Dose reduction and its influence on diagnostic accuracy and radiation risk in digital mammography: an observer performance study using an anthropomorphic breast phantom

This study aimed to investigate the effect of dose reduction on diagnostic accuracy and radiation risk in digital mammography. Simulated masses and microcalcifications were positioned in an anthropomorphic breast phantom. Thirty digital images, 14 with lesions, 16 without, were acquired of the phantom using a Mammomat Novation (Siemens, Erlangen, Germany) at each of three dose levels. These corresponded to 100%, 50% and 30% of the normally used average glandular dose (AGD; 1.3 mGy for a standard breast). Eight observers interpreted the 90 unprocessed images in a free response study, and the data were analysed with the jackknife free response receiver operating characteristic (JAFROC) method. Observer performance was assessed using the JAFROC figure of merit (FOM). The benefit of radiation risk reduction was estimated based on several risk models. There was no statistically significant difference in performance, as described by the FOM, between the 100% and the 50% dose levels. However, the FOMs for both the 100% and the 50% dose were significantly different from the corresponding quantity for the 30% dose level (F-statistic = 4.95, p-value = 0.01). A dose reduction of 50% would result in three to nine fewer breast cancer fatalities per 100,000 women undergoing annual screening from the age of 40 to 49 years. The results of the study indicate a possibility of reducing the dose to the breast to half the dose level currently used. This has to be confirmed in clinical studies, and possible differences depending on lesion type should be examined further.     

Topographic organization in the auditory brainstem of juvenile mice is disrupted in congenital deafness

There is an orderly topographic arrangement of neurones within auditory brainstem nuclei based on sound frequency. Previous immunolabelling studies in the medial nucleus of the trapezoid body (MNTB) have suggested that there may be gradients of voltage-gated currents underlying this tonotopic arrangement. Here, our electrophysiological and immunolabelling results demonstrate that underlying the tonotopic organization of the MNTB is a combination of medio-lateral gradients of low-and high-threshold potassium currents and hyperpolarization-activated cation currents. Our results also show that the intrinsic membrane properties of MNTB neurones produce a topographic gradient of time delays, which may be relevant to sound localization, following previous demonstrations of the importance of the timing of inhibitory input from the MNTB to the medial superior olive (MSO). Most importantly, we demonstrate that, in the MNTB of congenitally deaf mice, which exhibit no spontaneous auditory nerve activity, the normal tonotopic gradients of neuronal properties are absent. Our results suggest an underlying mechanism for the observed topographic gradient of neuronal firing properties in the MNTB, show that an intrinsic neuronal mechanism is responsible for generating a topographic gradient of time-delays, and provide direct evidence that these gradients rely on spontaneous auditory nerve activity during development.     

Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care

After myeloablative treatment and allogeneic stem cell transplantation (SCT), patients are kept in isolation rooms in the hospital to prevent neutropenic infections. During a 3-year period, patients were given the option of treatment at home after SCT. Daily visits by an experienced nurse and daily phone calls from a physician from the unit were included in the protocol. We compared 36 patients who wished to be treated at home with 18 patients who chose hospital care (control group 1). A matched control group of 36 patients treated in the hospital served as control group 2. All home care patients had hematologic malignancies and 19 were in first remission or first chronic phase. Of the donors, 25 were unrelated. The patients spent a median of 16 days at home (range, 0-26 days). Before discharge to the outpatient clinic after SCT, patients spent a median of 4 days (range, 0-39 days) in the hospital. In the multivariate analysis, the home care patients were discharged earlier (relative risk [RR] 0.33, P =.03), had fewer days on total parenteral nutrition (RR 0.24, P <.01), less acute graft-versus-host disease (GVHD) grades II-IV (RR 0.25, P =.01), lower transplantation-related mortality rates (RR 0.22, P =.04), and lower costs (RR 0.37, P <.05), compared with the controls treated in the hospital. The 2-year survival rates were 70% in the home care group versus 51% and 57% (not significant) in the 2 control groups, respectively (P <.03). To conclude, home care after SCT is a novel and safe approach. This study found it to be advantageous, compared with hospital care.     

Long-term follow-up of patients treated at home during the pancytopenic phase after allogeneic haematopoietic stem cell transplantation

To prevent neutropenic infections, patients are kept in isolation rooms after allogeneic haematopoietic stem cell transplantation (ASCT). Patients living within one hours' driving distance from our unit were given the opportunity of treatment at home after ASCT during the pancytopenic phase. We compared 36 patients treated at home during March 1998 until December 2000, with 54 controls treated in the hospital during September 1995 and September 2001. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was lower in the home care group compared to the controls, that is, 17 vs 44% (P < 0.01). The cumulative incidence of chronic GVHD was 52% in the home care group, compared to 57% in the controls. Transplant-related mortality (TRM) was 13% in the home care patients vs 44% in the controls (P = 0.002). The probability of relapse was similar in the two groups. The 4-year survival was 63% in the home care patients compared to 44% in the controls (P = 0.04). Home care after ASCT is a novel approach that resulted in less TRM, similar incidence of chronic GVHD and relapse, and improved long-term survival compared to controls treated in the hospital.     

Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anaemia in Caucasian population

Interferon-gamma (IFN-gamma) mediates the final damage of the stem cell compartment in Aplastic Anaemia (AA). Normal subjects homozygous for 12 (CA) repeats of polymorphism variable number of dinucleotide (CA) repeat (VNDR) in position 1349 of the IFN-gamma gene (IFNG) were shown to overproduce IFN-gammain vitro. We studied the distribution of polymorphism VNDR 1349 of IFNG in 67 Caucasian AA patients and in normal controls. Genotype (CA)12-12, (homozygosis for allele 2) and the single allele 12 were significantly more frequent (P = 0.005 and 0.004 respectively) in patients versus controls. The polymorphism was equally distributed in AA patients regardless of their response to immunosuppression. Homozygosity for 12 (CA) repeats of polymorphism VNDR 1349 of IFNG is strongly associated with the risk of AA in Caucasian subjects.     

Increased costs after allogeneic haematopoietic SCT are associated with major complications and re-transplantation

We wanted to evaluate factors associated with high costs after allogeneic haematopoietic SCT (HSCT). We collected all in-patient and outpatient costs during the first year after HSCT over 5 years, from 2003 to 2007. Mean 1-year costs per patient were \[euro]141,493 (95% confidence interval (95% CI)=125,019-157,967). Patients treated with non-myeloablative conditioning (NMC) had reduced costs, but patients treated with reduced-intensity or myeloablative conditioning had similar 1-year costs. Multivariate analysis showed that increased 1-year costs were seen in post-transplant complications: rejection (relative hazard (RH) 1.24, P<0.001), acute GVHD of grades III-IV (1.31, P<0.001) and invasive fungal infection (1.15, P=0.02). In addition, increased costs were associated with re-transplantation (1.21, P=0.001), mesenchymal stem-cell therapy (1.26, P<0.001), unrelated donor transplants (1.20, P=0.002) and the need for G-CSF treatment due to poor engraftment (1.12, P=0.047). In patients without any of these risk factors, mean 1-year costs were \[euro]84,773 (95% CI=71,145-98,400) (n=51). With three risk factors, the cost increased to \[euro]249,775 (95% CI=166,824-332,727) (n=14). To conclude, major complications increased the costs of HSCT. Unrelated donor transplants were more expensive than HLA-identical sibling transplants. Costs were reduced in patients treated with NMC.     

Breast tomosynthesis and digital mammography: a comparison of diagnostic accuracy

Objective

Our aim was to compare the ability of radiologists to detect breast cancers using one-view breast tomosynthesis (BT) and two-view digital mammography (DM) in an enriched population of diseased patients and benign and/or healthy patients.

Methods

All participants gave informed consent. The BT and DM examinations were performed with about the same average glandular dose to the breast. The study population comprised patients with subtle signs of malignancy seen on DM and/or ultrasonography. Ground truth was established by pathology, needle biopsy and/or by 1-year follow-up by mammography, which retrospectively resulted in 89 diseased breasts (1 breast per patient) with 95 malignant lesions and 96 healthy or benign breasts. Two experienced radiologists, who were not participants in the study, determined the locations of the malignant lesions. Five radiologists, experienced in mammography, interpreted the cases independently in a free-response study. The data were analysed by the receiver operating characteristic (ROC) and jackknife alternative free-response ROC (JAFROC) methods, regarding both readers and cases as random effects.

Results

The diagnostic accuracy of BT was significantly better than that of DM (JAFROC: p=0.0031, ROC: p=0.0415). The average sensitivity of BT was higher than that of DM (∼90% vs ∼79%; 95% confidence interval of difference: 0.036, 0.108) while the average false-positive fraction was not significantly different (95% confidence interval of difference: −0.117, 0.010).

Conclusion

The diagnostic accuracy of BT was superior to DM in an enriched population.About 1 in 8–10 females develop breast cancer during their lifetime [1,2]. Screening mammography plays a key role in the detection of breast cancer at an early stage. Based on incidence of interval cancers it has been suggested that a radiologist reading screen-film mammograms might miss 16–30% of cancers detectable on the mammograms [3]. Mammography cancer detection varies widely: estimates of sensitivity have been reported from 68% (or as low as 48% for extremely dense breasts) to 88%, with specificities ranging from 82% to 98%. These results suggest that there is considerable room for improvement in mammography [4,5]. Digital mammography (DM) was expected to improve the performance of breast cancer detection compared with screen-film mammography (SFM). In most clinical trials the overall sensitivity has been higher for DM, but, since the specificities have also been lower, only a few studies have been statistically significant in favour of DM [5]. In a subset of females under 50 years of age in the Digital Mammographic Imaging Screening Trial study, there was a significantly improved diagnostic accuracy in DM compared with SFM [5].Because a mammogram is a two-dimensional (2D) projection of the breast onto the detector plane, overprojected healthy tissue (anatomical noise) can hamper breast cancer detectability. Anatomical noise is known to have a greater impact than quantum noise on the detection of certain breast cancers (e.g. masses) [6,7]. Two views—mediolateral oblique (MLO) and craniocaudal (CC)—can partially compensate for the overlapping anatomical noise, but this depends on the radiologist''s ability to mentally fuse the two images.Breast tomosynthesis (BT) collects 2D projection views over a limited angular range, which allows reconstruction of thin slices of the breast volume. Reduced anatomical noise from superimposed tissues is expected to improve breast cancer detection compared with DM. In CT where hundreds of projection images are acquired covering 360°, the anatomical noise can be reduced to a larger degree, but it is difficult to image the entire breast volume using CT, particularly close to the chest wall. Moreover, the average glandular dose is higher with CT, as is imaging time and the cost of the device. While there is ongoing research that may solve these issues [8-10], BT has a number of potential advantages and there are currently commercialised units.Previous studies of observer performance of BT compared with DM have shown contradictory results, varying from a statistically significant advantage for BT [11-13] to no clear advantage for BT [14-18]. Non-blinded pilot studies have been performed at our institution that suggest improved sensitivity of BT over DM [19,20].The aim of the current study was to compare the diagnostic accuracy of one-view BT with conventional two-view DM using an enriched population.     

A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors

The study included 110 consecutive patients with hematological malignancies receiving fludarabine‐based reduced intensity conditioning (RIC) and hematopoietic stem cell transplantation (HSCT) from matched unrelated donors. The median age was 55 yr (range 11–68) and all but 15 patients received peripheral blood stem cell grafts. Antithymocyte globulin (ATG) (Thymoglobulin, Genzyme) at a total dose of 6 mg/kg (n = 66) or 8 mg/kg (n = 44) was given to all patients according to protocol. The ATG dose did not affect time‐to‐neutrophil or platelet engraftment. The incidences of acute GVHD grades II–IV were 34% and 18% (p = 0.11) and of chronic GVHD were 40% and 26% (p = 0.46) in patients receiving 6 and 8 mg/kg of ATG, respectively. The five‐yr relapse‐free survival (RFS) was 61% and 36% (p = 0.14) in patients, given low and high ATG dose, respectively. In patients given low‐dose ATG, the incidence of relapse was lower compared to those given high‐dose ATG, 19% vs. 41% (p = 0.04). In multivariate analysis, age >50 yr (p < 0.001), absence of acute (p < 0.001) and chronic GVHD (p = 0.001) were correlated to relapse, and low‐dose ATG was associated with improved RFS (p < 0.05). A high dose (8 mg/kg) of ATG in RIC HSCT with unrelated donors increased the risk for relapse and reduced the RFS.