Guiding Breast-Conserving Surgery in Patients After Neoadjuvant Systemic Therapy for Breast Cancer: A Comparison of Radioactive Seed Localization with the ROLL Technique

Background

Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-^99mTc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 (¹²⁵I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated.

Methods

All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-^99mTc technique (n = 83) or with ¹²⁵I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed.

Results

Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-^99mTc technique and ¹²⁵I seed localization.

Conclusions

The ROLL-^99mTc technique and ¹²⁵I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because ¹²⁵I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer ¹²⁵I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.     

Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla

Background

If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential ¹⁸F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.

Methods

A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUV_max) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.

Results

A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUV_max was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.

Conclusions

¹⁸F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.     

Comparing deaf and hearing Dutch infants: Changes in the vowel space in the first 2 years

The influence of the mother tongue on vowel productions in infancy is different for deaf and hearing babies. Audio material of five hearing and five deaf infants acquiring Dutch was collected monthly from month 5–18, and at 24 months. Fifty unlabelled utterances were digitized for each recording. This study focused on developmental paths in vowel productions. The applied automated band filtering analysis is F₀‐independent and results in a spectral envelope, sampled in a 40‐dimensional space. Via a Principal Component Analysis (PCA, data reduction), a vowel space for normally hearing 2‐year‐olds was constructed, enabling the projection of the individual developmental data of the infants in a two‐dimensional reference plane. Comparison of the results for the hearing and the deaf infants over 2 years indicates individual as well as group differences. The amount of hearing loss as well as the communication styles seem to be important factors in explaining differences between the infant categories.     

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children,during active and passive movements,and tactile stimulation? An fMRI study

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.     

Does somatosensory discrimination activate different brain areas in children with unilateral cerebral palsy compared to typically developing children? An fMRI study

Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during somatosensory discrimination exercises, are lacking in CP children. Therefore, this study investigated brain activation with functional magnetic resonance imaging (fMRI) during passively guided somatosensory discrimination exercises in 18 typically developing children (TD) (age, M = 14 ± 1.92 years; 11 girls) and 16 CP children (age, M = 15 ± 2.54 years; 8 girls). The demographic variables between both groups were not statistically different. An fMRI compatible robot guided the right index finger and performed pairs of unfamiliar geometric shapes in the air, which were judged on their equality. The control condition comprised discrimination of music fragments. Both groups exhibited significant activation (FDR, p < .05) in frontoparietal, temporal, cerebellar areas, and insula, similar to studies in adults. The frontal areas encompassed ventral premotor areas, left postcentral gyrus, and precentral gyrus; additional supplementary motor area (SMA_proper) activation in TD; as well as dorsal premotor, and parietal operculum recruitment in CP. On uncorrected level, p < .001, TD children revealed more left frontal lobe, and right cerebellum activation, compared to CP children. Conversely, CP children activated the left dorsal cingulate gyrus to a greater extent than TD children. These data provide incentives to investigate the effect of somatosensory discrimination during rehabilitation in CP, on clinical outcome and brain plasticity.     

Effect of residual doxycycline concentrations on resistance selection and transfer in porcine commensal Escherichia coli

Pig feed may contain various levels of antimicrobial residues due to cross-contamination. A previous study showed that a 3% carry-over level of doxycycline (DOX) in the feed results in porcine faecal concentrations of approximately 4?mg/L.The aim of this study was to determine the effect of residual DOX concentrations (1 and 4?mg/L) in vitro on selection of DOX–resistant porcine commensal Escherichia coli and transfer of their resistance plasmids.Three different DOX–resistant porcine commensal E. coli strains and their plasmids were characterised. These strains were each brought in competition with a susceptible strain in a medium containing 0, 1 and 4?mg/L DOX. Resistant bacteria, susceptible bacteria and transconjugants were enumerated after 24?h and 48?h.The tet(A)–carrying plasmids showed genetic backbones that are also present among human E. coli isolates. Ratios of resistant to susceptible bacteria were significantly higher at 1 and 4?mg/L DOX compared with the blank control, but there was no significant difference between 1 and 4?mg/L. Plasmid transfer frequencies were affected by 1 or 4?mg/L DOX in the medium for only one of the resistance plasmids.In conclusion, DOX concentrations of 1 and 4?mg/L can select for resistant E. coli in vitro. Further research is needed to determine the effect of these concentrations in the complex environment of the porcine intestinal microbiota.     

Inclusion of equity in economic analyses of public health policies: systematic review and future directions

Objectives : To assess current approaches to inclusion of equity in economic analysis of public health interventions and to recommend best approaches and future directions. Methods : We conducted a systematic review of studies that have used socioeconomic position (SEP) in cost‐effectiveness analyses. Studies were identified using MedLine, EconLit and HEED and were evaluated based on their SEP specific inputs and methods of quantification of the health and financial inequalities. Results : Twenty‐nine relevant studies were identified. The majority of studies comparing two or more interventions left interpretation of the size of the health and financial inequality differences to the reader. Newer approaches include: i) use of health inequality measures to quantify health inequalities; ii) inclusion of financial impacts, such as out‐of‐pocket expenditures; and iii) use of equity weights. The challenge with these approaches is presenting results that policy makers can easily interpret. Conclusions : Using CEA techniques to generate new information about the health equity implications of alternative policy options has not been widely used, but should be considered to inform future decision making. Implications for public health : Inclusion of equity in economic analysis would facilitate a more nuanced comparison of interventions in relation to efficiency, equity and financial impact.