Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.

System validation and work practice efficiency gains of a new localization method for stereotactic radiotherapy.

The increased procedural demands of stereotactic localization techniques when compared with conventional treatment practices reduces machine efficiency, an outcome likely to be greatly magnified by the introduction of fractionation to stereotactic techniques. Currently in Australia and New Zealand there are no guidelines for the definition of efficiency. We sought to devise a system to simultaneously validate the accuracy and efficiency of the technique. The frameless relocation methods employed in the Medtronic Sofamor Danek (MSD) stereotactic radiotherapy (SRT) system were studied in the clinical setting. Accuracy has been determined according to the accumulation of errors throughout the planning and treatment process. The clinical demands of the system (staffing and resources) were analysed relative to conventional treatment approaches. Timing studies indicate a mean time of 19.7 min for treatment of a daily SRT fraction (4-5 arcs, single isocentre). Cost and staffing requirements are similar to those for conventional radiotherapy. It is concluded that with the system used, SRT is efficient for routine clinical implementation, with the level of efficiency increasing with increasing patient numbers. It is recommended that a common acceptance standard be developed to allow cross-institutional comparison of the clinical efficiency of new treatment techniques.

Boar taint in pigs selected for components of efficient lean growth rate.

Genetic and nutritional effects on the boar taint traits of androstenone, skatole and indole and the eating quality traits associated with boar taint were examined by testing animals from four selection lines and a control line on isoenergetic diets, which differed in ileal digestible lysine: digestible energy (0.40, 0.76 and 1.12 g lysine/MJ DE). The selected lines resulted from seven generations of selection for high daily food intake, lean food conversion ratio (LFC) and lean growth rate on ad libitum (LGA) or restricted (LGS) feeding regimes in a Large White population. During performance test, from 30 to 90 kg, boars were fed on either ad libitum or restricted (0.75 g/g ad libitum daily food intake) feeding regimes. A sensory panel assessed heated fat samples for androstenone odour, skatole odour and abnormal odour. There were no significant differences between the selection and control lines or diets for log transformed fat content of androstenone, skatole, indole. The significant diet with feeding regime interaction for log transformed fat content of skatole and indole were essentially due to significantly higher log transformed fat contents with ad libitum feeding of the high lysine diet compared to restricted feeding (skatole: -1.94 vs -3.06, s.e.d. 0.43; indole: -3.44 vs -4.22, s.e.d. 0.28), as differences between feeding regimes on diets A and C were not significantly different from zero. There were no significant differences between selection and control lines for sensory panel score for abnormal odour or androstenone odour, but the LFC and LGA selection lines had a significantly higher skatole odour score than the LGS selection line. Neither diet nor feeding regime had any significant effect on sensory panel assessment of odour. Log transformed fat content of androstenone and skatole were significantly correlated with sensory panel score for skatole odour (0.37 and 0.46, s.e. 0.12), but not with sensory panel score for androstenone odour (0.06 and 0.09), such that they would not be useful predictors of androstenone odour.

Genotype with nutrition interaction on fatty acid composition of intramuscular fat and the relationship with flavour of pig meat.

The effects of genotype, diet and the genotype with diet interaction on fatty acid composition of neutral lipid and phospholipid of intramuscular fat in pigs were examined. Pigs from four selection lines and a control line were fed isoenergetic diets, which differed in ileal digestible lysine:digestible energy (A: 0.40, C: 0.76 and E: 1.12 g lysine/MJ DE). The selected lines resulted from seven generations of selection for high daily food intake (DFI), lean food conversion ratio (LFC) and lean growth rate on ad-libitum (LGA) or restricted feeding regimes in a Large White population. During performance test, from 30 to 90 kg, pigs were fed on either ad-libitum or restricted (0.75 g/g ad-libitum daily food intake) feeding regimes. A trained sensory panel assessed intensities of pork flavour and abnormal flavour and the hedonic characteristics of flavour liking and overall acceptability. The proportion of neutral lipid in the LGA line was lower (0.64 v 0.75, s.e.d. 0.03) while the polyunsaturated:saturated (P:S) ratio of the LFC line (0.53 v 0.41, s.e.d. 0.05) was higher than the control line and other selection lines. The DFI line had a higher phospholipid n-6:n-3 ratio than other selection lines (14 v 11, s.e.d. 1.0). Diets C and E resulted in lower neutral lipid:phospholipid ratio (0.7 v 0.8, s.e.d. 0.01), n-6:n-3 ratios for both neutral lipid (5 v 13, s.e.d. 0.8) and phospholipids (7 v 20, s.e.d. 0.6) and a higher P:S ratio (0.5 v 0.3, s.e.d. 0.03) for neutral lipid than diet A. Neutral lipid fatty acids C18:2 n-6, C18:3 n-3, C20:3 n-6, C20:4 n-6, C20:5 n-3, C22:5 n-3 and C22:6 n-3 were negatively correlated with pork flavour (-0.30, s.e.d. 0.10), flavour liking (-0.33) and overall acceptability (-0.30). In contrast, the fatty acids C16:1, C18:1 ω9 and C18:1 ω11 were positively correlated with pork flavour (0.36), flavour liking (0.39) and overall acceptability (0.40). However, correlations for fatty acids in the phospholipid class were positive for C18:2 n-6, C20:4 n-6 and C22:4 n-6 with pork flavour (0.33), flavour liking (0.23) and overall acceptability (0.23). The proportion of neutral lipid had non-significant correlations with flavour traits; pork flavour (0.01), abnormal flavour (0.08), flavour liking (-0.03) and overall acceptability (0.03). The selection lines responded in a similar manner to the different diets, such that there was little evidence for genotype with nutrition interactions for fatty acid concentrations of neutral lipids and phospholipids. Selection for high lean growth will reduce intramuscular fat, but the increased relative amount of phospholipid and concentration of polyunsaturated fatty acids are unlikely to reduce eating quality. Nutritional effects on intramuscular fat characteristics were greater than genetic effects, such that nutritional approaches to feeding pigs will provide effective methods of reducing the n-6:n-3 fatty acid ratio of human dietary fat from pigmeat and improving human health.

Implementation of a stereotactic radiotherapy system.

The tests carried out on a recently-installed stereotactic radiotherapy system capable of fully frameless stereotaxy are outlined. The two principle investigations carried out on the planning system were a dosimetry test, and a test to verify the accuracy of localisation from CT examination through to patient treatment. The method employed in frameless relocation for fractionated stereotactic radiotherapy--position detection using stereoscopic infra-red cameras and a set of fiducials attached to a bite-block--was tested for reproducibility. The results of these tests suggest a mean accuracy in treatment localisation of 1.23 mm (maximum 2.72 mm) for single fraction techniques, and 1.77 mm (maximum 4.53 mm) for treatments involving repeated (frameless) localisation. The implications of these accuracies for treatment with single, multiple-fraction and multi-isocentre techniques are discussed.

Effects of feeding, watering and resting intervals on lambs transported by road and ferry to France.

Three lorry loads, each of approximately 530 lambs, were monitored during August 1994 while they were transported from the Midlands to France. Each lorry underwent a similar journey, designed to study the effects of a) 22 hours on a lorry broken by two hours of feed, water and rest after 15 hours, b) 34 hours on a lorry broken by eight hours of feed, water and rest after 24 hours and c) 24 hours on a lorry and lairage for the following 48 hours. Measurements were made on 180 lambs in each load, of liveweight, plasma betahydroxybutyrate (BHB), non-esterified fatty acids (NEFA), urea, total protein, albumin, osmolality, creatine kinase (CK), cortisol and glucose, before, during and after transport. Twenty-four hours of transport resulted in changes in some of the variables measured that were little different from those observed after 24 hours of feed and water deprivation; however, the high ambient temperatures during the transport resulted in a greater degree of dehydration. For journeys longer than 15 hours a two-hour rest in lairage with access to water and a palatable food source was beneficial in allowing some slight recovery. Although all the differences were in the direction that would be expected with recovery, they were often small and, within the sensitivity of the study, were only significant for NEFA and C.K. For journeys longer than 24 hours, an eight-hour rest in lairage with access to water and a palatable food source was beneficial and allowed material realimentation and rehydration before further transport for up to 10 hours. After 24 hours of transport, however, liveweight, plasma urea, total protein and albumin had only returned to basal levels after 24 hours in lairage and plasma BHB, CK and osmolality after 48 hours of lairage.

Effects of breed, feed level and conditioning time on the tenderness of pork.

This study of 80 pigs compared the effects of breed (Duroc vs Large White), feed level (High vs 0.8 High, termed Low) and conditioning time (1 vs 10 days at 1 °C) on the tenderness and other aspects of the eating quality of pork. Conditioning time had the biggest effect (increase of 1.0 units on 1-8 taste panel scale between 1 and 10 days) and this was associated with an increase in the myofibrillar fragmentation index (MFI) from 19 to 24 units. Tenderness was not different between the two breeds although pork flavour intensity and overall liking scores were higher in Durocs. Durocs had higher concentrations of total lipid (marbling fat) in muscle (13.7 and 5.4 mg/g) and most polyunsaturated fatty acids except α-linolenic (C18:3 n-3) were at lower concentrations in Durocs, reflecting dilution of phospholipid fatty acids within a larger total lipid pool. Pigs fed at the high level were fatter than those fed restrictedly in terms both of P2 fat thickness and marbling fat. There was also a tendency, although not significant, for the meat to be more tender. When the data from all pigs were pooled, MFI was shown to correlate well with tenderness (r = 0.45) and marbling fat with juiciness (r = 0.36).

Improving pork quality by electricalstimulation or pelvic suspension ofcarcasses.

This investigation compared the separate and combined effects on meat quality of electrical stimulation (ES) and pelvic suspension of pig carcasses chilled rapidly or conventionally. Sides from 80 pigs, 80-90 kg live weight, were allocated to one of four treatments followed by either conventional chilling (1°C for 24 h) or rapid chilling (-20°C for 2-3 h, before 1°C until 24 h post-slaughter). The four treatments were: Achilles suspended, with and without high voltage ES, and pelvic suspended, with and without ES. The quality attributes: pH, colour and opacity, drip loss, instrumental and sensory texture were measured in M. longissimus thoracis et lumborum, at 10 days post-slaughter. Rapid chilling reduced the evaporative weight loss by 0·5% There were no significant effects of treatment on colour or opacity, although ES samples were slightly paler. Drip loss was also slightly greater with ES, particularly when combined with pelvic suspension, but in no case was the meat classified as PSE. Instrumental measurements of 'texture showed improved tenderness from both ES and pelvic suspension, even after 10 days ageing. The improvement was less pronounced when ES and pelvic suspension were combined Taste panelling confirmed that samples treated by ES or pelvic suspension, separately or combined, were significantly more tender than samples from non-ES, Achilles hung sides. ES and pelvic suspension were equally effective in improving the tenderness of pork loin. Pelvic suspension did not suffer the disadvantage of increased drip loss that occurred with ES in this study.

Potential interactions between the effects of preslaughter stress and post-mortem electrical stimulation of the carcasses on meat quality in pigs.

The experiment examined the influence on pork quality of the electrical stimulation of carcasses from pigs subjected to different ante-mortem handling treatments. The carcasses were subjected to a slow chilling regimen to reflect less than ideal commercial practice. A total of 288 pigs (mean live weight 89 kg) of both sexes and a range of genotypes were used. They came from the Meat and Livestock Commission 's Pig Development Unit at Stotfold and were processed in 12 equal batches. Prior to slaughter they were transported for 2 h (80 km) at a stocking density of 0.5 m(2)/100 kg live weight. Preslaughter handling included being mixed or not with unfamiliar animals and being given a 3 h rest in lairage or not. One group received handling to simulate that in stunning races immediately before slaughter. There were no material interactions between the effects of ante- and post-mortem handling. Pigs rested 3 h in lairage had lower plasma cortisol levels irrespective of whether mixed with unfamiliar animals. Plasma lactate concentrations increased with greater ante-mortem stress. Pigs subjected to the simulated stunning race treatment had elevated carcass temperature. Greater ante-mortem stress progressively elevated pHu in the muscles and tended to reduce eating quality. Electrical stimulation followed by slow chilling raised initial muscle temperature, reduced pH(45) and pHu, and produced meat that was paler, had higher hue and saturation values and lost more drip during storage. Neither instrumentally-determined texture nor taste panel texture was affected, but electrical stimulation decreased juiciness and increased pork flavour. Overall eating quality was not affected by stimulation.

Data acquisition for linac based stereotactic radiosurgery.

In September 1991 a Philips Stereotactic Radiosurgery System (SRS 200) was installed in the Radiotherapy Department at Sir Charles Gairdner Hospital for use with an existing 6MV linear accelerator. The treatment planning software requires tables of Output Factors, Tissue Maximum Ratios (TMRs) and Off-Axis Ratios (OARs) for each specific linac/collimator set combination. Conventional techniques of acquiring radiation dose data for patient treatment planning were not suitable for the very small field sizes (5-30mm diameter) to be measured. Output Factors relative to a 100 x 100 mm field were measured using a large water tank and solid state diode detectors. The SRS 200 base frame which usually supports the special collimators could not be used with the tank in place and so a method for aligning the central axis of the beam, the SRS 200 collimators and diode was developed to improve the accuracy of measurement. TMRs were measured using two independent methods, similarly for the OARs. The first method of measuring TMRs made use of the large water tank and diode detectors. The second method employed the use of solid water phantom slabs seated on the base frame of the SRS 200. OARs were first measured with the solid water phantom slabs and diode; the second method made use of the technique of film dosimetry. Finally, a spherical water phantom was designed and built to check the total system accuracy. Agreement between sets of results measured by the independent methods was within 0.3% on average for TMRs and 0.25mm at the 50% dose level in most cases for the OARs.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereotactic radiosurgery.

Stereotactic radiosurgery is the accurate focusing of ionising radiation onto an intracranial target, and was pioneered in Sweden in the early 1950's. It has proven effective in the treatment of arteriovenous malformations, acoustic tumours and many other small brain lesions. In the last decade the commercial availability of a gamma ray system has led to other centres following the work in Stockholm; more recently, various techniques utilising linear accelerators, (LINACs), have been developed. Both types of system necessitated special dosimetry and treatment planning methods for the small, high dose-gradient circular fields. Localization of the lesions requires angiography, computerised tomography (CT) or magnetic resonance imaging (MRI).

Dose response experiments using the mouse tail model.

Radiation induced tail necrosis in BALB/c mice was used to investigate the effects of tissue temperature and local oxygenation on the radiation response. Single doses of 250 kV roentgen-rays were given over the temperature range 32.5 to 37 degrees C and dose response curves obtained. The temperature dependence of the response was shown to be consistent with changing hypoxic status by the derivation of a simple model; this has practical implications for the treatment of patients using simultaneously combined radiation therapy and hyperthermia.

An investigation of the alternating fractionation formula of the Cumulative Radiation Effect.

The alternating fractionation formula of the Cumulative Radiation Effect (CRE) system was investigated using the mouse intestinal crypt system as a method of assessment of the amount of radiation damage in a normal tissue. The experimental results revealed that the formula is correct in predicting an increased effect with alternating large and small sized fractions, when compared with a standard schedule where the fraction size was kept constant but achieved the same total dose. However, the results also demonstrated that the order in which the alternate fractions were administered affected the amount of radiation damage produced in the tissue. This observation is in contradiction to another prediction of the formula, that the order in which equal numbers of fractions of different magnitudes are administered, will have no effect on the biological end point. The formula, therefore, is only an approximate model of radiation damage in normal tissue and much more information is required before it can be improved upon.

Investigation of time-gap formulae on the CRE system using mouse tissue as a biological model.

The cumulative radiation effect (CRE) is one of several empirical scalar descriptions of biological effect which enable corrections to be made for gaps in radiotherapy treatment. Predictions of this theory were tested using mouse crypt regeneration and mouse skin as biological models. These experimental results are discussed in terms of the dependence of tissue regeneration potential during a gap on the biological effect achieved before the gap, and on gap length. A hypothesis is proposed to reconcile the apparent conflict between the two experiments. While the simple exponential gap formulation of the CRE is seen to be inadequate, insufficient data are available at present to modify it.