Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review

Simple SummaryGlioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient survival. Chemoradiotherapy is a also safe and efficacy treatment in patients with multiple lesions. Survival advantages from extensive resection remain unclear.AbstractGlioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.     

Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration

BACKGROUND/AIMS: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases. METHODS: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples. CONCLUSION: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake.     

Tumor’host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds

Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy. Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126), and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions and to improve the antineoplastic efficacy of paclitaxel-based combination treatments.     

Reduction of carbonylic and carboxylic groups by plant cell cultures

The transformation of aliphatic and aromatic acids to their corresponding alcohols, involving two reductive steps, is difficult to perform biologically due to its low redox potential. For this reason, the reduction of nonactivated carboxylic acids has been described for only a limited number of substrates and confined to a few microbial groups (fungi, clostridia, and archea). Nine species of cultured plant cells were able to reduce cinnamic, hexanoic, and octanoic acids to the corresponding primary alcohols with yields ranging from 2 to 80% (w/w). Aldehyde was detected only for three species during the reduction of cinnamic acid, confirming that the second reductive step from aldehyde to alcohol is faster than the first, from acid to aldehyde. Lyophilized cells from some of the cultures were used in buffer and solvent-water systems to obtain the reduction of carbonylic (ethyl acetoacetate) and carboxylic (cinnamic and hexanoic acids) groups.     

Nitric oxide levels in women with missed and threatened abortion: results of a pilot study

The aim of this study was to evaluate the systemic production of nitric oxide (NO) in missed and threatened abortion and in nonpregnant and regular pregnant controls with the purpose of defining its role in the mechanisms regulating the first-trimester pregnancy toward either positive or negative evolution. Patients with missed abortion showed serum NO levels clearly decreased compared with nonpregnant patients and patients with regular pregnancy and threatened abortion, supporting a direct functional role of the NO mediator in early embryonic development and confirming its importance in the uterus and cervix during abortion.     

A critical analysis on Italian perinatal mortality in a 50-year span

BACKGROUND: Perinatal mortality rate is used as an indicator of reproductive health worldwide. In western countries, national mortality registers are usually accurate and reliable. METHODS AND AIMS: We reviewed the data recorded in the past 50 years in Italy on perinatal and infant mortality. Each single class of mortality rate (according to WHO definitions) was assessed on temporal trends allowing a critical speculative analysis, mainly focusing on the last 20 years, in an attempt to evaluate the impact of prenatal diagnosis. RESULTS: Infant mortality rate (IMR) constantly decreased in the study period whereas early neonatal mortality rate progressively diminished in a 5-year comparison till the early 1990s. Perinatal mortality showed a linear negative trend until the 1980s, after which the decrease steadied at about 23% in the following 5-year period. Infant mortality attributable to congenital anomalies throughout a 20-year span (1980-2000) was steady at about 23% although a progressive reduction in general infant mortality was reported. CONCLUSIONS: A higher reduction in neonatal and perinatal mortality rate was found before the wide availability of the ultrasonographic prenatal diagnosis and the introduction of the law on voluntary abortion in Italy. Given these data, it seems that advances in neonatal care have improved the infant survival rates more than prenatal diagnosis, whereas obstetric care is linked to a reduction of the early perinatal mortality rate.     

Placental insufficiency and intrauterine growth retardation

AIM: Placental insufficiency is a pathological condition consisting of a placental functional deficit with multifactorial etiology; it can cause maternal complications such as edema, proteinuria, hypertension, etc. Our study aims to establish if placenta analysis after birth can lead to the identification of basic morphological alterations which can be easily documented and useful for the diagnosis of feto-neonatal pathologies. METHODS: We examined 60 pregnant women (45 primipara, 15 multipara). They were hospitalized in the period from March 1998 to March 2004 in different pregnancy periods because of fetus growth delay. After birth, a careful examination of the placenta has been carried out soon after spontaneous birth (weight, thickness, possible morphological alterations which could be macroscopically observed) and it was followed by an anatomo-pathological examination carried out at the Anatomopathology Unit of Ospedali Riuniti in Foggia. RESULTS: Macroscopic examination, in the group of women at the first pregnancy, showed that there were no morphological alterations in the placenta in all the cases, but the weight was normal (400- 500 g) in 8 cases and it was less than 400 g in the other 37 cases. In the group of multipara, placenta did not shown morphological alterations in all the cases, but the weight was normal in only 3 cases and it was lower in the remaining 12 cases. The placental microscopic examination pointed out: infarct focus in 34 cases (60%), 12 (35%) of which were recent and 22 (65%) were old infarct focuses; immaturity of chorionic villus in 15 (30%) of the examined placentas; increase in the cytotrophoblast mitotic index in 49 cases (90%) and placenta with normal histological appearance in 11 cases (10%). CONCLUSION: Placental examination, both with macroscopic and microscopic techniques, can lead to the identification of basic morphological alterations which can be easily documented and useful for the diagnosis of feto-neonatal pathologies. A good placental functionality influences both fetal life and postnatal life. Thus, a greater attention to the placental examination in obstetric practice is suggested, especially for maternal and fetal pathologies.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...