A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. PATIENT SUMMARY There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND.

The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study

OBJECTIVES: To map the primary prostatic lymphatic landing sites using a multimodality technique. METHODS: Thirty-four patients with organ-confined prostate cancer (cT1-cT2; cN0) underwent single-photon emission computed tomography fused with data from computed tomography (SPECT/CT) (n=33) or magnetic resonance imaging (SPECT/MRI) (n=1) 1h after ultrasound-guided intraprostatic injection of technecium (Tc-99m) nanocolloid. The presence of lymph nodes (LNs) containing Tc-99m was confirmed intraoperatively with a gamma probe. A backup extended pelvic lymphadenectomy (PLND) was performed to preclude missed primary lymphatic landing sites. The SPECT/CT/MRI data sets were used to generate a three-dimensional projection of each LN site. RESULTS: A total of 317 LNs (median, 10 per patient; range, 3-19) were detected by SPECT/CT/MRI, 314 of which were confirmed by gamma probe. With an "extended" PLND, two thirds of all primary prostatic lymphatic landing sites are resected compared with only one third with a "limited" PLND. CONCLUSIONS: The multimodality technique presented here enables precise mapping of the primary prostatic lymphatic landing sites. PLND for prostate cancer should include not only the external and obturator regions as well as the portions medial and lateral to the internal iliac vessels, but also the common iliac LNs at least up to the ureteric crossing, thus removing approximately 75% of all nodes potentially harbouring metastasis.

Catheter ablation of recurrent scar-related ventricular tachycardia using electroanatomical mapping and irrigated ablation technology: results of the prospective multicenter Euro-VT-study

Ventricular tachycardia (VT) late after myocardial infarction is an important contributor to morbidity and mortality. This prospective multicenter study assessed the efficacy and safety of electroanatomical mapping in combination with open-saline irrigated ablation technology for ablation of chronic recurrent mappable and unmappable VT in remote myocardial infarction.

Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study

Background Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex. Methodology/Principal Findings We searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions. Conclusions Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.

Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study)

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents.

Evaluation of articular cartilage in patients with femoroacetabular impingement (FAI) using T2* mapping at different time points at 3.0 Tesla MRI: a feasibility study

To define the feasibility of utilizing T2* mapping for assessment of early cartilage degeneration prior to surgery in patients with symptomatic femoroacetabular impingement (FAI), we compared cartilage of the hip joint in patients with FAI and healthy volunteers using T2* mapping at 3.0 Tesla over time.

Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice

BACKGROUND: Opportunistic screening for genital chlamydia infection is being introduced in England, but evidence for the effectiveness of this approach is lacking. There are insufficient data about young peoples' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population-based approach. AIM: To estimate use of primary care services by young men and women; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach. DESIGN OF STUDY: Population based cross-sectional study. SETTING: Twenty-seven general practices around Bristol and Birmingham. METHOD: A random sample of patients aged 16-24 years were posted a chlamydia screening pack. We collected details of face-to-face consultations from general practice records. Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated 60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to 76.9%) of women aged 16-24 years attended their practice at least once in a 1-year period. During this period, an estimated 21.3% of patients would not attend their general practice but would be reached by postal screening, 9.2% would not receive a postal invitation but would attend their practice, and 11.8% would be missed by both methods. CONCLUSIONS: Opportunistic and population-based approaches to chlamydia screening would both fail to contact a substantial minority of the target group, if used alone. A pragmatic approach combining both strategies might achieve higher coverage.

Systematic counselling by general practitioners for promoting physical activity in elderly patients: a feasibility study

RESEARCH QUESTIONS: To investigate how the daily physical activities of elderly patients can be enhanced by systematic counselling conducted by general practitioners (GPs). METHODS: In this feasibility study with pre-post design, 29 people (14 females, mean age 72.2 years, SD = 6.1) were enrolled during routine visits by two general practitioners. A baseline assessment of current physical activity based on the stages according to the Transtheoretical Model was followed by a counselling session. The target behaviour was defined by performance of 30 minutes of daily moderate-intensity activities that increase the breathing rate, on five days per week. At the 2-month follow-up, subjects were assessed for improvement in stage of physical activity since baseline. After the end of the intervention, participating GPs and patients were asked questions focusing on the feasibility, acceptance and usefulness of counselling. RESULTS: Interview results showed that the two GPs considered the counselling protocol easy to handle and useful for promoting physical activity. Counselling sessions were especially encouraging for the not sufficiently active people. Most of them would like to have additional counselling session. At baseline, 9 of 29 people were sufficiently active. After 2 months, this proportion was 21 of 29. The mean of the number of minutes of physical activity during the previous 4 weeks increased from 247 to 436 minutes (weekly). CONCLUSIONS: The programme was judged positively by the general practitioners and the participating elderly patients. Systematic counselling by general practitioners led to an increase in the physical activity behaviour. Therefore, a more rigorous randomised controlled trial with adequate followup is recommended.

T2 mapping of hip articular cartilage in healthy volunteers at 3T: a study of topographic variation

PURPOSE: To perform baseline T(2) mapping of the hips of healthy volunteers, focusing on topographic variation, because no detailed study has involved hips. T(2) mapping is a quantitative magnetic resonance imaging (MRI) technique that evaluates cartilage matrix components. MATERIALS AND METHODS: Hips of 12 healthy adults (six men and six women; mean age = 29.5 +/- 4.9 years) were studied with a 3.0-Tesla MRI system. T(2) measurement in the oblique-coronal plane used a multi-spin-echo (MSE) sequence. Femoral cartilage was divided into 12 radial sections; acetabular cartilage was divided into six radial sections, and each section was divided into two layers representing the superficial and deep halves of the cartilage. T(2) of these sections and layers were measured. RESULTS: Femoral cartilage T(2) was the shortest (-20 degrees to 20 degrees and -10 degrees to 10 degrees , superficial and deep layers), with an increase near the magic angle (54.7 degrees ). Acetabular cartilage T(2) in both layers was shorter in the periphery than the other parts, especially at 20 degrees to 30 degrees . There were no significant differences in T(2) between right and left hips or between men and women. CONCLUSION: Topographic variation exists in hip cartilage T(2) in young, healthy adults. These findings should be taken into account when T(2) mapping is applied to patients with degenerative cartilage. J. Magn. Reson. Imaging 2007;26:165-171. (c) 2007 Wiley-Liss, Inc.

Systematic review of the empirical evidence of study publication bias and outcome reporting bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Ability of dGEMRIC and T2 mapping to evaluate cartilage repair after microfracture: a goat study

OBJECTIVE: To investigate the ability of delayed gadolinium-enhanced magnetic resonance (MR) imaging of cartilage (dGEMRIC) and T2 mapping to evaluate the quality of repair tissue after microfracture. DESIGN: Twelve knees from 12 goats were studied. An osteochondral defect (diameter, 6mm; depth, 3mm) with microfracture was created in the weight-bearing aspect of both the medial and lateral femoral condyles. Goats were euthanized at 24 weeks (n=6) and 48 weeks (n=6) postsurgery. Pre-contrast R1 (R1pre) and post-contrast R1 (R1post) measurements for dGEMRIC and a pre-contrast T2 measurement for T2 mapping were performed with a 3T MR imaging system. MR imaging findings were compared with histological and biochemical assessments. RESULTS: In native cartilage, significant correlations were observed between the R1post and the glycosaminoglycan (GAG) concentration, as well as DeltaR1 (difference between the R1pre and R1post) and the GAG concentration (P<0.05). In repair tissue, a significant correlation was observed between DeltaR1 and the GAG concentration (P<0.05), but not between the R1post and the GAG concentration. In both repair tissue and native cartilage, no correlation was observed between T2 and the water concentration or between T2 and the hydroxyproline (HP) concentration. A zonal variation of T2 and a clear dependence of T2 on the angles relative to B0 were observed in native cartilage, but not in repair tissue. CONCLUSION: dGEMRIC with DeltaR1 measurement might be useful for the evaluation of the GAG concentration in repair tissue after microfracture. T2 mapping might be useful for the differentiation of repair tissue after microfracture from native cartilage; however, its potential to assess the specific biochemical markers in native cartilage as well as repair tissue may be limited.

Feasibility of T2* mapping for the evaluation of hip joint cartilage at 1.5T using a three-dimensional (3D), gradient-echo (GRE) sequence: a prospective study

This study defines the feasibility of utilizing three-dimensional (3D) gradient-echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T.

Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.