Comparison Between Living Donor Liver Transplantation Recipients Who Met the Milan and UCSF Criteria After Successful Downstaging Therapies

Background and Aims

Various downstaging therapies were introduced to liver recipients who could not meet the relative criteria for liver transplantation, and many endpoints were reported. The most common criteria used were the Milan criteria and the University of California, San Francisco (UCSF) criteria. However, no comparison was made between them, and we attempted to find possible differences between the living donor liver transplantation (LDLT) patients who met the Milan criteria and those who met the UCSF criteria after accepting preoperative downstaging therapies.

Materials and Methods

We performed a retrospective study of all 72 patients at our center from January 2003 to March 2009 who were diagnosed with advanced hepatocellular carcinoma but accepted various downstaging therapies. Some patients met the Milan criteria (group 1), and some met the UCSF criteria (group 2) but not the Milan criteria. We collected the data from the two groups and then compared the preoperative demographic data, downstaging therapies, intraoperative data from LDLT, and the recovery and complications after LDLT. Survival rates were compared using Kaplan?CMeier analysis.

Results

Only 44 patients (61.1?%) met the criteria for liver transplantation, 21 cases met the Milan criteria (group 1), and 23 cases met the UCSF criteria (group 2) but not the Milan criteria. All of the 44 patients accepted right lobe living liver donor liver transplantation in our center. The difference in the baseline characteristics between the two groups did not reach statistical significance. The mean number of downstaging treatments per patient was 1.81?±?0.35 in group 1 and 1.83?±?0.41 in group 2 (P?=?0.928). Most of the patients received only one downstaging treatment, and transcatheter arterial chemoembolization (TACE) was the most common downstaging therapy. Four patients suffered complications after downstaging therapies: intra-abdominal hemorrhage after right hepatectomy, upper gastrointestinal hemorrhage after TACE, biliary fistula after resection, and hand?Cfoot syndrome after taking sorafenib. All complications after LDLT, classified according to the Clavien?CDindo system, were compared within the two groups, and the calculated score of the complications in group 1 was 1.48?±?1.63, which was greater than that of group 2 (1.39?±?1.64), but this difference did not reach statistical significance (P?=?0.865). The 1-, 3-, and 5-year survival rates were 90.4, 76.2, and 71.4?% in group 1 and 91.3, 73.9, and 69.6?% in group 2, respectively (P?>?0.05). Seven patients (three in group 1 and four in group 2) had tumor recurrence after a median follow-up period of 72?months. The pathology findings were not different between the two groups.

Conclusion

Recipients who meet the Milan or UCSF criteria after accepting successful preoperative downstaging therapy in LDLT can achieve the same result.     

Indane-1,3-diones IX, synthèse et activité anti-inflammatoire de 2-polyaza-arylindane-1,3-diones et de leurs dérivés N- ou O-substitués

Les auteurs étudient les voies d'accès à des 2-polyaza-arylindane-1,3-diones et à leurs dérivés diversement substitués sur l'hétérocycle et l'homocycle ainsi que la pharmacomodulation de leur activité anti-inflammatoire. Ces β dicétoénamines fournissent en milieu alcalin des anions multidents conduisant en présence d'agents électrophiles à une C, N ou O-substitution; la mise en œuvre de la réaction de Mitsunobu a abouti à une N-(ω-amino-)-alkylation régiospécifique ou régiosélective. Parmi les diverses modifications structurales, la N-éthylation de la molécule de base, éventuellement couplée avec une méthoxylation en 5 sur l'homocycle s'est avérée efficace pour l'émergence d'une activité anti-inflammatoire en séries pyridazinyle, pyrimidinyle et tétrazolyle. Parmi les 3 molécules les plus actives 31, 43 et 50, la seconde a fait l'object d'une étude plus approfondie.     

Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation

Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferation and/or differentiation is undefined. In the present study, the response of erythroid precursors at different stages of differentiation to Epo was examined. Erythroblasts were derived from adult blood erythroid progenitors (BFU- E) at day 7 or day 10 of culture. [Cac] was measured in individual Fura- 2 loaded cells with fluorescence microscopy coupled digital video imaging. The dynamic range (Rmax/Rmin) of intracellular Fura-2 was similar to that measured in free solution, suggesting insignificant amounts of intracellular Ca insensitive forms of Fura-2. Baseline [Cac] of erythroid cells calculated with an in vitro calibration method was 44 +/- 4 nmol/L and with an in vivo method was 46 +/- 4 nmol/L. Treatment of day 7 BFU-E derived erythroblasts with Epo resulted in no significant increase in [Cac]. In contrast, in more mature erythroblasts (day 10 of culture), Epo stimulated a large increase in [Cac] from 49 +/- 11 nmol/L at baseline to 279 +/- 47 nmol/L. This [Cac] increase occurred in phosphate buffered saline (PBS) containing no added calcium. The increase in [Cac] persisted for 18 minutes and was dose dependent. Day 7 and day 10 control cells treated with either insulin or media showed no significant change in [Cac] during 18 minutes of observation. Our data demonstrate that early (day 7) and late (day 10) erythroblasts display different responses to Epo, at least in terms of intracellular Ca++ fluxes. The differential [Cac] response observed in early and late erythroid precursors to growth factor stimulation suggests that [Cac] may be an important signal in cell differentiation.     

纳米羟基磷灰石沉积层/钛酸钾薄层/钛合金生物复合材料体外培养成骨细胞的研究

在制备出具有表面活性的纳米羟基磷灰石沉积层/钛酸钾薄层/钛合金（HA/K2Ti6O13/β-Ti）生物复合材料的基础上,将体外培养的成骨细胞与HA/K2Ti6O13/β-Ti生物复合材料、未经处理β钛合金两种骨替代材料共同培养,在既定时间内观察两种骨替代材料对成骨细胞生长、附着的影响。结果表明两种骨替代材料对成骨细胞生长无明显抑制或促进作用,均具有良好的细胞相容性,它们皆能使成骨细胞附着于各自材料表面,分泌形成胶原纤维样基质。HA/K2Ti6O13/β-Ti生物复合材料较β钛合金具有更优异的的生物活性和成骨性能,是一种很好的生物植入材料。     

胶原-生物衍生骨材料与兔成骨细胞的相容性及其体外附着特点

目的:观察胶原-生物衍生骨复合材料与兔成骨细胞的相容性及体外附着规律,为进一步的体内实验提供参考数据。方法:实验于2003-10/2005-02在华西医科大学组织工程实验室进行。①材料制备:新鲜捐献骨(人),经脱脂、脱蛋白等工艺制成单纯生物衍生骨材料,以Ⅰ型胶原通过真空吸附法修饰单纯生物衍生骨材料表面,构建出胶原生物衍生骨材料。②实验方法:将体外培养的兔骨膜成骨细胞分别复合于单纯生物衍生骨材料和胶原生物衍生骨材料,共同培养7d。③观察指标:分别于培养第1,3,5和7天取材,扫描电镜观察成骨细胞形态及附着情况;用紫外/荧光/可见光高效分析仪测定成骨细胞产生的碱性磷酸酶活性;MTT检测成骨细胞增殖情况;用流式细胞仪检测兔成骨细胞的细胞周期、DNA含量及倍体水平。结果:①扫描电镜结果:胶原生物衍生骨材料组成骨细胞黏附和增殖优于生物衍生骨材料组。②碱性磷酸酶活性:生物衍生骨材料组低于胶原生物衍生骨材料组(0.019±0.003,0.038±0.004,P<0.05)。③细胞增殖情况:在培养第1,3,5,7天胶原生物衍生骨材料组成骨细胞A值均高于生物衍生骨材料组(P<0.05)。④流式细胞检测生物衍生骨材料、胶原生物衍生骨材料对兔成骨细胞的细胞周期影响不大,各组细胞皆为正常的二倍体细胞,未见异倍体细胞形成,胶原修饰后无细胞毒性。结论:以单纯生物衍生骨作为载体,其表面经胶原修饰后的复合材料与成骨细胞有良好的细胞相容性,无细胞毒性。     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome (Ph1) in more than 95% of these patients. The Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. In CML, the product of the fused BCR- ABL gene is typically a protein of approximately 2,000 amino acids termed P210 BCR-ABL. We have developed an assay for the BCR-ABL protein involving Western blotting of circulating white blood cells (WBC) with an anti-ABL monoclonal antibody that can detect P210 BCR-ABL and P145 ABL in peripheral blood cells from chronic phase Ph1-positive leukemia patients. This assay was used to analyze the BCR-ABL protein content of circulating WBC from CML patients before and after various treatments. In parallel to changes in percentages of Ph1-positive blood cells as determined by cytogenetic analyses of bone marrow samples, BCR-ABL protein expression in blood cells decreased or increased as patients entered remission or underwent relapse. Of interest, six Ph1-negative CML patients were BCR-ABL protein-positive. All except one had a rearrangement in the major breakpoint cluster region and that patient expressed P185 BCR-ABL and not P210. Our results indicate that the BCR- ABL Western blotting assay has clinical applications for both diagnosis and prospective evaluation of Ph1-positive and Ph1-negative CML patients.     

Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease

Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferential survival of F cells versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kinetics of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease in HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state levels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non--F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.