Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

[A randomized controlled trial of metastases-directed treatment in patients with metastatic prostate cancer using stereotactic body irradiation: A GETUG-AFU trial]. / Rôle de la radiothérapie ablative des métastases chez les patients atteints de cancer de la prostate oligométastatique hormonosensible : un essai du Groupe d'étude des tumeurs urogénitales et de l'Association française d'urologie.

The goal of treatment of metastatic prostate cancer remains palliation. The oligometastatic state could be the right time to intensify therapy by introducing metastases directed treatments. The aim of this trial was to evaluate the benefit of radiotherapy to all macroscopic metastatic sites and to the primary disease in patients with hormone sensitive oligometastatic prostate cancer.

Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial.

BACKGROUND: Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. PATIENTS AND METHODS: This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients. Overall survival was partitioned into three periods, namely toxic phase of treatment (TOX), time before progression without toxicity (TWIST), and progression (PROG). These health states were weighted according to patients' utility to determine quality-adjusted survival times. In threshold analyses, utility for TOX and PROG were varied from 0 to 1. RESULTS: A better quality-adjusted survival was found in the ADT + D arm when the utility for PROG and TOX states were ≤0.2 and ≥ 0.8, respectively. When the utility for PROG was 0.4 or more, ADT + D and ADT alone yielded similar quality-adjusted survival. When patients were stratified into high-volume versus low-volume disease, we found a significant Q-TWiST benefit in favour of the ADT + D arm only for high-volume patients when the utility for PROG was less than 0.35, while we found no benefit in low-volume disease patients, whatever the coefficients tested. CONCLUSION: Early docetaxel may provide significant quality-adjusted survival benefits for patients with mCNPC, especially those with high-volume disease, depending on the values assigned to the times spent in the toxicity phase and after PROG. The Q-TWiST methodology is a useful tool for decision-making regarding trade-offs between survival, PROG and toxicity.

Effects of using eucalyptus (Eucalyptusglobulus L.) leaf powder and its essential oil on growth performance and immune response of broiler chickens.

The aim of this study was to evaluate the effects of eucalyptus leaf powder (ELP) and eucalyptus essential oil (EEO) on growth performance and immune response of broiler chickens. A total of 160 broiler chicks were assigned randomly into five dietary treatments from 7-42 days of age. Dietary treatments included: a control diet, control diets plus 1,000 or 3,000 mg/kg of ELP, and control diets plus 250 or 500 mg/kg of EEO. Dietary inclusion of ELP decreased body weight gain (BWG) during 7-28 days of age. Broilers fed diet containing 3,000 mg/kg of ELP had lower feed intake (FI) during 7-28 days compared to the other treatments. Broilers fed ELP or EEO had greater primary antibody response to sheep red blood cells (SRBC) compared to the control, but differences in secondary antibody response were not significant. In conclusion, dietary EEO has the potential to enhance immune response of broiler chickens.

Effects of different levels of organic and inorganic chromium on growth performance and immunocompetence of broilers under heat stress.

This experiment was carried out to investigate the effects of different levels of organic and inorganic chromium on the performance, immune function and some serum mineral concentrations of broilers under heat stress condition (23.9-37°C cycling). A total of 150 one-day-old broiler chicks according to a completely randomized design were assigned into five treatment groups. Each treatment consisted of three replicates and each replicate contained ten chicks. Chicks were fed on corn-soybean meal basal diets with added different concentrations of chromium (0, 600 and 1,200 µg kg(-1) chromium chloride or 600 and 1,200 µg/kg chromium L-methionine) from 1 to 49 days of age. Humoral immunity was assessed by intravenous injection of 7% sheep red blood cell (SRBC) followed by evaluation of serum for antibody titers in primary and secondary responses. Cell-mediated immunity was assessed by the cutaneous basophil hypersensitivity (CBH) test to phytohemagglutinin (PHA)-P at day 32 and PHA-M at day 48. Heterophil/lymphocyte (H/L) ratio was also measured as a reliable indicator of stress. The body mass, feed intake and conversion ratio were not influenced by dietary chromium (P > 0.05). Dietary supplementation of both organic and inorganic chromium significantly increased primary and secondary antibody responses (P < 0.01), and also improved H/L ratio (P < 0.05), CBH response (P < 0.01) as well as relative weights of thymus (P < 0.05) and spleen (P < 0.01). Both dietary organic and inorganic chromium caused an increase in serum concentrations of Cr and Zn (P < 0.01), but decreased the serum concentration of Cu (P < 0.01). These results suggest that supplemental chromium especially in organic form offers a good management practice to reduce heat stress-related depression in immunocompetence of broiler chicks.

New imaging tools for the diagnosis of infection.

Infection imaging became widespread in 1971 with the release of 67Ga citrate. Multiphase skeletal scintigraphy and radiolabeled white blood cells (WBCs) have since become the most widespread clinically used agents for the imaging of infection. A wide variety of other radiolabeled probes are under investigation, based on antibodies, cytokines, assorted proteins and other molecules, alone or in various combinations. However, these latter agents, with a few exceptions, are not routinely used clinically. Radiolabeled ciprofloxacin represents the first attempt to develop an infection-specific imaging agent (most infection-imaging probes localized nonspecifically to inflammation as well), but it has not proven superior to radiolabeled WBCs or 18F-fluoro-deoxy-glucose (FDG) PET. Because of the ability to combine exquisite anatomic detail with focal uptake of 18F-FDG, PET-computed tomography has achieved great success in the detection and localization of infection, including in clinically adverse conditions. Despite these advances, at this time an infection-specific imaging agent does not exist.

Identification of an infected left ventricular assist device after cardiac transplant by indium-111 WBC scintigraphy.

PURPOSE: The purpose of this case report is to demonstrate the utility of multimodality imaging in the diagnosis of infection within a retained prosthetic device in the posttransplant setting. MATERIAL AND METHODS: Autologous leukocytes were labeled in vitro with indium-111 oxine and were reinjected. Whole-body and SPECT images were acquired at 24 hours and correlated with contemporary CT images. RESULTS: Through the use of combined indium-labeled WBC scintigraphy and CT we were able to identify infection within retained left ventricular assist device tubing status postcardiac transplantation in a patient with a diagnosis of fever of unknown origin. CONCLUSION: Localization of possible infectious etiologies within the transplant population is of utmost concern. Multimodality imaging, often utilizing scintigraphic techniques, is recommended.

Perceived information needs in respect of orthodontics amongst 11-12-year-old girls: a study through health visitor sessions in schools.

AIM: The aims of this study were: to explore: (i) the knowledge and views regarding orthodontics of a group of 11-12-year-old girls attending a school in Southeast London and (ii) the terms that they used to obtain the information. METHODS AND SUBJECTS: The study used Dental Health Education sessions to investigate the aims of the study. Eight DHE sessions at a secondary school for girls were tape recorded. In order to raise the issue of orthodontics and trigger the formation of questions during health education session, a worksheet containing true/false questions, a crossword puzzle regarding orthodontics and some open ended questions was designed and sent to students. They were required to read and complete the worksheet before each session. They were not required to return the completed worksheets to the investigators but did return them to their teachers. The sessions were tape recorded and supplemented by notes taken at the sessions by the investigator. A total of eight DHE sessions, attended by 14 girls each, were tape-recorded. Each tape recording was immediately transcribed verbatim. The next stage was to organize the data and to single out the orthodontic questions and discussions and categorize them. RESULTS: A total of 117 girls aged 11-12-year-old comprised the study group: 77% were white and 23% black children. After reading the transcripts several times, certain themes on orthodontics emerged. The results showed that children questioned different aspects of orthodontics. Nine themes emerged from their questions and discussions. They wanted to know why orthodontic treatment was carried out and when was the right time to start treatment. They were very keen to find out the differences between different orthodontic appliances. The psychosocial impacts of wearing an orthodontic appliance, i.e., experience of pain as well as the need for extraction of some permanent teeth as part of the treatment were of concern. They asked some questions on the need for repair, adjustment and taking care of appliances. The aetiology of malocclusion was another theme that emerged. The students tended to ask questions and describe problems in their own lay terms. CONCLUSION: The methodology used in this study provided an opportunity to assess the information needs with regards to orthodontics of a group of children attending a school in Southwark, London, UK. It was successful in discovering the views and concerns, and to some extent, their knowledge regarding orthodontics and the terms pupils used in asking questions and making comments.

Dietary habits and dental health over the first 18 months of life.

OBJECTIVES: The main objective of this study was to describe the dental health of infants and toddlers with special reference to their dietary habits and oral hygiene behaviour over the first 18 months of life. METHODS: The longitudinal dietary data were obtained at 6, 12 and 18 months of age by using a 3-day weighed diet diary. Dental examinations were carried out at 12, and again at 18 months of age. The information on demographic factors and oral hygiene behaviours over the first 18 months of life was gathered by using a structured questionnaire at 12 and 18 months. RESULTS: 163 children were studied. Visible dental plaque was present in 18% and 25% of children at 12 and 18 months of age, respectively. No child had dental caries at either 12 or 18 months of age. There was a statistically significant correlation between visible plaque measured as plaque index at 12 months and the mean daily eating/drinking episodes at 6 months (r=0.25, P=0.001) and 12 months (r=0.15, P=0.05). The correlations between plaque index at 18 months and the mean eating/drinking episodes at both 12 months (r=0.2, P=0.04) and 18 months (r=0.2, P=0.02) were low but statistically significant. Nevertheless, there was no significant correlation between accumulation of plaque at either 12 or 18 months and the mean daily frequency consumption of food and drink containing non-milk extrinsic sugars (NMES) at any age. Children who brushed their teeth themselves were more likely to have visible plaque compared with children whose teeth were cleaned by their parents. The partial correlation showed that positive relation between mean daily eating/drinking episodes and plaque was not influenced by tooth brushing.

Chiaroscuro hematopoietic stem cell.

These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in such diseases as sickle cell anemia or thalassemia. A similar approach could be useful in obtaining cell engraftment with minimal toxicity in therapies employing cellular immune (T-cell and NK-cell) attack against cancer. These areas of clinical application are outline in Table 3.

Noninflammatory entities and the differential diagnosis of positive three phase bone imaging.

The greater sensitivity of skeletal imaging over radiography (93% vs. 50%) for the detection of early osteomyelitis is well known. The introduction of the three phase protocol has improved the specificity of skeletal imaging by eliminating various noninfectious entities; however, the occurrence of false-positive studies is not unusual. Four such cases have been observed by the authors in a group of 34 patients suspected of having osteomyelitis and who had positive three phase skeletal imaging. These includes a patient with giant cell tumor, synovial cell sarcoma, gouty arthritis, and Reiter's syndrome. A description of these cases and a brief review of several other entities associated with positive three phase bone imaging is the subject of this atlas article, which should serve as an aid in the differential diagnosis of this commonly performed scintigraphic procedure.

Lateral position test and quantitative lung scan in the preoperative evaluation for lung resection.

The postpneumonectomy FEV1 was predicted in 24 patients with severe chronic obstructive pulmonary disease (FEV1 less than or equal to 2.0 L) and a lung mass using the quantitative lung scan (QLS) and lateral position test (LPT). Although a good correlation (r = .72, p = 0.0006) was found between the FEV1 predicted by QLS and LPT, there was more than 10 percent difference between the result in 59 percent of the subjects. A subgroup of these patients performed multiple (two to five) LPTs, and the results were calculated blindly to assess variability. The variation seen was 14 times greater than in previously reported normal subjects. Calculations suggest that as many as 37 tracings would be needed on each patient to obtain an acceptably low measurement error. Whereas there was a good overall correlation between the predicted postpneumonectomy FEV1 using both methods, the variability found with LPT would suggest extreme caution in its use.

Gallium citrate Ga 67 scans in febrile patients.

Scanning with gallium citrate Ga 67 is a sensitive technique for the detection of localized inflammatory disease. In a group of 22 febrile patients, 17 had one or more abnormal areas of radioactive gallium localization. Eight patients showed localized areas of inflammation; five showed no area of local inflammation within the field of the scan. The remaining patients had excellent clinical and laboratory confirmation of neoplastic or inflammatory disease. These cases illustrate the usefulness of radioactive gallium in febrile patients in whom the cause of the fever cannot be otherwise determined.

Diagnosis of an enteric duplication with pertechnetate 99mTc scanning.

A case of enteric duplication is reported in which preoperative pertechnetate (99m)Tc scanning demonstrated localized uptake in the region of the anatomic abnormality. This test is recommended for use in the evaluation of lower gastrointestinal bleeding in infants and children.

Technetium 99m sulfur colloid spleen/liver ratio and other liver tests in the diagnosis of cirrhosis.

The results of seven laboratory tests of liver function, including spleen/liver activity ratios obtained by densitometric analysis of scans, are analyzed in 50 patients with proven Laennec's cirrhosis. In this series, the liver scan not only disclosed the liver gross anatomy and structural abnormality and established the best possible site for biopsy examination, but also, the increased splenic activity served as a useful diagnostic indication of Laennec's cirrhosis. Of 50 proven cases of Laennec's cirrhosis, 41 (82%) had abnormal spleen/liver ratios. An abnormal spleen/liver ratio in combination with abnormal results from any one or two other tests was relatively effective in the detection of cirrhosis. The accuracy is improved if the other laboratory tests are chosen from among tests for serum albumin, serum bilirubin, and SGOT. (Liver abnormalities other than cirrhosis can also present an abnormal spleen/liver ratio.) This simple determination extends the value of the liver scan commonly requested in search of metastases, primary lesions, or inflammatory processes, or in preparation for needle biopsy examination.