When TACE is not totally effective, it may induce a significant neoangiogenetic reaction, as suggested by an increase in VEGF and b-FGF following treatment; this affects patient survival. VEGF emerges as the most reliable prognostic parameter, so it could be measured for judging TACE efficacy. Finally, antiangiogenic drugs may be indicated in TACE-treated HCC.
The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.
BackgroundA consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in "very early" and "early" stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment.MethodsData were collected in 530 "very early" and "early" HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P-value < 0.05 was considered statistically significant.Results"Very early" HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In "early" HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival.Conclusionpatients with very early" HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The "early" stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.
Background & Aims. Circulating albumin in cirrhosis can be dysfunctional due to accumulating structural damages, leading to the concept of effective albumin concentration (eAlb) referring to the albumin portion presenting structural and functional integrity. We aimed to estimate eAlb in patients with decompensated cirrhosis and analyze its relationships with albumin function and clinical outcomes as compared to total albumin concentration (tAlb). Approach & Results. We evaluated 319 cirrhotic patients hospitalized for acute decompensation (AD) with and without acute-on-chronic liver failure (ACLF) and 18 age-and sex-comparable outpatients with compensated cirrhosis. tAlb was quantified by standard assay, while eAlb was estimated combining liquid chromatography-electrospray ionization-mass spectrometry and standard methods. Albumin binding and detoxification efficiency were evaluated by electron paramagnetic resonance analysis. Circulating albumin in patients with decompensated cirrhosis displayed multiple structural abnormalities, with reversible oxidation and glycation being the most frequent. As a result, eAlb progressively declined with the worsening of cirrhosis, and was superior to tAlb in stratifying patients between compensated cirrhosis, AD and ACLF, as well as patients with and without complications. Moreover, eALB, but not tAlb, was closely associated with binding capacities in ACLF. Finally, eALB at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than tAlb. Conclusion: This large observational study provides the evidence in patients with decompensated cirrhosis that eAlb can be quantified and differentiated from tAlb routinely measured in clinical practice. As compared to tAlb, eAlb is more closely associated with disease severity and albumin dysfunction, and carries a greater prognostic power. These results prompt future research assessing eAlb as a novel biomarker for predicting prognosis and treatment response.
Objectives Gonadotropin-releasing hormone (GnRH) agonists like deslorelin are being increasingly used in tom cats for their efficacy in controlling reproductive behaviour and fertility. Deslorelin implants have been widely available in Europe since 2008. Little, if anything, is known about the interval between treatment and onset of sterility, as well as semen quality, after treatment in tom cats. The purpose of this study was to investigate semen quality and interval to sterility in tom cats treated with a 9.4 mg deslorelin implant. Methods Fifteen healthy adult tom cats were treated with a 9.4 mg deslorelin implant (Suprelorin 12). For each cat, semen collection and a GnRH stimulation test (intramuscular administration of 50 μg gonadorelin [Fertagyl], followed by blood sampling 1 h later, to assay serum testosterone) were performed on the first consultation and then repeated every 15 days until complete sterility was achieved. Semen collection was performed by introducing a 14 cm, open-end feline catheter (Argyle) 9 cm into the distal urethra 10 mins after sedation by intramuscular injection of 100 μg/kg medetomidine (Domitor). Results Semen collection was not successful in all cats at each attempt. In the first month after treatment, the semen of only four cats could be evaluated, while the semen of eight cats could be evaluated during the second and third months of the study. Semen quality (ejaculate volume, progressive motility and morphological abnormalities) improved slightly during the first 19-25 days in 2/4 cats, and in 1/4 cats motility was still very high (80%) 25 days post-treatment (PT), but we have no data regarding fertility prior to treatment in this cat. The last cat never produced spermatozoa. Subsequently, semen quality gradually worsened in all cats from 30 days onwards. At 70 days PT, one cat was still potentially fertile. After 72 days all cats were sterile. Conclusions and relevance Semen quality increased slightly in treated cats during the first month after treatment, and then gradually decreased over the following months. Complete sterility was reached within 40-72 days following implantation.
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