Mediastinal Blood Research Articles

Correlation between EGFR mutation status and F18 -fluorodeoxyglucose positron emission tomography-computed tomography image features in lung adenocarcinoma.

BackgroundThe purpose of this study was to investigate an association between EGFR mutation status and 18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG PET‐CT) image features in lung adenocarcinoma.MethodsRetrospective analysis of the data of 139 patients with lung adenocarcinoma confirmed by surgical pathology who underwent preoperative 18F‐FDG PET‐CT was conducted. Correlations between EGFR mutation status, clinical characteristics, and PET‐CT parameters, including the maximum standardized uptake value (SUVmax), the mean of the SUV (SUVmean), the peak of the SUV (SUVpeak) of the primary tumor, and the ratio of SUVmax between the primary tumor and the mediastinal blood pool (SUVratio), were statistically analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutation. Receiver operating characteristic curves of statistical quantitative parameters were compared.Results EGFR mutations were detected in 74 (53.2%) of the 139 lung adenocarcinomas and were more frequent in non‐smoking patients. Univariate analysis showed that the SUVmax, SUVmean, SUVpeak, and SUVratio were lower in EGFR‐mutated than in wild‐type tumors. The receiver operating characteristic curves showed no significant differences between their diagnostic efficiencies. Multivariate logistic regression analysis showed that being a never smoker was an independent predictor of EGFR mutation.ConclusionQuantitative parameters based on 18F‐FDG PET‐CT have modest power to predict the presence of EGFR mutation in lung adenocarcinoma; however, when compared to smoking history, they are not good or significant predictive factors.

Bone Marrow Tracer Uptake Pattern of PET/CT in Multiple Myeloma: Image Interpretation Criteria and Prognostic Value

The clinical significance of 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography (PET/CT) in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the value of bone marrow (BM) imaging pattern assessed by PET/CT in MM. And no standardized imaging interpretation criteria have been established to define different imaging pattern. Besides, the lack of standardized interpretation criteria hampered the routine use of PET/CT and led to low interobserver reproducibility in interpreting results. We herein report a study that aimed at finding out the appropriate interpretation criteria to define different tracer uptake pattern on PET/CT and analyzing the prognostic implications of baseline BM FDG uptake pattern in patients with multiple myeloma.We retrospectively studied 52 healthy individuals who had undergone PET/CT scan for cancer screening and 172 newly diagnosed MM patients. In our healthy cohort, BM FDG uptake (represented by the average SUVmean of L1 and L2 vertebral body) were higher than that of liver (SUVmean), spleen (SUVmean) and mediastinal blood pool (SUVmax) in 1 (1.9%), 11 (21.2%) and 4 (7.7%) patients, respectively, in physiological status. Hence, we proposed new PET/CT interpretation criteria for evaluation of BM tracer uptake pattern in MM. According to these criteria, 60 (34.9%) patients had focal (focal lesion in BM with FDG uptake higher than liver, Figure 1A), 6 (3.5%) had diffuse (diffuse homogenous BM FDG uptake higher than liver, Figure 1B), 66 (38.4%) had mixed pattern (innumerable hypermetabolic foci on a background of BM with diffusely increased tracer uptake, Figure 1C) and 40 (23.3%) had normal BM uptake. The bone marrow FDG uptake was correlated to bone marrow plasma cell infiltration rate (r = 0.228, P < 0.01). Besides, plasma cell infiltration rate differed in different uptake pattern: patients with diffuse/mixed bone marrow FDG uptake pattern had the highest mean bone marrow plasma cell infiltration rate, followed by those with focal pattern (Kruskal-Wallis test, P < 0.0001). Furthermore, BM tracer uptake pattern demonstrated correlations with prognostically relevant baseline parameters: diffuse/mixed pattern was correlated with higher BM plasma cell infiltration rate, more advance ISS stage, lower hemoglobin level, higher level of β2-microglobulin and serum creatinine. Diffuse/mixed BM tracer uptake pattern (Figure 2A-B), more than ten FDG-avid focal lesions (PET-FL) at baseline (Figure 2C-D), presence of extramedullary disease (EMD, Figure 2I-J), and a standardized uptake value (SUV-FL) > 5.3 (Figure 2E-F) adversely affected estimated 3-year progression free survival (3-yr PFS; diffuse/mixed pattern: 26.8%; PET-FL > 10: 54.2%; EMD: 0.0%; SUV-FL > 5.3: 32.5%) and overall survival (3-yr OS; diffuse/mixed pattern: 50.6%; PET-FL > 10: 44.8%; EMD: 0.0%; SUV-FL > 5.3: 51.0%). Presence of paramedullary soft tissue lesion adjacent to bone marrow shortened PFS with borderline adverse influence on OS (Figure 2K-L). Clinical outcomes were not significantly influenced by the number of osteolytic lesion on CT images (Figure 2G-H). In multivariate analysis (Table 1), the following factors were found to be independent prognostic factors for inferior outcome: diffuse/mixed BM uptake pattern, PET-FL > 10, EMD, hypercalcemia, hypoalbuminemia and level of blood lactate dehydrogenase > upper limit. Diffuse/mixed BM FDG uptake pattern was an independent predictor associated with inferior OS (HR 7.10; 95% CI 1.33-37.95) and PFS (HR 5.98; 95% CI 1.30-27.54).In conclusion, we propose an FDG uptake higher than that of liver is an appropriate positivity cut-off to discriminate physiological and pathological uptake in bone marrow for patients with multiple myeloma. With these interpretation criteria, the bone marrow PET/CT pattern can be defined as four types: normal, focal, diffuse and mixed. A diffuse/mixed BM FDG uptake pattern is a reliable predictor of inferior outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Targeted Molecular Imaging of Translocator Protein (TSPO) Using 18FGE180-PET for the Diagnosis of Gastrointestinal Graft Versus host Disease (GI-GVHD)

Introduction:Acute Gastrointestinal Graft Versus Host Disease (GI-GVHD) is a life-threatening complication following haematopoietic progenitor cell transplantation (HPCT). Recent data suggest that the current gold standard diagnostic test (endoscopic biopsy) fails to identify 26% of those patients requiring treatment. The mitochondrial translocator protein TSPO is upregulated in activated macrophages and inflammatory bowel diseases, and thus may be a biomarker of acute GI-GVHD. 18FGE180 is a novel TSPO-targeting radioligand for use in positron emission tomography imaging (18FGE180-PET).Methods:We performed a prospective observational pilot study evaluating 18FGE180-PET in adults with clinically suspected acute GI-GVHD occurring within 100 days following HPCT. Participants underwent a baseline 18FGE180-PET within 7 days of diagnostic endoscopy, and a follow-up 18FGE180-PET 1-4 weeks later. Tissue avidity was assessed visually in four sections of the gastrointestinal tract (GIT; stomach, duodenum, sigmoid and rectum) and rated by standardised uptake variable (SUV), with “positive” defined by SUV greater than mediastinal blood pool (MBP). Imaging findings were correlated with patient demographics, symptom severity (defined by modified Glucksberg stage), endoscopic findings, and histologic diagnosis. For patients in whom GI-GVHD treatment was initiated (defined as minimum prednisone 1mg/kg or equivalent), the clinical response was correlated with GIT avidity during the second 18FGE180-PET.Results:Six (6) patients were recruited, with median age 57 years (range 53-68 years), at a median 66 days post HPCT (range 26-95 days). Median Glucksberg stage of presumptive GI-GVHD was 2 (range 1-3). The histological diagnosis was GI-GVHD in 4 (66%) patients, and drug toxicity in the remaining two patients. Concordance between histological findings and 18FGE180-PET avidity by GIT section were 50% (stomach), 100% (duodenum), 100% (sigmoid) and 80% (rectum). 18FGE180-PET was highly accurate in duodenum and sigmoid (sensitivity 100%, specificity 100%), moderately accurate in rectum (sensitivity 66%, specificity 100%), and non-specific in stomach (sensitivity 100%, specificity 25%). Five (83%) patients subsequently underwent treatment for GI-GVHD, and of these 4 (80%) underwent repeat 18FGE180-PET for response assessment, seven days after the first. In these patients, high concordance between clinical response and 18FGE180-PET avidity was demonstrated in sigmoid (100%), rectum (100%) and duodenum (75%), compared with poor concordance in stomach (25%). The final patient, whose biopsies were negative for GI-GVHD and did not undergo GVHD treatment, was non-avid at all sites on both initial and subsequent 18FGE180-PET.Conclusion:18FGE180-PET appears to show utility in the diagnosis of GI-GVHD in small and large bowel. Larger prospective studies, correlating with histological TSPO expression, are warranted. DisclosuresNo relevant conflicts of interest to declare.

PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group

Background. Combined modality treatment (CMT) consisting of two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and 20 Gy of involved-field radiotherapy (IFRT) is widely accepted standard of care for early-stage favorable Hodgkin lymphoma (HL). Recent clinical research suggests that metabolic response assessment after two cycles of chemotherapy using FDG-PET (PET-2) can predict the individual outcome and PET-2 negativity might allow reducing the overall treatment intensity.Aims. We assessed whether omitting consolidating radiotherapy in patients with negative PET-2 is feasible without loss of efficacy as determined by progression-free survival (PFS). Furthermore, we analyzed the prognostic impact of PET-2 among patients receiving CMT.Methods. Between November 2009 and December 2015, we recruited patients with newly diagnosed, early-stage favorable HL aged 18-75 years from Germany, Switzerland, Austria, and the Netherlands for this double-blind, randomized, parallel-group phase 3 trial. Patients were randomly assigned to receive standard CMT with 2x ABVD and 20 Gy IFRT or PET-guided treatment, whereby IFRT was restricted to those patients with a positive PET after 2xABVD. PET-2 was centrally assessed by a panel blinded towards the randomization result, with FDG uptake not higher than the mediastinal blood pool (i.e., Deauville score 1-2) defined as negative. The trial was designed to exclude inferiority of 10% or more in 5-year PFS of ABVD only compared with CMT in a per-protocol analysis among PET-negative patients, corresponding to a non-inferiority margin of 3.01 for the hazard ratio, and to detect a 5-year PFS difference of 5% or more between PET-2-positive and -negative patients receiving CMT, each with 80% power.Results. A total of 1150 patients were enrolled; 628 patients with negative PET-2 were eligible for the per-protocol non-inferiority analysis and were treated with CMT (n=328) or ABVD alone (n=300). With a median follow-up of 47 months, the estimated 5-year PFS was 93.4% (90.4-96.5) with CMT and 86.1% (81.4-90.9) with chemotherapy only (difference 7.3%, 95% CI 1.6%-13.0%). The hazard ratio was 1.78 with a 95% CI ranging from 1.02 to 3.12, including the non-inferiority margin of 3.01. The PFS difference primarily resulted from a significant increase in disease recurrences with in-field recurrence rates of 2.1% vs. 8.7% (p=0.0003); there was no relevant difference regarding out-field recurrences (3.7% vs. 4.7%, p=0.55). Estimated 5-year overall survival in the per-protocol population was 98.1% (96.5-99.8) with CMT and 98.4% (96.5-100.0) with ABVD.693 patients assigned to receive CMT were eligible for the analysis of the PET objective and had a negative (n=353) or positive (n=340) PET-2. With a median follow-up of 46 months, estimated 5-year PFS was 93.2% (90.2-96.2) among PET-2-negative and 88.1% (83.8-92.3) among PET-2-positive patients (p=0.035). When using the more common liver cutoff (Deauville score 4) for the definition of PET-2 positivity, the difference was more pronounced (5-year PFS 93.1% [90.7%-95.5%] vs. 80.1% [71.2%-88.9%], p=0.0004).Conclusion. In early-stage favorable HL, radiotherapy cannot be safely omitted from standard CMT without a clinically relevant loss of tumor control in patients with negative PET-2. PET positivity after 2xABVD represents a risk factor for PFS in HL patients treated with standard CMT, particularly when a Deauville score of 4 is considered as cutoff for positivity. DisclosuresGreil:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Sandoz: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. von Tresckow:MSD: Honoraria, Other: Travel support, Research Funding; Novartis: Honoraria, Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding. Borchmann:Novartis: Consultancy, Honoraria.

Standardization of 18F-FDG PET/CT According to Deauville Criteria for MRD Evaluation in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Joined Analysis of Two Prospective Randomized Phase III Trials

Standardization of 18F-FDG PET/CT According to Deauville Criteria for MRD Evaluation in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Joined Analysis of Two Prospective Randomized Phase III Trials

Interim PET-Based Outcome Prediction in Diffuse Large B-Cell Lymphoma Patients Participating in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) Trial: Comparison of the Delta SUV Max Method and the Deauville 5-Point Scale

Introduction: The recently published randomized PETAL trial (JCO 36:2024, 2018) aimed at improving outcome of aggressive non-Hodgkin lymphomas by changing therapy based on the response to the first 2 cycles of standard (R-)CHOP as assessed by interim PET (iPET). Outcome remained unaffected by treatment changes, which provided an opportunity to use the study to define the prognostic value of iPET. This report details the iPET results in the subgroup of patients (pts.) with diffuse large B-cell lymphoma (DLBCL), by comparing the deltaSUVmax method (J Nucl Med 48:1626, 2007) used in the course of the trial, with the Deauville 5-point scale (DS) which has been recommended for iPET-based outcome prediction in DLBCL (JCO 32:3048, 2014). With deltaSUVmax, a positive iPET indicating insufficient treatment response is defined as a reduction of the maximum standardized uptake value (SUV) by <66% compared to baseline. With DS, a positive iPET is variably defined as unphysiological residual activity above that of the mediastinal blood pool (DS >2) or the liver (DS >3) on the same interim scan.Methods: iPET scans for a post-hoc investigation using the Deauville criteria were available from 597 of 609 DLBCL pts. treated in the PETAL trial. For the binary cut-off variables of deltaSUVmax and DS, concordance and Spearman correlation were calculated and hazard ratios (HR) regarding event-free (EFS), overall (OS), progression-free survival (PFS), and time to progression (TTP) were determined by Cox regression. Time-dependent receiver operating characteristic (ROC) analysis (Biometrics 56:337-44, 2000) for the raw values of deltaSUVmax and DS yielded area under the curve (AUC), sensitivity, specificity, and predictive values that were accompanied with median and 95% confidence intervals (CI) obtained from a simple bootstrap with 1,000 repetitions. The integrated Brier score was used as a measure of model calibration.Results: The numbers of DLBCL pts. with a positive iPET scan were 62 for deltaSUVmax, 408 for DS >2, and 278 for DS >3. Concordance between a positive iPET according to deltaSUVmax and the DS cut-offs was 40.4% and 60.1%, and Spearman correlation was 0.17 and 0.24, respectively. HRs for a positive iPET according to deltaSUVmax were higher than for the two DS cut-offs in any time-to-event endpoint: 3.13 [CI: 2.22 - 4.46] in EFS as compared to 1.36 [0.99 - 1.85] for DS >2 and 1.38 [1.05 - 1.81] for DS >3; 3.48 [2.29 - 5.27] in OS versus 1.56 [1.03 - 2.36] and 1.91 [1.33 - 2.73]; 3.06 [2.11 - 4.43] in PFS compared to 1.22 [0.88 - 1.69] and 1.34 [1.00 - 1.80]; and 3.04 [1.97 - 4.67] versus 1.28 [0.88 - 1.88] and 1.46 [1.04 - 2.07] in TTP. ROC analysis confirmed this tendency as AUCs were higher for deltaSUVmax than for DS in all four endpoints (Table 1). Also, the difference of predictive values of the two markers favored deltaSUVmax over DS >3 in EFS (Figure 1). Similar results were obtained in the remaining endpoints and for DS >2. Calibration assessed by the Brier score was slightly better for deltaSUVmax than for DS in EFS, PFS, and TTP, and was equal in OS. Of note, when investigating the survival curves in subgroups defined by both deltaSUVmax and DS >3, pts. with negative deltaSUVmax but positive DS showed similar survival as pts. with deltaSUVmax and DS both negative, presumably indicating DS false-positives (Figure 2). The same was true for deltaSUVmax positive/DS negative pts. whose unfavorable survival curve resembled that of double-positive pts..Conclusion: DeltaSUVmax seems to be a more potent prognostic factor than DS in terms of discrimination and calibration with respect to EFS, OS, PFS, and TTP. Superior performance was shown for raw values as well as for dichotomized variables. The DS appeared unreliable due to a high number of false-positive results. Although the AUCs for deltaSUVmax were relatively low, it still seems to be a good prognostic tool with regard to HRs. Given its high positive predictive value, it may be a suitable tool to select poor-prognosis pts. in first-line for treatment approaches that have so far been reserved for later lines of therapy. [Display omitted] DisclosuresHüttmann:Roche: Other: Travel expenses; Celgene: Other: Travel expenses. Duehrsen:Amgen: Research Funding; Gilead: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Impacts of time interval on 18F-FDG uptake for PET/CT in normal organs: A systematic review.

Background:To perform a systematic review of the effect of time interval on 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) uptake in normal organs.Methods:PubMed, EMBASE, Ovid, and Cochrane databases were searched to identity all potential eligible literature. The study characteristics and relevant data were extracted and analyzed. We adopted the effect size (ES) and the coefficient of determination (R2) to best measure the magnitude of the relation between time interval and 18F-FDG uptake in normal organs.Results:Seven articles and 860 participants were included. The time interval on liver and mediastinal blood pool were relatively medium (R2=0.01–0.03, ES = –0.57 and –0.60) but noticeable (R2 = 0.06, ES = –0.68 and –0.39), respectively. The uptake of 18F-FDG on cerebellum, spleen, bone marrow, muscle, bowel, and adipose remains to be verified as the rare studies. In addition, other factors such as body mass index and blood glucose level appeared to be important which also affect 18F-FDG uptake in normal organs.Conclusion:The impact of time interval on SUVs in liver and mediastinal blood pool were relatively medium but clinically noticeable. More studies need to be done to solve the relation between the SUVs of other organs and time interval.

Reduced re-exploration and blood product transfusion after the introduction of the Papworth haemostasis checklist†.

Between 2% and 8% of patients return to the theatre for mediastinal bleeding following cardiac surgery. In the majority of patients, a surgical source of bleeding is identified. Both mediastinal bleeding and re-exploration are associated with increased morbidity and mortality and the use of blood products. The aim of this study was to develop a 'haemostasis checklist' with the intention of reducing mediastinal bleeding and re-exploration following cardiac surgery. The Papworth haemostasis checklist was developed with a multidisciplinary collaboration. It consists of 2 components: surgical sites and coagulation status. The checklist is completed at a 'time-out' prior to sternal wire insertion. The analysis compared the outcomes of patients undergoing cardiac surgery in the 1 year before and after implementation. A propensity analysis assessed the impact of re-exploration on outcomes. Three thousand eight hundred and eleven patients underwent cardiac surgery during the study period. Re-exploration for bleeding was associated with inferior outcomes. Following checklist implementation, there was a significant reduction in the re-exploration rate (3.47% vs 2.08%, P = 0.01) and proportion of patients bleeding >1 l in 12 h (6.1% vs 3.49%, P < 0.001). There was a significant reduction in consumption of blood products saving £102165 ($134198). The checklist implementation was associated with reduced intensive care unit length of stay and hospital length of stay, adding to the financial benefit. The haemostasis checklist represents a simple intervention which is quick and easy to use but has had a substantial impact on clinical outcomes. We have observed a significant reduction in the mediastinal blood loss, return-to-theatre rate and consumption of blood products, which is associated with a significant clinical and financial benefit.

Utility of FDG PET/CT in the Characterization of Sinonasal Neoplasms: Analysis of Standardized Uptake Value Parameters.

We aimed to evaluate the contribution of different standardized uptake value (SUV) parameters generated from pretreatment 18F-FDG PET/CT in the characterization of sinonasal neoplasms with histopathologic correlations. This retrospective study included 97 consecutive patients (58 men, 39 women; age range, 20-93 years; mean age, 62 years) with pathologically proven untreated sinonasal neoplasms who underwent FDG PET/CT from February 2010 to August 2017. Semiquantitative analysis of primary tumors were performed to evaluate the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and the ratio of the SUVmax of the primary tumor to the SUVmean of mediastinal blood pool, which we refer to here as " SUVratio." Various sinonasal tumor histopathologic subgroups (n = 14) were analyzed. The Kruskal-Wallis test was used to compare the SUVmax, SUVmean, and SUVratio with the histopathologic diagnosis. Mean values of SUVmax, SUVmean, and SUVratio for the sinonasal neoplasms were 16.6 ± 9.7 (SD), 8.6 ± 5.1, and 5.9 ± 3.7, respectively, and each parameter was significantly different between histopathologic types (p < 0.05). Mean values of SUVmax, SUVmean, and SUVratio were higher in sinonasal undifferentiated carcinoma (SNUC) than in olfactory neuroblastoma, metastasis, and adenoid cystic carcinoma (p < 0.05). Mean values of SUVmax and SUVmean were higher in squamous cell carcinoma (SCC) than in olfactory neuroblastoma and metastasis (p < 0.05). Also, mean SUVmax was higher in SCC and SNUC than in poorly differentiated carcinoma (p < 0.05). Mean SUVratio was higher in SCC than in small cell carcinoma, olfactory neuroblastoma, and adenoid cystic carcinoma (p < 0.05). We conclude that different SUV parameters from FDG PET/CT can be used as so-called "metabolic biopsy" to categorize sinonasal neoplasms into different histopathologic subgroups because it can help in the characterization of some of the more common subgroups of sinonasal neoplasms. However, we found that there is overlap in FDG uptake values among some of the rare histologic subgroups; hence, surgical biopsy is still needed for differentiation of histologic subtypes of aggressive sinonasal masses.

An Unusual Cause of Suspected Pulmonary Hypertension: Iatrogenic Left Internal Mammary Artery Pseudoaneurysm

A 73-year-old man was referred to our clinic because of increasing fatigue, shortness of breath, and new-onset pulmonary hypertension (pulmonary artery pressure 73 mm Hg). Echocardiography and thoracic computed tomography scan showed a 75 × 67-mm mediastinal blood thickening with diffuse luminal

Tumor to cervical spinal cord standardized uptake ratio (SUR) improves the reproducibility of 18F-FDG-PET based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting

BackgroundIn quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting. Materials and methodsNinety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland–Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients. ResultsBland–Altman’s analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort. ConclusionThe use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches.

Diagnosing polymyalgia rheumatica on 18F-FDG PET/CT: typical uptake patterns.

The diagnosis of polymyalgia rheumatica (PMR) is often challenging, since similar clinical features and laboratory findings can be observed in several inflammatory conditions. PMR involves affected sites in a specific manner, and 18F-FDG PET/CT has the advantage for assessing the disease activity of each site. The purpose of this study was to identify the patterns of 18F-FDG uptake that suggest the diagnosis of PMR. We studied 60 patients who had undergone 18F-FDG PET/CT scans for workup of suspected PMR, arthritis, enthesitis, or myopathy. Final diagnoses were made by board-certified rheumatologists. The incidence of significant 18F-FDG uptake, higher than mediastinal blood pool, of the following sites were compared among PMR patients and patients with other diseases: wrists, elbows, shoulders, sternoclavicular joints, acromioclavicular joints, spinous processes, ischial tuberosities, and greater trochanters. For the spinous processes, the incidence of "Y"-shaped uptake along the interspinous bursae was also evaluated. A definitive diagnosis of PMR was given to 16 of 60 patients. The incidence of significant 18F-FDG uptake in the definitive PMR group was 6% for wrists and for elbows, 88% for glenohumeral and sternoclavicular joints, 25% for acromioclavicular joints, 81% for spinous processes, 69% for ischial tuberosities, and 81% for greater trochanters. Patients with PMR showed a significantly higher incidence of "Y"-shaped uptake along the interspinous bursae than the other patients (38 vs. 9%) (P = 0.016). 18F-FDG uptake distribution patterns and morphology can contribute to the diagnosis of PMR. Significant 18F-FDG uptake in the sternoclavicular joints is one of the characteristic findings in patients with PMR as well as the uptake in the shoulders, ischial tuberosities, and greater trochanters. "Y"-shaped spinous process uptake may be one of the specific findings for PMR.

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

The aim of this study was to determine the performance of 18F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P<0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P<0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Assessment of Hormone Receptor Profile in Breast Cancer Using 18F‐Fluro‐Estradiol PET CT: A Pilot Study

Hormone Receptor (HR) status has vital implications in prognosis and therapy of breast cancer. Currently, HR status is assessed by immunohistochemistry (IHC) of core needle biopsy or surgical specimen. In this technique tumor is not studied in entiretyThis technique &amp; has 3–5% false negative rate.AimEvaluate use of 18F‐FES PET‐CT in determining receptor status of breast cancer.MethodsER expression on IHC: Core needle biopsy/excision specimens were fixed in formalin and paraffin embedded sections made &amp; subjected to IHC. Proportion of positive cells was given score of 0 to 5 &amp; intensity of uptake was given a score of 0 to 3. Total score was then calculated by summing up the total. Imaging with FES PET CT performed using standard protocol and images acquired. SUV of lesion, SUV ratio between lesion and background activity &amp; visual interpretation grading were correlated to ER expression on IHC. For SUV ratio, SUV of the breast lesion was compared to the SUV of the mediastinal blood pool in the thoracic aorta. Visual grading of the breast lesion on 18F‐FES PET‐CT CT was done as follows:Grade 1‐ no uptake on 18F‐FES PET‐CT;Grade 2‐uptake of lesion less than mediastinal blood pool; Grade 3‐uptake of lesion similar to mediastinal blood pool.; Grade 4‐Lesion well defined, uptake more than mediastinal blood pool/similar to liver. Correlation between lesion SUV, SUV ratio of lesion and mediastinal blood pool &amp; visual grading score with ER score as on IHC was calculated using the Spearman's correlation coefficient. The value of SUV ratio above which the lesion was considered ER positive was calculated using the receiver operating characteristic curve (ROC curve). P value of &lt; 0.05 was considered significant. Data analysis was done using Stata 11.2.ResultsTwenty four patients were enrolled for the study. Most of the patients were females (F:M= 22:2). All patients had invasive ductal carcinoma (NST) except for a 55 yr old lady who had high grade DCIS and no invasive component was found. IHC done on core needle biopsy specimens was used to determine the receptor status of the breast lumps. 16 patients were HR +ve ( 12 strongly +ve and 4 moderately +ve) and 8 were HR −ve. ROC curve (Fig 1) was plotted for SUV and tumours with SUV of &gt;/= 1.8 on 18F‐FES PET‐CT were categorized as ER+ (AUC=0.8190, sensitivity =73.33% &amp; specificity=71.43%). Comparison of HR status as assessed by FES PETCT and IHC is given in Table I. The sensitivity, specificity, false negative rates of of FES PETCT in evaluating HR status were 87.5%, 100% and 12,5% respectively. Out of the two false negative patients, one patient was on tablet anastrazole (anti estrgoen medication). Correlation between HR status of tumor as assessed by IHC &amp; SUV of tumour, tumour to background ratio and visual grading (Table II) was assessed and it was found that correlation was strongest for visual grading (0.7737) followed by tumour to background ratio (0.6640) &amp; SUV of lesion(0.5305).Conclusions18FES PETCT shows promise in evaluating HR status of breast cancer as it is high sensitive and specific. It scores over the currently used technique of IHC as it assesses the tumor in its entirety. Among the various parameters of assessment of HR expression on FES PETCT, we recommend visual grading as it correlates the best with HR expression on IHC. Limitations of the Study: Small sample size. Larger studies are needed before FES PET CT is recommended to be included in the routine clinical armamentarium for management of breast cancer.Support or Funding InformationnoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

IMH aortic arch with mediastinal blood products

IMH aortic arch with mediastinal blood products

Effects of blood glucose level on 18F-FDG uptake for PET/CT in normal organs: A systematic review.

PurposeTo perform a systematic review of the effect of blood glucose levels on 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) uptake in normal organs.MethodsWe searched the MEDLINE, EMBASE and Cochrane databases through 22 April 2017 to identify all relevant studies using the keywords “PET/CT” (positron emission tomography/computed tomography), “standardized uptake value” (SUV), “glycemia,” and “normal.” Analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Maximum and mean SUVs and glycemia were the main parameters analyzed. To objectively measure the magnitude of the association between glycemia and 18F-FDG uptake in different organs, we calculated the effect size (ES) and the coefficient of determination (R2) whenever possible.ResultsThe literature search yielded 225 results, and 14 articles met the inclusion criteria; studies included a total of 2714 (range, 51–557) participants. The brain SUV was related significantly and inversely to glycemia (ES = 1.26; R2 0.16–0.58). Although the liver and mediastinal blood pool were significantly affected by glycemia, the magnitudes of these associations were small (ES = 0.24–0.59, R2 = 0.01–0.08) and negligible (R2 = 0.02), respectively. Lung, bone marrow, tumor, spleen, fat, bowel, and stomach 18F-FDG uptakes were not influenced by glycemia. Individual factors other than glycemia can also affect 18F-FDG uptake in different organs, and body mass index appears to be the most important of these factors.ConclusionThe impact of glycemia on SUVs in most organs is either negligible or too small to be clinically significant. The brain SUV was the only value largely affected by glycemia.

ACT Values after Neutralization Lower than Pre-heparinization ACT Leads to Lower Operative Times, Bleeding, and Post-Operative Transfusions in CABG Patients: an Observational Study.

ObjectiveTo evaluate if lower activated coagulation time (ACT) value after neutralization than preoperative ACT value was effective in reducing bleeding, operative times, and post-operative transfusions in patients underwent coronary artery bypass grafting (CABG).MethodsRetrospective selection of 398 patients from January 2014 to May 2017. Patients were divided into 2 groups according to final ACT after neutralization: A - final ACT lower than preoperative ACT; and B - final ACT higher than or equal to preoperative ACT. Hemostatic time, intraoperative blood loss, ACT after final neutralization, mediastinal blood loss, and transfusion requirements were observed.ResultsThe hourly blood loss in the Group A was generally lower than in the Group B at first 3 hours, which has significant difference (P<0.05). However, there was no difference after 3 hours between the two groups. Operative time, intraoperative blood loss, mediastinal blood loss, transfusion requirements, and drainage in the first postoperative 12 hours in the Group A were lower than in Group B, which has significant difference (P<0.05).ConclusionAs a result, final ACT values lower than pre-heparinization ACT values are safe and lead to lower operative times, bleeding, and post-operative transfusions.

Impact of FDG-PET on the Detection of Patients with Lung Cancer at High Risk for ILD.

Idiopathic pulmonary fibrosis IPF is a type of interstitial lung disease (ILD) with poor prognosis. Lung cancer (LC) is a frequent complication in IPF, where all therapeutic options are potential triggers for acute exacerbation of IPF. Patients with 2-deoxy-2-fluoro-D-glucose-positron emission tomography/computer tomography (FDG-PET/CT) results before lobectomy for LC with and without (n=10 each) signs of ILD in initial imaging and after-care CT were retrospectively analyzed. FDG uptake was calculated as the maximum standardized uptake value (SUVmax) in the lung periphery divided by the SUVmax of the mediastinal blood pool (rSUVmax). Regional increase of fibrosis and ground-glass features in lobe-based CT analysis was used as standard reference. Patients with LC with ILD presented a significantly higher rSUVmax of 0.57 compared to patients without ILD with rSUVmax 0.47 (p<0.001). rSUVmax seems to be a valuable imaging surrogate in predicting patients with LC with increased risk for progressive ILD associated with thoracic surgery.

Strategies for Prevention and Management of Bleeding Following Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Scoping Review.

We aimed to systematically describe, via a scoping review, the literature reporting strategies for prevention and management of mediastinal bleeding post pediatric cardiopulmonary bypass surgery. MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL Register. Two authors independently screened publications from 1980 to 2016 reporting the effect of therapeutic interventions on bleeding-related postoperative outcomes, including mediastinal drain loss, transfusion, chest re-exploration rate, and coagulation variables. Inclusions: less than 18 years, cardiac surgery on cardiopulmonary bypass. Data from eligible studies were extracted using a standard data collection sheet. Overall, 299 of 7,434 screened articles were included, with observational studies being almost twice as common (n = 187, 63%) than controlled trials (n = 112, 38%). The most frequently evaluated interventions were antifibrinolytic drugs (75 studies, 25%), blood products (59 studies, 20%), point-of-care testing (47 studies, 16%), and cardiopulmonary bypass circuit modifications (46 studies, 15%). The publication rate for controlled trials remained constant over time (4-6/yr); however, trials were small (median participants, 51; interquartile range, 57) and overwhelmingly single center (98%). Controlled trials originated from 22 countries, with the United States, India, and Germany accounting for 50%. The commonest outcomes were mediastinal blood loss and transfusion requirements; however, these were defined inconsistently (blood loss being reported over nine different time periods). The majority of trials were aimed at bleeding prevention (98%) rather than treatment (10%), nine studies assessed both. Overall, this review demonstrates small trial sizes, low level of evidence, and marked heterogeneity of reported endpoints in the included studies. The need for more, higher quality studies reporting clinically relevant, comparable outcomes is highlighted. Emerging fields such as the use of coagulation factor concentrates, goal-directed guidelines, and anti-inflammatory therapies appear to be of particular interest. This scoping review can potentially guide future trial design and form the basis for therapy-specific systematic reviews.

Shed-blood-separation and cell-saver: an integral Part of MiECC? Shed-blood-separation and its influence on the perioperative inflammatory response during coronary revascularization with minimal invasive extracorporeal circulation systems - a randomized controlled trial.

The postoperative systemic inflammatory response after cardiopulmonary bypass (CPB) is still an undesirable side-effect after cardiac surgery. It is most likely caused by blood contact with foreign surfaces and by the surgical trauma itself. However, the recirculation of activated shed mediastinal blood is another main cause of blood cell activation and cytokine release. Minimal invasive extracorporeal circulation (MiECC) comprises a completely closed circuit, coated surfaces and the separation of suction blood. We hypothesized that MiECC, with separated cell saved blood, would induce less of a systemic inflammatory response than MiECC with no cell-saver. The aim of this study was, therefore, to investigate the impact of cell washing shed blood from the operating field versus direct return to the ECC on the biomarkers for systemic inflammation. In the study, patients with MiECC and cell-saver were compared with the control group, patients with MiECC and direct re-transfusion of the drawn blood shed from the surgical field. High amounts of TNF-α (+ 120% compared to serum blood) were found in the shed blood itself, but a significant reduction was demonstrated with the use of a cell-saver (TNF-α ng/l post-ECC 10 min: 9.5±3.5 vs. 19.7±14.5, p<0.0001). The values for procalcitonin were not significantly increased in the control group (6h: 1.07±3.4 vs. 2.15±9.55, p=0.19) and lower for C-reactive protein (CRP) (24h: 147.1±64.0 vs.134.4±52.4 p=0.28). The use of a cell-saver and the processing of shed blood as an integral part of MiECC significantly reduces the systemic cytokine load. We, therefore, recommend the integration of cell-saving devices in MiECC to reduce the perioperative inflammatory response.