Interval Cancer Detection Using a Neural Network and Breast Density in Women with Negative Screening Mammograms.

Background Inclusion of mammographic breast density (BD) in breast cancer risk models improves accuracy, but accuracy remains modest. Interval cancer (IC) risk prediction may be improved by combining assessments of BD and an artificial intelligence (AI) cancer detection system. Purpose To evaluate the performance of a neural network (NN)-based model that combines the assessments of BD and an AI system in the prediction of risk of developing IC among women with negative screening mammography results. Materials and Methods This retrospective nested case-control study performed with screening examinations included women who developed IC and women with normal follow-up findings (from January 2011 to January 2015). An AI cancer detection system analyzed all studies yielding a score of 1-10, representing increasing likelihood of malignancy. BD was automatically computed using publicly available software. An NN model was trained by combining the AI score and BD using 10-fold cross-validation. Bootstrap analysis was used to calculate the area under the receiver operating characteristic curve (AUC), sensitivity at 90% specificity, and 95% CIs of the AI, BD, and NN models. Results A total of 2222 women with IC and 4661 women in the control group were included (mean age, 61 years; age range, 49-76 years). AUC of the NN model was 0.79 (95% CI: 0.77,0.81), which was higher than AUC of the AI cancer detection system or BD alone (AUC, 0.73 [95% CI: 0.71, 0.76] and 0.69 [95% CI: 0.67, 0.71], respectively; P < .001 for both). At 90% specificity, the NN model had a sensitivity of 50.9% (339 of 666 women; 95% CI: 45.2, 56.3) for prediction of IC, which was higher than that of the AI system (37.5%; 250 of 666 women; 95% CI: 33.0, 43.7; P < .001) or BD percentage alone (22.4%; 149 of 666 women; 95% CI: 17.9, 28.5; P < .001). Conclusion The combined assessment of an artificial intelligence detection system and breast density measurements enabled identification of a larger proportion of women who would develop interval cancer compared with either method alone. Published under a CC BY 4.0 license.

Impact of artificial intelligence support on accuracy and reading time in breast tomosynthesis image interpretation: a multi-reader multi-case study.

OBJECTIVES: Digital breast tomosynthesis (DBT) increases sensitivity of mammography and is increasingly implemented in breast cancer screening. However, the large volume of images increases the risk of reading errors and reading time. This study aims to investigate whether the accuracy of breast radiologists reading wide-angle DBT increases with the aid of an artificial intelligence (AI) support system. Also, the impact on reading time was assessed and the stand-alone performance of the AI system in the detection of malignancies was compared to the average radiologist. METHODS: A multi-reader multi-case study was performed with 240 bilateral DBT exams (71 breasts with cancer lesions, 70 breasts with benign findings, 339 normal breasts). Exams were interpreted by 18 radiologists, with and without AI support, providing cancer suspicion scores per breast. Using AI support, radiologists were shown examination-based and region-based cancer likelihood scores. Area under the receiver operating characteristic curve (AUC) and reading time per exam were compared between reading conditions using mixed-models analysis of variance. RESULTS: On average, the AUC was higher using AI support (0.863 vs 0.833; p = 0.0025). Using AI support, reading time per DBT exam was reduced (p < 0.001) from 41 (95% CI = 39-42 s) to 36 s (95% CI = 35- 37 s). The AUC of the stand-alone AI system was non-inferior to the AUC of the average radiologist (+0.007, p = 0.8115). CONCLUSIONS: Radiologists improved their cancer detection and reduced reading time when evaluating DBT examinations using an AI reading support system. KEY POINTS: • Radiologists improved their cancer detection accuracy in digital breast tomosynthesis (DBT) when using an AI system for support, while simultaneously reducing reading time. • The stand-alone breast cancer detection performance of an AI system is non-inferior to the average performance of radiologists for reading digital breast tomosynthesis exams. • The use of an AI support system could make advanced and more reliable imaging techniques more accessible and could allow for more cost-effective breast screening programs with DBT.

One-view digital breast tomosynthesis as a stand-alone modality for breast cancer detection: do we need more?

PURPOSE: To compare the performance of one-view digital breast tomosynthesis (1v-DBT) to that of three other protocols combining DBT and mammography (DM) for breast cancer detection. MATERIALS AND METHODS: Six radiologists, three experienced with 1v-DBT in screening, retrospectively reviewed 181 cases (76 malignant, 50 benign, 55 normal) in two sessions. First, they scored sequentially: 1v-DBT (medio-lateral oblique, MLO), 1v-DBT (MLO) + 1v-DM (cranio-caudal, CC) and two-view DM + DBT (2v-DM+2v-DBT). The second session involved only 2v-DM. Lesions were scored using BI-RADS® and level of suspiciousness (1-10). Sensitivity, specificity, receiver operating characteristic (ROC) and jack-knife alternative free-response ROC (JAFROC) were computed. RESULTS: On average, 1v-DBT was non-inferior to any of the other protocols in terms of JAFROC figure-of-merit, area under ROC curve, sensitivity or specificity (p>0.391). While readers inexperienced with 1v-DBT screening improved their sensitivity when adding more images (69-79 %, p=0.019), experienced readers showed similar sensitivity (76 %) and specificity (70 %) between 1v-DBT and 2v-DM+2v-DBT (p=0.482). Subanalysis by lesion type and breast density showed no difference among modalities. CONCLUSION: Detection performance with 1v-DBT is not statistically inferior to 2v-DM or to 2v-DM+2v-DBT; its use as a stand-alone modality might be sufficient for readers experienced with this protocol. KEY POINTS: • One-view breast tomosynthesis is not inferior to two-view digital mammography. • One-view DBT is not inferior to 2-view DM plus 2-view DBT. • Training may lead to 1v-DBT being sufficient for screening.

Burn patients, parents and doctors; are we in agreement?

BACKGROUND: Burns in children present a serious challenge for patients, parents and doctors. This study aimed to investigate differences in desire for burn reconstruction in paediatric patient, parent and surgeon groups. METHODS: This study is a case series (n=21). Questionnaires were administered to patients, their parents and surgeons. Medical records were also reviewed. Data were analysed to ascertain how different factors affected desire for reconstruction between parents, patients and surgeons. RESULTS: Surgeons and parents were more likely to desire surgery than paediatric patients (76.2 vs 61.9 vs 52.4% respectively). Surgeons were more likely to recommend surgery for pre-pubescent patients (81.8 vs 70%). All groups were more likely to desire surgery for female patients. Patients and parents desired surgery more for hidden scars. Higher VSS scores were associated with a higher desire for surgery in all groups. Agreement between patients and parents was highest (Kappa=0.81) with poor-moderate agreement between surgeons, patients and parents (Kappa=0.12-0.24). CONCLUSIONS: This study suggests that paediatric patients are less likely to want burn reconstruction compared to parents and surgeons. Gender and age may impact on desire for surgery. Opportunities for improving patient, parent and surgeon agreement may exist. Further research is warranted to validate these results.

Increased caloric intake on a fat-rich diet: role of ovarian steroids and galanin in the medial preoptic and paraventricular nuclei and anterior pituitary of female rats.

Previous studies in male rats have demonstrated that the orexigenic peptide galanin (GAL), in neurones of the anterior parvocellular region of the paraventricular nucleus (aPVN) projecting to the median eminence (ME), is stimulated by consumption of a high-fat diet and may have a role in the hyperphagia induced by fat. In addition to confirming this relationship in female rats and distinguishing the aPVN-ME from other hypothalamic areas, the present study identified two additional extra-hypothalamic sites where GAL is stimulated by dietary fat in females but not males. These sites were the medial preoptic nucleus (MPN), located immediately rostral to the aPVN, and the anterior pituitary (AP). The involvement of ovarian steroids, oestradiol (E(2)) and progesterone (PROG), in this phenomenon was suggested by an observed increase in circulating levels of these hormones and GAL in MPN and AP with fat consumption and an attenuation of this effect on GAL in ovariectomised (OVX) rats. Furthermore, in the same four areas affected by dietary fat, levels of GAL mRNA and peptide immunoreactivity were stimulated by E(2) and further by PROG replacement in E(2)-primed OVX rats and were higher in females compared to males. Because both GAL and PROG stimulate feeding, their increase on a fat-rich diet may have functional consequences in females, possibly contributing to the increased caloric intake induced by dietary fat. This is supported by the findings that PROG administration in E(2)-primed OVX rats reverses the inhibitory effect of E(2) on total caloric intake while increasing voluntary fat ingestion, and that female rats with higher GAL exhibit increased preference for fat compared to males. Thus, ovarian steroids may function together with GAL in a neurocircuit, involving the MPN, aPVN, ME and AP, which coordinate feeding behaviour with reproductive function to promote consumption of a fat-rich diet at times of increased energy demand.

Gonadal steroids and hypothalamic galanin and neuropeptide Y: role in eating behavior and body weight control in female rats.

The neuropeptides, galanin (GAL) and neuropeptide Y (NPY), based on studies in male rodents, are believed to have a role in controlling energy balance, both nutrient ingestion and metabolism. Whereas these peptides are also involved in reproduction, little is known about their specific function in energy balance in females. In rats consuming lab chow or macronutrient diets, measurements across the estrous cycle were taken of hypothalamic GAL and NPY, using RIA and immunohistochemistry; of the circulating hormones, estradiol, progesterone, and LH; and also of food intake and body weight. Levels of GAL and NPY peak during the proestrous phase of the female cycle when circulating estradiol and progesterone also rise. As previously reported for GAL, this peak is detected in two areas, the medial preoptic area (MPOA; +110%; P < 0.05) and the external zone of the median eminence (+57%; P < 0.05). In addition, this proestrous peak is seen in the paraventricular nucleus (PVN), specifically the anterior parvocellular portion (+35%; P < 0.05). Similarly, NPY rises during proestrous in the medial region of the PVN (+21%; P < 0.05) in addition to the MPOA (+78%; P < 0.05) and arcuate nucleus (+35%; P < 0.05). This peak in peptide levels is accompanied by an increase in caloric intake in rats receiving the lab chow diet and a specific increase in preference for fat in rats receiving macronutrient diets. Animals showing a preference for a fat-rich diet exhibit higher levels of GAL in the MPOA as well as the PVN and median eminence and also of NPY specifically in the MPOA. These peptides in the MPOA are similarly enhanced in animals with greater body fat, independent of diet. This evidence suggests that in the female rat, both GAL and NPY in the MPOA may contribute to the overeating and increased weight gain that occur during a fat-rich diet.

A cadaveric and clinical evaluation of endoscopically assisted zygomatic fracture repair.

An endoscopic method of malar arch repair without a bicoronal incision has been recently described. To determine the effectiveness of this new technique, a cadaver study was performed to evaluate the capacity of this technique to (1) restore the anatomic position of a fractured malar arch, (2) rigidly fixate the arch, and (3) avoid injury to the frontal branch of the facial nerve. The technique of endoscopically assisted fracture repair was then applied to a clinical series of consecutive patients presenting with displaced zygomatic fractures with comminution at the malar arch. All cadaveric specimens repaired with this endoscopic technique demonstrated anatomic reduction and rigid fixation of the arch without disruption of the frontal branch of the facial nerve. In all clinical cases, four-point rigid plate fixation (zygomaticofrontal, infraorbital, malar arch, and zygomaticomaxillary buttress) was achieved endoscopically with limited access incisions. All clinical cases demonstrated excellent skeletal restoration of the zygoma on postoperative computed tomography scans. On clinical examination, facial symmetry and normal facial nerve function were observed in all patients after operation.

Galanin-containing neurons in the paraventricular nucleus: a neurochemical marker for fat ingestion and body weight gain.

The physiological function of the peptide galanin (Gal) remains to be established. It is known to exist in high concentrations within the hypothalamus and to modulate the secretion of specific hormones, as well as to potentiate food consumption. Our study provides evidence for an essential function of neuronal Gal, within a specific hypothalamic area, in stimulating the behavioral process of fat ingestion and body weight gain. Through analyses of peptide levels via RIA and of gene expression via in situ hybridization, a close positive association is established between Gal in the paraventricular nucleus (PVN), particularly its midlateral region, and fat ingestion. No such relationship is detected for Gal in other brain areas or between PVN Gal and ingestion of carbohydrate or protein, supporting the behavioral and anatomical specificity of this relationship. Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a dramatic decline in fat ingestion and body weight suggests that endogenous Gal contributes to the natural appetite for fat. Thus, Gal in the PVN is identified as a neurochemical marker for fat ingestion and, consequently, body weight gain.

Meal pattern analysis of macronutrient intake after PVN norepinephrine and peripheral clonidine administration.

Norepinephrine (NE) injected into the paraventricular nucleus (PVN) of the hypothalamus of rats is a potent stimulant of food intake, more specifically ingestion of the carbohydrate nutrient. In 2 experiments of the present study, this effect was found to be dose-dependent, and the effectiveness of NE in potentiating total food consumption was greatly reduced when the carbohydrate diet was removed. In addition, experiments using a computer-automated data acquisition apparatus were performed to characterize, in detail, the impact of PVN injection of NE and peripheral administration of the alpha2-noradrenergic agonist clonidine (CLON) on the macrostructure of feeding behavior in animals given 3 pure macronutrient diets. These 2 compounds, injected at the onset of the nocturnal feeding cycle, had very similar effects on meal patterns, with both affecting nutrient intake by increasing meal size and duration rather than by increasing meal frequency. They both affected primarily the first meal of the dark cycle, selectively enhancing carbohydrate ingestion by increasing Kcal intake, percent composition in the total diet and feeding time, and also by decreasing the satiating impact of this macronutrient. These stimulatory effects of NE and CLON on carbohydrate ingestion during the first meal were followed by complete recovery over the next 1 to 2 hours after injection. In addition to these predominant effects on carbohydrate intake, PVN NE at the highest doses tested (10 and 20 nmoles) produced a small increase in fat intake, whereas peripheral CLON actually decreased intake of fat and protein over the 12-hour cycle. The similarities in the impact of NE and CLON on carbohydrate feeding patterns support the hypothesis that both agonists may be acting via the same PVN alpha2-noradrenergic system controlling ingestion of the carbohydrate-rich meals which predominate at dark onset.

Pregnancy and discogenic disease of the spine.

Low back pain is common during pregnancy and is of moderate or severe intensity in about one fourth of all pregnancies. The etiology is multifactorial but in most cases is related to the physical and physiologic changes brought about by pregnancy. For most women, the pain resolves spontaneously, although they remain at higher risk for increased LBP in future pregnancies and for the development of symptomatic disc disease in later life. Many of the common treatments for LBP are contraindicated or must be modified in this setting. Neurologically symptomatic herniated discs are rare during pregnancy, yet, when indicated, pregnant women can safely undergo surgery.

A simple method of removing residual intrathoracic air post-thoracotomy in children.

A simple and effective method of aspirating residual intrathoracic air is described. This method can be used when air leaks or persistent fluid accumulations are not expected. This technique may be easily adapted for use in older children or adults when similar circumstances are present. Standard postoperative monitoring, including serial roentgenogram of the chest, should be used to verify appropriate pulmonary re-expansion.

The effect of intravenous interleukin-2 on brain water content.

Parenteral treatment with interleukin-2 (IL-2) is effective against certain advanced cancers outside the central nervous system. Prior to commencement of Phase II trials in patients with brain tumors, the neurological and neuroradiological features of 10 patients treated with intravenous administration of repeated doses of IL-2 were studied. Three patients had malignant gliomas, and seven patients had extracranial cancer without evidence of intracranial metastasis. All were treated with intravenous doses of 10(5) U/kg three times daily for up to 5 days. The patients with gliomas received cranial computerized axial tomography (CT) scans before IL-2 therapy was initiated and during the later stages of treatment. The patients with extracranial cancer underwent T2-weighted magnetic resonance (MR) imaging before and later during therapy. After two to 11 doses of IL-2, the patients with gliomas had marked neurological deterioration that was associated with a mild to marked increase in peritumoral edema and mass effect visible on CT scans. With cessation of treatment and appropriate supportive care, all returned to their pretreatment state. The patients with extracranial cancer were either neurologically unchanged or underwent minor transient changes in mental status (lethargy and confusion). In these patients, the MR signal intensity was quantified and compared in eight anatomic regions of interest. In six of the seven patients, there were increases in gray and white matter signal intensity consistent with increased cerebral water content. The percentage changes (means +/- standard error of the means) were 12.6% +/- 7.3% in the gray matter and 17.0% +/- 6.2% in the white matter. This study demonstrates that treatment with a high parenteral dose of IL-2 is not tolerated by patients with gliomas due to increased cerebral edema. In patients with extracranial cancer but no brain disease, parenteral IL-2 induces an increase in the cerebral water content of both gray and white matter.

The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model.

Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 +/- 14.6 and 35.8 +/- 6.0, respectively, mean +/- standard error of the mean) were larger (p less than 0.05) than in control animals (61.4 +/- 6.4 and 14.6 +/- 2.2, respectively). In contrast, in normal frontal and occipital tissue contralateral to the tumor-bearing hemisphere, there was no significant difference between the transfer constants in IL-2-treated and control animals. Furthermore, treatment of animals with IL-2 excipient caused no change in permeability as compared to animals treated with Hanks' balanced salt solution. Parenteral injection of IL-2 increases blood-brain barrier disruption in tumor-bearing rat brain but does not increase the vascular permeability of normal brain. Methods to prevent this increased tumor vessel permeability are required before parenteral IL-2 can be used safely for the treatment of primary or metastatic brain tumors.

Myasthenia in frogs immunized against cholinergic-receptor protein.

Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals.