Synergy theory for murine Harderian gland tumours after irradiation by mixtures of high-energy ionized atomic nuclei.

Experimental studies reporting murine Harderian gland (HG) tumourigenesis have been a NASA concern for many years. Studies used particle accelerators to produce beams that, on beam entry, consist of a single isotope also present in the galactic cosmic ray (GCR) spectrum. In this paper synergy theory is described, potentially applicable to corresponding mixed-field experiments, in progress, planned, or hypothetical. The "obvious" simple effect additivity (SEA) approach of comparing an observed mixture dose-effect relationship (DER) to the sum of the components' DERs is known from other fields of biology to be unreliable when the components' DERs are highly curvilinear. Such curvilinearity may be present at low fluxes such as those used in the one-ion HG experiments due to non-targeted ('bystander') effects, in which case a replacement for SEA synergy theory is needed. This paper comprises in silico modeling of published experimental data using a recently introduced, arguably optimal, replacement for SEA: incremental effect additivity (IEA). Customized open-source software is used. IEA is based on computer numerical integration of non-linear ordinary differential equations. To illustrate IEA synergy theory, possible rapidly-sequential-beam mixture experiments are discussed, including tight 95% confidence intervals calculated by Monte-Carlo sampling from variance-covariance matrices. The importance of having matched one-ion and mixed-beam experiments is emphasized. Arguments are presented against NASA over-emphasizing accelerator experiments with mixed beams whose dosing protocols are standardized rather than being adjustable to take biological variability into account. It is currently unknown whether mixed GCR beams sometimes have statistically significant synergy for the carcinogenesis endpoint. Synergy would increase risks for prolonged astronaut voyages in interplanetary space.

Multimodality, anatomical, and diffusion-weighted fetal imaging of a spontaneously thrombosing congenital dural sinus malformation.

We report on the conventional and diffusion-weighted (DWI) magnetic resonance imaging (MRI) findings of a partially thrombosed torcular Herophili dural sinus malformation. DWI confirmed the intralesional partial thrombosis/blood clot characterized by restricted diffusion. In addition, focal or global intracerebral complications were excluded by fetal DWI. Our findings suggest that DWI is a valuable adjunct to the standard T1- and T2-weighted fetal MRI sequences.

Superior vena cava obstruction evaluation with MDCT.

OBJECTIVE: The purpose of this article is to review the CT findings associated with superior vena cava obstruction and to illustrate collateral venous pathways bypassing the obstruction as shown on MDCT. CONCLUSION: Multiple collateral venous pathways can form to bypass an obstruction of the superior vena cava. With its ability to acquire near isotropic data, MDCT allows high-quality reformations and thus exquisitely displays these venous collaterals and has the potential to aid in planning therapy to bypass the obstruction.

The energy requirements of performance horses in training.

The aim of this study was to estimate the energy requirements of performance horses in active, variable training in the field. Sixty horses in England and Switzerland were measured over 2-wk periods and, for 15 of these, the measurement period was extended, ranging from 21 to 42 wk. Energy intake was estimated by measuring daily feed consumption. Energy output was measured using heart rate (HR) monitors during 608 training sessions, relating HR to volume of oxygen (VO2) and converting VO2 to energy. Field maintenance requirements were calculated by deducting the marginal energy cost of training from energy input. The mean field maintenance expenditure for performance horses with a normal temperament was found to be 0.118 MJ of metabolizable energy (ME) per kilogram of body weight (BW) per day (SD = 0.008, CI = 0.005, n = 60 horses). This result is between 1.9% (P = 0.086) and 20.9% (P < 0.001) greater than the official guidance found in the United States, France, Germany, and Holland. Heart rate monitoring of training revealed a mean energy expenditure (EE) per ridden session of 0.023 MJ ME (SD = 0.001, CI = 0.001, n = 175 training sessions). The mean daily EE for exercise based on a full week's training was 0.018 MJ ME/kg BW/d (SD = 0.005, CI = 0.001, n = 60 horses), representing a multiple of maintenance of 15.3%. This implies that the official guidance in the United States and France may overstate expenditure for exercise by 111% and 15%, respectively (P < 0.01). Daily EE between countries and within disciplines was consistent, allowing for the creation of user-friendly tables that can be used in budgeting the energy component of diets.

The energy requirements of racehorses in training.

The aim of this study was to estimate the energy requirements of Thoroughbred racehorses in active training for flat racing. Twenty-two Thoroughbred racehorses in England were measured over periods from 6 to 15 wk, which included periods of active race training and temporarily reduced training. Energy intake was determined by measuring daily feed consumption. Energy output was measured using heart rate monitors during 730 training sessions, relating heart rate (HR) to oxygen consumption (VO2) and converting VO2 to energy. Field maintenance requirements were calculated by deducting the marginal energy cost of training from energy input. The mean field maintenance expenditure during periods of active race training was 0.1731 megajoules (MJ) of metabolizable energy (ME)/kg of bodyweight (BW)/d (SD = 0.0174, CI = 0.0073, n = 22 horses, 193 wk). This result is 11% to 66% greater than the official guidance found in the United States, France, Germany, and the Netherlands. Heart rate monitoring revealed a mean energy expenditure for exercise of 0.0212 MJ ME/d (SD = 0.0049, CI = 0.0007, n = 22 horses) for racehorses in active race training, a result 70% to 82% below the official guidance. The total mean energy expenditure for racehorses in active race training was 0.1943 MJ ME/kg/d (SD = 0.0177, CI = 0.0078, n = 20 horses 193 wk), 4% to 22% less than the official guidance. Horses actively racing had a 12% higher maintenance requirement than those in training but not yet racing (P = 0.01). The 2- and 3-yr-old horses did not gain weight during active race training, but grew slowly during breaks in training. This study explores the factors affecting energy balance in racehorses, and provides updated findings for their maintenance and training requirements.

Utilization of Radiographic Imaging for Infant Hydronephrosis over the First 12 Months of Life.

PURPOSE: The workup and surveillance strategies for infant hydronephrosis (HN) vary, although this could be due to grade-dependent differences in imaging intensity. We aimed to describe the frequency of imaging studies for HN within the first year of life, stratified by initial HN grade, within a large regional healthcare system. Study Design and Data Source. Retrospective cohort using Intermountain Healthcare Data Warehouse. Inclusion criteria: (1) birth between 1/1/2005 and 12/31/2013, (2) CPT code for HN, and (3) ultrasound (U/S) confirmed HN within four months of birth. Data Collection. Grade of HN on initial postnatal U/S; number of HN-associated radiologic studies (renal U/Ss, voiding cystourethrograms (VCUGs), and diuretic renal scans); demographic and medical variables. Primary Outcome. Sum of radiologic studies within the first year of life or prior to pyeloplasty. Statistical Analysis. Multivariate poisson regression to analyze association between the primary outcome and the initial HN grade. RESULTS: Of 1,380 subjects (993 males and 387 females), 990 (72%), 230 (17%), and 160 (12%) had mild, moderate, and severe HN, respectively. Compared with those with mild HN, patients with moderate (RR: 1.57; 95% CI: 1.42-1.73) and severe (RR: 2.09; 95% CI: 1.88-2.32) HN had a significantly higher rate of imaging use over 12 months (or prior to surgery) after controlling for potential confounders. CONCLUSIONS: In a large regional healthcare system, imaging use for HN is proportional to its initial grade. This suggests that within our system, clinicians treating this condition are using a risk-stratified approach to imaging.

Necrotizing pneumonia caused by community-acquired methicillin-resistant Staphylococcus aureus: an increasing cause of "mayhem in the lung".

Although long recognized as a nosocomial organism, methicillin-resistant Staphylococcus aureus (MRSA) has been noted to have an increasing incidence in both immunocompromised and otherwise healthy people in the community. Community-acquired MRSA (CA-MRSA) is genetically distinct from hospital-acquired MRSA and frequently expresses the Panton-Valentine leukocidin toxin, which confers an aggressive necrotizing phenotype and is accompanied by a poor prognosis. We present a case of CA-MRSA pneumonia with the aim to alert the radiologist of the radiographic manifestations of this increasingly encountered and frequently fatal disease.

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Local recurrence in lumpectomy patients after imprint cytology margin evaluation.

BACKGROUND: This is a follow-up study to our previously reported data on local recurrence rates in patients whose lumpectomy margins were evaluated by intraoperative imprint cytology (IIC(M)). The purpose of this study was to compare local recurrence rates for patients whose lumpectomy margins were evaluated with IIC(M) with local recurrence rates of those not evaluated by IIC(M). METHODS: A total of 1713 patients underwent lumpectomy treatment for breast cancer from 1988 to 2001 were prospectively entered into a computerized database and subsequently included in this study. Of the patients, 520 (group 1) had their surgery performed at an outside institution where conventional margin analysis was performed. Another 1193 (group 2) had their surgery performed at our institution where margins were evaluated by IIC(M). For each histologic type and for the overall sample, probabilities of recurrence with time were estimated using the method of Kaplan and Meier. RESULTS: IIC(M) overcomes sampling error inherent in the frozen section analysis and results in a diminished incidence of overall 5-year local recurrence from 8.8% to 2.8% (P <0.0001). The recurrence rates for each respective histologic subtype are reported for both absolute recurrences and probability of recurrence with time. CONCLUSIONS: IIC(M) provides an accurate evaluation of lumpectomy margins for patients undergoing breast-conservation treatment. IIC(M) was associated with an overall lower local recurrence rate. This series defined the utility of intraoperative imprint cytology for evaluation of margins in patients undergoing breast-conservation treatment.

The clinical relevance of positive sentinel nodes only versus positive nonsentinel lymph nodes in breast cancer patients.

BACKGROUND: The purpose of this study was to determine the difference in clinical outcomes for patients with histologically positive sentinel lymph nodes (SLN+) compared with patients with histologically positive nonsentinel second echelon lymph nodes (NSLN+). METHODS: Eight hundred thirteen node positive patients from a prospectively accrued database of 3200 patients who underwent sentinel node mapping were evaluated. In all, 506 of the 813 patients (62%) were SLN+ only and 307 of the 813 patients (38%) were SLN+ plus at least one NSLN+. Patients' overall survival and disease-free survival were obtained and statistical analyses performed comparing the two groups. RESULTS: As the number of NSLN+ increased, there was a significant difference in disease-free survival (P = 0.001) and overall survival (P = 0.003) between those patients who had 0 to 4 NSLN+ and those who had 5 or more NSLN+. The SLN+ only patients did not show significant differences with respect to survival, based on the number of SLN+ (overall survival, disease-free survival; P = 0.742). CONCLUSIONS: The survival (overall survival, disease-free survival) for patients with 3 or more SLN+ was not statistically different than for patients with 1 or 2 SLN+ (P = 0.742). However, an alteration of biologic behavior was observed when multiple NSLN+ contain metastatic breast cancer. Involvement of 5 or more NSLN+ portends a significantly (P = 0.001) worse prognosis, regardless of the number of SLN+.

Effect of 0.5 Tesla magnetic resonance imaging on the surgical management of breast cancer patients.

BACKGROUND: This trial examines the utility of breast magnetic resonance imaging (MRI) for detection of occult breast disease and its effect on surgical treatment. METHODS: Between October 2000 and March 2002, 76 of 1289 patients underwent bilateral breast MRI within 4 months of a mammogram. The MRI scan, mammogram, pathology reports, and physicians' notes were reviewed to determine impact of MRI on surgical treatment. RESULTS: Magnetic resonance imaging detected 23 additional lesions in 19 patients not detected by mammogram. Cancer occult to mammography was detected by MRI in 6 women, constituting 7.9%. Magnetic resonance imaging impacted surgical treatment plans in 10 of 76 (13.2%) patients. CONCLUSIONS: Magnetic resonance imaging is effective at identifying new subclinical breast disease not seen on mammography. Ten of 76 patients (13.2%) who underwent MRI had their surgical management altered due to MRI findings. Specific criteria should be studied to know which subgroups would benefit most from breast MRI.

Completion axillary lymph node dissection minimizes the likelihood of false negatives for patients with invasive breast carcinoma and cytokeratin positive only sentinel lymph nodes.

OBJECTIVE: To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). METHODS: Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. RESULTS: A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. CONCLUSIONS: Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Novel techniques in sentinel lymph node mapping and localization of nonpalpable breast lesions: the Moffitt experience.

The concept of lymphatic mapping has helped to redefine the clinical significance of lymph nodes with respect to breast cancer. The combination technique using both blue dye and radiocolloid is the most effective method of lymphatic mapping. The data in the literature support the concept that all patients undergoing lumpectomy or especially mastectomy should undergo lymphatic mapping if a diagnosis of invasive cancer is remotely possible. The low morbidity, high sensitivity, and specificity of mapping indicate its use for increasing numbers of patients thought initially not to be candidates for the procedure.

Breast cancer in patients with prior augmentation: presentation, stage, and lymphatic mapping.

The purpose of this study was to determine whether breast cancer patients who had prior breast augmentation presented at a more advanced stage than nonaugmented breast cancer patients, and to determine the mode of presentation and effectiveness of lymphatic mapping and sentinel lymph node biopsy in this same group of patients. A total of 4186 breast cancer patients from 1987 to 2002 were reviewed. Patients who had augmentation before their diagnosis of breast cancer were compared with a control group of nonaugmented breast cancer patients. The Wilcoxon rank sum test was used to compare tumor size, node positivity, and stage. The patient's age at presentation was also compared by the two-sided pooled t test. Seventy-six patients who previously underwent augmentation were identified with 78 breast cancers. Seventy percent (48 of 69) were initially detected by palpation, whereas 30 percent (21 of 69) were initially identified mammographically. Fifty-three percent (n = 41) underwent mastectomy and 47 percent (n = 37) underwent a lumpectomy. This compares with a 63.6 percent (2615 of 4110) breast conservation rate in the nonaugmented population during the same time period. The two groups did not differ regarding (tumor) size (p = 0.77), nodal positivity (p = 0.32), or stage (p = 0.34). The mean time between implant placement and a diagnosis of breast cancer was 14 years. The average age of the patients who had previously undergone augmentation at breast cancer diagnosis was 49.5 years (SD, 9.0 years) versus 57.1 years (SD, 13.5 years) for the nonaugmented patients (p < 0.0001). Forty-nine of the patients underwent lymphatic mapping, with a 100 percent success rate in identifying the sentinel lymph node. There have been no clinically detected axillary recurrences in the patients who had a negative sentinel lymph node biopsy. Breast cancer patients who have undergone previous augmentation are more likely to present with a palpable mass. This initial mode of detection does not appear to translate into a larger tumor size or worse prognosis. Breast conservation and lymphatic mapping can be performed successfully in previously augmented patients.

Age and body mass index may increase the chance of failure in sentinel lymph node biopsy for women with breast cancer.

Age and body mass index (BMI) have been shown to correlate with an increased incidence of failure in identifying a sentinel lymph node (SLN). Mapping senior, overweight adults is common; therefore, the relationship of patient age and BMI on SLN biopsy success is essential. This study examines the mapping failures as they relate to age and BMI. From April 1994 to May 1999, patients underwent an injection of radiocolloid (450 mci) and blue dye (5 cc) prior to SLN biopsy. SLN biopsy failure was defined as lymph nodes being unidentifiable by blue dye or having an in vivo node radiocolloid count of less than 3:1 over background count. BMI was measured as (weight in pounds)(703)/(height in inches)(2); 1,356 patients were attempted for SLN mapping, and 54 failed (3.98%). The radioactive node count was inversely proportional to age ( p < 0.0001). The radioactive node count decreased by a mean of 34 counts per node with each additional year ( p < 0.001). The estimated odds ratios for success were 0.945 for age and 0.946 for BMI. Therefore, every increase of 1 year of age or one unit of BMI decreased the odds of success by approximately 5%. The mean BMI was 29.54 in failed patients and was 26.42 in successful mapping patients ( p = 0.042). Surgeons should be aware that node counts will decrease with increasing age and that increased age and BMI are potential risk factors for SLN mapping failure. However, increased age and/or BMI alone do not appear to be contraindications for SLN biopsy in older or overweight patients.

Effect of lymphatic mapping on diagnosis and treatment of patients with T1a, T1b favorable breast cancer.

OBJECTIVE: To investigate the incidence of nodal metastasis in a consecutive series of patients treated at the authors' institution with highly selective criteria, and to determine the impact that lymphatic mapping and sentinel node biopsy have on the detection of nodal metastases in this carefully selected patient population. METHODS: Study patients were selected from the 7,750 breast cancer patients entered into the authors' database from April 1989 to August 2001, based on the following criteria: nonpalpable, T1a and T1b, non-high nuclear grade tumors, without lymphovascular invasion. RESULTS: Of the 7,750 patients in the database 1,327 (17%) were found to have T1a and T1b lesions. Three hundred eighty-nine patients were confirmed to meet all four selection criteria. This represents 5% (389/7,750) of the authors' breast cancer patients and 29.3% (389/1,327) of the authors' T1a/T1b tumors. One hundred sixty patients were diagnosed before routine use of lymphatic mapping, and only one patient had a positive axillary lymph node. Two hundred twenty-nine patients underwent lymphatic mapping and sentinel lymph node biopsy, and 10 had a positive axillary lymph node. The difference in proportions of nodal positivity between the mapped and unmapped patients was significant. CONCLUSIONS: This study clearly demonstrates the ability of lymphatic mapping and a more detailed examination of the sentinel node to increase the accuracy of axillary staging. It has been argued that this highly selected group of breast cancer patients possessing retrospectively identified "favorable" characteristics does not require axillary staging. This select population represents only 5% of breast cancer patients in this series, and the authors do not believe they can be accurately identified preoperatively. Therefore, the authors strongly argue for evaluation of the axillary nodal status by lymphatic mapping.

Radioactive seed localization breast biopsy and lumpectomy: can specimen radiographs be eliminated?

BACKGROUND: Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. METHODS: A total of 134 women were entered onto an institutional review board-approved study. RSL was performed by placing a titanium seed containing.29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. RESULTS: Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. CONCLUSIONS: After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.