Muriel Rabilloud

Mid-term Results Demonstrate Salvage High-Intensity Focused Ultrasound (HIFU) as an Effective and Acceptably Morbid Salvage Treatment Option for Locally Radiorecurrent Prostate Cancer

BACKGROUND Local occurrence of prostate cancer (PCa) after external beam radiation (EBRT) may benefit from definitive local therapy. OBJECTIVE To evaluate the safety and efficacy of salvage high-intensity focal ultrasound (HIFU) in local PCa recurrence after EBRT and to determine prognostic factors for optimal patient selection. DESIGN, SETTING, AND PARTICIPANTS Between 1995 and 2006, patients with a local PCa recurrence after EBRT were retrospectively included. INTERVENTION All patients received salvage HIFU with the Ablatherm device. MEASUREMENTS Prognostic factors (pre-EBRT risk group, androgen-deprivation [AD] use, pre-HIFU prostate-specific antigen [PSA], Gleason score and positive biopsy percentage) were studied in univariate and multivariate analyses. Progression was defined as positive biopsy and/or last PSA > nadir + 2 ng/ml and/or adjuvant therapy introduction. All complications were recorded. RESULTS AND LIMITATIONS Some 194 HIFU sessions for 167 patients were performed. Local cancer control was achieved with negative biopsy results in 122 (73%) patients. The median PSA nadir was 0.19 ng/ml. The mean follow-up period was 18.1 mo (range: 3-121 mo). Seventy-four patients required no hormone therapy. The actuarial 5-yr overall survival rate was 84%. The actuarial 3-yr progression-free survival rate was significantly lower in three circumstances: (1) worsening of the pre-EBRT stage with 53%, 42%, and 25% for low-, intermediate-, and high-risk patients, respectively, (2) increase in the pre-HIFU PSA, and (3) use of AD during PCa management. In multivariate analyses, the risk ratio for intermediate- and high-risk patients were 1.32 and 1.96, respectively. The risk ratio was 2.8 if patients had received AD. No rectal complications were observed. Urinary incontinence accounted for 49.5% of the urinary sphincter implantations required in 11% of patients. This is a retrospective study in which the role of the PSA doubling time and the time until recurrence was not evaluated. CONCLUSIONS Salvage HIFU is a curative treatment option for local relapse after EBRT with acceptable morbidity. Careful patient selection is imperative depending upon the aforementioned prognostic factors.

Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: Data from the French-Italian HHT network

Purpose: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations (AVM), mostly cutaneous and mucous (telangiectases), but also involving the lungs (PAVM), liver (HAVM) and brain (CAVM). We studied the relationship between the phenotype and genotype in patients with a proven mutation in either ENG (HHT1) or ACVRL1 (HHT2).Methods: Clinical features and their age of onset were compared between HHT1 and HHT2. The type of mutation was also analyzed. Clinical manifestations were distinguished from lesions found by screening.Results: Ninety-three HHT1 patients and 250 HHT2 patients were included. Epistaxis occurred later in HHT2, with incomplete penetrance (P < 0.0001). Symptomatic PAVMs were more frequent in HHT1 (34.4 vs. 5.2%, P < 0.001), as were cerebral abscesses (7.5 vs. 0.8%, P = 0.002). Gastrointestinal bleeding occurred more frequently in HHT2 (16.4 vs. 6.5%, P = 0.017). Symptomatic hepatic involvement was only seen in HHT2 patients. PAVMs were more frequently detected in asymptomatic HHT1 patients (54 vs. 12.8%, P < 0.0001). PAVMs and HAVMs were often family clustered in HHT1 and HHT2, respectively. Truncating mutations were associated with a higher frequency of epistaxis and telangiectasis, in HHT2.Conclusion: This study shows major differences between HHT1 and HHT2 phenotypes, which should be taken into account for future clinical studies.

Evaluation of T2-weighted and dynamic contrast-enhanced MRI in localizing prostate cancer before repeat biopsy

We assessed the accuracy of T2-weighted (T2w) and dynamic contrast-enhanced (DCE) 1.5-T magnetic resonance imaging (MRI) in localizing prostate cancer before transrectal ultrasound-guided repeat biopsy. Ninety-three patients with abnormal PSA level and negative prostate biopsy underwent T2w and DCE prostate MRI using pelvic coil before repeat biopsy. T2w and DCE images were interpreted using visual criteria only. MR results were correlated with repeat biopsy findings in ten prostate sectors. Repeat biopsy found prostate cancer in 23 patients (24.7%) and 44 sectors (6.6%). At per patient analysis, the sensitivity, specificity, positive and negative predictive values were 47.8%, 44.3%, 20.4% and 79.5% for T2w imaging and 82.6%, 20%, 24.4% and 93.3% for DCE imaging. When all suspicious areas (on T2w or DCE imaging) were taken into account, a sensitivity of 82.6% and a negative predictive value of 100% could be achieved. At per sector analysis, DCE imaging was significantly less specific (83.5% vs. 89.7%, p < 0.002) than T2w imaging; it was more sensitive (52.4% vs. 32.1%), but the difference was hardly significant (p = 0.09). T2w and DCE MRI using pelvic coil and visual diagnostic criteria can guide prostate repeat biopsy, with a good sensitivity and NPV.

Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation

Objective To improve prediction of ovulation in normal cycles.

Prostate cancer transrectal HIFU ablation: detection of local recurrences using T2-weighted and dynamic contrast-enhanced MRI

The objective was to evaluate T2-weighted (T2w) and dynamic contrast-enhanced (DCE) MRI in detecting local cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. Fifty-nine patients with biochemical recurrence after prostate HIFU ablation underwent T2-weighted and DCE MRI before transrectal biopsy. For each patient, biopsies were performed by two operators: operator 1 (blinded to MR results) performed random and colour Doppler-guided biopsies (“routine biopsies”); operator 2 obtained up to three cores per suspicious lesion on MRI (“targeted biopsies”). Seventy-seven suspicious lesions were detected on DCE images (n = 52), T2w images (n = 2) or both (n = 23). Forty patients and 41 MR lesions were positive at biopsy. Of the 36 remaining MR lesions, 20 contained viable benign glands. Targeted biopsy detected more cancers than routine biopsy (36 versus 27 patients, p = 0.0523). The mean percentages of positive cores per patient and of tumour invasion of the cores were significantly higher for targeted biopsies (p < 0.0001). The odds ratios of the probability of finding viable cancer and viable prostate tissue (benign or malignant) at targeted versus routine biopsy were respectively 3.35 (95% CI 3.05–3.64) and 1.38 (95% CI 1.13–1.63). MRI combining T2-weighted and DCE images is a promising method for guiding post-HIFU biopsy towards areas containing recurrent cancer and viable prostate tissue.

Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster‐randomised controlled trial

Please cite this paper as: Deneux‐Tharaux C, Dupont C, Colin C, Rabilloud M, Touzet S, Lansac J, Harvey T, Tessier V, Chauleur C, Pennehouat G, Morin X, Bouvier‐Colle M, Rudigoz R. Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster‐randomised controlled trial. BJOG 2010;117:1278–1287.

Relationship between dual-task related gait changes and intrinsic risk factors for falls among transitional frail older adults

Background and aims: Gait changes in dual-task conditions have been associated with an increased risk of falling in older adults, and become more important in increasingly frail older adults. We studied the relationship between commonly known intrinsic risk factors for falls and dual-task related gait changes among transitional frail older adults. Methods: Walking time and number of steps were measured while walking alone and while walking with counting backward on a 10-m walkway in 66 transitional frail older adults (mean age 83.6±6.1, 84.9% women). Uni- and multiple linear regression analyses were performed to explore the relationship between dual-task related gait changes (walking time and number of steps) and age over 85 years, polymedication, psychoactive drugs, poor distance vision, abnormal mobility and cognitive impairment. Results: Compared with walking alone, both walking time and number of steps increased significantly while counting backward (p<0.001). Polymedication and abnormal mobility were associated with a significant increase of walking time and number of steps (p<0.01 for unadjusted change, p<0.05 for adjusted change). Conclusions: Dual-task related gait changes were closely correlated with polymedication and impaired mobility in our sample of transitional frail older adults. These findings give some insight into the complexity of performing attention-demanding tasks while walking and accentuate the need for multi-factorial, personalized intervention strategies, to prevent decline in dual-task performance in this fall-prone population.

Spatial distribution of soil contamination by Toxoplasma gondii in relation to cat defecation behaviour in an urban area

In urban areas, there may be a high local risk of zoonosis due to high densities of stray cat populations. In this study, soil contamination by oocysts of Toxoplasma gondii was searched for, and its spatial distribution was analysed in relation to defecation behaviour of cats living in a high-density population present in one area of Lyon (France). Sixteen defecation sites were first identified. Cats were then repeatedly fed with marked food and the marked faeces were searched for in the defecation sites. Of 260 markers, 72 were recovered from 24 different cats. Defecation sites were frequented by up to 15 individuals. Soil samples were also examined in order to detect the presence of T. gondii using real-time PCR. The entire study area was then sampled according to cat density and vegetation cover type. Only three of 55 samples were positive and all came from defecation sites. In a second series of observations, 16 defecation sites were sampled. Eight of 62 samples tested positive, originating in five defecation sites. Laboratory experiments using experimental seeding of soil showed that the inoculated dose that can be detected in 50% of assays equals 100-1000oocysts/g, depending on the strain. This study shows that high concentrations of oocysts can be detected in soil samples using molecular methods and suggests that spatial distribution of contamination areas is highly heterogeneous. Positive samples were only found in some of the defecation sites, signifying that at-risk points for human and animal infection may be very localised.

Outcome and prognostic factors in neonates with septic shock.

Objective: Few accurate data are available on the outcome of septic shock in the neonatal period. The objective was to describe outcome and to determine variables associated with death or adverse outcome in neonates with septic shock. Design: Retrospective cohort study. Setting: A tertiary neonatal intensive care unit in a university hospital. Patients: All patients admitted to the neonatal intensive care unit over a 6-yr period meeting the following criteria: hypotension and/or need for intravenous fluid administration or vasoactive drugs, in the presence of proven or highly probable infection. Interventions: None. Measurements and Main Results: Main outcomes were 28-day mortality and adverse outcome at 18 months of corrected age, defined as death or severe sequelae (cerebral palsy, severe developmental delay, hearing impairment, blindness, or short bowel syndrome). Forty-eight infants were included. Follow-up data at 18 months were obtained for 46 of 48 infants. The 28-day mortality was 40% (19 deaths). Adverse outcome at 18 months of corrected age was observed in 24 of 46 infants (52%; death = 19, severe sequelae = 5). Twenty-eight percent of the infants were alive and had a normal examination at 18 months. Infants with adverse outcome had significantly lower gestational age, birth weight, Apgar score, weight at onset of sepsis, and pH and more often had Gram-negative infection, fetal growth restriction, hypoglycemia, and thrombocytopenia. Significant predictors (multivariate analysis) of 28-day mortality and of adverse outcome at 18 months of corrected age were weight (kg) at the onset of sepsis (odds ratio 0.14, 95% confidence interval 0.03–0.55; odds ratio 0.21, 95% confidence interval 0.06–0.74, respectively) and Gram-negative infection (odds ratio 10.1, 95% confidence interval 1.5–65.7; odds ratio 45.5, 95% confidence interval 3–637, respectively). Conclusions: Septic shock in the neonatal period has a very poor outcome. Data underscore the extreme vulnerability of very low birth weight infants to septic shock, particularly to Gram-negative species.

Creatinine‐ versus cystatine C‐based equations in assessing the renal function of candidates for liver transplantation with cirrhosis

Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre‐OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR‐predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD‐EPI‐Pcr, CKD‐EPI‐CystC, and CKD‐EPI‐Pcr‐CystC) and the more classical ones (4‐ and 6‐variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR‐predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC‐based equations showed a better performance than Pcr‐based ones (lower bias and higher 10% and 30% accuracies). CKD‐EPI‐CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/min/1.73 m2). Conclusion: Pcr‐based GFR predicting equations are not reliable in pre‐OLT patients even when an IDMS‐traceable enzymatic Pcr assay is used. Whenever a CystC‐assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC‐based equations, especially CKD‐EPI‐CystC, may be recommended to evaluate renal function and for KDOQI staging. (Hepatology 2014;59:1522‐1531)