A Pilot Study of the Impact of Microwave Ablation on the Dielectric Properties of Breast Tissue.

Percutaneous microwave ablation (MWA) is a promising technology for patients with breast cancer, as it may help treat individuals who have less aggressive cancers or do not respond to targeted therapies in the neoadjuvant or pre-surgical setting. In this study, we investigate changes to the microwave dielectric properties of breast tissue that are induced by MWA. While similar changes have been characterized for relatively homogeneous tissues, such as liver, those prior results are not directly translatable to breast tissue because of the extreme tissue heterogeneity present in the breast. This study was motivated, in part by the expectation that the changes in the dielectric properties of the microwave antenna's operation environment will be impacted by tissue composition of the ablation target, which includes not only the tumor, but also its margins. Accordingly, this target comprises a heterogeneous mix of malignant, healthy glandular, and adipose tissue. Therefore, knowledge of MWA impact on breast dielectric properties is essential for the successful development of MWA systems for breast cancer. We performed ablations in 14 human ex-vivo prophylactic mastectomy specimens from surgeries that were conducted at the UW Hospital and monitored the temperature in the vicinity of the MWA antenna during ablation. After ablation we measured the dielectric properties of the tissue and analyzed the tissue samples to determine both the tissue composition and the extent of damage due to the ablation. We observed that MWA induced cell damage across all tissue compositions, and found that the microwave frequency-dependent relative permittivity and conductivity of damaged tissue are lower than those of healthy tissue, especially for tissue with high fibroglandular content. The results provide information for future developments on breast MWA systems.

Quantitative assessment of distant recurrence risk in early stage breast cancer using a nonlinear combination of pathological, clinical and imaging variables.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence. In addition to clinical and pathological variables, we enhanced our model using intraoperatively determined global mammographic breast density (MBD) and local breast density (LBD). LBD was measured with optical spectral imaging capable of sensing regional concentrations of tissue constituents. A cohort of 56 ER+ patients with an OncotypeDx score was evaluated. We demonstrated that combining MBD/LBD measurements with clinical and pathological variables improves distant recurrence risk prediction accuracy, with high correlation (r = 0.98) to the OncotypeDx recurrence score.

Uterine Sarcoma Presenting with Sepsis from Clostridium perfringens Endometritis in a Postmenopausal Woman.

Clostridium perfringens is an anaerobic gram positive rod that is found in normal vaginal and cervical flora in 1-10% of healthy women. Uterine infection with Clostridium perfringens is seen rarely but is often related to underlying uterine pathology and can progress quickly to sepsis. Early recognition of sepsis, prompt treatment with antibiotics, and source control with surgical management allow for optimal chance of recovery. We present a case of a postmenopausal woman who presented with sepsis, vaginal bleeding, and back pain who was found to have Clostridium perfringens infection in the setting of undifferentiated uterine sarcoma.

Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.

BACKGROUND: Estrogen receptor beta (ERß) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERß has antiproliferative effects in TNBC cells expressing ERß. This phase 2 study evaluated single-agent high-dose estradiol in patients with advanced TNBC. PATIENTS AND METHODS: Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB, and PFS by ERß status were also examined. RESULTS: Seventeen evaluable women were enrolled. Median age was 58 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with one lasting more than 16 weeks. ERß expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERß-positive patients and 0% (0 of 4) in ERß-negative patients (P = 1). PFS was poor (median, 1.9 months) and not statistically significantly different between ERß-positive versus -negative patients. No new adverse events from estradiol were identified. The study closed after the first stage as a result of limited responses in these unselected patients. CONCLUSION: In unselected TNBC, high-dose estradiol has limited efficacy. However, further evaluation of ERß selective agonists in TNBC selected by ERß expression may be warranted.

Identification of Selective Lead Compounds for Treatment of High-Ploidy Breast Cancer.

Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple-negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase 1 (HPRT1), suggesting an elevated gene-dosage of HPRT1 in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy. Mol Cancer Ther; 15(1); 48-59. ©2015 AACR.

Dynamic and quasi-static mechanical testing for characterization of the viscoelastic properties of human uterine tissue.

Ultrasound elastography is envisioned as an optional modality to augment standard ultrasound B-mode imaging and is a promising technique to aid in detecting uterine masses which cause abnormal uterine bleeding in both pre- and post-menopausal women. In order to determine the effectiveness of strain imaging, mechanical testing to establish the elastic contrast between normal uterine tissue and stiffer masses such as leiomyomas (fibroids) and between softer pathologies such as uterine cancer and adenomyosis has to be performed. In this paper, we evaluate the stiffness of normal uterine tissue, leiomyomas, and endometrial cancers using a EnduraTEC ElectroForce (ELF) system. We quantify the viscoelastic characteristics of uterine tissue and associated pathologies globally by using two mechanical testing approaches, namely a dynamic and a quasi-static (ramp testing) approach. For dynamic testing, 21 samples obtained from 18 patients were tested. The testing frequencies were set to 1, 10, 20, and 30 Hz. We also report on stiffness variations with pre-compression from 1% to 6% for testing at 2%, 3%, and 4% strain amplitude. Our results show that human uterine tissue stiffness is both dependent on percent pre-compression and testing frequencies. For ramp testing, 20 samples obtained from 14 patients were used. A constant strain rate of 0.1% was applied and comparable results to dynamic testing were obtained. The mean modulus contrast at 2% amplitude between normal uterine tissue (the background) and leiomyomas was 2.29 and 2.17, and between the background and cancer was 0.47 and 0.39 for dynamic and ramp testing, respectively.

Metastasis of primary lung carcinoma to the breast: a systematic review of the literature.

BACKGROUND: The purpose of this systematic review was to summarize previously published case reports of primary lung carcinoma metastasis to the breast to assess common clinical and pathologic features and management strategies. MATERIALS AND METHODS: Case reports describing breast metastasis of primary lung carcinoma were systematically evaluated in MEDLINE and EMBASE. RESULTS: Thirty-one reported cases of non-small-cell lung carcinoma (NSCLC) metastasized to the breast were identified, along with eight cases of small-cell lung carcinoma. Sixty-seven percent of reported NSCLC metastases to the breast were detected metachronously with the primary lung abnormality, whereas 80% of small-cell lung carcinoma breast metastases appeared synchronously. Thyroid transcription factor 1 was found to be expressed in 58% of total NSCLC breast metastases, including 83% of those of adenocarcinoma origin. Therapeutic strategies among NSCLC cases varied widely, and only 36% of NSCLC breast metastasis patients were administered chemotherapy. Additional sites of metastasis in these cases are summarized as well. CONCLUSIONS: It is recommended to include metastatic lung cancer in the differential diagnosis of patients presenting with a breast abnormality in the context of a suspected lung cancer. Thyroid transcription factor 1 expression should be examined in these cases. The metachronous versus synchronous nature of lung carcinoma metastasis to the breast has consequences for both detection of the primary and secondary lesions and patient outlook. Clinical correlation is vital to effective management of the care of patients harboring these atypical secondary lesions.

A new diagnostic test for endometrial cancer?: Cytology analysis of sonohysterography distention media.

OBJECTIVE: During saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures. METHODS: Thirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology. RESULTS: Of the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5 mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%-51%), 36% (17%-59%), and 42% (22%-63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%-53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated. CONCLUSIONS: Most patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures.

A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent. METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated. RESULTS: Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients. CONCLUSION: The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles.

Endoscopic ultrasound fine-needle aspiration characteristics of primary adenocarcinoma versus other malignant neoplasms of the pancreas.

BACKGROUND: Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic). OBJECTIVE: To compare and characterize primary pancreatic adenocarcinoma versus other malignant neoplasms, hereafter referred to as nonprimary pancreatic adenocarcinoma (NPPA), diagnosed by EUS-guided FNA. METHODS: The present study was a retrospective analysis of a prospectively maintained database. The setting was a tertiary care, academic medical centre. Patients referred for suspected pancreatic neoplasms were evaluated. Based on EUS-FNA characteristics, primary pancreatic adenocarcinoma was differentiated from other malignant neoplasms. The subset of other neoplasms was defined as malignant lesions that were 'NPPAs' (ie, predominantly solid or solid/cystic based on EUS appearance and primary malignant lesions or metastatic lesions to the pancreas). Pancreatic masses that were benign cystic lesions (pseudocyst, simple cyst, serous cystadenoma) and focal inflammatory lesions (acute, chronic and autoimmune pancreatitis) were excluded. RESULTS: A total of 230 patients were evaluated using EUS-FNA for suspected pancreatic mass lesions. Thirty-eight patients were excluded because they were diagnosed with inflammatory lesions or had purely benign cysts. One hundred ninety-two patients had confirmed malignant pancreatic neoplasms (ie, pancreatic adenocarcinoma [n=144], NPPA [n=48]). When comparing adenocarcinoma with NPPA lesions, there was no significant difference in mean age (P=0.0675), sex (P=0.3595) or average lesion size (P=0.3801). On average, four FNA passes were necessary to establish a cytological diagnosis in both lesion subtypes (P=0.396). Adenocarcinomas were more likely to be located in the pancreatic head (P=0.0198), whereas masses in the tail were more likely to be NPPAs (P=0.0006). Adenocarcinomas were also more likely to exhibit vascular invasion (OR 4.37; P=0.0011), malignant lymphadenopathy (P=0.0006), pancreatic duct dilation (OR 2.4; P=0.022) and common bile duct dilation (OR 2.87; P=0.039). CONCLUSIONS: Adenocarcinoma was more likely to be present in the head of the pancreas, have lymph node and vascular involvement, as well as evidence of pancreatic duct and common bile duct obstruction. Of all malignant pancreatic lesions analyzed by EUS-FNA, 25% were NPPA, suggesting that FNA is crucial in establishing a diagnosis and may be helpful in preoperative planning.

Uterine leiomyosarcoma diffusely express disialoganglioside GD2 and bind the therapeutic immunocytokine 14.18-IL2: implications for immunotherapy.

Uterine leiomyosarcoma comprises <1 % of uterine malignancies and is known for its clinically aggressive course. Extrapelvic recurrences are common and often lethal. No adjuvant therapies have been shown to significantly improve overall survival, highlighting the need for new and novel therapies. Our objective was to determine whether GD2-specific immunocytokine therapy may be explored for the treatment for uterine leiomyosarcoma. To do so, frozen tissue sections were obtained from the Gynecologic Oncology Group tumor bank and evaluated by immunohistochemistry (IHC) for GD2 expression using both the parent mouse monoclonal antibody 14G2A and immunocytokine 14.18-IL2 generated from the 14G2A sequence. Immunoreactivity was detected by avidin-biotin complex with DAB substrate. Specimens were reviewed by a pathologist with light microscopy and classified as negative, 1+, 2+ or 3+, compared to human melanoma cells as positive control and tissue incubated in the absence of primary antibody as negative control. GD2 was diffusely present in all evaluable samples. 10 tumors (67 %) demonstrated 3+ IHC intensity for GD2, two tumors (13 %) demonstrated 2+ intensity, and 3 (20 %) tumors demonstrated 1+ intensity. Eleven cases had sufficient tissue to assess 14.18-IL2 binding. All 11 cases bound 14.18-IL2 in a pattern identical to the parent antibody. Uterine leiomyosarcoma diffusely express GD2 and bind the therapeutic immunocytokine 14.18-IL2. This warrants further exploration to determine whether immunocytokine therapy may have a clinical role in the management of these aggressive tumors.

Growing mammary choristoma masquerading as a lumbosacral lipomyelomeningocele in a pubertal girl.

The authors report, to the best of their knowledge, the first case of lumbosacral choristoma of breast origin, presenting in a young girl with lumbosacral lipomyelomeningocele. Although choristomas are considered to be benign, the regrowth of this mass when the patient was 15 and 16 years of age, and its involvement in the conus medullaris and cauda equina, warranted 2 additional resections with spinal cordotomy resulting in cessation of any further growth. The authors describe the case and provide a review of pertinent literature and a discussion of the mechanisms involving the development and growth of this lesion.

Analysis of human fibroadenomas using three-dimensional impedance maps.

Three-dimensional impedance maps (3DZMs) are virtual volumes of acoustic impedance values constructed from histology to represent tissue microstructure acoustically. From the 3DZM, the ultrasonic backscattered power spectrum can be predicted and model based scatterer properties, such as effective scatterer diameter (ESD), can be estimated. Additionally, the 3DZM can be exploited to visualize and identify possible scattering sites, which may aid in the development of more effective scattering models to better represent the ultrasonic interaction with underlying tissue microstructure. In this study, 3DZMs were created from a set of human fibroadenoma samples. ESD estimates were made assuming a fluid-filled sphere form factor model from 3DZMs of volume 300×300×300 µm. For a collection of 33 independent human fibroadenoma tissue samples, the ESD was estimated to be 111±40.7 µm. The 3DZMs were then investigated visually to identify possible scattering sources which conformed to the estimated model scatterer dimensions. This estimation technique allowed a better understanding of the spatial distribution and variability of the estimates throughout the volume.

Compression-dependent viscoelastic behavior of human cervix tissue.

We have characterized the viscoelastic properties of human cervical tissue through a range of precompressional loads and testing frequencies. Mechanical testing is necessary to develop robust elasticity-based techniques for the diagnosis of cervical abnormalities. The storage modulus (E') and material damping (tan 6) were measured in 13 patients, 40 to 76 years old. Our results showed that E' increased monotonically from approximately 4.7 to 6.3 kPa over the precompression range (1-6%) for a testing frequency of 1 Hz. Increases in precompressions of 4% or greater significantly increased E' obtained after dynamic compression testing when data were normalized to 1% precompression. Tan delta remained fairly constant (approximately 0.35) and was not significantly affected by changes in precompression. E' and tan delta increased significantly with frequency. E 'monotonically increased from 4.7 to 7.9 kPa for the 1-3% compression range (lowest precompression for 2% amplitude) and from 6.3 to 10.3 kPa for the 6-8% range (highest precompression for 2% amplitude) when increasing frequency from 1 to 30 Hz. Tan delta increased montonically from 0.35 to 0.45 for 2% amplitude compressions from 1 to 30 Hz regardless of initial precompression. Our results show that precompression and testing frequency must be taken into account in order to obtain consistent measurements in mechanical diagnostic tests developed for cervical abnormalities.

Fluorescence spectroscopy: an adjunct diagnostic tool to image-guided core needle biopsy of the breast.

We explored the use of a fiber-optic probe for in vivo fluorescence spectroscopy of breast tissues during percutaneous image-guided breast biopsy. A total of 121 biopsy samples with accompanying histological diagnosis were obtained clinically and investigated in this study. The tissue spectra were analyzed using partial least-squares analysis and represented using a set of principal components (PCs) with dramatically reduced data dimension. For nonmalignant tissue samples, a set of PCs that account for the largest amount of variance in the spectra displayed correlation with the percent tissue composition. For all tissue samples, a set of PCs was identified using a Wilcoxon rank-sum test as showing statistically significant differences between: 1) malignant and fibrous/benign; 2) malignant and adipose; and 3) malignant and nonmalignant breast samples. These PCs were used to distinguish malignant from other nonmalignant tissue types using a binary classification scheme based on both linear and nonlinear support vector machine (SVM) and logistic regression (LR). For the sample set investigated in this study, the SVM classifier provided a cross-validated sensitivity and specificity of up to 81% and 87%, respectively, for discrimination between malignant and fibrous/benign samples, and up to 81% and 81%, respectively, for discriminating between malignant and adipose samples. Classification based on LR was used to generate receiver operator curves with an area under the curve (AUC) of 0.87 for discriminating malignant versus fibrous/benign tissues, and an AUC of 0.84 for discriminating malignant from adipose tissue samples. This study demonstrates the feasibility of performing fluorescence spectroscopy during clinical core needle breast biopsy, and the potential of this technique for identifying breast malignancy in vivo.

Electromagnetic spectroscopy of normal breast tissue specimens obtained from reduction surgeries: comparison of optical and microwave properties.

Techniques utilizing electromagnetic energy at microwave and optical frequencies have been shown to be promising for breast cancer detection and diagnosis. Since different biophysical mechanisms are exploited at these frequencies to discriminate between healthy and diseased tissue, combining these two modalities may result in a more powerful approach for breast cancer detection and diagnosis. Toward this end, we performed microwave dielectric spectroscopy and optical diffuse reflectance spectroscopy measurements at the same sites on freshly excised normal breast tissues obtained from reduction surgeries at the University of Wisconsin Hospital, using microwave and optical probes with very similar sensing volumes. We found that the microwave dielectric constant and effective conductivity are correlated with tissue composition across the entire measurement frequency range (|r| approximately 0.5-0.6, p<0.01) and that the optical absorption coefficient at 460 nm and optical scattering coefficient are correlated with tissue composition (|r| approximately 0.4-0.6, p<0.02). Finally, we found that the optical absorption coefficient at 460 nm is correlated with the microwave dielectric constant and effective conductivity (r=-0.55, p<0.01). Our results suggest that combining optical and microwave modalities for analyzing breast tissue samples may serve as a crosscheck and provide complementary information about tissue composition.

Podoplanin (d2-40): a new immunohistochemical marker for reactive follicular dendritic cells and follicular dendritic cell sarcomas.

The diagnosis of follicular dendritic cell (FDC) sarcoma can be challenging because of its morphologic overlaps with many other spindle cell neoplasms and, therefore, new phenotypic markers will be helpful in its differential diagnosis. Podoplanin is a mucin-type transmembrane glycoprotein that has recently been detected in reactive FDCs. In this study, we investigated the expression patterns of podoplanin using a new mouse monoclonal antibody D2-40, and compared them with CD21, a well-established FDC marker, in a comprehensive panel of cases. The panel included 4 FDC sarcomas, 38 spindle cell neoplasms of other types, 25 reactive lymphoid hyperplasia, and 117 lymphoid and 5 myeloid malignant hematopoietic neoplasms. Our study revealed that D2-40 strongly stained 3 of 4 FDC sarcomas. In contrast, D2-40 stained only 2/38 other spindle cell neoplasms tested. Furthermore, we observed that D2-40 highlighted more FDC meshworks than CD21 in Castleman's disease, follicular lymphoma, nodular lymphocyte predominance Hodgkin lymphoma, and residual reactive germinal centers in a variety of lymphoma types. D2-40 and CD21 stained an equal number of cases of reactive lymphoid hyperplasia, progressively transformed germinal centers and angioimmunoblastic T-cell lymphoma. No expression of podoplanin was detected in normal or neoplastic lymphoid and myeloid cells. We conclude that podoplanin (D2-40) is a sensitive and specific FDC marker, which is superior or equal to CD21 in evaluating both reactive and neoplastic FDCs. In addition, our results suggest that podoplanin (D2-40) can be used to support the diagnosis of FDC sarcoma.

Model based and empirical spectral analysis for the diagnosis of breast cancer.

We explored the use of both empirical (Partial Least Squares, PLS) and Monte Carlo model based approaches for the analysis of fluorescence and diffuse reflectance spectra measured ex vivo from freshly excised breast tissues and for the diagnosis of breast cancer. Features extracted using both approaches, i.e. principal components (PCs) obtained from empirical analysis or tissue properties obtained from model based analysis, displayed statistically significant difference between malignant and non-malignant tissues, and can be used to discriminate breast malignancy with comparable sensitivity and specificity of up to 90%. The PC scores of a subset of PCs also displayed significant correlation with the tissue properties extracted from the model based analysis, suggesting both approaches likely probe the same sources of contrast in the tissue spectra that discriminate between malignant and non-malignant breast tissues but in different ways.

Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach.

We explore the use of Monte-Carlo-model-based approaches for the analysis of fluorescence and diffuse reflectance spectra measured ex vivo from breast tissues. These models are used to extract the absorption, scattering, and fluorescence properties of malignant and nonmalignant tissues and to diagnose breast cancer based on these intrinsic tissue properties. Absorption and scattering properties, including beta-carotene concentration, total hemoglobin concentration, hemoglobin saturation, and the mean reduced scattering coefficient are derived from diffuse reflectance spectra using a previously developed Monte Carlo model of diffuse reflectance. A Monte Carlo model of fluorescence described in an earlier manuscript was employed to retrieve the intrinsic fluorescence spectra. The intrinsic fluorescence spectra were decomposed into several contributing components, which we attribute to endogenous fluorophores that may present in breast tissues including collagen, NADH, and retinol/vitamin A. The model-based approaches removes any dependency on the instrument and probe geometry. The relative fluorescence contributions of individual fluorescing components, as well as beta-carotene concentration, hemoglobin saturation, and the mean reduced scattering coefficient display statistically significant differences between malignant and adipose breast tissues. The hemoglobin saturation and the reduced scattering coefficient display statistically significant differences between malignant and fibrous/benign breast tissues. A linear support vector machine classification using (1) fluorescence properties alone, (2) absorption and scattering properties alone, and (3) the combination of all tissue properties achieves comparable classification accuracies of 81 to 84% in sensitivity and 75 to 89% in specificity for discriminating malignant from nonmalignant breast tissues, suggesting each set of tissue properties are diagnostically useful for the discrimination of breast malignancy.

Sonohysterography and endometrial cancer: incidence and functional viability of disseminated malignant cells.

OBJECTIVE: The purpose of this study was to evaluate sonohysterography in patients with endometrial cancer and to determine whether (1) transtubal fluid spill occurs during routine sonohysterography, (2) a critical infusion volume for spill exists, or (3) disseminated cancer cells demonstrate viability. STUDY DESIGN: At laparotomy, sonohysterography was performed on 16 patients with endometrial adenocarcinoma. Volumes at which tubal spill occurred were recorded. Collected specimens were processed and incubated. After evaluation for viable cells, cytologic analysis was undertaken. RESULTS: The median volume that was required for adequate sonohysterography was 8.5 mL. Five patients (31%) had transtubal spill. With an additional saline solution flush, the median total volume for a spill was 20.5 mL. Two patients (12.5%) had viable benign cells that were cultured after routine sonohysterography. One patient (6%) had nonviable carcinoma cells that were identified. CONCLUSION: Transtubal spill occurs during sonohysterography. No critical spill volume was identified. A highly diagnostic tool when abnormal bleeding is evaluated, sonohysterography has a low probability of cancer cell dissemination.