Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation

BACKGROUND: The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. METHODS: we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. RESULTS: Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. CONCLUSION: Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.     

Spinal myoclonus with giant somatosensory evoked potentials and enhanced long-loop reflex: a case report

We describe a patient with an ischaemic lesion of the cervical spinal cord who presented with clinical evidence of stimulus-sensitive, multisegmental myoclonic jerks restricted to the truncal and proximal limb muscles and accompanied by electrophysiological features (giant somatosensory evoked potentials and enhanced long-loop reflex) of cortical myoclonus. We hypothesize that these features might result from a loss of inhibitory influences on the sensory input to cortical structures: a concomitant contribution of spinal and cortical hyperexcitability seems to have played a crucial role in inducing myoclonus in our patient.     

A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism

BACKGROUND: Mutations in polymerase gamma cause progressive external ophthalmoplegia and a variety of associated symptoms and signs, including neuropathy, ataxia, hypogonadism, hearing loss, muscle weakness, and psychiatric problems. Extrapyramidal signs have been rarely described. OBJECTIVE: To describe a family with a novel polymerase gamma mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism. DESIGN: Case report. PATIENTS: The proband, a 49-year-old woman with incipient parkinsonism, and her 59-year-old brother with overt parkinsonian features. MAIN OUTCOME MEASURES: Mutation in the proband by sequencing the polymerase gamma gene and in affected relatives by restriction fragment length polymorphism analysis. RESULTS: We found multiple mitochondrial DNA deletions in the proband's muscle and a novel missense mutation in the polymerase gamma gene (A2492G) in the proband and in her affected siblings. CONCLUSION: Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gamma gene.     

Predictive value of biological markers for hepatocellular carcinoma patients treated with orthotopic liver transplantation.

PURPOSE: To help stratify candidates with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT), biomarkers are needed that are capable of predicting recurrence of disease (ROD). We investigated the prognostic role in this setting of immunohistochemical markers reported previously to predict poor prognosis in HCC patients treated with resection. EXPERIMENTAL DESIGN: Eighty-three patients with HCC who underwent OLT between 1987 and 2001 with a minimum clinical follow up of 12 months were included in this retrospective study. We analyzed immunohistochemical expression of the adhesion molecules E-cadherin and beta-catenin (membrane/nuclear localization), MIB-1 proliferative index and the cyclin-dependent kinase inhibitor p27, alongside the main clinical-pathological variables. RESULTS: At univariate analysis, vascular thrombosis, high MIB-1 index, lower membrane expression of E-cadherin and beta-catenin, and nuclear beta-catenin localization were associated with ROD. At multivariate analysis, only MIB-1 index, low equal E-cadherin (with respect to non-neoplastic surrounding tissue), and nuclear beta-catenin appeared as independent predictors of ROD. The logistic regression analysis model indicated that detection of any one parameter was associated with at least 88% estimated risk of ROD (up to 99% for all three). CONCLUSIONS: We propose these three molecular parameters as an additional tool for rational selection of OLT candidates among HCC patients (stratification according to the risk of ROD might help provide a similar life expectancy for cirrhotic candidates with and without HCC).     

Laparoscopic-ultraminilaparotomic myomectomy (LUM)-laparoscopic-ultraminilaparotomic embolized myomectomy (LUEM). Surgical techniques

Laparoscopic myomectomy has been performed for more than 20 years. More recently other techniques such as laparoscopically assisted vaginal myomectomy (LAVM) and laparoscopically assisted myomectomy (LAM) have also been introduced. Laparoscopic-ultraminilaparotomic myomectomy (LUM) and laparoscopic-ultraminilaparotomic embolized myomectomy (LUEM), a new surgical technique which integrates laparoscopy and ultraminilaparotomy and embolization, has been created by our group and has been found to be superior to the conventional laparoscopy for the treatment of uterine fibromas especially in large myomas > 9 cm. This technique allows us to apply a suture on the uterine incision totally similar to the suture of a conventional laparotomy, by using the small breach of the cutaneous incision of the uterine morcellator (25 mm) and drawing the uterus below this abdominal aperture. This kind of surgical procedure is associated with presurgical embolization, that we call LUEM (laparoscopic ultraminilaparotomic embolized myomectomy) of the afferent vessels to the myoma in myomas with diameters equal or superior to 14 cm to avoid blood loss during the surgical procedure. Between June 1999 and March 2002, a total of 62 patients wishing to become pregnant were treated with this method. LUM allows us to increase the feasibility and safety of the operation, while assuring a better stability of the uterine suture and reduction of surgical time. LUEM has the advantages of LUM but permits in an absolutely hemostatic situation the application of laparoscopy in the surgery of large myomas superior to 14 cm.     

Psychomotor performance in healthy young adult volunteers receiving lormetazepam and placebo: a single-dose, randomized, double-blind, crossover trial

BACKGROUND: Lormetazepam is a hypnotic benzodiazepine currently used in the treatment of insomnia. When this agent is used appropriately, its pharmacologic properties predict a high therapeutic index with a good tolerability profile. OBJECTIVE: The primary aim of this study was to compare the effects on psychomotor performance of lormetazepam and placebo in healthy young adult subjects. A secondary objective was to evaluate the clinical tolerability of lormetazepam. METHODS: This was a randomized, double-blind,placebo-controlled, crossover study in healthy young adult volunteers. All volunteers received single doses of lormetazepam 1 mg and placebo, with a 1-week interval between doses. The primary study variables were visual simple reaction time (VSRT) and visual choice reaction time (VCRT), measured before dosing with lormetazepam or placebo and at 20, 60, 120, 180, 240, and 360 minutes after dosing using a standard computerized apparatus. To increase the sensitivity of the results, visual reaction times were also recorded using a validated mobile computerized device. Secondary variables were the duration and quality of sleep on the night before each study session, rated by subjects using a 100-mm visual analog scale; the Epworth Sleepiness Scale for daytime drowsiness; and the Critical Flicker Fusion Threshold test. Spontaneously reported adverse events were recorded and monitored throughout the study. RESULTS: The study included 18 healthy young adult volunteers (12 women, 6 men; mean [SD] age, 26.7 [2.8] years [range, 21-30 years]; mean body weight, 58 [9.5] kg). There were no significant differences in either VSRT or VCRT after administration of lormetazepam or placebo. Independent of study drug but consistent with the accepted range of variability between the 2 devices, overall reaction times were significantly shorter with the use of the mobile device compared with the standard apparatus (P < 0.01). Analysis of the results showed no sequence effects or other evidence of learning. There were no changes in the secondary study variables after administration of the test drugs. Administration of lormetazepam was associated with dizziness in 2 subjects, in 1 case occurring in association with somnolence. These adverse events were mild and subsided spontaneously 3 hours after drug intake. After administration of placebo, 1 subject reported slight somnolence 60 minutes after dosing that persisted through 180 minutes. CONCLUSION: In this small, selected group of healthy young adult subjects, a single dose of lormetazepam 1 mg did not affect psychomotor performance, assessed in terms of visual reaction times, compared with placebo.     

G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives

The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 825 locus 461 participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study (age, 18 to 45 years) at low cardiovascular risk, according to 1999 ISH/WHO criteria. The study end point was eligibility for antihypertensive medication, that is, progression to grade II hypertension during the first year of observation or office systolic blood pressure > or =150 mm Hg and/or office diastolic blood pressure > or =95 mm Hg in two later consecutive visits during follow-up. At baseline, there was no statistically significant difference among genotypes with respect to body mass index, blood pressure, and heart rate. During follow-up (mean, 4.7 years), 113 (51.1%) patients with CC genotype and 145 (60.4%) patients with TT/TC genotype reached the end point. According to survival analysis, the patients carrying the 825T allele had an increased risk of reaching the blood pressure end point (CI, 1.108 to 1.843; P=0.006). In young patients with grade I hypertension, the 825T allele is associated with increased risk of progression to more severe hypertension requiring antihypertensive therapy. The GNB3 825T allele may be considered a genetic marker of predisposition for hypertension.     

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.