Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT.

BACKGROUND/OBJECTIVES: Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids (FAs) on quality of life, performance status, handgrip strength and physical activity in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. SUBJECTS/METHODS: In a double-blind experiment, 40 patients with stage III NSCLC were randomised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs (2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day) or an isocaloric control supplement, during multimodality treatment. Quality of life, Karnofsky Performance Status, handgrip strength and physical activity (by wearing an accelerometer) were assessed. Effects of intervention were analysed by generalised estimating equations. P-values <0.05 were regarded as statistically significant. RESULTS: The intervention group reported significantly higher on the quality of life parameters, physical and cognitive function (B=11.6 and B=20.7, P<0.01), global health status (B=12.2, P=0.04) and social function (B=22.1, P=0.04) than the control group after 5 weeks. The intervention group showed a higher Karnofsky Performance Status (B=5.3, P=0.04) than the control group after 3 weeks. Handgrip strength did not significantly differ between groups over time. The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks (B=6.6, P=0.04 and B=2.5, P=0.05). CONCLUSION: n-3 Polyunsaturated FAs may beneficially affect quality of life, performance status and physical activity in patients with NSCLC undergoing multimodality treatment.

Correlating quantitative MR imaging with histopathology in X-linked adrenoleukodystrophy.

BACKGROUND AND PURPOSE: Quantitative MR imaging techniques may improve the pathologic specificity of MR imaging regarding white matter abnormalities. Our purposes were to determine whether ADC, FA, MTR, and MRS metabolites correlate with the degree of white matter damage in patients with X-ALD; whether differences in ADC, FA, and MTR observed in vivo are retained in fresh and formalin-fixed postmortem brain tissue; and whether the differences predict histopathology. MATERIALS AND METHODS: MRS metabolites, MTR, ADC, and FA, were determined in 7 patients with X-ALD in 3 white matter areas (NAWM, active demyelination, and complete demyelination) and were compared with values obtained in 14 controls. MTR, ADC, and FA were assessed in postmortem brains from 15 patients with X-ALD and 5 controls. Values were correlated with the degree of astrogliosis and density of myelin, axons, and cells. Equations to estimate histopathology from MR imaging parameters were calculated by linear regression analysis. RESULTS: MRS showed increased mIns, Lac, and Cho and decreased tNAA in living patients with X-ALD; the values depended on the degree of demyelination. MTR, ADC, and FA values were different in postmortem than in vivo white matter, but differences related to degrees of white matter damage were retained. ADC was high and FA and MTR were low in abnormal white matter. Correlations between histopathologic findings and MR imaging parameters were strong. A combination of ADC and FA predicted pathologic parameters best. CONCLUSIONS: Changes in quantitative MR imaging parameters, present in living patients and related to the severity of white matter pathology, are retained in postmortem brain tissue. MR imaging parameters predict white matter histopathologic parameters.

Fetal cardiac function assessed with four-dimensional ultrasound imaging using spatiotemporal image correlation.

OBJECTIVES: The goal of this study was to use spatiotemporal image correlation (STIC) to provide reference values for left and right ventricle volumes, and indices of fetal cardiac function. METHODS: In this prospective longitudinal study, STIC volumes were acquired periodically from 12 weeks of gestation onwards. The STIC volumes were frozen in end-systole and end-diastole, and volumetric data were measured by manual tracing and summation of multiple slices. These ventricle volumes were used to calculate stroke volume, ejection fraction and cardiac output. RESULTS: Some 202 STIC volumes of 63 fetuses were included in the analysis. Mean left and right ventricle stroke volume increased from 0.02 mL at 12 weeks to 1.41 mL and 1.46 mL, respectively, at 30 weeks, while the mean right to left stroke volume ratio remained stable at around 1.2. Mean left and right ventricle cardiac output increased from 2.40 mL/min and 2.60 mL/min at 12 weeks to 197.74 mL/min and 204.81 mL/min, respectively, at 30 weeks. Both left and right mean ejection fraction remained constant at around 0.45 with advancing gestational age. Bland-Altman analysis showed a coefficient of variation for measured stroke volume of 13.7%. CONCLUSIONS: This study establishes reference values for fetal cardiac volumes and indices for fetal cardiac function from 12 to 30 weeks of gestation using STIC. STIC seems to overcome many of the pitfalls of conventional ultrasound methods and has the potential to become the method of choice.

Jugular lymphatic sacs in first-trimester fetuses with normal nuchal translucency.

OBJECTIVE: To assess the ultrasonographic appearance of the jugular lymphatic sacs (JLS) in first-trimester fetuses with a normal nuchal translucency (NT). METHODS: Seventy-five fetuses with a normal NT thickness (< 95(th) percentile) were examined weekly between 11 and 17 weeks of gestation. After measurement of the NT thickness, the neck region was examined using both transvaginal and transabdominal ultrasonography for the presence of JLS. If present, their dimensions were measured in three directions and the volume was calculated using the formula for a spheroid. Data were analyzed using multilevel analysis. RESULTS: Seventy-five fetuses were evaluated and a total of 243 ultrasound examinations of the neck region were performed. In 25 (33%) of the 75 fetuses, the JLS could be observed once or more than once. In 19 fetuses JLS were visualized once, in five fetuses twice and in one fetus three times. In total, the JLS were visualized 32 times (n = 15 bilaterally, n = 15 only the left JLS and n = 2 only the right JLS). Relatively greater NT thickness was associated with a higher probability of the presence of JLS, although this was not statistically significant (NT < 1 mm, probability 0.07; NT 1-2 mm, probability 0.15, P = 0.10; NT > 2 mm, probability 0.20, P = 0.08). Gestational age was predictive for the presence of JLS, with the highest probability between 13 and 15 weeks of gestation (P < 0.01). No relationship was found between gestational age and the volumes of the left and right JLS. CONCLUSION: The JLS can be visualized on ultrasound examination in a significant proportion of fetuses with normal NT, most often between 13 and 15 weeks of gestation, and this does not seem to be associated with any abnormality in these fetuses.

Early first-trimester free beta-hCG and PAPP-A serum distributions in monochorionic and dichorionic twins.

BACKGROUND: In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free beta-hCG and PAPP-A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first-trimester free beta-hCG and PAPP-A between mono- and dichorionic twins. METHODS: A total of 202 twin pregnant women participated in the study and agreed to donate first-trimester serum for research. RESULTS: The data of 200 twins with normal outcome were used for setting up reference values for free beta-hCG and PAPP-A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight-corrected MoM was 1.99 for free beta-hCG, and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower free beta-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p=0.002) and a significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U, p=0.003) compared to dichorionic. CONCLUSION: This study strengthened the need to make a distinction between mono- and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins.

[18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study.

Increased 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) uptake is the most commonly used marker for positron emission tomography in oncology. However, a proliferation tracer such as 3'-deoxy-3'-[18F]fluorothymidine (FLT) might be more specific for cancer. 3'-deoxy-3'-[18F]fluorothymidine uptake is dependent on thymidine kinase 1 (TK) activity, but the effects of chemotherapeutic agents are unknown. The aim of this study was to characterise FDG and FLT uptake mechanisms in vitro before and after exposure to chemotherapeutic agents. The effects of 5-fluorouracil (5-FU), doxorubicin and paclitaxel on FDG and FLT uptake were measured in MDA MB231 human breast cancer cells in relation to cell cycle distribution, expression and enzyme activity of TK-1. At IC50 concentrations, 5-FU resulted in accumulation in the G1 phase, but doxorubicin and paclitaxel induced a G2/M accumulation. Compared with untreated cells, 5-FU and doxorubicin increased TK-1 levels by >300. At 72 h, 5-FU decreased FDG uptake by 50% and FLT uptake by 54%, whereas doxorubicin increased FDG and FLT uptake by 71 and 173%, respectively. Paclitaxel increased FDG uptake with >100% after 48 h, whereas FLT uptake hardly changed. In conclusion, various chemotherapeutic agents, commonly used in the treatment of breast cancer, have different effects on the time course of uptake of both FDG and FLT in vitro. This might have implications for interpretation of clinical findings.

Preoperative [18F] FDG-PET after chemotherapy in locally advanced breast cancer: prognostic value as compared with histopathology.

BACKGROUND: Established prognosis-based criteria determine the need for further treatment after primary surgery for breast cancer. Such criteria are lacking after neo-adjuvant chemotherapy. We determine the prognostic value of preoperative [(18)F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography ((18)FDG-PET) after chemotherapy in locally advanced breast cancer (LABC), both as independent indicator and as add-on to postoperative histopathology. PATIENTS AND METHODS: Preoperative PET was carried out in 40 LABC patients. Two expert readers assessed residual (18)FDG uptake in the primary tumor. At histopathological examination of the surgical specimen, chemotherapy response was graded using the Honkoop criteria. Cox proportional hazards analysis was used to determine prognostic relevance of PET and histopathology. RESULTS: Median follow-up was 60 months (range 15-94), during which 13 patients had recurrent disease, eight of whom died. (18)FDG uptake in the primary tumor was inversely related with disease-free survival (DFS) [hazard ratio (HR) 4.09; 95% confidence interval (CI) 1.26-13.31; P = 0.02] and this was superior to histopathology (HR 2.52; 95% CI 0.77-8.23; P = 0.13). Observer agreement of PET was excellent (intraclass correlation coefficient 0.88). Multivariate Cox regression revealed no added value of histopathology versus PET results. CONCLUSION: (18)FDG uptake in the primary tumor at PET was inversely associated with DFS and may help to guide adjuvant therapy.

A systematic analysis of the feasibility of four-dimensional ultrasound imaging using spatiotemporal image correlation in routine fetal echocardiography.

OBJECTIVES: To investigate the feasibility of incorporating spatiotemporal image correlation (STIC) into a tertiary fetal echocardiography program. METHODS: During the study period all pregnant women fitting our inclusion criteria were enrolled consecutively. Four sonographers participated in the study, one of whom had substantial previous experience of STIC volume acquisition and three of whom did not. STIC volumes were acquired within the time slot allocated for the usual examination and all attempts were recorded. STIC volumes were assessed on acquisition conditions, the quality (as defined by a checklist of cardiac structures that could be visualized), and the rendering abilities. Furthermore, possible learning effects and the influence of experience with STIC on volume acquisition were studied. RESULTS: STIC volume acquisition was successful in 75.7% (112/148) of cases in which it was attempted. The more experienced sonographer had a higher success rate in STIC volume acquisition (experienced vs. less experienced, 88.4% vs. 70.5%, P = 0.02). Of all analyzed STIC volumes, 64.8% were of high or sufficient quality. STIC volume quality and rendering ability correlated strongly with the acquisition conditions. High-quality STIC volumes successfully rendered the intracardiac septa in 84.6% of cases. The coronal atrioventricular plane was rendered in 12/26 cases (46.2%). CONCLUSIONS: This study shows that incorporation of STIC volume acquisition into the daily practice of a tertiary fetal echocardiography program is feasible. Sonographers do not have to be specifically experienced in three- or four-dimensional ultrasound imaging to acquire high-quality STIC volumes. For successful STIC acquisition and subsequent successful analysis, correct acquisition conditions are of major importance. Finally, our results demonstrate that STIC is as susceptible as conventional two-dimensional ultrasound imaging to individual variations and limitations in scanning windows.

Pulmonary embolism causes endomyocarditis in the human heart.

BACKGROUND: Pulmonary embolism (PE) is a significant cause of morbidity and mortality. In a recent study in patients with PE, an increased level of macrophages was found in the right ventricle. OBJECTIVE: To evaluate the presence of inflammatory cells, myocytolysis and intracavitary thrombi in the left and right ventricle of patients who died because of PE as a putative new source of heart failure. PATIENTS AND METHODS: 22 patients with PE were studied. For comparison, eight controls and 11 patients who died of chronic pulmonary hypertension (PHT) were used. Slides of the left and right ventricle were stained with antibodies, identifying neutrophilic granulocytes, lymphocytes and macrophages, which were subsequently quantified. Myocytolysis was visualised using complement staining. Thrombi were identified by conventional staining. RESULTS: Compared with controls, in patients with PE a significant increase in extravascular localisation of all three inflammatory cells was found both in the right and left ventricle, coinciding with myocytolysis, indicative for myocarditis. No increase in inflammatory cells was found in patients with PHT. Endocardial cellular infiltration was also found, partly coinciding with the presence of ventricular thrombi. CONCLUSIONS: In patients with PE, endomyocarditis and intracavitary thrombi in the left and right ventricle were found. These abnormalities may be an additional new explanation for the observed cardiac enzyme release and functional abnormalities of the heart in these patients and may contribute to the morbidity and mortality of the disease.

Color Doppler ultrasound of spiral artery blood flow for prediction of hypertensive disorders and intra uterine growth restriction: a longitudinal study.

OBJECTIVE: To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. METHODS: Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann-Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. RESULTS: One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (