Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predominantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase 'paradigm shift' in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and colleagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the management of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples' dogma makes his contribution truly a genuine paradigm shift.

Risk factors associated with increased prevalence of abdominal aortic aneurysm in women.

BACKGROUND: Four randomized trials of men aged 65-80 years showed that aneurysm-related mortality was reduced by 40 per cent by ultrasound screening. Screening is considered economically viable when the prevalence of abdominal aortic aneurysm (AAA) is 1·0 per cent or higher. This is not the case for women, in whom the prevalence of AAA is less than 1 per cent. The aim of the present investigation was to determine the prevalence of AAA 3·0 cm or larger in women screened with ultrasound imaging, the risk factors associated with AAA in this population, and whether high-risk groups can be identified with an AAA prevalence of 1 per cent or greater. METHODS: Demographic data and risk factors were collected from the first 50 000 women who attended for private cardiovascular screening in the UK. Tests included ultrasound screening for AAA, ankle : brachial pressure index (ABPI), carotid duplex imaging for carotid atherosclerosis, and electrocardiography for atrial fibrillation. RESULTS: AAA was detected in 82 of 50 000 women screened; these aneurysms were rare below the age of 66 years (7 of 24 499). In the 66-85-years age group there were 72 AAAs in 25 170 women (0·29 per cent). Univariable analysis demonstrated that a history of stroke/transient ischaemic attack (TIA), hypertension, smoking, atrial fibrillation, ABPI of less than 0·9 and internal carotid artery stenosis of at least 50 per cent were associated with an increased prevalence of AAA (P < 0·001). In multivariable linear logistic regression of risk factors, age 76 years or more, history of stroke/TIA, hypertension and smoking were independent predictors of AAA. This model had an area under the receiver operating characteristic (ROC) curve (AUC) of 0·711 (95 per cent c.i. 0·649 to 0·772) and could identify 2235 women who had 22 AAAs (prevalence 0·98 per cent). By adding ABPI, atrial fibrillation and carotid stenosis, the prediction improved to an AUC of 0·775 (0·724 to 0·826). This model could identify 3701 women who had 58 AAAs (prevalence 1·57 per cent). CONCLUSION: This report should stimulate consideration of a targeted AAA screening programme for women aged over 65 years.

Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications for Statin Therapy.

OBJECTIVE: Recent studies with asymptomatic carotid patients on best medical management have shown that the annual risk of stroke has decreased to approximately 1%. There is no evidence that a similar decrease in mortality has occurred. In addition, the intensity of statin therapy for these patients has not yet been determined. The aims of this review were to determine (a) the reported long-term all-cause and cardiac-related mortality in patients with asymptomatic carotid stenosis (ACS) > 50%, (b) whether there has been a decrease in mortality in recent years, (c) the available methods of mortality risk stratification, and (d) whether the latest ACC/AHA guidelines on the treatment of serum lipids can be applied to this group of patients. METHODS: Systematic review of PubMed, EuroPubMed, and Cochrane Library and meta-analysis using random effects for pooled proportions were performed regarding long-term all-cause and cardiac-related mortality and the associated risk factors in ACS patients. The last day for literature search was October 30, 2014. RESULTS: Seventeen studies were retrieved reporting 5-year all-cause mortality in 11,391 patients with ACS >50%. The 5-year cumulative all-cause mortality across all 17 studies was 23.6% (95% CI 20.50-26.80). Twelve additional studies, reporting both all-cause and cardiac mortality with a minimum of 2 year follow-up and involving 4,072 patients were identified. Of the 930 deaths reported, 589 (62.9%; 95% CI 58.81-66.89) were cardiac-related. This translates into an average cardiac-related mortality of 2.9% per year. CONCLUSIONS: All-cause and cardiac mortality in ACS patients are very high. Although risk stratification is possible, most patients are classified as high risk. In view of this high risk, aggressive statin therapy is indicated if the new ACC/AHA guidelines on serum lipids are to be adhered to.

Descending phlebography in patients with venous ulceration: hemodynamic implications.

AIM: The aim of this paper is to report on the hemodynamic significance of the various degrees reflux as demonstrated on descending phlebography, by comparing the phlebographic findings with ambulatory venous pressure (AVP) measurements. METHOD: Thirty-two patients (45 affected limbs) with active or healed venous ulceration were admitted to the study. Descending phlebography with grading of reflux (0-4 using Herman's grading), AVP and refilling time 90 (RT90) were performed in all patients. In addition, the presence of deep to superficial reflux into the great saphenous vein at the sapheno-femoral junction, thigh incompetent perforating veins, small saphenous vein at the saphenopopliteal junction and incompetent calf perforating veins was recorded using ascending functional phlebography. The examined limbs were separated into two groups according to the Grade of reflux. Group I consisted of limbs in which popliteal valve incompetence was not demonstrated on descending phlebography, i.e., Grades 0-2 (18 limbs). Group II consisted of limbs with popliteal reflux as demonstrated by descending venography, i.e., grades 3 and 4 (27 limbs). RESULTS: In Group I the mean AVP ± SD was 47.2 ± 9.3 mmHg (range 31-67 mmHg). After the application of the ankle tourniquet to exclude the effects of the superficial venous incompetence on the pressure recordings, the mean AVP ± SD became 28.1 ± 9.9 mmHg (range 11-44) (paired t test: P < 0.001). In Group II (limbs with incompetent popliteal valves) the mean AVP ± SD was 71.6 ± 12.7 mmHg (range 49-95 mmHg) before the tourniquet. This was significantly higher than in Group I (t test: P < 0.001). The application of the ankle tourniquet in this group produced a small but significant decrease in the AVP (mean AVP ± SD: 66 ± 14.5 mmHg) (paired t test: P < 0.001). CONCLUSION: Incompetence of the femoral valves in the presence of competent popliteal valves adds very little to the hemodynamic abnormality produced by superficial venous reflux. In the majority of these patients, there is co-existing reflux from deep to superficial veins with associated superficial valve incompetence which is responsible for the venous hypertension, skin changes and ulceration. The hemodynamic changes which in the past had been associated with deep venous insufficiency (AVP >45 mmHg and RT90 < 14 seconds despite the application of an ankle tourniquet) occur only when there is popliteal incompetence.

Automated calcium burden measurement in internal carotid artery plaque with CT: a hierarchical adaptive approach.

AIM: Calcium burden measurement in internal carotid artery (ICA) plaque could play an important role in assessing stroke risk and stenosis quantification in the ICA. We propose an automatic method for labelling calcified plaques in ICA in CT images. METHODS: Our approach builds upon the mean shift paradigm via an adaptive thresholding strategy. The data consists of single CT slices from 75 patients, with variety of plaque sizes and number of calcium regions. The manual measurements were carried out by a neuroradiologist for benchmarking. The calcium burden was measured as the area of the labelled plaque. Various metrics were employed to compare manual and automated measurements including correlation coefficient (CC), dice similarity (DS), Jacard Index (JI), polyline distance metric (PDM) and precision of merit (PoM). RESULTS: We found that our automated method of calcium area characterization performed accurately compared to manual measurements with CC=0.978, and PoM=0.915. The PDM, DS, and JI, also indicate a good performance with a mean DS=0.85 (SD=0.085), a mean JI=0.747 (SD=0.12), and a mean PDM=0.195 (SD=0.177). CONCLUSION: The proposed approach for calcium burden measurement, yields reasonably accurate labelling of calcified plaque when benchmarked against manual measurements. The approach is independent of the number and size of calcium regions, and the prototype design shows encouraging results to be adaptable to clinical practice.

Comparison between insulin resistance indices and carotid and femoral atherosclerosis: a cross-sectional population study.

AIM: The aim of this study was to investigate the association between commonly used insulin resistance (IR) indices and the presence and extent of carotid and femoral atherosclerosis in a general population setting. METHODS: Cross-sectional analysis of 762 volunteers from the ongoing epidemiological Cyprus Study (46.6% male; mean age=60.5±10.2). 1) Carotid intima-media thickness (IMTcc), 2) carotid and femoral atherosclerotic plaque presence, 3) total plaque area in the carotid/femoral bifurcations (sum of the largest plaques in each carotid/femoral bifurcation-SPAcar/fem), and 4) total plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured using ultrasound at baseline. The HOMA-IR, QUICKI and McAuley indices as well as fasting insulin levels were estimated and their quartiles were used in linear and logistic regression analysis. RESULTS: All IR indices studied were strongly associated with IMTcc (P<0.01for all) even after adjustment for age and sex and exclusion of diabetic subjects. However, when looking at plaque presence and size (i.e.area) only the HOMA-IR and especially the McAuley Index were associated with both carotid plaque presence (ORadj=1.17; 95%CI=1.01 to 1.36; P=0.03 and ORadj=0.86; 95%CI=0.74 to 0.99; P=0.04 respectively) and area (ORadj=0.10; 95%CI=0.008 to 0.20; P=0.03 and ORadj=-0.11; 95%CI=-0.20 to -0.009; P=0.03 respectively), after adjustment. The McAuley Index remained a significant predictor of both carotid plaque presence and area even after exclusion of diabetic subjects (P=0.04). CONCLUSION: Our results show that while all indices were associated with carotid IMT, supporting a strong role for IR in intimal-medial thickening, only the HOMA-IR and especially the McAuley Index were associated with both carotid plaque presence and area, after adjustment. This highlights the importance of including triglyceride levels in estimating the risk for atherosclerotic plaque in the carotids as well as the possible differences in determinants for atherosclerosis between arterial sites.

A survey of the European Venous Forum on education and training in venous surgery and phlebology in Europe.

AIM: Venous training in Europe is lacking a formal curriculum among various specialties related to management of venous diseases. We conducted a survey in order to have a snapshot on the actual education and training level among physicians practicing currently venous surgery and phlebology in Europe. METHODS: From April 7, 2014 to June 11, 2014 a survey was carried out using the Survey Monkey system, including 11 main questions covering all the domains of training and education in venous surgery and phlebology. The questionnaire was sent to all physicians included in the current mailing list of the European Venous Forum (EVF) and the Mediterranean League of Angiology and Vascular Surgery. Two questions were particularly addressed to those physicians who had attended the EVF hands-on workshop (HOW) at least once. RESULTS: The response rate was 24% (97/400) and 51.5% of them were practicing in a hospital service. Most responders were vascular surgeons (67.7%), followed by angiologists (19.4%). Only half of the responders felt as being competent to manage the whole spectrum of venous diseases successfully after completion of their training, while a few were able to perform endovenous ablations and even less more advanced venous interventions. Formal training in Duplex ultrasound was undertaken only in 55.2%. The majority suggested that a venous training program should be a separate part of their specialty rotation and should be organized at a national or European level, or even by a specific scientific society. Over 95% of those physicians who already participated in the EVF HOW considered the knowledge they acquired there as useful for their practice. CONCLUSION: There is currently an important need for more specialized venous training for all physicians involved in the diagnosis and management of venous diseases. Therefore all local, national and international initiatives should be encouraged to improve education in this field.

Prediction of the time period of stroke based on ultrasound image analysis of initially asymptomatic carotid plaques.

Non-invasive ultrasound imaging of carotid plaques can provide information on the characteristics of the arterial wall including the size, morphology and texture of the atherosclerotic plaques. Several studies were carried out that demonstrated the usefulness of these feature sets for differentiating between asymptomatic and symptomatic plaques and their corresponding cerebrovascular risk stratification. The aim of this study was to develop predictive modelling for estimating the time period of a stroke event by determining the risk for short term (less or equal to three years) or long term (more than three years) events. Data from 108 patients that had a stroke event have been used. The information collected included clinical and ultrasound imaging data. The prediction was performed at base line where patients were still asymptomatic. Several image texture analysis and clinical features were used in order to create a classification model. The different features were statistically analyzed and we conclude that image texture analysis features extracted using Spatial Gray Level Dependencies method had the best statistical significance. Several predictive models were derived based on Binary Logistic Regression (BLR) and Support Vector Machines (SVM) modelling. The best results were obtained with the SVM modelling models with an average correct classifications score of 77±7% for differentiating between stroke event occurrences within 3 years versus more than 3 years. Further work is needed in investigating additional multiscale texture analysis features as well as more modelling techniques on more subjects.

Medical management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence- based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤7%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.

Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Quantitation of reflux and outflow obstruction in patients with CVD and correlation with clinical severity.

AIM: Chronic venous disease (CVD) is the result of venous reflux, obstruction or a combination of both. So far, attempts to correlate venous hemodynamic measurements with symptoms and signs of CVD have produced poor to moderate results, probably because of lack of methods to quantitate obstruction and combine measurements of reflux and obstruction. Our hypothesis is that the combination of quantitative measurements of (a) overall reflux (superficial and deep) and (b) overall outflow resistance i.e. including the collateral circulation would provide a hemodynamic index that should be related to the severity of the disease. METHODS: Twenty-five limbs with chronic venous disease and 1 limb from a healthy volunteer (VCSS 0-13) were studied. The clinical CEAP classification was C0 in one limb, C1 in 2 limbs, C2 in 10 limbs, C3 in 3 limbs, C4 in 1 limb, C5 in 6 limbs and C6 in 3 limbs. Air-plethysmography was used to measure reflux (VFI in mL/s) when the subject changed position from horizontal to standing. Subsequently, with the subject horizontal and the foot elevated 15 cm, simultaneous recordings of pressure and volume were made on release of a proximal thigh cuff inflated to 70 mmHg. Pressure change was recorded with a needle in the foot and volume change with air-plethysmography. Flow (Q in mL/min) was calculated at intervals of 0.1 seconds from tangents on the volume outflow curve. Outflow resistance (R) was calculated at 0.1 second intervals by dividing pressure by the corresponding flow (R=P/Q). R increased markedly at pressures lower than 25 mmHg due to decrease in vein cross-sectional area, so resistance at 25 mmHg (R25) was used in this study. RESULTS: In a multivariable linear regression analysis with VCSS as the dependent variable, both VFI and R25 were independent predictors (P<0.001). Using the constant (0.595) and regression coefficients, the regression equation provided a Hemodynamic Index (HI) or estimated VCSS=0.595 + (VFI x 0.41) + (R25 x 98). Thus, HI could be calculated for every patient by substituting VFI and R25 in the equation. HI or calculated VCSS was linearly related to the observed VCSS (r=0.86). CONCLUSION: The results indicate that the combination of quantitative measurements of reflux and outflow resistance provide a hemodynamic index which is linearly related to the VCSS. These findings need to be confirmed in larger series.

Despeckle Filtering for Multiscale Amplitude-Modulation Frequency-Modulation (AM-FM) Texture Analysis of Ultrasound Images of the Intima-Media Complex.

The intima-media thickness (IMT) of the common carotid artery (CCA) is widely used as an early indicator of cardiovascular disease (CVD). Typically, the IMT grows with age and this is used as a sign of increased risk of CVD. Beyond thickness, there is also clinical interest in identifying how the composition and texture of the intima-media complex (IMC) changed and how these textural changes grow into atherosclerotic plaques that can cause stroke. Clearly though texture analysis of ultrasound images can be greatly affected by speckle noise, our goal here is to develop effective despeckle noise methods that can recover image texture associated with increased rates of atherosclerosis disease. In this study, we perform a comparative evaluation of several despeckle filtering methods, on 100 ultrasound images of the CCA, based on the extracted multiscale Amplitude-Modulation Frequency-Modulation (AM-FM) texture features and visual image quality assessment by two clinical experts. Texture features were extracted from the automatically segmented IMC for three different age groups. The despeckle filters hybrid median and the homogeneous mask area filter showed the best performance by improving the class separation between the three age groups and also yielded significantly improved image quality.

Association between serum levels of pro-metalloproteinase 1, tissue inhibitor of metalloproteinases 1 and 2 and prevalent cardiovascular disease in a population-based study.

AIM: The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. METHODS: Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models. RESULTS: Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P(for trend)=0.006 and P=0.001, respectively) and inflammatory factors (P(for trend)=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (OR(adjusted)=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (OR(adjusted)=0.25; 95% CI=0.11 to 0.60; P(for trend)=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease. CONCLUSION: A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.

Association of ultrasonic texture and echodensity features between sides in patients with bilateral carotid atherosclerosis.

OBJECTIVES: Our objective was to estimate the correlation of echodensity and textural features, using ultrasound and digital image analysis, between plaques in patients with bilateral carotid stenosis. DESIGN: Cross-sectional observational study. METHODS: Patients undergoing carotid endarterectomy were recruited from Vascular Surgery at the Royal Victoria and Jewish General hospitals in Montreal, Canada. Bilateral pre-operative carotid ultrasound and digital image analysis was performed to extract echodensity and textural features using a commercially available Plaque Texture Analysis software (LifeQMedical Ltd). Principal component analysis (PCA) was performed. Partial correlation coefficients for PCA and individual imaging variables between surgical and contralateral plaques were calculated with adjustment for age, sex, contralateral stenosis, and statin use. RESULTS: In the whole group (n = 104), the six identified PCA variables and 42/50 individual imaging variables were moderately correlated (r = .211-.641). Correlations between sides were increased in patients with ≥50% contralateral stenosis and symptomatic patients. CONCLUSION: Textural and echodensity features of carotid plaques were similar between two sides in patients with bilateral stenosis, supporting the notion that plaque instability is determined by systemic factors. Patients with unstable features of one plaque should perhaps be monitored more closely or treated more aggressively for their contralateral stenosis, particularly if this is hemodynamically significant.