S. Ackermann

Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions.

OBJECTIVE To investigate whether it is possible to use detection of the human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). STUDY DESIGN Pap smears from 279 women in whom CIN 1 and CIN 2 had been diagnosed by cytology and histology, who were known to have a high-risk HPV status and had a median follow-up of 25 months, were immunohistochemically stained for the HPV L1 protein. The staining results were correlated with the clinical course of the disease. RESULTS HPV L1-positive patients showed regression in 49.1% of cases, stable disease in 41.5%, and progressive disease in 9.4%, whereas HPV L1-negative women had progression in 25.9% of cases (regression 33.3%, stable disease 40.7%; p=0.001). The effect was clearest in the group under 30 years of age. HPV L1-negative patients experienced progression significantly more often than women with a positive HPV L1 test (odds ratio 3.391). CONCLUSIONS HPV L1-positivity was found to have prognostic significance in relation to disease progression in women with CIN 1 and CIN 2 and particularly in those less than 30 years of age.

Awareness of general and personal risk factors for uterine cancer among healthy women.

Participation rates in gynaecological cancer screening are influenced by different factors. The knowledge of general and personal risk factors for uterine cancer among women might influence their interest in gynaecological cancer screening. Two thousand nine hundred women in 23 gynaecological outpatient services were invited to answer a structured questionnaire regarding general and personal risk factors for cervical and endometrial carcinoma; 2108 women participated. Women with a history of cancer were excluded from the study. It was found that levels of knowledge about uterine carcinoma were low. Only 47.4% of women knew the difference between the sites of origin of cervical and endometrial cancer. Seventy-seven per cent of participants assessed their knowledge about uterine malignancies as insufficient; 96.3% would appreciate more information about uterine cancer. Younger women were significantly less well informed than postmenopausal women. Known risk factors such as smoking or human papillomavirus (HPV) infection as factors for cervical cancer were underestimated; most women assessed genetic factors as most important for the development of uterine cancer. The level of information about risk factors as well as general facts about gynaecological cancer in women is low. Ameliorating this lack of information might influence the perception of uterine cancer and result in higher participation rates in gynaecological cancer screening.

Use of intensified early cancer detection in high-risk patients with familial breast and ovarian cancer.

A prospective follow-up study was carried out to evaluate the influence of risk and genetic counselling on use of early cancer detection. Five hundred and fifty-six subjects who fulfilled inclusion criteria for a genetic analysis of the BRCA1/2 genes (the high-risk group A) and 205 who did not fulfil the inclusion criteria (the lower risk group B) attended primary consultation in the interdisciplinary cancer genetic clinic. Information about participation in the early cancer detection programme was documented. Information about changes in use after consultation could be evaluated from 349 women (94 group B and 255 group A). Methods such as monthly self-palpation, breast palpation by gynaecologist, ultrasound of the breast, transvaginal ultrasound and pelvic examination had all been commonly used. Consultees at higher risk used mammography less often than women at lower risk. Magnetic resonance imaging of the breast was used rarely. Most methods were used more often at the recommended interval by women at higher risk during the follow-up period. In conclusion, at present intensified early cancer detection programmes for women at risk provide a less invasive option than chemoprevention or prophylactic surgery. Although the methods are used at high frequency it seems feasible to motivate women at risk to participate. This can be done by providing information and counselling in the cancer genetic clinic.

Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

Introduction Some 5–10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. Methods The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. Results Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. Conclusion Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.

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

Purpose: 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. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

Krebsfrüherkennung bei Frauen

ZusammenfassungEines der Hauptarbeitsgebiete in der frauenärztlichen Praxis ist die Früherkennung bzw. Nachsorge bei Frauen mit Genital- und Mammakarzinom. Grundlage sind die Krebsfrüherkennungsrichtlinien der Bundesärztekammer, die verschiedene Untersuchungsmethoden und deren Einsatz zu bestimmten Alterszeitpunkten beinhalten. Die Anleitung zur Selbstuntersuchung der Mamma, die Tastuntersuchung der Mamma und des inneren Genitales sowie die Zytologie sind hierbei die hauptsächlich eingesetzten Methoden. Die Effektivität des gesetzlichen Krebsfrüherkennungsprogramms ist neben der Sensitivität und Spezifität der eingesetzten Methoden direkt von der Teilnahmerate der Zielpopulation abhängig. Neues Wissen um Karzinominzidenz, Morbidität und Mortalität, Risikomodulatoren und -determinanten, die Definition von Hochrisikofrauen und neuen Untersuchungsmethoden muss in den nächsten Jahren integriert werden. Zusätzlich müssen neue Aufgaben wie zum Beispiel Risikoberatung, Aufklärung über Prävention etc. aufgenommen und als ein Krebsvorsorgeprogramm aufgebaut werden. Nur so ist der immer wichtiger werdende Aspekt eines effektiven Kosten-Nutzen-Quotienten gewährleistet.AbstractIn the daily work early cancer detection for breast and genital cancer and follow-up care of women with these cancer types are important medical tasks. The guideline for early cancer detection of the Bundesärztekammer is applied. It includes the methods applied and the time points of their use. The teaching of self breast assessment, the professional examination of the breasts and the female genital tract and pap smear are the main methods used. Effectivity of the early cancer detection as well as sensitivity and specificity of the methods are in direct correlation to the participation in the early cancer detection program. The knowledge about cancer incidence, morbidity and mortality, risk modulators and determinants, the definition of high risk women and the integration of new methods have to be integrated in the early cancer detection program. In addition new aspects like risk counseling, information about prevention etc. have to be added to form cancer care programs. This is necessary to support the important aspect of effectivity and costs-relation.

Aspects of molecular diagnostics and therapy in obstetrics and gynecology.

Scientific progress and information relating to the theoretical and clinical work being carried out in the field of obstetrics and gynecology has dramatically increased due to recent developments in molecular biology. Molecular obstetrics and gynecology is therefore the link between the different sections in obstetrics and gynecology. At present, the molecular understanding of cellular pathways is much greater than that of the direct integration of molecular diagnostics and therapy in routine clinical practice. The use of molecular diagnostics, such as preimplantation diagnostics or predictive genetic testing, still has technical problems as well as novel, and to date unclear, social, ethical and legal implications. To date, the technical elements of molecular therapy have not yet fulfilled their expectations. In the broad spectrum of obstetrics and gynecology, new molecular discoveries are influenced not only by technical but also by socioeconomic and political considerations. These include, for example, free access to genetic testing, patents for genes and the financial monopoly over molecular medication. Society must propose rules for the potential integration of the knowledge of molecular obstetrics and gynecology into the daily care of those seeking aid or advice.

Comparison of pretreatment assessment of intrauterine tumor spread in endometrial carcinoma using ultrasonography, hysteroscopy, and fractional curettage

Due to their age, patients with endometrial carcinoma are often in an impaired general condition and have other concomitant diseases. To prevent overtreatment or undertreatment, invasive and noninvasive diagnostic procedures such as ultrasonography, hysteroscopy, and fractional curettage were compared with regard to their capacity to assess tumor extent (in) to the cervix. In 75 patients with endometrial carcinoma, the results of transvaginal ultrasonography, diagnostic hysteroscopy, and fractional curettage in assessing tumor spread to the cervix were compared with the final pathology report on the hysterectomy specimen. Cervical involvement was demonstrated in the hysterectomy specimen in 25.3% of the patients (19 of 75). Ultrasound identified evidence of cervical involvement with a sensitivity of 15.8% (3 of 19) and a specificity of 98.1% (53 of 54); hysteroscopy had a sensitivity of 42.9% (6 of 14) and a specificity of 89.5% (34 of 38); and fractional curettage had a sensitivity of 57.9% (11 of 19) and a specificity of 66.1% (37 of 56). None of the procedures on its own is suitable for pretreatment assessment of cervical involvement. However, negative endocervical curettage and hysteroscopical exclusion of cervical infiltration may often identify patients correctly without cervical involvement, thereby avoiding overtreatment.

Vulväre intraepitheliale Neoplasie (VIN)

Vulvare intraepitheliale Neoplasien (VIN) sind uberwiegend plattenepithelial und HPV-assoziiert. Zwei Unterformen werden unterschieden: die HPV-assoziierte uVIN und die seltenere HPV-unabhangige dVIN. Neben der HPV-Infektion gelten Immunsuppression und Nikotinabusus sowie ein Lichen sclerosus als Risikofaktoren. Damit bieten sich die HPV-Impfung und das Nichtrauchen zur primaren Pravention an. Therapieresistente Symptome vermeldet die Halfte der Patientinnen. Die Diagnose kann histologisch zumeist an Stanzbiopsaten gestellt werden. Die Behandlung hat die Entfernung der Lasion im Gesunden zum Ziel. Als wesentliche Verfahren gelten die Exzision und die Laserdestruktion. Bei uVIN konnen Immunmodulatoren lokal in speziellen Fallen eingesetzt werden (“off-label use”). Die Rezidivraten liegen bei 25 %, davon sind etwa 3 % invasiv. VIN-Patientinnen sollen nach der Behandlung regelmasig in einer qualifizierten Nachsorge verbleiben, im besten Fall lebenslang. Als Sonderform einer intradermalen potenziellen Praneoplasie gilt der Morbus Paget der Vulva. Die Therapie bestand uber lange Zeit in der chirurgischen Entfernung der Haut. In neuerer Zeit werden die Lasionen – insbesondere bei wiederholten Rezidiven nach operativer Therapie – erfolgreich lokal mit immunmodulatorischen Substanzen behandelt (“off-label use”).

Invasives Karzinom der Vulva

Vulvakarzinome werden immer haufiger. Als Risikofaktoren gelten HPV-Infektion, Lichen sclerosus und Nikotinabusus. Damit wird ein primarer Praventionseffekt durch die HPV-Impfung erwartet. Eine spezifische Fruherkennungsuntersuchung ist nicht etabliert. Die definitive Diagnose wird histologisch gesichert, in fortgeschrittenen Stadien erfolgt ein Staging durch zusatzliche apparative Diagnostik. Eine Metastasierung in die Leistenlymphknoten ist nicht zu erwarten bei Basalzellkarzinomen und verrukosen Karzinomen und bei Karzinomen mit einer Infiltrationstiefe ≤1 mm. Die Therapie erfolgt uberwiegend operativ. Zumeist erfolgt nach weiter lokaler Resektion ein primarer Wundverschluss, nur bei grosen Resektionen sind plastische Rekonstruktionen erforderlich. Bei multifokalen Primartumoren ist eine Vulvektomie indiziert. Das Lymphknoten-Staging wird durch getrennte Leistenschnitte durchgefuhrt (“triple incision”). Die inguinalen und femoralen Lymphknoten mussen entfernt werden (LNE). Die postoperative Morbiditat der Lymphonodektomie ist hoch, das Sentinel-Verfahren verspricht bessere Vertraglichkeit. Dafur bestehen onkologische Risiken, die sich genau beziffern lassen. Prazise Aufklarung und Abwagung sind unabdingbar.