Cilengitide in bevacizumab-refractory high-grade glioma: two case reports and critical review of the literature

High-grade gliomas (HGG) are aggressive and highly vascularized brain tumours. Despite multimodality therapy including surgery, radiation therapy and in many cases temozolomide chemotherapy, the prognosis is dismal. Salvage therapies following progression after radiation therapy and chemotherapy have historically yielded disappointing results. Bevacizumab is an interesting antiangiogenic drug used as a second-line treatment but although most patients benefit, essentially all patients ultimately progress. Moreover, some clinical studies have documented low activity of a second attempt at vascular endothelial growth factor pathway inhibition after failure of a first. The use of another drug with a different angiogenic pathway inhibition may probably result in a higher activity. Here, we describe, to our knowledge for the first time, the activity and safety of cilengitide, an agent with a different antiangiogenic and anti-invasive activity, administered in two bevacizumab-refractory patients with HGG. In addition, we present a rapid review of the activity of cilengitide in HGG.     

Cephalometric findings in facioscapulohumeral muscular dystrophy patients with obstructive sleep apneas

Purposes

The purposes of the study are: (1) to establish if cephalometry and upper airway examination may provide tools for detecting facioscapulohumeral (FSHD) patients at risk for obstructive sleep apnea syndrome (OSAS); and (2) to correlate cephalometry and otorhinolaryngologic evaluation with clinical and polysomnographic features of FHSD patients with OSAS.

Methods

Patients were 13 adults affected by genetically confirmed FSHD and OSAS, 11 men, with mean age 47.1?±?12.8 years (range, 33?C72 years). All underwent clinical evaluation, Manual Muscle Test, Clinical Severity Scale for FSHD, Epworth Sleepiness Scale, polysomnography, otorhinolaryngologic evaluation, and cephalometry.

Results

Cephalometric evidence of pharyngeal narrowing [posterior airways space (PAS)?<?10 mm] was present in only one patient. The mandibular planus and hyoid (MP-H) distance ranged from 6.5 to 33.1 mm (mean, 17.5?±?7.8 mm). The mean length of soft palate (PNS-P) was 31.9?±?4.8 mm (range, 22.2 to 39.7 mm). No patient presented an ANB angle?>?7°. There was no significant correlation between cephalometric measures, clinical scores, and PSG indexes. PAS and MP-H were not related to the severity of the disease.

Conclusions

Upper airway morphological evaluation is of poor utility in the clinical assessment of FSHD patients and do not allow to predict the occurrence of sleep-related upper airway obstruction. This suggests that the pathogenesis of OSAS in FSHD is dependent on the muscular impairment, rather than to the anatomy of upper airways.     

Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

Objectives

To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC).

Methods

Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis.

Results

Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4–35), minimum follow-up was 12 months. In the adenocarcinoma group (n?=?31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n?=?22). GL*U did not correlate with overall survival.

Conclusions

TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy.

Key Points

? Contrast enhanced computed tomography is currently used to stage lung cancer. ? Texture analysis allows tumour heterogeneity to be quantified on CT images. ? Texture parameters seem to predict chemotherapy response in advanced NSCLC.     

Isolated sphenoid inflammatory diseases associated with visual impairment: 15-year experience at a single institution

We present a retrospective series of 11 patients treated for isolated sphenoid inflammatory disease (ISID) with visual impairment in the period between 1994 and 2008. The series included 7 females and 4 males. All patients, preoperatively assessed by CT or MR, underwent endoscopic sinus surgery and broad-spectrum antibiotic therapy. The procedure was always performed in an emergency setting, with an interval from the onset of visual impairment ranging between 1 and 40 days (mean 9 days). The possibility of recovery was related to both the modality of onset and severity of the deficit. All patients with reduction of the visual field reported significant improvement after surgery. Patients with decreased visual acuity obtained partial or complete resolution, while in patients with preoperative blindness no improvement was observed. Moreover, no postoperative improvement was noticed in the case of severe deficits with sudden onset, whereas the treatment of mild deficits was successful even some weeks after their occurrence. In conclusion, although some factors may predict the likelihood of recovery, any patient with ISID associated with visual impairment should receive immediate medical and surgical treatment. Endoscopic surgery should be considered the technique of choice.     

Evaluation of esophageal motility and reflux in children treated for congenital diaphragmatic hernia with the use of combined multichannel intraluminal impedance and pH monitoring

Background

Gastroesophageal reflux (GER) is frequently observed in children treated for congenital diaphragmatic hernia (CDH) at birth, as well as esophageal dysmotility, that has been hypothesized to be caused by innervatory anomalies. The aim of this study is to evaluate GER and dysmotility in young patients with CDH using pH-multichannel intraluminal impedance.

Methods

Thirty children (17 boys and 13 girls) who underwent repair for CDH between 2002 and 2007 with a median age of 5.2 years (range, 3-10 years) were included in the study. All patients were operated on with a subcostal laparotomy incision and had a left-sided diaphragmatic defect. The defect repair required an artificial patch (Goretex, Gore Medical, Flagstaff, AZ) in 8 patients (27%) because of its size. We described impedance reflux parameters and some specific motility parameters studied on 10 standardized swallows.

Results

The incidence of GER was 86%. Reflux was mainly nonacidic, postprandial, and short-term and reached only the distal esophagus. Esophageal dysmotility was observed only in the distal esophagus.

Conclusions

With the use of pH-multichannel intraluminal impedance, both GER and esophageal motility in patients with congenital malformations can be analyzed. In patients with CDH, impaired motility seems to involve only the distal esophagus. In this group, the specific pattern of reflux is probably caused by the involvement of gastroesophageal junction, without significant intrinsic innervation abnormalities as observed in patients with esophageal atresia.