Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.     

ENDOSCOPY ASSISTED REMOVAL OF FERROMAGNETIC COINS WITH NOVEL MAGNETIC INSTRUMENT

Background: Ingestion of coins is a common clinical problem in children. Many of the coins are ferromagnetic and can be retrieved with the help of a magnet. We describe the use of a novel endoscopic accessory for removing ferromagnetic coins. Material and methods: Two magnet discs of 1.5 cm diameter were joined to a 200 cm steel wire of 0.75 mm thickness with a terminal 5 cm spring. A Teflon tube (160 cm, 7 F) was used along with this instrument as a sleeve. The use of this accessory was analyzed prospectively in subjects presenting with a history of coin ingestion. The time taken for removal of coins, complications during the procedure and failure rate was noted. Effect of the magnet on cardiac rhythm was also noted during the procedure. Results: A total of 55 children (mean age 5.1 ± 2.3 years) with coin ingestion presented over a period of 1 year. Forty‐four coins were ferromagnetic. All ferromagnetic coins were removed successfully. Mean time for removal was 68 ± 22 s. No complications were encountered. Conclusion: The novel magnetic instrument is precise, safe and quick for the removal of ferromagnetic coins under direct vision.     

Teratoma tongue: Case report and review of literature

Teratomas are true neoplasms composed of tissues from all three germinal layers and may exhibit variable levels of maturity. They have an unknown origin and eccentric microscopic appearance. Teratomas arising from the oral cavity are rare in the newborn; only 22 cases have been reported in the literature. We describe a female neonate with an oral teratoma originating from the tongue that was successfully treated with surgery.     

Clinical significance of serum and cerebro spinal fluid bilirubin indices in neonatal jaundice

To assess the value of unbound bilirubin (UB) and saturation index (SI) in serum and CSF as indicators of Kernicterus, we studied 50 icteric neonates (serum indirect bilibrubin (IB) greater than or equal to 7 mg/dl) and 20 controls (IB less than 7 mg/dl) during the first week of life. Serum and CSF were obtained simultaneously in all neonates. Of 36 neonates with IB greater than 12 mg/dl 19 had evidence of kernicterus. UB was estimated by Sephadex gel filtration and SI by salicylate displacement technique. Positive correlation (r = +0.85) was obtained between serum and CSF UB levels. There was a significant difference (p less than 0.05) between mean serum and CSF UB levels in kernicterus and non-kernicterus neonates (kernicterus serum UB = 0.71 +/- 0.22) mg/dl, CSF UB = 0.16 +/- 0.06 mg/dl: non-kernicteric serum UB = 0.40 +/- 0.10 mg/dl, CSF UB = 0.10 +/- 0.03 mg/dl). A critical serum UB level 0.5 mg/dl and a danger zone of CSF UB (0.1 to 0.15 mg/dl) was observed in presence of kernicterus. Neonates with kernicterus and 30% non-kernicteric had serum SI greater than or equal to 8. Mean values of serum and CSF SI were comparable in all neonates. The serum and CSF UB and SI, and the mean percentage cross over of UB from serum to CSF when statistically compared were not significantly influenced by risk factors.