The relationship between dietary inflammatory potential and cancer outcomes among cancer survivors: A systematic review and meta-analysis of cohort studies.

Cancer remains the second leading cause of death globally. Chronic inflammatory environments promote the growth of tumors, and the intake of certain food items can increase systemic inflammation. This study examined the relationship between the inflammatory potential of diet, measured by the Dietary Inflammatory Index (DII), and recurrence, all-cause, and cancer-specific mortality among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched in April 2022. Two independent reviewers screened all searches. Of the 1,443 studies, 13 studies involving 14,920 cancer survivors passed all the screening stages. Three studies reported cancer recurrence, 12 reported all-cause mortality, and six reported cancer-specific mortality. Seven studies calculated DII from pre-diagnosis diets, five from post-diagnosis diets, and one from both pre-and post-diagnosis diets. A random-effects model meta-analysis showed that high DII was not associated with an increased risk of recurrence (HR = 1.09, 95 % CI = 0.77, 1.54, n = 4) and all-cause (HR = 1.08, 95 % CI = 0.99, 1.19, n = 14) and cancer-specific mortality (H = 1.07, 95 % CI = 0.92, 1.25, n = 6). Analysis by the timing of dietary assessment showed that only post-diagnosis DII was associated with an increased risk of all-cause mortality (HR = 1.34, 95 % CI = 1.05, 1.72, n = 6) by 34 %; however, cancer type did not modify these associations. The quality of the study assessed using the Newcastle Ottawa Scale indicated all but one studies were good. The risk of all-cause mortality among cancer survivors could be reduced by consuming more anti-inflammatory diets after cancer diagnosis.

Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.

Oocyte Cryopreservation for Medical and Planned Indications: A Practical Guide and Overview.

Oocyte cryopreservation (OC) is the process in which ovarian follicles are stimulated, the follicular fluid is retrieved, and mature oocytes are isolated and vitrified. Since the first successful pregnancy utilizing previously cryopreserved oocytes in 1986, OC has become increasingly utilized as an option for future biologic children in patients facing gonadotoxic therapies, such as for the treatment of cancer. Planned OC, also termed elective OC, is growing in popularity as a means to circumvent age-related fertility decline. In this narrative review, we describe both medically indicated and planned OC, focusing on the physiology of ovarian follicular loss, OC technique and risks, timing of when OC should be performed, associated financial considerations, and outcomes.

AMH predicts miscarriage in non-PCOS but not in PCOS related infertility ART cycles.

BACKGROUND: To study whether AMH levels were associated with miscarriage rates in index ART cycles undergoing fresh autologous transfers in PCOS and non-PCOS related infertility. METHODS: In the SART CORS database 66,793 index cycles underwent fresh autologous embryo transfers with AMH values reported within the last 1-year between 2014 and 2016. Cycles that resulted in ectopic or heterotopic pregnancies, or were performed for embryo/oocyte banking were excluded. Data were analyzed using Graphpad Prism-9. Odds ratios (OR) were calculated with 95% confidence intervals (CI) along with multivariate regression analysis adjusting for age, body mass index (BMI), and number of embryos transferred. Miscarriage rates were calculated as miscarriage per clinical pregnancies. RESULTS: Of the total 66,793 cycles, the mean AMH was 3.2 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 1.1, CI 0.9-1.4, p = 0.3). Of the 8,490 PCOS patients, the mean AMH was 6.1 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 0.8, CI 0.5-1.1, p = 0.2). Of the 58,303 non-PCOS patients, the mean AMH was 2.8 ng/ml and there was a significant difference in miscarriage rates for AMH < 1 ng/ml (OR 1.2, CI 1.1-1.3, p < 0.01). All findings were independent of age, BMI and number of embryos transferred. This statistical significance did not persist at higher thresholds of AMH. The overall miscarriage rate for all cycles, and cycles with and without PCOS were each 16%. DISCUSSION: The clinical utility of AMH continues to increase as more studies investigate its predictive abilities regarding reproductive outcomes. This study adds clarity to the mixed findings of prior studies that have examined the relationship between AMH and miscarriage in ART cycles. AMH values of the PCOS population are higher than the non-PCOS. The elevated AMH associated with PCOS decreases its utility in predicting miscarriages in IVF cycles as it may be representing the number of developing follicles rather than oocyte quality in the PCOS patient population. The elevated AMH associated with PCOS may have skewed the data; removing this sub-population may have unmasked significance within the non-PCOS associated infertility. CONCLUSIONS: AMH < 1 ng/mL is an independent predictor of increased miscarriage rate in patients with non-PCOS infertility.

Healthy Eating and Mortality among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

This systematic review examined the effect of diet quality, defined as adherence to healthy dietary recommendations, on all-cause and breast cancer-specific mortality. Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by May 2021. We used a random-effects model meta-analysis in two different approaches to estimate pooled hazard ratio (HR) and 95% confidence interval (CI) for highest and lowest categories of diet quality: (1) each dietary quality index as the unit of analysis and (2) cohort as the unit of analysis. Heterogeneity was examined using Cochran's Q test and inconsistency I2 statistics. The risk of bias was assessed by the Newcastle-Ottawa Scale for cohort studies, and the quality of evidence was investigated by the GRADE tool. The analysis included 11 publications from eight cohorts, including data from 27,346 survivors and seven dietary indices. Both approaches yielded a similar effect size, but cohort-based analysis had a wider CI. Pre-diagnosis diet quality was not associated with both outcomes. However, better post-diagnosis diet quality significantly reduced all-cause mortality by 21% (HR = 0.79, 95% CI = 0.70, 0.89, I2 = 16.83%, n = 7) and marginally reduced breast cancer-specific mortality by 15% (HR = 0.85, 95% CI = 0.62, 1.18, I2 = 57.4%, n = 7). Subgroup analysis showed that adhering to the Diet Approaches to Stop Hypertension and Chinese Food Pagoda guidelines could reduce breast cancer-specific mortality. Such reduction could be larger for older people, physically fit individuals, and women with estrogen receptor-positive, progesterone receptor-negative, or human epidermal growth factor receptor 2-positive tumors. The risk of bias in the selected studies was low, and the quality of evidence for the identified associations was low or very low due to imprecision of effect estimation, inconsistent results, and publication bias. More research is needed to precisely estimate the effect of diet quality on mortality. Healthcare providers can encourage breast cancer survivors to comply with healthy dietary recommendations to improve overall health. (Funding: University of Central Florida Office of Undergraduate Research, Registration: PROSPERO-CRD42021260135).

Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier.

INTRODUCTION: Inhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases. METHODS: We investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, Scnn1b-Tg) and in air-liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis. A plasmid designed to silence epithelial sodium channel (ENaC) hyperactivity, which causes airway surface dehydration and mucus stasis, was intratracheally administered via DNA-MPP to evaluate therapeutic effects in vivo with or without pretreatment with hypertonic saline, a clinically used mucus-rehydrating agent. RESULTS: DNA-MPP exhibited marked greater reporter transgene expression compared with a mucus-impermeable formulation in in vivo and in vitro models of muco-obstructive lung diseases. DNA-MPP carrying ENaC-silencing plasmids provided efficient downregulation of ENaC and reduction of mucus burden in the lungs of Scnn1b-Tg mice, and synergistic impacts on both gene transfer efficacy and therapeutic effects were achieved when DNA-MPP was adjuvanted with hypertonic saline. DISCUSSION: DNA-MPP constitutes one of the rare gene delivery systems providing therapeutically meaningful gene transfer efficacy in highly relevant in vivo and in vitro models of muco-obstructive lung diseases due to its unique ability to efficiently penetrate airway mucus.

Prevalence of cerebral small vessel disease in a Fabry disease cohort.

OBJECTIVE: To characterize the prevalence of brain ischemia and cerebral small vessel disease in a cohort of patients with Fabry disease (FD) seen at an academic medical center. BACKGROUND: FD is an inherited X-linked lysosomal storage disorder with central nervous system involvement. Limited data are available in the literature on the cerebrovascular neuroimaging findings in FD, and the reported prevalence of stroke symptoms and cerebral small vessel disease has varied widely. DESIGN/METHODS: Brain MRI was performed in 21 patients with FD followed at University of California Irvine Medical Center. Stroke symptoms were assessed and quantification of cerebral microvascular disease was performed using small vessel disease (SVD) score. Lacunes and deep white matter hyperintensities were scored on a four-point scale of 0 (absent) and 1-3 to account for increasing severity; microbleeds were scored 0 (absent) or 1 (present). The total SVD score is the sum of the three components and ranges from 0 to 7. RESULTS: Nearly 43% (9/21) of our FD cohort (aged 32-81 years, mean = 50) had a SVD score of one or higher, all of whom were aged 50 or more years. The most common MRI-defined SVD was white matter hyperintensities (9/9, 100%), followed by microbleeds (6/9, 66%), and lacunes (3/9, 33%). The three patients with previous strokes had some of the highest SVD scores reported in the cohort (scores 3-5). CONCLUSIONS: In this cohort, the prevalence of SVD (43%) was three times higher than prevalence of stroke symptoms. SVD score was highest in the those who had experienced a stroke. These findings emphasize the importance of routine MRI screening of patients with FD in order to identify and treat high risk patients.

Valve or No Valve: A Prospective Randomized Controlled Trial of Casting Options for Pediatric Forearm Fractures.

The purpose of this study was to determine the rate of cast-related complications when using split or intact casts. A total of 60 patients aged 3 to 13 years with closed shaft or distal third radius and ulna fractures requiring reduction were recruited for this study. Patients underwent closed reduction under sedation and were placed into a long-arm fiberglass cast with 1 of 3 modifications: no valve, univalve, or bivalve. Patients were followed to 6 weeks after reduction or surgical treatment if required. The frequency of neurovascular injury, cast saw injury, unplanned office visits, and cast modifications, the need for operative intervention, and pain levels through the follow-up period were recorded. The results showed no incidents of compartment syndrome or neurovascular injury. Additionally, there were no differences between complications associated with cast type (P=.266), frequency of cast modifications (P=.185), or subsequent need for surgical stabilization (P=.361). Therefore, cast splitting following closed reduction of low-energy pediatric forearm fractures does not change clinical outcomes with respect to neurovascular complications, cast modifications, pain levels, or the need for repeat reduction. Consideration should be given to minimizing cast splitting after reduction of low-energy pediatric forearm fractures for practice efficiency and to potentially decrease saw-related injury. [Orthopedics. 2017; 40(5):e849-e854.].

Bilateral Myelomatous Pleural Effusion in a Patient with IgA Kappa Multiple Myeloma.

Multiple myelomas is a neoplastic plasma cell disorder that accounts for one percent of all cancers and 13% of hematologic malignancies. Although primarily known to be a bone marrow disorder, it can metastasize to extramedullary sites or it can present as a solitary extramedullary plasmacytoma. Primary pleural effusion from myeloma is rare, occurring in less than one percent of the patients. The following case report highlights a case of bilateral pleural effusion, directly attributable to multiple myeloma after other causes were ruled out. The diagnosis was made using cytology and immunohistochemical (IHC) staining of the pleural fluid. Myelomatous pleural effusion (MPE) is a poor prognostic feature heralding an aggressive underlying disease state, as represented in this case.

Self-gated 4D multiphase, steady-state imaging with contrast enhancement (MUSIC) using rotating cartesian K-space (ROCK): Validation in children with congenital heart disease.

PURPOSE: To develop and validate a cardiac-respiratory self-gating strategy for the recently proposed multiphase steady-state imaging with contrast enhancement (MUSIC) technique. METHODS: The proposed SG strategy uses the ROtating Cartesian K-space (ROCK) sampling, which allows for retrospective k-space binning based on motion surrogates derived from k-space center line. The k-space bins are reconstructed using a compressed sensing algorithm. Ten pediatric patients underwent cardiac MRI for clinical reasons. The original MUSIC and 2D-CINE images were acquired as a part of the clinical protocol, followed by the ROCK-MUSIC acquisition, all under steady-state intravascular distribution of ferumoxytol. Subjective scores and image sharpness were used to compare the images of ROCK-MUSIC and original MUSIC. RESULTS: All scans were completed successfully without complications. The ROCK-MUSIC acquisition took 5 ± 1 min, compared to 8 ± 2 min for the original MUSIC. Image scores of ROCK-MUSIC were significantly better than original MUSIC at the ventricular outflow tracts (3.9 ± 0.3 vs. 3.3 ± 0.6, P < 0.05). There was a strong trend toward superior image scores for ROCK-MUSIC in the other anatomic locations. CONCLUSION: ROCK-MUSIC provided images of equal or superior image quality compared to original MUSIC, and this was achievable with 40% savings in scan time and without the need for physiologic signal. Magn Reson Med 78:472-483, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous acquisition of T1ρ and T2 quantification in knee cartilage: repeatability and diurnal variation.

PURPOSE: To develop a robust sequence that combines T1ρ and T2 quantifications and to examine the in vivo repeatability and diurnal variation of T1ρ and T2 quantifications in knee cartilage. MATERIALS AND METHODS: Six healthy volunteers were scanned in the morning and afternoon on 2 days using a combined T1ρ and T2 quantification sequence developed in this study. Repeatability of T1ρ and T2 quantification was estimated using root-mean-square coefficients-of-variation (RMS-CV). T1ρ and T2 values from morning scans were compared to those from afternoon scans using paired t-tests. RESULTS: The overall RMS-CV of in vivo T1ρ and T2 quantification was 5.3% and 5.2%, respectively. The RMS-CV of am scans was 4.2% and 5.0% while the RMS-CV of pm scans was 6.0% and 6.3% for T1ρ and T2 , respectively. No significant difference was found between T1ρ or T2 values in the morning and in the afternoon. CONCLUSION: A sequence that combines T1ρ and T2 quantification with scan time less than 10 minutes and is robust to B0 and B1 inhomogeneity was developed with excellent repeatability. For a cohort with low-level daily activity, although no significant diurnal variation of cartilage MR relaxation times was observed, the afternoon scans had inferior repeatability compared to morning scans.

Perfusion imaging of cerebral arteriovenous malformations: a study comparing quantitative continuous arterial spin labeling and dynamic contrast-enhanced magnetic resonance imaging at 3 T.

Assessment of hemodynamics in arteriovenous malformations (AVMs) is important for estimating the risk of bleeding as well as planning and monitoring therapy. In tissues with perfusion values significantly higher than cerebral cortex, continuous arterial spin labeling (CASL) permits both adequate representation and quantification of perfusion. Thirteen patients who had cerebral AVMs were examined with two magnetic resonance imaging (MRI) techniques: perfusion imaging using a CASL technique with two delay times, 800 and 1200 ms, and T(2)-weighted dynamic contrast-enhanced MRI (T(2)-DCE-MRI). The signal-to-noise ratio obtained in our study with the CASL technique at 3 T was sufficient to estimate perfusion in gray matter. Both nidal and venous perfusion turned out larger by factors of 1.71±2.01 and 2.48±1.51 in comparison to T(2)-DCE-MRI when using CASL at delay times of 800 and 1200 ms, respectively. Moreover, the venous and nidal perfusion values of the AVMs measured at T(2)-DCE-MRI did not correlate with those observed at CASL. Evaluation of average perfusion values yielded significantly different results when using a shorter versus a longer delay time. Average gray matter perfusion was 15.8% larger when measured at delay times of w=800 ms versus w=1200 ms, while nidal perfusion was 15.7% larger and venous perfusion was 34.6% larger, respectively. In conclusion, the extremely high perfusion within an AVM could be successfully quantified using CASL. A shorter postlabeling delay time of w=800 ms seems to be more appropriate than a longer time of w=1200 ms because of possible inflow of unlabeled spins at the latter.

Mass spectrometry-based plasma peptide profiling of acute exacerbation in HBeAg-positive chronic hepatitis B.

BACKGROUND: Acute exacerbations (AE) of serum alanine aminotransferase activities that are 5 times above the normal upper limit frequently occur during the immune clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB). It is unclear how the varying clinical severities of AE reflect differences in the underlying immune responses against the hepatitis B virus. METHODS: We utilized magnetic bead-based purification methods coupled with MALDI-TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB patients experiencing AE without and with clinical decompensation. RESULTS: Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory spectral profile than immobilized Cu(2+) metal ion affinity chromatography did for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support Vector Machine, a classification model consisting of 5 classifiers was determined to give a sensitivity of 94.7% and a specificity of 75% for differentiating patients with and without decompensation. Classifiers identified as fragments derived from transthyretin and apolipoprotein A-IV were significantly decreased and increased in patients with decompensation, respectively. CONCLUSIONS: Our study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass spectrometry can be used for differentiating AE with and without decompensation in patients with HBeAg-positive CHB.

Prospective motion correction improves diagnostic utility of pediatric MRI scans.

A new technique for prospectively correcting head motion (called PROMO) during acquisition of high-resolution MRI scans has been developed to reduce motion artifacts. To evaluate the efficacy of PROMO, four T1-weighted image volumes (two with PROMO enabled, two uncorrected) were acquired for each of nine children. A radiologist, blind to whether PROMO was used, rated image quality and artifacts on all sagittal slices of every volume. These ratings were significantly better in scans collected with PROMO relative to those collected without PROMO (Mann-Whitney U test, P < 0.0001). The use of PROMO, especially in motion-prone patients, should improve the accuracy of measurements made for clinical care and research, and potentially reduce the need for sedation in children.

Quantitative T(1)(ρ) imaging using phase cycling for B0 and B1 field inhomogeneity compensation.

T(1)(ρ) imaging is useful in a number of clinical applications. T(1)(ρ) preparation methods, however, are sensitive to non-uniformities of the B0 magnetic field and the B1 RF field. These common system imperfections can result in image artifacts and quantification errors in T(1)(ρ) imaging. We report on a phase-cycling method which can eliminate B1 RF inhomogeneity effects in T(1)(ρ) imaging. This method does not only correct for image artifacts but also for T(2)(ρ) contamination caused by B1 RF inhomogeneity. The presence of B0 magnetic field inhomogeneity can compromise the effectiveness of this method for B1 RF inhomogeneity correction. We demonstrate that, by combining the spin-locking scheme reported by Dixon et al. (Myocardial suppression in vivo by spin locking with composite pulses. Magn Reson Med 1996; 36:90-94) with phase cycling, we can simultaneously correct B0 magnetic field inhomogeneity effects and B1 RF inhomogeneity effects in T(1)(ρ) imaging. Phantom and in vivo data sets are used to demonstrate the proposed methods and to compare them with other existing T(1)(ρ) preparation methods.

Comparison of T1rho measurements in agarose phantoms and human patellar cartilage using 2D multislice spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot techniques at 3 T.

OBJECTIVE: The purpose of this article is to compare in vitro T1rho measurements in agarose phantoms and articular cartilage specimens using 2D multislice spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot MRI sequences. MATERIALS AND METHODS: Six phantoms (agarose concentration, 2%, 3%, and 4%; n = 2 each) and 10 axially sliced patellar specimens from five cadaveric donors were scanned at 3 T. T1rho-weighted images were acquired using 2D spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot sequences. Regions of interest were analyzed to measure T1rho values centrally within phantoms, to evaluate effects of pulse sequence and agarose concentration. In patellar specimens, regions of interest were analyzed to measure T1rho values with respect to anatomic location (the medial and lateral facets and the median ridge in deep and superficial halves of the cartilage) as well as location that exhibited magic angle effect in proton density-weighted images, to evaluate the effects of pulse sequence, anatomic location, and magic angle. RESULTS: In phantoms, T1rho values were similar (p = 0.9) between sequences but decreased significantly (p < 0.001), from ∼55 to ∼29 milliseconds, as agarose concentration increased from 2% to 4%. In cartilage specimens, T1rho values were also similar between sequences (p = 0.3) but were significantly higher (p < 0.001) in the superficial layer (95-120 milliseconds) compared with the deep layer (45-75 milliseconds). CONCLUSION: T1rho measurements of human patellar cartilage specimens and agarose phantoms using 2D spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot sequences gave similar values. Lower T1rho values for phantoms with higher agarose concentrations and proteoglycan concentrations that are higher in deeper layers of cartilage than in superficial layers suggest that our method is sensitive to concentration of macromolecules in biologic tissues.

Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. METHODS: MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. RESULTS: A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. CONCLUSIONS: Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.

Radiofrequency pulses for simultaneous short T2 excitation and long T2 suppression.

Magnetic resonance imaging of short T(2) musculoskeletal tissues such as ligaments, tendon, and cortical bone often requires specialized pulse sequences to detect sufficiently high levels of signal, as well as additional techniques to suppress unwanted long T(2) signals. We describe a specialized radiofrequency technique for imaging short T(2) tissues based on applying hard 180° radiofrequency excitation pulses to achieve simultaneous short T(2) tissue excitation and long T(2) tissue signal suppression for three-dimensional ultrashort echo time applications. A criterion for the pulse duration of the 180° radiofrequency pulses is derived that allows simultaneous water and fat suppression. This opens up possibilities for direct imaging of short T(2) tissues, without the need for additional suppression techniques. Bloch simulations and experimental studies on short T(2) phantoms and specimen were used to test the sequence performance.

Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy.

BACKGROUND: The purposes of this study were to address a persistent controversy as to whether the ER status of a primary tumor remains stable during progression to metastasis and to evaluate the influence of disease course and prior systemic therapy on ER status. METHODS: Breast carcinomas from 227 women with known ER status in both primary tumor and paired metastasis were retrospectively reviewed. ER status was compared between primary and metastatic tumors with respect to metastatic site, interval between two ER assays, and intervening chemotherapy and endocrine therapy. Semiquantitative comparison of ER values was performed for 92 tumor pairs. RESULTS: ER status agreed in 210 (92.5%) patients, including 147 positive and 63 negative. Of the 17 patients (7.5%) with discordant ER status, both negative to positive conversion (n = 7) and positive to negative conversion (n = 10) were observed. ER discordance was not significantly associated with metastatic site (locoregional vs distant), time interval between assays (< 5 years vs. ≥ 5 years), or intervening chemotherapy and endocrine therapy. Semiquantitative levels of ER expression were similar between primary and metastatic tumors. In discordant cases, variations in testing methods and marginal scores were common. CONCLUSIONS: ER status in breast carcinoma is generally stable during progression to metastasis. Preanalytical and analytical variability may contribute to discordance in some cases. Given the importance of ER status for clinical management, ER testing in metastatic breast carcinoma should be repeated, especially for patients whose clinical courses are not compatible with stated ER status.