Incidence and clinical features of endometriosis in 2484 consecutive female patients undergoing appendectomy for suspected appendicitis-a retrospective analysis.

INTRODUCTION: Endometriosis is a common condition affecting 5 to 10% of women of childbearing age. The true incidence of endometriosis of the appendix is currently unknown. Since symptoms often overlap with those of acute appendicitis, endometriosis of the appendix presents a diagnostic challenge in the emergency department. This large retrospective study investigates the incidence and perioperative clinical, radiologic, and laboratory findings, as well as possible differences between patients with and without endometriosis. METHODS: Data from consecutive patients who underwent appendectomy for suspected appendicitis without a history of endometriosis were analyzed. Perioperative clinical, laboratory, perioperative, and histopathologic findings were compared between women with and without endometriosis. RESULTS: Between January 2008 and June 2023, 2484 consecutive patients without a history of endometriosis underwent urgent appendectomy for suspected appendicitis. Endometriosis was detected on histopathologic examination in 17 (0.7%) patients. Signs of appendicitis were found less frequently on ultrasound in the endometriosis group compared to the non-endometriosis group (23.4% vs. 61.5%; p = 0.002; OR = 0.193; 95% CI 0.063-0.593). There were no differences in physical examination findings, duration of symptoms, degree of inflammation, surgical outcomes, or complication rates. CONCLUSION: The incidence of endometriosis of the appendix in patients undergoing appendectomy for suspected appendicitis was higher than suggested by data from autopsy series and populations with biopsy-proven endometriosis. Patients with endometriosis of the appendix were less likely to have a positive ultrasound finding, but perioperative and histopathologic findings and severity of inflammation did not differ from patients without endometriosis, presenting diagnostic challenges for clinicians.

Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients.

BACKGROUND: According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS: Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS: Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS: The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

Prevalence of oral HPV infection in cervical HPV positive women and their sexual partners.

PURPOSE: Human papillomavirus (HPV) infection represents the primary cause of anogenital premalignant and malignant disease. Regarding the high prevalence of cervical HPV infection and the increasing incidence of HPV associated oropharyngeal cancer in recent years, a significant viral transmission from the cervical to the oral site, possibly depending on the sexual behavior must be considered. The present study aims to determine the prevalence of oral HPV infection in cervical HPV positive and negative women and their sexual partners. METHODS: Cervical HPV positive and negative women and their sexual partners took part in the study. Cervical smears, oral smears and mouthwashes were taken from women attending gynecological outpatient clinics in two different institutions. Further, oral smears as well as mouthwashes of their sexual partners were obtained whenever possible. HPV genotyping was performed using the Cobas® polymerase chain reaction and nucleic acid hybridization assay for the detection of 14 high-risk HPV types. In addition, all participants were invited to complete a personal questionnaire. RESULTS: 144 HPV positive and 77 HPV negative women and altogether 157 sexual partners took part in the study. Age, sexual behaviour, medication, smoking and alcohol consumption were distributed equally in both groups. Cervical HPV positive women had a significantly higher number of sexual partners. One woman with a HPV positive cervical smear and one partner of a woman with a HPV positive cervical smear showed an oral HPV infection. No oral HPV infections were detected in the HPV negative control group. The overall incidence of oral HPV infection was 0.5%, the incidence of oral HPV infection in women with a positive cervical smear was 0.7%. CONCLUSION: The data demonstrate that the overall risk of an oral HPV infection is low. HPV transmission to the oropharynx by autoinoculation or oral-genital contact constitute a rare and unlikely event.

Quality assurance and improvement in oncology using guideline-derived quality indicators - results of gynaecological cancer centres certified by the German cancer society (DKG).

PURPOSE: Based on the example of Gynaecological Cancer Centres (GCCs) certified by the German Cancer Society, this study evaluates the results of medical-guideline-derived quality indicators (QIs) for cervical cancer (CC) and ovarian cancer (OC), examines the development of indicator implementation over time as well as the status of guideline-compliant care and identifies improvement measures. METHODS: QI results for patients with CC and OC treated in GCCs between 2015 and 2019 are analysed. The median, overall proportion and standard deviation of each QI were calculated. Two-sided Cochran-Armitage tests were applied. RESULTS: QIs are divided into two categories: process-organization (PO-QIs) and treatment-procedures (TP-QIs), to allow a differentiated analysis for identifying improvement measures. PO-QIs that reflect the implementation of processes and structures show a high degree of application. PO-QIs have a tremendous influence on the quality of care and are easy to implement through SOPs. TP-QIs report on treatments that are performed in the GCC. TP-QIs that report on systemic therapies reach a plateau where the guideline is known, but patient-related-factors meaningfully prevent further increase. TP-QIs that report on surgical interventions fluctuate. The most relevant factors are practitioners' personal skills. Besides the discussion of results amongst peers during the audit, improvement measures could include surgical courses or coaching. CONCLUSION: The analysis shows that a combination of different measures is necessary to anchor quality sustainably in health care and thus improve it.

Diagnostic efficacy of backscattering intensity measurements in optical coherence tomography of cervical intraepithelial dysplasia.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the diagnostic efficacy of backscattering intensity measurements in optical coherence tomography in identifying different grades of cervical intraepithelial dysplasia. STUDY DESIGN/MATERIALS AND METHODS: OCT images were taken from 153 unsuspicious and suspicious areas of 30 fresh conisation and hysterectomy specimens, evaluated by two blinded investigators using a six-grade classification (normal, inflammation, CIN1, CIN2, CIN3, squamous carcinoma) and later compared to the corresponding histology. Differences between judgments based on either the histology or the OCT images were investigated employing Correspondence Analysis (CA). Further, we explored the extent as to which backscattering intensity profiles of OCT images contained the essential information required for a reliable and valid diagnosis, using Linear Discriminant Analysis (LDA). RESULTS: The CA of histology- and OCT-based judgments suggests that the diagnostic process may be characterized in terms of two stochastically independent underlying ("latent") variables, the first of them reflecting the definiteness with which CIN classes are identified, the second reflecting a bias towards diagnosing inflammation on the side of the OCT-based judgments. This finding is supported by the results of LDAs, where histology and OCT categorizations differ in particular with respect to the positions of inflammation and CIN1. Possibly, a second canonical variable has to be assumed accounting for the evaluation of carcinoma. CONCLUSIONS: The systematic differences between histology-based and OCT-based diagnoses suggest that the use of available information is influenced by perceptual and/or cognitive biases. Apart from this it seems that the profiles appear to provide a remarkably large amount of information determining the main course of the diagnostic process.

3D optical coherence tomography of cervical intraepithelial neoplasia--early experience and some pitfalls.

OBJECTIVES: To compare two different systems for optical coherence tomography for the diagnosis of cervical dysplasia and to assess potential benefits of three-dimensional imaging. MATERIALS AND METHODS: OCT images were taken from unsuspicious and suspicious areas of fresh conisation specimens using two different imaging systems, one with the capability to produce three-dimensional images. All OCT images were separately evaluated by two blinded investigators based on a 6-grade classification (normal, inflammation, CIN 1, CIN 2, CIN 3, squamous carcinoma) and later compared to the corresponding histology. Sensitivity and specificity of OCT in detecting cervical dysplasia were determined. RESULTS: OCT images using both OCT systems were taken from 46 sites in ten conisation specimens and later compared to the corresponding histology. CIN lesions were diagnosed correctly by the two-dimensional OCT system with a sensitivity and specificity of 91% and 78% accordingly. Using the three-dimensional system sensitivity and specificity were 82% and 86% accordingly. CONCLUSIONS: Both OCT systems used were highly sensitive in identifying cervical intraepithelial neoplasia. Despite technical problems experienced in the present series, we believe that three-dimensional imaging has the potential to further improve the accuracy of optical coherence tomography.

Optical coherence tomography as a non-invasive imaging technique for preinvasive and invasive neoplasia of the uterine cervix.

OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features of tissue up to 2 mm in depth in real time. The purpose of this study was to evaluate the feasibility of OCT for the identification of precancerous (cervical intraepithelial neoplasia (CIN)) and cancerous lesions of the uterine cervix. METHODS: We conducted a prospective study on the use of OCT in women with suspected CIN. OCT images were obtained on colposcopy from non-suspicious and suspicious areas, and were evaluated independently by two investigators and later compared with the corresponding histology. The sensitivity, specificity, negative and positive predictive values and accuracy of the new technique in identifying CIN or carcinoma were calculated. RESULTS: Of a total of 610 OCT images, 97 from suspicious areas in 60 women were compared with the corresponding histology. Sixty-three of 67 CIN lesions and four invasive carcinomas were diagnosed correctly on evaluation of the OCT images by the first observer. There were 69 true-positive, 11 true-negative, 13 false-positive and four false-negative results, giving a sensitivity of 95% and a specificity of 46%. CONCLUSION: OCT is a rapid, easy-to-use modality that provides real-time, microarchitectural information of the cervical epithelium. Further refinement of this technology will lead to OCT systems with a significantly higher resolution and may result in better differentiation of cancerous and precancerous lesions.

The significance of HPV in the follow-up period after treatment for CIN.

PURPOSE OF INVESTIGATION: High-risk anogenital human papillomavirus (HPV) infections are causally related to cervical cancer. Successful treatment of cervical intraepithelial neoplasia (CIN) results in complete eradication of HPV in most cases. There is an increasing interest regarding the role of HPV testing in the follow-up period after treatment for CIN. PATIENTS AND METHODS: This retrospective study includes 107 women who underwent conization for histologically verified CIN. All of them had HPV testing pre- and postoperatively. HPV testing was carried out using a hybrid capture assay (HC2). The mean follow-up period was 21.4 months (range 2-76 months). The data were analyzed with respect to success of conization, HPV persistence/recurrence and CIN recurrence. Sensitivity, specificity and negative predictive value (NPV) of HPV testing were assessed and compared to the cytological results. RESULTS: Preoperatively, 97 of 107 women were HPV positive. Ninety-seven conizations showed negative resection margins with 86 women becoming HPV negative. In the following months, nine of these HPV negative women became HPV positive again. Out of ten conizations with positive resection margins, six women became HPV negative. Recurrent CIN 2/3 lesions were observed in 11 women, nine of whom had persistent positive HPV testing throughout the entire study period. Regarding CIN recurrence HPV testing showed a sensitivity of 93%, a specificity of 85% and a NPV of 99%. CONCLUSIONS: The sensitivity of HPV testing concerning persistent or recurrent CIN as well as the NPV are high. The present data suggest that HPV testing should be integrated in a follow-up algorithm after treatment for CIN by conization.

[Optical coherence tomography: preliminary results with a new noninvasive technique for evaluating uterine cervical tissue and vulvar epithelium]. / La tomografia a coerenza ottica, una nuova tecnica non invasiva per valutare il tessuto cervicale uterino e l'epitelio vulvare. Risultati preliminari.

AIM: Optical coherence tomography (OCT) is a noninvasive diagnostic imaging technique that captures high-definition real-time images at near-microscopic resolution (1-2 mm below the surface) of biological tissue morphology. The aim of this study was to define the characteristics of uterine cervical and vulvar pathologies by means of OCT and to compare OCT findings versus histopathological features. MATERIALS AND METHODS: This prospective single-center study was approved by the regional ethical committee. The OCT scans were performed in women with suspected cervical intraepithelial neoplasia (CIN) or vulvar intraepithelial neoplasia (VIN). The suspicious lesions were identified using colposcopy, visualized by OCT, and then biopsied. The OCT scans were evaluated by two independent examiners. The results were then compared with the histopathological findings. The sensitivity and specificity of OCT were calculated. RESULTS: Overall, 50 of the 54 CIN and 2 carcinomas confirmed on histology were correctly diagnosed with OCT, yielding a sensitivity of 93%; specificity was 33%, with 8 false positives and 4 true negatives. In 10 patients with suspected VIN, 19 OCT images were compared with the corresponding biopsies. Three states of tissue structure could be distinguished, with typical features of normal tissue and tissue altered by neoplastic transformation. CONCLUSION: OCT is a noninvasive, fast and simple technique to obtain real-time information on tissue microstructure. Further study is needed to assess its use in routine diagnostic imaging; however, these preliminary results indicate its high sensitivity.

Trends in surgery and outcomes of squamous cell vulvar cancer patients over a 16-year period (1998-2013): a population-based analysis.

PURPOSE: The objective was to identify trends in surgery and the outcomes of squamous cell vulvar cancer in a population-based setting. METHODS: A total of 1113 patients with squamous cell vulvar cancer diagnosed between 1998 and 2013 in the catchment area of the Munich Cancer Registry (population approximately 4.6 million) were analysed. Trends in prognostic factors and treatment were examined by comparing patients diagnosed between 1998 and 2008 with those diagnosed between 2009 and 2013. Cumulative incidence was used to calculate time to local (LR) and lymph node recurrence (LNR). Survival was analysed by the Kaplan-Meier method, calculation of relative survival (RS), and a Cox model. RESULTS: The high median age at diagnosis of 75 years did not change significantly over time. In addition, no changes in the subsite of tumour or grading were noted. A decrease in patients undergoing complete vulvectomy from 27.7 to 17.8 % (p < 0.001) as well as an increase in the use of sentinel lymph node biopsy from 11.4 to 39.1 % (p < 0.001) was observed. However, time to LR (from 19 to 19 %) and time to LNR (from 9 to 9 %) as well as 5-year overall survival (from 55 to 55 %) and RS (from 66 to 63 %) were not significantly altered. After adjustment for prognostic factors, less radical locoregional surgery had no influence on survival. CONCLUSION: Less radical locoregional surgery in vulvar cancer is increasingly implemented. Locoregional recurrence and survival have not been affected by these changes and are likely accompanied by an improvement in quality of life.

HPV Vaccination: Attitude and Knowledge among German Gynecologists.

Purpose: In order to achieve a higher vaccination rate, education on HPV as well as options for prophylaxis performed by doctors is of great importance. One opportunity to increase the protection against HPV would be vaccinating boys. This study evaluated attitude and knowledge among German gynecologists regarding HPV vaccination, especially in boys. Material and Methods: A questionnaire with 42 questions about demographics, attitude and knowledge about HPV and HPV vaccination was sent to members of the German Society for Gynecology and Obstetrics (DGGG). Results: 998 out of 6567 addressed gynecologists participated. Knowledge about HPV, associated diseases and possible HPV vaccines was high among participants. The attitude towards vaccination in boys as well as girls was positive. Only 8.2 % refused to vaccinate their sons whereas 2.2 % refused to do this for their daughters. However, only few gynecologists vaccinated their daughters and sons against HPV. Main reason for girls was an age outside of vaccination guidelines; for boys it was the lack of cost coverage. Conclusion: The willingness of gynecologists to perform HPV vaccination in boys is as high as for girls. However, sons of gynecologists are only rarely vaccinated against HPV. Main reason is the lack of cost coverage. Vaccinating boys could decrease the disease burden in males, as well as protect women by interrupting ways of transmission. Since the main argument against vaccination of boys is only of financial nature, the necessity of a vaccination recommendation for boys needs to be re-evaluated taking into account the cost-reduced 2-dose vaccination scheme.

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.

Localization and staging of cervical intraepithelial neoplasia using double ratio fluorescence imaging.

A phase zero evaluation of a new fluorescence imaging technique for diagnosing cervical intraepithelial neoplasia (CIN) was performed. The fluorescence imaging prototype performed quantitative imaging of Protoporphyrin induced by a topically applied aminolevulinic acid using double ratio (DR) fluorescence imaging technique developed by our group. A total of 38 patients were in the protocol, with 16 colposcopically selected for biopsy. Fluorescence images of these 16 patients were taken, 19 sites were biopsied, and the disease was staged histopathologically. DR fluorescence imaging of the cervix using our general purpose prototype appeared to be cumbersome but feasible. In four cases strongly localized fluorescent hotspots were observed at the location where the disease was colposcopically visible. In the other cases the fluorescence showed a more diffuse multifocal image. The value of the DR determined at the site of biopsy correlated in a statistically significant way with the histopathologically determined stage of the disease [Spearman rank correlation, r=0.881, p<0.001 (confidence interval 0.7044-0.9552)]. This suggests that noninvasive staging of CIN using this technique is feasible. We believe that the results of this study justify the development of a dedicated device that combines regular white light colposcopy with DR fluorescence imaging.

[Influence of abdominal sacrocolpopexy and vaginal sacrospinal fixation (according to Amreich-Richter) on the anterior compartment]. / Einfluss der abdominalen Sakrokolpopexie und der vaginalen sakrospinalen Fixation (nach Amreich-Richter) auf das vordere Kompartiment.

OBJECTIVE: The aim of the study was to investigate the postoperative effect of abdominal sacrocolpopexy (aSCP) versus vaginal sacrospinal fixation (vssF) on the anterior compartment. PATIENTS AND METHODS: In a retrospective study, 25 patients at 24 months following aSCP (group 1) and 28 patients at 60 months following vssF (group 2) were examined and data collected as to vaginal prolapse, recurrent cystocele or stress incontinence, de novo stress incontinence and urge symptoms. In addition, a review of the literature published from 1970 to 2002 was performed. RESULTS: Both methods achieved comparable results. We recorded no recurrent vaginal prolapse in either study group. Moderate to severe cystoceles were found postoperatively in 38 % of group 1 and 43 % of group 2. There was no difference in occurrence of urge symptoms. These results are comparable to those published; however, the published rate of occurring cystoceles is slightly lower (11.6 % following vssF, 21.6 % following aSCP). CONCLUSIONS: Both methods are equally successful at achieving a permanent fixation of the vaginal vault. We postulate that higher success rates can only be achieved by a more frequent combination with other operative techniques.

The effects of childbirth on the pelvic-floor.

Basically, vaginal delivery is associated with the risk of pelvic floor damage. The pelvic floor sequelae of childbirth includes anal incontinence, urinary incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk factors for the development of the respective problems are reviewed. Where possible, recommendations for reducing the risk of pelvic floor damage are given.

Induction of TGF-beta by an antiprogestin in the human breast cancer cell line T-47D.

BACKGROUND: Antiprogestins appear to be a new approach for the endocrine therapy of breast cancer. Most breast cancer cells are growth inhibited by TGF-beta. Any change of tumorcellular TGF-beta secretion could have some impact on tumorcellular growth. We addressed our question to whether the antiprogestin onapristone can induce TGF-beta secretion in breast cancer cells in vitro and whether a possible induction correlates with the antiproliferative effect and the receptor status of the cells. MATERIALS AND METHODS: We examined the ER and PR positive breast cancer cell lines MCF7 and T-47D and an ER and PR negative variant T-47D/x. Hormone receptor levels were determined by EIA, total (LTGF-beta + active TGF-beta) and active TGF-beta by a radioreceptor assay. All cell biological and antiproliferative effects were measured during basal, not estrogen-stimulated growth. RESULTS: To our knowledge, we are the first to describe, that the TGF-beta secretion of tumor cells can be increased by an antiprogestin (total: 4.8-fold, active 2.9-fold). A stimulation was found only in the markedly PR positive T-47D cells, in which onapristone proved to have strong antiproliferative potency. In the MCF7 and T-47D/x cells onapristone showed no induction of TGF-beta. Moreover, those cells were not growth inhibited. Whereas onapristone did not influence the ER-content, it dramatically downregulated the PR-content of the T-47D and MCF7 cells (93% and 65%, respectively). CONCLUSIONS: These observations make it likely, that the antiproliferative potency of the antiprogestin onapristone is at least partly due to the ability of onapristone, to stimulate the strong growth inhibitor TGF-beta. In contrast to the antiprogestin RU 486, onapristone showed no estrogenic activity (stimulation of growth and PR), which could be a decisive advantage in the therapy of breast cancer, taking into account, that many breast carcinomas grow estrogen dependent.

Obstetric risks and vertical transmission of hepatitis C virus infection in pregnancy.

BACKGROUND: Reports of obstetric complications of mothers infected with hepatitis C virus (HCV) are limited and the risk of mother-to-infant transmission varies widely. We assessed the course of pregnancy in HCV-infected women and the rate of vertical transmission. METHODS: Between October 1992 and December 1996, 3712 pregnant patients of the university hospital Grosshadern Munich, Germany, were screened for anti-HCV and analyzed for HCV-RNA by polymerase chain reaction. Clinical and biochemical parameters were monitored. Children born to HCV-positive women were followed up at 6, 12 and 18 month intervals and screened for anti-HCV and HCV-RNA. RESULTS: Thirteen (42%) of 31 anti-HCV positive patients had a cesarean section which was twice the rate of that in the HCV-negative group (p=0.004). None of the cesarean deliveries was due to complications directly caused by HCV infection. Nine (29%) of 31 anti-HCV positive women had preterm delivery compared to 19% in the anti-HCV negative patients, the difference being statistically not significant. Fetal outcome parameters such as APGAR score, umbilical pH and birth weight of HCV infected pregnancies were not impaired. All 29 babies tested for anti-HCV were seropositive after birth. Between 12 and 18 months of age, 10% of the infants still were anti-HCV positive, whereas only one baby was HCV-RNA positive beyond 12 months yielding a vertical transmission rate of 5% among HCV-RNA positive mothers. CONCLUSION: Anti-HCV positive pregnancies have an increased risk of cesarean delivery, probably due to the high-risk collective of anti-HCV positive mothers. The mother-to-child transmission rate is low and linked to maternal HCV-RNA positivity.