Search

Background Sarcopenia is defined as either low pre-operative muscle mass or low muscle density on abdominal CT imaging. It has been associated with worse short-term outcomes after surgery for colorectal liver metastases. This study aimed to evaluate whether sarcopenia also impacts long-term survival outcomes in these patients. Methods A random-effects meta-analysis was conducted following the PRISMA guidelines. Overall survival (OS) and disease-free survival (DFS) outcomes were evaluated. Results Eleven studies were included, ten reporting on the impact of low muscle mass and four on low muscle density. Sample sizes ranged between 47 and 539 (2124 patients in total). Altogether, 897 (42%) patients were considered sarcopenic, although definitions varied between studies. Median follow-up was 21–74 months. Low muscle mass (hazard ration (HR) 1.35, 95%CI 1.08–1.68) and low muscle density (HR 1.97, 95%CI 1.07–3.62) were associated with impaired OS. Low muscle mass (pooled HR 1.17, 95%CI 0.94–1.46) and low muscle density (pooled HR 1.13, 95%CI 0.85–1.50) were not associated with impaired RFS. Discussion Sarcopenia is associated with poorer OS, but not RFS, in patients with CRLM. Additional studies with standardized sarcopenia definitions are needed to better assess the impact of sarcopenia in patients with CRLM.

BACKGROUND: Sarcopenia is associated with impaired short- and long-term outcomes in gastrointestinal cancers. Whether sarcopenia is associated with impaired survival after local therapy of Colorectal Cancer Liver Metastases (CRLM) remains controversial. This study aimed to determine the influence of sarcopenia on long-term outcomes after curative-intent therapy for CRLM.METHODS: Patients undergoing local therapy for CRLM between 2003 and 2019 were retrospectively analyzed using the skeletal muscle index at the level of the third lumbar vertebra as an indicator of sarcopenia. Factors associated with overall (OS) and disease-free (DFS) survival were analyzed using univariable and multivariable cox regression.RESULTS: In total 213/465 patients (46%) were considered sarcopenic. Sarcopenic patients had no impaired 5-year OS or DFS compared to non-sarcopenic patients, 38% vs 44% (p = 0.153) and 19 vs 23% (p = 0.339) respectively. Sarcopenia was not associated with impaired OS (HR = 1.11, 95%CI = 0.85-1.46, p = 0.43) or DFS (HR = 0.99, 95%CI = 0.77-1.28, p = 0.96) in multivariable analysis. There were no significant differences in postoperative complications (p = 0.47), the incidence (p = 0.65) and treatment (p = 0.37) of recurrent metastases. Five-year OS after resection for recurrences was 14% (sarcopenic) and 22% (non-sarcopenic) p 0.716.CONCLUSION: Sarcopenia assessed by computed tomography was not associated with impaired survival outcomes in the group of CRLM patients overall.

Breast cancer screening has been shown to reduce breast cancer-associated mortality. However, screening is limited to the targeted age group of 45 to 69 years in New Zealand despite the recognized increased risk with age. This study aims to compare the outcomes of women aged over 70 years with screen-detected and clinically detected cancers.A retrospective review was performed of prospectively collected data from June 2000 to May 2013 by the Auckland Breast Cancer Register. Demographic and tumor characteristics of women with invasive cancer and ductal carcinoma in situ diagnosis aged 70 years and over were compared between those screened and clinically detected. Five-year disease-free and overall survival outcomes were reviewed.A total of 2128 women aged 70 years and over were diagnosed with breast cancer (median, 77 years; interquartile range [IQR], 74-84 years). Of these, 416 (19.5%) were diagnosed through mammography screening, with a median age of 74 years (IQR, 71-77 years) compared with 79 years (IQR, 74-85 years) for those with clinical detected cancer diagnosis. Screen-detected cancers accounted for a significantly higher proportion of diagnoses in those aged 70 to 74 years compared with older patients (P .001). Screen-detected cancers were of lower T and N stages. Disease-specific survival was significantly longer in screen-detected cancers versus other cancers (5-year survival, 93.7% vs. 81.9%; P .001), as was overall survival (5-year survival, 84.7% vs. 57.4%; P .001).Screening in those aged 70 years and over continues to identify breast cancer at early stages and with improved survival. Although aware of the potential for lead-time bias and the healthy volunteer effect, there should still be consideration to extend breast cancer screening to patients aged to up 74 years after appropriate assessment of comorbidities and functional status.

Although calcium (Ca) precipitation may play a pathogenic role in atherosclerosis, information on temporal patterns of microcalcifications in human coronary arteries, their relation to expression of calcification-regulating proteins, and colocalization with iron (Fe) and zinc (Zn) is scarce. Human coronary arteries were analyzed post mortem with a proton microprobe for element concentrations and stained (immuno)histochemically for morphological and calcification-regulating proteins. Microcalcifications were occasionally observed in preatheroma type I atherosclerotic intimal lesions. Their abundance increased in type II, III, and IV lesions. Moreover, their appearance preceded increased expression of calcification-regulating proteins, such as osteocalcin and bone morphogenetic protein-2. In contrast, their presence coincided with increased expression of uncarboxylated matrix Gla protein (MGP), whereas the content of carboxylated MGP was increased in type DI and IV lesions, indicating delayed posttranslational conversion of biologically inactive into active MGP. Ca/phosphorus ratios of the microcalcifications varied from 1.6 to 3.0, including amorphous Ca phosphates. Approximately 75% of microcalcifications colocalized with the accumulation of Fe and Zn. We conclude that Ca microprecipitation occurs in the early stages of atherosclerosis, inferring a pathogenic role in the sequel of events, resulting in overt atherosclerotic lesions. Microcalcifications may be caused by local events triggering the precipitation of Ca rather than by increased expression of calcification-regulating proteins. The high degree of colocalization with Fe and Zn suggests a mutual relationship between these trace elements and early deposition of Ca salts. (Ant J Pathol 2011, 178:2879-2887; DOI: 10.1016/j.ajpath.2011.02.004)

BackgroundVascular calcification is associated with poor cardiovascular outcome. Histochemical analysis of calcification and the expression of proteins involved in mineralization are usually based on whole section analysis, thereby often ignoring regional differences in atherosclerotic lesions. At present, limited information is available about factors involved in the initiation and progression of atherosclerosis.Aim of This StudyThis study investigates the intra-section association of micro-calcifications with markers for atherosclerosis in randomly chosen section areas of human coronary arteries. Moreover, the possible causal relationship between calcifying vascular smooth muscle cells and inflammation was explored in vitro.Technical ApproachTo gain insights into the pathogenesis of atherosclerosis, we performed analysis of the distribution of micro-calcifications using a 3-MeV proton microbeam. Additionally, we performed systematic analyses of 30 to 40 regions of 12 coronary sections obtained from 6 patients including histology and immuno-histochemistry. Section areas were classified according to CD68 positivity. In vitro experiments using human vascular smooth muscle cells (hVSMCs) were performed to evaluate causal relationships between calcification and inflammation.ResultsFrom each section multiple areas were randomly chosen and subsequently analyzed. Depositions of calcium crystals at the micrometer scale were already observed in areas with early pre-atheroma type I lesions. Micro-calcifications were initiated at the elastica interna concomitantly with upregulation of the uncarboxylated form of matrix Gla-protein (ucMGP). Both the amount of calcium crystals and ucMGP staining increased from type I to IV atherosclerotic lesions. Osteochondrogenic markers BMP-2 and osteocalcin were only significantly increased in type IV atheroma lesions, and at this stage correlated with the degree of calcification. From atheroma area type III onwards a considerable number of CD68 positive cells were observed in combination with calcification, suggesting a pro-inflammatory effect of micro-calcifications. In vitro, invasion assays revealed chemoattractant properties of cell-culture medium of calcifying vascular smooth muscle cells towards THP-1 cells, which implies pro-inflammatory effect of calcium deposits. Additionally, calcifying hVSMCs revealed a pro-inflammatory profile as compared to non-calcifying hVSMCs.ConclusionOur data indicate that calcification of VSMCs is one of the earliest events in the genesis of atherosclerosis, which strongly correlates with ucMGP staining. Our findings suggest that loss of calcification inhibitors and/or failure of inhibitory capacity is causative for the early precipitation of calcium, with concomitant increased inflammation followed by osteochondrogenic transdifferentiation of VSMCs.

Although sarcomas are the most frequent primary malignant tumor of the heart, they very rarely involve only the left heart valves. A 72-year-old woman was diagnosed with a severe mitral valve disease and referred for cardiac surgery. Preoperative transthoracic echocardiography revealed a cardiac mass involving the mitral and aortic valves. The aortic valve had an unusual appearance, with a cystic mass protruding to the left ventricular outflow tract. The mitral valve apparatus was also involved, with chordal rupture. Extended resection and dual valve replacement was performed. A histological examination revealed an undifferentiated sarcoma. Postoperatively, neither chemotherapy nor radiotherapy therapy was used. Although most patients may benefit from adjunctive therapy, some respond well in the short term with only surgical resection, despite the poor prognosis of this rare entity.

The current paradigm reads that calcifications characterize the advanced and complex lesions in the atherosclerotic process. To explore the possibility that coronary artery wall calcifications already commence at an early stage of atherosclerosis, a combination of proton beam techniques with a (sub-) micrometer resolution, i.e., micro-proton induced X-ray emission, backward and forward scattering spectroscopy, was applied on human coronary arteries with lesions preceding overt atheromas. The detection limits of phosphorus and calcium in each separate pixel, 0.88*0.88 microm2 in size, were approximately 150 and 80 microg/g dry weight, respectively. Calcium distributions of entire coronary artery cross section were obtained, and calcifications were demonstrated at a preatheroma stage of the atherosclerotic process. The size of the microcalcifications varied between 1 and 10 microm. The composition of the microcalcifications was deduced from the calcium-to-phosphorus ratio. In order to quantify this ratio, the thickness of the specific X-ray absorber used for PIXE had to be accurately determined. Also, thick target PIXE calculations were performed and the method was validated. The calcium-to-phosphorus ratios of the microcalcifications were assessed with good accuracy and varied from 1.62 to 2.79, which corresponds with amorphous calcium phosphate.

Introduction To assess an optimized 3D imaging protocol for intracranial nitinol stents in 3D C-arm flat detector imaging. For this purpose, an image quality simulation and an in vitro study was carried out. Methods Nitinol stents of various brands were placed inside an anthropomorphic head phantom, using iodine contrast. Experiments with objects were preceded by image quality and dose simulations. We varied X-ray imaging parameters in a commercially interventional X-ray system to set 3D image quality in the contrast–noise–sharpness space. Beam quality was varied to evaluate contrast of the stents while keeping absorbed dose below recommended values. Two detector formats were used, paired with an appropriate pixel size and X-ray focus size. Zoomed reconstructions were carried out and snapshot images acquired. High contrast spatial resolution was assessed with a CT phantom. Results We found an optimal protocol for imaging intracranial nitinol stents. Contrast resolution was optimized for nickel–titanium-containing stents. A high spatial resolution larger than 2.1 lp/mm allows struts to be visualized. We obtained images of stents of various brands and a representative set of images is shown. Independent of the make, struts can be imaged with virtually continuous strokes. Measured absorbed doses are shown to be lower than 50 mGy Computed Tomography Dose Index (CTDI). Conclusion By balancing the modulation transfer of the imaging components and tuning the high-contrast imaging capabilities, we have shown that thin nitinol stent wires can be reconstructed with high contrast-to-noise ratio and good detail, while keeping radiation doses within recommended values. Experimental results compare well with imaging simulations.