Determination of endometrial cancer molecular subtypes using a whole exome-sequencing based single-method approach.

AIM: Endometrial cancer (EC) is heterogeneous with respect to epidemiology, clinical course, histopathology and tumor biology. Recently, The Cancer Genome Atlas (TCGA) network has identified four molecular subtypes with distinct clinical courses by an integrated multi-omics approach. These subtypes are of critical importance in the clinical management of EC. However, determination of TCGA molecular subtypes requires a complex methodological approach that is resource intensive and difficult to implement in diagnostic routine procedures. In this context, Talhouk et al. reported the precise determination of modified subtypes based on molecular surrogates obtained by a two-method approach comprising immunohistochemistry and DNA-sequence analysis (Proactive Molecular Risk Classifier for Endometrial Cancer; ProMisE). In this study, we aimed to identify EC molecular subtypes in analogy to TCGA and ProMisE applying an innovative whole exome-sequencing (WES) based single-method approach. METHODS: WES was performed in a cohort comprising N = 114 EC patients. WES data were analyzed using the oncology treatment decision support software MH Guide (Molecular Health, Heidelberg, Germany) and EC molecular subtypes in analogy to TCGA and ProMisE were determined. Results from both classifications were compared regarding their prognostic values using overall survival and progression-free survival analyses. RESULTS: Applying a single-method WES-approach, EC molecular subtypes analogue to TCGA and ProMisE were identified in the study cohort. The surrogate marker-analogue classification precisely identified high-risk and low-risk EC, whereas the TCGA-analogue classification failed to obtain significant prognostic values in this regard. CONCLUSION: Our data demonstrate that determination of EC molecular subtypes analogue to TCGA and ProMisE is feasible by using a single-method WES approach. Within our EC cohort, prognostic implications were only reliably provided by applying the surrogate marker-analogue approach. Designation of molecular subtypes in EC will be increasingly important in routine clinical practice. Thus, the single-method WES approach provides an important simple tool to tailor therapeutic decisions in EC.

Anterior enterocele after cystectomy: case report and review of the literature.

PURPOSE: Anterior enterocele is a rare but potentially serious complication after cystectomy with heterogeneous treatment options. METHODS: Here we report on the management of a 71-year-old patient with recurrence of anterior enterocele after cystectomy and provide a systematic review of the literature using the PubMed/MEDLINE database. RESULTS: The 71-year-old patient with recurrence of anterior enterocele after cystectomy was successfully treated with colpocleisis and anterior colporrhaphy at the Department of Gynecology and Gynecological Oncology, University Hospital Bonn. The use of a synthetic mesh was not needed. At 16-month follow-up postoperatively, the patient was asymptomatic and had no signs of recurrence. n = 14 publications including n = 39 patients were identified for the systematic review including case reports and reviews. The median duration of developing an anterior enterocele after cystectomy was 9 months (range 3 months to 8 years). Patients had a median age of 71 years (range 44-84). In all cases, a surgical approach was described using a wide variety of surgical procedures. In total, 36% of all patients developed a recurrence with an average time period of 7 months after primary surgery. A rare complication represents a vaginal evisceration with the need of urgent surgery. Furthermore, the occurrence of a fistula is a possible long-term complication. CONCLUSION: Anterior enterocele after cystectomy is a rare complication requiring an individual and interdisciplinary treatment.

Intraoperative Utilization of Indocyanine Green (ICG) Dye for the Assessment of Ovarian Perfusion-Case Report and Review of the Literature.

The assessment of ovarian perfusion after detorsion is crucial in the surgical management of patients with ovarian torsion. In current routine clinical practice, the surgical decision (preservation of the ovary versus oophorectomy) is based on the subjective impression of the surgeon. Intraoperative indocyanine green (ICG) angiography has been shown to sufficiently reflect tissue perfusion with a potential impact on the surgical procedure. Currently, there are only sparse data available on the utilization of ICG in the surgical treatment of ovarian torsion. Here, we describe the successful intraoperative use of ICG in a 17-year-old female patient with ovarian torsion who underwent ovary-preserving surgery. Further, a systematic literature review was performed. Based on the data available to date, the use of ICG in the surgical treatment of ovarian torsion is feasible and safe. The extent to which this might reduce the necessity for oophorectomy has to be evaluated in further investigations.

Analysis of the cervical microbiome in women from the German national cervical cancer screening program.

PURPOSE: Cervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia. METHODS: The microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters. RESULTS: Most patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum. CONCLUSION: In our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.

Comparison of balloon kyphoplasty with the new Kiva® VCF system for the treatment of vertebral compression fractures.

BACKGROUND: Vertebral compression fractures are common among the elderly, which is conditioned by osteoporosis. They cause back pain and limit the patient's activities. The Kiva® VCF Treatment System is a new device to treat vertebral compression fractures. Compared to other methods, the utilization of the Kiva System reduces the risk for complications and delivers improvements in back pain reduction and functionality. OBJECTIVES: Evaluation of safety and effectiveness of the Kiva System in comparison to balloon kyphoplasty on the basis of matched pairs. METHODS: 52 patients (47 - 89 years, 68 fractures) were treated with balloon kyphoplasty or with the new Kiva System. Back pain and impairment of motility were assessed preoperatively and 6 months postoperatively, with the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). The operation time and cement extravasation were recorded. Control radiographs were evaluated for new fractures and vertebral heights. RESULTS: Mean VAS values in both groups improved from preoperatively 87.6 ± 12.8 and 83.1 ± 14.9 to 10.8 ± 20.8 and 24.6 ± 11.0 6 months after the treatment. The improvement after 6 months in the Kiva group was significantly better than in the balloon kyphoplasty group (P < 0.0001). Mean ODI scores in both groups also improved from 68.7% ± 15.8% in the Kiva group and 80.6% ± 8.6% in the balloon kyphoplasty group preoperatively to 24.8 ± 18.6% and 33.2 ± 6.3% 6 months after treatment. The mean operation time for the Kiva group was 12.7 ± 3.7 minutes per vertebra and cement leakage occurred in 6 patients. The mean operation time for the balloon kyphoplasty group was 34.1 ± 7.0 minutes per vertebra and cement leakage occurred in 8 patients. Anterior and mid vertebral height in the Kiva group increased from preoperatively 21.06 ± 7.44 mm and 18.36 ± 5.64 mm to postoperatively 22.41 ± 7.14 mm and 20.41 ± 6.00 mm. Anterior and mid vertebral height in the balloon kyphoplasty group increased from preoperatively 21.68 ± 2.06 mm and 21.97 ± 1.78 mm to postoperatively 25.09 ± 2.54 mm and 25.29 ± 2.10 mm. Vertebral height restoration could be therefore maintained with both procedures for 6 months. In the Kiva group 2 cases of nonadjacent fractures and one case of adjacent fractures were observed. In the balloon kyphoplasty group 9 cases of adjacent, as well as 5 cases of nonadjacent, fractures were observed. In the Kiva group significant fewer fractures occurred. LIMITATIONS: The study includes only 26 patients for each procedure, which were compared on the basis of matched pairs. CONCLUSION: The Kiva System appears to be a safe and effective procedure for the treatment of vertebral compression fractures. Six months after treatment with the Kiva System, better VAS values than the values after the treatment with balloon kyphoplasty were recorded. Reduction in functional impairment was as successful as it was after balloon kyphoplasty. Vertebral height restoration was observed in both groups, which was sustained for 6 months. The risk of cement extravasation during the Kiva Treatment is nearly the same as in balloon kyphoplasty; however, it requires a shorter operation time and produces less new fractures.