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     

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Stability of transverse expansion in the mandibular arch.

This was a retrospective, longitudinal cephalometric and cast study of 29 white patients at pretreatment, posttreatment, and an average of 6 years 3 months postretention. The goal was to assess changes with treatment and retention with the expanding mandibular lingual arch appliance in conjunction with fixed edgewise treatment. Seven mandibular cast measurements were assessed, including arch crowding, arch perimeter, arch length, and arch width at the permanent canines, first premolars, second premolars, and first molars. Cephalometric radiographs were digitized, and 16 cephalometric measurements were made. Repeated-measures analysis of variance and 2-sample t tests were used to determine statistically significant changes. It was found that the expanding lingual arch used for less than 6 months with the mandibular fixed edgewise appliance caused an increase in both the transverse and sagittal dimensions of the mandibular dental arch. Transverse expansion was more stable in the posterior region of the mandibular dental arch than in the anterior region. Mandibular intercanine width increase could be maintained only by fixed retention. Although the maxillary and mandibular incisors were advanced and proclined, lip protrusion did not occur.     

Endoscopic sclerotherapy in the treatment of gastric varices

Of 309 patients with portal hypertension, gastric varices were found in 48 (16 per cent). While the majority (88 per cent) of the patients had gastric varices in association with oesophageal varices, 6 (12 per cent) patients had 'isolated' gastric varices. Gastric varices were seen significantly (P less than 0.01) more often with grade 4 than with grade 3 varices. In 11 (28 per cent) of the 40 patients who completed sclerotherapy for oesophageal varices, gastric varices disappeared concurrently on eradication of oesophageal varices or during the following 6 months. Of the initial five patients with gastric varices who received direct intravariceal injections, four rebled; this technique was therefore replaced by combination (paravariceal + intravariceal) gastric variceal sclerotherapy. Emergency combination sclerotherapy successfully controlled bleeding from gastric varices in six of the eight treated patients. Thirty-two patients entered a programme of elective combination gastric variceal sclerotherapy. Variceal obliteration was achieved in 12 cases (38 per cent) and reduction in size was noted in another 7 patients (22 per cent) after a minimum of four courses. There were 11 (23 per cent) deaths, 8 due to uncontrolled bleeding from gastric varices and 3 due to hepatic coma. The other complications of gastric variceal sclerotherapy were minor and included retrosternal pain, fever and dysphagia. It is concluded that gastric varices often coexist with large oesophageal varices. If they persist for 6 months after eradication of oesophageal varices, a combination of paravariceal and intravariceal sclerotherapy should be attempted for their obliteration.     

A Survey of Childhood Psoriasis in Kuwait

Abstract: One hundred ninety cases of childhood (age birth-12 yrs) psoriasis constituted 0.3% of the total of new dermatologic outpatients. Girls outnumbered boys by a ratio of 1.5:1. Plaque psoriasis was the commonest clinical variant (84%), followed by guttate psoriasis. The scalp was the most common site of onset (22%). Sites predominantly affected later were the extensor surfaces of the legs and the scalp (63% and 53%, respectively). A majority of the children had a milder form of disease. Nail involvement was seen in 36%, with pitting the most common feature (87%). Seven percent had mucosal involvement. A positive family history of psoriasis was obtained in 28%. Topical therapy (coal tar, anthralin, steroids) was the main treatment in the majority of patients (92%). Sixteen patients (8%) required more aggressive intervention (ultraviolet B, psoralin-UVA, retinoids). This is the first study of this kind from the Middle East, the findings are compared with those reported from other parts of the world.