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1.
Thromb Res ; 202: 84-89, 2021 06.
Article in English | MEDLINE | ID: mdl-33784534

ABSTRACT

INTRODUCTION: Venous thrombosis is the leading cause of pregnancy-related maternal morbidity and mortality. The thrombosis risk is increased by caesarean section and blood loss, though underlying mechanisms of these prothrombotic changes remain unknown. MATERIALS AND METHODS: This prospective study recruited 50 pregnant women at term undergoing elective caesarean section at University Hospital Magdeburg, Germany. Blood loss during surgery was correlated with the changes in total protein S, full length TFPI (TFPIfl), prothrombin, the endogenous thrombin potential (ETP) and resistance to activated protein C (APCsr) determined via calibrated automated thrombography. RESULTS: Mean blood loss was 506 ml (95%CI: 456 to 557 ml). Total protein S was 0.63 (95%CI: 0.60 to 0.67) U/ml preoperatively, decreased by 14.8% after caesarean section and almost normalised five days later. TFPIfl was 0.47 (95%CI: 0.41 to 0.53) U/ml before, remained unchanged immediately after and increased by 11.5% five days after surgery. Prothormbin was 1.10 (95%CI: 1.03 to 1.16) U/ml preoperatively, reduced by 10.4% immediately after and increased again five days after caesarean section, exceeding the preoperative values by 4.4% (-0.7 to 9.6). The ETP decreased by 3.9%, whereas the APCsr increased by 37.0% immediately after caesarean section. The changes in total protein S, prothrombin, thrombin generation and APC resistance showed a trend to be more pronounced in the subgroups with higher blood loss. DISCUSSION: Moderate blood loss during caesarean section hardly reduces thrombin generation but aggravates pregnancy-induced APC resistance and combined deficiency of TFPI and protein S, which can account for the increased thrombosis risk in early puerperium.


Subject(s)
Activated Protein C Resistance , Cesarean Section , Blood Coagulation , Cesarean Section/adverse effects , Female , Germany , Humans , Pregnancy , Prospective Studies
2.
Arch Gynecol Obstet ; 300(6): 1637-1644, 2019 12.
Article in English | MEDLINE | ID: mdl-31631250

ABSTRACT

PURPOSE: Although puerperal mastitis is a common disease, published data are poor. Increasing rates of community-acquired MRSA (CA-MRSA) cases are reported in the USA. However, information about common pathogens and CA-MRSA in Germany is still insufficient. The aim of this study was to investigate the most common pathogens of puerperal mastitis in the last decade, its therapy, resistance rate and the effectiveness of the current treatment strategies. METHODS: The pathogens, the respective antibiograms and the treatment strategies of patients treated for puerperal mastits at the University Clinic Magdeburg (Germany) between 2006 and 2016 were retrospectively reviewed. Statistical analysis was performed using SPSS Version 21. RESULTS: In our series, 59 cases with puerperal mastitis were reviewed, 26 (44.1%) of these developed a breast abscess. In 37 of 59 (67.3%) cases the symptoms occurred in the first 8 weeks postpartum. The most common pathogens were Staphylococcus aureus (64.9%) and Coagulase-negative Staphylococcus (13.5%). Methicillin-resistant Staphylococcus aureus (MRSA) was found in one case. Of the 19 cases with Staphylococcus aureus, 17 were resistant to Penicillin. Conservative management was mainly performed with Flucloxacillin (60%), which was successful in most cases. Sixteen of 26 (61.5%) women with abscesses underwent ultrasound (US)-guided needle aspiration. CONCLUSION: In this cohort, MRSA was not a main pathogen responsible for breast abscesses. Conservative treatment strategies remained constant during the observed period and Flucloxacillin was the most frequent antibiotic used. The analysis of the courses of diseases leads to the conclusion that surgical incision is progressively replaced by US-guided needle aspiration.


Subject(s)
Mastitis/drug therapy , Puerperal Disorders/drug therapy , Abscess/drug therapy , Abscess/microbiology , Adult , Anti-Bacterial Agents/therapeutic use , Female , Humans , Mastitis/microbiology , Puerperal Disorders/microbiology , Retrospective Studies , Staphylococcus aureus/isolation & purification
3.
Arch Gynecol Obstet ; 297(2): 479-485, 2018 02.
Article in English | MEDLINE | ID: mdl-29302807

ABSTRACT

OBJECTIVE: To compare the impact of peritoneal closure on postoperative pain after vaginal (VH) and laparoscopic-assisted vaginal hysterectomy (LAVH). STUDY DESIGN: A prospective, randomized, double-blind study was designed to investigate as primary outcome the postoperative pain after VH and LAVH with and without peritoneal closure. The postoperative pain was measured using visual analogue scale (VAS). RESULTS: The patients were recruited between August, 2007 and July, 2014. A total of 192 patients with benign uterine diseases were eligible for analysis and were divided in four groups: LAVH and VH with and without peritoneal closure (PC), respectively. The patients' characteristics including parity, BMI, previous abdominal operations, and uterus weight were well balanced between the groups. The patients who received LAVH were significantly younger (p = 0.0443). LAVH was associated with increased postoperative pain and reduced patients' mobility in the first 72 and 24 h, respectively, after surgery. The use of analgesics remained similar in all four groups. The operating time was significantly shorter after VH (VH + PC 59 ± 17; VH - PC 56 ± 19) than after LAVH (LAVH + PC 106 ± 29 min; LAVH - PC 99 ± 30) (p < 0.0001). The PC did not affect the patients' outcome. The blood loss, the hemoglobin drop, the hospital stay, and the rate of intra- and postoperative complications rate were similar in all four groups. No conversation to laparotomy occurred in whole study population. CONCLUSION: VH is associated with shorter operating time and reduced postoperative pain compared to LAVH.


Subject(s)
Hysterectomy, Vaginal/methods , Laparoscopy/methods , Uterine Diseases/surgery , Adult , Aged , Double-Blind Method , Female , Humans , Hysterectomy, Vaginal/instrumentation , Laparotomy , Length of Stay , Middle Aged , Operative Time , Pain Measurement , Pain, Postoperative/epidemiology , Postoperative Complications/epidemiology , Prospective Studies , Treatment Outcome , Visual Analog Scale
4.
Eur J Cancer ; 64: 12-21, 2016 09.
Article in English | MEDLINE | ID: mdl-27323347

ABSTRACT

BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/prevention & control , Bone Neoplasms/secondary , Breast Neoplasms/drug therapy , Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Adult , Aged , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm, Residual , Zoledronic Acid
5.
J Cancer Res Clin Oncol ; 142(5): 1109-16, 2016 May.
Article in English | MEDLINE | ID: mdl-26809246

ABSTRACT

INTRODUCTION: Elderly breast cancer patients aged ≥75 years are underrepresented in most studies. Therefore, data on cancer characteristics, adjuvant treatment and survival in elderly patients are missing. PATIENTS AND METHODS: In this retrospective study, we compared tumor characteristics and adjuvant therapy in 973 women with invasive, non-metastasized breast cancer aged ≥75 years with 3377 younger postmenopausal patients (50-74 years old). Time dynamics of tumor characteristics were investigated, comparing two observation periods between the years 2000-2004 versus 2005-2008. RESULTS: Compared to younger women, older patients were more often treated with mastectomy and less likely to receive adjuvant treatment. Although the overall survival rate increased over the observation period in both age groups, the older study group was characterized by shorter disease-free survival. Additionally, we observed an increase in about 1.65 years in the age at diagnosis as well as an increasing rate of breast-conserving surgery and sentinel lymph node biopsy for the whole study population between 2000 and 2008. Furthermore, we found a reduction in the proportion of estrogen receptor-positive tumors in the younger women and a decrease in G3-tumors in both age groups over the study time. CONCLUSION: The older group's reduced disease-free survival could be explained by the tumor characteristics and differences in the adjuvant treatment. Remarkably, elderly women are more likely to be overtreated surgically while being undertreated in terms of adjuvant therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/therapy , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/mortality , Carcinoma, Lobular/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Sentinel Lymph Node Biopsy , Survival Rate
6.
Z Gastroenterol ; 53(9): 1080-3, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26367023

ABSTRACT

AIM: Typical symptoms of gastroesophageal reflux disease (GERD) are known to be frequent in pregnancy. The aim of this study was to gain a first estimation of the occurrence of extraesophageal symptoms in this context. METHODS: A prospective longitudinal study was performed on 166 pregnant women and in a control group of 285 women. The diagnosis of GERD was based on the Montreal classification using the reflux disease questionnaire (RDQ). Extraesophageal symptoms were recorded with a self-administered questionnaire. Typical GERD symptoms and extraesophageal GERD symptoms were recorded in each trimester of pregnancy. RESULTS: The prevalence of GERD during pregnancy was 16.9% in the first, 25.3% in the second and 51.2% in the third trimester. The prevalence of GERD in the control group was 6.3%. Asthma was reported by 3.5% of controls and by 6% of pregnant women during pregnancy. Chest pain occurred in 6% of the controls and in 1.8%, 2.4% and 2.4% during the trimesters of pregnancy, chronic cough was reported by 1.1% of controls and 1.2% of pregnant women. With the diagnosis of GERD the odds ratios and 95% confidence intervals for asthma, chronic cough and chest pain in the third trimester of pregnancy were as follows: 1.56 (0.58-4.22) for asthma, 0.91 (0.08-10.28) for chronic cough and 2.04 (0.49-8.46) for chest pain. CONCLUSION: GERD is very frequent during pregnancy with progressive incidence during the course of pregnancy. Extraesophageal symptoms of GERD have an unexpected low prevalence during pregnancy.


Subject(s)
Asthma/epidemiology , Chest Pain/epidemiology , Cough/epidemiology , Gastroesophageal Reflux/epidemiology , Pregnancy Complications/epidemiology , Adult , Asthma/diagnosis , Chest Pain/diagnosis , Comorbidity , Cough/diagnosis , Female , Gastroesophageal Reflux/diagnosis , Germany/epidemiology , Humans , Incidence , Longitudinal Studies , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Trimesters , Prospective Studies , Risk Factors , Symptom Assessment/statistics & numerical data
7.
Geburtshilfe Frauenheilkd ; 75(8): 839-843, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26366004

ABSTRACT

Placentation disorders are the result of impaired embedding of the placenta in the endometrium. The prevalence of these disorders is estimated to be around 0.3 %. A history of previous prior uterine surgery (especially cesarean section and curettage) is the most common risk factor. Impaired placentation is differentiated into deep placental attachment; marginal, partial and total placenta previa; and placenta accreta, increta and percreta. Treatment depends on the severity of presentation and ranges from expectant management to emergency hysterectomy. In most cases, preterm termination of pregnancy is necessary. We report here on the case of a 39-year-old woman with placenta accreta and total placenta previa who underwent hysterectomy in the 19th week of pregnancy.

8.
Geburtshilfe Frauenheilkd ; 75(6): 556-565, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26166836

ABSTRACT

For the first time, this year's St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but - for logistical reasons - in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this year's votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility.

9.
Cancer Invest ; 33(5): 193-6, 2015 May.
Article in English | MEDLINE | ID: mdl-25831456

ABSTRACT

Elevated platelet count occasionally is associated with gynecologic malignancies. We investigated the level of platelet count in 450 patients with gynecologic tumors. Ovarian cancer patients have increased platelet count associated with the course of treatment and disease progression. In multivariate analysis, the decrease of platelet count less than 25% after chemotherapy was an unfavorable prognostic factor for PFS (HR, 1.948; 95% CI, 1.083-3.505; p = 0.026) and overall survival (HR, 2.093; 95% CI, 1.022-4.287; p = 0.043). An insufficient decrease of the platelet count increased the risk of recurrence. Thus platelet count could be used for monitoring the disease progression and to predict treatment response.


Subject(s)
Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Platelet Count , Prognosis , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Risk Factors , Thrombocytosis , Treatment Outcome
10.
Z Geburtshilfe Neonatol ; 219(1): 45-51, 2015 Feb.
Article in German | MEDLINE | ID: mdl-25734477

ABSTRACT

Thrombophilia is a prothrombotic state that can be caused by genetic disorders, such as the factor-V-Leiden or prothrombin mutation, as well as by acquired changes like oestrogen-induced APC resistance and the antiphospholipid syndrome. Pregnancy induces multiple procoagulant changes in the haemostatic system, increasing the risk of venous thromboembolism in women with a thrombophilia even further. Additionally, thrombophilias are suggested to be associated with a number of pregnancy complications such as recurrent miscarriage, stillbirth, preeclampsia and HELLP syndrome. Increased local activation of coagulation may directly influence trophoblast expansion and invasion, causing thereby an impaired trophoblast development and insufficient widening of spiral arteries in the first trimenon, which results in placenta-mediated pregnancy complications like preeclampsia or HELLP syndrome. Besides, macro- and microthrombosis in the vessels of placental stemm villi and spiral arteries may lead to multiple infarctions with release of necrotic trophoblast fragments and inflammatory cytokines playing an important role in the pathogenesis of recurrent pregnancy loss and stillbirth. For women with a known thrombophilia it is recommended to carry out either only postpartal or combined ante- and postpartal thrombosis prophylaxis with low-molecular weight heparins (LMWH) depending on the individual risk stratification. The effectiveness of the LMWH administration for prevention of thrombophilia-induced pregnancy complications and improvement of the pregnancy outcome is currently a matter of debate. Furthermore, an additional application of acetyIsalicylic acid (ASA) should be considered in the management of women with the antiphospholipid antibody syndrome. In the current article we present the case of a 28-year-old woman with the heterozygous prothrombin mutation, HELLP syndrome, a late miscarriage and a stillbirth in the anamnesis, who delivered 3 healthy babies under antenatal LMWH prophylaxis combined with intensive interdisciplinary prenatal care.


Subject(s)
HELLP Syndrome/diagnosis , HELLP Syndrome/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Pregnancy Complications, Cardiovascular/drug therapy , Thrombophilia/drug therapy , Thrombophilia/prevention & control , Adult , Diagnosis, Differential , Female , Fibrinolytic Agents/therapeutic use , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Outcome , Treatment Outcome
11.
Thromb Res ; 134(5): 1032-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25260941

ABSTRACT

INTRODUCTION: Oral contraceptives (OC) increase the risk of venous thromboembolism that depends on the OC formulation and could at least partially be explained by impaired function of the protein C-system (APC resistance) and the tissue factor pathway inhibitor (TFPI)-system. There is limited information available on the effects of OC, containing a newer progestogen- drospirenone (DRSP-OC) on these two major anticoagulant pathways, thrombin generation, reflecting the overall state of coagulation, and other coagulation parameters. METHODS: In a study population consisting of 14 healthy women (age 21-33 years) we investigated the effect of the menstrual cycle and subsequent use of DRSP-OC on APC resistance, the function of the TFPI-system, thrombin generation and on their major determinants, i.e. prothrombin, antithrombin, FV, FX, FVIII, protein C, protein S(total and free) and TFPI(full-length and free). RESULTS: All studied parameters remained unchanged during the menstrual cycle. During DRSP-OC use we observed a significant increase in APC resistance (~2.4-fold), thrombin generation measured at low (~2.2-fold) and high tissue factor concentrations (~1.4-fold), plasma concentrations of prothrombin (19%), FX (31%), FVIII (17%) and protein C (43%). DRSP-OC use impaired the function of the TFPI-system and decreased plasma levels of antithrombin (-6%), FV (-22%), protein Stotal (-21%), protein Sfree (-20%), TFPIfull-length (-36%) and TFPIfree (-46%). CONCLUSIONS: DRSP-OC caused procoagulant changes in all studied haemostatic parameters. The impairment of the protein C- and TFPI-systems was more pronounced than the impairment of the coagulation pathways and can at least partially account for the increased risk of venous thromboembolism in users of DRSP-OC.


Subject(s)
Androstenes/pharmacology , Contraceptives, Oral/pharmacology , Hemostasis/drug effects , Adult , Blood Coagulation/drug effects , Female , Humans , Lipoproteins/metabolism , Menstrual Cycle , Protein S/metabolism , Thrombin/metabolism , Young Adult
12.
J Cancer Res Clin Oncol ; 140(9): 1457-63, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24825122

ABSTRACT

BACKGROUND: The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum-taxane-based therapy in sporadic ovarian cancer. PATIENTS AND METHODS: BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients. RESULTS: BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum-taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32-0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation. CONCLUSIONS: BRCA1 promoter methylation is predictive for better response to platinum-taxane-based therapy in EOC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BRCA1 Protein/genetics , Biomarkers, Tumor/genetics , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Promoter Regions, Genetic/genetics , Adult , Aged , Aged, 80 and over , Bridged-Ring Compounds/administration & dosage , Carcinoma, Ovarian Epithelial , Disease-Free Survival , Female , Humans , Methylation/drug effects , Middle Aged , Organoplatinum Compounds/administration & dosage , Prognosis , Taxoids/administration & dosage , Young Adult
13.
Ann Oncol ; 25(1): 81-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24273046

ABSTRACT

BACKGROUND: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. RESULTS: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. CONCLUSIONS: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/mortality , Capecitabine , Carcinoma, Ductal, Breast/mortality , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Neoadjuvant Therapy , Proportional Hazards Models , Taxoids/administration & dosage , Trastuzumab , Treatment Outcome
14.
Breast Cancer Res Treat ; 141(2): 205-12, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24026861

ABSTRACT

The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.


Subject(s)
BRCA1 Protein/genetics , DNA Methylation , Promoter Regions, Genetic , Triple Negative Breast Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , BRCA1 Protein/metabolism , Female , Humans , Lymphatic Metastasis , Middle Aged , Mutation , Neoplasm Grading , Prognosis , Treatment Outcome , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology , Tumor Burden
15.
Ann Surg Oncol ; 20(11): 3438-45, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23709056

ABSTRACT

PURPOSE: To evaluate the oncologic safety and cosmetic results after breast cancer surgery for central breast cancer by the B technique. METHODS: Seventy women with operable breast cancer located in the central portion of the breast that had received resection surgery with the B technique were recruited. The primary outcome was the oncological safety, quantified as rate of positive resection margins and the cosmetic outcome evaluated by postsurgical self-assessment of the cosmetic outcome via questionnaire. The median follow-up period was 61.4 months (range 7.9-142.6 months). RESULTS: With one exception all patients had T1-2 tumors less than 5 cm in diameter. Most patients had invasive ductal breast cancers (57.1 %), followed by ductal carcinoma-in situ (27.1 %) and invasive lobular breast cancers (8.6 %). The incidence of positive resection margins was 17.1 %. No local tumor recurrence occurred during follow-up; one patient had distant metastases. In total, 80 % of the patients reported that the cosmetic results met or exceeded their expectations. CONCLUSIONS: The B technique is a safe breast conservation surgery for the excision of tumors located in the central portion of the breast and yields a high rate of satisfactory cosmetic results.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/surgery , Mastectomy, Segmental , Neoplasm Recurrence, Local/surgery , Patient Satisfaction , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Breast Neoplasms/psychology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/psychology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/psychology , Carcinoma, Lobular/pathology , Carcinoma, Lobular/psychology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/psychology , Neoplasm Staging , Postoperative Complications , Prognosis , Retrospective Studies
16.
Biophys Chem ; 172: 1-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23333594

ABSTRACT

The insertion of local anaesthetics into a cell membrane is a key aspect for explaining their activity at a molecular level. It has been described how the potency and response time of local anaesthetics is improved (for clinical applications) when they are dissolved in a solution of sodium bicarbonate. With the aim of gaining insight into the physico-chemical principles that govern the action mechanism of these drugs at a molecular level, simulations of benzocaine in binary lipid bilayers formed by DPPC/DPPS were carried out for different ionic strengths of the aqueous solution. From these molecular dynamic simulations, we observed how the thermodynamic barrier associated with benzocaine insertion into the lipid bilayers diminished exponentially as the fraction of DPPS in the bilayer increased, especially when the ionic strength of the aqueous solution increased. In line with these results, we also observed how this thermodynamic barrier diminished exponentially with the phospholipid/water interfacial tension.


Subject(s)
Anesthetics, Local/metabolism , Benzocaine/metabolism , Cell Membrane/metabolism , Lipid Bilayers/chemistry , Anesthetics, Local/chemistry , Benzocaine/chemistry , Cell Membrane/chemistry , Computer Simulation , Humans , Models, Chemical , Osmolar Concentration , Surface Tension , Thermodynamics , Water/chemistry , Water/metabolism
17.
Geburtshilfe Frauenheilkd ; 73(10): 1028-1034, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24771892

ABSTRACT

Purpose: The aim of this study was to investigate the value of intraoperative ultrasound in breast-conserving operations and to compare it with standard procedures. Methods: For this purpose 307 women with palpable breast cancers and 116 patients with non-palpable breast cancers were compared retrospectively. In the group with palpable breast cancers 177 patients were treated by US-guided operations and 130 patients underwent palpation-guided breast-conserving operations. As primary outcomes, the resection margins and the rate of re-operations were evaluated. Results: With regard to disease-free resection margins, intraoperative ultrasound was significantly superior to palpation alone. In the group of patients in whom the tumours were extirpated with the help of palpation, R1 resections were observed almost twice as often (16.9 %) as in the US-guided group (8.5 %). In the group with non-palpable breast cancers, intraoperative ultrasound was employed in 61 patients. As a control, 43 cases were evaluated in whom the breast-conserving operation was performed after wire marking. In this group US-guided tumour removal proved to be superior to that after wire marking for tumours that did not exhibit any intraductal components. Otherwise the redo resection rate was reduced by use of ultrasound. Furthermore, the surgeon was able by means of intraoperative ultrasound to identify "problematic" margins and to excise them in the same sitting. Conclusions: The US-guided, breast-conserving operations led to a lower rate of R1 resections and redo operations in comparison to operations with palpation alone or those after wire marking.

18.
Clin Exp Metastasis ; 29(8): 889-900, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22552371

ABSTRACT

We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions. It was correlated to the expression of hMLH1 protein, microsatellite instability (MSI) of ECs and to the well-known clinico-pathological variables of cancer. The hMLH1 promoter methylation was detected in 24 out of 64 (37.5 %) primary ECs but only in one out of 18 (5.6 %) metastatic lesions investigated. Promoter hMLH1 hypermethylation was found more often in early stage ECs and was associated with a decrease of hMLH1 protein expression immunohistochemically. An inverse relationship between hMLH1 expression and clinical stage of the disease was found (p = 0.048). Interestingly, there was a significant correlation between MSI and hMLH1 protein expression level (p = 0.042). MSI phenotype was found more often in EC metastases compared to the primary tumors (66.7 % vs 29.3 %; p = 0.039). However, neither hMLH1 promoter hypermethylation nor MSI was independent predictive factors for patient's outcome. Using an in vitro model we showed that hMLH1 methylation is reversible. These data showed that hMLH1 methylation with a consequent protein decrease occurred early during EC tumorigenesis and may cause a MSI phenotype, which occurs relatively late. MSI may be an important mechanism supporting further the tumor progression. These findings may have importance for the specific chemosensitization of the primary tumors/metastases and can improve our understanding of endometrial carcinogenesis in humans.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , DNA Methylation , DNA Repair Enzymes/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Microsatellite Instability , Neoplasm Metastasis/genetics , Nuclear Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adult , Aged , Aged, 80 and over , Azacitidine/pharmacology , Cell Line, Tumor , DNA Methylation/drug effects , DNA Repair , DNA Repair Enzymes/genetics , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/mortality , Female , Humans , Microsatellite Repeats/genetics , Middle Aged , MutL Protein Homolog 1 , Neoplasm Grading , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nuclear Proteins/genetics , Phenotype , Prognosis , Promoter Regions, Genetic
19.
Geburtshilfe Frauenheilkd ; 72(9): 840-845, 2012 Sep.
Article in English | MEDLINE | ID: mdl-25328165

ABSTRACT

Caesarean section is one of the most common operations worldwide and more than 30 % of procedures in perinatal centres in Germany are caesarean sections. In the last few years the technique used for caesarean sections has been simplified, resulting in a lower postoperative morbidity. But persistent problems associated with all caesarean section techniques include high intraoperative loss of blood, the risk of injury to the child during uterotomy and postoperative wound dehiscence of the uterine scar. We present here a modification of the most common Misgav-Ladach method. The initial skin incision is done along the natural skin folds and is extended intraoperatively depending on the circumference of the baby's head. After blunt expansion of the uterine incision using an anatomical forceps, the distal uterine wall is pushed behind the baby's head. The baby's head is rotated into the occipito-anterior or posterior position and delivery occurs through the application of gentle pressure on the uterine fundus. Closure of the uterotomy is done using 2 continuous sutures, which are then knotted together resulting in a short double-layer closure. The two ends of the skin suture are left open to allow for natural drainage. Our experience at the University Gynaecological Hospitals in Novi Sad and Magdeburg has shown that this modification is associated with shorter operating times, minimal blood loss and shorter in-hospital stay of patients as well as high rates of patient satisfaction.

20.
Eur Surg Res ; 47(4): 231-9, 2011.
Article in English | MEDLINE | ID: mdl-22056494

ABSTRACT

OBJECTIVE: The aim of the present retrospective study was to compare two breast-conserving techniques, segmental resection and standard lumpectomy, for the treatment of breast cancer regarding their oncological safety. Quality of life aspects were evaluated by assessing the respective postsurgical cosmetic results. PATIENTS AND METHODS: 190 women with breast cancer located in the superior and lateral quadrant were included in the study. Sixty patients were treated with segmental resection (group 1), whereas 130 underwent standard lumpectomy (group 2). Tumor sizes were determined and excised tissue specimens were analyzed for positive or negative resection margins. Patients were given a 16-item questionnaire for the postsurgical self-assessment of the cosmetic outcome. RESULTS: No statistically significant difference was found concerning the number of positive resection margins between the groups (25 vs. 30%, p = 0.46). Exceptions were ventral margins, which predominated in group 2 (p = 0.016). Group 1 revealed a significantly larger maximum tumor size with negative margins as compared to group 2 (26.6 vs. 17.0 mm). General satisfaction with the cosmetic results was comparable between groups. CONCLUSIONS: Segmental resection surgery, as a method of breast conservation therapy, can be used to treat larger breast lesions as compared to standard lumpectomy.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Mastectomy, Segmental , Adult , Aged , Aged, 80 and over , Female , Humans , Mammaplasty , Middle Aged , Patient Satisfaction , Quality of Life , Retrospective Studies
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