Probing lipids relaxation times in breast cancer using magnetic resonance spectroscopic fingerprinting.

OBJECTIVES: To investigate the clinical relevance of the relaxation times of lipids within breast cancer and normal fibroglandular tissue in vivo, using magnetic resonance spectroscopic fingerprinting (MRSF). METHODS: Twelve patients with biopsy-confirmed breast cancer and 14 healthy controls were prospectively scanned at 3 T using a protocol consisting of diffusion tensor imaging (DTI), MRSF, and dynamic contrast-enhanced (DCE) MRI. Single-voxel MRSF data was recorded from the tumor (patients) - identified using DTI - or normal fibroglandular tissue (controls), in under 20 s. MRSF data was analyzed using in-house software. Linear mixed model analysis was used to compare the relaxation times of lipids in breast cancer VOIs vs. normal fibroglandular tissue. RESULTS: Seven distinguished lipid metabolite peaks were identified and their relaxation times were recorded. Of them, several exhibited statistically significant changes between controls and patients, with strong significance (p < 10-3) recorded for several of the lipid resonances at 1.3 ppm (T1 = 355 ± 17 ms vs. 389 ± 27 ms), 4.1 ppm (T1 = 255 ± 86 ms vs. 127 ± 33 ms), 5.22 ppm (T1 = 724 ± 81 ms vs. 516 ± 62 ms), and 5.31 ppm (T2 = 56 ± 5 ms vs. 44 ± 3.5 ms, respectively). CONCLUSIONS: The application of MRSF to breast cancer imaging is feasible and achievable in clinically relevant scan time. Further studies are required to verify and comprehend the underling biological mechanism behind the differences in lipid relaxation times in cancer and normal fibroglandular tissue. KEY POINTS: •The relaxation times of lipids in breast tissue are potential markers for quantitative characterization of the normal fibroglandular tissue and cancer. •Lipid relaxation times can be acquired rapidly in a clinically relevant manner using a single-voxel technique, termed MRSF. •Relaxation times of T1 at 1.3 ppm, 4.1 ppm, and 5.22 ppm, as well as of T2 at 5.31 ppm, were significantly different between measurements within breast cancer and the normal fibroglandular tissue.

Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals.

AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls 179/137 and 30/15, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (NSCLC) sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. CONCLUSIONS: Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.

Margin assessment before intraoperative radiotherapy during breast conserving surgery-Does the addition of MarginProbe decrease the need for addition of fractionated whole breast radiation?

When performing Breast Conserving Surgery (BCS) with Intraoperative Radiation Therapy (IORT), positive resection margin necessitates not only re-lumpectomy-but also the addition of fractionated whole breast radiation. This retrospective study of 106 patients undergoing BCS and IORT aims to evaluate intraoperative margin assessment use in our center, and the contribution of the MarginProbe device (MP) to achieving negative surgical margins. Eleven out of 106 lumpectomy specimens had a total of 17 margins positive for tumor cells. Intraoperative gross pathology identified 6 (43%) involved margins, MarginProbe detected 8 (50%), and their combined use allowed for detection of 12 (70.5%) involved margins. In conclusion, the adjunctive use of intraoperative gross pathology and MarginProbe reduced the number of lumpectomies with positive resection margins by more than 50%, decreasing the need for re-lumpectomy and the addition of whole breast radiation.

Breast MRI during lactation: effects on tumor conspicuity using dynamic contrast-enhanced (DCE) in comparison with diffusion tensor imaging (DTI) parametric maps.

PURPOSE: To investigate the effect of lactation on breast cancer conspicuity on dynamic contrast-enhanced (DCE) MRI in comparison with diffusion tensor imaging (DTI) parametric maps. MATERIALS AND METHODS: Eleven lactating patients with 16 biopsy-confirmed pregnancy-associated breast cancer (PABC) lesions were prospectively evaluated by DCE and DTI on a 1.5-T MRI for pre-treatment evaluation. Additionally, DCE datasets of 16 non-lactating age-matched breast cancer patients were retrospectively reviewed, as control. Contrast-to-noise ratio (CNR) comprising two regions of interests of the normal parenchyma was used to assess the differences in the tumor conspicuity on DCE subtraction images between lactating and non-lactating patients, as well as in comparison against DTI parametric maps of λ1, λ2, λ3, mean diffusivity (MD), fractional anisotropy (FA), and maximal anisotropy index, λ1-λ3. RESULTS: CNR values of breast cancer on DCE MRI among lactating patients were reduced by 62% and 58% (p < 0.001) in comparison with those in non-lactating patients, when taking into account the normal contralateral parenchyma and an area of marked background parenchymal enhancement (BPE), respectively. Among the lactating patients, DTI parameters of λ1, λ2, λ3, MD, and λ1-λ3 were significantly decreased, and FA was significantly increased in PABC, relative to the normal lactating parenchyma ROIs. When compared against DCE in the lactating cohort, the CNR on λ1, λ2, λ3, and MD was significantly superior, providing up to 138% more tumor conspicuity, on average. CONCLUSION: Breast cancer conspicuity on DCE MRI is markedly reduced during lactation owing to the marked BPE. However, the additional application of DTI can improve the visualization and quantitative characterization of PABC, therefore possibly suggesting an additive value in the diagnostic workup of PABC. KEY POINTS: • Breast cancer conspicuity on DCE MRI has decreased by approximately 60% among lactating patients compared with non-lactating controls. • DTI-derived diffusion coefficients and the anisotropy indices of PABC lesions were significantly different than those of the normal lactating fibroglandular tissue. • Among lactating patients, breast cancer conspicuity on DTI-derived parametric maps provided up to 138% increase in contrast-to-noise ratio compared with DCE imaging.

Noncontrast Breast MRI During Pregnancy Using Diffusion Tensor Imaging: A Feasibility Study.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is often a delayed diagnosis and contrast-enhanced MRI is contraindicated because gadolinium agents are known to cross the placenta. PURPOSE: To investigate the feasibility and clinical utility of noncontrast breast MRI using diffusion tensor imaging (DTI) in the diagnostic workup of PABC. STUDY TYPE: Prospective. POPULATION: Between November 2016 and January 2018, 25 pregnant participants (median gestational age: 17 weeks) were recruited from eight referral breast-care centers nationwide. Imaging indications included: newly-diagnosed PABC (n = 10, with 11 lesions), palpable mass/mastitis (n = 4), high-risk screening (n = 10), and monitoring neoadjuvant-chemotherapy response (n = 1). FIELD STRENGTH/SEQUENCE: 1.5T, T2 -weighted, and DTI sequences, prone position, with a scan duration of ∼12 minutes. ASSESSMENT: DTI parametric maps were generated and analyzed at pixel resolution, with reference to ultrasound (US) and pathology. STATISTICAL TESTS: Two-tailed Student's t-test was applied for evaluating differences between DTI parameters of PABC vs. healthy fibroglandular tissue. Pearson's correlation test was applied to measure the agreements between λ1-based longest tumor diameter, US, and pathology. RESULTS: All scans were technically completed and reached diagnostic quality, except one with notable motion artifacts due to positional discomfort, which was excluded. Nine out of 11 known PABC lesions and one newly-diagnosed lesion were visible on λ1, λ2, λ3, mean diffusivity (MD), and λ1-λ3 maps, with substantial parametric contrast compared with the apparently normal contralateral fibroglandular tissue (P < 0.001 for all). Two lesions of 0.7 cm were not depicted by the diffusivity maps. Tumor diameter measured on a thresholded λ1 map correlated well with US (r = 0.97) and pathology (r = 0.95). Malignancy was excluded by DTI parametric maps in scans of symptomatic and high-risk patients, in agreement with US follow-up, except for one false-positive case. DATA CONCLUSION: Noncontrast breast MRI is feasible and well-tolerated during pregnancy. Further studies with a larger and homogeneous cohort are required to validate DTI's additive diagnostic value, albeit this study suggests a potential adjunct role for this noninvasive approach in breast evaluation during pregnancy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:508-517.

Mapping breast tissue types by miniature radio-frequency near-field spectroscopy sensor in ex-vivo freshly excised specimens.

BACKGROUND: Receiving real-time information on tissue properties while performing biopsy procedures has the potential of improving biopsy accuracy. The study goal was to test the ability of a miniature flexible Radio-Frequency (RF) sensor (Dune Medical Devices), designed to be mounted on the surface of surgical tools, in measuring and mapping the various breast tissue types and abnormalities in terms of electrical properties. METHODS: Between January and October 2012, 102 patients undergoing lumpectomy, open-biopsy or mastectomy, in 3 medical centers, were enrolled in this study. The device was applied to freshly excised specimens, with registration between device measurements and histology analysis. Based on histology, the dielectric properties of the various tissue types were derived. Additionally, the ability of the device to differentiate between malignant and non-malignant tissue was assessed. RESULTS: A total of 4322 measurements from 106 specimens from 102 patients were analyzed. The dielectric properties of 10 tissue types in the low RF-frequency range were measured, showing distinct differences between the various types. Based on the dielectric properties, a score variable was derived, which showed a correlation of 90 % between the RF measurements and the tissue types. Differentiation ability between tissue types was characterized using ROC curve analysis, with AUC of 0.96, and sensitivity and specificity of 90 and 91 % respectively, for tissue feature sizes at or above 0.8 mm. CONCLUSIONS: Using a radio-frequency near-field spectroscopy miniature flexible sensor the dielectric properties of multiple breast tissue types, both normal and abnormal, were evaluated. The results show promise in differentiating between various breast tissue types, and specifically for differentiation between cancer and normal tissues.

Percutaneous aspiration of the gall bladder for the treatment of acute cholecystitis: a prospective study.

BACKGROUND: Urgent laparoscopic cholecystectomy has been established as the best treatment for acute cholecystitis. However, conservative treatment is advocated for high-risk patients. Failure of conservative treatment can result in high-risk operations with relatively high rates of operative morbidity. Percutaneous cholecystostomy is a good option for these patients. Recently, percutaneous aspiration of the gall bladder without drain has been described. METHODS: A protocol of initial conservative management in high-operative-risk patients admitted with acute cholecystitis was prospectively assessed. Patients who did not respond to antibiotics were treated with percutaneous trans-hepatic aspiration of the gall bladder under ultrasound guidance. Following discharge, the patients were seen in the outpatient clinic and elective laparoscopic cholecystectomy was considered and scheduled as necessary. RESULTS: Between January 2011 and December 2012, 33 patients with persistent clinical and sonographic signs of acute cholecystitis after failure of initial antibiotic treatment underwent gall bladder aspiration under ultrasound guidance. No complications related to the procedure were reported. In 25 patients (76 %), the procedure was successful and they were discharged. Seven patients needed repeated aspiration. Eight patients (24 %) who did not improve underwent percutaneous cholecystostomy and were discharged with a drain and later reevaluated for elective surgery. The mean hospital stay of patients with successful aspiration was 3 days. During the follow-up period, 23 patients underwent elective interval laparoscopic cholecystectomy. Two were converted to open surgery (8.7 %). CONCLUSIONS: Conservative treatment and delayed operation is an acceptable option for acute cholecystitis. Percutaneous gall bladder aspiration is a simple and effective procedure, with a high success rate and low morbidity. Laparoscopic cholecystectomy after drainage of the gall bladder has low morbidity with a relatively low conversion rate.

Assessment of surgical discharge summaries and evaluation of a new quality improvement model.

BACKGROUND: Discharge summaries after hospitalization provide the most reliable description and implications of the hospitalization. A concise discharge summary is crucial for maintaining continuity of care through the transition from inpatient to ambulatory care. Discharge summaries often lack information and are imprecise. Errors and insufficient recommendations regarding changes in the medical regimen may harm the patient's health and may result in readmission. OBJECTIVES: To evaluate a quality improvement model and training program for writing postoperative discharge summaries for three surgical procedures. METHODS: Medical records and surgical discharge summaries were reviewed and scored. Essential points for communication between surgeons and family physicians were included in automated forms. Staff was briefed twice regarding required summary contents with an interim evaluation. Changes in quality were evaluated. RESULTS: Summaries from 61 cholecystectomies, 42 hernioplasties and 45 colectomies were reviewed. The average quality score of all discharge summaries increased from 72.1 to 78.3 after the first intervention (P < 0.0005) to 81.0 following the second intervention. As the discharge summary's quality improved, its length decreased significantly. CONCLUSIONS: Discharge summaries lack important information and are too long. Developing a model for discharge summaries and instructing surgical staff regarding their contents resulted in measurable improvement. Frequent interventions and supervision are needed to maintain the quality of the surgical discharge summary.

Laparoscopic repair of giant diaphragmatic hernias: evolving technical aspects and outcomes.

BACKGROUND: Laparoscopic repair of giant diaphragmatic hernias (GDH) can be challenging, especially when partial or complete volvulus of the herniated stomach is encountered. OBJECTIVES: To review our experience with laparoscopic repair of GDH, emphasizing preoperative investigation, technical aspects, and outcome. METHODS: We conducted a retrospective review of patients operated on for GDH who were diagnosed when at least half the stomach was found in the mediastinum at surgery. Technical aspects and surgical outcomes were evaluated. RESULTS: Fifty patients underwent laparoscopic GDH repair during an 8 year period. Four patients admitted with acute symptomatic volvulus of the stomach were initially treated by endoscopic decompression followed by surgery during the same admission. Two cases were converted to open surgery. Initial surgery was successful in 45 patients; 3 had an immediate recurrence, 1 was reoperated for dysphagia during the same admission, and 1 had a mediastinal abscess. During long-term follow-up, six patients required reoperation for recurrent hernias. Another four patients had asymptomatic partial herniation of the stomach. The main reason for failure was incomplete reduction of the hernia sac, especially the posterior component. No correlation was found between the type of repair and surgical failure. Most patients who did not undergo an anti-reflux procedure had postoperative reflux unrelated to their preoperative workup. CONCLUSIONS: Laparoscopic repair of GDH is challenging, but practical and safe. It should be the treatment of choice for this potentially life-threatening condition. Careful attention to pitfalls, such as the posterior element of the sac, and routine performance of an anti-reflux procedure are crucial.

Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1ß with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition.

BACKGROUND: The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1ß were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course. METHODS: The expression of CCL2, CCL5, TNFα and IL-1ß was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments. RESULTS: CCL2, CCL5, TNFα and IL-1ß were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1ß in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1ß expression. These results suggest progression-related roles for TNFα and IL-1ß in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1ß compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1ß) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1ß acts jointly with other pro-malignancy factors to promote disease relapse. CONCLUSIONS: Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1ß may be important for disease course, and that TNFα & IL-1ß may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.