This study examined early treatment response in obesity treatment, defined as early change in body mass index (BMI) and early change in eating behaviour, as a predictor of ongoing weight loss in obese patients. METHODS: We conducted a repeated measures analysis of eating behaviour, emotional factors (depression, stress, perfectionism) and BMI, over a 9 month period. Subjects were 344 females, aged 18-65 (mean = 41.8), with a BMI of at least 25 (mean BMI = 33.7), engaged in very-low calorie (VLCD) or low-calorie (LCD) diets. RESULTS: Multi-level modelling identified four significant predictors of ongoing weight loss (weight loss occurring between 5 weeks and 9 months after the start of treatment). These included: type of diet, early BMI change (start to 5 weeks), number of weigh-ins and the early change in uncontrolled eating (start to 5 weeks). Estimates based on multi-level modelling indicate that patients with strong versus weak early treatment responses would be expected to show large differences in ongoing weight loss. CONCLUSIONS: Early improvements in eating behaviour and weight appear to have additive effects in the prediction of ongoing weight change. Future research is required to identify the optimal rate of weight loss, whether there are critical periods for behaviour change, and factors which influence the likelihood of early behaviour change.

Convergent validity of the Larocque Obesity Questionnaire and self-reported behavior during obesity treatment.

A validation study of the Larocque Obesity Questionnaire designed for use in obesity treatment was performed. Unlike other measures of obesity, this questionnaire includes scales measuring general emotional state as well as eating behavior. Subscales measured uncontrolled eating, physical stress responses, depression, and perfectionism. Subjects were 458 women and 79 men in treatment for obesity by general practitioners. The subscales showed acceptable internal consistency and related in predictable ways to measures of eating behavior, depression, self-criticism, stress, physical complaints and weight-control motivation. Subjects in the heaviest weight category (Body Mass Index > or = 40) showed higher scores on Stress Response and Depression subscales. There were no significant sex differences, after controlling for weight. All four subscales showed significant improvement after 5 wk., which indicates their sensitivity to changes during treatment.

Effectiveness of an intensive speech perception training program for adult cochlear implant recipients.

A staggered multiple baseline single-subject experimental design was used to assess the effectiveness of a postimplant intensive aural rehabilitation program. Four adults with an acquired profound hearing loss were provided with a Nucleus 22-channel cochlear implant. The subjects completed a speech perception test protocol once before their cochlear implant operation and at 3-month intervals for a period of 12 months postimplantation. Each subject participated in a 12-week postimplant intensive aural rehabilitation program. A comparison of the prerehabilitation and postrehabilitation results failed to reveal any systematic improvements in performance on the speech perception tests that could be attributed unequivocally to the aural rehabilitation program.

Seeding mechanism of urothelium over nonepithelialized surfaces.

To study urothelial spreading over nonepithelialized tissue surfaces, bladder defects in rabbits were patched with pedicled prevesical fat. Using serial sections and scanning electron microscopic studies, it was concluded that urothelium in the process of covering nonepithelialized surfaces is able to seed at a distance from the periphery of the defect as one means of epithelializing a defect.

Shunt surgery for priapism: review of results.

In a review of the literature on shunt operations for priapism, 100 case reports were found. The over-all result in terms of potency is 61 per cent. In general there is little difference in outcome between the cavernosus-saphenous vein and cavernosus-spongiosum shunts. If the former surgical procedure is to be performed, a unilateral operation appears to yield better results than a bilateral one. Various causes of priapism are noted in relation to results of surgery, and the complications of shunt procedures are discussed. Equally good results are noted whether the operation is performed early or relatively late in the disease.