Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

BACKGROUND: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). PATIENTS AND METHODS: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. RESULTS: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. CONCLUSIONS: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.

Adult ovarian granulosa cell tumors: analysis of outcomes and risk factors for recurrence.

OBJECTIVE: Adult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall survival. METHODS: Patients with primary adult granulosa cell tumors treated in three international referral centers between July 1999 and December 2018 were included. The following data were anonymously exported from the prospective database: age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, surgical procedures, progression-free survival, and overall survival. Descriptive statistical analysis regarding tumor and treatment characteristics was performed. Survival analyses included Kaplan-Meier functions and Cox proportional hazard ratios (HR). RESULTS: A total of 168 patients with primary adult granulosa cell tumors were included. Median age was 50 years (range 13-82). With regard to stage distribution, 54.2% (n=91) of patients were FIGO stage IA, 1.2% (n=2) were stage IB, 26.8% (n=45) were stage IC, and 17.9% (n=30) were FIGO stage II-IV. 66.7% (n=112) of patients underwent surgical restaging, of whom 17.9% (n=20) were moved to a higher stage. In addition, 36 (21.4%) patients underwent fertility-sparing surgery. After a median follow-up of 61 months (range 0-209), 10.7% of patients (n=18) had recurrent disease and 4.8% (n=8) died of disease. Five-year progression-free survival was 86.1% and estimated overall survival was 95.7%. Five-year progression-free survival was worse for patients with advanced stages (FIGO stage IA/B vs IC: HR 5.09 (95% CI 1.53 to 16.9); FIGO stage IA/B vs II-IV: HR 5.62 (95% CI 1.58 to 19.9)). Nineteen patients receiving adjuvant chemotherapy had lower estimated 5-year progression-free survival compared with patients not receiving chemotherapy (49.7% vs 91.1%, p<0.001; HR 9.15 (95% CI 3.62 to 23.1)). CONCLUSION: The prognosis of patients with primary adult granulosa cell tumors is mainly determined by FIGO stage. The outcome of patients with FIGO stage IC is comparable to those with advanced stages. Fertility-sparing surgery seems to be a safe procedure in stage IA. Our data do not support the use of adjuvant chemotherapy in early and advanced stages of adult granulosa cell tumors.

HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients.

BACKGROUND: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. METHODS: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). RESULTS: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. CONCLUSIONS: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

Genotype-specific high-risk human papillomavirus infections and risk factors for cervical dysplasia in women with human immunodeficiency virus in Germany: results from a single-center cross-sectional study.

OBJECTIVE: Women living with HIV have an increased risk of human papillomavirus (HPV) infection and cervical cancer. Little is known about genotype-specific HPV prevalence, the impact of antiretroviral therapy, immunological status, and additional risk factors in women living with HIV in Germany. The goal of this study was to characterize the risk profile for cervical dysplasia in these women. METHODS: Patients with HIV infection presenting at Charité-Universitätsmedizin Berlin from October 2017 to September 2020 were included and underwent gynecological examination, colposcopy, cervical cytology and HPV genotype testing. HPV genotypes were stratified by carcinogenicity. Atypical squamous cells of undetermined significance or higher were considered abnormal cytology. Data were analyzed by SPSS software (version 26, 2019). A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: A total of 84 women were evaluated. The majority (95.2%) received antiretroviral therapy. Median CD4 cell count was 564 cells/µl (range 20-1969). 95.2% were previously screened for cervical cancer. High-risk HPV prevalence was 44%. High-high-risk HPV subtypes (16, 18, 31, 33, 45, 52, 58) were significantly associated with abnormal cytology (p<0.001). HPV16 was the most common genotype (23%), was significantly associated with abnormal cytology (p=0.002) and was the main risk factor for abnormal cytology (OR 8.55, 95% CI 2.15 to 34.13, p=0.002), followed by age <35 years (OR 4.96, 95% CI 1.23 to 19.61, p=0.033) and cigarette smoking (OR 3.944, 95% CI 0.98 to 15.88, p=0.053). CONCLUSIONS: Antiretroviral therapy and adherence to cervical cancer screening was high. High-high-risk HPV, especially HPV16, coincided with high incidence of cytological abnormalities. Women living with HIV in Germany have adequate immune status and are often pre-screened for cervical cancer, and therefore have a different risk profile for cervical dysplasia than in low-income or medium-income countries. Adapted screening programs should be defined.

Preoperative Uterine Artery Embolization in Women Undergoing Uterus-Preserving Myomectomy for Extensive Fibroid Disease: A Retrospective Analysis.

OBJECTIVES: The aim of this study was to determine if a long versus short interval between preoperative uterine artery embolization (PUAE) and subsequent myomectomy impact perioperative blood loss and the complication rate in cases of enlarged multi-fibroid uterus. DESIGN: In cases of an enlarged multi-fibroid uterus, operative myomectomy can lead to heavy blood loss and consequently increases the risk for transfusion and hysterectomy. PUAE can possibly contribute to a reduction of these risks. Our study was designed to determine if a long versus short interval between PUAE and subsequent surgery impacts perioperative blood loss and complication rate. PARTICIPANTS AND METHODS: PUAE was performed 24 h before the planned myoma enucleation in 21 patients between January 2011 and March 2016 (group 1) or 19 days before the operation in 23 patients from March 2016 to May 2018 (group 2). A comparison was made to a historical sample of 57 patients with large myomas (>10 cm) without PUAE (group 3). Perioperative blood loss, need for postoperative blood transfusion, and postoperative complications were recorded. Subjective improvement of myoma-related symptoms was assessed for each group by a questionnaire. RESULTS: PUAE was carried out successfully without complications in all patients. Conversion to hysterectomy was not needed in any of the PUAE patients but was necessary in one of the control patients. In the three groups' comparison, there was a significant lower risk for high blood loss (≥500 mL) in group 1 and a lower but not significant lower risk in group 2 compared to group 3 without an embolization preoperatively. Also, a significant lower risk for postoperative blood transfusion for group 1 (OR 0.02; 0.001-0.328; p = 0.01) and 2 (OR 0.02; 0.001-0.277; p = 0.01) compared to group 3 was observed. The postoperative complication risk was lower in group 2 (model 1: OR 0.12; 0.016-0.848; p = 0.03; model 2 OR 0.07; 0.009-0.588; p = 0.01) compared to group 3. In the context of the postoperative questionnaire, 10 of 11 patients in group 1, 12 of 12 patients in group 2, and 31 of 36 patients from the control group reported an improvement of their complaints. CONCLUSION: PUAE is beneficial for uterus-preserving removal of myomas from patients with a substantially enlarged uterus. There is a significant reduction of high blood loss (≥500 mL), need for postoperative blood transfusion, and postoperative complications in patients with extensive fibroid disease after PUAE compared to no intervention before myoma enucleation.

[Use of emergency rooms by so-called multiple users: results of a prospective study with special consideration of the migration status]. / Inanspruchnahme von Notaufnahmen durch sog. Mehrfachnutzer/-innen: Ergebnisse einer prospektiven Studie unter besonderer Berücksichtigung des Migrationsstatus.

Objectives: Can we identify predictive factors for the group of so-called multiple users (MU; 4 and more uses of an emergency department [ED] in the past 12 months)? Are people with a migration background more likely to be classified in the MU group? Methodology: Included were consecutive patients who visited three EDs in Berlin from July 2017 to July 2018. Using a questionnaire, diseases, reasons for visiting the ED and socioeconomic factors were recorded. Comparisons between migrants (1st generation), their descendants (2nd generation) and nonmigrants were assessed using logistic regression. Results: A total of 2339 patients were included in the evaluation (repeat rate 56%), of which 901 had a migration background. Young women (<30 years), chronically ill, pregnant women, patients with severe complaints and people with (self-assessed) moderate and poor health quality as well as those without medical referral had a greater chance of multiple use of ED. Conclusion: MU burden the already increasing patient volume of ED. However, they represent a heterogeneous group of patients, among whom people with a migration background are not common. Further research is warranted to better understand the factors that lead to frequent use and to develop effective strategies to address the complex health needs of MUs.

Frailty Index for prediction of surgical outcome in ovarian cancer: Results of a prospective study.

BACKGROUND: Complete macroscopic tumor resection is the strongest prognostic factor for patients with ovarian cancer, which requires complex surgery for achievement. Based on the mostly advanced tumor stage and high symptom burden many patients are classified as frail which may limit optimal surgical outcome. Aim of this study is to evaluate the predictive ability of Frailty Index for surgical outcomes in patients with ovarian cancer. METHODS: This prospective study enrolled patients with ovarian cancer undergoing cytoreductive surgery. We classified frailty proposed by Mitnitski et al. regarding the cumulative deficit model of frailty. Utilizing Receiver Operator Characteristic (ROC) analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. The Kaplan-Meier method and log-rank test were used for overall survival analysis. RESULTS: Out of f 144 enrolled patients, the overall prevalence of frailty based on a Frailty Index >0.26 and Frailty Index >0.15 was 33% and 74%, respectively. The logistic regression shows that frail patients with a Frailty Index >0.26 (Odds ratio (OR): 3.64, 95% CI: 1.34-9.85, p = 0.01), ECOG PS > 1 (OR 6.33, 95% CI:1.31-30.51, p = 0.02) and high surgical complexity score (OR 8.86, 95% CI:1.88-41.76, p = 0.006) had a significant higher risk for severe postoperative complications. According to multivariable cox regression Frailty Index >0.15 (hazard ratio (HR) (HR 1.87, 95% CI: 1.01-3.47, p = 0.048), residual tumor <1 cm (HR 2.75, 95%CI: 1.53-4.99, p = 0.001), residual tumor >1 cm (HR 5.00, 95% CI: 2.74-9.13, p < 0.001) and albumin<35.5 g/dl (HR 1.92, 95% CI: 1.08-3.43, p = 0.03) resulted as significant parameters for poor overall survival. Resulted as significant parameters for poor overall survival. CONCLUSION: Next to surgical complexity score, ECOG PS > 1 and recurrent surgery, Frailty Index >0.26 is associated with severe postoperative complications in patients with ovarian cancer. Besides tumor residuals and low albumin levels a Frailty Index >0.15 predicts poor survival.

Lymphovascular space invasion and Ki67 as predictors of lymph node metastasis in primary low grade serous ovarian cancer.

OBJECTIVE: Low grade serous ovarian cancers characterize a unique clinical pattern and likely less frequent incidence of lymphatic metastasis. The expression level of Ki67 is associated with differences in prognosis and therapy outcome. However, its expression in combination with lymphovascular space invasion has not been evaluated in the prediction of lymphatic metastasis. METHODS: Patients with low grade serous ovarian cancer were identified in an institutional database. Patients with primary low grade serous ovarian cancer diagnosed and/or treated at our center between September 2000 and December 2018 were identified. Receiver operator characteristics curve analysis was performed to find the cut-off values of per cent Ki67 to discriminate patients with lymph node metastasis. The association between the presence of lymphovascular space invasion and lymph node involvement was analyzed. RESULTS: A total of 109 patients with primary low grade serous ovarian cancer were identified in our institution's database. Of these, 72 (66.1%) patients underwent primary surgery with pelvic and para-aortic lymph node dissection. Complete data for Ki67 expression and lymphovascular space invasion were obtained for 61 (84.7%) of these patients. Among them, 37 (60.7%) patients had lymph node metastasis. The presence of lymphovascular space invasion was associated with an increased risk of lymph node metastases (odds ratio (OR)=12.78, 95% confidence interval (CI) 3.15 to 51.81; p<0.001). In multivariate analysis including age >65 years, peritoneal carcinomatosis, and ascites>500 mL, lymphovascular space invasion remained a significant risk factor for lymphatic metastases (OR=35.11, 95% CI 2.38 to 517.69; p=0.010). Ki67 ≥6% was associated with a higher risk of lymphovascular space invasion (OR=3.67, 95% CI 1.26 to 10.64; p=0.017). No significant correlation between Ki67 expression level and nodal metastases was found (OR=2.19, 95% CI 0.76 to 6.26; p=0.14). Neither presence of lymphovascular space invasion or nodal metastases was associated with a statistically poorer prognosis. CONCLUSIONS: We showed an association between lymphovascular space invasion, Ki67 expression, and risk of lymph node metastasis in primary low grade ovarian cancer. Further prospective trials evaluating lymphovascular space invasion and Ki-67 as predictors of lymph node metastasis are needed.

Evaluation of Biomarkers in Myoma Patients: A Prospective Study Investigating the Role of LDH, CA 125, and IGF-1 after Uterus-Preserving Surgical Therapy.

OBJECTIVE: Myomas are one of the most common tumors of the lower abdomen in women. At present, sonography and clinical examination are the prevalent diagnostic standards for these tumors, and no biomarkers have been established yet. The primary aim of this study was to determine if the surgical removal of myomas leads to a drop of lactate dehydrogenase (LDH), CA 125, and/or insulin-like growth factor (IGF-1) and therefore if these parameters are suitable as potential biomarkers for the presence or recurrence of a myoma. STUDY DESIGN: The blood levels of LDH, CA 125, and IGF-1 were determined in 83 patients (age 18-50) with a verified diagnosis of myomas and surgical therapy at 3 different timepoints: preoperative (T0), 2 days postoperative (T1), and 6 months postoperative (T2). Vaginal sonography was performed preoperatively and once again at 6 months postoperatively. RESULTS: The median (Q1-Q3) LDH values dropped significantly postoperatively: 239 (217-266) U/L at T0 versus 217 (190-255) U/L at T1, p < 0.001. The median (Q1-Q3) IGF-1 values also dropped: 140.4 (118.6-179.0) ng/mL versus 112.4 (99.5-143.0), p < 0.001. By contrast, the CA 125 values rose slightly but not significantly. At 6 months (n = 34), the LDH values were not significantly different from either the preoperative or the immediate postoperative values. This was observed both in patients with and without a recurrence of myoma. In contrast, the median (Q1-Q3) IGF-1 level at T2 was significantly elevated both in patients with sonographic evidence of new myomas (129.0 [116.0-163.1] ng/mL, p = 0.023) and in patients with sonographic proof of no new myomas (161.0 [130.2-198.5] ng/mL, p < 0.001). CONCLUSION: Both LDH and IGF-1 dropped significantly in the immediate postoperative days in women with myomas after uterus-preserving surgeries were performed. The postoperative concentration of IGF-1 was correlated with the evidence of new myomas and can be potentially used for further monitoring. Future studies should be able to confirm these results. This study concludes that myomas do influence LDH and IGF-1 and could possibly be suitable as biomarkers.

Effects of epigallocatechin gallate-enriched green tea extract capsules in uterine myomas: results of an observational study.

PURPOSE: The daily ingestion of green tea extract (GTE) capsules in women with oligo- or asymptomatic uterine myomas was monitored over 6 months with regard to their quality of life, myoma-associated complaints and side effects. METHODS: The participants were interviewed and examined at the beginning of the study (T1) and then again after 6 months (T3). Quality of life was assessed using a SF-12 questionnaire while their myoma-associated complaints were ascertained by using a self-developed myoma symptom questionnaire. Changes in the size of the myomas were evaluated by vaginal sonography. Side effects after 3 months (T2) and 6 months were documented by systematic interviews. RESULTS: Overall; 25 participants (median 45 years) have been enrolled. The analysis of the SF-12 questionnaire showed a significant improvement of the physical cumulative score of the SF-12 during the 6 month GTE capsule ingestion (T1: mean value (M) = 52.731; 95% confidence interval (KI95%): 49.791-55.671; T3: M = 55.862; KI95%%: 55.038-56.685; p = 0.019). However, the mental cumulative score of the SF-12 did not change significantly (p = 0.674). No significant correlation could be established between the capsule ingestion and changes in the symptom questionnaire, the laboratory parameters nor the myoma size. No relevant adverse side effects were reported. CONCLUSION: Women who took GTE capsules showed a significant improvement in their physical cumulative score on the SF-12, but not in the global QoL score. Myoma size or other objective parameters did not change.

ECOG and BMI as preoperative risk factors for severe postoperative complications in ovarian cancer patients: results of a prospective study (RISC-GYN-trial).

BACKGROUND: Accompanying co-morbidities in patients with ovarian cancer are of major relevance for scheduling debulking surgery, especially in the anesthesiological consultations. Aim of this study was to evaluate the impact of co-morbidities and patient characteristics on postoperative complications. METHODS: Patients undergoing maximal cytoreductive surgery were prospectively enrolled from October 2015 to January 2017. Various variables were recorded, such as the Charlson comorbidity index, Eastern cooperative oncology group scale of performance status (ECOG PS) and the American society of anesthesiologists physical status classification system (ASA PS). Surgical complications were graded using the Clavien-Dindo criteria. Logistic regression models were used to analyze risk factors for severe postoperative complications. RESULTS: Of 106 enrolled patients, 19 (17.9%) developed severe postoperative complications grade ≥ IIIb according to Clavien-Dindo criteria. In the multivariable regression analysis impaired (ECOG PS) > 1 (odds ratio OR) 13.34, 95% confidence interval (CI) 1.74-102.30, p = 0.01), body mass index (BMI) > 25 kg/m2 (OR 10.48, 95% CI 2.38-46.02, p = 0.002) along with the use of intraoperative norepinephrine > 0.11 µg/kg/min (OR 4.69, 95% CI 1.13-19.46, p = 0.03) and intraoperative fresh frozen plasma (FFP) > 17 units (OR 4.11, 95% CI 1.12-15.14, p = 0.03) appeared as significant predictors of severe postoperative complications. CONCLUSION: We demonstrated that neither the presence of a certain comorbidity nor the summation of the co-morbidities were associated with adverse outcome. Patient characteristics, such as ECOG PS > 1 and obesity (BMI > 25 kg/m2), are highly predictive factors for severe postoperative complications. The analysis of intraoperative data showed that the need for more than > 0.11 µg/kg/min of norepinephrine and transfusions of FFPs more than 17 units were strongly associated with severe postoperative complications.

Preoperative quality of life as prediction for severe postoperative complications in gynecological cancer surgery: results of a prospective study.

PURPOSE: The aim of this study was to investigate preoperative quality of life (QoL) as a predictive tool for severe postoperative complications (POC) in gynecological cancer surgery. METHODS: This is a prospective study of patients undergoing gynecologic cancer surgery at an academic center in Germany. QoL was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) and the NCCN Distress Thermometer (DT). Several geriatric assessment tools have been applied. POC were graded using Clavien-Dindo criteria. Using multivariable logistic regression models, we identified predictive clinical characteristics for postoperative complications. RESULTS: Within 30 days of surgery, 40 patients (18%) experienced grade ≥ 3b complications including 9 patients (4%) who died. The dominant complication was anastomosis insufficiency with 13 patients (5.8%). In the multivariable stepwise logistic regression through all univariate significant variables, we found that impaired physical functioning was predictive of POC, defined by an EORTC score < 70 (OR 5.08, 95% CI 2.23-11.59, p < 0.001). Regarding symptoms nausea/vomiting assessed as an EORTC score > 20 (OR 3.08, 95% CI 1.15-8.26, p = 0.025) indicated a significant predictive value. Being overweight or obese (BMI > 25) were also identified as predictive factors (OR 5.44, 95% CI 2.04-14.49, p = 0.001) as were reduced Mini Mental State Examination (MMSE) results < 27 (OR 7.94, 95% CI 1.36-45.46, p = 0.02). CONCLUSION: Preoperative QoL measurements could help to predict postoperative complications in patients with gynecological cancer. Patients with limitations of mobility, debilitating symptoms and cognitive impairment have an increased risk for developing severe POC.

[Effects of hyperemesis gravidarum on the course of pregnancy and birth, with special attention to the risk factor of migration background]. / Auswirkungen einer Hyperemesis gravidarum auf Schwangerschaftsverlauf und Geburtsausgang unter besonderer Berücksichtigung des Risikofaktors Migrationshintergrund.

MAIN QUESTIONS: In this investigation of hospitalized cases of HG and subsequent births, we examine differences between patients who have and who have not experienced migration as well as the effect of HG on perinatal outcome. METHODS: Retrospective quantitative data of hospitalized patients suffering from HG (1997-2015) was analyzed. Also analyzed was a retrospective record of perinatal data on a subgroup of patients (2002-2016), and a control group (matched pairs) based on the register of births created. RESULTS: 1103 women with HG were hospitalized; in 434 cases birth outcome data could be evaluated as well. Migrants suffer from HG earlier in pregnancy; they are, however, less frequently exposed to psychosocial stress (according to anamnestic data). HG patients are younger and have more multiple pregnancies; the newborns are lighter (-70g) but have fewer congenital malformations (aOR 0.32, 95% CI 0.11-0.96) and are less frequently in need of treatment on the neonatology ward (aOR 0.59, 95% CI 0.36-0.97). CONCLUSION: Pregnant migrants are a special risk group for HG, possibly because of migration-caused stress. With severe HG, there are no adverse outcomes on the rest of the pregnancy.

Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation): a novel surgical technique for advanced ovarian cancer.

BACKGROUND: A Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in advanced ovarian cancer. The study prescribed and analysed the results of this novel technique for primary cytoreductive surgery. METHODS: The study included 208 patients operated between January 2015 and December 2017 in Charité, Berlin. The TROMP operation was performed in 58 patients, whereas the other 150 patients were operated with the conventional cytoreductive method. RESULTS: The complete tumor resection rate accounts for 87.9% in TROMP group and 61.3% in the conventional surgery group. (p=0.001). This difference was even stronger in the sub-group of very advanced stages (T3c+T4) (85.1% of TROMP group and in only 53.1% in the conventional surgery group, p=0.001). The duration of the primary cytoreductive surgery was about 33 minutes shorter in TROMP group (median: 335 minutes vs 368 minutes; TROMP vs conventional, respectively) in spite of the fact that the most advanced cytoreductive procedures were performed statically significant more in TROMP operation arm in comparison with the conventional surgery arm. There was no statistically significant difference between the groups regarding the postoperative complication, blood loss or the length of stay in intensive care unit. CONCLUSION: Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) is a feasible and very effective technique of surgical therapy in advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9% without increasing the blood loss, postoperative complications or the duration of surgery. A prospective randomized study is advised to validate these results.

Pre-operative serum CA125, peritoneal cancer index and intra-operative mapping score as predictors of surgical results in primary epithelial ovarian cancer.

OBJECTIVE: Prediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer and their predictive value for post-operative outcome. METHODS: A total of 70 patients with primary epithelial ovarian cancer, who underwent primary cytoreductive surgery at Charité, Berlin between January 2013 and February 2014 were included. In all patients, pre-operative CA125 values, intra-operative peritoneal cancer index, and intra-operative mapping of ovarian cancer were determined. RESULTS: Using a receiver operating characteristic analysis, cut-off values for CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer score could be defined. Patients with pre-operative serum CA125 >600 U/mL had a three times higher risk for residual tumor after primary cytoreductive surgery (p=0.037). A peritoneal cancer index score >20 indicated a nine times increased risk for residual tumor (p=0.003). More than six affected abdominopelvic fields on the intra-operative mapping of ovarian cancer was associated with a 25 times higher risk of residual tumor after primary cytoreductive surgery (p≤0.05). The combination of all three values predicted residual tumor in up to 90% of patients. CONCLUSION: We found that pre-operative CA125 >600 U/mL, peritoneal cancer index >20, and intra-operative mapping of ovarian cancer score >6 could be used as predictors of complete tumor resection. The combination of all these three values predicted the incomplete resection of disease in up to 90% of patients even in experienced centers.

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer.

OBJECTIVE: Low-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy. METHODS: Patients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI). RESULTS: A total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response). CONCLUSIONS: This is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

Role of predictive markers for severe postoperative complications in gynecological cancer surgery: a prospective study (RISC-Gyn Trial).

BACKGROUND: Surgery for gynecological cancer involves highly invasive and complex procedures potentially associated with various complications, which can cause extended hospital stays and delay of subsequent therapy, with a detrimental effect on the prognosis. The aim of this study was to explore and define the predictors of severe postoperative complications in patients undergoing surgery for gynecologic cancer. METHODS: Patients undergoing surgery for gynecologic cancers were analyzed prospectively from October 2015 through January 2017. Using validated assessment tools preoperatively, we assessed comorbidities, performance status, quality of life, nutritional and body composition by bioelectrical impedance analysis, and the surgical data of each patient. Surgical complications were graded using the Clavien-Dindo criteria. Using stepwise logistic regression models, we identified predictive markers for postoperative complications. RESULTS: Of the 226 enrolled patients, 40 (17.7%) experienced a grade ≥IIIb complication according to the Clavien-Dindo criteria. In the regression analysis, overweight/obesity (body mass index >25) (OR 6.41, 95% CI 2.38 to 17.24; p<0.001) and impaired physical functioning defined by a quality of life questionnaire (OR 4.19, 95% CI 1.84 to 9.50; p=0.001) emerged as significant predictors of postoperative complications. Moreover, postoperative complications were predicted by phase angle of bioelectrical impedance analysis <4.75° (OR 3.11, 95% CI 1.35 to 7.16; p=0.008) and Eastern Cooperative Oncology Group (ECOG) performance status >1 (OR 2.51, 95% CI 1.06 to 5.92; p=0.04). Intraoperative factors associated with higher risk of postoperative complications were increased use of norepinephrine (>11 µg/kg/min) (OR 5.59, 95% CI 2.16 to 14.44; p<0.001) and performance of large bowel resection (OR 4.28, 95% CI 1.67 to 10.97; p=0.002). CONCLUSION: In patients undergoing surgery for gynecological cancer, preoperative evaluation of performance status according to ECOG, domains of quality of life and nutritional status, as well as intraoperative monitoring of risk factors, might help to identify patients at high risk for severe postoperative complications, and thus reduce surgical morbidity and mortality.

Perioperative management of positioning in gynecological cancersurgery: a national NOGGO-AGO intergroup survey.

INTRODUCTION: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany. METHODS: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management. RESULTS: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively. DISCUSSION: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications.

Expectations and preferences of patients with primary and relapsed ovarian cancer to maintenance therapy: A NOGGO/ENGOT-ov22 and GCIG survey (Expression IV).

BACKGROUND: Maintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients' preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer. METHODS: A 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy. RESULTS: Overall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer. CONCLUSION: Patients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings.

3D ultrasound as a surgical quality control of conization in patients with severe dysplasia: a prospective study.

PURPOSE: To compare the techniques for cone measurement with ultrasound to determine the size of the resected tissue and to evaluate parameters which may be relevant for stratifying women at risk who need surveillance when pregnant. METHODS: The present study included women with a pathological cervical biopsy. Cervical length and volume were determined by transvaginal ultrasound prior to conization. The pathologist measured the volume of the removed tissue by the fluid displacement technique and using a ruler. A repeat transvaginal ultrasound was performed during a follow-up visit. Factors affecting cone volume as well as the correlation between measurement techniques were analyzed. RESULTS: A total of 28 patients underwent cervical excision treatment. The mean cervical volumes measured sonographically before and after the operation were 17.72 ± 7.34 and 13.21 ± 5.43 cm3, respectively. The proportion of volume excised was 25.50 ± 17.43%. A significant correlation was found between the cone depth and the cone volume measured by the fluid displacement technique, and histopathologically and sonographically measured difference in cervical volume. The interobserver reliability coefficient was > 0.9. Analyzing influential parameters, only age affected the extent of cone volume and the correlation between the three measurement techniques. CONCLUSION: Commonly applied techniques of cervical and cone measurement are equivalent and interchangeable. Our ultrasound data show variety in the volume and length of the cervix, and in the proportion of the volume excised at conization. Ultrasound measurements may help the surgeon to estimate not only the dimension of the remaining cervix but also its function.