Therapeutic potential of exosomes in rotator cuff tendon healing.

Rotator cuff tears are common musculoskeletal injuries that can cause significant pain and disability. While the clinical results of rotator cuff repair can be good, failure of tendon healing remains a significant problem. Molecular mechanisms underlying structural failure following surgical repair remain unclear. Histologically, enhanced inflammation, disorganization of the collagen fibers, calcification, apoptosis and tissue necrosis affect the normal healing process. Mesenchymal stem cells (MSCs) have the ability to provide improved healing following rotator cuff repair via the release of mediators from secreted 30-100 nm extracellular vesicles called exosomes. They carry regulatory proteins, mRNA and miRNA and have the ability to increase collagen synthesis and angiogenesis through increased expression of mRNA and release of proangiogenic factors and regulatory proteins that play a major role in proper tissue remodeling and preventing extracellular matrix degradation. Various studies have shown the effect of exosomes on improving outcome of cutaneous wound healing, scar tissue formation, degenerative bone disease and Duchenne Muscular Dystrophy. In this article, we critically reviewed the potential role of exosomes in tendon regeneration and propose the novel use of exosomes alone or seeded onto biomaterial matrices to stimulate secretion of favorable cellular factors in accelerating the healing response following rotator cuff repair.

Radiographer reporting: A literature review to support cancer workforce planning in England.

OBJECTIVE: Clinical Imaging contributes to screening, diagnosis, planning and monitoring of treatment and surveillance in cancer care. This literature review summarises evidence about radiographer reporting to help imaging service providers respond to Health Education England's 2017 Cancer Workforce Plan project to expand radiographer reporting in clinical service provision. KEY FINDINGS: Papers published between 1992 and 2018 were reviewed (n = 148). Evidence related to dynamic examinations (fluoroscopy, ultrasound) and mammography was excluded. Content was analysed and summarised using the following headings: clinical scope of practice, responsibilities, training, assessment, impact in practice and barriers to expansion. Radiographer reporting is well established in the United Kingdom. Scope of practice varies individually and geographically. Deployment of appropriately trained reporting radiographers is helping the NHS maintain high quality clinical imaging service provision and deliver a cost-effective increase in diagnostic capacity. CONCLUSION: Working within multiprofessional clinical imaging teams, within a defined scope of practice and with access to medical input when required, reporting radiographers augment capacity in diagnostic pathways and release radiologist time for other complex clinical imaging responsibilities.

The UK breast screening program - what you need to know.

Breast cancer is the most commonly diagnosed cancer in women with a lifetime risk of 1 in 8 in the UK. The disease is associated with considerable morbidity and mortality. The UK breast screening program has been in place for almost 30 years and has evolved with improved diagnostic imaging. The overall benefits of the screening program are subject to continued heated debate with multiple potential harms. The aim of this review is to provide the non-breast specialist health-care professional an overview of the evolution of the breast screening program, a summary of the evidence of the benefits, and a description of the harms. In addition, the diagnostic methods currently employed as well as potential future changes to the screening program and imaging techniques will be covered.

Breast fat volume measurement using wide-bore 3 T MRI: comparison of traditional mammographic density evaluation with MRI density measurements using automatic segmentation.

AIM: To compare magnetic resonance imaging (MRI)-derived breast density measurements using automatic segmentation algorithms with radiologist estimations using the Breast Imaging Reporting and Data Systems (BI-RADS) density classification. MATERIALS AND METHODS: Forty women undergoing mammography and dynamic breast MRI as part of their clinical management were recruited. Fat-water separated MRI images derived from a two-point Dixon technique, phase-sensitive reconstruction, and atlas-based segmentation were obtained before and after intravenous contrast medium administration. Breast density was assessed using software from Advanced MR Analytics (AMRA), Linköping, Sweden, with results compared to the widely used four-quartile quantitative BI-RADS scale. RESULTS: The proportion of glandular tissue in the breast on MRI was derived from the AMRA sequence. The mean unenhanced breast density was 0.31±0.22 (mean±SD; left) and 0.29±0.21 (right). Mean breast density on post-contrast images was 0.32±0.19 (left) and 0.32±0.2 (right). There was "almost perfect" correlation between pre- and post-contrast breast density quantification: Spearman's correlation rho=0.98 (95% confidence intervals [CI]: 0.97-0.99; left) and rho=0.99 (95% CI: 0.98-0.99; right). The 95% limits of agreement were -0.11-0.08 (left) and -0.08-0.03 (right). Interobserver reliability for BI-RADS was "substantial": weighted Kappa k=0.8 (95% CI: 0.74-0.87). The Spearman correlation coefficient between BI-RADS and MRI breast density was rho=0.73 (95% CI: 0.60-0.82; left) and rho=0.75 (95% CI: 0.63-0.83; right) which was also "substantial". CONCLUSION: The AMRA sequence provides a fully automated, reproducible, objective assessment of fibroglandular breast tissue proportion that correlates well with mammographic assessment of breast density with the added advantage of avoidance of ionising radiation.

Invasive Scedosporium sternal osteomyelitis following lung transplant: Cured.

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant but rarely causes invasive infection. Treatment remains challenging, particularly due to inherent resistance to multiple antifungal agents. We present a young man with CF who developed invasive sternal and rib infection 10-months following lung transplant. The infection has been clinically and radiologically cured with extensive surgery and triazole therapy. This case highlights the importance of adjunctive surgery in addition to prolonged triazole treatment to manage invasive Scedosporium infections in immunosuppressed patients.

Changing trends in diagnosis, staging, treatment and survival in lung cancer: comparison of three consecutive cohorts in an Australian lung cancer centre.

BACKGROUND: Lung cancer accounts for significant morbidity and mortality worldwide. The effect of recent changes in demographics and management on outcomes in Australia has not been clearly defined. AIMS: To compare three consecutive lung cancer cohorts to evaluate emergent differences in diagnosis, management and mortality. METHODS: For comparative analysis, 2119 lung cancer patients were divided into three successive cohorts. Current death data were sought from the Victorian Cancer Registry. RESULTS: Age at diagnosis, mode of presentation and pathology did not significantly differ between the groups. Significantly more females were diagnosed with lung cancer in the most recent cohort (P = 0.04). Amongst non-small-cell lung cancer patients, there were more adenocarcinomas and less large cell carcinomas in the latest cohort (P = <0.01). More patients from the most recent cohort were staged pathologically and via positron emission tomography and fewer were clinically staged (P = <0.01). The most recent cohort had a greater proportion of Stage IV disease (P = <0.01) and more curative surgical or combined modality radiotherapy and chemotherapy versus palliative radiotherapy or supportive care (P = <0.01). Overall 5-year survival improved significantly in the most recent cohort, even after adjustment for age, gender and stage (P = <0.01). CONCLUSION: Comparison of three lung cancer patient cohorts diagnosed between 2001 and 2013 highlights emergent changes in lung cancer demographics, management and outcomes. These include recent increases in proportion of females, pathological and positron emission tomography staging, and Stage IV disease, as well as improved survival despite later stage disease.

Practitioner compression force variability in mammography: a preliminary study.

OBJECTIVE: This preliminary study determines whether the absolute amount of breast compression in mammography varies between and within practitioners. METHODS: Ethics approval was granted. 488 clients met the inclusion criteria. Clients were imaged by 14 practitioners. Collated data included Breast Imaging Reporting and Data System (BI-RADS) density, breast volume, compression and practitioner code. RESULTS: A highly significant difference in mean compression used by different practitioners (p<0.0001 for each BI-RADS density) was demonstrated. Practitioners applied compression in one of three ways using either low, intermediate or high compression force, with no significant difference in mean compression within each group (p=0.99, p=0.70, p=0.54, respectively). Six practitioners showed a significant correlation (p<0.05) between compression and BI-RADS grade, with a tendency to apply less compression with increasing BI-RADS density. When compression was analysed by breast volume there was a wide variation in compression for a given volume. The general trend was the application of higher compression to larger breast volumes by all three practitioner groups. CONCLUSION: This study presents an insight into practitioner variation of compression application in mammography. Three groups of practitioners were identified: those who used low, intermediate and high compression across the BI-RADS density grades. There was wide variation in compression for any given breast volume, with trends of higher compression demonstrated for increasing breast volumes. Collation of further studies will facilitate a new perspective on the analysis of practitioner, client and equipment variables in mammography imaging. ADVANCES IN KNOWLEDGE: For the first time, it has been practically demonstrated that practitioners vary in the amount of compression applied to breast tissue during routine mammography.

Pressure and breast thickness in mammography--an exploratory calibration study.

OBJECTIVE: To perform a calibration study to provide data to help improve consistency in the pressure that is applied during mammography. METHODS: Automatic readouts of breast thickness accuracy vary between mammography machines; therefore, one machine was selected for calibration. 250 randomly selected patients were invited to participate; 235 agreed, and 940 compression data sets were recorded (breast thickness, breast density and pressure). Pressure (measured in decanewtons) was increased from 5 daN through 1-daN intervals until the practitioner felt that the pressure was appropriate for imaging; at each pressure increment, breast thickness was recorded. RESULTS: Graphs were generated and equations derived; second-order polynomial trend lines were applied using the method of least squares. No difference existed between breast densities, but a difference did exist between "small" (15×29 cm) and "medium/large" (18×24/24×30 cm) paddles. Accordingly, data were combined. Graphs show changes in thickness from 5-daN pressure for craniocaudal and mediolateral oblique views for the small and medium/large paddles combined. Graphs were colour coded into three segments indicating high, intermediate and low gradients [≤-2 (light grey); -1.99 to -1 (mid-grey); and ≥-0.99 (dark grey)]. We propose that 13 daN could be an appropriate termination pressure on this mammography machine. CONCLUSION: Using patient compression data we have calibrated a mammography machine to determine its breast compression characteristics. This calibration data could be used to guide practice to minimise pressure variations between practitioners, thereby improving patient experience and reducing potential variation in image quality. ADVANCES IN KNOWLEDGE: For the first time, pressure-thickness graphs are now available to help guide mammographers in the application of pressure.

Influence of imaging on touch imprint cytology of breast lesions.

PURPOSE: Touch imprint cytology (TIC) facilitates rapid diagnosis of breast diseases in women attending triple assessment clinics. Some pathologists, in our centre, feel that pathological interpretation of TIC slides is contentious when the lesions are radiologically indeterminate (R3), as these can lead to potentially higher false positive or false negative cytology results. We hypothesised that: '(R3) lesions are more likely to have higher false positive or false negative TIC and/or be inadequate for TIC assessment'. In other words, 'imaging influences cytological classification especially when indeterminate'. METHODS: Review of the data collected in our centre between December 2003 and July 2005. All patients who attended the one stop symptomatic breast clinic and had a TIC performed following an ultrasound (US) guided core biopsy (CB) were included. Demographic, radiological, cytological and core biopsy grading data were collected. Cytology grading was correlated with radiology classification to assess our hypothesis. RESULTS: A total of 248 patients underwent 254 CB/TIC. The average patient's age of the group was 54 years (range of 29-95). On TIC, 186 (73%) were deemed malignant, 23(9%) benign while 33(13%) were inadequate for assessment. There was no false positive or false negative TIC. There was good correlation between TIC and CB results (p<0.0001). Thirty-three cases were inadequate (C1) for cytology assessment, of these 16 (48.5%) were indeterminate on imaging. R3 lesions were 6 times more prone to have C1 cytology (p<0.0001). CONCLUSION: Touch imprint cytology is a reliable and efficient method in running a one stop breast clinic, with the backup of full tissue diagnosis. Careful selection of cases that would benefit from this technique is highly recommended as a significant number of radiologically indeterminate lesions are likely to be insufficient for cytological assessment. Further prospective trials are required to assess this further. Until then the diagnosis in this sub-group should depend on core biopsy.

A novel breast tissue density classification methodology.

It has been shown that the accuracy of mammographic abnormality detection methods is strongly dependent on the breast tissue characteristics, where a dense breast drastically reduces detection sensitivity. In addition, breast tissue density is widely accepted to be an important risk indicator for the development of breast cancer. Here, we describe the development of an automatic breast tissue classification methodology, which can be summarized in a number of distinct steps: 1) the segmentation of the breast area into fatty versus dense mammographic tissue; 2) the extraction of morphological and texture features from the segmented breast areas; and 3) the use of a Bayesian combination of a number of classifiers. The evaluation, based on a large kappa = 0.81 and 0.67 for the two data sets) between automatic and expert-based Breast Imaging Reporting and Data System mammographic density assessment.

Acute visual loss induced by dexamethasone during neoadjuvant docetaxol.

We present a case of a female patient who developed acute onset of visual loss due to central serous retinopathy as a consequence of steroid premedication for docetaxol given as second line neoadjuvant chemotherapy for breast cancer. Central serous retinopathy is a recognised association with steroids but has not been previously reported in association with the management of solid tumours. Reduction in steroid dose and duration permitted recovery of her visual acuity while allowing completion of the prescribed chemotherapy regimen. An overview of the presentation, pathogenesis, aetiologies and management of central serous retinopathy is given.

Can radiographers read screening mammograms?

AIM: To evaluate the ability of radiographers to read screening mammograms in the National Health Service Breast Screening Programme (NHSBSP). MATERIALS AND METHODS: Two radiographers read a test set of 1000 screening mammograms previously reported by a consultant radiologist. Three radiographers then acted as a second reader for 54,000 screening mammograms, their recall results are presented. Four consultant radiologists and three film reading radiographers were timed while reading 2500 mammograms each. RESULTS: When reading the test mammograms the two radiographers recalled all the cancers previously detected by the radiologist at the original screen read. They also recalled 32/90 women who subsequently presented with interval cancers. As a second reader the radiographers had similar recall and cancer detection rates to the radiologists (P>0.05). Double reading detected 9% more cancers. The radiographers take the same length of time to film read as radiologists (P>0.05). CONCLUSION: Radiographers are able to read screening mammograms at least as well as radiologists and do not take longer to do so.

Multiple 14G stereotactic core biopsies in the diagnosis of mammographically detected stellate lesions of the breast.

AIM: The aim of this retrospective study was to measure the accuracy of stereotactic guided 14 gauge core biopsy in distinguishing between benign and malignant causes of a mammographically detected stellate breast lesion and to assess the impact of the number of core samples taken on the sensitivity for detection of malignancy. MATERIALS AND METHODS: Seventy-two patients with mammographically detected stellate lesions of the breast formed the study group. All patients in the study group underwent multiple 14 gauge core biopsies using prone stereotactic breast biopsy equipment. The diagnostic accuracy of the technique was measured by retrospectively comparing the outcome with the core biopsy results. The result of each core sample was separately recorded to allow analysis of the effect of increasing the number of samples on accuracy. RESULTS: Nine of 72 (12%) did not have surgery. Forty of 72 (56%) had a benign surgical outcome and 23/72 (32%) a malignant surgical outcome [7/72 (10%) non-invasive, 16/72 (22%) invasive carcinoma]. The absolute sensitivity for multiple stereotactic guided core biopsies of stellate lesions for the detection of malignancy was 78% with a complete sensitivity of 100%. The sensitivity for the detection of invasive carcinoma was 94% (15 out of 16 patients). No statistically significant improvement in sensitivity was shown for multiple samples vs one sample, but in two patients, malignant tissue was only found in core samples 6-9, the first five cores showing atypia only. CONCLUSION: Multiple stereotactic guided 14 gauge core biopsies accurately distinguish malignant from benign causes of stellate breast lesions. When core biopsy histology is malignant, therapeutic surgery can be planned. When the core biopsy shows typical features of a benign radial scar, diagnostic surgical excision may not be required to confirm the diagnosis.Kirwan, S. E., (2000). Clinical Radiology55, 763-766.

One year's clinical experience with unenhanced spiral computed tomography for the assessment of acute loin pain suggestive of renal colic.

OBJECTIVE: To assess the use of unenhanced spiral computed tomography (CT) as the primary investigation of choice for suspected acute renal colic in clinical urological practice. Patients and Methods Between 1 August 1997 and 31 July 1998, all patients attending a hospital accident and emergency department with acute loin pain suggestive of renal colic underwent a physical examination, urine analysis, plain abdominal radiography (if clinically indicated) and unenhanced spiral CT. The effective radiation dose and financial cost of unenhanced spiral CT and standard three-film emergency intravenous urography (IVU) were calculated. RESULTS: In all, 116 patients were assessed, 63 of whom had calculi and related secondary phenomena of obstruction identified on unenhanced spiral CT. There were two false-positive and one false-negative result. An alternative urinary tract diagnosis was made in four patients, including two with renal cell carcinoma and one ureteric transitional cell carcinoma. Causes other than in the urinary tract were diagnosed in three patients, i.e. two with ovarian cyst and one with sigmoid diverticulitis. The effective radiation dose of unenhanced spiral CT was 4.7 mSv and that for three-film IVU was 1.5 mSv. The costs of both IVU and unenhanced spiral CT were identical. CONCLUSIONS: Unenhanced spiral CT allows a rapid, contrast-medium-free, anatomically accurate diagnosis of urinary tract calculi and in the present series had a sensitivity of 98% and a specificity of 97%. CT provided an alternative diagnosis in 6% of patients. These advantages must be weighed against the threefold greater radiation dose of unenhanced spiral CT than with three-film IVU, and in practice the requirement for a radiologist to interpret routine axial scans.

Use of the site percutaneous breast biopsy device.

A new technique is described for image guided percutaneous diagnostic excision biopsy of non-palpable mammographically detected breast lesions. This method involves insertion of a localizing guide wire under stereotactic guidance followed by insertion of the 15 mm diameter biopsy device which is positioned within the breast immediately proximal to the target lesion. A cylindrical cannula is advanced over the lesion which is then separated from the surrounding breast tissue by deploying a garrote wire at the distal end of the cannula. The biopsy device is then removed with the target lesion contained within the cannula. The mammographic lesion is excised without removing any excess adjacent breast tissue, and in one piece, so allowing histological examination of the whole lesion. The experience of the first three cases is described with imaging and histological correlation.

Comparison and evaluation of rigid, affine, and nonrigid registration of breast MR images.

PURPOSE: A new nonrigid registration method, designed to reduce the effect of movement artifact in subtraction images from breast MR, is compared with existing rigid and affine registration methods. METHOD: Nonrigid registration was compared with rigid and affine registration methods and unregistered images using 54 gadolinium-enhanced 3D breast MR data sets. Twenty-seven data sets had been previously reported normal, and 27 contained a histologically proven carcinoma. The comparison was based on visual assessment and ranking by two radiologists. RESULTS: When analyzed by two radiologists independently, all three registration methods gave better-quality subtraction images than unregistered images (p < 0.01), but nonrigid registration gave significantly better results than the rigid and affine registration methods (p < 0.01). There was no significant difference between rigid and affine registration methods. CONCLUSION: Nonrigid registration significantly reduces the effects of movement artifact in subtracted contrast-enhanced breast MRI. This may enable better visualization of small tumors and those within a glandular breast.

Unenhanced helical CT for renal colic--is the radiation dose justifiable?

AIM: The purpose of this study was to define and compare the radiation doses to patients undergoing computed tomography (CT) or intravenous urography (IVU) for the investigation of renal colic. METHODS: The IVU dose was calculated from dose area product measurements for 27 abdominal films (AXR) and a review of 30 IVUs performed to investigate renal colic. The effective dose to a patient undergoing CT was calculated using anthropomorphic model data. Fifty patients underwent CT for the investigation of renal colic over a 6-week period. RESULTS: CT following our protocol confers an average effective dose of 4.7 mSv. An IVU to investigate renal colic used 2.5 AXRs. A 3 film IVU gives an average dose of 1.5 mSv. Forty-two CT examinations were abnormal and the findings are described in the text. CONCLUSION: Although unenhanced CT confers diagnostic advantages and avoids the risks of intravenous contrast medium, this should be considered against the increased radiation dose to the patient which in our institution is over three times that of an IVU.

Cystic kidney disease presenting in infancy.

AIM: The clinical, histological and imaging findings of 12 children with ultrasound features of severe renal cystic disease presenting in the first year of life were reviewed. METHODS AND RESULTS: Two children had cystic dysplasia and four had autosomal dominant polycystic disease. Two had a malformation syndrome, one a variant of Meckel syndrome and the other Bardet Biedl syndrome. One had autosomal recessive polycystic disease and in three there was no final diagnosis. Intravenous urography gave non-specific information. In six cases clinical findings combined with imaging established a diagnosis. Diagnosis was established by biopsy in two and gave supportive evidence in one. Outlook for renal function is variable. One child has had a transplant and one is on dialysis awaiting a transplant. Three have a degree of renal failure and one has died. Six have normal renal function. Renal cystic disease is the common pathway for a heterogeneous group of disorders as shown in these children. CONCLUSION: It is emphasized that a specific diagnosis could not be made from the renal sonographic appearances alone, nor could any prognostic implications for renal function be made. Contrast retention on intravenous urography was also insufficiently specific to be of value. Ultrasound of the parents was the most useful imaging procedure and should be done in all cases.

High resolution ultrasound assessment of the carotid artery: its relevance in postmenopausal women and the effects of tibolone on carotid artery ultrastructure.

OBJECTIVES: Hormone replacement therapy protects from cardiovascular disease at the menopause in part by reduction of menopausal pro-atherogenic serum lipid changes. Tibolone has beneficial effects on lipids, although serum high density lipoprotein levels decrease. This study aimed primarily to establish the effects of long-term administration of tibolone on a new surrogate marker for cardiovascular disease risk, the measurement of carotid artery intima-media thickness (CIMT) using high-resolution ultrasound. METHODS: Measurement of CIMT and assessment of carotid atherosclerotic plaques were undertaken in 31 women on tibolone and 30 voluntary controls from an ongoing open-label study of tibolone. RESULTS: The two groups were comparable, except for mean age and prevalence of current smokers. Repeatability of CIMT measurements was acceptable (CV, 10.0%). CIMT was significantly thicker in those with atherosclerotic plaques and increased systolic blood pressure. Prevalence of plaques was raised in those who had ever smoked, and those with elevated systolic blood pressure. There was no influence of tibolone on CIMT, whether plaques were present or not. CONCLUSIONS: This reliable technique demonstrates associations between CIMT and established risk factors. CIMT was significantly thicker in those with existing plaques. We did not demonstrate an effect of long-term tibolone use on either CIMT or prevalence of plaques.