Implementation of quality indicators for vulvar cancer in gynaecological cancer centres certified by the German Cancer Society (DKG).

Purpose: In 2018, the first guideline-based quality indicators (QI) for vulvar cancer were implemented in the data-sheets of certified gynaecological cancer centres. The certification process includes guideline-based QIs as a fundamental component. These indicators are specifically designed to evaluate the level of care provided within the centres.

[Interdisciplinary S2k guidelines on the diagnosis and treatment of vaginal carcinoma and its precursors-recommendations on surgical pathology for histopathological workup, diagnostics, and reporting].

Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer.

Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018).

This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited.

Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015.

This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals.

Characterization of squamous cell cancers of the vulvar anterior fourchette by human papillomavirus, p16INK4a, and p53.

Objective: The incidence of vulvar squamous cell carcinomas located between the clitoris and urethra in young women is rising in distinct geographic regions, but characteristics of the tumors indicating certain carcinogenic mechanisms are unknown. The present study aimed at characterizing these vulvar cancers for their human papillomavirus (HPV), p16(INK4a), and p53 status, revealing potential pathways of carcinogenesis.

Materials And Methods: Squamous cell vulvar cancers of the anterior fourchette were retrospectively collected from 8 German hospitals, with additional squamous cell cancers located at other sites of the vulva from 2 of the hospitals.

[Pathoanatomical preparation and reporting of specimens from precancerous lesions and carcinomas of the vulva].

On the basis of varying morphology and pathogenesis, two types of vulvar intraepithelial neoplasias (VIN) have been defined: the common type (approximately 98%), classic VIN, is characterised by strong association to high-risk HPV infection (up to 90%), occurrence at younger age (median age 30-40 years) and multifocality. The differentiated (or simplex) type is rare (1%-2%) and is associated with older age (median age 65 years) and p53 alterations. It is usually diagnosed in combination with vulvar (keratinizing) squamous cell carcinoma.

Red blood cells express a functional endothelial nitric oxide synthase.

The synthesis of nitric oxide (NO) in the circulation has been attributed exclusively to the vascular endothelium. Red blood cells (RBCs) have been demonstrated to carry a nonfunctional NO synthase (NOS) and, due to their huge hemoglobin content, have been assumed to metabolize large quantities of NO. More recently, however, RBCs have been identified to reversibly bind, transport, and release NO within the cardiovascular system.

[Recommendations for the handling and oncologic pathology report of lymph node specimens submitted for evaluation of metastatic disease in gynecologic malignancies].

The nodal status is one of the strongest prognostic factors in gynecologic malignancies. Metastatic involvement of regional and distant lymph nodes represents the selection basis for adjuvant therapy in a large number of solid neoplasms. The number of resected lymph nodes is one of the most important parameters in the quality control of the surgical procedure, in particular with respect to radicality.

[Vulvar carcinoma. Diagnosis and therapy].

Vulvar cancer is a rare entity. It appears mostly in older women aged 70-79 years with a slow tendency to younger age. More than 90% of the tumors show a squamous differentiation.

Antitumor effect of MAb EMD 55900 depends on EGF-R expression and histopathology.

The proliferative stimulus of the epidermal growth factor (EGF) in human epithelial cells is mediated by its binding to the external domain of the EGF receptor (EGF-R). The purpose of this study was to investigate whether growth arrest of tumors treated with anti-EGF-R MAb (EMD 55900) was dependent on EGF-R expression and distinct histopathologic criteria of those neoplasms. Nine different adenocarcinomas, squamous cell carcinomas and two neoplastic epithelial cell lines (A431 and Detroit 562), which were characterized by high EGF-R expression, were xenotransplanted onto NMRI-nu/nu mice and treated with an anti-EGF-R antibody (EMD 55900).

A novel 7-transmembrane receptor expressed in nerve growth factor-dependent sensory neurons.

This study reports on the full-length cDNA cloning of a gene identified on the basis of its preferential expression in nerve growth factor, compared with neurotrophin-3-dependent neurons. It encodes a putative 7-transmembrane polypeptide that is distantly related to other members of the G protein-coupled receptor superfamily. Unique features of this receptor include a very long carboxy-terminal tail of 360 amino acids and a specific expression pattern in the chick peripheral nervous system, including nerve growth factor-dependent sensory and sympathetic neurons, as well as enteric neurons.

Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons.

Neurotrophins influence the epigenetic shaping of the vertebrate nervous system by regulating neuronal numbers during development and synaptic plasticity. Here we attempt to determine whether these growth factors can also regulate neurotransmitter plasticity. As a model system we used the selection between noradrenergic and cholinergic neurotransmission by paravertebral sympathetic neurons.

[Reconstructive surgery of the efferent urinary tract in pelvic exenteration of gynecological tumors].

In locally advanced or recurrent tumors of the female genital tract anterior or total exenteration may be mandatory in case of tumor invasion into the lower urinary tract or if a second course of radiation therapy is not feasible. The management of resection and reconstruction of the affected lower urinary tract has to be well integrated into the gynecological therapeutic concept. In 11/32 patients the reconstruction of the partially resected lower urinary tract was feasible with preservation of a functionally intact urinary bladder.

[Pelvic exenteration from the surgical viewpoint].

Pelvic exenteration (PE) is associated with specific problems in the indication of excision and reconstructive surgery. Indication are colorectal cancer or cervical cancer recurrence. In each case intensive and early cooperation of gynecologist, surgeon and urologist is warranted.

[Tumor risk consultation for predisposed women from high risk cancer families].

Germline mutations of the cancer susceptibility genes BRCA1 and BRCA2 seem to lead to a very high risk for breast and/or ovarian cancer. Therefore, genetic counselling and identification of high-risk families may be essential to offer the opportunity to participate in a specific early cancer detection program and to provide individualized psychological support. In a two year period (August 1994-August 1997) 304 consultees present for genetic counselling at the interdisciplinary cancer genetic clinic (Department of Obstetrics & Gynecology and Human Genetics, Heinrich-Heine-Universität, Düsseldorf).

[Relative indicators for disease outcome in breast carcinoma].

Tumor size, axillary nodal status, histologic grading and the hormonal receptor status are the established prognostic factors for breast carcinoma. Concurrent to these factors the clinical validation of the new innovative tumor characteristics from molecular biology is difficult to achieve. Clinicians are more and more interested in indicators of response to particular treatments (predictive factors) and less in prognostic factors relevant for the natural course.

Identification of genes differentially expressed by nerve growth factor- and neurotrophin-3-dependent sensory neurons.

The neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT3) support the survival of subpopulations of primary sensory neurons with defined and distinct physiological characteristics. Only a few genes have been identified as being differentially expressed in these subpopulations, and not much is known about the nature of the molecules involved in the processing of sensory information in NGF-dependent nociceptive neurons or NT3-dependent proprioceptive neurons. We devised a simple dorsal root ganglion (DRG) explant culture system, allowing the selection of neuronal populations preferentially responsive to NGF or NT3.

int-2 and c-erbB-2 gene amplification detected in 70 frozen human breast carcinomas by quantitative polymerase chain reaction.

Gene amplification is a common mechanism of proto-oncogene activation and contributes to tumor progression. Analysis of such genetic alterations is relevant to our understanding of tumor genetics and can provide prognostic information for the patients. A rapid, non-radioactive approach based on qdPCR and fluorescent DNA technique was applied for determination of int-2 and c-erbB2 gene amplification and correlated with other prognostic factors in 70 breast cancer samples.

Multistep carcinogenesis of breast cancer and tumour heterogeneity.

Breast cancer emerges by a multistep process which can be broadly equated to transformation of normal cells via the steps of hyperplasia, premalignant change and in situ carcinoma. The elucidation of molecular interdependencies, which lead to development of primary breast cancer, its progression, and its formation of metastases is the main focus for new strategies targetted at prevention and treatment. Cytogenetic and molecular genetic analysis of breast cancer samples demonstrates that tumour development involves the accumulation of various genetic alterations including amplification of oncogenes and mutation or loss of tumour suppressor genes.

Detection of sequential genetic alterations relevant for breast cancer development.

Breast cancer emerges as a multistep process with transformation of normal cells via steps of hyperplasia, premalignant change and in situ carcinoma. Cytogenetic and molecular genetic analyses of breast cancer samples indicate that tumour development involves the accumulation of various genetic alterations, including amplification of oncogenes and mutation or loss of tumour suppressor genes. Microdissection of histological sections is needed to correlate the specific histological change and the genetic alteration.

Early cancer detection programmes for women at high risk for breast and ovarian cancer: a proposal of practical guidelines.

Women from families with multiple breast and/or ovarian cancers may be at increased risk to develop breast/ovarian cancer themselves. Due to personal experience with family members having these diseases they are anxious and ask for specific prophylactic measurements or treatment. The detection of two susceptibility genes, BRCA1 and BRCA2, has given insight into the genetic background of part of the familial breast/ovarian cancer syndromes.

Expression analyses of epidermal growth factor receptor and HER-2/neu: no advantage of prediction of recurrence or survival in breast cancer patients.

The overexpression of two members of the erbB oncogene family-the epidermal growth factor receptor protein (EGF-R) and the HER-2/neu protein-in breast cancer has been investigated by numerous authors. Their exact role in breast cancer is still not defined. The simultaneous investigation of EGF-R and HER-2/neu in the same study population has only rarely been performed in breast cancer.

pS2 protein detected by immunohistochemistry in archival primary breast cancer.

It has been proposed that pS2 protein in breast cancer provides information on the individual prognosis and biological properties of the tumor with respect to response to endocrine treatment. In this retrospective study the pS2 protein expression was detected by immunohistochemistry in formalin-fixed, paraffin-embedded breast cancer sections from 219 patients with primary breast cancer. The data were compared with patients' age, disease stage and tumor grading tumor estrogen and progesterone receptor status, disease-free interval and overall survival.

Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer.

The development of familial and sporadic breast cancer is based on genetic alterations of tumour-suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation. To investigate LOH of BRCA1 (17q21) and BRCA2 (13-q12-13) in sporadic breast cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for detection of microsatellite polymorphisms was applied. A total of 137 breast cancer and 15 benign breast specimens with matched normal tissue were examined.

Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system.

An early step in the formation of the extraembryonic and intraembryonic vasculature is endothelial cell differentiation and organization in blood islands and vascular structures. This involves the expression and function of specific adhesive molecules at cell-to-cell junctions. Previous work showed that endothelial cells express a cell-specific cadherin (vascular endothelial [VE]-cadherin, or 7B4/cadherin-5) that is organized at cell-to-cell contacts in cultured cells and is able to promote intercellular adhesion.