Bullous Melanoma: should the thickness of the bullous lesion be included in Breslow depth measurement?

Bullous melanoma represents a rare variant of melanoma, especially in patients without underlying bullous cutaneous disease. Few cases have been described in the literature, including cases of melanoma in patients with bullous epidermolysis or Hailey-Hailey disease. The histopathological diagnosis of bullous melanoma does not show any difficulties, except for the measurement of the Breslow index. The rarity of this case, the dilemma of how to measure the Breslow index and the importance of an early diagnosis motivated this report.     

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection

BACKGROUND: Increased serum gamma-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. METHODS: Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi2 test and multivariate logistic regression analysis. RESULTS: Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Initially, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level. CONCLUSIONS: A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.     

Epidemiology of achondroplasia: A population‐based study in Europe

Achondroplasia is a rare genetic disorder resulting in short‐limb skeletal dysplasia. We present the largest European population‐based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991–2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14–4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011–2015 vs. 36% in 1991–1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.     

Acute appendicitis. Experimental model in rabbits

The evolving phases of acute appendicitis were studied experimentally. Sixty female rabbits (Oryctogalus cuniculus) of New Zealand lineage weighing about 2510 to 3040 g were divided in two groups: a control group and experimental group. The experimental group was divided into three subgroups for observation after 12, 24 and 48 hours of the operation, that consisted on a 4-0 polypropylene circular suture at 8 cm from the distal part of the cecal appendix. The control group was sham operated. The macroscopic exam (increase of the appendix volume, necrosis, perfuration, adherence and secretion in the abdominal cavity) and the microscopic finding showed a progression in the anatomopathological alterations. There was a close relationship between the histopathological findings and time after the appendiceal obstruction. We conclude that the method causes acute appendicitis and that the anathomo pathological alterations depends on the time elapsed between the operation and the postoperation findings.     

Apoptosis,PCNA and p53 in hepatocellular carcinoma

BACKGROUND/AIMS: The regulation of cell number is present in normal tissues but is lost in malignant neoplasms. The real meaning of these alterations is not well known. Apoptosis is the programmed cell death. p53, a tumor suppressor gene, has an important function in DNA repair and in regulation of apoptosis. Mutations of p53 were described in malignant tumors and can be the cause of the alterations of this balance. Proliferating cell nuclear antigen is an auxiliary protein present during G1-late phase and S phase. The aim of this study was to compare cell proliferation, apoptosis and expression of p53 in hepatocellular carcinoma. METHODOLOGY: Fifteen patients with hepatocellular carcinoma were included. Ten patients were men. The mean age of the patients was 55.53 years old. Cirrhosis was positive in nine patients, 5 were HBsAg positive and none were anti-HCV positive. The mean level of AST and ALT were respectively, 62.79 and 50.64. Formalin-fixed and paraffin-embedded tissues from these patients were examined retrospectively. Apoptosis were measured by counting the number of apoptotic bodies in 500 tumoral cells. The expression of p53 oncogene and the PCNA were determined by immunohistochemical method, using avidin-biotin method (DAKO). The p53 were considered positive when the number of positive nuclei was more than 5% of the tumoral cells. The proliferative activity was determined by proliferating cell nuclear antigen labeling index. RESULTS: The proliferating cell nuclear antigen-labeling index ranged from 0.48 and 0.95 (mean: 0.82). The p53 was positive in five patients. The number of apoptotic bodies counted ranged from 0 to 15 (mean: 4.20). There were no differences among p53 and the mean levels of proliferating cell nuclear antigen labeling index or p53 and the number of apoptotic bodies. CONCLUSIONS: A high index of proliferation has been shown in the patients studied. Positivity of p53 was seen in less than a half of the patients (35.71%). The index of apoptotic bodies observed was very low. Our results suggest that high-grade proliferation is not associated with increase of apoptosis in hepatocellular carcinoma.     

Beckwith Wiedemann syndrome: A population-based study on prevalence,prenatal diagnosis,associated anomalies and survival in Europe

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8?±?6.2 (11–39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3?±?2.4 (11–22) gestational weeks, and the mean gestational age at termination was 19.3?±?4.1 (13–26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.     

Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX‐3 index

Summary. HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV‐infected patients. This cross‐sectional study included 102 KT individuals with positive HCV‐RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR ≥ F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX‐3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ≤4.0 of TX‐3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX‐3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX‐3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX‐3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV‐infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.