Incidentally detected splenic lesions in ultrasound: does contrast-enhanced ultrasonography improve the differentiation of benign hemangioma/hamartoma from malignant lesions?

PURPOSE: The aim of the study was to identify and validate enhancing features for differentiating benign vascular neoplasms of the hemangioma/hamartoma type from malignant splenic lesions on contrast-enhanced ultrasonography (CEUS). MATERIALS AND METHODS: 136 splenic lesions (58 benign vascular neoplasms, 78 malignant) in 136 patients underwent baseline US and pulse-inversion CEUS after sulfur hexafluoride-filled microbubble injection. Two on-site readers assessed lesion enhancement features during arterial and parenchymal phase in consensus. Best predicting CEUS features for lesion diagnosis were identified through univariate and multivariate analyses. Two blinded off-site readers independently issued a confidence rating for lesion diagnosis in baseline US and CEUS using extracted diagnostic CEUS features. Diagnostic performance, receiver operating curves (Az-value), and interreader agreement were calculated. The reference standards were histopathology or CT and/or MR imaging with clinical follow-up.  RESULTS: Multivariate analysis outlined arterial hyperenhancement or isoenhancement to be an independent CEUS predictor of benign vascular neoplasms (odds ratio, 3.558; p < 0.0017). Within the subgroup of isoechoic or hypoechoic lesions, arterial hyperenhancement was virtually diagnostic for benign vascular neoplasm (odds ratio, 21.333; p < 0.001). The diagnostic accuracy and confidence (Az-value) of the two readers was 63.2 % and 70.6 % (0.785 and 0.818) for baseline US, which improved significantly to 87.5 % and 88.2 % (0.915 and 0.908) for CEUS (p < 0.001). Interreader agreement also increased with CEUS (қ = 0.88) compared to baseline US (қ = 0.52). CONCLUSION: Sulfur hexafluoride-enhanced CEUS improves differentiation between benign vascular and malignant splenic tumors and may be especially useful in clinical scenarios in which the incidental hypoechoic splenic lesion is unclear on conventional US.

Molecular characterisation of linezolid resistance in two vancomycin-resistant (VanB) Enterococcus faecium isolates using Pyrosequencing.

In this paper, we describe the phenotypic and molecular characteristics of two clinically relevant, vancomycin-resistant (VanB), linezolid-resistant Enterococcus faecium isolates. Pyrosequencing showed the G to T single nucleotide polymorphism at bp 2576 in the genes coding for 23S rRNA and was used to quantify the proportion of G to T mutations among six different 23S rRNA genes in E. faecium as a marker for the molecular level of resistance to linezolid. In both isolates, the G to T mutation was found in two of six alleles, and no further mutations in the genes coding for 23S rRNA were found. The dynamic process of linezolid resistance could be demonstrated by the complete reversion of resistant alleles back to only wild type alleles in consecutive isolates of one isolate. Pyrosequencing being used to detect and quantify resistance to linezolid has been proven as a fast and reliable molecular screening method for monitoring linezolid resistance.

Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS).

We investigated a dose-reduced conditioning regimen consisting of treosulfan and fludarabine followed by allogeneic stem cell transplantation (SCT) in 26 patients with secondary AML or MDS. Twenty patients were transplanted from matched or mismatched unrelated donors and six from HLA-identical sibling donors. The median age of the patients was 60 years (range, 44-70). None of the patients was eligible for a standard myeloablative preparative regimen. No graft-failure was observed, and leukocyte and platelet engraftment were observed after a median of 16 and 17 days, respectively. Acute graft-versus-host disease (GvHD) grade II-IV was seen in 23% and severe grade III GvHD in 12% of the patients. No patients experienced grade IV acute GvHD. Chronic GvHD was noted in 36% of the patients, which was extensive disease in 18%. The 2-year cumulative incidence of relapse was 21%. The relapse rate was higher in patients beyond CR1 or with intermediate two or high risk MDS (P = 0.02). The treatment-related mortality at day 100 was 28%. The 2-year estimated overall and disease-free survival was 36-34%, respectively. No difference in survival was seen between unrelated and related SCT.

Comparable results in patients with acute lymphoblastic leukemia after related and unrelated stem cell transplantation.

We report the results of 84 patients with ALL after related (n = 46) or unrelated (n = 38) allogeneic SCT. Mean recipient age was 23 years (range: 1-60) and median follow-up was 18 months (range: 1-133). Forty-three patients were transplanted in CR1; 25 in CR2 or CR3; four were primary refractory; four in PR; eight in relapse. The conditioning regimen consisted of TBI/VP16/CY (n = 76), TBI/VP16 (n = 2), TBI/CY (n = 2), Bu/VP16/CY (n = 4). The OS at 3 years was 45% (44% unrelated, 46% related). Univariate analysis showed a significantly better OS for patients <18 years (P=0.03), mismatched sex-combination (P = 0.03), both with a stronger effect on increasing OS after unrelated SCT. Factors decreasing TRM were patient age <18 years (P = 0.004), patient CMV-seronegativity (P = 0.014), female recipient (P = 0.04). There was no significant difference in TRM and the relapse rate was similar in both donor type groups. Multivariate analysis showed that factors for increased OS which remained significant were mismatched sex-combination (RR: 0.70,95% CI: 0.51-0.93, P = 0.015), patient age < 18 years (RR: 0.66, 95% CI: 0.47-0.93, P = 0.016). A decreased TRM was found for female patients (RR: 0.56, 95% CI: 0.33-0.98, P=0.042), negative CMV status of the patient (RR: 0.57, 95% CI: 0.36-0.90, P = 0.015). Unrelated stem cell transplantation for high-risk ALL patients with no HLA-compatible family donor is justifiable.

[Unrelated donor stem cell transplantation in children: low toxicity using a GvHD-prophylaxis regimen with CSA, MTX, metronidazole,iv-immunoglobulin and ATG]. / Hämatopoetische Stammzelltransplantation vom Fremdspender bei Kindern: Niedrige Toxizität durch GvHD-Prophylaxe mit CSA, MTX, Metronidazol, iv-Immunglobulin und ATG.

BACKGROUND: Unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) is accepted as a therapy for leukaemic diseases and varying inborn diseases if a suitable related donor cannot be found. The goal of immunosuppressive therapy with UD-HSCT is an effective prevention of graft-versus-host-disease (GvHD) on one hand. On the other hand an optimal balance with immunocompetence of the transplanted bone marrow is desirable in order to prevent graft failure, infection and, in the case of leukaemic diseases, potentially control the underlying disease. PATIENTS AND METHODS: Between 1992 and 2000 49 patients aged 11 months to 16.7 years received an UD-HSCT in Hamburg. Underlying diseases were leukaemia or MDS in 35, of these ALL in 21, hemophagocytic lymphohistiocytosis (HLH) in 9, immunodeficiency or inborn error of metabolism in 5 patients. GvHD-prophylaxis consisted of a combination of Cyclosporin A (CSA), methotrexate (MTX), metronidazole, IgM-enriched iv-immunoglobulin (ivIg) (Pentaglobin(R)) or ivIgG and anti-thymocyte-globulin (ATG). Within the same time span 10 patients with ALL received a matched related donor HSCT (MRD-HSCT). GvHD-prophylaxis in these patients was done without ATG in 8 of 10 cases. UD-HSCT were analyzed for survival, relapse and toxicity. Probability of survival of the patients with ALL after UD-HSCT was compared with results of MRD-HSCT in children with ALL. RESULTS: The Kaplan-Meier estimates of three year overall-survival (OS) were 74 % for all patients. Probability of disease-free survival (DFS) at three years was 62 % for leukaemia/MDS-patients and 100 % for the HLH-patients. Acute GvHD (aGvHD) grades II or III occurred in 51 % of patients. Chronic GvHD (cGvHD) occurred in 22 % of patients. There were 5 cases of treatment-related mortality (TRM). Probability of DFS for patients with ALL at three years was 65 % after UD-HSCT and 30 % in the patients after MRD-HSCT. CONCLUSIONS: UD-HSCT in children is an effective and safe therapy. A GvHD-prophylaxis regimen combining the standard immunosuppressive agents CSA and MTX with ivIg, metronidazole and serotherapy using ATG may result in a low incidence of severe GvHD-complications and low TRM rate without increase in relapse rates.

Liver MR imaging: comparison of respiratory triggered fast spin echo with T2-weighted spin-echo and inversion recovery.

BACKGROUND: The purpose of this study was to compare a fast spin-echo sequence combined with a respiratory triggering device (R. trig. FSE) with conventional T2-weighted spin-echo (CSE) and inversion recovery (STIR) sequences for the detection of focal hepatic lesions. METHODS: We performed a prospective study of 33 consecutive patients with known or suspected hepatic tumors. All patients underwent R. trig. FSE, CSE, and STIR imaging at 1.5 T. Acquisition times were 10.7 min for the CSE sequence and ranged from 12 to 15 min for STIR and from 5 to 7 min for R. trig FSE. For each sequence, liver-spleen contrast-to-noise ratio (CNR) and liver-lesion CNR were determined quantitatively. Image artifact and sharpness were graded by using a four-point scale on each sequence by two independent readers. Both readers also independently identified hepatic lesions (up to a maximum of eight per patient). For patients with focal lesions, the total number of lesions detected (on each sequence) and the minimum size of detected lesions were also determined by each reader. RESULTS: No significant difference was detected between R. trig. FSE and CSE or STIR in either liver-spleen CNR or liver-lesion CNR. R. trig. FSE images were equivalent to CSE and superior to STIR in sharpness (p < 0.01) and presence of artifact (p < 0.01). R. trig. FSE detected a higher number of lesions (reader 1: n = 92, reader 2: n = 86) than CSE (reader 1: n = 70, reader 2: n = 69) and a significantly higher number than STIR (reader 1: n = 71, reader 2: n = 76). Lesion structure was significantly better defined with R. trig. FSE than with STIR (p < 0.01) and CSE (p < 0.05). CONCLUSIONS: Compared with CSE and STIR, R. trig. FSE produces hepatic images of comparable resolution and detects an increased number of focal hepatic lesions in a shorter period of time.