Apostolos Athanasiadis

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m−2) was given on d1, L-OHP (65 mg m−2) on d2, LV (200 mg m−2) on days 2 and 3 and 5-FU (400 mg m−2 as i.v. bolus and 600 mg m−2 as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m−2) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature.

Biomarkers in pre-eclampsia: A novel approach to early detection of the disease

Pre-eclampsia is a unique disorder of human pregnancy with a great impact on maternal and perinatal morbidity and mortality worldwide and especially in developing countries. The aetiology is still unknown and the pathophysiology of the disease is the subject of extensive investigation. Recently, much of the interest of the investigators for the prediction of pre-eclampsia has been aimed at measurable manifestations of abnormal placentation, endothelial dysfunction and feto-maternal unit perfusion. Biomarkers constitute a novel approach to an early detection of the disease. Low maternal serum levels of PAPP-A and PP13 early in pregnancy are predictive for emerging pre-eclampsia. On the other hand, increased levels of homocysteine, ADMA, sEng, leptin and sFlt-1 in the 1st trimester, signal the onset of the disease later in pregnancy. After the onset of pre-eclampsia, increased serum levels of PAPP-A, ADMA, homocysteine and sFlt-1 are associated with the severity of the disease. The identification of biomarkers which can contribute to the early detection of pre-eclampsia is essential. It could then be possible to apply better surveillance and treatment protocols in such patients.

Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: A phase II study

BACKGROUND Based on the high activity of single-agent paclitaxel and the superior one-year survival rates of patients with non-small-cell lung cancer (NSCLC) treated with carboplatin, a phase II trial was initiated using both agents in patients with inoperable stages III and IV disease to investigate the efficacy and toxicity of the combination. PATIENTS AND METHODS Since July 1995, 60 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a three-hour infusion, and carboplatin dosed to an area under the concentration-time curve of seven, every three weeks. No granulocyte colony-stimulating factor was given. Of the 56 male and four female patients, the median age was 57 years (range 29 to 75 years) and the median Eastern Co-Operative Oncology Group performance status was one. Most of the patients had stage IV (34) adenocarcinoma (31) with low differentiation (28). The median number of chemotherapy cycles was three, with a range of one to eight. RESULTS Of 55 evaluable patients, 15 (27.3%) achieved partial responses, 15 (27.3%) had stable disease, and 25 (45.4%) had progressive disease. The median survival was 8.95 months and 21.6% of the patients survived more than one year. Grade 2/3 nonhematologic toxicity included alopecia (59%), neurotoxicity (3%), and myalgia/arthralgia (10%). Grade 2/3 neutropenia occurred in 14% of patients, whereas grade 3/4 thrombocytopenia was seen in only 4%. One patient died of complications of a severe allergic reaction. CONCLUSION Combination treatment using paclitaxel and carboplatin is active and well tolerated in patients with inoperable non-small-cell lung cancer. The dose-response relationship to paclitaxel and results of comparison with other platinum-based regimens remain to be determined.

Biomarkers of endothelial dysfunction in preeclampsia and neonatal morbidity: a case–control study

OBJECTIVE To investigate the association of preeclampsia with angiogenic imbalance, and the correlation of levels of angiogenic and anti-angiogenic factors to complications in mother and fetus. STUDY DESIGN Serum samples were obtained from 40 women with established preeclampsia (study group) and from 40 normotensive women (control group). Epidemiological characteristics of the two groups were analyzed. The levels of the angiogenic (VEGF and PlGF) and anti-angiogenic (sFlt-1) factors of the two study groups were determined in serum using ELISA. Neonatal adverse outcomes (late preterm, early term, low birth weight (LBW), very LBW (VLBW), intrauterine growth restriction (IUGR), and neonatal intensive care unit (NICU) admission) between the groups of the study were analyzed, as well as the association between the biomarkers of the study and neonatal adverse outcomes of the preeclamptic group of patients. RESULTS sFlt-1 levels were significantly higher in the preeclamptic women compared to normotensive women (median (range): 21297 (690-32637)pg/ml vs. 846.45 (363-2867)pg/ml, respectively), whereas there was a significant decrease in the levels of VEGF (90 (90-211)pg/ml vs. 90.55 (90-521)pg/ml, respectively), as well as in the levels of PlGF (13.62 (8-532)pg/ml vs. 239.86 (61-685)pg/ml, respectively). The increased serum values of the anti-angiogenic sFlt-1 were associated with increased rates of late preterm and early term births and VLBW. CONCLUSION An imbalance between angiogenic and anti-angiogenic factors exists in preeclampsia and is associated with adverse maternal and neonatal outcomes.

Clinical outcome of elderly patients with metastatic colorectal cancer treated with FOLFOXIRI versus FOLFIRI: Subgroup analysis of a randomized phase III trial from the Hellenic Oncology Research Group (HORG)

BACKGROUND A subgroup analysis of oxaliplatin (LOHP)+irinotecan (CPT-11)+5-fluorouracil (5FU) and leucovorin (LV) (FOLFOXIRI regimen) versus irinotecan+5FU/LV (FOLFIRI regimen) as first-line treatment of patients >65 years old with metastatic colorectal cancer is presented. PATIENTS AND METHODS Eighty-two (56%) and 75 (55%) patients with metastatic colorectal cancer aged >65 years were enrolled in the FOLFOXIRI and FOLFIRI regimen, respectively. RESULTS There was no statistically statistical difference in terms of overall survival or time-to-tumor progression between young and aged patients between the two chemotherapy arms. The objective response rate was significantly lower in older patients treated with FOLFOXIRI (32% vs. 52%; OR: 1.45, 95% CI: 1.06-2.09; p=0.03). Elderly patients experienced a significantly higher incidence of grade 3/4 diarrhea compared to younger patients, irrespectively of the chemotherapy regimen (p=0.005 for FOLFIRI; p=0.017 for FOLFOXIRI). Dose reductions and treatment delays were more frequent in the FOLFOXIRI arm. CONCLUSION FOLFOXIRI does not seem to offer substantial benefit compared to FOLFIRI regimen in elderly patients with metastatic colorectal cancer.

Apert Syndrome: The Current Role of Prenatal Ultrasound and Genetic Analysis in Diagnosis and Counselling

Apert syndrome is a rare congenital malformation syndrome characterized by the triad of cutaneous and progressive bony syndactyly, midfacial hypoplasia and craniosynostosis. Two missense mutations of the gene encoding the fibroblast growth factor receptor 2 (FGFR2) have been implicated in most cases. We report a case of Apert syndrome detected on prenatal ultrasound. Postnatal genetic analysis showed, for the first time, that the previously reported P253R mutation of the FGFR2 gene is also prevalent in southeast Europe. After prenatal sonographic detection of anomalies suggestive of Apert syndrome, parents should be counselled about prognosis and risk of recurrence, and the option of amniocentesis should be offered.

Case report: Laparoscopic treatment of a ruptured interstitial pregnancy

Interstitial pregnancy is a rare but life-threatening condition. A case of a 28-year-old woman with a partially ruptured interstitial pregnancy treated with operative laparoscopy is presented. A laparoscopic cornual resection and a left salpingectomy were performed uneventfully. Serum beta-human chorionic gonadotrophin concentrations were measured serially at weekly intervals until resolved on day 20 postoperatively. It seems, therefore, that laparoscopic treatment is still an effective option for management even in ruptured interstitial pregnancy, preserving the anatomical integrity of the uterus and future fertility, and that rupture of interstitial ectopic pregnancy is not a contra-indication for laparoscopy.

Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities. Evaluation of 13,500 cases with consideration of using QF-PCR as a stand-alone test according to referral indications.

Evaluate the results obtained from Quantitative Fluorescent (QF)‐PCR and conventional karyotype analysis to determine the advantages and disadvantages of dual testing in prenatal diagnosis.

Turner's syndrome and pregnancy: has the 45,X/47,XXX mosaicism a different prognosis? Own clinical experience and literature review

Turners syndrome is characterized by an ovarian failure which occurs in most cases before puberty and leads to infertility. In less than 10% of women with Turner syndrome, puberty may occur and spontaneous pregnancies is possible but with a high risk of fetal loss, chromosomal and congenital abnormalities. We present the case of a 33-year-old woman with a mosaic Turners syndrome karyotype 45,X/47,XXX who conceived spontaneously and had two successful pregnancies. Short stature was the only manifestation of Turners syndrome. In the present report, we reviewed the available literature on the fertility of women with Turners syndrome and the phenotypic effects of mosaicism for a 47,XXX cell line in Turners syndrome.

Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases.

This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5‐Mb resolution.