Persistent infections with high-risk human papillomaviruses (HPVs) induce dysplastic lesions of the lower genital tract. Some of these lesions eventually progress to invasive cancers, particularly of the uterine cervix. In many advanced preneoplastic cervical lesions and most derived carcinomas, HPV genomes are found to be integrated into the host cell chromosomes. Although HPV integration seems to play an important role in the progression of cervical dysplasia, the underlying mechanisms are still unclear. To investigate the pathogenic role of genomic integration of HPV genomes in greater detail, we analysed integration sites of HPV16 and 18 genomes in 21 anogenital precancerous and cancerous lesions using a ligation-mediated chain reaction (DIPS) and the recently described amplification of papilloma virus oncogene transcripts (APOT) assay. On the genomic level, only singular integration events were observed in individual neoplastic cell clones. At many integration sites, a short overlap between HPV and genomic sequences was observed, suggesting that the integration of HPV genomes is mediated by nonhomologous sequence-specific recombination. APOT analysis revealed that the majority of integrated HPV genomes was actively transcribed. These data suggest that in the progression of cervical preneoplasia to invasive carcinomas, integration of viral genomes occurs only at single or few chromosomal loci in a given cell clone. Disruption of cellular genes might support malignant transformation in rare cases; however, it is not a pathogenic prerequisite. The main function of HPV integration seems to be the stabilization of oncogene transcription.

No abstract

No abstract

These data indicate that high-grade dysplastic lesions in the female lower genital tract may emerge primarily as monoclonal lesions from a transformed cell population derived from the uterine cervix.

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease. The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m(2)), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001). Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.

Few cancer patients with psychiatric disorders receive professional mental health care early enough. If patients are unemployed or if they suffer from fatigue or pain, special attention should be paid because the risk of having a mental health condition is increased in these patients.

A case of an intact primary ovarian pregnancy with ultrasonographic demonstration of heart motion following ovarian stimulation is presented. After preoperative ultrasonographic confirmation of an extrauterine pregnancy, proof of the ovarian localization was achieved by intra-operative ultrasonographic visualization during a diagnostic laparoscopy on post-menstrual day 48. A moderate ovarian hyperstimulation syndrome with a concomitant increase in size, vulnerability and vascularity of the ovaries presented an additional challenge for the surgical approach. However, thanks to the early diagnosis of the ectopic pregnancy localization, a laparoscopic organ-preserving removal of the intact ovarian pregnancy was successfully performed. In this way, the fertility of the patient, who had previously undergone contralateral ovariectomy, was preserved. To our knowledge, this represents the first such treatment to be reported in the medical literature. Improvements in diagnosis and therapy of ovarian pregnancy are reviewed.

Infrared (IR) spectroscopic imaging coupled with microscopy has been used to investigate thin sections of cervix uteri encompassing normal tissue, precancerous structures, and squamous cell carcinoma. Methods for unsupervised distinction of tissue types based on IR spectroscopy were developed. One-hundred and twenty-two images of cervical tissue were recorded by an FTIR spectrometer with a 64x64 focal plane array detector. The 499,712 IR spectra obtained were grouped by an approach which used fuzzy C-means clustering followed by hierarchical cluster analysis. The resulting false color maps were correlated with the morphological characteristics of an adjacent section of hematoxylin and eosin-stained tissue. In the first step, cervical stroma, epithelium, inflammation, blood vessels, and mucus could be distinguished in IR images by analysis of the spectral fingerprint region (950-1480 cm(-1)). In the second step, analysis in the spectral window 1420-1480 cm(-1) enables, for the first time, IR spectroscopic distinction between the basal layer, dysplastic lesions and squamous cell carcinoma within a particular sample. The joint application of IR microspectroscopic imaging and multivariate spectral processing combines diffraction-limited lateral optical resolution on the single cell level with highly specific and sensitive spectral classification on the molecular level. Compared with previous reports our approach constitutes a significant progress in the development of optical molecular spectroscopic techniques toward an additional diagnostic tool for the early histopathological characterization of cervical cancer.