Cost-effectiveness of radioguided occult lesion localization using 125I seeds versus hookwire localization before breast-conserving surgery for non-palpable breast cancer.

BACKGROUND: The aim was to determine the cost-effectiveness of radioguided occult lesion localization using 125I-labelled seeds (125I seeds) versus hookwire localization in terms of incremental cost per reoperation avoided for women with non-palpable breast cancer undergoing breast-conserving surgery. METHODS: This study was based on a multicentre RCT with eight study sites comprising seven public hospitals and one private hospital. An Australian public health system perspective was taken. The primary effectiveness outcome for this study was reoperations avoided. Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to explore uncertainty. The willingness to pay (additional cost of localization using 125I seeds justified by reoperation cost avoided) was set at the weighted, top-down cost of reoperation. Costs were in 2019 Australian dollars ($1 was equivalent to €0.62). RESULTS: The reoperation rate was 13.9 (95 per cent confidence interval 10.7 to 18.0) per cent for the 125I seed group and 18.9 (14.8 to 23.8) per cent for the hookwire localization group. The ICER for 125I seed versus hookwire localization was $4474 per reoperation averted. The results were most sensitive to uncertainty around the probability of reoperation. Accounting for transition probability and cost uncertainty for 125I seed localization, there was a 77 per cent probability that using 125I seeds would be cost-effective, with a willingness to pay of $7693 per reoperation averted. CONCLUSION: Radioguided occult lesion localization using 125I seeds is likely to be cost-effective, because the marginal (additional) cost compared with hookwire localization is less than the cost of reoperations avoided.

Surgical outcomes after radioactive 125I seed versus hookwire localization of non-palpable breast cancer: a multicentre randomized clinical trial.

BACKGROUND: Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer. METHODS: Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Randomization was stratified by lesion type (pure ductal carcinoma in situ (DCIS) or other) and study site. Primary endpoints were rates of re-excision and margin positivity. Secondary endpoints were resection volumes and weights. RESULTS: A total of 690 women were randomized at eight sites; 659 women remained after withdrawal (125I seed, 327; HWL, 332). Mean age was 60.3 years in the 125I seed group and 60.7 years in the HWL group, with no difference between the groups in preoperative lesion size (mean 13.2 mm). Lesions were pure DCIS in 25.9 per cent. The most common radiological lesion types were masses (46.9 per cent) and calcifications (28.2 per cent). The localization modality was ultrasonography in 65.5 per cent and mammography in 33.7 per cent. The re-excision rate after 125I seed localization was significantly lower than for HWL (13.9 versus 18.9 per cent respectively; P = 0.019). There were no significant differences in positive margin rates, or in specimen weights and volumes. CONCLUSION: Re-excision rates after breast-conserving surgery were significantly lower after 125I seed localization compared with HWL. Registration number: ACTRN12613000655741 (http://www.ANZCTR.org.au/).

Non-mass versus mass-like ultrasound patterns in ductal carcinoma in situ: is there an association with high-risk histology?

AIM: To review the ultrasound (US) patterns of pure ductal carcinoma in situ (DCIS) using a non-mass-like (NML) versus mass-like (ML) classification and to investigate histopathological associations. MATERIALS AND METHODS: The present study was a retrospective analysis of sonographically evident pure DCIS lesions detected in a mammographic (MG) screening programme over a 7-year period from 2008. All lesions had undergone US-guided 14 G core biopsies with no upgrades to invasive disease on surgical histopathology. Lesions that were three-dimensional with convex margins were classified as ML and all others as NML. ML lesions were subdivided into solid, cystic, or mixed, and NML lesions into ductal and non-ductal. Imaging and pathological characteristics of NML versus ML lesions were investigated using logistic regression. RESULTS: There were 78 lesions in 75 participants. NML lesions accounted for 45 (58%) lesions, comprising 27 (60%) ductal and 18 (40%) non-ductal subtypes. There were 33 (42%) ML lesions; the largest subgroup being solid (n=21, 64%). Significant associations between lesion type and lesion size on US (<15 versus ≥15 mm), presence of US and mammographic calcification and posterior shadowing on sonography were identified. NML lesions had fivefold higher odds (OR=5.41 95% confidence interval [CI]: 2.03, 14.39, p=0.001) to be high grade and sevenfold higher odds (OR=7 95% CI: 1.75, 27.99, p=0.006) to have comedo necrosis on histopathology. CONCLUSION: DCIS lesions can be successfully classified using ML and NML lesion descriptors and NML morphology on US is associated with histological features of "high-risk" DCIS.

Could parenchymal enhancement on contrast-enhanced spectral mammography (CESM) represent a new breast cancer risk factor? Correlation with known radiology risk factors.

AIM: To compare background parenchymal enhancement (BPE) on contrast-enhanced (CE) spectral mammography (CESM) with CE magnetic resonance imaging (MRI), and evaluate how these relate to hormonal status, mammographic breast density (MBD) and MRI fibroglandular tissue volume (FGTV). METHODS AND MATERIALS: Between June 2012 to October 2015, participants in a cancer staging study underwent full-field digital mammography (FFDM), CEMRI, and CESM. Two readers independently rated FGTV, MBD, and BPE using the Breast Imaging-Reporting and Data System (BI-RADS) criteria. Inter-reader reliability was estimated using weighted kappa (k) and correlations between BPE, MBD, and FGTV calculated using Spearman's correlation coefficient. Associations with hormonal status were evaluated using multilevel ordinal regression analysis. RESULTS: Of the 96 eligible participants, 66 women (35-77 years) underwent CESM and CEMRI. Reasons for exclusion were declined or withdrawn consent (n=18), inadequate renal function (n=2), claustrophobia (n=2), previous reaction to contrast medium (n=2), mild reaction to contrast medium following CESM (n=2), lack of vascular access (n=1), neoadjuvant chemotherapy (n=1), CESM equipment failure (n=1), and unclear in one case. Inter-reader agreement was substantial (k=0.67) for CESM BPE, slight (k=0.19) for CEMRI BPE, moderate (k=0.57) for MRI FGTV and fair (k=0.35) for MBD. CESM BPE showed significant correlation with MBD (rho=0.36, p<0.0001), FGTV (rho=0.52, p<0.0001), and MRI BPE (rho=0.49, p<0.0001). BPE was significantly reduced in the post-menopausal group for CEMRI and CESM (p<0.05). CESM BPE did not significantly fluctuate during the menstrual cycle. CONCLUSION: CESM BPE is correlated with MBD, FGTV, and CEMRI BPE, has better inter-reader reliability than CEMRI, and is not influenced by the menstrual cycle. Grading the degree of BPE on CESM could be a useful addition to breast cancer risk assessment tools.

Analysing breast tissue composition with MRI using currently available short, simple sequences.

AIM: To determine the most robust commonly available magnetic resonance imaging (MRI) sequence to quantify breast tissue composition at 1.5 T. MATERIALS AND METHODS: Two-dimensional (2D) T1-weighted, Dixon fat, Dixon water and SPAIR images were obtained from five participants and a breast phantom using a 1.5 T Siemens Aera MRI system. Manual segmentation of the breasts was performed, and an in-house computer program was used to generate signal intensity histograms. Relative trough depth and relative peak separation were used to determine the robustness of the images for quantifying the two breast tissues. Total breast volumes and percentage breast densities calculated using the four sequences were compared. RESULTS: Dixon fat histograms had consistently low relative trough depth and relative peak separation compared to those obtained using other sequences. There was no significant difference in total breast volumes and percentage breast densities of the participants or breast phantom using Dixon fat and 2D T1-weighted histograms. Dixon water and SPAIR histograms were not suitable for quantifying breast tissue composition. CONCLUSION: Dixon fat images are the most robust for the quantification of breast tissue composition using a signal intensity histogram.

Behavioural responses of stable flies to cattle manure slurry associated odourants.

Stable flies (Stomoxys calcitrans [Diptera: Muscidae] L.) are blood-feeding synanthropic pests, which cause significant economic losses in livestock. Stable fly antennae contain olfactory sensilla responsive to host and host environment-associated odours. Field observation indicated that the abundance of stable flies increased significantly in grasslands or crop fields when cattle manure slurry was applied. Major volatile compounds emanating from manure slurry were collected and identified. Behavioural responses of stable flies to those compounds were investigated in laboratory bioassays and field-trapping studies. Results from olfactometer assays revealed that phenol, p-cresol and m-cresol were attractive to adult stable flies. When tested individually, attraction was higher with lower dosages. Stable flies were most attracted to blends of phenol and m-cresol or p-cresol. Traps with binary blend lures caught more stable flies in field trials as well.

Fibromatosis of the breast: a pictorial review of the imaging and histopathology findings.

Fibromatosis of the breast is a rare condition that predominantly affects middle-aged women. It is locally aggressive, and exhibits a high incidence of local recurrence. The clinical presentation and radiological appearance are highly suspicious for carcinoma. Definitive diagnosis is made by diagnostic open biopsy. The aim of this review is to illustrate the main radiological and histopathological characteristics of this rare disease to increase awareness of this entity and discuss the role of magnetic resonance imaging (MRI) in its management.

Efficacy of cyromazine to control immature stable flies (Diptera: Muscidae) developing in winter hay feeding sites.

Hay mixed with manure and urine residues at sites where hay has been provided as supplemental winter feed for cattle provide an excellent substrate for the development of immature stable flies, Stomoxys calcitrans (L.). Such sites are primary sources of early summer stable flies in the central United States and no effective measures are currently available to control fly development in them. A single application of granular cyromazine in May provided 97% reduction in the number of adult stable flies emerging from hay feeding sites. Stable fly control did not decline during the 12 wk season. A small decline in control was observed relative to anthomyiid, sarcophagid, and syrphid flies developing in the hay feeding sites. However, none of those flies are considered to be pests and > or = 50% control of those flies was maintained for 65 d after application. Cyromazine offers a safe and affordable option for the control of immature stable flies developing in winter hay feeding sites. Controlling those flies should reduce the estimated $2 billion per year of lost production in U.S. cattle industries attributable to stable flies.

Substrate properties of stable fly (Diptera: Muscidae) developmental sites associated with round bale hay feeding sites in eastern Nebraska.

Residues at sites where stationary feeders were used to provide hay as supplemental forage for cattle during the winter are developmental substrates for immature stable flies, Stomoxys calcitrans (L.), in the central United States. Spatial patterns in physical (substrate depth, temperature, water content), chemical (pH, electrical conductivity [EC(lab)], total nitrogen [N] and carbon [C], ammoniacal nitrogen [NH(4)-N], extractable phosphorus [P]), and biological (microbial respiration rate) substrate properties for two feeding sites were estimated and the correlations between these properties and adult emergence were characterized. Hay feeding sites had a circular footprint with residues extending ≈7 m from the feeder. With the exception of extractable P and total N, all substrate properties exhibited spatial patterns centered on the feeder location. Adult stable fly emergence densities were significantly correlated with substrate microbial respiration rate, NH(4)-N concentration, EC(lab), total C concentration, pH, and moisture content. Logistic regression indicated that EC best predicted the probability of stable flies emerging from a substrate and that the other properties did not provide additional information. A better understanding of the physical, chemical, and biological conditions needed for stable fly larval development may help in identifying previously unrecognized developmental habitats and management of this pest. Targeted implementation of management practices such as sanitation and chemical treatments can be applied to smaller areas reducing labor and improving cost effectiveness.

Dewatered sewage biosolids provide a productive larval habitat for stable flies and house flies (Diptera: Muscidae).

Species diversity and seasonal abundance of muscoid flies (Diptera: Muscidae) developing in biosolid cake (dewatered biosolids) stored at a wastewater treatment facility in northeastern Kansas were evaluated. Emergence traps were deployed 19 May through 20 October 2009 (22 wk) and 27 May through 18 November 2010 (25 wk). In total, 11,349 muscoid flies were collected emerging from the biosolid cake. Stable flies (Stomoxys calcitrans (L.)) and house flies (Musca domestica (L.)), represented 80 and 18% of the muscoid flies, respectively. An estimated 550 stable flies and 220 house flies per square-meter of surface area developed in the biosolid cake annually producing 450,000 stable flies and 175,000 house flies. Stable fly emergence was seasonally bimodal with a primary peak in mid-July and a secondary peak in late August. House fly emergence peaked with the first stable fly emergence peak and then declined gradually for the remainder of the year. House flies tended to emerge from the biosolid cake sooner after its deposition than did stable flies. In addition, house fly emergence was concentrated around midsummer whereas stable fly emergence began earlier in the spring and continued later into the fall. Biosolid age and temperature were the most important parameters affecting emergence for house flies and stable flies, whereas precipitation was not important for either species. This study highlights the importance of biosolid cake as a larval developmental habitat for stable flies and house flies.

Dispersal of stable flies (Diptera: Muscidae) from larval development sites in a Nebraska landscape.

Seven mark-recapture studies were conducted over 3 yr to assess dispersal of newly emerging adult stable flies, Stomoxys calcitrans L., from larval development sites in a mixed agricultural environment in northeastern Nebraska. Infested hay debris piles were marked by dusting their surfaces with fluorescent pigments, adults were captured with surrounding grids of Alsynite sticky traps, and specimens were dissected to determine feeding histories and reproductive age. Distances and directions of 3,889 marked specimens indicated males and females dispersed equally and in all directions. Midguts of males and females were equally likely to contain blood-meal remnants. Percentage with blood remnants and percentage of females with yolk increased with distance from mark origin, indicating survival and spread were positively associated with host finding success. A time-integrated diffusion model fit to results from the seven studies indicated 50% of stable fly adults had dispersed beyond 1.6 km of their natal site, but only 5% had dispersed beyond 5.1 km. These results indicate that stable fly adults on cattle in a given area are most likely to have originated from larval development sites within an ≈ 5 km radius of the subject cattle.

Assessing nuclear and mitochondrial DNA sequence variation within steinernema (rhabditida: steinernematidae).

DNA sequence analysis was used to characterize the nuclear ribosomal DNA ITS1 region and a portion of the COII and 16S rDNA genes of the mitochondrial genome from Steinernema entomopathogenic nematodes. Nuclear ITS1 nucleotide divergence among seven Steinernema spp. ranged from 6 to 22%, and mtDNA divergence among five species ranged from 12 to 20%. No intraspecific variation was observed among three S. feltiae strains. Phylogenetic analysis of both nuclear and mitochondrial DNA sequences confirms the existing morphological relationships of several Steinernema species. Both the rDNA ITS1 and mtDNA sequences were useful for resolving relationships among Steinernema taxa.

Genetic similarity among pheromone and voltinism races of Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae).

The genetic variability of seven European corn borer populations, Ostrinia nubilalis, from North America and Europe was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. The nuclear ribosomal internal transcribed spacer 1 (ITS-1) region (approximately 500 base pair [bp]) and four mitochondrial (mtDNA) regions (1550 bp total) were examined. The smartweed borer, Ostrinia obumbratalis, and south-Western corn borer, Diatraea grandiosella, were used for comparisons. Of 106 restriction sites identified (80 in mtDNA and 26 in ITS-1), none differentiated geographical populations, pheromone races, or voltine ecotypes of the European corn borer. The lack of variation in the ITS-1 of European corn borer was confirmed by DNA sequence analysis. The genetic similarity of European corn borer populations, despite their wide geographical range and physiological differences, may be explained by a relatively recent origin for the voltinism and pheromone races, gene flow among races, and/or expansion from genetic bottlenecks.

Genetic variation in geographical populations of western and Mexican corn rootworm.

Genetic variation in the nuclear rDNA ITS1 region of western corn rootworm, Diabrotica virgifera virgifera (WCR), and Mexican corn rootworm, D. v. zeae (MCR) was studied. Two sites were detected which differentiated WCR and MCR in the 642-base sequence. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the first internal transcribed spacer region (ITS1) sequence revealed no variation within or among the twelve WCR and two MCR populations. PCR-RFLP of 75% of the mitochondrial DNA genome detected one significant polymorphic site out of the approximately 190 restriction sizes observed in WCR. The polymorphism did not differentiate geographical populations of WCR and is not diagnostic for the subspecies. The low levels of variation observed in WCR suggests either high levels of gene flow or a recent geographical expansion from a relatively small base. Gene flow would facilitate the rapid spread of traits that could compromise control programmes, such as insecticide resistance or behavioural modifications. The minimal genetic differentiation between WCR and MCR raises questions about the evolutionary history of these subspecies and how the distinct phenotypes are maintained.

The peptide LSARLAF causes platelet secretion and aggregation by directly activating the integrin alphaIIbbeta3.

A novel peptide (designed to bind to alphaIIbbeta3) caused platelet aggregation and aggregation-independent secretion of the contents of alpha-granules in an alphaIIbbeta3-dependent fashion. The agonist peptide induced secretion in the presence of prostaglandin E1. In cell-free assays, alphaIIbbeta3 bound specifically to immobilized agonist peptide and the peptide enhanced the binding of fibrinogen to immobilized alphaIIbbeta3. The agonist peptide apparently activates alphaIIbbeta3 by directly inducing a conformational change in the receptor. This change activates the platelets and causes secretion in a manner independent of fibrinogen binding.

Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis.

A novel inhibitor of human platelet aggregation, named variabilin, was isolated from salivary glands of the hard tick Dermacentor variabilis using a combination of gel filtration and high pressure liquid chromatography. Variabilin was a potent antagonist of the fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa; alphaIIbbeta3) and the vitronectin receptor alphavbeta3. Amino acid sequence analysis by Edman degradation revealed that it has 47 residues, with a molecular weight of 4968.5. Like many other naturally occurring antagonists of GPIIb-IIIa, variabilin contains the RGD (Arg-Gly-Asp) motif. However, unlike the RGD-containing antagonists of GPIIb-IIIa, the RGD sequence of variabilin is not positioned in a loop bracketed by cysteine residues. It has little sequence homology to the other known naturally occurring antagonists of GPIIb-IIIa, including the disintegrins from snakes, decorsin and ornatin from leeches, and disagregin from soft ticks. Variabilin is the first RGD-containing antagonist isolated from ticks.

Population genetics and gene variation of stable fly populations (Diptera:Muscidae) in Nebraska.

Genetic variation in stable fly, Stomoxys calcitrans (L.), populations from Nebraska, Canada, and Texas was sampled. Four of 12 allozyme loci were polymorphic, with an average of 1.7 alleles per locus. Observed and expected heterozygosities were 0.086 and 0.070, respectively. Nei's genetic distance between populations averaged 0.001 and ranged from 0.000 to 0.005. Wright's F statistics revealed greater variation within than among populations. Allele frequencies were homogeneous among temporal samples from a single population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of 6.4 kb of the mitochondrial DNA genome with 16 restriction enzymes revealed no variation in stable fly populations from Canada, Nebraska, and Texas. PCR-RFLP analysis of a 2.0-kb fragment of the nuclear ribosomal DNA internally transcribed spacer region also revealed no variation. The lack of genetic differentiation among stable fly populations indicates high levels of gene flow among populations. The low levels of variation observed with biochemical and molecular techniques are consistent with a genetic bottleneck during stable fly colonization of North America.

Mitochondrial DNA variation in screwworm.

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to characterize mitochondrial DNA (mtDNA) variation in screwworms, Cochliomyia hominivorax, and secondary screwworm, C.macellaria, from the Caribbean, North America and South America. Four amplicons, totaling 7.1 kb, were analysed with sixteen restriction enzymes. A total of 133 restriction sites was observed in the two species, 104 in C.hominivorax, of which nineteen were variable, and ninety-five in C.macellaria, none of which was variable. Fourteen mtDNA haplotypes were observed among eighteen C.hominivorax examined. Mean divergence between C.hominivorax haplotypes (d) was 0.0064 substitutions per base-pair and genotypic diversity (G) was 0.97. Mean divergence between C.hominivorax and C.macellaria was 0.0824. Cochliomyia hominivorax haplotypes could be divided into three assemblages representing North America, South America and Jamaica, based on UPGMA clustering with d values. The assemblages did not exhibit complete geographic fidelity. These data were discordant with previously published allozyme data indicating little differentiation between screwworm populations. A scenario invoking historically isolated populations coming into contact with the introduction and movement of European livestock is proposed to explain the observed population structure of screwworm.

Population genetics and gene variation in screwworms (Diptera: Calliphoridae) from Brazil.

Allozyme variation in New World screwworm, Cochliomyia hominivorax (Coquerel), populations from Brazil was examined. Variability was observed in 8 of 13 enzyme loci and the frequency of the most common allele was < 0.95 for seven loci. Observed and expected heterozygosities were 0.159 and 0.165, respectively. Comparisons of the Brazilian populations with previously studied populations from Costa Rica resulted in Nei's genetic distances of between 0.000 and 0.006, with the greatest distance being between populations within Brazil. Comparisons with Mexican populations using only three loci resulted in genetic distances < or = 0.031. Goodness-of-fit statistics for Hardy-Weinberg equilibrium and Wright's F statistics indicated small deviations from expected equilibrium genotype frequencies and low levels of differentiation between populations within Brazil. Differentiation among screwworm populations from Brazil, Costa Rica, and Mexico was minimal.

Identification of screwworm species by polymerase chain reaction-restriction fragment length polymorphism.

Restriction fragment length polymorphisms in polymerase chain reaction amplified fragments (PCR-RFLP) of mitochondrial DNA were used to differentiate species of New World screwworms (Diptera: Calliphoridae). Twenty-seven restriction enzymes were screened on five regions of mtDNA. Eleven restriction fragment length patterns differentiated New World screwworm, Cochliomyia hominivorax (Coquerel), from secondary screwworm, Cochliomyia macellaria (F.). Five restriction fragment length patterns were polymorphic in C.hominivorax while all fragment patterns were fixed in C.macellaria. Diagnostic restriction fragment length patterns were used for species diagnosis, whereas intraspecific variable patterns were used to characterize field samples and laboratory strains. The PCR-RFLP technique is flexible with regard to developmental stage of the sample and method of preservation. We were able to characterize specimens of all life stages from egg to adult including larvae preserved in alcohol and pinned adults. PCR-RFLP is rapid and inexpensive, enabling specimens to be characterized within 24 h for less than $2.50.