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We report on the incidental finding of a FOXL2 mutated adult granulosa cell tumour of the ovary with thecoma-like foci, a rare entity recently described by Jennifer N. Stall and Robert H. Young in a series of sixteen cases in 2019, displaying features differing from conventional adult granulosa cell tumour. Our aim is to specify the morphologic and molecular particularities of this presumably underrecognized finding, with a short presentation of the typical clinical context. Awareness of this rare and challenging neoplasm with indeterminate clinical course is crucial in routine diagnostics.

Purpose Squamous cell carcinoma of the vulva (SQCV) is the fifth common cancer in women. Necessity of inguinal lymph node surgery depends on the depth of stromal invasion, inducing lymph node surgery, if depth of invasion is more than 1 mm. In this study we tested the prediction of stromal infiltration depth by measurements in preoperative biopsies. Methods We analyzed whether a different operative strategy in respect to lymph node surgery would have been chosen based on the pre- or postoperative depth of stromal invasion for each patient. Examination of infiltration depth in preoperative biopsies and surgical specimen were compared. Results In total 77 patients were included in this study. Of those 89.6% showed different depths of stromal invasion comparing the pre- and postoperative specimen. Within seventeen patients (22.1%) preoperative depth was 1 mm or less and a postoperative depth was > 1 mm. Conclusion We pointed, that only in 77.9% of the patients who should have undergo lymph node surgery based on the postoperative depth of infiltration underwent this procedure. Consequentially in 22.1% of the cases a second operation could not be prevented with a preoperative taken biopsy as indicator for the necessity of lymph node surgery.

Background/Aim: Labor is induced in 1 out of 5 pregnancies. This is why we aimed to compare two different protocols of orally administered misoprostol for the induction of labor (IOL), with special regard to maternal and fetal outcome, delivery mode and duration. Patients and Methods: One hundred and twenty four patients with a medical indication for IOL were divided into two groups: Group A (n=63), which initially received 50 μg misoprostol escalated to 100 and, subsequently, to 200 μg every 4 h with a daily maximum of 600μg, between 11/2007 and 01/2008; and Group B (n=61), which initially received 25 μg misoprostol followed by 100 μg every 4 h with a daily maximum of 300 μg, between 12/2009 and 04/2010. Results: The mean administration-delivery interval was significantly lower in Group A (19.0 h) compared to Group B (27.1 h, p

Simple Summary In node-positive vulvar squamous cell cancer, questions of when and how to perform pelvic lymphadenectomy (LAE) as well as the optimal extent of pelvic treatment in general have been surrounded by considerable controversy. In Germany, systematic pelvic LAE is currently recommended as a staging procedure in patients at risk for pelvic nodal involvement in order to prevent morbidity caused by pelvic radiotherapy (RT) in patients without histologically-confirmed pelvic involvement. However, the population at risk for pelvic metastases remains insufficiently described, resulting in the potential overtreatment of a considerable proportion of patients with groin-positive disease. This applies to the indication to perform surgical staging but also to adjuvant RT of the pelvis without previous pelvic staging. Our study aims to describe the risk for pelvic lymph node metastasis with regard to positive groin nodes and to clarify the indication criteria for pelvic treatment in node-positive vulvar cancer. Abstract The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Background/aim Surgical margin status remains an important determinant for recurrence of invasive breast cancer and ductal carcinoma in situ. We compared the number of positive margins in initial histology with rates of residual tumor in re-excision specimens. Furthermore, we analysed cost-effectiveness of re-excisions. Patients and methods 101 patients treated with secondary surgery were included. The first group underwent breast conserving surgery and secondary mastectomy. The second group was primarily treated with subcutaneous mastectomy followed by secondary surgery. Results Within the first group, 22.7% did not show residual tumor in the re-excision specimen. Of the second group, 54.3% had no residual tumor. Consequentially 45.7% needed a re-excision to achieve R0 status. Cost-effectiveness was determined as secondary endpoint. If a patient needs a secondary mastectomy the hospital gains 602,65€ in comparison to a primary breast conserving operation. Conclusion In every second patient who had first received a subcutaneous mastectomy, no tumor could be detected in the secondary operation despite a previous R1 status.

Background/aim The aim of this study was to evaluate the difference in clinical outcomes in patients with histologically confirmed cervical cancer of the uterus treated with either laparoscopy or laparotomy with curative intent between 2011 and 2017 at the Department of Gynecology and Obstetrics of University Hospital Cologne. Materials and methods This retrospective analysis included all patients who received surgical treatment with curative intent between January 2011 and December 2017 for stages IA1 to IIB cervical carcinoma. Patients receiving primary or secondary surgery after neoadjuvant chemotherapy were also included. Results In total, 75 patients were included, of whom 34 patients underwent minimally invasive surgery and 41 underwent open surgery. Neoadjuvant chemotherapy was performed in 10 patients in the minimally-invasive group and in 14 patients in the laparotomy group. Statistically, no significant difference in overall survival (OS) was observed in both groups. Disease-free survival showed a significant difference in favor of the minimally invasive group. Conclusion Minimally invasive surgical therapy for cervical cancer improves disease-free-survival. Prospective trials are needed to further confirm these results.

The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte subsets and also expression of immune-regulatory molecules on tumor-infiltrating lymphocytes showed site-specific variation. Multiparametric analyses of these data identified similarities of renal and liver or lung with head and neck cancer. Co-expression of immune-inhibitory ligands on tumor cells was most frequent in colorectal, lung and ovarian cancer. Genes related to antigen presentation were frequently dysregulated in liver and lung cancer. Expression of co-inhibitory molecules on tumor-infiltrating T cells accumulated in advanced stages while T-cell abundance was related to enhanced expression of genes related to antigen presentation. Our results promote evaluation of cancer-specific or even personalized immunotherapeutic combinations to overcome primary or secondary resistance as major limitation of immune-checkpoint inhibition.

Background Immune-checkpoint inhibition (CKI) demonstrated remarkable therapeutic efficacy in several kinds of cancer. However, immune escape mechanisms lead to primary or secondary resistance in the majority of patients. Most predictive biomarkers failed, as the primary target of CKI is not the tumor cell itself, but the crosstalk between immune- and cancer cells. We aimed to characterize the immune evasion landscape in primary tumors across different entities. Materials and Methods Expression of 32 immune-regulatory molecules on lymphocytes was analyzed in peripheral blood and tumor infiltrating lymphocytes (TILs) of 146 primary tumor patients across 10 different entities using flow cytometry. NanoString was applied to determine RNA expression of the respective ligands and 20 genes associated with antigen presentation. Expression of coinhibitory ligands on tumor cells was assessed by immunohistochemistry. To quantify the immune cell infiltration, digital pathology was used and the Immunoscore was generated for each patient. Results While an increase of regulatory T cells was a common feature across all entities, we found site-specific differences regarding other lymphocyte subsets and expression of immune-regulatory molecules by TILs and tumor cells. Expression of co-inhibitory molecules on tumor infiltrating T cells accumulated especially in advanced stage cancers whereas immune cell infiltration was mainly associated with enhanced antigen presentation. Co-expression of multiple immune-inhibitory ligands was most frequent in colorectal, lung and ovarian carcinoma. Genes related to antigen presentation were frequently dysregulated in seminoma, liver and lung cancer. Conclusions Immune evasion is a common feature of cancer and frequently detected co-occurrence of multiple mechanisms probably contributes to resistance against immunotherapy. We describe substantial heterogeneity regarding immune escape mechanisms between patients with the same primary tumor. Individualized immunotherapeutic strategies based on pretherapeutic evaluation of the immune evasion landscape might help to improve response to CKI. Disclosure Information M. Thelen: None. K. Wennhold: None. J. Lehmann: None. E. Staib: None. M.A. Garcia Marquez: None. P. Lohneis: None. A. Lechner: None. S. Wagener-Ryczek: None. P.S. Plum: None. D. Pfister: None. F. Dorr: None. D. Beutner: None. F. Thangarajah: None. D. Ratiu: None. W. Malter: None. S. Merkelbach-Bruse: None. C.J. Bruns: None. A. Quaas: None. M.S. von Bergwelt-Baildon: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; Astellas. F. Consultant/Advisory Board; Modest; Bristol-Myers Squibb. H.A. Schloser: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; Astra Zeneca.

Background/Aim: In Germany, performance of an emergency Cesarean section (ECS) is recommended within an interval of ≤20 min from decision to delivery (DDI). The aim of the study was to assess the duration of DDI in ECS as well as its impact on neonatal outcome. Patients and Methods: Data from 437 patients at a single, tertiary care hospital were retrospectively analysed regarding influence on the duration of DDI. Subsequently the impact of DDI on neonatal outcome and incidence of adverse neonatal outcome was analysed. Results: DDI of ECS performed outside core working hours was significantly prolonged (p

Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in previous transient testing by this group. It was shown that a single suture, yielding an ultimate load of 35 N, was equivalent to continuous suturing. This was demonstrated in an in vitro cadaver study. This transient data were used to establish an elastic stress–strain envelope. It was now possible to proceed to dynamic in vitro analysis of this surgical method to establish time to functional stability. Cyclic testing of this fixation method was performed on human female embalmed cadaver (cohort 1) and fresh, non-embalmed cadaver (cohort 2) pelvises. The testing envelope was 5–25 N at a speed of 1 mm/s. 100 load regulated cycles were applied. 100 cycles were completed with each model; no overall system failure occurred. Steady state, i.e., functional stability was reached after 14.5 (± 2.9) cycles for the embalmed group and after 19.1 (± 7.2) cycles for the non-embalmed group. This difference was statistically significant p = 0.00025. This trial showed in an in vitro cyclic testing of the pectopexy method that functional stability may be achieved after no more than 19.1 cycles of load exposure. When remaining within the established load envelope of below 25 N, patients do not need to fear global fixation failure. Testing did demonstrate differences in non-embalmed and embalmed cadaver testing. Embalmed cadaver testing tends to underestimate time to steady state by 26.3%.

Major advances have been achieved in targeted immunotherapy with significant clinical benefits for patients. However, on-target/off-tumor toxicity is a major concern. This issue highlights the clinical need for better targets to improve the safety profile of immunotherapies. On-target/off-tumor toxicity is mainly based on the expression of tumor-associated antigens (TAA) in healthy tissues under physiological conditions. Thus, new approaches have to be developed to restrict specificity of targeted immunotherapy selectively towards cancerous cells. One way to improve target specificity is multi-targeting of cancer cells, i.e. targeting more than one TAA per cancer cell. We developed a workflow to identify new tumor markers employing an unbiased high throughput flow cytometry-based screen on primary ovarian cancer samples. Co-expression of THY1, a marker of fibroblasts and hematopoietic stem cells, was revealed on cancer cells characterized by EPCAM expression, a marker of epithelial cells. We confirmed our findings by high content imaging analyzing several ovarian carcinoma samples. Next we assessed the safety profile of the target combination THY1-EPCAM by analyzing the expression across a multitude of healthy human tissue samples using again high content imaging. Cluster analysis showed correlation patterns within the datasets confirming our previous findings. In order to investigate the functionality of THY1-EPCAM as therapeutic t we combined this target pair with the adaptor CAR technology, a modular system composed of a CAR recognizing biotin and biotinylated antibodies which are specific for a certain antigen. This technology combines the flexibility and controllability of antibodies with the efficacy of CAR T cell-dependent killing of target cells. The functional in vitro characterization of adaptor CAR T cells targeting the THY1-EPCAM pair shows high specificity and efficacy. Moreover, we are going to conduct in vivo studies with adaptor CAR T cells to investigate the efficacy and safety of targeting THY1-EPCAM in a solid tumor model. In conclusion, we successfully identified a novel target combination in ovarian cancer utilizing flow cytometry-based screening complemented by high content imaging. The new target pair combination shows promising results in vitro in combination with adaptor CAR T cells indicating its potential use as future immunotherapy. Citation Format: Christoph Herbel, Vera Dittmer, Manuel Martinez-Osuna, Sandy Reiß, Peter Mallmann, Dominik Ratiu, Michael Mallmann, Paurush Praveen, Werner Müller, Dominik Eckardt, Andreas Bosio. Identification of a novel tumor marker combination THY1-EPCAM for adaptor CAR T cell therapy in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2813.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide. Addition of the VEGF antibody bevacizumab in combination with platinum-containing chemotherapy achieved an improvement in overall survival in advanced cervical cancer. To date there are no data on neoadjuvant use of bevacizumab. We therefore studied the benefit of neoadjuvant combined therapy with bevacizumab in a group of cervical cancer patients. Patients and Methods This retrospective cohort study analysed 14 patients with cervical cancer FIGO stages 1b1 to IV who received neoadjuvant platinum-containing chemotherapy in combination with bevacizumab. The comparative cohort consisted of 16 patients who were treated with neoadjuvant platinum-containing chemotherapy alone. The response rates were determined by means of preoperative clinical examination, diagnostic imaging (RECIST), changes in tumour markers (SCC) and by histopathology. Results A clinical response was found in 93.8% (n = 15) of patients after bevacizumab-free therapy and in 100% (n = 14) of the patients who were treated with bevacizumab in addition. Combined therapy with bevacizumab led to a higher rate of clinical complete remission (42.9 vs. 12.5%; p = 0.072) and significantly improved the reduction in tumour size (Δ longest diameter: 3.7 vs. 2.5 cm; p = 0.025). Downgrading was observed in 100% of all patients treated with bevacizumab compared with 75% in the control arm. The rate of pathological complete remission (pCR) was not altered significantly (28.6% [n = 4] vs. 37.5% [n = 6]; p = 0.460). Discussion Overall, combined therapy with bevacizumab led to a better clinical response. Operability was therefore improved more often. Because of the small patient cohort, larger prospective studies are necessary to validate the effect of neoadjuvant combined therapy with bevacizumab.

Background/Aim: Numerous risk factors have been reported to influence the development of urinary incontinence (UI). In this study, we took a closer look on the different forms of UI and tried to identify differences in regard to potential risk factors. Of special interest was the onset of UI symptoms and its relation to menopausal status. Patients and Methods: This was a hospital-based analysis of patients who presented with urinary incontinence in the outpatient ward of a tertiary hospital. The diagnosis of urinary incontinence was based on the subjective complaints of patients. Data concerning menopausal status, hormone replacement therapy, prior hysterectomy were assessed. Results: The mean age was 53.8 years in the SUI group, 62.7 years in the MUI group and 66.1 years in the UUI group, respectively (p

Background/aim The aim of this study was to determine the value of Doppler indices and notching assessment of uterine artery between the 19th and 22nd week of gestation in the prediction of pregnancy outcome such as delivery mode, birth weight, Apgar score, afterbirth pH, fetal presentation, preeclampsia and fetal growth restriction in singleton pregnancy. Patients and methods This is a retrospective cohort study of Doppler ultrasound of the uterine arteries at 19-22 week of gestation in 1,472 women with singleton pregnancies. Results Patients with bilateral high resistance-index (RI) and pulsatility-index (RI) or with the presence of a notch showed a significantly higher prevalence of small for gestational age (SGA) fetuses and intrauterine growth restriction (IUGR), low Apgar Scores at the 1st and the 5th min, high c-section rate, preterm birth, breech birth, placental insufficiency and placental abruption. The presence of a notch significantly increased the prevalence of severe preeclampsia, HELLP-syndrome and oligohydramnios. Also, patients with a bilateral uterine notching had a higher c-section rate along with higher prevalence of SGA and IUGR at screening time. Conclusion Uterine artery Doppler waveform analysis as well as the assessment of the presence of a notch in the second trimester can be used as a screening method to identify women who will thereafter develop a severe adverse outcome.

Background Breast cancer is a heterogenous and complex disease. A rare site of metastatic breast cancer disease is the neck. Data about supraclavicular metastases in patients with metastatic breast cancer are still lacking. Hence, our study aimed to analyze histological subtypes of supraclavicular metastases compared to the primary site. Materials and methods This was a retrospective hospital-based cohort study of patients with breast cancer who developed supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed by biopsy or diagnostic lymph node extirpation. Histological subtypes were analyzed and Kaplan-Meier estimates were calculated for overall survival. Results A total of 20 patients were included in the analysis. The majority of the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20 patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20 patients and basal-like in 4/20 patients. Total discordance rates for estrogen receptor, progesterone receptor and HER2 between primary and metastatic tumors were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%, whereas the 5-year survival after the onset of neck metastasis was 45%. Conclusion As a rare site of metastatic breast cancer, supraclavicular metastases are associated with a worse median overall survival from their onset. The high rate of discordance of histological subtype stresses the necessity for biopsies in patients with supraclavicular metastasis.

Inguinal lymph node (LN) metastasis is a crucial prognostic factor in vulva carcinoma. The aim of this study was to determine the prognostic value of the number of resected LNs in patients with vulvar carcinoma on recurrence rates. This retrospective study includes patients with vulvar squamous cell carcinoma who underwent inguinofemoral lymphadenectomy (IFL) between 1998 and 2011. Dissected groins were stratified by the number of removed lymph nodes (

Eine neoadjuvante Systemtherapie kann nach den aktuellen S3-Leitlinien fur Patientinnen mit einer primar fortgeschrittenen Erkrankung unter bestimmten Bedingungen empfohlen werden. Fur dieses verhaltnismasig kleine Kollektiv kann der zytoreduktive Effekt einer neoadjuvanten Systemtherapie bei Vorhandensein definierter Risikofaktoren wie einem Bulky Disease oder einem positiven Lymphknotenstatus einen moglichen Benefit hinsichtlich des chirurgischen Outcomes bedeuten. Ziel ist es, die Operabilitat zu verbessern und die Notwendigkeit einer adjuvanten Radiochemotherapie zu reduzieren. Ziel dieser Analyse war es den Effekt von Bevacizumab analog der Ergebnisse der GOG 240 Studie in der Primartherapie des Zervixkarzinoms zu evaluieren. Alle Patientinnen mit der Diagnose eines lokal fortgeschrittenen oder metastasierten Zervixkarzinom welche zwischen 2008 und 2015 in der onkologischen Ambulanz der Universitatsfrauenklink Koln eine primar systemische, platin- und taxanbasierte Polychemotherapie mit oder ohne Bevacizumab erhielten wurden in diese retrospektive Evaluation eingeschlossen. Die primar systemische Polychemotherapie ist definiert als eine Kombination aus Cisplatin (40 mg/m2/KOF) und Docetaxel (35 mg/m2/KOF) appliziert in einem wochentlichen Schema. Insgesamt wurden 32 Patientinnen primar chemotherapiert bzw. radiochemotherapiert. 26 Patientinnen erhielten eine Polychemotherapie mit Cisplatin/Taxotere (40/35 mg/m2/KOF/q7). 3 weitere Patientinnen erhielten dieses Schema erganzt durch eine VEGF-Blockade mit Bevacizumab 5 mg/Kg/KG/q7. Fur eine Patientin im FIGO Stadium IV (M1 hepatisch) erfolgte eine Modifikation des definierten Schemas zu Gunsten eines dosisintensivierten Protokolls mit 12x Paclitaxel 90 mg/m2/KOF/q7, Carboplatin AUC6/q28 und Bevacizumab 15 mg/Kg/KG/q21. In der Gesamtschau ergab sich, dass Patientinnen ohne VEGF-gerichteter Therapie im Stadium I allesamt eine postoperative Komplettremission zeigten. Im Stadium II zeigte sich bei gleicher Therapie nur in 12,5% der Falle eine Komplettremission, in 50% eine partielle und in 37,5 5 keinerlei Therapieansprechen. Ahnliche Ergebnisse stellten sich fur die Stadien III und IV ein. Insgesamt erhielten 4 Patientinnen im Stadium II-IV die zusatzliche VEGF-gerichtete Therapie. Im Einzelnen ergab sich fur eine 29-jahrige Patientin eine postoperative Komplettremission im Stadium IIb. Fur die zwei Patientinnen im Stadium IVa ergaben sich eine komplette und eine Teilremission bei nicht komplettierter Chemotherapie. Fur die Patientin im Stadium IVb, welche ein dosisintensiviertes Schema erhielt stellte sich ebenfalls die Komplettremission ein. In fruhen Erkrankungsstadien (