INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

Diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced endoscopic ultrasound (ECEUS) for the differentiation of pancreatic lesions: a systematic review and meta-analysis.

PURPOSE: To evaluate CEUS for the diagnosis of pancreatic diseases and its application in the clinical routine with a focus on the value of CEUS in ductal pancreatic carcinoma and its use for the differentiation of neoplastic and non-neoplastic lesions. MATERIALS AND METHODS: All prospective and retrospective studies published in any language by March 6, 2014 were included based on the following criteria: use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced endoscopic ultrasound (ECEUS) as the imaging methods, use of histology as the reference method and availability of a complete translation. Two authors analyzed the titles and abstracts of the search results to identify all relevant publications. Two independent readers then analyzed the full articles to identify those meeting the inclusion criteria. Details regarding study design, patient characteristics, interventions, and results were then independently extracted by two radiologists and one reviewer with methodological expertise. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. RESULTS: 1293 articles were initially identified. 27 studies met the inclusion criteria. CEUS was the index test in 23 studies while ECEUS was the index test in 4 studies. The primary study objective was met by 20 studies with respect to ductal adenocarcinoma. CEUS sensitivity was evaluated in all studies. The pooled estimate of CEUS sensitivity for the diagnosis of ductal adenocarcinoma was 0.89 (95 % CI, 0.85 - 0.92). 15 out of 20 studies examined CEUS specificity. The average specificity was 0.84 (95 % CI, 0.77 - 0.89). The pooled estimate for DOR was 61.12 (95 % CI, 34.81 - 107.32). With regard to the secondary study objective, the pooled sensitivity and specificity were 0.95 (95 % CI, 0.93 - 0.96) from 14 studies and 0.72 (95 % CI, 0.58 - 0.83) from 13 studies, respectively. The pooled DOR was 57.63 (95 % CI, 33.62 - 98.78). CONCLUSION: The sensitivity, specificity, and DOR results show the high value of CEUS for the characterization and differentiation of ductal adenocarinomas from other pancreatic diseases and for cystic pancreatic lesions. For this reason and due to their noninvasive nature, CEUS and ECEUS should be used as the first methods for characterizing neoplastic pancreatic lesions, especially since these are often incidental findings. The methods improve the quality of ultrasound diagnostics and result in faster diagnosis and better disease management.

Glycosilated fetal hemoglobin in neonates of diabetic mothers.

In diabetic patients, the correlation between glycosilated adult hemoglobin (HbA1c) levels and average glucose concentration over the preceding weeks is well known. We have, therefore, sought the possibility to identify newborns at risk measuring cord blood levels of fetal glycosilated hemoglobin (HbF1) in neonates of diabetic mothers. HbF1 was tested by the isoelectrofocusing method. Mean values of HbF1 have been proven to be higher in in infants born to diabetic mothers as compared to normal newborns. The highest levels were encountered in those babies whose mothers had shown a poor glycemic control during the last few weeks of pregnancy.

Met-enkephalin-like immunoreactivity (MELI) and enkephalinase activity (EKA) in cord blood and newborns in the first hours of life.

Recently, the presence and the concomitant release with catecholamines of metenkephalin and other pro-enkephalin A deriving peptides have been demonstrated in the adrenal medulla of various mammals and man. As high amounts of catecholamines are released in the newborn at delivery, probably following the stress of parturition, a similar release of met-enkephalin and other pro-enkephalin A deriving peptides from the newborn chromaffin tissue may be hypothesized. In the present study we investigate the occurrence of met-enkephalin-like immunoreactivity and enkephalinase (quite a specific enkephalin degrading enzyme) in cord and newborn plasma at different hours after birth. Our results show the presence of high met-enkephalin-like immunoreactivity levels in cord and newborn plasma with respect to normal adult values. On the contrary, cord blood enkephalinase activity was lower than in adult subjects and further decreased during the first hours of life. A positive correlation was found between the two parameters. These data seem to indicate a release of met-enkephalin-like peptides from the newborns' sympathoadrenal tissue following the stress of delivery and in the first hours of life.

[Increase of the "null cells" in children with persistent hepatitis (author's transl)]. / Aumento delle cellule "nulle" im bambini con epatite persistente.

Some membrane and functional properties of lymphocytes have been examined in a group of children affected with persistent hepatitis. Both absolute and percentage values of B lymphocytes (cells bearing surface Ig) were normal, whereas T lymphocytes (E rosette technique) were decreased in percentage but not as absolute numbers. Only in a close range of mitogen concentration PHA responsiveness was altered, and no modification was found in the percentage of EA and EAC rosettes. A marked increase in lymphocytes lacking both T and B cell markers was observed, which may be related to an increase in precursors of mature cells or to a masking of receptors on the membrane of lymphocytes, but which is probably independent of an increase in the number of K cells, since cells bearing receptors for the Fc fragment were normal.

Proteolytic activity of maternal serum on newborn IgD-positive lymphocytes. Study with protease inhibitors.

We studied the effect of maternal serum on the surface IgD of newborn lymphocytes in the presence of protease inhibitors (epsilon-aminocaproic acid and Trasylol). Contact with maternal serum caused a significant reduction (p less than 0.000001) in the percentage of neonatal IgD-positive cells. The addition of either epsilon-aminocaproic acid or Trasylol significantly reduced this action of maternal serum (p l-ess than 0.00001 and p less than 0.0001), without difference between the effects of the two inhibitors (p greater than 0.05). We suggest, therefore, that activity of maternal serum is due, at least in part, to proteolytic enzymes, such as plasmin. The relative role of plasminogen and alpha2-macroglobulin in the incapacity of the newborn serum to reduce the number of IgD-positive lymphocytes is discussed.