Wirkungsmechanismen von Steroidhormonen und Steroidhormonantagonisten und ihre Bedeutung für die Tumorkarzinogenese

Zum Thema Die Steroidhormone, ?strogene und Gestagene, vermitteln ihre organspezifische Funktion zumeist über Steroidhormonrezeptoren. Nach Bindung des Ligand-Rezeptor-Komplexes wird u. a. die Mitoserate gesteigert und steroidhormonabh?ngige Gene stimuliert. Steroidhormonrezeptoren werden ubiquit?r in der Mamma, dem Endometrium etc. exprimiert, so da? das steroidhormonvermittelte Signal in diesen Organen ausgeführt werden kann. Parallel zur steroidhormonvermittelten Signalkette werden physiologische Zellfunktionen einschlie?lich Zellproliferation zus?tzlich von Protoonkogenen und Tumorsuppressorgenen reguliert. Physiologische Interaktionen zwischen den unterschiedlichen Signalketten bzw. Fehlregulationen in einem oder mehrere dieser Systeme sind Schlüsselschritte zur malignen Transformation von Zellen. Trotz vorhandener Steroidhormonrezeptorexpression wird nicht immer die Funktion des Steroidhormons bzw. bei therapeutischem Einsatz die des Steroidhormonantagonisten vermittelt. Patientinnen mit Mammakarzinom sprechen zumeist auf eine Hormontherapie mit Tamoxifen an, wohingegen Patientinnen mit Endometriumkarzinom nur sehr selten auf diese Therapie ansprechen. Zus?tzlich induziert Tamoxifen Endometriumkarzinome. Diese Befunde lassen auf organspezifische, regulative Kofaktoren des Steroidhormonrezeptors und seiner Wirkung schlie?en. Der therapeutische Einsatz von Hormonen im Rahmen einer Hormonersatztherapie zeigt keine wesentliche Risikoerh?hung für die Entstehung eines Mamma- oder Ovarialkarzinoms, bei Kombinationstherapien auch nicht für die Entstehung eines Endometriumkarzinoms. In der Diskussion ist derzeit der Einsatz der Hormonersatztherapie bei Patientinnen mit Zustand nach Mamma- oder Endometriumkarzinom.     

Prevalence of unrepaired third- and fourth-degree tears among women taken to the operating room for repair of presumed obstetric fistula during two fistula camps in Kenya

Introduction and hypothesis

More than 2 million women on earth today are said to be suffering from obstetric fistula (OF), a communication between the vagina and either the urinary tract or rectum. Since unrepaired third- and fourth-degree perineal tears often manifest with symptoms identical to OF, we hypothesized that the global burden of OF is in part due to these unrepaired deep obstetric tears.

Methods

Four consultant gynecologists retrospectively reviewed the medical and operative records of all obstetric fistula cases that underwent surgical repair during the July and August, 2014, Kenyatta National Hospital and Embu Provincial Hospital Fistula Camps in Kenya.

Results

One hundred and eighty charts were reviewed. All 180 women had fecal incontinence (FI), urinary incontinence (UI), or both as their primary complaint. Sixty of the 180 (33 %) women had isolated FI as their presenting symptom, and at operation, 57 of these 60 (95 %) were found to have unrepaired third- and fourth-degree obstetric tears. Ninety-two of the 180 (51 %) women with OF symptoms ultimately had true OF confirmed at operation.

Conclusion

These findings suggest that many women with OF symptoms in Kenya may harbor unrepaired third- and fourth-degree tears. Additionally, women with isolated FI may be more likely to suffer from third- and fourth-degree tears than from true OF. Immediate postpartum diagnosis and repair of third- and fourth-degree perineal tears could significantly reduce the overall burden of women with symptoms of OF.

     

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases. Key words: neuroendocrine neoplasia of the breast, invasive breast cancer with neuroendocrine differentiation, neuroendocrine breast cancer, neuroendocrine markers, somatostatin receptor 2A     

Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial.

BACKGROUND: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high-risk breast cancer (HRBC) patients with >9 involved lymph nodes, who received different chemotherapy dose-intensification strategies within a prospective randomized WSG AM-01 trial. MATERIALS AND METHODS: Paraffin-embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E(90)C(600) followed by three cycles of C(600)M(40)F(600) every 2 weeks (DD) or a rapidly cycled tandem high-dose regimen with two cycles of E(90)C(600) every 2 weeks followed by two cycles of E(90)C(3000)Thiotepa(400) every 3 weeks (HD), were available for retrospective central pathological review (116 HD/120 DD). Expression of estrogen receptor (ER), progesterone receptor (PR), MIB-1, epidermal growth factor receptor, and Her-2/neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow-up data and treatment effects by proportional hazard Cox regression models (including interaction analysis). RESULTS: After a median follow-up of 61.7 months, 5-year event-free survival (EFS) as well as overall survival (OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [hazard ratio (HR) = 0.60, 95% CI 0.43-0.85, P = 0.004]; OS: 76% versus 61% (HR = 0.58, 95% CI 0.39-0.87, P = 0.007). In multivariate analysis, HD, tumor size <3 cm, positive PR, negative MIB-1 staining, and grade 1/2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative (ER/PR/Her-2/neu) and G3 tumors derived most benefit from HD. CONCLUSION: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple-negative tumors and/or G3 with their poor prognostic marker profile.     

Quality control in ambulatory health care. Results of an area-wide study by the public medical service of the Baden-Württemberg health insurance

Discussions surrounding the quality of nursing care, fueled by recurring press reports, prompted the State Nursing Insurance Associations in Baden-Wuerttemberg to request the Health Insurance Medical Service to perform a quality control of outpatient nursing care services in the state. Based on a coordinated concept and for the first time in the Federal Republic of Germany, all authorized ambulatory institutions area-wide were subjected to a uniform assessment (total survey) during an official inquiry time period. The end results of these controls failed to verify the judgement often propagated by the press based on individual cases that high-quality nursing care can no longer be afforded under the present circumstances. On the average, 55% of the personnel provided to patients by outpatient nursing services were health care professionals. What is more, this professional staff rendered 75% of all nursing care services. The evaluation of the accompanied medical visits indicated that the vast majority attempted to take active nursing care into account. With regard to quality assurance, a great optimisation potential was indicated primarily in the area of nursing documentation. Only in about 35% of the nursing documents inspected was the nursing procedure always clearly evident. A future problem could arise from the fact that of all nursing professionals with leadership responsibilities, at the time of the survey only about 37% had completed the requisite professional training qualification programme of 460 training hours. If the time before the interim deadline (March 31, 2002) is not utilised, the institutions in question could face consequences that could threaten their very existence. It is evident that a large number of outpatient nursing care services in the state of Baden-Wuerttemberg do not have their economic foundation in the domain of the Nursing Care Insurance Law, which affects both patient structure and care intensity. As a consequence, there is no quality control or inspection whatsoever for the majority of nursing care services rendered by ambulatory nursing care services at present because they are not under the jurisdiction of the German Federal Social Legislation SGB XI.     

The reality of mammography utilization in the state of Arkansas

The Arkansas Mammography Data Collection Project, funded by the Arkansas Department of Health, aimed to determine the mammography screening patterns throughout the state of Arkansas. Data were obtained from 92 mammoraphy centers out of 112 centers (82%). A total of 157,976 mammography data sets were obtained for 148,586 women. Mammography rate was 22.7% for women 40 years and older and 24.1% for women 50 years and older. Mammography rates per county varied from 0.3% to 42.6%. The overall low rate of mammography utilization reflects the need to intensify public health interventions and continuous evaluations of these interventions.