Abstract Background Radiofrequency ablation (RFA) of liver tumors is associated with a risk of incomplete ablation or local recurrence. Methods One hundred sixty-eight patients with 311 unresectable ...liver tumors were included. Effects of different variables on incomplete ablation and local recurrence were analyzed. Results There were 132 hepatocellular carcinomas and 179 liver metastases. Tumor size was 24 (±13) mm. Two hundred twenty-six tumors were treated percutaneously, and 85 through open approach (associated with liver resection in 42 cases). There was no mortality. Major morbidity rate was 7%. Incomplete ablation and local recurrence rates were 14% and 18.6%. Follow-up was 29 months. On multivariate analysis, factors associated with incomplete ablation were tumor size (>30 mm vs ≤30 mm, P = .004) and approach (percutaneous vs open, P = .0001). Factors associated with local recurrence were tumor size (>30 mm vs ≤30 mm, P = .02) and patient age (>65 years vs ≤65 years, P = .05). Conclusions RFA is effective to treat unresectable liver tumors. However, there is a risk of incomplete ablation when percutaneously treating tumors >30 mm. When tumor ablation is completely achieved, the main factor associated with local recurrence is tumor size >30 mm.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The narrow therapeutic range of tacrolimus requires therapeutic drug monitoring to prevent transplant rejection and to minimize nephrotoxicity. The aim of this study was to evaluate the analytical ...performance of the tacrolimus chemiluminescent microparticle immunoassay (CMIA) in everyday practice comparatively with other methods. CMIA imprecision and accuracy were tested using low, medium, and high concentrations in control samples. The limits of quantification (LOQ) of CMIA and antibody-conjugated magnetic immunoassay (ACMIA) were evaluated using negative whole-blood samples containing 0.4–5.7
ng/ml of tacrolimus from a stock solution. CMIA was compared with ACMIA, enzyme multiplied immunoassay (EMIT), and liquid chromatography–tandem mass spectrometry (LC–MS/MS), using 176 samples from recipients (135 men and 41 women) of heart (
n
=
19), kidney (
n
=
107), or liver (
n
=
50) transplants. CMIA total precision was 5.7%, 3.7% and 3.6% with the low-, medium-, and high-concentration controls, respectively; corresponding values for accuracy were 98%, 104%, and 104%. LOQ was 0.5 (95%CI, 0.22–1.38) with CMIA and 2.5
ng/ml with ACMIA. Linear regression results were as follows: CMIA
=
1.2LC–MS/MS
+
0.14 (
r
=
0.98); CMIA
=
0.93EMIT
+
0.36 (
r
=
0.975); CMIA
=
1.15ACMIA
−
0.25 (
r
=
0.988); and, for tacrolimus concentrations in the 1–15
ng/ml range, of special interest as many transplant recipients are given low-dose tacrolimus, CMIA
=
1.05LC–MS/MS
+
0.38 (
r
=
0.94). Two patients had falsely elevated tacrolimus concentrations due to interference in the ACMIA assay; one was a renal transplant recipient who stopped her treatment and had tacrolimus concentrations of 12.5
ng/ml by ACMIA and <0.5
ng/ml by CMIA; the other was an HIV-positive renal transplant recipient whose tacrolimus concentrations by ACMIA were 1.8–43.7-fold those by CMIA. Such interferences with ACMIA, which may be related to endogenous antibodies in the plasma, are likely to negatively impact patient care. In conclusion, the tacrolimus CMIA assay is suitable for routine laboratory use and does not suffer from the interferences seen with ACMIA in some patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Zoological institutions often encourage cooperative interactions between keepers and animals so as to promote animals' welfare. One useful technique has been conditioning training, whereby animals ...learn to respond to keepers' requests, which facilitates a number of, otherwise sensitive, daily routines. As various media have been used to convey keepers' instructions, the question remains of which modality is best to promote mutual understanding. Here, we explored this question with two captive female orangutans. In the first experiment, we compared orangutans' understanding of previously acquired instructions when those were performed with verbal signals only, gazes only, gestures only, and when all those modalities were combined. Our results showed that gestures were sufficient for successful comprehension by these two apes. In the second experiment, we asked whether this preference could be driven by the non-arbitrary relationship that gestures bear to what they refer to, through iconicity or pointing. Our results revealed that neither iconicity nor pointing helped the subjects comprehend the keepers' instructions. Our results indicate a preference for instructions given through gestural signals in two captive female orangutans, although its cause remains elusive. Future practice may encourage the use of gestures in communication between keepers and orangutans in general or potentially other animals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Cette synthèse fait le point sur les principales évolutions de l’amélioration génétique du porc en France depuis la loi sur l’élevage de 1966. Elle évoque rapidement les 20 premières années, qui ont ...fait l’objet d’une synthèse en 1986, puis décrit plus en détail les évolutions ultérieures. Les objectifs de sélection, initialement limités aux caractères de production, se sont complexifiés avec la prise en compte de la qualité de la viande, puis de la prolificité et enfin des aptitudes maternelles des truies. La mise en place d’une évaluation génétique utilisant la méthodologie du « BLUP - modèle animal » au milieu des années 1990 et le développement de l’insémination artificielle ont profondément changé le travail des sélectionneurs. Une nouvelle évolution majeure, la sélection génomique, a récemment été mise en place. La sélection a conduit à des améliorations importantes des performances pour les principaux caractères de l’objectif de sélection depuis 1970 : plus de 200 g de gain moyen quotidien, plus de 0,5 point d’indice de consommation, plus de 12 points de taux de viande maigre dans la carcasse, jusqu’à près de six porcelets nés vifs par portée supplémentaires. Ces évolutions favorables ont réduit l’empreinte environnementale de la production, mais ont également eu des effets défavorables : une augmentation la mortalité des porcelets avant sevrage et une plus grande hétérogénéité des performances. Les enjeux pour l’avenir en termes d’objectifs d’amélioration génétique (prise en compte de caractères liés au bien-être, à la robustesse et à l’adaptation…), de méthodes et d’outils sont ensuite discutés.
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Control of chemotherapies preparations are now an obligation in France, though analytical control is compulsory. Several methods are available and none of them is presumed as ideal. ...We wanted to compare them so as to determine which one could be the best choice.
We compared non analytical (visual and video-assisted, gravimetric) and analytical (HPLC/FIA, UV/FT-IR, UV/Raman, Raman) methods thanks to our experience and a SWOT analysis. The results of the analysis show great differences between the techniques, but as expected none us them is without defects. However they can probably be used in synergy.
Overall for the pharmacist willing to get involved, the implementation of the control for chemotherapies preparations must be widely anticipated, with the listing of every parameter, and remains according to us an analyst’s job.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background & Aims Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) and it is the most commonly used treatment for HCC worldwide. ...However, no prognostic indices, designed to select appropriate candidates for repeat conventional TACE, have been incorporated in the guidelines. Methods From January 2007 to April 2012, 139 consecutive HCC patients, mainly with an alcohol- or viral-induced disease, were treated with TACE. Using a regression model on the prognostic variables of our population, we determined a score designed to help for repeat TACE and we validated it in two cohorts. We also compared it to the ART score. Results In the multivariate analysis, four prognostic factors were associated with overall survival: BCLC and AFP (>200 ng/ml) at baseline, increase in Child-Pugh score by ⩾2 from baseline, and absence of radiological response. These factors were included in a score (ABCR, ranging from −3 to +6), which correlates with survival and identifies three groups. The ABCR score was validated in two different cohorts of 178 patients and proofed to perform better than the ART score in distinguishing between patients’ prognosis. Conclusions The ABCR score is a simple and clinically relevant index, summing four prognostic variables endorsed in HCC. An ABCR score ⩾4 prior to the second TACE identifies patients with dismal prognosis who may not benefit from further TACE sessions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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The aim of our study was to investigate the influence of pH and temperature on the stability of ziconotide in analgesic admixtures containing morphine and ropivacaine.
All admixtures ...were combined using a wide range of concentrations, in implantable pumps and syringes, using temperatures from 4°C to 37°C. Quantification was made thanks to a specific chromatographic technique. pH has also been measured throughout the study.
Admixtures confirm excellent stability for morphine and ropivacaine. Concerning ziconotide, an acid hydrolysis has been observed, reducing the time of use of our admixtures in a significant way, but producing non-toxic degradation products. The degradation was linear in all conditions. Inside the implantable pumps at body temperature turned out to be the best conditions for lower protein breakdown. Finally the degradation process showed a high correlation with the pH and the morphine concentration with a median loss of concentration delay due to degradation of 3.5 days 3; 5 when pH<4.5 and 13 days 13; 24 when pH≥4.5.
Our admixtures showed different stability depending on the drug concentrations, pH and temperature. The great majority of mixtures in real life in our institution have stability highly compatible with our practice and with the delay between two pump refilling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
OBJECTIVETo evaluate the biliary penetration of ciprofloxacin and cefotaxime in patients with obstructed bile ducts and to determine simple predictive markers of effective biliary concentrations of ...these drugs.
METHODSSixty-two patients treated with endoscopic biliary drainage were prospectively included in a nonrandomized way and received intravenous ciprofloxacin (200 mg twice daily) or cefotaxime (1 g three times a day) for more than 24 h before exploration. Blood and bile samples were collected at the time of drainage. Ciprofloxacin and cefotaxime concentrations were measured using high-performance liquid chromatography. Biliary penetration was assessed by the bile-to-plasma ratio of the concentrations of both antibiotics.
RESULTSBiliary penetration ranged from 0.06 to 42.7 for ciprofloxacin and from 0.01 to 1.14 for cefotaxime. The ratio was more than one in only 10 patients (35%) and three patients (9%) in ciprofloxacin and cefotaxime groups, respectively. Biliary concentration of the drug was more than 10 times the minimal inhibitory concentration in only 10 patients (35%) and in 12 patients (35%) in ciprofloxacin and cefotaxime groups, respectively. Serum bilirubin, alkaline phosphatase or gamma-glutamyl-transpeptidase were not good predictive markers of the biliary diffusion of the antibiotics.
CONCLUSIONIn patients with obstructed bile ducts, the biliary penetration of ciprofloxacin is poor and reaches effective biliary concentrations in a minority of patients. Cefotaxime biliary penetration is even poorer. No liver test can predict accurately the biliary penetration of the drugs.
The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with ...transarterial radioembolisation (TARE) or sorafenib.
This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models.
A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval CI 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively.
HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.
•Deterioration for global health status was lower in the TARE group compared to sorafenib.•Deterioration in physical functioning was lower in the TARE group compared to sorafenib.•Deterioration in role functioning was lower in the TARE group compared to sorafenib.•Deterioration in social functioning was lower in the TARE group compared to sorafenib.•TARE and tumour burden ≤25% were associated with a lower risk of deterioration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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