Cervical biopsies and cytological smears - a comparison of sample materials in HPV diagnostics.

BACKGROUND: Cervical cancer is causally related to cervical infections by oncogenic human papillomavirus (HPV) genotypes. To improve the quality of diagnosis evaluation of screening methods and their HPV type detection rate is an important part for this item. OBJECTIVES: Two different cervical specimens of the same patients were analysed simultaneously with molecular HPV subtyping methods to find the most sensitive sample material for cervical cancer screening. STUDY DESIGN: Biopsy specimens and cytological smears of the cervix of 443 patients were analysed for human papilloma virus (HPV) subtyping by a macroarray from Chipron, Germany, which allows a differentiation of 16 high and 16 low risk types. Results were compared for reliability and differences were studied. RESULTS: Both sample material groups showed HPV conformity of 70%, 23% more subtypes could be detected in smears in contrary to biopsies but only 6% vice versa. 14 biopsies and 7 smears were HPV negative although the concerning second sample type of the patients was HPV positive. HPV 16 as one of the most relevant subtypes in cervical cancer pathogenesis was missed in the biopsies' group with 34.3% out of 35 HPV 16 positive smear cases, whereas only one smear failed to discover this subtype contrariwise. CONCLUSION: Comparison of the examination results shows that subtyping of smear samples is able to detect more subtypes than by biopsy specimens. The probability to underdiagnose HPV 16 and to get a false negative result in bioptic sample material favours smear as method of choice for HPV subtyping.

Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) guideline for prophylaxis with granulocyte colony-stimulating factors (G-CSF) in gynecologic malignancies, including breast cancer.

The current knowledge and recommendations on the clinical use of granulocyte colony-stimulating factors (G-CSF) in gynecologic cancers including breast cancer, along with the clinical experience of the members of the working group of the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO), have been summarized. G-CSF is either administered as primary or secondary prophylaxis of febrile neutropenia. The term "primary prophylaxis" denotes the prophylactic use of G-CSF as early as during the first cycle of a new chemotherapeutic regimen. Secondary prophylaxis, on the other hand, defines the use of G-CSF after development of grade 4 neutropenia or febrile neutropenia in a preceding cycle of a particular chemotherapeutic regimen. When chemotherapy regimens are associated with a > 20 % risk of febrile neutropenia such as TAC (docetaxel-doxorubicin-cyclophosphamide), primary prophylaxis with G-CSF is indicated. When chemotherapy regimens are associated with a 10-20 % risk of febrile neutropenia, the decision for primary prophylaxis with G-CSF is based upon patient-related risk factors such as age > 65 years, previous cytotoxic treatment(s) and/or radiation therapy, preexisting tumor-related neutropenia or bone marrow involvement, preexisting neutropenia, infections/open sores, reduced Karnofsky performance status/WHO performance status and reduced nutritional status, advanced malignant disease, history of prior febrile neutropenia, impaired kidney function, and hepatic failure particularly with hyperbilirubinaemia. The patient's individual overall febrile neutropenia risk should be assessed prior to each chemotherapy cycle.

Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy.

Intratumoral immune cells and ERCC1 expression are likely to play a role in the response of ovarian carcinoma to chemotherapy, but their impact on therapy outcome is still unclear. Therefore, 41 cases of optimally resected high grade serous ovarian carcinomas were examined retrospectively for stromal and intraepithelial lymphocyte populations and ERCC1 status in relation to response to platinum-based therapy. Based on RECIST criteria, 27 patients were classified as responsive and 14 as therapy resistant, respectively. Using immunohistochemistry for CD3, CD8, CD4, TIA1, MUM1 and FOX P3 on representative tumor sections, we quantitatively evaluated the intratumoral density of lymphocyte subpopulations. In addition, ERCC1 protein and mRNA expression were determined by immunohistochemistry using the Steffensen score and quantitative RT-PCR, respectively. Furthermore, ERCC1 SNP's C8092A and codon 118 were analysed. Response to chemotherapy was significantly associated with higher numbers of stromal CD3+ (mean 21.33 lymphocytes/HPF versus 8.21 lymphocytes/HPF, p = 0.002) and CD8+ lymphocytes (mean 9.22 lymphocytes/HPF versus 4.57 lymphocytes/HPF, p = 0.013). Counts of intraepithelial CD3+ and CD8+ lymphocytes, stromal and intraepithelial FOXP3+ and TIA1+ cells, CD4+ lymphocytes, and MUM1+ plasma cells did not reach statistical significance. Neither ERCC1 protein expression (p = 0.232) nor SNPs codon 118 and C8092A of the ERCC1 gene (p = 0.269 and p = 0.543) showed an association with therapy response. The same was true for ERCC1 mRNA levels (p = 0.896), probably due to intratumoral lymphocyte contamination. In conclusion, the density of CD3+ and CD8+ T-cells in tumor stroma proved to be a significant predictor for response to platinum-based therapy, whereas examination of ERCC1 failed to identify therapy-responsive patients.

Lymphoepithelioma-like carcinoma of the vulva, an underrecognized entity? Case report with a single inguinal micrometastasis detected by sentinel node technique.

This report describes an unusual EBV-negative lymphoepithelioma-like carcinoma of the vulva in a 73-year-old patient. The lesion was localised at the right minor labium and was resected by partial vulvectomy. A synchronous sentinel lymph node biopsy revealed a single micrometastasis in the right inguinal region, which prompted local radiotherapy. Follow-up nine months later showed only slight vulvar atrophy, without signs of local recurrence or distant metastases.Although lymphoepithelioma-like carcinomas of the skin and the female genital tract are presumed to have a better prognosis than their counterparts in the upper aerodigestive tract, possibly due to earlier detection and therapy, this case documents their potential for early metastasis.

Clinical consequences of the Calypso trial showing superiority of PEG-liposomal doxorubicin and carboplatin over paclitaxel and carboplatin in recurrent ovarian cancer: results of an Austrian gynecologic oncologists' expert meeting.

The Calypso trial showed an improved progression-free survival with PEG-liposomal doxorubicin (PLD) and carboplatin (P) as compared with the standard regimen paclitaxel (PCLTX) and P in the second- or third-line treatment of platinum-sensitive epithelial ovarian cancer [1]. A panel of Austrian gynecologic oncologists discussed the clinical consequences of the data from the Calypso study for the routine practice. PLD + P had a significantly lower rate of alopecia and neuropathy than the taxane regimen, both toxicities which compromise the quality of life. Due to possible significant thrombocytopenia, the blood counts of patients undergoing PLD + P therapy should be monitored weekly. Patients receiving PLD/P are at higher risk of nausea and vomiting. Palmoplantar erythrodysesthesia (hand-foot syndrome) is a significant toxicity of PLD + P most prevalent after the third or fourth cycle. Prophylaxis consists of avoiding pressure on feet and hands and other parts of the body. Similarly, prophylaxis of mucositis seems important and includes avoiding consumption of hot, spicy and salty foods and drinks. Mouth dryness should be avoided. Premedication with antiemetics and dexamethasone dissolved in 5% glucose is done to prevent hypersensitivity to PLD. In conclusion, the therapeutic index is more favorable for PLD + P than for PCTX + P.

Visualization of the endopelvic fascia by transrectal three-dimensional ultrasound.

The aim of our pilot study was to explore the feasibility of visualizing the endopelvic fascia by transrectal three-dimensional (3D) ultrasound. Transrectal 3D ultrasound was performed in 12 nulliparous women and 11 women with a history of vaginal delivery. A 6-10 MHz volume probe was used to examine the suburethral anterior vaginal wall. In all women, an echogenic layer was identified at an average of 3-5 mm from the vaginal surface. This echogenic layer was found to be contiguous to the lateral pelvic sidewall and uninterrupted in 10 of 12 nulliparous women, whereas gaps in this layer were identified in all 11 parous women. We hypothesize that this echogenic layer may represent the suburethral component of the endopelvic fascia. Depending on the number and localization of the interruptions in this echogenic layer, the mechanical support of the pelvic floor seems to be weakened corresponding to a higher incidence of descensus of the anterior vaginal wall, which frequently was associated with urinary incontinence.