[Paget disease of the vulva: resolution after local treatment with imiquimod--report of a case and review of the literature]. / Morbus Paget der Vulva: Remission durch Lokalbehandlung mit Imiquimod--Fallbericht und Literaturübersicht.

Paget disease is a rare disorder of the skin of the vulva, comprising less than 1% of vulvar neoplasms. Surgical excision is considered the standard of care. While the invasive variant of Paget disease is rare, frequent local recurrences from non-invasive disease, which are inoperable, constitute a major clinical problem. In this article we report on a 71-year-old patient with recurrent disease treated successfully with imiquimod cream. Symptoms such as local itching subsided shortly after initiation of treatment. Four weeks later, first signs of resolution could be demonstrated colposcopically. Within 8 weeks, complete clinical remission was achieved. Thus, topical imiquimod is not only effective as treatment of vulvar intraepithelial neoplasia, but may also be used for selected patients with recurrent Paget disease as an alternative to repeat surgical interventions.

[Comparison of the ThinPrep monolayer technique and conventional cervical Pap smears in a high-risk population using the Munich II nomenclature]. / Vergleich der ThinPrep-Dünnschichtzytologie mit der konventionellen zervikalen Exfoliativzytologie in einem Risikokollektiv unter Verwendung der Münchener Nomenklatur II.

OBJECTIVE: In this prospective study using the Munich II nomenclature for cervical cytology. Pap smear results obtained by the ThinPrep monolayer technique and those obtained by the conventional method were compared. METHODS: Pap smears were obtained from 1,000 women using an Ayre spatula/endocervical brush combination. Following transfer of the cell sample onto a slide, the same collection devices were rinsed in a liquid medium and processed using ThinPrep-2000 processor (split-sample technique). RESULTS: Specimen inadequacies due to drying artefacts, cell overlap or low number of epithelial cells were rare with both methods without any significant differences. However, ThinPrep slides were significantly less often compromised by red or white blood cells or by cytolysis. In contrast, endocervical cells were missing in 11.6% of slides compared to only 2.3% in conventional Pap smears. ThinPrep yielded results of unknown significance (Pap III) significantly less often (4.2 vs 6.3%). CONCLUSIONS: ThinPrep slides are less frequently compromised by blood components or cytolysis. Inconclusive results of Pap III are slightly less frequent when using ThinPrep. However, there is a significant percentage of slides lacking the endocervical component. Using a combination of spatula and cytobrush, this may not necessarily be due to non-representative cell sampling.

Prevalence of human papilloma virus infection in women in rural Ethiopia.

In Ethiopia cervical carcinoma is the most frequent cancer in women. HPV infection is a prerequisite for this disease. However, to date there have been no data on human papilloma virus (HPV) prevalence in Ethiopia. Outpatients attending Attat hospital in rural Ethiopia were examined for the presence of HPV DNA using the Digene HPV test. 15.9% of patients were found to be HPV positive. The proportion of HPV high risk types was 13.2% [age-standardised rates: HPV: 14.4% (95% CI: 8.5-20.2); HPV high risk: 11.6% (95% CI: 6.3-16.9)]. Compared to other countries HPV prevalence is high, especially of high risk types. Until vaccination programmes take effect, screening programmes should not be based on HPV testing alone as this will lead to significant overtreatment of healthy women.

[Management of gynecological tumors associated with BRCA1 and BRCA2 germline mutations. Case report and literature review]. / Management dei tumori ginecologici associati a mutazioni germinali BRCA1 e BRCA2. Caso clinico e review della letteratura.

Genetic investigation of BRCA1 and BRCA2 germline mutations is, nowadays, a diagnostic procedure with practical clinical applications. The role of this genes in DNA repair and stability and in cancer development is now well recognised. Most involved are breast and ovarian cancers, but, less frequently, other gynecological cancers like cervical, corpus uteri and Fallopian tubes cancers and also other non gynecological malignancies. We report the case of a 67-year-old patient with strong familiarity for breast cancer, with a BRCA2 germline mutation, who developed in 30 months 4 primary malignancies: in chronological order, breast cancer, chronic lymphatic leukemia, and synchronous ovarian and endocervical adenocarcinoma. A better knowledge of the biological and clinical behaviour of BRCA related cancers is of strategical importance in the management of patients with strong familiar neoplastic history or with genetic test positivity. An adequate counselling can help in the management of these cancers in the prevention and early diagnosis taking also into consideration the possibility of a prophylactic surgery.

Outcome of surgical intervention for rectoneovaginal fistulas in Mayer-Rokitansky-Kuester-Hauser syndrome.

Creation of a neovagina to treat vaginal atresia or aplasia in Mayer-Rokitansky-Kuester-Hauser syndrome must always be followed by long-term application of dilators to avoid shrinkage. However, rectoneovaginal fistulas are caused by chronic alteration and consecutive necrosis of the posterior neovaginal wall. We evaluated retrospectively the postoperative outcome of rectal wall and neovaginal reconstruction using a standardized surgical technique in an exclusive collection of women. Eight women with a mean age of 28 years (range 22-31 years) were treated for rectoneovaginal fistulas in our clinic. Preoperatively, proctoscopy, sphincter manometry, endoluminal rectal ultrasonography, and colonoscopy were performed; and regular postoperative follow-up by digital examination and rectoscopy were obligate. The standard surgical procedure via a perineal approach included fistulectomy and closure of the mucosa and rectal wall followed by a levatorplasty. All but one woman had a temporary colostomy. After 2 weeks the patients were allowed to wear vaginal dilators of a smaller size. Within the mean follow-up period of 20 months, reintervention was necessary twice because of late fistula relapse detected by proctoscopy, barium enema, and subjective symptoms. Morbidity was 25% (n = 2) due to secondary superficial wound healing or urinary tract infection. The average time of the hospital stay was 13 days (10-14 days). One patient complained of vaginal shrinkage and underwent local estrogen therapy with a good functional result 3 months later. Proper fistulectomy and surgical reconstruction with interpositioning of well perfused muscle layers achieved good functional outcome with an acceptable number of minor morbidities. Local estrogen treatment is helpful for avoiding scarification and decreasing the neovaginal size.

Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use.

AIMS: This study was performed to test the validity of different methods for determining the status of the erbB-2/HER-2 oncogene in breast cancer tissues for diagnostic use. METHODS AND RESULTS: Forty formalin-fixed, paraffin-embedded breast carcinomas were investigated by fluorescence in situ and comparative genomic hybridization (FISH, CGH) as well as by immunohistochemistry (IHC) using Dako-HercepTest and CB11 antibody (Ventana). Additionally, competitive-differential polymerase chain reaction (cdPCR) was performed on frozen samples to estimate gene dosage alterations of erbB-2/HER-2. Amplification was detected in 12-23% and protein overexpression in 16-68% of the cases, depending on the methodology and/or the reagent used. Perfect concordance (100%) was found between the results of cdPCR and CB11-IHC, and a 97% concordance between FISH and CB11-IHC. The concordance between Dako-HercepTest and CB11-IHC was 78%: seven of eight 2+ carcinomas with the Dako-HercepTest were classified as nonamplified using FISH. CONCLUSIONS: Our results indicate that high-level expression as well as normal erbB-2/HER-2 status of breast carcinomas can be detected reliably both by IHC and gene dosage assessment in paraffin material for diagnostic use. However, borderline results, especially those with 2 + immunopositivity, should be interpreted with caution and increased emphasis should be given to other clinical and prognostic information available.

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma.

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.

Blood-borne cancer cells--quo vadis?

The detection of blood-borne cancer cells may help in clinical staging and further understanding of cancer metastasis. We developed a cytokeratin-based immunomagnetic method to isolate epithelium-derived cells from the circulating blood of patients. The number of cell clusters positive for cytokeratin/prostate-specific antigen (PSA) from the peripheral blood of prostate cancer patients and cytokeratin/p185c-erbB-2 from the peripheral blood of breast cancer patients has been related to stage of the disease. Breast cancer patients who presented cytokeratin/p185c-erbB-2-positive cell clusters showed a decrease in such cells under adriamycin adjuvant therapy with Further molecular characterization by a highly sensitive microsatellite multiplex-PCR enabled reproducible detection of microsatellite alterations. The impact of these individually targeted results may contribute to an individual diagnostic and therapeutic strategy.

Recurrent rectoneovaginal fistula caused by an incidental squamous cell carcinoma of the neovagina in Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: Mayer-Rokitansky-Küster-Hauser syndrome is a congenital malformation characterized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract but functional ovaries. Surgical correction requires the creation of a neovaginal canal by the performance of a neovaginoplasty and an accurate long-term application of an artificial phallus phantom to avoid secondary shrinkage of the canal. Due to the chronic alteration of the posterior neovaginal wall, ulcers and consecutive fistulae may occur. We report the clinical course of a female who required surgical intervention for a rectoneovaginal fistula and developed a recurrence of the fistula due to one of the extremely rare squamous cell carcinomas of the neovaginal epithelium in order to show potential diagnostic and therapeutic features. METHOD: The systematic report of a case is presented. RESULT: Almost 13 years following the initial construction of a neovagina the patient developed a single-tract rectoneovaginal fistula. After surgical repair she represented with a recurrence due to a vast squamous cell carcinoma of the former operation site. Tumor en bloc resection was performed and currently (follow-up: 4 months) she has no signs of new tumor progression. CONCLUSION: Creation of a neovagina is the standard procedure for treating vaginal atresia or aplasia. Because of the long clinical course postoperatively, complications may occur. This report of a case of a malignant transformation in neovaginal epithelium shows the potential risk of malignancy and underlines the necessity of a close follow-up.

[Optimizing performance documentation in gynecology--assistance from the internet]. / Optimierung der Leistungsdokumentation in der Frauenheilkunde--Hilfestellungen aus dem Internet.

The documentation of operations in the field of gynecology and obstetrics is regulated by social laws in Germany. Only by optimal encoding of diagnoses and procedures an efficient cashing with the health insurance's can be achieved. This requires profound knowledge of the invoice modalities and usually support by computer systems. The Internet offers in this respect some assistance, which in the following is pointed out and evaluated critically.

Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44.

AIMS: This study was performed to investigate whether immunohistochemical expression of E-cadherin (E-cad) and beta-catenin (beta-cat) in conjunction with CD44 may correlate with the clinical evolution and prognosis of breast cancer. METHODS AND RESULTS: One-hundred and forty-two routinely processed breast tissue samples including normal breast, benign lesions, in situ and invasive carcinomas were investigated. E-cad and beta-cat were strongly expressed by luminal and basal cells in normal glands, benign proliferative and early neoplastic intraductal lesions. Contrarily, CD44 was expressed exclusively by myoepithelial cells in normal breast, whereas different isoform expression patterns were observed in premalignant and malignant lesions. Simultaneous lack of E-cad/beta-cat expression was detected in in situ and invasive lobular carcinomas in contrast to ductal lesions, in which the differential loss of the molecules was associated with poorer differentiation, irrespective of CD44 immunophenotype. Reduced E-cad (P = 0.003), beta-cat (P = 0.03) and increased CD44v4 (P = 0.005) and v7 (P = 0.007) expression were significantly associated with positive lymph node status. Decreased E-cad and lack of CD44v6 expression correlated with poor survival. There was no difference between the expression of either molecule in in situ and invasive components within the same tumour. CONCLUSIONS: Our results indicate that changes in E-cad, beta-cat and CD44 expression occur early in breast carcinogenesis; they are involved in tumour differentiation, but events additional to their deranged expression are needed to acquire an invasive phenotype.

[The millenium switch on 01 January 2000--a foreseeable crash for gynecologic and obstetrical software applications?]. / Der Jahrtausendwechsel am 01.01.2000--ein absehbarer Crash für gynäkologische und geburtshilfliche Softwareapplikationen?

The switch to the new millennium causes greater difficulties in computing concerning hard- and software. It is not foreseeable how much each computer will be hit by that. Due to the common use of computers in all parts of medicine the possible crash of data banks and networks across hospitals could afflict the regular care of patients in wards and outpatient clinics. The ability of each computer to go to the new millennium can be checked by simply performed tests or by highly specialized programmes as well. As many mistakes occur in co-operation of hardware and software, it is hard to fix the system. To continue the use of a data bank it is necessary to change the data bank's date format and all applications at the same time. Programmers and providers offer their advice via internet.

Isolation of blood-borne epithelium-derived c-erbB-2 oncoprotein-positive clustered cells from the peripheral blood of breast cancer patients.

Clinical studies including thousands of breast cancer patients have shown that c-erbB-2 is amplified and overexpressed in 20-30% of invasive human breast cancers and that it is associated with distant metastasis in specified patient subgroups. To isolate and characterize hematogeneously spreading c-erbB-2-positive epithelium-derived cells from the peripheral blood of breast cancer patients, a combined buoyant density gradient and immuno-magnetic separation method has been used. The method utilizes a biotinylated anti-cytokeratin monoclonal antibody (MAb) for capturing the epithelium-derived cells. The expression of c-erbB-2 by the captured cells was detected using an anti-c-erbB-2 rabbit antibody (21N) coupled to an anti-rabbit gold-labeled anti-body, whereby immunoenzymatic cytokeratin staining was performed using a silver-enhanced immunogold double staining protocol. In total, 29 of the 46 patients tested had either cytokeratin (24/29) or cytokeratin/c-erbB-2 (19/29) positive clustered cells in their peripheral blood. We thus report here the presence and the frequency of clone-specifically stained clustered cells in the peripheral blood of breast cancer patients. The frequency of cytokeratin/c-erbB2 double-positive clustered cells in the peripheral blood was on average 10 times higher than that of double-positive single cells. The numbers of cytokeratin/c-erbB-2 double-positive clustered cells were positively correlated with the stage of tumors. Results of in vitro motility experiments using single and clustered cells from primary breast cancer tissue strongly support the assumption that cytokeratin/c-erbB-2 double-positive clustered cells have a high potential for locomotion. We suggest that blood-borne epithelium-derived c-erbB-2-positive clustered cells are the possible precursor cells responsible for the formation of distant metastases and bone marrow micrometastases.

[Congress organization and the internet--new structures in scientific communication for gynecology?]. / Kongressorganisation und Internet--Neue Strukturen der wissenschaftlichen Kommunikation für die Frauenheilkunde?

For decades scientific sessions and conferences were a proven way to spread and exchange scientific results worldwide--not only in the field of medicine. With growing availability and accessibility of information on the internet and WWW conferences are now not only listed and announced on a multitude of websites, but also are prepared ahead from simple registration to online discussions. By means of selected examples information is provided on how keeping oneself informed about former or planned conferences by using the internet.

[Friedrich Rumpf and his contributions to modern gynecologic surgery]. / Friedrich Rumpf und seine Beiträge zur modernen gynäkologischen Chirurgie.

The German gynecologist Friedrich Rumpf from Berlin performed the first radical hysterectomy in Europe. This pioneering achievement is even more remarkable as Rumpf was working in private practice without the support of one of the major Berlin university hospitals. Very few biographical data can be found. Fortunately, his views of gynecologic surgery are expressed in his publications. This aim of this article is to remind us of Rumpf's reflections on surgical technique which are still relevant today and to contribute to Rumpf's memory.

[Rhesus prophylaxis--history and current status]. / Die Rhesusprophylaxe--Geschichte und aktueller Stand.

The varying symptoms of rhesus incompatibility were recognized and described approximately sixty years ago. Jörg Schneider, then at the Freiburg University Hospital in Germany, had been the very first investigator to perform rhesus prophylaxis in pregnant women. The exact date of this achievement is August 9, 1963. One year later, Schneider could report on nine women, who-following delivery of a rhesus-positive child-did not develop rhesus antibodies during a subsequent pregnancy with a rhesus-positive fetus. Since the late sixties, rhesus prophylaxis has been an integral part of prenatal care in Germany. In the meantime, the role of ante-partum prophylaxis has also been established. Since the introduction of post-partum rhesus prophylaxis, fetal morbidity and mortality has been reduced by 90 percent.

[The internet--new information sources on reproductive medicine?]. / Das Internet--Neue Informationensquellen zur Reproduktionsmedizin?

Within the last two years Internet pages have become a highly interesting source of up-to-date information. The scientific value of those homepages for reproductive medicine differ in a wide range. The Internet still remains a very interesting source for up-to-date information covering the field of infertility treatment with a growing influence on patient decisions and with increasing economical impact.