Overview of prognostic systems for hepatocellular carcinoma and ITA.LI.CA external validation of MESH and CNLC classifications

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described

Glucocorticoids are preferable to thionamides as first-line treatment for amiodarone-induced thyrotoxicosis due to destructive thyroiditis: a matched retrospective cohort study

Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive thyroiditis usually responsive to glucocorticoids; however, recent surveys showed that many expert thyroidologists worldwide use thionamides for type 2 AIT patients. OBJECTIVE: The objective of the study was to compare the effectiveness of methimazole (MMI) or prednisone (GLU) in type 2 AIT patients who had a short cure time according to a published predictive model. DESIGN: This was a matched retrospective cohort study. SETTING: The study was conducted at a university center. PATIENTS: Forty-two untreated type 2 AIT patients with a predicted cure time < or = 40 d were divided into two groups (MMI and GLU groups). After matching for the predicted cure time, patients in the GLU group were selected in a 1:1 ratio to patients in the MMI group. INTERVENTION: Patients were treated with GLU or MMI for 40 d. Patients still thyrotoxic after 40 d continued glucocorticoids if in the GLU group or were switched to prednisone (MMI-GLU group) if in the MMI group. MAIN OUTCOME MEASURE: Time and rate of cure (healing) at 40 d were measured. RESULTS: Patients still thyrotoxic after 40 d were 23.8 +/- 9.3% in the GLU group and 85.7 +/- 7.6% in the MMI group (P = 0.000). The GLU and MMI-GLU groups did not significantly differ in the nonhealing rate at 40 d (P = 0.730). When patients in the MMI group were treated with glucocorticoids, 94.1% patients achieved euthyroidism within 40 d. However, the global median cure time (MMI period + prednisone period) was longer (60 d, 95% confidence interval 53.5-66.5 d) in the MMI-GLU group than the GLU group (21 d, 95% confidence interval 15.1-26.9 d). CONCLUSIONS: Glucocorticoids are the first-line treatment in type 2 AIT, whereas thionamides play no role in this destructive thyroiditi

Cigarette smoking and treatment outcomes in Graves ophthalmopathy

Background: It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes. Objective: To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Craves ophthalmopathy receiving orbital radiation therapy and glucocorticoids. Design: Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2). Setting: University medical center. Patients: 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2). Intervention: In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks). Measurements: Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy). Results: In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001). Conclusions: Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy

Proportion of type 1 and type 2 amiodarone-induced thyrotoxicosis has changed over a 27-year period in Italy

Context: Two main forms of amiodarone-induced thyrotoxicosis (AIT) exist. Type 1 AIT is a form of iodine-induced hyperthyroidism. Its management is complex and includes thionamides, potassium perchlorate and, occasionally, thyroidectomy. Type 2 AIT is a destructive thyroiditis, responds to glucocorticoids, and usually does not require further thyroid treatment once euthyroidism has been restored. Objective: To assess retrospectively the prevalence and relative proportion of type 1 and type 2 AIT over a 27-year period at a tertiary referral centre in Italy. Patients: Consecutive AIT patients (n = 215) seen at the department of endocrinology of the University of Pisa between 1980 and 2006. Results: Type 1 AIT constituted the most frequent AIT form (60%) during the first years covered by this study. The annual mean number of type 1 AIT patients was 3.6 at the beginning of the study period, and 2.5 during the later years. In contrast, the mean annual number of new cases of type 2 AIT progressively increased from 2.4 to 12.5. Likewise, the proportion of type 2 AIT increased in a significant linear manner (P < 0.0001), currently accounting for 89% of AIT cases. Type 2 AIT patients showed a male preponderance, higher serum FT4/FT3 ratio (P < 0.002), lower 3-h and 24-h thyroidal radioactive iodine uptake values (P < 0.0001), and received a higher cumulative dose of amiodarone (P < 0.0001) than type 1 AIT patients. Conclusions: Over a 27-year period, the epidemiology of AIT changed, as the prevalence of type 2 AIT progressively increased and that of type 1 remained constant. Thus, under most circumstances, endocrinologists nowadays deal with type 2 AIT, which is a destructive thyroiditis, generally treated successfully with glucocorticoids. Although no additional treatment is usually required after the destructive process subsides, periodic assessment of thyroid function is warranted, because of the occurrence of hypothyroidism (up to 17%) during long-term follow-up of these patients. \ua9 2007 The Authors

Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: Results of a prospective, single-blind, randomized study

Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 \ub1 3.0 to 21.6 \ub1 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 \ub1 1.8 to 21.7 \ub1 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 \ub1 2.5 to 11.8 \ub1 2.2 mm, and from 13.6 \ub1 2.0 to 11.5 \ub1 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 \ub1 1.2 to 1.7 \ub1 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 \ub1 1.1 to 2.2 \ub1 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects