Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography

Purpose: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. Methods: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. Results: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. Conclusion: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens

Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?

Purpose!#!Infertility is a debilitating situation that millions of women around the world suffer from, but the causal relationship between infertility and endometriosis is still unclear. We hypothesize that the immune cell populations of uterine natural killer cells (uNK) and plasma cells (PC) which define chronic endometritis could differ in patients with or without endometriosis and therefore be the link to endometriosis-associated infertility.!##!Methods!#!Our retrospective study includes 173 patients that underwent an endometrial scratching in the secretory phase of the menstrual cycle and subsequently immunohistochemical examination for uNK cells and PC. Sixty-seven patients were diagnosed with endometriosis, 106 served as the control cohort.!##!Results!#!The risk for an elevated number of uNK cells in women with endometriosis is not increased as compared to the control group. Our findings suggest that patients with endometriosis are 1.3 times more likely to have chronic endometritis (CE) as compared to those without and that the treatment with doxycycline might increase pregnancy rates. Endometriosis and an increased number of uNK cells seem to be unrelated.!##!Conclusions!#!In contrast to the lately published connection between endometriosis, infertility and increased uNK cells, we could not find any evidence that patients with endometriosis are more prone to elevated uterine uNK cells. Counting of PC in endometrial biopsies might be a new approach in the search of biomarkers for the nonsurgical diagnosis of endometriosis since our findings suggest a connection

Shear-wave elastography as a supplementary tool for axillary staging in patients undergoing breast cancer diagnosis

Abstract Background Preoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics. Methods One hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden’s index. Results Lymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p < 0.0001). The statistically optimal cutoff to differentiate between malignant and benign lymph nodes was 2.66 m/s with a sensitivity of 69.8% and a specificity of 87.5%. Conclusions Lymph node metastases assessed with SWE showed significantly higher elasticity values compared to benign lymph nodes. Thus, SWE provides an additional useful and quantifiable parameter for the sonographic assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support the guidance of definitive biopsy work-up. Critical relevance statement Shear-wave elastography provides an additional useful and quantifiable parameter for the assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support guiding the definitive biopsy work-up. Key Points SWE is a quantifiable ultrasound parameter in breast cancer diagnosis. SWE shows a significantly higher velocity in malignant lymph nodes. SWE is useful in improving the sensitivity and specificity of axillary staging. Graphical Abstrac

Does conventional specimen radiography after neoadjuvant chemotherapy of breast cancer help to reduce the rate of second surgeries?

Purpose!#!This is the first study to systematically evaluate the diagnostic accuracy of intraoperative specimen radiography on margin level and its potential to reduce second surgeries in patients treated with neoadjuvant chemotherapy.!##!Methods!#!This retrospective study included 174 cases receiving breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. Conventional specimen radiography (CSR) was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions.!##!Results!#!1044 margins were assessed. Of 47 (4.5%) histopathological positive margins, CSR identified 9 correctly (true positive). 38 infiltrated margins were missed (false negative). This resulted in a sensitivity of 19.2%, a specificity of 89.2%, a positive predictive value (PPV) of 7.7%, and a negative predictive value (NPV) of 95.9%. The rate of secondary procedures was reduced from 23 to 16 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 25. In the subgroup of patients with cCR, the prevalence of positive margins was 10/510 (2.0%), PPV was 1.9%, and the NNT was 85.!##!Conclusion!#!Positive margins after NACT are rare and CSR has only a low sensitivity to detect them. Thus, the rate of secondary surgeries cannot be significantly reduced by recommending targeted re-excisions, especially in cases with cCR. In summary, CSR after NACT is inadequate for intraoperative margin assessment but remains useful to document removal of the biopsy site clip

Evaluation of the FUSION-X-US-II prototype to combine automated breast ultrasound and tomosynthesis

Objective!#!The FUSION-X-US-II prototype was developed to combine 3D automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device. We evaluated the performance of ABUS and tomosynthesis in a single examination in a clinical setting.!##!Methods!#!In this prospective feasibility study, digital breast tomosynthesis and ABUS were performed using the FUSION-X-US-II prototype without any change of the breast position in patients referred for clarification of breast lesions with an indication for tomosynthesis. The tomosynthesis and ABUS images of the prototype were interpreted independently from the clinical standard by a breast diagnostics specialist. Any detected lesion was classified using BI-RADS® scores, and results of the standard clinical routine workup (gold standard) were compared to the result of the separate evaluation of the prototype images. Image quality was rated subjectively and coverage of the breast was measured.!##!Results!#!One hundred one patients received both ABUS and tomosynthesis using the prototype. The duration of the additional ABUS acquisition was 40 to 60 s. Breast coverage by ABUS was approximately 80.0%. ABUS image quality was rated as diagnostically useful in 86 of 101 cases (85.1%). Thirty-three of 34 malignant breast lesions (97.1%) were identified using the prototype.!##!Conclusion!#!The FUSION-X-US-II prototype allows a fast ABUS scan in combination with digital breast tomosynthesis in a single device integrated in the clinical workflow. Malignant breast lesions can be localized accurately with direct correlation of ABUS and tomosynthesis images. The FUSION system shows the potential to improve breast cancer screening in the future after further technical improvements.!##!Key points!#!• The FUSION-X-US-II prototype allows the combination of automated breast ultrasound and digital breast tomosynthesis in a single device without decompression of the breast. • Image quality and coverage of ABUS are sufficient to accurately detect malignant breast lesions. • If tomosynthesis and ABUS should become part of breast cancer screening, the combination of both techniques in one device could offer practical and logistic advantages. To evaluate a potential benefit of a combination of ABUS and tomosynthesis in screening-like settings, further studies are needed

The focus of temperature monitoring with zero-heat-flux technology (3M Bair-Hugger) : a clinical study with patients undergoing craniotomy

In the noninvasive zero-heat-flux (ZHF) method, deep body temperature is brought to the skin surface when an insulated temperature probe with servo-controlled heating on the skin creates a region of ZHF from the core to the skin. The sensor of the commercial Bair-Hugger ZHF device is placed on the forehead. According to the manufacturer, the sensor reaches a depth of 1–2 cm below the skin. In this observational study, the anatomical focus of the Bair-Hugger ZHF sensor was assessed in pre- and postoperative CT or MRI images of 29 patients undergoing elective craniotomy. Assuming the 2-cm depth from the forehead skin surface, the temperature measurement point preoperatively reached the brain cortex in all except one patient. Assuming the 1-cm depth, the preoperative temperature measurement point did not reach the brain parenchyma in any of the patients and was at the cortical surface in two patients. Corresponding results were obtained postoperatively, although either sub-arachnoid fluid or air was observed in all CT/MRI images. Craniotomy did not have a detectable effect on the course of the ZHF temperatures. In Bland–Altman analysis, the agreement of ZHF temperature with the nasopharyngeal temperature was 0.11 (95% confidence interval − 0.54 to 0.75) °C and with the bladder temperature − 0.14 (− 0.81 to 0.52) °C. As conclusions, within the reported range of the Bair-Hugger ZHF measurement depth, the anatomical focus of the sensor cannot be determined. Craniotomy did not have a detectable effect on the course of the ZHF temperatures that showed good agreement with the nasopharyngeal and bladder temperatures.Peer reviewe

Potential of Lesion-to-Fat Elasticity Ratio Measured by Shear Wave Elastography to Reduce Benign Biopsies in BI-RADS 4 Breast Lesions

Objectives—We evaluated whether lesion-to-fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BIRADS) 3 or 4 lesions has the potential to further refine the assessment of Bmode ultrasound alone in breast cancer diagnostics. Methods—This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI-RADS 3 and 4a–c by conventional B-mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI-RADS 3 and BI-RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion-to-fat ratio measured by shear wave elastography were evaluated. Results—Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B-mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI-RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI-RADS 3. Additional lesion-to-fat ratio in BI-RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives. Conclusions—Adding lesion-to-fat ratio measured by shear wave elastography to conventional B-mode ultrasound in BI-RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI-RADS 3 definition of <2% of undetected malignancies