MarginProbe®--final results of the German post-market study in breast conserving surgery of ductal carcinoma in situ.

The goal in breast conserving surgery (BCS) of ductal carcinoma in situ (DCIS) is removal of the tumor with a clear surgical margin. However, re-excision rates are regrettably high. To date, there are no adequate procedures for intraoperative margin assessment of DCIS. A multicenter, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe®) in intraoperative margin assessment during BCS of DCIS, the associated reduction of re-excisions and the cosmetic outcome of the treated patients. We present results of 42 patients enrolled in 3 German institutions. The device was used as an adjunctive tool to standard of care. The device use was associated with a reduction in re-excision rates by 56%, from 39% to 17% (p = 0.018).

Characteristics and therapy of premenopausal patients with early-onset breast cancer in Germany.

PURPOSE: The objective of the study is to investigate what kind of tumors young, premenopausal breast cancer patients in Germany show at diagnosis and how they are treated adjuvantly in comparison with a normally distributed cohort. METHODS: The study describes the data of 535 patients who were treated adjuvantly between 2002 and 2006 and participated in a resident mother-child program for rehabilitation (Groemitz cohort). The data includes TNM categories, biology of tumor and therapies. This population is being compared to an age-heterogeneous cohort from the state of Schleswig-Holstein and the DMP-report of the state of North Rhine-Westphalia. RESULTS: 45.8 % of the patients were diagnosed with tumor category pT1, 37 % pT2, 7.3 % pT3 and 1.9 % pT4. 5 % had merely DCIS. 48.8 % of the patients were pN0, 31.4 % pN1 and 17.4 % had a more intense manifestation of lymph nodes. 43.5 % of the tumors showed a grading classified as G3, 64.3 % were estrogen and progesterone hormone receptor positive and 26.2 % Her2 positive. 21 % of the examined cohort members/patients showed a triple negative carcinoma. 59.1 % of the patients with pT1 underwent breast-conserving surgery, 56.1 % of those with pT2 and 25.6 % of those with pT3. Overall 31.0 % of the women received mastectomy and 14.8 % received mastectomy with subsequent reconstruction. 97.6 % of the patients received axillary surgery, 89.9 % chemotherapy. Overall 23.7 % of the patients received their treatment in connection with clinical studies. 95.3 % of the patients with hormone receptor positive tumor received endocrine therapy, 61.3 % of them with GnRH-analogs. In comparison with the OVIS and DMP cohorts patients of the Groemitz cohort were on average 20 years younger. Their tumors were of bigger size and had more often reached the axillary lymph nodes (pN0 48.8 % Groemitz/62.0 % OVIS/66.7 % DMP). The hormone receptor status was more often negative (35.7/16.6/16.5 %) and tumor grading higher (G3 43.5/29.0/28.5 %). Surgery was more extensive even with small tumors (breast conserving surgery with tumor stage pT1 59.1/81.2/77.6 %) and axillary surgery was performed more often in the young collective (97.6/89.3/62.5 %). More patients of the young collective received chemotherapy (89.9/58.4 %/unknown) and more patients of the young collective with hormone receptor positive tumor received endocrine therapy (95.3/77.4/90.6 %). CONCLUSION: Our study shows that young breast cancer patients in Germany can be regarded as a special group. At the time of diagnosis the tumor has frequently reached a more advanced stage, and carcinomas are more aggressive. Operative and medical treatment will often be more aggressive.

Influence of calcitriol on prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cell lines.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a potential molecular prognostic factor for breast cancer, and calcitriol [1,25(OH)(2)D(3)], the biologically active form of vitamin D, is a promising target in breast cancer therapy. MATERIALS AND METHODS: The influence of calcitriol on the proliferation and the effects of calcitriol on the expression of prostaglandin- and vitamin D-metabolising enzymes were examined in benign and malignant breast cells. RESULTS: Calcitriol inhibited the proliferation of MCF-10F and MCF-7 cells but not of invasive MDA-MB-231 cells and reduced the expression of COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the benign breast cell line MCF-10F. Furthermore, dysregulation in vitamin D-metabolising proteins was detected, especially in MDA-MB-231 cells. CONCLUSION: These results suggest dysregulation of vitamin D metabolism and a lack of a possible influence of calcitriol on the metabolism of prostaglandins in the malignant breast cell lines.

Expression of prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cells.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays a crucial role in prognosis of malignancy and has been associated with carcinogenesis, particularly neoangiogenesis and tumor progression. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumour suppressor in cancer. The antiproliferative effects of calcitriol [1,25(OH)(2)D(3)] mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. MATERIALS AND METHODS: The expression of prostaglandin (PG)-metabolizing enzymes, vitamin D-metabolising enzymes and VDR were determined in benign and malignant breast cell lines using western blot analysis. RESULTS: We detected an inverse correlation between the two types of metabolism, a reduced VDR expression in the malignant breast cell lines, and therefore an insufficient induction of 24-hydroxylase in the malignant cells. CONCLUSION: We suggest the possibility of dysregulation of vitamin D-metabolizing enzymes in malignant breast cell lines.

Impact of cyclooxygenase-2 in breast cancer.

Prostaglandin metabolism plays a pivotal role in inflammatory processes and has also been demonstrated to have a role in carcinogenesis, tumor differentiation and tumor growth in breast cancer. Cyclooxygenase-2 (COX-2) is the key involved enzyme, as it triggers prostaglandin synthesis. We reviewed the current literature regarding the impact of prostaglandin metabolism on breast cancer and illustrated the current evidence of the COX-2 influence on breast cancer, delineating possible future prophylactic and therapeutic strategies.

Intraoperative assessment of surgical margins during breast conserving surgery of ductal carcinoma in situ by use of radiofrequency spectroscopy.

Assessment of margins when excising ductal carcinoma in situ (DCIS) of the breast is difficult. Frozen section is unreliable and specimen intraoperative radiography only provides information regarding the extent of the visualized lesion or the microcalcifications. A multi-center, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe) in intraoperative margin assessment during breast conserving surgery (BCS) of DCIS, and the associated reduction of re-excisions. We present results for 22 patients, from those enrolled in our institution. The device was used as an adjunctive tool to current practice. Based on permanent histology reporting, the rate of successful procedures was 86%. The improvement in intraoperative assessment with device use was associated with a reduction in re-excision rates, from 38.8 to 18%.

Successful application of vacuum-assisted closure therapy for treatment of mastitis-associated chronic breast wounds.

INTRODUCTION: Although non-puerperal mastitis is rare and its cause is rather unclear, the number of patients diagnosed with this defect is increasing. In some cases, standard therapy fails and it progresses to a chronic disease. Vacuum-assisted closure (VAC) therapy has shown good results in healing complex wounds. PATIENTS AND METHODS: The goal of this study was to evaluate our experiences with VAC therapy and to answer the question whether or not should be accepted as an effective treatment in healing chronic wounds caused by non-puerperal mastitis. Retrospectively, we identified five patients with a non-puerperal mastitis chronic wound that was treated using VAC and report on their outcome. RESULTS: We reached both wound control and closure of the breast wounds in all patients. CONCLUSION: According to our findings, the VAC therapy can be considered when managing challenging breast wounds, particularly when other therapeutic options have failed. The role of VAC therapy as a primary therapeutic option has not yet been evaluated.

Prostaglandin metabolising enzymes and PGE2 are inversely correlated with vitamin D receptor and 25(OH)2D3 in breast cancer.

BACKGROUND: Breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression. The antiproliferative effects of calcitriol (1,25(OH)(2)D(3)) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. First data suggest a correlation between vitamin D and prostaglandin metabolism. MATERIALS AND METHODS: We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP(2)/EP(4) in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)(2)D(3) and PGE(2) plasma levels from healthy and breast cancer patients. RESULTS: Significantly higher COX-2, lower VDR and lower EP(2) and EP(4) receptor protein levels in the malignant tissue and a significantly lower 15-PGDH protein level in normal breast tissue were detected. Breast cancer patients older than 45 years, diagnosed and sampled in the winter time had significantly lower 25(OH)(2)D(3) and higher PGE(2) serum levels. CONCLUSION: The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE(2) and 25(OH)(2)D(3) levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism.

Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients.

Ovarian carcinomas are associated with increased inflammation which is based upon an up-regulation of inducible cyclooxygenase-2 (COX-2). Moreover, based on our previous published data, the extra-renal vitamin D metabolism seems to be dysregulated in comparison to healthy tissue. In order to gain further insight into the prostaglandin (PG)- and vitamin D-metabolism in ovarian carcinomas, the study aimed to evaluate the expression of the PG metabolising enzymes COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) compared to the vitamin D receptor (VDR) in benign and malignant ovarian tissues. Additionally, we determined the 25-hydroxycholecalciferol (25(OH2)D3) serum levels. Expression of VDR, COX-2 and 15-PGDH was determined by Western blot analysis. Serum levels of 25(OH2)D3 and PGE2 were measured by chemiluminescence-based and colorimetric immunoassay. We detected significantly higher expressions of the PG metabolising enzymes 15-PGDH and COX-2 in malignant tissue and PGE2 serum levels were 2-fold higher in tumour patients. Furthermore, we found an inverse correlation to the VDR-expression which was 62.1% lower in malignant tissues compared to that in benign tissues. Surprisingly, we could not detect any differences between the 25(OH2)D3 serum levels in either group (n=20). These data suggest a correlation between PG- and vitamin D-metabolism in ovarian carcinomas.

Prostaglandin metabolizing enzymes in correlation with vitamin D receptor in benign and malignant breast cell lines.

BACKGROUND: The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR), render the biologically active form of vitamin D a promising target in breast cancer therapy. Furthermore, breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression, the prostaglandin E2 (PGE2) synthesizing enzyme. The PGE2 metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumor suppressor in cancer. First references suggest a correlation between vitamin D and prostaglandin metabolism through the impact of 1,25(OH)2D3 on the expression of COX-2 and 15-PGDH. MATERIALS AND METHODS: The expression of VDR, COX-2 and 15-PGDH in benign MCF-10F and malignant MCF-7 breast cells was determined by real-time PCR (RT-PCR) and Western blot analysis. RESULTS: Although the RT-PCR data were divergent from those obtained from the Western blot analysis, the COX-2 protein expression was MCF-7 2-fold higher in the MCF-7 compared to the MCF-10F cells. Moreover, a correlation of 15-PGDH to VDR by RT-PCR was found in both cell lines. The VDR protein levels were inversely correlated to the 15-PGDH protein levels and revealed that the MCF-10F cells had the highest VDR expression. CONCLUSION: A possible link between VDR-associated target genes and prostaglandin metabolism is suggested.

Metastasized hemangiopericytoma of the breast: a rare case.

Sarcoma of the mammary glands is extremely rare. Liposarcoma, leiomyosarcoma, rhabdomyosarcoma, as well as hemangiopericytoma, are part of the soft tissue sarcoma group. Little is known about the progress, prognosis and dissemination of this infrequent tumor entity. We present the case of a woman, who received primary diagnosis of a malignant hemangiopericytoma of the left breast. She underwent a mastectomy with an axillary lymph node sampling (stage pT3 pN0 cM0), as adjuvant therapy was not mandatory. Eight months after diagnosis, the patient presented with lumbar back pain, gluteal pain and right accentuated adynamia in both legs because of a disseminated osseous metastasis. Diagnostic investigation presented a cerebral, pulmonary, cutaneous, hepatic and pleural metastatic disease. Two months after initiation of chemotherapy the patient died. Diagnostic criteria and treatment principles in the metastatic situation are presented in addition to the literature to give a review about this rare malignancy.

Language dominance in mesial temporal lobe epilepsy: a functional transcranial Doppler sonography study of brain plasticity.

Functional transcranial Doppler sonography was used to study hemispheric language dominance (HLD) in 24 right-handed patients with left temporal lobe epilepsy (TLE) and a structural lesion in the left temporal lobe and in 69 healthy controls. Twenty-five percent of the patients and 4% of controls showed atypical (right or bilateral) HLD. Degree of HLD was not correlated with age, Full Scale IQ, Verbal IQ, spike frequency, seizure frequency, age at seizure onset, or duration of TLE. Atypical HLD appears to be lesion-induced, independent of epilepsy characteristics.

Language lateralization in patients with temporal lobe epilepsy: a comparison of functional transcranial Doppler sonography and the Wada test.

This study prospectively investigates whether noninvasive functional transcranial Doppler sonography (fTCD) is a useful tool to determine hemispheric language lateralization in the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). fTCD results were compared with the Wada test as the gold standard. Wada test and fTCD were performed in 13 patients suffering from TLE. fTCD continuously measured blood flow velocities in both middle cerebral arteries, while the patient was performing a cued word generation task. During the Wada test, spontaneous speech, comprehension, reading, naming, and repetition were investigated. A laterality index (LI) was obtained by both procedures. Due to a lack of an acoustic temporal bone window, fTCD could not be performed in two patients (15%). In 9 of the remaining 11 patients hemispheric language dominance was found on the left side, in 1 patient on the right side, and 1 patient showed bihemispheric language representation. In all patients fTCD and the Wada test were in good agreement regarding hemispheric language lateralization, and the LI of both techniques were highly correlated (r = 0.776, P = 0.005). fTCD gives predictions of hemispheric language dominance consistent with the Wada test results even in children, patients with low IQ, and nonnative speakers. It is an alternative to the Wada test in determining language lateralization in patients with temporal lobe epilepsy.