Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation-a randomized trial.

BACKGROUND: Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. OBJECTIVE: This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. RESULTS: Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. CONCLUSION: Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: 'writers' (METTL3, METTL4, METTL14, WTAP, KIAA1429), 'erasers' (FTO, ALKBH5), and 'readers' (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC. METHODS: Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC. RESULTS: In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the 'writers' METTL3, METTL14 and the 'reader' YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC. CONCLUSION: Our study suggests dysregulated m6A modification in HPV-associated VSCC.

Clinical value of pre-operative scoring systems to predict leiomyosarcoma: results of a validation study in 177 patients from the NOGGO-REGSA Registry.

OBJECTIVES: Benign leiomyomas are the most common uterine tumors. In contrast, uterine leiomyosarcomas are malignancies with a poor prognosis due to difficulties in early diagnosis and inappropriate surgical treatment. Most often they are diagnosed incidentally after surgery performed for treatment of leiomyoma. As the appropriate surgical treatment is crucial for survival of the patient, there is a high demand to predict leiomyosarcoma pre-operatively. Available scoring systems to discriminate leiomyoma from leiomyosarcoma are based on retrospective studies with limited numbers of patients and are not implemented in routine clinical practice. METHODS: The aim of our study was to evaluate a recently published score-the pre-operative leiomyosarcoma (pLMS) score-to determine whether it would have been predictive of leiomyosarcoma in 177 patients from the NOGGO-REGSA study, a German register of histologically proven gynecological sarcoma detected during routine clinical investigation. RESULTS: The threshold of the pLMS score for 'leiomyosarcoma not probable' (< -3) failed for 7.5% of the patients and the threshold 'indicator for leiomyosarcoma' (>+1) was true for 39.1% of the patients. 53.4% of the patients were attributed to the group 'additional investigations are recommended' (-3 to +1). The most relevant parameters in our analysis were suspicious sonography and rapid growth, but neither have been quantitatively defined. CONCLUSION: In our validation cohort, the pLMS score seems not to be a reliable tool to predict leiomyosarcoma and therefore we do not recommend its clinical implementation to identify leiomyosarcoma.

Comprehensive Analysis of N6-Methyladenosine (m6A) Writers, Erasers, and Readers in Cervical Cancer.

There is growing scientific evidence for the crucial role of post-transcriptional RNA modifications in carcinogenesis, progression, metastasis, and drug resistance across various cancer entities. N6-methyladenosine (m6A) is the most abundant type of RNA modification. m6A is coordinated by a dynamic interplay of 'writers' (METTL3, METTL4, METTL14, WTAP, KIAA1429), 'erasers' (FTO, ALKBH5), and 'readers' (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In this study, we comprehensively examined protein and mRNA expression levels of m6A writers, readers, and erasers in two cervical cancer (CC) cohorts (UHB CC cohort, N = 118; TCGA CC cohort, N = 307) with regard to clinical outcomes. In the UHB CC cohort, high protein expression levels of METTL14 (p = 0.016), WTAP (p = 0.007), KIAA1439 (p < 0.001), ALKBH5 (p < 0.001), HNRNPC (p = 0.012), YTHDC1 (p < 0.001), and YTHDF3 (p = 0.004) were significantly associated with a shorter overall survival (OS). In the TCGA CC cohort, mRNA expression levels of METTL14 (p = 0.012), WTAP (p = 0.041), KIAA1429 (p = 0.016), and YTHDC1 (p = 0.026) showed prognostic values. However, after correction for multiple testing, statistical significance remained only for m6A protein expression levels (q < 0.1). Our study points towards dysregulated m6A modification in CC. Hence, m6A might serve as a promising prognostic biomarker and therapeutical target in CC.

Testosterone serum levels are not predictive of maternal virilization in hyperreactio luteinalis.

BACKGROUND: Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization. METHODS: A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in one case of HL managed at our institution. RESULTS: In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2-37.3 nmol/l and 13.7-197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l. CONCLUSION: From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC-MS/MS should preferably be used for reporting concentrations of circulating testosterone.

Analysis of Surface Levels of IL-1 Receptors and Macrophage Scavenger Receptor I in Peripheral Immune Cells of Patients With Alzheimer Disease.

Increased concentrations of interleukin 1 (IL-1) in the cerebrospinal fluid and serum of patients with Alzheimer disease (AD) reduced phagocytic capacity point to an inflammatory activation of mononuclear phagocytes in AD. Interleukin 1 receptors (IL-1R) and the macrophage scavenger receptor I (MSRI) are important players in IL-1 signaling and phagocytosis. In 20 patients with AD and 17 controls, IL-1RI, IL-1RII, and MSRI were assessed on peripheral blood mononuclear cells by flow cytometry. IL-1ß, soluble IL-1 receptors, and IL-1R antagonist (IL-1Ra) were measured by enzyme-linked immunosorbent assay. The fraction of IL-1RI+ monocytes was increased by 10% and the expression of MSRI was reduced by 12% in AD. A 3.6% increased fraction of IL-1RI+ lymphocytes was accompanied by a 6.1% reduced expression of IL-1RII. The IL-1RI on monocytes and lymphocytes discriminated patients with AD with an accuracy of 0.79 and 0.75, respectively. The IL-1Ra was elevated in AD. Changes in the expression of IL-1 receptors and MSRI on peripheral blood cells fit to the concept of a proinflammatory state of the peripheral immune system. However, the observed differences are not strong enough to suggest their application as biomarkers for AD.

N-truncation and pyroglutaminylation enhances the opsonizing capacity of Aß-peptides and facilitates phagocytosis by macrophages and microglia.

Abnormal accumulations of amyloid-ß (Aß)-peptides are one of the pathological hallmarks of Alzheimer's disease (AD). The precursor of the Aß-peptides, the amyloid precursor protein (APP), is also found in peripheral blood cells, but its function in these cells remains elusive. We previously observed that mononuclear phagocytes release Aß-peptides during activation and phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we show that supplementing the media with soluble N-terminally truncated Aß(2-40) and Aß(2-42) as well as Aß(1-42) induced the phagocytosis of polystyrene particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with Aß-peptides, phagocytosis was induced by all tested Aß-peptide species. N-terminally truncated Aß(x-42) induced the phagocytosis of PSPs significantly more effectively than did Aß(x-40). Similarly, the phagocytosis of Escherichia coli by GM-CSF- and M-CSF-elicited macrophages as well as microglia was particularly facilitated by pre-incubation with N-terminally truncated Aß(x-42). The proinflammatory polarization of monocytes was indicated by the reduced MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with Aß(1-42), Aß(2-42) and Aß(3p-42). Polarization of the macrophages by GM-CSF reduced the phagocytic activity, but it did not affect the capabilities of Aß-peptides to opsonize prey. Taken together, Aß-peptides support phagocytosis as soluble factors and act as opsonins. Differential effects among the Aß-peptide variants point to distinct mechanisms of interaction among monocytes/macrophages, prey and Aß-peptides. A proinflammatory polarization induced by the phagocytosis of Aß-peptide coated particles may provide a model for the chronic inflammatory reaction and sustained plaque deposition in AD.

Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

The incidence rates of vulvar squamous cell cancer (VSCC) have increased over the past decades, requiring personalized oncologic approaches. Currently, lymph node involvement is a key factor in determining prognosis and treatment options. However, there is a need for additional immune-related biomarkers to provide more precise treatment and prognostic information. Here, we used IHC and expression data to characterize immune cells and their spatial distribution in VSCC. Hierarchical clustering analysis identified distinct immune subtypes, of which the macrophage-rich subtype was associated with adverse outcome. This is consistent with our findings of increased lymphogenesis, lymphatic invasion, and lymph node involvement associated with high macrophage infiltration. Further in vitro studies showed that VSCC-associated macrophages expressed VEGF-A and subsequently induced VEGF-A in the VSCC cell line A-431, providing experimental support for a pro-lymphangiogenic role of macrophages in VSCC. Taken together, immune profiling in VSCC revealed tumor processes, identified a subset of patients with adverse outcome, and provided a valuable biomarker for risk stratification and therapeutic decision making for anti-VEGF treatment, ultimately contributing to the advancement of precision medicine in VSCC. SIGNIFICANCE: Immunoprofiling in VSCC reveals subtypes with distinct clinical and biological behavior. Of these, the macrophage-rich VSCC subtype is characterized by poor clinical outcome and increased VEGF-A expression, providing a biomarker for risk stratification and therapeutic sensitivity.

Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial.

BACKGROUND: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. OBJECTIVE: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. STUDY DESIGN: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. RESULTS: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. CONCLUSION: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

TROP-2 is widely expressed in vulvar squamous cell carcinoma and represents a potential new therapeutic target.

PURPOSE: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Etiologically, HPV-dependent and HPV-independent VSCC are distinguished. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Research has identified trophoblast cell surface antigen 2 (TROP-2) to be broadly expressed across different tumor entities. The aim of the present study was to systematically investigate the expression of TROP-2 in VSCC. METHODS: TROP-2 protein expression was investigated by immunohistochemistry in a cohort comprising n = 103 patients with primary VSCC. A four-tier scoring system (0: no staining, 1 + : low staining, 2 + : moderate staining, 3 + : high staining) was applied for quantification of protein expression. For further analyses, two groups (low TROP-2 expression: 0/1 + ; high TROP-2 expression: 2 + /3 +) were generated. The entire study cohort, as well as HPV-dependent and HPV-independent VSCC were considered separately. RESULTS: In the entire VSCC study cohort, TROP-2 expression was present in 97.1% of all cases (n = 100) with 74.8% displaying high TROP-2 expression (2 + /3 +). Only 2.9% of tumors showed absent TROP-2 expression. Of note, all HPV-dependent VSCC (n = 18) demonstrated high TROP-2 expression (2 + /3 +). In the subgroup of HPV-independent VSCC (n = 70), high TROP-2 expression was associated with favorable clinical outcomes based on log rank test and univariate cox analysis. CONCLUSION: TROP-2 protein expression is of prognostic value in HPV-independent VSCC. The broad expression of TROP-2 in VSCC indicates the TROP-2 directed ADC Sacituzumab govitecan as a potential new therapeutic strategy for VSCC patients.

Comprehensive immunohistochemical analysis of N6-methyladenosine (m6A) writers, erasers, and readers in endometrial cancer.

PURPOSE: N6-methyladenosine (m6A) is the most frequent type of messenger RNA (mRNA) modification and is implicated in diverse physiological processes. The procedure of m6A RNA modification is regulated by a dynamic interaction of writers (METTL3, METTL4, METTL14, WTAP, KIAA1429), erasers (FTO, ALKBH5), and readers (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In the oncological context, alterations in m6A were identified to be critically involved in tumorigenesis, proliferation, angiogenesis, and drug resistance across diverse cancer entities including endometrial cancer (EC). METHODS: In this study, we comprehensively examined the protein expression of m6A writers, readers and erasers by immunohistochemical staining in a cohort of N = 65 EC patients. Protein expression data were analyzed with regard to clinical outcomes. RESULTS: We identified enhanced protein expression levels of METTL3, METTL14, FTO, HNRNPA2B1, and HNRNPC, respectively to be of prognostic value and linked to a shortened overall survival in EC. CONCLUSION: Overall, our study points toward dysregulated m6A modification in EC and its possibility to serve as a promising prognostic biomarker.

The Role of P16, P53, KI-67 and PD-L1 Immunostaining in Primary Vaginal Cancer.

BACKGROUND: To analyze clinical, pathological and immunohistochemical correlates of survival in vaginal cancer patients. METHODS: Retrospective analysis of primary vaginal cancer patients, treated at the Department of Gynecology and Gynecological Oncology of the University Hospital Bonn between 2007 and 2021. RESULTS: The study cohort comprised 22 patients. The median age was 63 years (range: 32-87 years). Squamous cell histology was present in 20 patients. Five-year OS in Stage I, II, III and IV was 100%, 56.25%, 0% and 41.67%, respectively (p = 0.147). Five-year DFS was 100%, 50%, 0% and 20.83%, respectively (p = 0.223). The 5-year OS was significantly reduced in the presence of nodal metastasis (p = 0.004), lymphangiosis (p = 0.009), hemangiosis (p = 0.002) and an age above 64 years (p = 0.029). Positive p 16 staining was associated with significantly improved OS (p = 0.010). Tumoral and immune cell PD-L1 staining was positive in 19 and in 16 patients, respectively, without significant impact on OS; 2 patients with metastastic disease are long-term survivors treated with either bevacizumab or pembrolizumab. CONCLUSION: P16 expression, absence of lymph- or hemangiosis, nodal negative disease and an age below 64 years show improved survival rates in PVC. Tumoral PD-L1 expression as well as PD-L1 expression on immune cells is frequent in PVC, without impacting survival. Within our study cohort, long-term survivors with recurrent PVC are treated with anti-VEGF and immunotherapy.

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.

Determination of the Cancer Genome Atlas (TCGA) Endometrial Cancer Molecular Subtypes Using the Variant Interpretation and Clinical Decision Support Software MH Guide.

BACKGROUND: The Cancer Genome Atlas (TCGA) network (United States National Cancer Institute) identified four molecular endometrial cancer (EC) subtypes using an extensive multi-method approach. The aim of this study was to determine the four TCGA EC molecular subtypes using a single-method whole-exome sequencing (WES)-based approach provided by MH Guide (Molecular Health, Heidelberg, Germany). METHODS: WES and clinical data of n = 232 EC patients were obtained from TCGA. The four TCGA EC molecular subtypes designated as (i) Mutated Polymerase ε (POLE), (ii) Microsatellite Instability (MSI), (iii) Copy Number (CN) low and, (iv) CN-high were determined using the MH Guide software. The prognostic value of the subtypes determined by MH Guide were compared with the TCGA classification. RESULTS: Analysis of WES data using the MH Guide software led to the precise identification of the four EC molecular subtypes analogous to the TCGA classification. Both approaches displayed high concordance in terms of prognostic significance. CONCLUSIONS: The multi-method-based TCGA EC molecular subtypes can reliably be reproduced by the single-method-based MH Guide approach. The easy-to-implement single-method MH Guide approach represents a promising diagnostic tool.

Evaluation of the Diagnostic Potential of Circulating MicroRNAs miR-1 and miR-21 in Patients With Ovarian Cancer.

BACKGROUND/AIM: MicroRNA (miR) is implicated in the development of ovarian cancer (OC), the emergence of therapy resistance, and metastatic spread. In the past decade, a variety of relevant miRs have been identified in the context of OC, including miR-1 and miR-21. miR-21 plays a crucial role in OC carcinogenesis via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase signaling and development of platinum resistance, and has prognostic value. miR-1 has been identified as a tumor suppressor across various cancer entities, with reduced expression in malignant tissue compared to benign. This evidence highlights the potential of miR-1 and miR-21 to serve as diagnostic and prognostic biomarkers in OC. PATIENTS AND METHODS: We studied the diagnostic potential of serum expression of miR-1 and miR-21 in a cohort comprising patients with malignant and benign ovarian tumors. Furthermore, levels of miR expression were analyzed with regard to clinical outcomes in patients with malignant ovarian tumors to evaluate their prognostic value. RESULTS: We identified significant differential expression of miR-1 (p=0.0397) and miR-21 (p=0.0154) in malignant and benign ovarian tumors: Higher expression of miR-1 was found in patients with benign ovarian tumors, whereas expression of miR-21 was higher in patients with malignant ovarian tumors. In receiver operating characteristic analyses, the diagnostic potential of both miRs was confirmed, however, diagnostic significance was inferior to that of cancer antigen 125. No further value, in particular no prognostic value, was obtained for miR-1 and miR-21 in patients with malignant ovarian tumors. CONCLUSION: Serum levels of miR-1 and miR-21 might serve as promising biomarkers in the diagnosis of ovarian cancer.

Tumor Load Matters - the Peritoneal Cancer Index in Patients With High-grade Serous Ovarian Cancer.

BACKGROUND/AIM: The aim of this study was to analyze the predictive and prognostic value of the peritoneal cancer index (PCI) with regard to complete cytoreduction and clinical outcomes in patients with high-grade serous ovarian cancer. PATIENTS AND METHODS: In a cohort comprising 188 patients with high-grade serous ovarian cancer, the PCI was retrospectively assessed. Clinical factors and perioperative complications were analyzed according to different PCI groups. Five-year disease-free survival (DFS) and overall survival (OS) were calculated based on the Kaplan-Meier Log rank analysis. Receiver operating characteristic (ROC) analysis was applied to detect associations of PCI and complete cytoreduction. Multivariate survival analysis was performed by Cox proportional hazards model. RESULTS: In our study, the PCI was predictive of complete cytoreduction (ROC analysis; AUC 0.8227). In patients with optimal cytoreduction, higher PCI scores were associated with poorer 5-year OS (p<0.001) and 5-year DFS (p<0.001). Complications (G1-G5) were significantly more frequent in patients with PCI scores >9 (p=0.0023). Five-year OS was reduced in patients with severe complications compared to patients with none or mild complications (30.88% versus 51.01%; p=0.001). There were significant OS (p<0.001) and DFS (p<0.001) differences between patients with none or mild versus severe complications following complete cytoreduction within the PCI subgroups (PCI: 9-11, PCI: 12-18, PCI >18). CONCLUSION: The PCI score showed high predictability for complete cytoreduction and was associated with clinical outcomes. In presence of severe complications, higher PCI scores were associated with poorer survival. Hence, in patients with high tumor load, the prevention of severe perioperative complications is of utmost importance in all cases where complete cytoreduction is deemed to be feasible.

Postoperative Femoral Nerve Palsy and Meralgia Paresthetica after Gynecologic Oncologic Surgery.

Femoral nerve palsy and meralgia paresthetica following gynecologic cancer surgery are rare, but severe and long lasting. Here, we aimed to study their incidence, severity, possible risk factors and its time to remission. Between January 2008 and December 2017 976 gynecologic cancer patients were identified in our institutional database receiving surgery. Complete patient charts were reviewed retrospectively. Possible risk factors were analyzed by Fisher's exact test. 441 (45.18%) out 976 were treated for Ovarian cancer. In total 23 patients were identified with a postoperative neurological leg disorder. A femoral nerve palsy was present in 15 patients (1.5%) and a meralgia paresthetica in 8 patients (0.82%). Three patients showed both disorders. Duration of surgery (p = 0.0000), positioning during surgery (p = 0.0040), femoral artery catheter (p = 0.0051), prior chemotherapy (p = 0.0007), nicotine abuse (p = 0.00456) and prior polyneuropathy (p = 0.0181) showed a significant association with a postoperative femoral nerve palsy. Nicotine abuse (p = 0.0335) and prior chemotherapy (p = 0.0151) were significant for the development of a meralgia paresthetica. Long lasting surgery, patient positioning and femoral arterial catheter placement are risk factors for a postoperative femoral nerve palsy in gynecologic cancer surgery. Polyneuropathy, nicotine abuse, and prior chemotherapy are predisposing risk factors for a femoral nerve palsy and a meralgia paresthetica. A resolution of symptoms is the rule for both disorders within different time schedules.

Risk Factors for Severe Complications in Ovarian Cancer Surgery.

Backround: Due to extensive surgical intervention for macroscopic complete cytoreduction in epithelial ovarian cancer (EOC) patients, severe complications in the postoperative course are possible. PATIENTS AND METHODS: A total of 345 EOC patients who underwent cytoreductive surgery were retrospectively evaluated regarding risk factors for an unfavorable postoperative course. Possible pre-, intra- and postoperative risk factors were statistically analyzed performing multivariate ordinal logistic regression. RESULTS: A total of 345 EOC patients underwent cytoreductive surgery. There were no complications in 114 patients, mild complications in 114 patients and severe complications in 117 patients. The risk factor evaluation identified age (p=0.049), smoking (p=0.032) and duration of surgery (p<0.0001) as significant factors for severe postoperative morbidity. CONCLUSION: In EOC patients age, smoking and the duration of surgery have significant impact on the postoperative course. Only the duration of surgery can be positively influenced by a well-trained EOC team.