Is the Incidence of Abdominal Aortic Aneurysm Declining in the 21st Century? Mortality and Hospital Admissions for England & Wales and Scotland

BackgroundBetween 1951 and 1995 there was a steady increase in age-standardised deaths from all aortic aneurysms in men, from 2 to 56 per 100,000 population in England &; Wales, supporting an increase in incidence. More recently, evidence from Sweden and elsewhere suggests that now the incidence of abdominal aortic aneurysm (AAA) may be declining.MethodsNational statistics for hospital admissions and deaths from AAA, after population age-standardisation, were used to investigate current trends in England &; Wales and Scotland.ResultsBetween 1997 and 2009 there has been a reduction in age-adjusted mortality from AAA from 40.4 to 25.7 per 100,000 population for England &; Wales and from 30.1 to 20.8 per 100,000 population in Scotland. The decrease in mortality was more marked for men than women. Mortality decreased more than 2-fold in those <75 years versus 25% only in those >75 years. During this same time period the elective hospital admissions for AAA repair have only increased in the population >75 years.ConclusionsThese data suggest that the age at which clinically-relevant aneurysms present has increased by 5–10 years and that incidence of clinically-relevant AAA in men in England &; Wales and Scotland is declining rapidly. The reasons for this are unclear.     

A systems-based modelling approach using transurethral resection of the prostate (TURP) specimens yielded incremental prognostic significance to Gleason when predicting long-term outcome in men with localized prostate cancer

Study Type – Prognosis (individual cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Systems models have been successfully utilised to accurately define risk in men with prostate cancer. This study addresses the challenges when using TURP specimens to yield predictive models.

OBJECTIVE

? To develop a systems‐based model for predicting prostate cancer‐specific survival (PCSS) using a conservatively managed cohort with clinically localized prostate cancer and long‐term follow‐up.

PATIENTS AND METHODS

? Transurethral prostate (TURP) specimens in tissue microarray format and medical records from a 758 patient cohort were obtained. ? Slides were stained with haematoxylin and eosin (H&E), imaged and digitally outlined for invasive tumour. ? Additional sections were analysed with two multiplex quantitative immunofluorescence (IF) assays for cytokeratin‐18 (epithelial cells), 4′‐6‐diamidino‐2‐phenylindole(nuclei), p63/high‐molecular‐weight keratin (basal cells), androgen receptor (AR) and α‐methyl CoA‐racemase, Ki67, phosphorylated AKT (pAKT)and CD34. ? Images were acquired with spectral imaging software. H&E and IF images were evaluated with image analysis algorithms; feature data were integrated with clinical variables to construct prognostic models for outcome.

RESULTS

? Using a training set of 256 patients with 24% events, one clinical variable (Gleason score) and two tissue‐specific characteristics (H&E morphometry and tumour‐specific pAKT levels) were identified (concordance index [CoI] 0.79, sensitivity 76%, specificity 86%, hazard ratio [HR] 6.6) for predicting PCSS. ? Validation on an independent cohort of 269 patients with 29% events yielded a CoI of 0.76, sensitivity 59%, specificity 80% and HR of 3.6. ? Both H&E and IF features were selected in a multivariate setting and added incremental prognostic value to the Gleason score alone (CoI 0.77 to CoI 0.79). ? Furthermore, global Ki67 expression and AR levels in Gleason grade 3 tumours were both univariately associated with outcome; however, neither was selected in the final model.

CONCLUSION

? A previously validated prostate needle‐biopsy systems modelling approach that integrates clinical data with reproducible methods to assess H&E morphometry and biomarker expression, provided incremental benefit to the TURP Gleason score for predicting PCSS. ? Ki67 and AR, known to be associated with outcome in the prostate needle biopsy, were not associated with PCSS in multivariate models using TURP specimens.     

Non-alcoholic fatty liver disease: is iron relevant?

Non-alcoholic fatty liver disease (NAFLD) is a common and ubiquitous disorder (Bedogni et al. in Hepatology 42:44–52, 2005; Bellentani et al. in Ann Intern Med 132:112–117, 2000) which in a proportion of subjects leads to non-alcoholic steatohepatitis (NASH), advanced liver disease and hepatocellular carcinoma. Although the factors responsible for progression of disease are still uncertain, there is evidence that insulin resistance (IR) is a key operative mechanism (Angulo et al. in Hepatology 30:1356–1362, 1999) and that two stages are involved. The first is the accumulation of triglycerides in hepatocytes followed by a “second hit” which promotes cellular oxidative stress. Several factors may be responsible for the induction of oxidative stress but hepatic iron has been implicated in various studies. The topic is controversial, however, with early studies showing an association between hepatic iron (with or without hemochromatosis gene mutations) and the progression to hepatic fibrosis. Subsequent studies, however, could not confirm an association between the presence of hepatic iron and any of the histological determinants of NAFLD or NASH. Recent studies have reactivated interest in this subject firstly, with the demonstration that hepatic iron loading increases liver cholesterol synthesis with increased lipid deposition in the liver increasing the cellular lipid burden and secondly, a large clinical study has concluded that hepatocellular iron deposition is associated with an increased risk of hepatic fibrosis, thus, strongly supporting the original observation made over a decade ago. An improvement in insulin sensitivity has been demonstrated following phlebotomy therapy but a suitably powered controlled clinical trial is required before this treatment can be implemented.     

Fluoroscopy as a surrogate for lung tumour motion

Objectives

The aim of this article was to test a simple approach of using pixel density values from fluoroscopy images to enable gated radiotherapy.

Methods

Anterior and lateral (LAT) from images were acquired from 18 patients referred for radical radiotherapy for non-small cell lung cancer for a period of 30–45 s. The amplitude of movement and the number of breathing cycles were determined in the right–left (RL) and superoinferior (SI) directions on the anterior images and the anteroposterior (AP) and SI directions on the lateral images. The breathing pattern was created by analysing the variation in a summation of pixel values within a defined area. The greatest and lowest 30% of pixel values were set as the duty cycle to represent inhale and exhale amplitude-based gating.

Results

A median of eight breathing cycles was captured for each patient with a duration of 2.2–11.8 s per cycle. The mean (range) motion was 4.7 mm (2.4–5.8 mm), 7.2 mm (2.3–17.6 mm), 6.2 mm (1.9–13.8 mm) and 4.8 mm (2.4–11.3 mm) in the RL, SI (AP), SI (LAT) and AP directions, respectively. A total of 10/14 anterior videos and 7/11 LAT videos had correlations between motion and breathing of >0.6. Margins of 5.5 mm, 6.8 mm and 6.6 mm in the RL, SI and AP directions, respectively, were determined to gate in exhale. The benefit of gating was greater when motion was >5 mm.

Conclusion

The simple approach of using pixel density values from fluoroscopy images to distinguish inhale from exhale and enable gating was successfully applied in all patients. This technique may potentially provide an accurate surrogate for tumour position.Tumour motion remains one of the challenges when delivering radical radiotherapy, particularly in lung cancer. The large margins required to encompass motion can increase the radiation dose to normal tissue. Techniques used to reduce margins involve synchronising the treatment delivery to the motion, which conventionally requires a surrogate for tumour location. Such surrogates for tumour location include infrared marker blocks placed on the xiphoid process (RPM; Varian Medical systems, Palo Alto, CA), spirometers [1] and temperature of breathing airflow [2].Fluoroscopy has been used to determine lung tumour motion either on its own [3,4] or in combination with CT [5], and has the advantage of being available on the majority of the new generation linear accelerators. However, verifying the tumour position using fluoroscopy either requires the tumour to be visible or requires markers to be implanted in the tumour. Implanting markers is an invasive procedure with associated morbidity, which lung cancer patients may not tolerate.This study tests a simple approach of using pixel density values from fluoroscopy images as a surrogate of tumour motion [6], to distinguish inhale from exhale and to enable gated radiotherapy and subsequent margin reduction.     

Technical note: 9-month repositioning accuracy for functional response assessment in head and neck chemoradiotherapy

The use of thermoplastic immobilisation masks in head and neck radiotherapy is now common practice. The accuracy of these systems has been widely studied, but always within the context and time frame of the radiation delivery—some 6–8 weeks. There is growing current interest in the use of functional imaging to assess the response to treatment, particularly in the head and neck. It is therefore of interest to determine the accuracy with which functional images can be registered to baseline CT over the extended periods of time used for functional response assessment: 3–6 months after radiotherapy. In this study, repeated contrast-enhanced diagnostic quality CT and mid-quality localisation CT from a positron emission tomography/CT scanner were available for five time points over a period of 9 months (before, during and up to 6 months after chemoradiotherapy) for a series of eight patients enrolled in a clinical pilot study. All images were acquired using thermoplastic immobilisation masks. The overall set-up accuracy obtained from this 9-month study of 5.5±3.2 mm (1 standard deviation) and 1.9±1.3° (1 standard deviation) is in agreement with published data acquired over 6–8 weeks. No statistically significant change in set-up error was seen with time. This work indicates that thermoplastic immobilisation masks can be used to accurately align multimodality functional image data for assessment of the response to treatment in head and neck patients over extended follow-up periods.Head and neck cancer accounts for 5% of cancers worldwide [1] with approximately 7000 new cases being diagnosed each year in the UK. The majority of patients with squamous cell carcinoma of the head and neck (SCCHN) present with locally advanced disease. Despite recent advances in multimodality therapy and technical delivery of radiotherapy, outcomes remain suboptimal with 5-year survival rates of 50–60%. However, functional image data, provided by positron emission tomography (PET) and dynamic contrast-enhanced MRI (DCE-MRI) or diffusion-weighted MRI (DW-MRI), have been shown to have a number of potentially important applications in external beam radiotherapy for head and neck cancer [2,3]. Functional imaging is routinely used in diagnosis and staging [4], and there is increasing current interest in its application to localisation and delineation of target volumes [5] and normal tissues [6]. There is also growing evidence to support the use of functional imaging for early assessment of the response to therapy [7].Ensuring accurate registration between functional and anatomical data is clearly of paramount importance and much work has been done to date developing and testing immobilisation systems for use in radiotherapy planning and delivery. Thermoplastic mask systems have been described providing set-up accuracy in the head and neck of 2.5±1.4 mm, with no increase in systematic error seen over an 8-week period [8]. Similar accuracy was demonstrated with a polyvinyl chloride mask system [standard deviation (SD)=2.1 mm], with cut-outs in the mask to improve dose sparing to the skin but not affecting accuracy [9]. Studies using cone-beam CT (CBCT) to assess set-up accuracy have shown mean vector lengths of 4.7±1.7 mm intercranially and 7.3±4.5 mm in the neck for the thermoplastic mask [10]. Very similar SDs have been shown by other groups using thermoplastic shells and repeat CT during therapy (1.9 mm, 1 SD, for the upper neck and 5.7 mm, 1 SD, for the lower neck) [11]. Set-up error with thermoplastic masks has been shown to increase linearly with treatment time, with a SD of 1.2 mm calculated for 32 intercranial patients treated supine over 15 min [12]. In a large recent study, 762 CBCT scans were analysed from 11 patients using standard and skin-sparing nine-point thermoplastic masks [13]. The interfraction population (SD) was 1.6 mm (1.1°) (random) and 1.0 mm (1.4°) (systematic). All set-up errors >2 mm for three fractions were corrected before calculating these figures.However, if functional image data are to be accurately aligned with baseline (pre-treatment) imaging to assess response at 3 or 6 months after therapy, use of immobilisation systems over longer time intervals than the 6 or 7 weeks of radiotherapy is clearly of interest. It is well known that head and neck patients often experience dramatic shrinkage of nodal masses in the neck and general weight loss during treatment. This in turn can mean that the thermoplastic shells no longer fit perfectly and may be expected to lead to increased set-up error over longer periods of time; alternatively, weight gain following treatment may potentially reduce immobilisation accuracy. In this paper, we describe an investigation of the accuracy of head and neck patient set-up using a standard five-point thermoplastic shell system during and up to 6 months after the end of induction chemotherapy and definitive chemoradiotherapy (CRT).