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Purpose To analyse the diagnostic performance of contrast-enhanced ultrasound (CEUS) in patients with vascular complications and transplant rejection compared to histopathological results. Materials and methods Our study consisted of 45 retrospectively analysed patients that underwent liver transplantations between January 1993 and December 2015 and developed post-transplant vascular complications with transplant rejection. CEUS examinations took place between September 2006 and December 2015. CEUS findings were correlated with histopathological results. Results CEUS showed a sensitivity of 61.5%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 86,5% in the detection of vascular complications with post-transplant rejection. 5 examinations were reported as normal whereas the histopathological result showed a transplant rejection (false-negative). Conclusion CEUS might be a useful additional non-invasive technique for the assessment of vascular complications with post-transplant rejection in patients after liver transplantation.

Im klinischen Alltag konnen die Charakterisierung und Beurteilung fokaler Lasionen mit dem Ultraschall anhand klassischer sonomorphologischer Kriterien nicht immer suffizient gelingen, sodass erganzende bildgebende Verfahren in Betracht gezogen werden mussen. Als radiologisches Standardverfahren sind in der klinischen Praxis die native B‑Bild-Sonographie sowie die farbkodierte Duplexsonographie etabliert. Durch die Ultraschallelastographie ist es moglich, die Gewebesteifigkeit eines Gewebes oder fokaler Lasionen zu beurteilen und somit zusatzliche Bildinformationen durch den nichtinvasiven Einsatz bildgebender Technik zu erlangen. Die Elastographie erlaubt z. T. die Differenzierung zwischen gut- und bosartigen Lasionen insbesondere bei Organen, die sonographisch gut zu evaluieren sind. Hierzu gehoren insbesondere die Leber, aber auch Schilddruse, Mamma sowie die Hoden. Bei der Leber eignet sich die Elastographie neben der Evaluation fokaler Leberlasionen zusatzlich zur Beurteilung der Gewebesteifigkeit im Rahmen der Abklarung einer Leberfibrose oder -zirrhose. Durch die zwischenzeitliche standardmasige Implementierung der Elastographie in moderne Ultraschallsysteme hat sich das Verfahren als wertvolle Erganzung zu den Standardverfahren etabliert. Bei sonomorphologisch unklaren Befunden eignet sich die Elastographie als zusatzliches bildgebendes Verfahren zur Differenzierung zwischen bos- und gutartigen Befunden.

Cowpox viruses are orthopoxviruses that may survive in the environment for years. Rodents are regarded as the primary hosts, but transmission to other species has been reported. This report describes a cowpox virus infection in a cat with subsequent transmission to its owner leading to protracted, atypical and severe clinical signs. A young cat presented with multiple crusts and plaques on the neck, muzzle and tail base. The owner developed an erythematous lesion with elevated margins, central necrosis and crust formation below the left breast, a neurogenic inflammation, enlarged regional lymph nodes, a colliquative lymphadenitis and concomitant flu-like symptoms. Cultures were taken at the first visit from the cat's lesional skin and the patient's skin, and polymerase chain reaction with sequencing of the haemagglutinin region of both were positive for cowpox virus. The patient was treated with various antibiotics and methylprednisolone and was in clinical remission after 7 months.

PURPOSE: To evaluate the value of contrast-enhanced ultrasound (CEUS) using a high-end ultrasound system in the characterization of endoleaks after endovascular aortic repair (EVAR). MATERIAL AND METHODS: In this mono-center study, 41 patients were retrospectively analyzed after being examined using a modern high-end ultrasound system (RS80A with Prestige, Samsung Medison Co., Ltd., Seoul, Korea). The maximum diameters of the aneurysms were measured in two planes (right-left and ventral-dorsal). The performance of Color Doppler in comparison to CEUS was evaluated and CEUS was considered as the gold standard in endoleaks detection. RESULTS: 41 patients were included in the study. Between June and December 2016, mostly male patients (n = 38;92,7%) were examined, corresponding to the incidence of abdominal aortic aneurysms in the population. Average age was 75 +/- 8 years (range 58-100 years). Average diameter of the treated aneurysm-sacs was 5,04 +/- 1.5 cm (range 2.7-10.5 cm) in the right-left plane and 4,75 +/- 1.36 cm (range 2.8-8.9 cm) in the ventral-dorsal plane. Using CEUS as the gold standard endoleaks could be detected in 28 patients (68,3%) with 13 patients not showing an endoleak after EVAR. Color Doppler showed a sensitivity of 32.1%, a specificity of 92.3%, a positive predictive value (PPV) of 90.0% and a negative predictive value (NPV) of 38,7% compared to CEUS being the gold standard. CONCLUSION: CEUS after EVAR using a modern high-end ultrasound system is a fast and cost-effective imaging modality for the detection and follow-up of endoleaks with superior benefits compared to Color Doppler. CEUS remains the initial standard-of-care examination for follow-up.

In the daily clinical routine characterization of focal lesions using native B‑mode classical ultrasound and color Doppler can be difficult or insufficient; therefore, additional diagnostic information must be taken into consideration.Standard radiological methods in the daily clinical routine include native B‑mode ultrasound and color Doppler ultrasound.Using sonoelastography it is possible to evaluate and characterize tissue properties and focal lesions regarding their stiffness to acquire additional information on a noninvasive basis.Sonoelastography enables the differentiation between benign and malignant lesions especially in organs that can be easily evaluated using ultrasound. This particularly includes the liver, the thyroid gland, the breasts and the testicles. Regarding the liver, sonoelastography techniques can also be used for evaluation of the tissue flexibility in the diagnostics of fibrosis and cirrhosis.Nowadays, elastography is implemented into every modern ultrasound system and has been established as a supplementary examination technique to the conventional ultrasound techniques.Sonoelastography should be used in cases with unclear findings as an additional noninvasive tool for the differentiation between benign and malignant lesions.

In den letzten Jahren hat die Elastographie als additives Verfahren zur besseren Charakterisierung sonographischer Herdbefunde der Brust in der klinischen Routine Einzug gehalten. Neben der Kompressionselastographie, die eine qualitative Messung der durch eine induzierte Kompression bewirkten Scherung des untersuchten Gewebes ermoglicht, stellt die Scherwellenelastographie ein Verfahren dar, welches untersucherunabhangig eine quantitative Beurteilung der Verschiebungsdeformation des Gewebes erlaubt. In zahlreichen Studien konnte durch den erganzenden Einsatz der Elastographie eine verbesserte Spezifitat bei der Differenzierung von Mammatumoren nachgewiesen werden, was insbesondere bei Lasionen der US-BI-RADS-Kategorie IV (Ultrasound Breast Imaging Reporting and Data System) zu einer Reduktion unnotiger Biopsien gutartiger Lasionen der Brust fuhren kann.

PURPOSE To compare the value of high-resolution contrast-enhanced ultrasound in the detection and characterisation of endoleaks after EVAR. MATERIAL AND METHODS In this retrospective study, a cohort of 80 patients underwent both standard examination using a curved array 5 MHz transducer and a second examination using a curved array 9 MHz transducer. The examination included B-mode, color Doppler and contrast-enhanced ultrasound using the Philips EPIQ 7 scanner. RESULTS 80 patients were included in the study. CEUS was used as the preferred examination in determining the presence of an endoleak. The sensitivity and specificity for the detection of endoleak using the 5 MHz transducer was: CEUS (96.8%, 100%), Color Doppler (47.6%, 94.1%), B-mode (15.8%, 94.1%), while for the 9 MHz transducer: CEUS (100%, 100%), Color Doppler (39.7%, 94.1%), B-mode (23.8%, 24.1%). CONCLUSION High resolution ultrasound (9 MHz) in detection and characterization of endoleaks after EVAR has some minor advantages in comparison to lower resolution ultrasound (5 MHz).

Purpose: The presence of isolated tumor cells in the bone marrow (ITC-BM) is an independent prognostic factor in all stages of breast cancer. Both the expression/amplification of human epithelial growth factor receptor 2 (HER2) and Topoisomerase IIα (TOP IIa), a key enzyme of DNA replication and main target of anthracyclins, in breast cancer tissue seem to have predictive value regarding the effectiveness of systemic therapies. Methods: To investigate the correlation between these factors and their influence on clinical outcome, tumor tissue of 54 patients who were screened for ITC-BM before and after anthracyclin-based chemotherapy (abCTX) was examined for HER2 and TOP IIa by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: By IHC, 31% of the tumors showed positive for HER2 (2+/3+), 14.6% were amplified in FISH. TOP IIa expression (>50%) was found in 13/53 patients (25%), FISH was positive in 5/47 cases (11%). TOP IIa amplification was not seen in cases without HER2 amplification, five of the seven HER2 amplified cases also were amplified for TOP IIa (71% co-amplification). Forty-three patients had adjuvant, seven neo-adjuvant, four palliative abCTX. ITC-BM were present in 24% of patients before and 31% after CTX. Patients with HER2 (IHC, P=0.29) and TOP IIa (FISH, P=0.16) positive tumors tended to stay or become negative in BM status after abCTX and vice versa. After a median follow-up of 44 months (6–127), none of the factors reached significance for overall survival. Yet, patients with HER2 (P=0.16) and TOP IIa (P=0.09) positive tumors showed a trend towards prolonged disease-free survival. Remarkably, none of the TOP IIa FISH-positive patients developed distant metastases (P=0.099) or died (P=0.19) after CTX so far. Conclusions: HER2- and TOP IIa positivity seem to improve the effect of abCTX. The combination of the prognostic value of ITC-BM and the predictive capacity of HER2 and TOP IIa could help to stratify patients for certain therapies. The direct examination of those factors on ITC-BM is the focus of ongoing studies.

Purpose: Over the last decades, breast conserving therapy increasingly occupied a leading role in breast cancer treatment. However, the typically long latency between primary diagnosis and relapse and adverse effects in breast cancer patients requires long term analyses within large patient populations. Method: 4799 women with breast cancer have been surgically treated at the University Hospital Berlin-Charlottenburg and the I. Frauenklinik of the Ludwig-Maximilians-University Munich between 1963 and 2000. Among these, 1098 patients with invasive early stage breast cancer (pT 1-2, N 0-1, M 0) received breast conserving therapy, consisting of lumpectomy with axillary lymphadenectomy followed by breast irradiation up to a target volume of 50 Gy. The baseline and follow-up data of these patients were contemporarily collected and analyzed in this longitudinal study. The significance of various prognostic parameters for overall and disease free survival was evaluated by univariate and multivariate analyses. The median follow-up time was 5.9 years (range: 2 months to 19 years). Results: 5 years after breast conserving therapy the overall survival was 89.4% and 82.0% after 10 years. 91 patients died related to breast cancer. Tumor size (p=0.002), lymph node involvement (p = 0.005), estrogen receptor status (p = 0.008) and histopathological grading (p=0.043) prevailed as independent prognostic parameters for overall survival in multivariate analysis. Disease free survival was 79.6% after 5 years and 68.3% after 10 years. During follow-up 136 local,18 regional and 230 generalized recurrences occurred, including 86 bone and 69 pulmonary metastases. For disease free survival, estrogen receptor status (p=0.008), lymph node involvement (p=0.010) and tumor size (p=0.038) were found to be significant prognostic parameters in multivariate analyses. Surgery associated complications comprised seromas (14.1%), hematomas (5.8%) and wound infections (4.6%). Complications attributed to radiation therapy included erythema (23.9%), mammary edema (12.7%), epidermiolysis (7.6%) and sclerosis/ fibrosis (3.5%). 8.1 % of the patients developed lymphedema as a consequence of both therapeutic modalities. Conclusion: At the two participating German University Hospitals, the therapeutic efficacy of breast conserving treatment for breast cancer compares to international studies. There is only minor treatment associated morbidity of breast conserving therapy. Therefore, breast conserving therapy should be further considered as preferable treatment option in early breast cancer.

BACKGROUND AND OBJECTIVE In the last few years special attention has been paid to the serum concentration of haemoglobin in patients with cancer. It was the aim of this study to ascertain whether at the time of the initial diagnosis low haemoglobin levels in patients with breast cancer denote a higher risk of primary haematogenous dissemination of tumour cells in bone marrow than that in those with higher levels. PATIENTS AND METHODS Between March 1994 and March 2000 bone marrow aspirates were performed and serum haemoglobin concentrations (g/dl) measured before primary surgical treatment in 360 consecutive patients (mean age 57.5 years) with primary breast cancer. Evidence of isolated tumour cells in bone marrow was obtained with the pancytokeratin antibody A45-B/B3. The cohort was divided into two groups on the basis of mean haemoglobin values, and the patients underwent follow-up examination a mean of 30.7 months after the initial diagnosis. Patients with metastases at first diagnosis or those who had received nonsurgical treatment at that time were excluded. RESULTS The mean pre-treatment haemoglobin concentration of the cohort was 13.8 g/dl (median 13.9 g/dl, S.D.1.2). There was no statistically significant difference in the frequency of cytokeratin-positive bone marrow findings between the two groups. While disseminated tumour cells were demonstrated in the bone marrow of 48 (28%) patients with a pre-treatment haemoglobin of 13.9 g/dl. There was also no difference between the two groups regarding median survival time (67.9 vs. 65.8 months; p = 0.46). However, there was a significant difference in probability of survival between patients with or without isolated tumour cells in the bone-marrow (59.7 vs. 69.2 months; p < 0.0001). CONCLUSION There is no evidence at present that the preoperative haemoglobin concentration is of prognostic value regarding the haematogenous dissemination of tumour cells and the survival time of patients with primary breast cancer.

PURPOSE To evaluate the use of color Doppler sonography and free hand sonoelastography in the assessment of breast fibroadenomas according to their size and shape. MATERIALS AND METHODS From December 2012 to March 2013 women with 16 solid breast masses, classified as BI-RADS category 3 or 4 were examined with B-mode ultrasound, sonoelastography and color Doppler sonography. Lesions were subdivided according to their shape in round, ovoid or macrolobulated and according to their size (

PURPOSE To compare compression elastography and contrast enhanced ultrasound in the follow-up after endovascular aortic aneurysm repair. MATERIAL AND METHODS In this retrospective study a cohort of 33 patients with both CEUS and elastography follow-up examinations after EVAR were included. The examinations were done with a Siemens S 2000 with curved array 4 MHz multi-frequency transducer. RESULTS Regarding our inclusion and exclusion criteria we obtained 33 patients. CEUS was used as the preferred examination in determining the presence of an endoleak. The true positive rate for the detection of Endoleaks with compression elastography was 42.4% (14/33), the false positive rate was 12.1% (4/33), the true negative rate was 15.2% (5/33) and the false negative rate was 30.3% (10/33). The sensitivity of compression elastography was therefore 58.3% and the specifity was 55.6%. Kappa coefficient was 0.115. CONCLUSION Compression elastography does not seem to have any additional advantages in the detection and classification of endoleaks in comparison to CEUS.

PURPOSE To evaluate the additional effect of higher frequent linear probes than 12.5 MHz in color Doppler sonography and free hand sonoelastography of benign and malignant breast masses and to compare different color encodings in sonoelastography. MATERIALS AND METHODS From December 2012 to March 2013, 37 patients with benign or malignant breast masses were prospectively included in this study. All solid masses have been histologically proven. Two readers assessed sonoelastographic findings at 12.5 MHz vs. 17 MHz according to the tsukuba elasticity score and additionally different color encodings were compared. Results of Doppler sonography using a score of 0, 1 or 2, depending on the degree of perfusion, also were assessed at 12.5 MHz vs. 17 MHz. RESULTS Among the 37 examined breast masses there were 10 cysts, 16 fibroadenomas and 11 carcinomas. Median participant age was 49.0 years. Use of color Doppler sonography enabled to distinguish cysts from solid breast masses (p < 0.001), without an improvement at 17 MHz. Additional sonoelastography significantly improved the specificity in solid breast masses (p < 0.001). No changes could be seen using different colors in sonoelastography. CONCLUSION Combination of color Doppler sonography and sonoelastography can increase the accuracy in distinguishing benign from malignant breast masses. The use of linear probes with a higher frequency than 12.5 MHz does not show any benefit, neither in color Doppler sonography nor in sonoelastography.

In recent years the use of elastography in addition to sonography has become a routine clinical tool for the characterization of breast masses. Whereas free hand compression elastography results in qualitative imaging of tissue stiffness due to induced compression, shear wave elastography displays quantitative information of tissue displacement. Recent studies have investigated the use of elastography in addition to sonography and improvement of specificity in differentiating benign from malignant breast masses could be shown. Therefore, additional use of elastography could help to reduce the number of unnecessary biopsies in benign breast lesions especially in category IV lesions of the ultrasound breast imaging reporting data system (US-BI-RADS).

Background: Breast-conserving therapy has been demonstrated to be just as safe and a less disruptive experience compared with mastectomy for surgically manageable breast cancer. There is, however, no agreement in the literature about the impact of these procedures on several important aspects of quality of life (QOL). The purpose of the present study is to compare the long-term impact of these two surgical approaches on QOL in patients with identical tumor stages and to suggest possible shortcomings of the standard QOL questionnaires. Method: Between August 1999 and May 2000, QOL questionnaires were answered by 152 pair-matched patients at the I. Frauenklinik, Ludwig-Maximilians University Munich, as part of routine follow-up examinations. The pairs of patients, each consisting of one patient after mastectomy and one after breast conservation, were selected according to the highest degree of equivalence in tumor stage. All patients had been initially treated for stage I-III breast cancer without evidence of distant metastases. The QOL was evaluated by using the QLQ-C30 questionnaire version 2.0 of the EORTC Study Group on Quality of Life. We formulated seven additional questions about the patients’ satisfaction with the primary surgical treatment modality as viewed from their current perspective. The QOL questionnaires were answered after a median interval of 46 months following primary treatment. Results: Tumor stage, prognostic factors, and adjuvant systemic treatment were well balanced between the two groups. No differences between the two groups were observed in terms of all QOL items measured by the QLQ-C30. Our additional questions, however, revealed that patients in the mastectomy group were less satisfied with the cosmetic result of their primary operation (P < .0001), were more likely to feel basic changes in their appearance (P < .0001), and were more likely to be emotionally stressed by these facts (P < .0001). From their perspective at the time of completing the questionnaires, 11 patients in the mastectomy group (15%) would decide differently about the surgical treatment modality, compared with only 3 patients (4%) in the breast conservation group (P = .025). Conclusion: While the primary surgical treatment modality seems to have no long-term impact on general QOL, certain body-image-related problems may be caused by mastectomy. Standard measuring instruments for QOL may fail to detect differences in satisfaction and adaptation with the primary surgical treatment modality.

Objective: Most studies have found survival after local recurrence of breast cancer to be poorer after mastectomy than after breast-conserving surgery. We studied whether this is the case because patients undergoing mastectomy have a more unfavorable risk profile and whether it applies also to patients with early stage disease. Methods: We conducted a matched-pair analysis (breast-conserving surgery vs. mastectomy) of 62 patients with local recurrence of early stage (pT1 -pT2 NO) breast cancer without evidence of systemic disease. Patients were matched for tumor size, histologic grade and age. Prognostic parameters at the time of primary diagnosis and at recurrence were evaluated with univariate and multivariate analyses with respect to survival after recurrence. The median follow-up was 7.5 years. Results: There were no significant differences between the two groups in the size of the primary tumor, histologic grading, and size of recurrent tumor. The disease-free interval between primary diagnosis and local recurrence was 8 months shorter in patients after mastectomy than in those after breast-sparing surgery (p = 0.35). Survival after recurrence was shorter in the patients after mastectomy but this difference was not statistically significant (98 vs. 208 months, respectively; p = 0.11). The disease-free interval before local recurrence (but not the type of primary surgery) was the only independent prognostic factor for subsequent survival in both the univariate (p = 0.02) and the multivariate (p = 0.01) analyses. Conclusion: The difference in survival after local recurrence after mastectomy compared with breast-sparing surgery for early breast cancer is small and appears to be associated with different disease-free intervals before local recurrence.

Depuis quelques annees, la collaboration entre le corps medical et l'industrie pharmaceutique est remise en cause de maniere critique dans plusieurs pays en ce qui concerne leur interdependance financiere. En meme temps, il est fondamentalement inconteste que cette cooperation est indispensable dans le cadre du developpement et du lancement de nouveaux moyens diagnostiques et therapeutiques. En Suisse, le nouveau droit penal en matiere de corruption stipule que les individus actifs dans des institutions publiques ou dans des institutions privees remplissant des tâches d'interet public ne doivent accepter aucun don. Par contre, les institutions en tant que telles sont habilitees a le faire. Pour la protection des collaborateurs, il est recommande d'edicter des directives internes claires sur le comportement a adopter relativement aux dons.

INTRODUCTION In several studies, low-molecular-weight-heparins (LMWH) have been shown to be as effective in the prevention of deep vein thrombosis (DVT) as unfractionated heparin. However, different LMWHs vary significantly in their pharmacokinetic profile and bioavailability pattern. It remains unknown, whether these pharmacological differences result in a clinically divergent behavior. METHODS Safety and antithrombotic efficacy of three LMWHs, certoparin (18 mg), dalteparin (30 mg) and enoxaparin (24 mg), were compared in a prospective, randomized controlled trial involving 188 patients undergoing knee or hip replacement or spinal surgery. Efficacy was assessed by changes in venous flow patterns between pre- and postoperative Doppler sonography. The clinical endpoint for the assessment of safety were intra- and postoperative bleeding, changes in activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), local hematoma and local infections. RESULTS Two verified DVTs (1.1%) were observed in the study, leading to no statistical difference in the antithrombotic efficacy of the used LMWHs. In 21 patients (11.2%) local hematoma or local infections complicated the postoperative course. Of these 21 patients, 13 belonged to the certoparin group, compared to 4 patients each in the other groups (p < 0.01). An allergic reaction occurred in only one case treated with dalteparin. No differences between the groups were observed in terms of intra- and postoperative bleeding, APTT, TCT and blood count. CONCLUSION The results of this study suggest, that all three LMWHs are equally efficacious in the prophylaxis of DVT in high risk patients after orthopedic surgery. Larger randomized controlled trials are necessary to confirm this conclusion and to evaluate the clinical relevance of the observed differences in postoperative complications.

Einleitung und Fragestellung: Durch die Dosisintensivierung und durch den Einsatz von neuen Substanzen wird zunehmend häufig eine klinisch relevante Myelosuppression durch adjuvante Chemotherapieschemata beobachtet. Häufig wird die Einschätzung der zu erwartenden Zytopenie durch den Mangel an direkt vergleichbaren Daten erschwert. Ziel der vorliegenden Arbeit war es, die chemotherapieassoziierte Myelosuppression von vier in der gynäkologischen Onkologie gebräuchlichen Chemotherapieschemata im eigenen Patientengut zu vergleichen. Methode: Bei 79 Patientinnen mit primärem Mammakarzinom und 26 Patientinnen mit epithelialem Ovarialkarzinom wurde eine zytostatische Therapie durchgeführt und die damit assoziierte Myelosuppression durch Erfassung der Zytopenie und der Notwendigkeit zur supportiven Therapie evaluiert. Die untersuchten Chemotherapieschemata umfassten das CMF-Schema (Cyclophosphamid 600 mg/m2, Methotrexat 40 mg/m2, 5-Fluorouracil 600 mg/m2, 6×q3w), das EC/CMF-Schema (Epirubicin 90 mg/m2, Cyclophosphamid 600 mg/m2, 4×q3w, gefolgt von CMF, 3×q3w), das DE-Schema (Docetaxel 75 mg/m2, Epirubicin 90 mg/m2, 6×q3w) und das CC-Schema (Cyclophosphamid 600 mg/m2, Carboplatin AUC 6, 6×q3w). Ergebnisse: Die Schemata EC/CMF und DE wurden signifikant häufiger bei fortgeschritteneren Tumorstadien durchgeführt, jedoch fanden sich keine Unterschiede in tumorbedingter, prächemotherapeutischer Myelosuppression. Die stärkste Beeinträchtigung der Hämatopoese fand sich in der CC-Gruppe mit einem durchschnittlichen Abfall des Serumhämoglobins von 1,5 g/dl bis Ende der zytostatischen Therapie. In dieser Gruppe wurden entsprechend die meisten Erythrozytenkonzentrattransfusionen nötig. Die stärkste Suppression der Leukopoese war in der DE-Gruppe mit einem durchschnittlichen Leukozytenabfall von 6,2 × 103/µl pro Zyklus zu verzeichnen; in dieser Gruppe wurden im Mittel 7,6 Fertigspritzen mit 263 µg Lenogastrim zur Leukopoesestimulation verabreicht. Der stärkste Abfall der durchschnittlichen Thrombozytenzahl fand sich mit 171,7 × 103/µl in der CC-Gruppe. Schlussfolgerung: Das CC-Schema führt zur stärksten Beeinträchtigung der Thrombo- und Erythropoese, während das DE-Schema zu einer ausgeprägten Leukopenie führt. Das Schema mit der geringsten Myelosuppression war das CMF-Schema. In keinem der untersuchten Fälle kam es zu einer schweren zytopenieassoziierten Komplikation.

Ein palpabler Befund in der Mamma ist haufig. Obwohl es sich dabei meistens um gutartige Veranderungen handelt, muss trotzdem auch immer an die Moglichkeit eines Karzinoms gedacht werden. Diese «Guideline» soll Arztinnen und Arzten Informationen und Empfehlungen zur weiteren Abklarung des palpablen Knotens liefern, um zielgerichtet und rasch ein Karzinom zu bestatigen oder auszuschliessen. Die Faktoren, welche die notwendigen Entscheidungen beeinflussen, wurden kritisch gepruft. Es wird bei jeder Empfehlung auf Begrundung und Evidenz eingegangen. Auf das Vorgehen bei einem zufallig mammographisch entdeckten Befund wird nicht eingegangen.

Objective: Chest wall irradiation after mastectomy for breast cancer is now usually reserved for patients with extensive carcinomatous lymphangiosis or positive surgical margins. However, recent studies suggest that the reduced risk for local recurrence following radiotherapy of the chest wall might improve the survival of these patients. We studied the influence of chest wall irradiation on local recurrence and overall survival rates in patients with breast cancer treated with mastectomy. Methods: We reviewed 1964 patients with pT 1-2 breast cancer treated with mastectomy since 1963. Patients treated before 1979 routinely received chest wall irradiation while those treated after 1979 received irradiation only if there was histologic evidence of extensive carcinomatous lymphangiosis or positive surgical margins. The groups were compared with Kaplan-Meier analysis and the log-rank test. Results: Patients, who received adjuvant radiotherapy had a significantly lower rate of local recurrence regardless of the nodal status. Ten years after primary diagnosis, 98% of patients who received irradiation are free of local recurrence, compared with 86% of those who did not (p

Die funktionelle Untereinheit der Brustdruse besteht aus den Azini und den Milchgangen, die von den kontraktilen Elementen (Myoepithelien) umhullt werden, und dem intralobularen Bindegewebe mit den senkrecht zur Thoraxwand verlaufenden Cooper-Ligamenten, die hauptsachlich den Stutzapparat des Drusenkorpers darstellen. Der gesamte Drusenkorper setzt sich aus ca. 15–20 dieser lobularen Untereinheiten zusammen. Nach Vereinigung der Milchgange aus den einzelnen Untereinheiten munden letztlich 8–15 Ausfuhrungsgange (Ductus lactiferi) an der Brustwarzenoberflache.

Examination of tumor biological factors for prognostic and predictive indicators is not part of routine testing in ovarian cancer. As in other tumors, the detection of hematogenous tumor spread could help to estimate the risk of metastatic disease. We examined the expression of p53, KI67, topoisomerase IIα (Top IIa), epidermal growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with ovarian cancer. All underwent bone marrow (BM) aspiration and screening for disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM aspiration, cytospin preparation, and immunocytochemical staining with the anticytokeratin antibody (A45-B/B3) were done following a standardized protocol. The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells or immunoreactive score (IRS). The prognostic impact of the individual factors together with standard histologic parameters was calculated by univariate and multivariate analyses. Expression rates for HER2 (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4) were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed weak staining. In 21/90 patients (23.3%), DTC-BM (≥1/2 × 106 cells) could be detected. The presence of DTC-BM was inversely related to nodal status (P= .015) but not to the other factors examined. Tumor stage (P= .02), lymph node involvement (P= .003), grade (P= .046), postoperative tumor residue (P <.001), peritoneal seeding (P= .02), and KI67 (P= .046) significantly correlated with overall survival (OS) after a median observation time of 28 months (2–105). The finding of ascites was borderline significant (P= .050). The presence of DTC-BM (P= .04) and KI67 positivity (P= .02) predicted reduced distant disease-free survival. By multivariate analysis, postoperative tumor residue remained an independent factor for OS (P= .02, relative risk = 4.6). As a primarily locoregional disease, tumor stage and postoperative tumor residue are the main determinants of prognosis in patients with ovarian cancer. However, even in advanced stages, examination of tumor biological factors could help to stratify subgroups of patients and establish targeted therapies.

Zielsetzung: Die prognostische Relevanz der intramammaren Tumorlokalisation (ITL, medial vs. lateral) wird seit einer Untersuchung von Lohrisch et al. (JCO 2000; 18: 2828) kontrovers diskutiert. Ziel der vorliegenden Untersuchung war, den Einfluss der ITL auf die Pravalenz axillarer Lymphknotenmetastasen und die Uberlebensprognose von Patientinnen mit und ohne systemische Therapie zu analysieren. Material: Retrospektive Analyse an 2.414 Patientinnen mit einem UICC I-III Mammakarzinom, die sich an den Universitatskliniken I. UFK, LMU Munchen und Berlin-Charlottenburg, einer R0-Resektion des Primartumors und einer axillaren Dissektion (=5 LK) unterzogen. Patientinnen mit unklarem Tumorsitz, multifokaler Tumorausbreitung, zentralem Tumorsitz oder Tumorsitz innerhalb von je 15° der Grenzen zwischen lateralen und medialen Quadranten wurde, aus der Studie ausgeschlossen. Die mediane Nachbeobachtungszeit betrug 6,7 Jahre. Ergebnisse: Die ITL war bei 33,6% der Patientinnen (n=810) in den medialen und bei 66,4% der Patientinnen (n=1.604) in den lateralen Quadranten der Brust. Es zeigten sich zwischen beiden Kollektiven keine Unterschiede hinsichtlich Tumorgrose, histopathologischem Grading und Hormonrezeptorstatus. Allerdings war eine laterale ITL signifikant mit dem Auftreten von axillaren Lymphknotenmetastasen assoziiert (P

The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment.Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R(0) resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15 degrees of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years.The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients ( n=810) and in the lateral hemisphere of the breast in 66.4% ( n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location ( P0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor ( P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98).We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.

A clinically important myelosuppression due to adjuvant chemotherapy is seen more frequently as dosage is intensified and new drugs are used. The assessment of the cytopenia expected is frequently hampered by a lack of directly comparable data. The aim of this study was to compare - in our own patient population - the chemotherapy-associated myelosuppression of four chemotherapeutic regimens used in gynecological oncology.79 patients with primary breast cancer and 26 patients with epithelial ovarian carcinoma underwent cytostatic treatment, and the associated myelosuppression was evaluated by the determination of cytopenia and the need for supportive therapy. The chemotherapy regimens investigated were CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), 6xq3w), EC/CMF (epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2), 4xq3w, followed by CMF, 3xq3w), DE (docetaxel 75 mg/m(2), epirubicin 90 mg/m(2), 6xq3w) and CC (cyclophosphamide 600 mg/m(2), carboplatin AUC 6, 6xq3w).The EC/CMF and DE regimens were used significantly more frequently for more advanced tumor stages, but there were no differences concerning tumor-dependent prechemotherapeutic myelosuppression. Hemopoiesis was most impaired in the CC group with a mean drop of serum hemoglobin of 1.5 g/dl to the end of the cytostatic treatment; correspondingly, most transfusions of concentrated erythrocytes were needed in this group. The strongest suppression of leukopoiesis was found in the DE group, with a mean drop in leukocyte counts of 6.2 x 10(3)/microliter per cycle; in this group, a mean of 7.6 ready-made syringes with 263 microgram Lenogastrim was used to stimulate leukopoiesis. The severest drop in the mean thrombocyte count, i.e. 171.7 x 10(3)/microliter, was found in the CC group.The CC regimen impairs thrombo- and erythropoiesis most, whereas the DE regimen causes marked leukopenia. The regimen with the smallest myelosuppression was CMF. No severe cytopenia-associated complications were detected in any of the cases investigated.

Data are emerging about the prognostic relevance of occult metastatic cells in the bone marrow of patients with various solid tumors. Discrepancies among different studies on the prognostic relevance of isolated tumor cells may be caused by tumor cell heterogeneity and the use of different immunoassays. There is increasing evidence that validated anticytokeratin antibodies (e.g., A45-B/B3) represent the present standard for the detection of isolated tumor cells. This immunocytochemical assay allows the identification of patients with occult tumor cell dissemination that cannot be identified by conventional screening methods in tumor staging. According to recent studies, these patients are at higher risk for subsequent development of distant metastases and might therefore benefit from early systemic therapy. At advanced stages of the disease, the micrometastatic tumor load after adjuvant therapy, or at the time of emerging recurrences, appears to reflect the tumor's ability to progress. Therapeutic monitoring and cell-cycle independent antibody-based therapy are among possible implications of this new, promising diagnostic tool. The present review also focuses on state of the art, reliable detection methods of occult metastatic cells in the bone marrow of breast cancer patients and on the prognostic relevance of these cells at different stages of the disease.

In the last few years special attention has been paid to the serum concentration of haemoglobin in patients with cancer. It was the aim of this study to ascertain whether at the time of the initial diagnosis low haemoglobin levels in patients with breast cancer denote a higher risk of primary haematogenous dissemination of tumour cells in bone marrow than that in those with higher levels.Between March 1994 and March 2000 bone marrow aspirates were performed and serum haemoglobin concentrations (g/dl) measured before primary surgical treatment in 360 consecutive patients (mean age 57.5 years) with primary breast cancer. Evidence of isolated tumour cells in bone marrow was obtained with the pancytokeratin antibody A45-B/B3. The cohort was divided into two groups on the basis of mean haemoglobin values, and the patients underwent follow-up examination a mean of 30.7 months after the initial diagnosis. Patients with metastases at first diagnosis or those who had received nonsurgical treatment at that time were excluded.The mean pre-treatment haemoglobin concentration of the cohort was 13.8 g/dl (median 13.9 g/dl, S.D.1.2). There was no statistically significant difference in the frequency of cytokeratin-positive bone marrow findings between the two groups. While disseminated tumour cells were demonstrated in the bone marrow of 48 (28%) patients with a pre-treatment haemoglobin of/= 13.9 g/dl (p = 0.50), this was so in 58 patients (31%) with a pre-treatment haemoglobin of13.9 g/dl. There was also no difference between the two groups regarding median survival time (67.9 vs. 65.8 months; p = 0.46). However, there was a significant difference in probability of survival between patients with or without isolated tumour cells in the bone-marrow (59.7 vs. 69.2 months; p0.0001).There is no evidence at present that the preoperative haemoglobin concentration is of prognostic value regarding the haematogenous dissemination of tumour cells and the survival time of patients with primary breast cancer.

Background: Local recurrence remains a major concern after primary treatment of breast cancer and has a major impact on subsequent survival. While most studies report a poorer survival rate in patients with a local recurrence after mastectomy than after breast conservation, it remains controversial whether different risk profiles at the time of primary diagnosis may account for this difference. Method: Matched pair analysis of 134 patients with newly diagnosed locoregional recurrence of breast cancer without evidence of systemic disease. Matching criteria included the primary surgical treatment, tumor size, nodal status, and age. The significance of various prognostic parameters at the time of primary diagnosis and at the time of recurrence were evaluated, by univariate and multivariate analyses, with respect to survival after recurrence. The median follow-up was 8.4 years. Results: Risk factors at the time of presentation, such as tumor size and lymph node status, were comparable between both groups. Local recurrence occurred on an average 9 months earlier in patients after mastectomy (P=0.08). Univariate analysis showed that lymph node status (P=0.0001) and disease-free interval from primary treatment to local recurrence (P=0.0002) were the most significant single prognostic factors for subsequent survival after local recurrence. The primary surgical treatment modality was shown to be of marginal statistical influence (only P=0.05). Conclusion: Local recurrence after mastectomy seems to be associated with worse survival than after breast-conserving therapy. Early onset of chest-wall recurrence, moreover, represents the highest independent risk for cancer-associated death.

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important. PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients’ prognosis. RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P = .032 and P = .014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P = .031) in our series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.

In several studies, low-molecular-weight-heparins (LMWH) have been shown to be as effective in the prevention of deep vein thrombosis (DVT) as unfractionated heparin. However, different LMWHs vary significantly in their pharmacokinetic profile and bioavailability pattern. It remains unknown, whether these pharmacological differences result in a clinically divergent behavior.Safety and antithrombotic efficacy of three LMWHs, certoparin (18 mg), dalteparin (30 mg) and enoxaparin (24 mg), were compared in a prospective, randomized controlled trial involving 188 patients undergoing knee or hip replacement or spinal surgery. Efficacy was assessed by changes in venous flow patterns between pre- and postoperative Doppler sonography. The clinical endpoint for the assessment of safety were intra- and postoperative bleeding, changes in activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), local hematoma and local infections.Two verified DVTs (1.1%) were observed in the study, leading to no statistical difference in the antithrombotic efficacy of the used LMWHs. In 21 patients (11.2%) local hematoma or local infections complicated the postoperative course. Of these 21 patients, 13 belonged to the certoparin group, compared to 4 patients each in the other groups (p0.01). An allergic reaction occurred in only one case treated with dalteparin. No differences between the groups were observed in terms of intra- and postoperative bleeding, APTT, TCT and blood count.The results of this study suggest, that all three LMWHs are equally efficacious in the prophylaxis of DVT in high risk patients after orthopedic surgery. Larger randomized controlled trials are necessary to confirm this conclusion and to evaluate the clinical relevance of the observed differences in postoperative complications.

Recent studies have renewed an old controversy about the efficacy of adjuvant radiotherapy following mastectomy for breast cancer. Radiotherapy is usually recommended for advanced disease, but whether or not to use it in pT1-T2 pN0 situations is still being debated. This study was designed to clarify whether or not routine radiotherapy of the chest wall following mastectomy reduces the risk of local recurrence and if it influences the overall survival rate.Retrospective analysis of patients treated with mastectomy for pT1-T2 pN0 tumors and no systemic treatment. Patients treated with radiotherapy of the chest wall following mastectomy (Group A) are compared with those treated with mastectomy alone (Group B).A total of 918 patients underwent mastectomy. Patients who received adjuvant radiotherapy after mastectomy (n = 114) had a significantly lower risk for local recurrence. Ten years after the primary diagnosis, 98.1% of the patients with radiotherapy were disease free compared to 86.4% of the patients without radiotherapy. The average time interval from primary diagnosis until local recurrence was 8.9 years in Group A and 2.8 years in Group B. The Cox regression analysis including radiotherapy, tumor size and tumor grading found the highest risk for local recurrence for patients without radiotherapy (p0.0004). In terms of overall survival however, the Kaplan-Meier analysis showed no difference between the two groups (p = 0.8787) and the Cox regression analysis failed to show any impact on overall survival.With observation spanning over 35 years, this study shows that adjuvant radiotherapy of the chest wall following mastectomy reduces the risk for local recurrence in node-negative patients with pT1-T2 tumors but has no impact on the overall survival rate.

9612 Background BCT is the most frequently performed surgical treatment for primary breast cancer resulting in optimal cosmetic outcome. Aim of this study was to evaluate safety and outcome in comp...

9515 Background: Patients with persisting ITC in the BM after primary therapy show an increased risk for distant relapse and shortened survival (Janni et al., Cancer 2001; Wiedswang et al., SABCS 2...