Therapy response evaluation of malignant lymphoma in a multicenter study: comparison of manual and semiautomatic measurements in CT.

PURPOSE: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. MATERIALS AND METHODS: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. RESULTS: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. CONCLUSION: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. KEY POINTS: ► Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients ► Manual lymph node evaluation with uni-dimensional parameters is inferior to semi-automatic analysis in a multicenter setting ► Semi-automatic quantitative software tools should be introduced in clinical study evaluation.

Volumetric response classification in metastatic solid tumors on MSCT: initial results in a whole-body setting.

PURPOSE: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. MATERIALS AND METHODS: 56 consecutive patients (32 female) aged 41-82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. RESULTS: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p<0.05, corrected). 4-8 patients' response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. CONCLUSION: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

Comparison of noninvasive imaging modalities for stenosis grading in mesenteric arteries.

OBJECTIVE: To prospectively analyze duplex sonography, CTA, and MRA with respect to stenosis grading of the celiac trunk (TC) and the superior mesenteric artery (SMA), with DSA as the reference. MATERIALS AND METHODS: 52 subjects were enrolled (mean age: 71). The image quality was graded: 1-insufficient, 2-bad, 3-moderate, 4-good or 5-excellent. Stenosis was graded: 1 (< 25 %), 2 (25 - < 50 %), 3 (50 - 75 %) or 4 (75 %). Two-sided chi-square tests were used to check for correlation of stenosis grading between modalities. The weighted Cohen's kappa was calculated to assess the strength of correlation. With a threshold of 50 % for non-relevant stenosis vs. relevant stenosis, the sensitivity, specificity, PPV, NPV, and accuracy were calculated. RESULTS: The mean image quality was 3.8 ± 0.7, 3.1 ± 1.0, 4.4 ± 0.7, and 3.8 ± 0.9 for DSA, duplex sonography, CTA, and MRA, respectively. For both TC and SMA, stenosis grading reached a significant level of correlation between each noninvasive modality with DSA (p < 0.001, each). The weighted Cohen's kappa for duplex sonography/CTA/MRA was 0.94/0.93/0.74, respectively, for the TC and 0.64/0.91/0.56, respectively, for the SMA. Highest sensitivity/specificity/NPV/PPV/accuracy were found for CTA with 100 %/95 %/85 %/100 %/96 % for the TC and with na/98 %/na/100 %/98 %, respectively, for the SMA. CONCLUSION: CTA provided the best image quality, reached the highest level of agreement and significance in correlation in stenosis grading, and offered the best diagnostic accuracy.

Outcome of immediate interventions in acute dysfunctional hemodialysis fistulas.

PURPOSE: To analyze the efficacy of interventions in acute dysfunctional hemodialysis fistulas, if intervention is performed immediately as recommended by European Best Practice Guidelines for Hemodialysis. MATERIALS AND METHODS: Over 3 years, all (n = 280) patients with an acute dysfunctional hemodialysis fistula were immediately referred to angiography, irrespective of the time of day. Angiography and, if possible, interventional revision (n = 241) were performed. Three groups of interest were established: interventionalist's experience (high/low), time of day (routine hours: 7 am-4 pm/emergency hours: 4 pm-7 am), lesion type (stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+thrombotic occlusion). For statistical analysis corresponding success rates, chi-square tests (p < 0.025) and logistic regression analysis (p < 0.05) were calculated. RESULTS: The total success rate was 62 % (149/241). The success rates were: interventionalist experience high/low 71 % (79/111)/54 % (70/130), p = 0.022; time of day routine/emergency hours 68 % (93/136)/53 % (56/105), p = 0.017; lesion type stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+occlusion 82 % (94/104)/39 % (13/33)/18 % (6/33)/59 % (36/61), p < 0.001. Relevant variables due to logistic regression analysis were high experience and the lesion types stenosis and combined stenosis+occlusion with odds ratios 2.300 (p = 0.012), 12.053 (p < 0.001), 3.189 (p = 0.003). CONCLUSION: Unrestricted implementation of immediate interventions in acute dysfunctional hemodialysis fistulas requires permanent availability of experienced interventionalists. The lesion types fibrosclerotic occlusion and thrombotic occlusion offer poor success rates for interventional revision.

Lung, liver and lymph node metastases in follow-up MSCT: comprehensive volumetric assessment of lesion size changes.

PURPOSE: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1. MATERIALS AND METHODS: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized. RESULTS: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p < .001). The limits of agreement were ± 9.8 to ± 11.2 % for volumetric assessment. CONCLUSION: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting.

Monoclonal antibodies against a synthetic peptide from human immunodeficiency virus type 1 Nef protein.

Monoclonal antibodies against a synthetic peptide (aa 138-152) from HIV-1 Nef protein were produced and characterized. Three hybridoma lines producing monoclonal antibodies (MAbs) against the synthetic peptide were generated by fusion between P3-X63 Ag8.653 myeloma cells and BALB/c splenocytes from mice immunized with the synthetic peptide coupled to keyhole limpet hemocyanin (KLH). The hybridomas were screened and selected by ELISA with the peptide coupled to bovine serum albumin (BSA) immobilized to the polystyrene surface and specificity for the peptide was confirmed by competitive ELISA with the peptide free in solution. The reactions of the MAbs with a 5-aa motif (WCYKL) included in the sequence were examined with synthetic peptides and two of the MAbs reacted with the motif. The recognitions of recombinant full-length Nef protein were also tested. One MAb reacted with the protein in both ELISA and dot blot, and one only in dot blot, whereas the last MAb did not recognize the recombinant full-length Nef protein.

Characterization of N-myristoyl transferase inhibitors and their effect on HIV release.

Acylation of virus proteins is an important covalent modification which has been shown, in many cases, to be necessary for their normal function. Furthermore, it has been shown that cerulenin, an inhibitor of this process, inhibits formation of vesicular stomatitis virus and Rous sarcoma virus in infected cultures, as well as acylation of HIV proteins. However, in agreement with earlier reports, we found that the acylating enzyme, N-myristoyl transferase, was unaffected by cerulenin which did, however, inhibit protein synthesis, thereby making interpretation of its effects difficult. Analogues of myristic acid were found to inhibit acylation in intact cells without toxic effects on protein synthesis or mitochondrial function. Myristic acid analogues were also shown by an in vitro assay to act directly on the acylating activity (N-myristoyl transferase). Furthermore, myristic acid analogues were found to inhibit HIV release from HIV-infected cells and glucosamine, which has recently been shown to be a non-competitive inhibitor of N-myristoyl-transferase, also inhibited HIV release.