Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients

Purpose

Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Aortic stenosis at young adult age

Aortic stenosis at young adult age is usually the result of a stenotic bicuspid aortic valve, which is the most common cardiac congenital anomaly. In clinical practice, exercise and pregnancy are important topics. Furthermore, the timing of intervention is under debate, as little information is available on the natural history and outcome after aortic valve replacement in these young adults. In older patients, there is a trend towards earlier intervention. With the increased knowledge of the pathophysiology of aortic stenosis, studies have focused on the dilatation of the ascending aorta with risk of dissection. Recently, it has been suggested that pharmacologic treatment of aortic stenosis could be beneficial for these young adults.     

Evaluation of left atrial systolic function in noncompaction cardiomyopathy by real-time three-dimensional echocardiography

Background Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. Methods The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II / III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF_3D-MAD) and area (LAEF_3D-MAA) using RT3DE. Results The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF_3D-MAD (3.8 ± 2.2 vs 2.3 ± 1.0 kdyne, P < 0.05) and LAEF_3D-MAA (12.7 ± 7.6 vs 4.9 ± 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. Conclusions LAEF as a characteristic of LA systolic function is increased in NCCM patients compared to normal individuals. These results can suggest compensating left atrial work against the dysfunctional LV in NCCM patients.     

Effects of lymphotoxin-alpha gene and galectin-2 gene polymorphisms on inflammatory biomarkers, cellular adhesion molecules and risk of coronary heart disease

The pro-inflammatory cytokine LTA (lymphotoxin-alpha) has multiple functions in regulating the immune system and may contribute to inflammatory processes leading to CHD (coronary heart disease). The aim of the present study was to investigate whether the common C804A (resulting in a Thr(26)-->Asp amino acid substitution) and A252G polymorphisms of the LTA gene and the C3279T polymorphism of the galectin-2 (LGALS2) gene, which affects LTA secretion, are associated with inflammatory parameters and cell adhesion molecules, and whether these polymorphisms are related to CHD in American women and men. We conducted a prospective nested case-control study within the Nurses' Health Study and Health Professionals Follow-Up Study. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow-up respectively, and we matched controls 2:1 based on age and smoking. The LGALS2 gene variant was significantly associated with a decreased risk of CHD in women [odds ratio (95% confidence interval), 0.70 (0.50-0.97); P=0.03]. In addition, the LGALS2 polymorphism was directly associated with CRP (C-reactive protein) levels in cases from both studies (P<0.05). The LTA gene polymorphisms were directly associated with levels of sTNFRs (soluble tumour necrosis factor receptors) and VCAM-1 (vascular cell adhesion molecule-1) in both women and men with CHD (P<0.05). However, no overall effect was demonstrated between LTA gene polymorphisms and risk of CHD.     

Usefulness of clinical, echocardiographic, and procedural characteristics to predict outcome after percutaneous transluminal septal myocardial ablation

This study was conducted to assess outcomes after percutaneous transluminal septal myocardial ablation (PTSMA) treatment in 131 patients (mean age 56+/-16 years) with obstructive hypertrophic cardiomyopathy. In-hospital and follow-up complications as well as late PTSMA failure (defined as unsatisfactory clinical outcome and a significant residual outflow tract gradient, necessitating reintervention) were noted. Baseline clinical, echocardiographic, and PTSMA characteristics were examined as determinants of outcomes. Also, the effect of ethanol volume and the role of a learning curve were investigated. PTSMA was successful in 90% of the patients. In-hospital and follow-up cardiac events were noted in 20 patients, including cardiac death (in-hospital n=4, follow-up n=1), acute myocardial infarction due to ethanol leakage (n=1), coronary dissection (n=2), nonfatal cardiac tamponade (n=1), and permanent pacemaker (n=6) or cardiac defibrillator (in-hospital n=4, follow-up n=1) implantation. Late PTSMA failure was noted in 12 patients. All baseline characteristics were comparable between successful and failed PTSMA. Ethanol volume was related to peak creatinine kinase value (p<0.0001) but not to late PTSMA failure or greater need for pacemaker implantation. Late PTSMA failure occurred more frequently in PTSMA procedures performed in the early, less experienced time period (p<0.001). In conclusion, this study confirms that PTSMA, although effective, has a relatively high complication rate. Late PTSMA failure could not be predicted by baseline characteristics but could partially be explained by a learning-curve effect. This finding implies that PTSMA procedures should be restricted to experienced centers.     

Early Mechanical Alterations in Phospholamban Mutation Carriers: Identifying Subclinical Disease Before Onset of Symptoms

ObjectivesThis study aimed to explore echocardiographic characteristics of phospholamban (PLN) p.Arg14del mutation carriers to investigate whether structural and/or functional abnormalities could be identified before onset of symptoms.BackgroundCarriers of the genetic PLN p.Arg14del mutation may develop arrhythmogenic and/or dilated cardiomyopathy. Overt disease is preceded by a pre-symptomatic phase of variable length in which disease expression seems to be absent.MethodsPLN p.Arg14del mutation carriers with an available echocardiogram were included. Mutation carriers were classified as pre-symptomatic if they had no history of ventricular arrhythmias (VAs), a premature ventricular complex count of <500/24 h, and a left ventricular (LV) ejection fraction of ≥45%. In addition, we included 70 control subjects with similar age and sex distribution as the pre-symptomatic mutation carriers. Comprehensive echocardiographic analysis (including deformation imaging) was performed.ResultsThe final study population consisted of 281 PLN p.Arg14del mutation carriers, 139 of whom were classified as pre-symptomatic. In comparison to control subjects, pre-symptomatic mutation carriers had lower global longitudinal strain and higher LV mechanical dispersion (both p < 0.001). In addition, post-systolic shortening (PSS) in the LV apex was observed in 43 pre-symptomatic mutation carriers (31%) and in none of the control subjects. During a median follow-up of 3.2 years (interquartile range: 2.1 to 5.6 years) in 104 pre-symptomatic mutation carriers, nonsustained VA occurred in 13 (13%). Presence of apical PSS was the strongest echocardiographic predictor of VA (multivariable hazards ratio: 5.11; 95% confidence interval [CI]: 1.37 to 19.08; p = 0.015), which resulted in a negative predictive value of 96% (95% CI: 89% to 98%) and a positive predictive value of 29% (95% CI: 21% to 40%).ConclusionsGlobal and regional LV mechanical alterations in PLN p.Arg14del mutation carriers precede arrhythmic symptoms and overt structural disease. Pre-symptomatic mutation carriers with normal deformation patterns in the apex are at low risk of developing VA within 3 years, whereas mutation carriers with apical PSS appear to be at higher risk.