An easy, fast, and accurate way for implementing the standards of care for the management of patients with endometrial carcinoma into daily clinical practice: the ESGO mobile app.

The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly published comprehensive evidence-based guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. In order to improve their implementation, a free downloadable easy-to-use mobile app was developed.Two interactive decision tools were created for (1) helping users to identify the recommended surgical steps, especially in terms of nodal staging approach based on the pre-operatively assumed risk group (tool #1), and (2) to facilitate prognostic risk group allocation and adjuvant treatment decision-making after primary surgery integrating both clinicopathological and molecular markers (if known) (tool #2). Algorithms and readable guidelines were also incorporated into the mobile app on all relevant issues of diagnosis and treatment. The scientific content presented in the app will be updated and modified in the future based on new evidence and user feedback.This article presents the decision tools and two practical examples of using these calculators to illustrate that the ESGO mobile app (available without the necessity of an internet connection) can provide fast and accurate responses to complex clinical questions that require the evaluation of numerous parameters.

The role of factor XIII in surgery for advanced stage of epithelial ovarian cancer.

INTRODUCTION: Hereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values > 75% as normal (group A), 55-75% as reduced (group B) and < 55% as low (group C). Complications were classified according to the Clavien-Dindo Classification, class III-V complications were defined as severe. RESULTS: 347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), > 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery (> 285 min.) were significant predictive factors for severe complications. CONCLUSION: FXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy.

Clinical outcome in patients with primary epithelial ovarian cancer and germline BRCA1/2-mutation - real life data.

BACKGROUND: We evaluated the clinical impact of germline (g)BRCA1/2-mutation on initial disease presentation, surgical implications, surgical morbidity and survival in patients with advanced epithelial ovarian cancer (EOC) undergoing debulking surgery (DS). METHODS: Data of all consecutive EOC patients with stage III/IV, high-grade serous disease and known gBRCA1/2 status (gBRCA; non-gBRCA), who underwent DS at our department between 01/2011 and 06/2019 were analyzed. Associations between gBRCA-status and severe postoperative complications and survival were analyzed. RESULTS: gBRCA-status was determined in 50.1% (612/1221) of all patients. gBRCA was present in 21.9% (134/612). Significant differences were observed in terms of median age (p = 0.001) and histology (high-grade serous histology gBRCA: 98.5%, non-gBRCA 76.2%; p < 0.001). gBRCA-status had no impact on intraoperative disease presentation, surgical complexity or complete resection rate (gBRCA: 74.4%, non-gBRCA: 69.0%; p = 0.274). gBRCA-status was not predictive for severe postoperative complication (gBRCA: 12.0%, non-gBRCA: 19.1%; p = 0.082). Median PFS and OS was 31/22 and 71/53 months in patients with/without gBRCA-mutation, respectively. gBRCA was a significant prognostic factor for PFS (HR 0.57 p < 0.001) and for OS (HR 0.64, p = 0.048) after adjusting for established prognostic factors. CONCLUSIONS: gBRCA-status had no impact on initial disease presentation, surgical results or postoperative complications. gBRCA patients have a significantly longer PFS but the impact on the long term prognosis is unclear. Complete resection remains the most important prognostic factor in patients with EOC independent of gBRCA-status.

Incorporating patient centered benefits as endpoints in randomized trials of maintenance therapies in advanced ovarian cancer: A position paper from the GCIG symptom benefit committee.

BACKGROUND: Quality of life and patient reported outcome measures (PROMs) are important secondary endpoints and incorporated in most contemporary clinical trials. There have been deficiencies in their assessment and reporting in ovarian cancer clinical trials, particularly in trials of maintenance treatment where they are of particular importance. The Gynecologic Cancer InterGroup (GCIG) symptom benefit committee (SBC) recently convened a brainstorming meeting with representation from all collaborative groups to address questions of how to best incorporate PROMs into trials of maintenance therapies to support the primary endpoint which is usually progression free survival (PFS). These recommendations should harmonize the collection, analysis and reporting of PROM's across future GCIG trials. METHODS: Through literature review, trials analysis and input from international experts, the SBC identified four relevant topics to address with respect to promoting the role of PROMs to support the PFS endpoint in clinical trials of maintenance treatment for OC. RESULTS: The GCIG SBC unanimously accepted the importance of integrating PROM's in future maintenance trials and developed four guiding principles to be considered early in trial design. These include 1) adherence to SPIRIT-PRO guidelines, 2) harmonization of selection, collection and reporting of PROM's; 3) combining Health Related Quality of Life (HRQL) measures with clinical endpoints and 4) common approaches to dealing with incomplete HRQL data. CONCLUSIONS: Close attention to incorporating HRQL and PROM's is critical to interpret the results of ovarian cancer clinical trials of maintenance therapies. There should be a consistent approach to assessing and reporting patient centered benefits across all GCIG trials to enable cross trial comparisons which can be used to inform practice.

The value of pretreatment serum butyrylcholinesterase level as a novel prognostic biomarker in patients with cervical cancer treated with primary (chemo-)radiation therapy.

BACKGROUND: Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy. METHODS: We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015. Pretreatment serum BChE levels were correlated with clinico-pathological parameters and response to treatment. Uni- and multivariate survival analyses were performed to assess the association between decreased serum BChE levels and progression-free (PFS), cancer-specific (CSS), and overall survival (OS). RESULTS: A total of 356 patients were eligible for inclusion into the present study. The median (IQR) pretreatment serum BChE level was 6180 (4990-7710) IU/l. Lower serum BChE levels were associated with lower BMI (p < 0.001), advanced tumor stage (p = 0.04), poor treatment response (p = 0.002), the occurrence of disease recurrence (p = 0.003), and the risk of death (p < 0.001). In uni- and multivariate analyses, low pretreatment serum BChE levels were independently associated with shorter PFS (HR 1.8 [1.2-2.6]; p = 0.002), CSS (HR 2.2 [1.4-3.5], p < 0.001), and OS (HR 2.0 [1.4-2.9]; p < 0.001). CONCLUSIONS: Low pretreatment serum BChE levels are associated with advanced tumor stage and poor response to treatment, and serve as an independent prognostic biomarker for shorter PFS, CSS, and OS in patients with cervical cancer treated with primary (chemo-)radiation therapy.

Lymph node ratio in inguinal lymphadenectomy for squamous cell vulvar cancer: Results from the AGO-CaRE-1 study.

OBJECTIVE: Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project. METHODS: The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival. RESULTS: In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of >0% < 20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (P < .001), advanced tumor stage (P < .001), high tumor grade (P < .001), and deep stromal invasion (P < .001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%, >0% < 20%, and ≥20%, respectively (P < .001, P < .001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01-14.98, P < .001), FIGO stage (HR 1.41, 95%-CI 1.18-1.69, P < .001), and patient's performance status (HR 1.59, 95%-CI 1.39-1.82, P < .001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64-28.78, P < .001), and performance status (HR 1.72, 95%-CI 1.44-2.07, P < .001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models. CONCLUSIONS: In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.

Pre-operative hypoalbuminemia is associated with complication rate and overall survival in patients with vulvar cancer undergoing surgery.

OBJECTIVE: Hypoalbuminemia, a known marker for malnutrition, has been associated with an increased risk for perioperative morbidity and poor prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic and predictive value of pre-treatment serum albumin levels for survival and postoperative complications in patients with vulvar cancer undergoing surgery. METHODS: Within in this retrospective study, we assessed data of 103 consecutive patients with vulvar cancer undergoing primary surgery into this study. Pre-treatment serum albumin levels were correlated with clinico-pathological parameters and complications. We performed univariate log-rank test and multivariable Cox regression models to evaluate the association between pre-treatment serum albumin and survival. RESULTS: We found hypoalbuminemia (< 35 mg/dl) in 9 of 103 (8.7%) patients. No difference in tumor characteristics was observed between patients with hypoalbuminemia and normal serum albumin levels. Difference in postoperative complications (55.6% and 37.8% of patients with hypoalbuminemia and normal serum albumin levels, respectively) was not statistically significant (p = 0.345). Shorter overall survival (OS) was observed in patients with hypoalbuminemia (5-year OS rate 17.1%) when compared to patients with normal serum albumin levels (5-year OS rate 58.6%, p = 0.004). In multivariable analysis, age (p = 0.017), FIGO stage (p = 0.011) and serum albumin levels (p = 0.013) were independently associated with OS. CONCLUSION: Pre-treatment hypoalbuminemia is an independent prognostic biomarker for OS in patients with vulvar cancer. We did not find an association between pre-treatment hypoalbuminemia and a higher risk for postoperative complications.

Predictive and Prognostic Implication of Bowel Resections During Primary Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer.

OBJECTIVES: The aims of this study were to assess anastomotic leakage (AL) rate and risk factors for AL in patients with advanced epithelial ovarian cancer (EOC) undergoing cytoreductive surgery including bowel resections and to evaluate the prognostic implication of AL. METHODS: Data of 350 consecutive patients with International Federation of Gynecology and Obstetrics EOC stage IIB-IV who underwent cytoreductive surgery at the Department of General Gynecology and Gynecologic Oncology of the General Hospital of Vienna between 2003 and 2017 were collected. Within this cohort, 192 patients (54.9%) underwent at least 1 bowel resection and were further analyzed. Preoperative risk factors for AL were computed using logistic regression models. Prognostic factors for overall survival were evaluated by using log-rank tests and multivariable Cox regression model. RESULTS: Overall, the AL rate was 4.7% for patients with advanced EOC undergoing cytoreductive surgery with at least 1 bowel resection, including patients with multiple large bowel resections. The AL rate for patients with isolated rectosigmoid resection was 1.9%. In univariate analysis, the number of anastomoses per surgery (P = 0.04) was associated with the occurrence of AL. In multivariable analysis, rectosigmoid resection with additional large bowel resection was associated with a higher risk of AL compared with isolated rectosigmoid resection (P = 0.046; odds ratio, 7.23 [95% confidence interval, 1.04-50.39]). Anastomotic leakage was associated with decreased overall survival (P = 0.04) in univariate but not in multivariable survival analysis. CONCLUSIONS: Anastomotic leakage rate after rectosigmoid resection in advanced EOC is acceptably low and outweighs increased perioperative risks when performed in a high-volume institution. Nonetheless, the occurrence of AL is a severe adverse event, which even seems to negatively affect patients' overall prognosis. As no factor could be identified to clearly predict AL, extensive procedures comprising multiple bowel resections, should be avoided particularly when complete resection cannot be achieved.

Influence of training level on cervical cone size and resection margin status at conization: a retrospective study.

OBJECTIVE: To explore whether a surgeon's training level influences the rate of incomplete resections or the amount of resected cervical tissue in women treated with large loop excision of the transformation zone (LLETZ). METHODS: The present study is a retrospective analysis of the data of women who had undergone LLETZ for cervical intraepithelial neoplasia (CIN) within the years 2004-2008 at the Medical University of Vienna. Women were grouped according to the level of training of the operating surgeon (i.e, resident or staff gynecologist) and univariate and multivariable analyses were performed to identify independent risk factors for excessive cone volume, depth and incomplete resection (i.e., positive resection margin). RESULTS: Data of 912 women were analysed. Residents had a significantly larger cone volume [median 2681 (interquartile range 1472-4109) mm3] than staff gynecologists [2094 (1309-3402) mm3] (p = 0.001) in univariate analysis. The depth of resection and the rate of incomplete resection were comparable between both groups. In a binary logistic multivariable analysis, the level of training as well as patient's age was significantly associated with a cone volume larger than 2500 mm3. CONCLUSION: Conization performed by residents as opposed to staff gynecologists does not compromise the procedure's effectiveness but may expose women to a potential additional risk for adverse obstetrical outcomes due to excessive resection of cervical tissue.

Human Bile Reduces Antimicrobial Activity of Selected Antibiotics against Enterococcus faecalis and Escherichia coli In Vitro.

It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant, and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilization of the bile fluid by gamma irradiation, its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM), and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller-Hinton broth (MHB) over 24 h. Bacterial counts (in CFU per milliliter after 24 h) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis, indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM, and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis This effect was strongest for TGC against the two strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail.

Increased genitourinary fistula rate after bevacizumab in recurrent cervical cancer patients initially treated with definitive radiochemotherapy and image-guided adaptive brachytherapy.

BACKGROUND AND PURPOSE: Patients with recurrent cervical cancer (RecCC) who received definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT) as primary treatment are currently treated in our institution with palliative intent by chemotherapy (CHT) combined with bevacizumab (BEV). We aim to evaluate the risk of gastrointestinal (GI)/genitourinary (GU) fistula formation in these patients. MATERIALS AND METHODS: Data of 35 consecutive patients with RecCC treated initially with radiochemotherapy and IGABT were collected. Known and presumed risk factors associated with fistula formation were evaluated. Fistula rate was compared between patients receiving CHT or CHT+BEV. RESULTS: Of the 35 patients, 25 received CHT and 10 patients received CHT+BEV. Clinical characteristics were comparable. Fistulae were reported in 6 patients: two fistulae (8%) in the CHT group, four (40%) in the CHT+BEV group. GU fistula occurred in the CHT+BEV group only (3/4). Of these 6 patients with fistulae, 5 (83%) had undergone previous invasive procedures after the diagnosis of RecCC and 1 patient had undergone pelvic re-irradiation; 3/6 patients had developed a local recurrence. No other risk factors for fistula formation were identified. CONCLUSION: In patients with RecCC after definitive radiochemotherapy including IGABT, the addition of BEV to CHT may increase the risk for GU fistula formation, particularly after invasive pelvic procedures. Future clinical studies are required to identify predictors for fistula formation to subsequently improve patient selection for the addition of BEV in the RecCC setting.

Prognostic value of lymph node ratio and number of positive inguinal nodes in patients with vulvar cancer.

OBJECTIVE: To estimate the prognostic significance of lymph node ratio and number of positive nodes in vulvar cancer patients. METHODS: This international multicenter retrospective study included patients diagnosed with vulvar cancer treated with inguinal lymphadenectomy. Lymph node ratio (LNR) is the ratio of the number of positive lymph nodes (LN) to the number of removed LN. Patients were stratified into risk groups according to LNR. LNR was correlated with clinical-pathological parameters. Survival analyses were performed. RESULTS: This analysis included 745 patients. In total, 292 (39.2%) patients had positive inguinal LN. The mean (SD) number of resected and positive LN was 14.1 (7.6) and 3.0 (2.9), respectively. High LNR was associated with larger tumor size and higher tumor grade. Patients with LNRs 0% (N0), >0<20%, and >20% had 5-year overall survival (OS) rates of 90.9%, 70.7%, and 61.8%, respectively (P<0.001). LNR was associated with both local and distant recurrence-free survival (P<0.001). Patients with 0, 1, 2, 3 or >3 positive lymph nodes had 5-year OS rates of 90.9%, 70.8%, 67.8%, 70.8% and 63.4% respectively (P<0.001). In multivariate analysis, LNR (P=0.01) and FIGO stage (P<0.001), were associated with OS, whereas the number of positive nodes (P=0.8), age (P=0.2), and tumor grade (P=0.7), were not. In high-risk patients, adjuvant radiotherapy was associated with improved survival. CONCLUSIONS: LNR provides useful prognostic information in vulvar cancer patients with inguinal LN resection in vulvar cancer. LNR allows for more accurate prognostic stratification of patients than number of positive nodes. LNR seems useful to select appropriate candidates for adjuvant radiation.

Preoperative C-reactive protein serum levels as a predictive diagnostic marker in patients with adnexal masses.

OBJECTIVE: To evaluate C-reactive protein (CRP) serum levels as a preoperative predictive marker for ovarian cancer in patients with adnexal masses. METHODS: CRP serum levels of 1843 adnexal masses and subsequent surgery were investigated (patients with benign ovarian tumors: n=1423; borderline tumor of the ovary [BTO]: n=83; EOC: n=337). Test characteristics and predictive values of CRP serum levels were investigated by univariate analysis and multivariate binary logistic regression models. RESULTS: Median (interquartile range) serum CRP levels in patients with benign ovarian tumors, BTO, and EOC were 0.4 (0.1-0.6)mg/dL, 0.5 (0.2-0.9)mg/dL, and 1.6 (0.5-5.4)mg/dL, respectively (p<0.001). Sensitivity and specificity of the combination of CRP and CA-125 was 80.1% and 90.8%, negative predictive value (NPV) and positive predictive value (PPV) was 92.2% and 76.9%, respectively. In univariate and multivariate analysis, CRP serum levels were independently associated with presence of BTO and EOC (HR 6.7 [5.2-8.5], p<0.001 and HR 2.2 [1.4-3.3], p<0.001). The combination of CRP and CA-125 serum levels resulted in a number needed to treat of 2.11 to detect one case of EOC or BTO. CONCLUSION: CRP serum levels independently predicted the presence of BTO and EOC in patients with suspicious adnexal masses. CRP serum levels seem to be of additional value to CA-125 in the preoperative differential diagnosis of adnexal masses and might be particularly in combination with CA-125 clinically useful.

Pharmacokinetics of doripenem in plasma and epithelial lining fluid (ELF): comparison of two dosage regimens.

PURPOSE: In 2014, FDA released a warning for prescription of doripenem for ventilator-associated bacterial pneumonia due to unsatisfactory clinical cure rates. The present study explores if the observed lack of efficacy might be explained by insufficient target site pharmacokinetics in intensive care patients after two different infusion schemes. METHODS: Plasma and bronchoalveolar lavage sampling was performed in 16 intubated patients with pneumonia receiving doripenem either as 1-h or as 4-h infusion. Doripenem concentrations were measured at steady state in plasma over 8 h, bronchoalvoelar lavage was performed in each patient once either after 0 h, 2 h, 4 h or 6 h. RESULTS: In plasma, mean values of Cmax, Tmax and AUC0-8 were 16.87 mg/L, 0.69 h and 52.98 mg/L×h after 1 h of infusion, and 12.94 mg/L, 3.21 h and 70.64 mg/L×h after 4 h of infusion, respectively. While the later tmax in plasma was with delay mirrored in the lung, for ELF, much lower concentrations were observed (Cmax, Tmax and AUC0-8 after 1-h infusion of 4.6 mg/L, 2 h and 15.3 mg/L×h and after 4-h infusion 6.9 mg/L, 4 h and 14.8 mg/L×h). CONCLUSION: The difference in plasma pharmacokinetics after 1-h and 4-h infusion reflects in the concentration versus time profile in the lung, but concentration at the target site was not only considerably lower but also subject to high inter-individual variability. We hypothesise that insufficient concentrations at the target site might have contributed to the previously described lack of clinical efficacy and confirmed the demand for assessment of target site pharmacokinetics in larger patient collectives.

Natural history of cervical intraepithelial neoplasia in pregnancy: postpartum histo-pathologic outcome and review of the literature.

BACKGROUND: To study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women. METHODS: A retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed. RESULTS: A total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9% of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4%, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5%, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8%, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9%) and no progression to invasive cancer was observed. CONCLUSIONS: CIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.

Acetylic Salicylic Acid for the Treatment of Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world. Current treatment options provide relief from symptoms rather than stop disease progress. Results from various preclinical experiments suggest a causal benefit of acetylic salicylic acid (ASA) in the treatment of COPD. Hence, this study set out to examine the clinical benefit of ASA in the treatment of COPD. COPD patients (Global Initiative for Chronic Obstructive Lung Disease II-III) received either once daily 500 mg of ASA or a matching placebo for 12 weeks in addition to their preexisting medication. Clinical response in terms of pulmonary function testing, symptomatic response and adverse events were assessed. After 40 subjects were included, the study was stopped and an interim analysis was performed. The addition of ASA to the treatment of subjects with COPD had no effect on clinical features or spirometry (forced expiratory volume in 1 s: F = 0.49, d.f.1 = 1, d.f.2 = 74, p = 0.486) and non-pulmonary markers. COPD represents a complex of different diseases, although currently classified mainly by markers of lung function. If future trials test the effects of anti-inflammatory therapies, COPD subpopulations should be predefined based on inflammatory features.

Prognostic Value of Lymph Node Ratio in Patients with Uterine Carcinosarcoma.

Uterine carcinosarcoma is a rare high-grade endometrial cancer. Controversy has surrounded a number of aspects in the diagnosis and management of this unique clinicopathological entity, including the efficacy of adjuvant therapy, which has been questioned. An unusual surgico-pathological parameter with prognostic significance in a number of tumour sites is the lymph node ratio (LNR). The availability of data in this respect has been scarce in the literature. The primary aim of this collaborative study was to evaluate the prognostic value of LNR in patients with uterine carcinosarcoma. LNR is a recognized lymph node metric used to stratify prognosis in a variety of malignancies. In this European multinational retrospective study, 93 women with uterine carcinosarcoma were included in the final analysis. We used t-tests and ANOVA for comparison between quantitative variables between the groups, and chi-square tests for qualitative variables. A multivariate analysis using Cox regression analysis was performed to determine potential prognostic factors, including the LNR. Patients were grouped with respect to LNR in terms of 0%, 20% > 0% and >20%. The analysis revealed LNR to be a significant predictor of progression-free survival (HR 1.69, CI (1.12-2.55), p = 0.012) and overall survival (HR 1.71, CI (1.07-2.7), p = 0.024). However, LNR did not remain a significant prognostic factor on multivariate analysis. Due to limitations of the retrospective study, a prospective large multinational study, which takes into effect the most recent changes to clinical practice, is warranted to elucidate the value of the pathophysiological metrics of the lymphatic system associated with prognosis.

Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria, Swiss AGO, BGOG, CEEGOG, GEICO, and SFOG regarding the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer.

An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.

Verification of the prognostic precision of the new 2023 FIGO staging system in endometrial cancer patients - An international pooled analysis of three ESGO accredited centres.

BACKGROUND: Recently, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer (EC) critically integrating new pathological and molecular features was published. The present study evaluated the clinical impact of the new 2023 FIGO staging system by comparing it to the previous 2009 system. METHODS: This is an international, pooled retrospective study of 519 EC patients who underwent primary treatment (and molecular characterisation) at three European Society of Gynaecological Oncology (ESGO) accredited centres in Austria/Italy. Patients were categorised according to the 2009 and the 2023 FIGO staging systems. Stage shifts were analysed and (sub)stage specific 5-year progression-free (PFS) and overall survival (OS) rates were calculated and compared. Different statistical tests were applied to evaluate the prognostic precision of the two FIGO staging systems and to compare them to each other. RESULTS: (Sub)stage shifts occurred in 143/519 (27.6%) patients: 123 upshifts (23.7%) and 20 (3.9%) downshifts. 2023 FIGO staging system identified a stage I cohort with a notably higher 5-year PFS rate compared to 2009 (93.0% versus 87.4%, respectively). For stage II disease, the 5-year PFS rate was similar in the 2023 and the 2009 FIGO staging systems (70.2% versus 71.2%, respectively). The two new molecularly defined 2023 FIGO substages IAmPOLEmut and IICmp53abn displayed distinct, particularly favourable and adverse oncologic outcomes within early stage disease, respectively. A remarkably lower 5-year PFS rate for stage III patients was revealed in the 2023 FIGO staging system compared to 2009 (44.4% versus 54.1%, respectively). All applied statistical tests confirmed a more accurate prediction of PFS and OS by the 2023 FIGO staging system compared to 2009. CONCLUSION: The new 2023 FIGO stating system led to a substantial stage shift in about one quarter of patients leading to a higher prognostic precision. In early stage disease, the new substages added further prognostic granularity and identified treatment relevant subgroups.