Ines Gruber

Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer

BackgroundTumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result.MethodsData from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups “ductal carcinoma in situ (DCIS)”, invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)”, “invasive ductal carcinoma (IDC)”, “invasive lobular carcinoma (ILC)” and “other tumours” (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes.ResultsTumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC.ConclusionsThe histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible.

Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast

Tumor cell dissemination in bone marrow (BM) and lymph nodes is considered an important step in systemic disease progression and is associated with poor prognosis. Only invasive cancers are assumed to shed isolated tumor cells (ITC) into the bloodstream and infiltrate lymph nodes. However, latest studies indicate that tumor cell dissemination may occur before stroma invasion, i.e., in ductal carcinoma in situ (DCIS). Therefore, the purpose of this study was to examine the incidence of ITC in bone marrow and sentinel lymph nodes (SN) in patients diagnosed with DCIS and its correlation with clinicopathological factors. 266 patients who were treated at the Department of Gynecology and Obstetrics (University Hospital Tuebingen, Germany) between 2003 and 2009 with DCIS were included into this study. BM aspirates were analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. SN were analyzed in 221 of these patients by extensive step sectioning and hematoxylin–eosin staining. In 34 of 266 patients (13%), ITC in BM could be detected. There was no correlation found between tumor size, grading, histology, or Van Nuys Prognostic Index and tumor cell dissemination. In two cases, metastatic spread into lymph nodes was observed (pN1mi), whereas in one case, ITC in lymph nodes were detected; however, additional sectioning and immunohistochemical staining of the primary lesion in the cases with positive SN did not reveal invasive cancer. Interestingly, all the three patients were BM negative. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Either these cells have started already to disseminate from preinvasive mammary lesions or from occult invasive tumors or represent the earliest step of microinvasion in a preinvasive lesion. The clinical relevance of these cells has to be further evaluated.

Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers

Purpose: There is evidence that some tumor patients are able to generate tumor-associated antigen (TAA)-specific T-cell immunity spontaneously. However, little is understood about the existence and nature of self-reactive T-cells that recognize TAA in healthy donors (HD). Methods: Human mucin (MUC-1), a highly glycosylated transmembrane protein, is a well characterized TAA expressed by epithelial tumors. We compared endogenous MUC-1-specific T-cell immunity of breast cancer patients (BCP) and healthy volunteers using two MUC-1-derived HLA-A*0201-restricted peptides (MUC-1950–958, MUC-112–20). Antigen-dependent interferon (IFN)-γ and Granzyme B expression of T-cells were analysed by a reverse transcription-polymerase chain reaction (qRT-PCR)-based assay. Results: A 32% of BCP and 43% of healthy volunteers revealed pre-existent CD8+ T-cells specific for MUC-1950–958 but not for MUC-112–20. In patients, MUC-1-specific T-cells have been detected mainly in early stage disease prior adjuvant therapy. Those T-cells showed MUC-1-dependent IFN-γ production after short-term stimulation but no clear Granzyme B expression. However, after repetitive in vitro stimulations using peptide-pulsed CD40-stimulated B-cell lines as autologous antigen presenting cells (APC) T-cell lines exhibited lytic capacity against HLA-A*0201+/MUC-1+ tumor cells. Conclusion: MUC-1950–958 is a dominant tumor antigen against which CD8+ T-cells were found frequently in BCP as well as in HD. Until now, this was only known for MelanA/MART-1. In contrast to previous reports, MUC-1-specific immunity was not linked to gender or number of pregnancies in women. Whether MUC-1950–958-related immunity highlights a yet unknown cross-reactivity in HD remains unclear. The presence of MUC-1-specific T-cells in some BCP may reflect a balance between immune tolerance and immune defence during aetiopathology.

Disseminated tumor cells from the bone marrow of patients with nonmetastatic primary breast cancer are predictive of locoregional relapse

BACKGROUND Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR). PATIENTS AND METHODS Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2). RESULTS A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037). CONCLUSIONS DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.BACKGROUND Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR). PATIENTS AND METHODS Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2). RESULTS A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037). CONCLUSIONS DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.

Mammotome ® versus ATEC ® : a comparison of two breast vacuum biopsy techniques under sonographic guidance

PurposeThe study evaluates the differences between the Mammotome® (MT) and ATEC® (A) vacuum biopsy (VB) of the breast in terms of diagnostic reliability, biopsy duration and complications.MethodsIn a prospective randomized study, 62 ultrasound-guided VBs of the breast were performed. MT and A were compared using Mann–Whitney U test.ResultsThe mean lesion size and the BI-RADS® distribution were equal in both groups. Representative tissue was extracted in all 62 biopsies; thus no repeat biopsies were necessary. A sonographically guided complete excision was possible in 46 cases. More imaging-guided complete excisions were achieved with the MT than with A (87 vs. 63%). Technical complications occurred twice with A and once with MT. No medical complications occurred in either group.ConclusionsBoth systems are suitable for the diagnostic clarification of unclear breast lesions as well as complete excision of benign lesions under sonographic imaging. Sonographically guided complete resection was achieved more often with the MT.

Komplikationen der gynäkologischen Endoskopie

ZusammenfassungMinimal-invasive Eingriffe gewinnen in der operativen Gynäkologie an immer größerer Bedeutung. Die technische Perfektionierung der Operationsverfahren und der endoskopischen Instrumente führten in den letzten Jahren zu einer bedeutenden Erweiterung des laparoskopischen und hysteroskopischen Operationsspektrums. Bei der Anwendung der endoskopischen Operationstechniken sollte Qualität und Minimierung von Komplikationen oberstes Ziel sein. Im Auftrag der Arbeitsgemeinschaft Gynäkologische Endoskopie (AGE) wurde diesbezüglich das Komplikationsregister entwickelt, welches durch die prospektive, standardisierte Datenerfassung einen klinikinternen/-externen Vergleich von endoskopischen Komplikationen ermöglicht. Es wurden in dem Zeitraum von 1996–2000 115.660 endoskopische Operationen erfasst, davon 75.584 Laparoskopien und 58.779 Hysteroskopien. Die multizentrische Analyse der Komplikationen ergab eine Gesamtkomplikationsrate von 0,6% bei hysteroskopischen Eingriffen und von 1,3% bei den Laparoskopien, wobei es sich in über 50% der Fälle um intraoperative Komplikationen auftraten. In der Hysteroskopie steht die Uterusperforation mit einer Häufigkeit von 0,3% an erster Stelle und in der Laparoskopie die Gefäßverletzungen/Blutungen (Häufigkeit 0,14%). Verglichen werden die Komplikationsraten des AGE-Registers mit denen der internationalen Literatur, um einen Gesamtüberblick bezüglich der Komplikationsinzidenz bei gynäkologisch-endoskopischen Eingriffen zu ermöglichen.AbstractMinimal surgical methods have an increasing significance in gynecology. The technical perfection of surgical methods and endoscopic instruments has led to wider use of laparoscopy and hysteroscopy. The aim of such techniques is high quality work with a minimum of complications. To this end, a registry for complications, commissioned by the Working Group for Gynecological Endoscopy (Arbeitsgemeinschaft Gynäkologische Endoskopie: AGE), was developed which makes the clinical internal/external comparison of endoscopic complications possible through prospective, standardised data collection. From 1996 to 2000, 115,660 endoscopic operations were recorded of which 75,584 were laparoscopic and 58,779 hysteroscopic. A multicenter analysis of the complications showed a total complication rate of 0.6% for laparoscopy and 1.3% for hysteroscopy. Some 50% of these occurred intra-operatively. For hysteroscopy, perforation of the uterus, with an incidence of 0.3%, was highest. For laparoscopy this was 0.14% for vessel damage/bleeding. The individual complication rates from the AGE registry are compared with those found in the international literature in order to provide an overview of the occurrence of complications in gynecological endoscopy.

Tension-free vaginal tape (TVT): our modified technique—effective solutions for postoperative TVT correction

Tension-free vaginal tape (TVT) is nowadays an established operation for the treatment of stress urinary incontinence. In this article, we will demonstrate our standardized TVT procedure and ways of possible postoperative correction. A tight vaginal tape can be individually expanded by a Prolene-interponate within days and also years after surgery. On the other hand, we developed a technique to shorten a loose vaginal tape. Moreover, we will discuss our approaches in the case of an eroded Prolene tape, local estrogen therapy, tape padding with vaginal tissue and blunt removal of the tape by a small vaginal incision.

Symptomatische Fibroadenome: Multimodales Therapiekonzept als Alternative zur operativen Exstirpation

Die 30-jährige Patientin stellte sich erstmalig im August 2009 mit einem störendenTastbefund linkszentraloben in3cm Mamillenabstand (MA) im UniversitätsBrustzentrum in Tübingen vor. Inspektorisch bestand eine leichte Anisomastie zugunsten der linken Seite bei einer BH-Größe von 75C. Sonographisch zeigten sich insgesamt drei BIRADS-3-Befunde (BIRADS: Breast Imaging Reporting and Data System) bei einer Brustdichte Grad 4 mit korrelierenden Tastbefunden ohne kosmetischeBeeinträchtigung.AlleBefunde waren prall-elastisch, glatt begrenzt und wurden histologisch als Fibroadenome (FA) gesichert. Aufgrund der Schmerzhaftigkeit und der störenden Palpabilität des sonographisch17× 16× 12mmgroßenFibroadenoms bei 12 Uhr entschied sich die Pati-

Prediction of Non-sentinel Lymph Node Metastases After Positive Sentinel Lymph Nodes Using Nomograms

Background/Aim: Only 30-50% of patients with sentinel lymph node (SLN) metastases present with further axillary lymph node metastases. Therefore, up to 70% of patients with positive SLN are overtreated by axillary dissection (AD) and may suffer from complications such as sensory disturbances or lymphedema. According to the current S3 guidelines, AD can be avoided in patients with a T1/T2 tumor if breast-conserving surgery with subsequent tangential irradiation is performed and no more than two SLNs are affected. Additionally, use of nomograms, that predict the probability of non-sentinel lymph node (NSLN) metastases, is recommended. Therefore, models for the prediction of NSLN metastases in our defined population were constructed and compared with the published nomograms. Patients and Methods: In a retrospective study, 2,146 primary breast cancer patients, who underwent SLN biopsy at the University Womens Hospital in Tuebingen, were evaluated by dividing the patient group in a training and validation collective (TC or VC). Using the SLN-positive TC patients, three models for the prediction of the likelihood of NSLN metastases were adapted and were then validated using the SLN-positive VC patients. In addition, the predictive power of nomograms from Memorial Sloan Kettering Cancer Center (MSKCC), Stanford, and the Cambridge model were compared with regard to our patient collective. Results: A total of 2,146 patients were included in the study. Of these, 470 patients had positive SLN, 295 consisted the training collective and 175 consisted the validation collective. In a regression model, three variants – with 11, 6 and 2 variables – were developed for the prediction of NSLN metastases in our defined population and compared to the most frequently used nomograms. Our variants with 11 and with 6 variables were proven to be a particularly suitable model and showed similarly good results as the published MSKCC nomogram. Conclusion: Our developed nomograms may be used as a prediction tool for NSLN metastases after positive SLN.