Carbon tattooing for targeted lymph node biopsy after primary systemic therapy in breast cancer: prospective multicentre TATTOO trial.

BACKGROUND: Several techniques for targeted lymph node biopsy in patients with node-positive breast cancer receiving primary systemic therapy are in use, each with their inherent advantages and disadvantages. The aim of the TATTOO trial was to evaluate the feasibility and accuracy of carbon tattooing of positive lymph nodes as a method for targeted lymph node biopsy avoiding radiation exposure, high costs, and preoperative localization procedures. METHODS: Patients with initially cT1-4c cN1-3 cM0 invasive breast cancer were included in this prospective multicentre trial. Before initiation of primary systemic therapy, a carbon suspension was injected into the most suspicious axillary lymph node. Targeted lymph node biopsy was performed in all patients after completion of primary systemic therapy. Additional sentinel lymph node biopsy was done in those with axillary downstaging, and completion axillary lymph node dissection in patients still presenting with suspicious lymph nodes. RESULTS: A total of 118 patients were included and 110 were eligible for data analysis. The detection rate for the targeted lymph node was 93.6 per cent (103 of 110), and the sentinel lymph node was identical to the targeted lymph node in 60 per cent. The false-negative rate for the combination of targeted and sentinel node lymph node biopsy (targeted axillary dissection) was 9 per cent. CONCLUSION: Targeted axillary dissection after carbon tattooing is associated with a high detection rate, an acceptable false-negative rate, and appears feasible for clinical use even in healthcare settings with limited resources.

Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1-2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial.

Axillary lymph node status remains an important prognostic factor in early breast cancer. It is regarded as an indicator for (neo)adjuvant systemic treatment and postoperative radiotherapy of the regional lymphatics. Commenced in September 2015, the INSEMA trial is investigating whether operative determination of nodal status as part of breast conserving therapy (BCT) for early stage breast cancer (c/iT1-2 c/iN0) can be avoided without reducing oncological safety. After inclusion of 1001 patients there was general acceptance of the complex study design by patients and study doctors so that recruitment for the first randomisation (axillary sentinel lymph node biopsy [SLNB]: yes or no) achieved predicted case numbers. The second randomisation however (SLNB alone versus complete axillary dissection when one or two macrometastases are present at SLNB) recruited fewer cases than expected for the following three reasons: a) the 13 % rate of one or two macrometastases after SLNB in the INSEMA trial collective was lower than expected; b) around 20 % of patients refused the second randomisation; c) there was delayed inclusion of the Austrian study centres, which only recruited for the second randomisation. Lack of knowledge of nodal status when SLNB is avoided represents a new challenge for the postoperative tumour board. In particular decisions on chemotherapy for luminal-like tumours and irradiation of the lymphatics (excluding axilla) must be guided by tumour biological parameters. The INSEMA trial does not provide answers to some important questions, e.g. it remains unclear whether patients without SLNB can be offered partial breast irradiation alone in low-risk situations and whether SLNB can also be avoided in patients with stage T1-2 tumours who have a mastectomy indication.

The role of specimen radiography in breast-conserving therapy of ductal carcinoma in situ.

BACKGROUND: To assess the role of intraoperative specimen radiography (SR) and to define risk factors for positive margins in breast-conserving therapy (BCT) of ductal carcinoma in situ (DCIS). METHODS: In a retrospective study in calcification-associated DCIS treated with BCT between January 2009 and December 2011, digital mammographs and SR were reviewed and radiological margin width was determined. Clinical, radiological, and histological data were correlated with surgical histological data, and a histologically free margin of at least 2 mm was taken as evidence of successful BCT. RESULTS: 47/91 patients (51.6%) fulfilling the inclusion criteria had histologically involved surgical margins. Univariate analyses revealed DCIS size, mammographic extension of calcification, presence of comedo necrosis, negative progesterone receptor status, and a small radiological margin on SR to be risk factors for unsuccessful BCT. Receiver Operating Characteristic (ROC) analysis showed a radiological margin width of 4 mm to be optimal, with a sensitivity of 72.3% and specificity of 52.3%. The likelihood of surgical free margins was increased 2.9-fold with a radiological margin width ≥4 mm. On multivariate logistic regression analysis, only histological DCIS size >20 mm clearly emerged as an independent predictive factor for surgically involved margins (p < 0.001), while an SR margin <4 mm trended toward significance (p = 0.066). CONCLUSIONS: SR is a reliable method for predicting free surgical margins in non-invasive breast cancer where a minimum radiological free margin of 4 Fmm is achieved. However, histological DCIS size remains the most important factor determining successful BCT.

Patient-Reported Outcomes in Implant-Based Breast Reconstruction Alone or in Combination with a Titanium-Coated Polypropylene Mesh - A Detailed Analysis of the BREAST-Q and Overview of the Literature.

Background: Complication rates and surgical outcomes are well reported for implant-based breast reconstruction (IBBR) using supportive materials for the inferior pole of the breast. Patient-reported outcomes (PRO) are underrepresented. The aim of this study was to compare PRO in IBBR using implants alone or in combination with a synthetic mesh. Methods and Methods: PRO was measured in patients undergoing IBBR alone or in combination with a titanium-covered polypropylene mesh (TiLOOP® Bra). In this non-randomized observational trial PRO was retrospectively assessed using the validated self-reporting BREAST-Q. The raw responses of all questions applied in each domain and transformed BREAST-Q data using the Q-Score are presented. Results: Of 90 eligible women, 42 received IBBR alone and 48 received IBBR in combination with mesh. No differences in complication rates were observed. The return rate was 67.7 % and was comparable between the groups (p = 0.117). PRO revealed no differences regarding satisfaction with breast shape (p = 0.079), outcome (p = 0.604), nipple sensitivity (p = 0.502), preoperative information (p = 0.195), office staff (p = 0.462), psychosocial well-being (p = 0.370), sexual well-being (p = 0.508) and physical well-being (p = 0.654). Significant differences were noted regarding satisfaction with the surgeon (p = 0.013) and medical staff (p = 0.035) as well as the response behavior of certain questions of the sub-domains, thus helping to further stratify PRO with regards to aesthetic outcome. However, no differences were observed in the main BREAST-Q results. Conclusion: Use of the TiLOOP® Bra in IBBR results in comparable BREAST-Q scores compared with IBBR alone. Evaluating the BREAST-Q sub-domains helps to stratify PRO more profoundly and assists in interpreting the overall results and specific research questions.

Patient-Report Satisfaction and Health-Related Quality of Life in TiLOOP® Bra-Assisted or Implant-Based Breast Reconstruction Alone.

INTRODUCTION: Implant-based breast reconstructions (IBBR) using alternatives to acellular dermal matrixes are increasing. Data on complications are limited, and information concerning health-related quality of life (HR-QoL) following the use of these synthetic meshes do not exist. METHODS: Between January 2006 and January 2013, patients undergoing immediate or delayed-immediate IBBR with or without titanium covered polypropylene mesh (TiLOOP® Bra) were investigated. HR-QoL was assessed using the validated self-reporting BREAST-Q questionnaire. Patient demographics and complications were evaluated retrospectively. Stepwise regression backward elimination analysis was performed to identify influential factors on each BREAST-Q domain. RESULTS: Of the 90 women, 42 had IBBR alone and 48 in combination with TiLOOP® Bra. The mean follow-up was 18 months in the TiLOOP® Bra and 17.5 months in the implant alone group (p = 0.827). The overall complication rate was 21.1 %, with 14.6 % in the TiLOOP® Bra and in 28.6 % in the implant alone group (p = 0.105). Capsular contraction rate was 4.4 % in the TiLOOP® Bra and 16.7 % in the implant alone group (p = 0.052). The analysis of the HR-QoL showed no significant differences between the groups. Surgeries prior to IBBR had a positive influence on HR-QoL. TiLOOP® Bra was associated with a negative effect on "satisfaction with breast" (ß = -5.72; p < 0.001), as it was no longer observed for "satisfaction with outcome" and other domains.

Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness.

PURPOSE: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. MATERIALS AND METHODS: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). RESULTS: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. CONCLUSION: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare.

Ruptured poly-implant protheses breast implant after aesthetic breast augmentation: diagnosis, case management, and histologic evaluation.

Since the scandal of the poly-implant protheses (PIP) breast implants, all patients with PIP are advised to have their implants removed. With approximately 400,000 PIP implants sold worldwide breast, surgeons will be confronted with these patients. Histologic examination in the reported case showed silicone infiltration into fatty tissue and breast tissue without signs of malignancy. A general histologic analysis for the rare event of an anaplastic large T cell lymphoma is not advised. The malignant potential of PIP implants currently is uncertain, and further investigation is required. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Differentiating between malignant and benign breast masses: factors limiting sonoelastographic strain ratio.

PURPOSE: We compared strain ratio vs. qualitative elastography for the further differentiation of focal breast lesions, with special focus on limiting factors. MATERIALS AND METHODS: 215 patients with 224 histologically proven breast masses (116 malignant, 108 benign) were prospectively examined using a high-end ultrasound system (Philips iU22) with serial elastography function. B-mode scans and available mammograms were reviewed according to the BIRADS classification, raw elastogram data was analyzed qualitatively using the Tsukuba score and semiquantitatively by calculating the strain ratio (fat to lesion ratio). For diagnostic performance, Receiver Operating Characteristic (ROC) curve analysis was obtained. A sub-group analysis regarding breast density, lesion size, lesion depth and histological subtypes was performed. RESULTS: Mean strain ratio values were 3.04 ± 0.9 for malignant and 1.91 ± 0.75 for benign lesions (p < 0,001). The areas under the ROC curve values were 0.832 (95 % CI 0.777; 0.888) for strain ratio, 0.869 (95 % CI 0.822; 0.917) for Tsukuba score, 0.822 (95 % CI 0.768; 0.876) for B-mode ultrasound and 0.853 (95 % CI 0.799; 0.907) for mammography. Sensitivity, specificity, positive predictive value and negative predictive value of the strain ratio were 90.7 %, 58.2 %, 70.3 % and 85.1 %, when a cutoff point of 2.0 was used. Only lesion depth ≤ 4 mm was associated with diagnostic failure in the multivariate analysis of factors influencing accuracy, whereas no significant correlation between breast density and lesion size and the accuracy of the strain ratio could be found. CONCLUSION: The addition of strain ratio to B-mode ultrasound increases specificity without loss of sensitivity in differentiating between malignant and benign breast tumors. Strain ratio measurements should not be carried out on tumors with a lesion depth ≤ 4 mm.

Smooth muscle tumours of the uterine corpus: a clinicopathologic study with immunohistochemical aspects.

BACKGROUND: Based on a clinicopathologic study conducted at the University of Rostock, Germany, between 1/1997 and 6/2003, the histological records of 1761 patients who had been hysterectomized were evaluated. 1422 of these patients were suffering from smooth muscle tumours: 1389 were diagnosed as multiple leiomyomas, 26 as leiomyomas of uncertain malignant potential and 7 as leiomyosarcomas. PATIENTS AND METHODS: The data about the microscopic findings were obtained by use of both conventional histology (HE and Giemsa) and immunohistochemistry with markers for leiomyosarcomas (desmin, actin, sm-actin, myoglobin, vimentin, MIB1) and evaluated by statistical methods. Three case reports are also presented: 2 patients with leiomyosarcoma and 1 patient with an UMP tumour. RESULTS: The statistical evaluation included the frequencies of the different tumours subdivided into age groups, their localizations (with 23 distinctions), the associated microscopic findings (with 12 distinctions and most important combinations) and, finally, the number of tumours per patient and their (grouped) sizes. The case reports showed the presence of nuclear atypia, a heightened mitotic index and tumour cell necrosis. Immunohistochemical methods confirmed the histological diagnosis of a leiomyosarcoma. CONCLUSION: In accordance with earlier studies, more than 95% of the smooth muscle tumours were leiomyomas. Leiomyosarcomas were rare (<1% in our study). In 3 out of 7 cases, a leiomyosarcoma had its origin in a leiomyoma.