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     

Total Hip Arthroplasty in Ankylosing Spondylitis With Extension Contracture of Hips

Background

Despite significant pain relief following total hip arthroplasty (THA) in patients with ankylosing spondylitis, a small subset of patients presenting with extra-articular extension contracture of hips remains unsatisfied.

Mirror movements in progressive hemifacial atrophy

Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand.     

Shortening peel-away sheaths prior to dialysis line insertion--potential decrease of patient risk.

Placement of tunnelled dialysis lines is effective using ultrasoundand fluoroscopic guidance [1] and has a higher success ratethan ‘blind’ insertion [2]. After the ultrasound guided access into a neck vein, wires andcatheters are guided in to a suitable position in the     

Giant mediastinal liposarcoma: a case report.

Liposarcomas are extremely rare in the mediastinum. They may achieve considerable size before causing any symptoms. Mediastinal liposarcomas may invade surrounding structures like the pericardium or the superior vena cava. Complete surgical excision is the optimal treatment in resectable cases. Excision of adjacent structures like the pericardium may be needed if the tumor infiltrates them. We report on a case of a giant liposarcoma of the mediastinum involving both hemithoraces and extending into the neck, which was successfully managed by complete surgical excision.     

Malignancy larynx presenting solely as pharyngo-cutaneous fistula

Malignancy larynx usually presents early, the common symptoms being hoarseness, pain thorat, cough and irritation of throat. An advanced malignancy is likely to be complicated by a pharyngo-cutaneous fistula. However it is an occurrence towards the end stage of the disease. Here we present a case of malignancy larynx primarily presenting as pharyngo-cutaneous fistula without any other symptoms.     

Late Dissection of Pulmonary Autograft Treated by Valve-Sparing Aortic Root Replacement

Abstract   Dissection of the pulmonary autograft is an extremely rare complication requiring emergent treatment as there is a chance of rupture and proximal aortic involvement. The autograft dissection can involve the aortic annulus, causing separation of leaflets from the annulus in addition to causing annular dilatation, thereby precluding resuspension of leaflets. The usual treatment in such cases is to perform the Bentall procedure, which involves placing a valved conduit (usually mechanical valve) and thereby necessitating anticoagulation. This report describes a case of successful valve-sparing aortic root replacement following the Ross procedure with dissection of autograft.     

Mechanism of multidrug resistance in relation to passive membrane permeation.

Passive uptake of drugs into cells is described in terms of the following steps: (1) massive immediate binding of the drugs to the outer leaflet of the plasma membrane resulting in practical equilibrium between extremely high drug concentrations at the cell surface compared to the drug concentration in the medium. (2) Due to their amphipathic nature, anticancer drugs are practically excluded from the lipid core of the membrane. They cross the lipid core by distinct flip-flop events that occur in the case of doxorubicin and daunorubicin after an average period of 0.7 and 0.15 min, respectively. (3) The drug reaching the inner leaflet of the plasma membrane is in practical equilibrium with the drug present in the cytoplasm. (4) Almost all the amounts of anticancer drugs present in the cells are bound by molecular sinks, such as DNA or cytoskeleton elements. The resistance afforded to multidrug resistant (MDR) cells by extrusion pumps, such as P-glycoprotein, is negatively correlated with the affinity of the drugs to the membranes and with their flip-flop rates across membranes. Binding rates of the drugs to membranes and intracellular sinks have no effect on drug concentration in the cytoplasm once equilibrium is reached between the passive uptake of drugs and their active extrusion.