Causes for delay before specialist consultation in head and neck cancer.

BACKGROUND: Head and neck cancers are often diagnosed at a late stage, thus resulting in a generally poor prognosis. This is partly attributable to patients' hesitancy in seeking treatment. However, the length and causes of these patient delays remain relatively unknown. MATERIAL AND METHODS: We included all new head and neck cancer patients treated at our tertiary care center between 2016 and 2017. Using a patient questionnaire, we collected data on patients' symptoms and other factors related to seeking medical care, and recorded both patient- and primary health care-related delays. We then compared the data collected from these patients to patient and tumor characteristics collected from hospital records, and analyzed various causes for delay before a specialist consultation to the Department of Otorhinolaryngology - Head and Neck Surgery. RESULTS: Among the patients (n = 142) in our study, the median patient delay was 35 d with 73% of patients seeking medical care within 3 months. In comparison, the median primary health-care delay was 20 d. Certain symptoms influenced patient delay. Hoarseness and breathing difficulties correlated with longer patient delay while patients with a lump on the neck had a shorter delay. Patient delay was associated with certain tumor-related factors such as the tumor site and the presence of regional metastases, which resulted in shorter patient delay. None of the patient-related factors appeared to impact delay. Important factors influencing primary health-care delay included the initial location visited and whether any follow-up visit was scheduled or not. CONCLUSIONS: Although most patients sought medical advice without a major delay and were adequately referred, we found that long delays existed. Raising awareness of the symptoms of head and neck cancer among general population and health-care providers is probably the best way to get patients to curative treatment without delay.

Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition.

In 1960 researchers reported that balanced translocation between chromosomes 22 and 9 resulted in the generation of Philadelphia chromosome. This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene. Research over the years has progressively and systematically improved our understanding of the genetic and proteomic basis of Leukemia. Genome-wide profiling studies, including genome sequencing and microarray analysis, have helped us in identification of different intracellular signaling cascades that are frequently mutated in Leukemia.  We partition this multi-component review into different sections related to biochemical characteristics of BCR-ABL+ cells, underlying mechanism of generation of mutations and crosstalk of BCR-ABL with various intracellular signaling cascades. We also summarize how BCR-ABL encoding mRNA is negatively regulated by different miRNAs and the strategies which are currently being used to effectively target BCR-ABL protein. We also provide an overview of the natural products which have been used for targeting of BCR-ABL protein. Better understanding of the protein network of Philadelphia positive leukemic cells will prove to be helpful in getting a step closer to personalized medicine.

Toll-like receptor 5 and 7 expression in adenoid cystic carcinoma of major salivary glands.

Adenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis and high metastatic rate. Toll-like receptors (TLRs) have been related to tumour progression but have also tumour growth-inhibiting responses. To the best of our knowledge, they have not been studied previously in ACC. We studied the immunoexpression of TLR 5 and 7 in ACC of the major salivary glands. From a cohort of 54 patients with ACC of the major salivary glands treated at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland in 1974-2009, there were 34 primary tumours and six metastases available for immunohistochemical analysis. Immunohistochemical expression of TLR 5 and 7 were correlated to clinicopathological findings and patient survival. Both TLR 5 and 7 were expressed in ACCs and their metastases, mostly on the cell membranes. The expression was heterogeneous in individual tumours. TLR 5 was expressed less in male samples, and TLR 7 had lower expression in ACCs with solid growth pattern. No correlation with survival was found. In the normal salivary gland, the TLR 5 and 7 expression was mainly negative. Both TLR 5 and 7 are expressed in salivary adenoid cystic carcinoma on the cell membranes as well as in cytoplasm.

Trends in the 15D health-related quality of life over the first year following diagnosis of head and neck cancer.

Management of head and neck cancer influences both physical and mental wellbeing. Measuring the health-related quality of life (HRQoL) is important, as various treatment modalities are associated with significant morbidity and mortality. In this prospective cohort study, we tested the feasibility of the generic 15D HRQoL instrument in 214 head and neck cancer patients managed with surgery, definitive (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at baseline and three times after treatment onset during 1 year, and compared with that of general population standardized for age and sex. At baseline, the patients' mean 15D score was significantly worse compared with general population. Overall HRQoL was at lowest at 3 months after treatment onset, it gradually improved towards 12 months but never reached baseline levels. The dimensions "vitality", "distress", "depression" and "sexual activity" showed marked deterioration at 3 months after the treatment onset, but improved gradually during 12 months. The 15D instrument seems useful for evaluation of HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing improved gradually after 3 months, but they seldom reached baseline levels. The support for patients at the time of diagnosis, during treatment, and recovery is emphasized.

Role of decompressive hemicraniectomy in extensive middle cerebral artery strokes: a meta-analysis of randomised trials.

BACKGROUND: Prognosis for patients with 'malignant' or space-occupying oedema post middle cerebral artery infarct remains poor despite maximal medical therapy delivered in the intensive care setting. AIM: We performed a meta-analysis to evaluate the value of surgical decompression versus medical management alone in patients suffering from malignant middle cerebral artery infarct. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct and Web of Science. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The overall OR for mRS 6 (death) at 6 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.19 (95% CI: 0.10-0.37). The frequency of patients with mRS 2, 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 3.29 (95% CI: 1.76-6.13). The overall OR for mRS 6 (death) at 12 months for decompressive surgery as compared with standard medical management revealed a statistically significant reduction with OR of 0.17 (95% CI: 0.10-0.29). The frequency of patients with mRS 3 and 5 outcomes was higher in the decompressive surgery cohort; however, these outcomes did not reach statistical significance. On the other hand, the number of patients with a mRS score of 4 was significantly higher in the decompressive surgery cohort with an OR of 4.43 (95% CI: 2.27-8.66). In the long run it was also observed that the number of patients with a mRS score of 2 was significantly higher in the decompressive surgery cohort an OR of 4.51 (95% CI: 1.06-19.24). CONCLUSIONS: Our results imply that surgical intervention decreased mortality of patients with fatal middle cerebral artery infarct at the expense of increasing the proportion suffering from substantial disability at the conclusion of follow up.

A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

Health-related quality of life of head and neck cancer patients with successful oncological treatment.

Oncological treatment of head and neck carcinoma is associated with high morbidity. Measuring of health-related quality of life (HRQoL) is crucial in this patient group but there is no consensus on which measure would be preferable to be used. In this study, HRQoL was measured with the generic 15D, which has not been used before for assessing this patient population. It is a prospective cohort study among 64 patients with laryngeal, pharyngeal or nasal cavity carcinoma treated with definitive (chemo) radiotherapy between November 2007-July 2012. HRQoL was assessed with the 15D before and at 3, 6 and 12 months after the treatment onset. HRQoL results of the patients were compared with those of the age-standardized general population. Overall HRQoL declined significantly during the first 3 months after the treatment onset but then gradually improved towards the end of the follow-up. At baseline or at 12 months, no significant differences were detected in overall HRQoL between the patients and the general population. Dimensions reflecting mental well-being showed gradual improvement, exceeding the baseline scores at the end of the follow-up. Nevertheless, on these dimensions, the patient group presented with consistently lower scores compared with the general population. The mean HRQoL was lower among patients with pharyngeal carcinoma compared with the laryngeal carcinoma patients. The 15D instrument is feasible for evaluation of HRQoL in oncologically treated head and neck cancer patients. It seems to detect differences among different patient subgroups. Multidisciplinary supportive management of this patient population is recommended to ensure improved mental well-being.

Functional polymorphisms of interleukin-18 gene and risk of breast cancer in a Brazilian population.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. In this case-control study, we tested whether IL-18 promoter polymorphism contributes to breast cancer susceptibility in Brazilian patients. The two groups studied were 154 patients with breast cancer and 118 healthy individuals. The frequency of IL-18 promoter single nucleotide polymorphisms (SNPs) at positions -607 (C/A) (rs1946518) and -137 (G/C) (rs187238) was determined by polymerase chain reaction analyses. The polymorphisms genotyped in this study showed a significant association with breast cancer under different genetic models. Both SNPs showed a positive association. For the IL18-607 polymorphism the best model was the codominant genetic model [CC vs AA, P = 0.004, odds ratio (OR) = 2.782, 95% confidence interval (CI) 1.385-5.589]. For IL18-137 statistical significance was found using the recessive genetic model (P = 0.008, OR = 3.896, 95% CI 1.427-10.639). The association between the haplotypes of the IL18 gene and breast cancer was further confirmed. Our results suggest that IL18-607 and IL18-137 polymorphism contributes to increase the breast cancer risk. To our knowledge, this is the first report regarding Brazilian breast cancer patients and IL18 promoter polymorphisms.

Lifestyle intervention on diet and exercise reduced excessive gestational weight gain in pregnant women under a randomised controlled trial.

OBJECTIVE: To examine the effect of an exercise and dietary intervention during pregnancy on excessive gestational weight gain (EGWG), dietary habit and physical activity in pregnant women. DESIGN: Randomised controlled trial. SETTING: Community-based study. POPULATION: Nondiabetic urban-living pregnant women (<26 weeks of gestation). METHODS: Participants in the intervention group were provided with community-based group exercise sessions, instructed home exercise and dietary counselling between 20 and 36 weeks of gestation. Participants in both groups received physical activity and food intake surveys at enrolment and 2 months after the enrolment. MAIN OUTCOME MEASURES: Prevalence of EGWG and measures of physical activity and food intakes between the two groups. RESULTS: A total of 190 pregnant women, 88 in the control group and 102 in the intervention group, completed the study. Decreased daily intakes of calorie, fat, saturated fat and cholesterol were detected in participants in the intervention group at 2 months after enrolment compared with the control group (P<0.01). Participants in the intervention group had higher physical activity 2 months after enrolment compared with the control group (P<0.01). The lifestyle intervention during pregnancy reduced the prevalence of EGWG in the intervention group compared with the control group (P<0.01) according to the guidelines of the Institute of Medicine. CONCLUSION: The findings suggest that lifestyle intervention during pregnancy increased physical activity, improved dietary habits and reduced EGWG in urban-living pregnant women.

The benefit method: fitting hearing aids in noise.

The most common complaint among individuals with hearing impairment is the inability to follow a conversation when several people are talking simultaneously, a noisy listening situation which is completely different from the quiet surrounding of the conventional pure tone audiometry used as basis for the hearing aid settings. The purpose of this report was to present important characteristics of the BeneFit Method (BFM), a procedure that fits the hearing aid under simulated conditions of competing speech and also a clinical pilot evaluation study comparing the BFM to the NAL-R recommendations and also to the Logic procedure, a GN resound proprietary fitting algorithm representing a modern digital hearing aid fitting procedure. Speech recognition scores in noise (SRSN) using monosyllabic words presented under different background noise levels were evaluated on 21 randomly selected subjects with hearing impairment. The subjects were fitted with the same type of hearing aid Danalogic 163D according to the BFM procedure as well as the logic procedure, the latter developed and recommended by the manufacturer. A comparison of the SRSN when using the subjects' current hearing aid fitted according to the NAL-R procedure was also made. Only the BFM procedure provided a significant SRSN improvement compared to the unaided condition (P< 0.01) in a signal/speech-noise level of 75/65 dB corresponding to a normal cocktail party condition. Moreover, patients performed significantly higher SRSN when fitted according to the BFM, than when fitted according the Logic or NAL-R procedures. The BFM procedure, which is based on individual and functional detection of hearing thresholds in noise levels corresponding to a cocktail party condition, can improve SRSN significantly. Hearing aids should be fitted under conditions similar to those when the hearing disability is perceived the most, i.e, in an environment with background noise.

Traditional tonsillectomy compared with bipolar radiofrequency thermal ablation tonsillectomy in adults: a pilot study.

OBJECTIVES: To assess the morbidity and efficacy of bipolar radiofrequency thermal ablation tonsillectomy and compare it with traditional cold dissection tonsillectomy with diathermy hemostasis. DESIGN: Prospective, randomized, single-blinded, controlled clinical study. SETTING: Helsinki University Central Hospital, Department of Otorhinolaryngology-Head & Neck Surgery, Helsinki, Finland. PATIENTS: Forty healthy volunteer patients aged 18 to 65 years admitted for elective tonsillectomy with recurrent or chronic tonsillitis, obstructive tonsillar hypertrophy, or history of quinsy. Two patients were excluded from the study and 1 patient cancelled the operation. INTERVENTIONS: Nineteen patients underwent a traditional cold dissection tonsillectomy with diathermy hemostasis, and 18 patients underwent a bipolar radiofrequency thermal ablation tonsillectomy. There was no intergroup difference in age, sex, weight, and indications for tonsillectomy. The subjects were not informed of the type of procedure until the telephone interview 3 weeks after the operation. MAIN OUTCOME MEASURES: Operating time and intraoperative blood loss; need for anesthetics during the operation; different recovery indicators in the recovery room (ie, duration and medications administered), surgical ward (ie, medications administered, use of corticosteroids, general condition, and status of the uvula on the first postoperative day), and in the 2 weeks following surgery (ie, visual analog scale scores on 6 symptoms, medications needed, the day patients returned to work, use of antibiotics, and retreatment acceptance); and complications and certain laboratory parameters. RESULTS: There was a statistically significant but clinically insignificant difference in operating time and intraoperative blood loss in favor of the traditional tonsillectomy group. The other outcome measures showed no statistically significant differences. CONCLUSION: Bipolar radiofrequency thermal ablation and traditional tonsillectomy were associated with similar postoperative morbidity.

Sleep-disordered breathing: radiofrequency thermal ablation is a promising new treatment possibility.

OBJECTIVES: The aim of this study was to assess the efficacy and morbidity of radiofrequency thermal ablation of the soft palate in subjects with sleep-disordered breathing. STUDY DESIGN: Prospective, nonrandomized study. Outpatient treatment and an extended follow-up time of 12 months. METHODS: Twenty-one healthy men who were 18 to 60 years of age (median age, 44 y) with sleep-disordered breathing were enrolled to the study. All the patients had habitual snoring for at least 1 year that was associated with excessive daytime sleepiness interfering with social or professional activities. Radiofrequency energy was delivered to the soft palate in two treatment sessions separated by 1 week at 460 +/- 1 kHz with an energy delivery of 600 and 300 J. Snoring Score, Epworth Sleepiness Scale, and cephalometric analysis were measured preoperatively and postoperatively. Certain inflammatory laboratory parameters and visual analogue scale scores of symptoms were measured related to the procedure. RESULTS: The changes in Snoring Score and Epworth Sleepiness Scale scores were statistically significant. The change in the length of the soft palate was statistically significant, whereas the change in palatal width was not. There were no notable changes in the laboratory parameters. The symptom visual analogue scores were low and transient, resolving within days. CONCLUSIONS: The radiofrequency thermal ablation of the soft palate in patients with sleep-disordered breathing seems to be effective. It is safe and associated with only a low morbidity. The promising results must be confirmed in a placebo-controlled study with a larger sample size and a long-term follow-up.

Physiological flow simulation in residual human stenoses after coronary angioplasty.

To evaluate the local hemodynamic implications of coronary artery balloon angioplasty, computational fluid dynamics (CFD) was applied in a group of patients previously reported by [Wilson et al. (1988), 77, pp. 873-885] with representative stenosis geometry post-angioplasty and with measured values of coronary flow reserve returning to a normal range (3.6 +/- 0.3). During undisturbed flow in the absence of diagnostic catheter sensors within the lesions, the computed mean pressure drop delta p was only about 1 mmHg at basal flow, and increased moderately to about 8 mmHg for hyperemic flow. Corresponding elevated levels of mean wall shear stress in the midthroat region of the residual stenoses, which are common after angioplasty procedures, increased from about 60 to 290 dynes/cm2 during hyperemia. The computations (Ree approximately equal to 100-400; alpha e = 2.25) indicated that the pulsatile flow field was principally quasi-steady during the cardiac cycle, but there was phase lag in the pressure drop-mean velocity (delta p - u) relation. Time-averaged pressure drop values, delta p, were about 20 percent higher than calculated pressure drop values, delta ps, for steady flow, similar to previous in vitro measurements by Cho et al. (1983). In the throat region, viscous effects were confined to the near-wall region, and entrance effects were evident during the cardiac cycle. Proximal to the lesion, velocity profiles deviated from parabolic shape at lower velocities during the cardiac cycle. The flow field was very complex in the oscillatory separated flow reattachment region in the distal vessel where pressure recovery occurred. These results may also serve as a useful reference against catheter-measured pressure drops and velocity ratios (hemodynamic endpoints) and arteriographic (anatomic) endpoints post-angioplasty. Some comparisons to previous studies of flow through stenoses models are also shown for perspective purposes.

Estimated flow resistance increase in a spiral human coronary artery segment.

Coronary flow estimates were made for a spiral coronary artery segment (identified from a post-mortem replica casting) by using a modified Dean number based on the approximate coil radius of curvature, as suggested earlier. The estimates were found to correlate experimental pressure drop data for helical coiled tubes. Over a physiological range of mean Reynolds numbers from 100 to 400 for blood flow through main coronary arteries, estimates of the flow resistance increase relative to a straight lumen segment ranged from about 20 to 80 percent, and were of similar magnitude to those found in a flow study in a sinuous coronary vessel segment with no spiral.

Catheter obstruction effect on pulsatile flow rate--pressure drop during coronary angioplasty.

The coupling of computational hemodynamics to measured translesional mean pressure gradients with an angioplasty catheter in human coronary stenoses was evaluated. A narrowed flow cross section with the catheter present effectively introduced a tighter stenosis than the enlarged residual stenoses after balloon angioplasty; thus elevating the pressure gradient and reducing blood flow during the measurements. For resting conditions with the catheter present, flow was believed to be about 40 percent of normal basal flow in the absence of the catheter, and for hyperemia, about 20 percent of elevated flow in the patient group. The computations indicated that the velocity field was viscous dominated and quasi-steady with negligible phase lag in the delta p(t)-u(t) relation during the cardiac cycle at the lower hydraulic Reynolds numbers and frequency parameter. Hemodynamic interactions with smaller catheter-based pressure sensors evolving in clinical use require subsequent study since artifactually elevated translesional pressure gradients can occur during measurements with current angioplasty catheters.

Beyond the racist/hooligan couplet: race, social theory and football culture.

This paper draws on recent research to explore the changing cultures of racism in English football. Starting from a critical analysis of key themes in the literature on football it seeks to show that existing analytical frameworks need to be reworked if they are going to adequately account for the complex forms through which racism is expressed in contemporary football cultures. In the course of this analysis we question some of the ways in which the issue of racism in football is collapsed into broader accounts of 'hooliganism' and other forms of violence among football fans. From this starting point the paper draws on some elements of our empirical research in order to outline an alternative way of framing the issues of racism and multicultrralism in football.

Hemodynamic consequences of stenosis remodeling during coronary angioplasty.

Quantitative hemodynamic assessment during various endovascular interventions including balloon angioplasty is lacking. Translesional pressure drops measured by angioplasty catheters can cause flow blockage and thus lead to inaccurate estimates of preintervention and postintervention flow rates. A new analytical model of the flow rate-pressure drop relation across vascular stenoses is utilized that is nonlinear yet relatively simple in principle, easily applicable in vivo, and compatible with the presence of catheters. The model incorporates in vitro experimental evidence, angiographic data on the dimensions and shapes of coronary arterial stenoses before and after balloon angioplasty, reported translesional pressure gradients, and measurements of coronary flow reserve. Reasonable estimates of mean coronary artery flow rates and translesional pressure drops in the absence of angioplasty catheters are obtained. Prior to angioplasty significant flow restriction across a 68% diameter stenosis exists during hyperemic flow conditions. Following successful balloon dilation, increased minimal cross-sectional area (residual 40% diameter stenosis) results in an improved flow rate-pressure drop relation. Despite minimal flow restriction during hyperemic conditions following angioplasty remodeling, residual luminal constriction leads to elevated wall shear stress levels within the entry region of the stenosis. The flow analysis described may be of clinical utility in evaluating the hemodynamic significance of the anatomic severity of stenoses in coronary and peripheral arteries before and after endovascular therapeutic interventions.

Flow measurements in an aortocoronary bypass graft casting.

Flow visualization and pressure measurements were carried out in a singel valve saphenous vein casting which was made from a saphenous vein segment obtained from a bypass patient at Cedars Sinai Medical Center. Dye was injected to understand the flow around the valve. The dye showed very complex flow patterns around the valve and in the valve sinus, and the cavity formed by a ligated branch. For steady flow, pressure drops across the valve were 0.72, 2.0 and 6.3 mmHg for the physiological flow rates of 45, 84, and 169 ml/min, respectively. Overall pressure drop across the casting (compared to Poiseuille flow for a straight tube) increased with the flow rate, being 130 to 290 percent higher over this flow rate range. In the case of pulsatile flow, pressure drops across the valve were 0.95 and 3.0 mmHg for the flow rates of 47 and 87 ml/min which were 26 and 43 percent higher than those of steady flow. Overall pressure drop was 220 and 360 percent higher for those flow rates compared to Poiseuille flow. The measured spatial pressure distributions along the casting and flow visualization indicated the global nature of the flow field with the accelerated flow through the valve separating and reattaching downstream along the wall in the pressure recovery region. Atherosclerosis may be prone to occur in the lower shear region along the wall beyond the valve tip in the reattachment region, as we have observed in vivo in rabbit experiments.