N-cadherin: A diagnostic marker to help discriminate primary liver carcinomas from extrahepatic carcinomas.

Distinguishing primary liver cancer (PLC), namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), from liver metastases is of crucial clinical importance. Histopathology remains the gold standard, but differential diagnosis may be challenging. While absent in most epithelial, the expression of the adherens junction glycoprotein N-cadherin is commonly restricted to neural and mesenchymal cells, or carcinoma cells that undergo the phenomenon of epithelial-to-mesenchymal transition (EMT). However, we recently established N- and E-cadherin expression as hallmarks of normal hepatocytes and cholangiocytes, which are also preserved in HCC and iCCA. Therefore, we hypothesized that E- and/or N-cadherin may distinguish between carcinoma derived from the liver vs carcinoma of other origins. We comprehensively evaluated E- and N-cadherin in 3359 different tumors in a multicenter study using immunohistochemistry and compared our results with previously published 882 cases of PLC, including 570 HCC and 312 iCCA. Most carcinomas showed strong positivity for E-cadherin. Strong N-cadherin positivity was present in HCC and iCCA. However, except for clear cell renal cell carcinoma (23.6% of cases) and thyroid cancer (29.2%), N-cadherin was only in some instances faintly expressed in adenocarcinomas of the gastrointestinal tract (0%-0.5%), lung (7.1%), pancreas (3.9%), gynecological organs (0%-7.4%), breast (2.2%) as well as in urothelial (9.4%) and squamous cell carcinoma (0%-5.6%). As expected, N-cadherin was detected in neuroendocrine tumors (25%-75%), malignant melanoma (46.2%) and malignant mesothelioma (41%). In conclusion, N-cadherin is a useful marker for the distinction of PLC vs liver metastases of extrahepatic carcinomas (P < .01).

Sonographic features of adenomyosis correlated with clinical symptoms and intraoperative findings: a case-control study.

PURPOSE: Adenomyosis is a common disease of females during their reproductive age. As of today, histologic examination of the uterus after hysterectomy constitutes the gold standard for diagnosis. The aim of this study was to determine the validity of sonographic, hysteroscopic, and laparoscopic criteria for the diagnosis of the disease. METHODS: This study included data collected from 50 women in the reproductive age of 18-45 years, who underwent a laparoscopic hysterectomy in the gynecology department of the Saarland University Hospital in Homburg between 2017 and 2018. The patients with adenomyosis were compared with a healthy control group. RESULTS: We collected data of anamnesis, sonographic criteria, hysteroscopic criteria and laparoscopic criteria and compared it with the postoperative histological results. A total 25 patients were diagnosed with adenomyosis postoperatively. For each of these; at least three sonographic diagnostical criteria for adenomyosis were found compared with a maximum of two for the control group. CONCLUSION: This study demonstrated an association between pre- and intraoperative signs of adenomyosis. In this way, it shows a high diagnostic accuracy of the sonographic examination as a pre-operative diagnostic method of the adenomyosis.

Influence of interdisciplinary frailty screening on perioperative complication rates in elderly ovarian cancer patients: results of a retrospective observational study.

PURPOSE: Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC). METHODS: Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. RESULTS: 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m2) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values > 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort. CONCLUSION: Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making.

Prognostic Impact of CD38- and IgκC-Positive Tumor-Infiltrating Plasma Cells in Triple-Negative Breast Cancer.

Due to a higher mutational load, triple-negative breast cancer (TNBC) is characterized by a higher immunogenicity compared to other subtypes. In this context, we analyzed the prognostic significance of tumor-infiltrating plasma cells in a cohort of 107 triple-negative breast cancer patients. Tumor-infiltrating plasma cells were analyzed via immunohistochemistry using the plasma cell markers CD38 and IgκC. The prognostic impact of the CD38 and IgκC expression was evaluated using the Kaplan-Meier plots and Cox regression analyses. A Spearman-Rho correlation coefficient was used to evaluate a possible association between plasma cell infiltration and the BRCA mutation status. The study cohort consisted of 107 patients with early-stage TNBC, who were treated between 2009 and 2016 at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany. The median follow-up was five years. The Kaplan-Meier survival analysis showed that higher tumor infiltration with CD38-positive plasma cells was associated with significantly longer metastasis-free survival (MFS) (p = 0.039 Log Rank). In the multivariate Cox regression analysis for metastasis-free survival, in which additional clinicopathological factors (age, tumor size, nodal status, and grading) were considered, CD38 was identified as an independent prognostic factor within the analyzed cohort (HR 0.438, 95% CI 0.195-0.983; p = 0.045). In addition to the CD38 expression, the nodal status was also identified as an independent prognostic factor in multivariate Cox regression. Regarding the IgκC expression, a higher IgκC expression was shown to be associated with a better outcome, although this effect was not statistically significant. Furthermore, we were able to show a significant correlation between plasma cell infiltration and the BRCA mutation status. A favorable prognostic significance of tumor-infiltrating plasma cells could be demonstrated in triple-negative breast cancer immunohistochemically analyzed for the CD38 and IgκC expression. CD38 was identified as an independent prognostic factor via multivariate Cox regression.

G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study.

BACKGROUND: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). METHODS: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. RESULTS: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056-3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. CONCLUSIONS: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

Role of integrins in the metastatic spread of high-grade serous ovarian cancer.

PURPOSE: Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. METHODS: The expression of integrin α2, α4, α5, α6, and ß1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher's exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan-Meier analyses. RESULTS: Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01-4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. CONCLUSION: Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and ß1 did not reveal any prognostic value.

Papillomavirus-Associated Tumor Formation Critically Depends on c-Fos Expression Induced by Viral Protein E2 and Bromodomain Protein Brd4.

We investigated the mechanism of how the papillomavirus E2 transcription factor can activate promoters through activator protein (AP)1 binding sites. Using an unbiased approach with an inducible cell line expressing the viral transcription factor E2 and transcriptome analysis, we found that E2 induces the expression of the two AP1 components c-Fos and FosB in a Brd4-dependent manner. In vitro RNA interference confirmed that c-Fos is one of the AP1 members driving the expression of viral oncogenes E6/E7. Mutation analysis and in vivo RNA interference identified an essential role for c-Fos/AP1 and also for the bromodomain protein Brd4 for papillomavirus-induced tumorigenesis. Lastly, chromatin immunoprecipitation analysis demonstrated that E2 binds together with Brd4 to a canonical E2 binding site (E2BS) in the promoter of c-Fos, thus activating c-Fos expression. Thus, we identified a novel way how E2 activates the viral oncogene promoter and show that E2 may act as a viral oncogene by direct activation of c-Fos involved in skin tumorigenesis.

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients.

Trends in Urogynecology-Transvaginal Mesh Surgery in Germany.

BACKGROUND: Pelvic organ prolapse constitutes a prevalent condition associated with a considerable impact on the quality of life. The utilization of transvaginal mesh surgery for managing POP has been a subject of extensive debate. Globally, trends in TVM surgery experienced significant shifts subsequent to warnings issued by the FDA. METHODS: This study aims to explore temporal patterns in transvaginal mesh surgery in the German healthcare system. A comprehensive analysis was conducted on in-patient data from the German Federal Statistical Office spanning 2006 to 2021. A total of 1,150,811 operations, each associated with specific codes, were incorporated into the study. Linear regression analysis was employed to delineate discernible trends. RESULTS: The trends in transvaginal mesh surgery within the anterior compartment exhibited relative stability (p = 0.147); however, a significant decline was noted in all other compartments (posterior: p < 0.001, enterocele surgery: p < 0.001). A subtle increasing trend was observed for uterine-preserving transvaginal mesh surgery (p = 0.045). CONCLUSION: Surgical trends over the specified timeframe demonstrate how POP management has evolved globally. Notably, despite observed fluctuations, transvaginal mesh surgery remains a viable option, particularly for specific cases with a high risk of relapse and contraindications to alternative surgical approaches.

Occurrence and Management of Immunotherapy-Associated Adverse Events in Patients with Gynecological Cancers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body's anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the side effects of conventional chemotherapy. It, therefore, requires special attention in the diagnosis and management of immunotherapy-related adverse events (irAEs). The present study aimed to retrospectively analyze the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received ICIs and to discuss these findings in the context of the recent literature. METHODS: In the present retrospective overview, we evaluated patients with gynecologic malignancies (breast, endometrial, cervical, ovarian) who received ICIs with regard to the incidence, type, and time to onset of irAEs. A total of 61 patients treated at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany, between 2018 and 2023 were included in the analysis. RESULTS: A total of 32.8% of patients developed an irAE of any grade or type. The median time to irAE was 24 weeks. The most frequently observed irAEs were grade 1 (20%) or 2 (35%). Immunotherapy-related grade 3 or 4 adverse events occurred in 45% of patients (40% grade 3, 5% grade 4). The most common type of irAE in our cohort was hypothyroidism, followed by hepatitis and colitis. Cox regression analysis identified the duration of ICI therapy as the only significant factor influencing the incidence of irAEs (p = 0.004). CONCLUSION: The broad spectrum of irAEs and the onset time of irAEs are important challenges of therapy with ICIs, requiring proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy.

BRCA1, BRCA2 and PALB2 mRNA Expression as Prognostic Markers in Patients with Early Breast Cancer.

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients. METHODS: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. RESULTS: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). CONCLUSIONS: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression.

Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis.

Introduction: Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer. Materials and methods: Following a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I2 and the Cochrane Q χ2 statistics. Results: Out of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses. Discussion and conclusion: This study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023391888.

Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study.

PURPOSE: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. METHODS: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan-Meier method and Cox-regression analysis. RESULTS: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9-16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). CONCLUSION: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer.

Physical Activity and the Impact of Continued Exercise on Health-Related Quality of Life Prior to and during Pregnancy: A German Cohort Study.

The goal of this study was to examine how regular physical activity before and during pregnancy affected life quality throughout pregnancy. Between July 2020 and May 2021, 218 pregnant women were recruited from 11 outpatient clinics for this survey. Data were collected prospectively in a panel format beginning with the 10th gestational week over a 20-week period. Prior to pregnancy, a previous time point was also defined. The International Physical Activity Questionnaire, the EQ-5D-3L questionnaire, and the EQ-VAS questionnaire were used to collect data on the duration and intensity of daily physical exercises, as well as to assess health-related quality of life and self-estimated health status. The final survey included data from 113 women. During pregnancy, physical activity decreased dramatically. The duration of strenuous activities, but not moderate activities, was significantly reduced. Continuous physical activity independently predicted higher life quality scores at all points of assessment. Cases who participated in moderate and strenuous activities on a regular basis had higher self-estimated health status scores than cases who only participated in moderate activity. Instead of focusing solely on specific types of physical activity, we believe that strategies for motivating all pregnant women to be constantly active should be developed.

The preoperative G8 geriatric screening tool independently predicts survival in older patients with endometrial cancer: results of a retrospective single-institution cohort study.

PURPOSE: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival. METHODS: Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan-Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters. RESULTS: 153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35-15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31-6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively). CONCLUSIONS: This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity.

Frailty assessment tools predict perioperative outcome in elderly patients with endometrial cancer better than age or BMI alone: a retrospective observational cohort study.

OBJECTIVE: Five commonly used global health assessment tools have been evaluated to identify and assess the preoperative frailty status and its relationship with perioperative in-hospital complications and transfusion rates in older women with endometrial cancer (EC). METHODS: Preoperative frailty status was examined by the G8 questionnaire, the Eastern Cooperative Oncology Group performance status, the Charlson Comorbidity Index and the American Society of Anesthesiologists Physical Status System, as well as the Lee-Schonberg prognostic index. The main outcome measures were perioperative laboratory values, intraoperative surgical parameters and immediately postoperative complications. RESULTS: 153 consecutive women ≥ 60 years with all stages of EC, who received primary elective surgery at the University Medical Center Mainz between 2008 and 2019 were classified with selected global health assessment tools according to their preoperative performance status. In contrast to conventional prognostic parameters like older age and higher BMI, increasing frailty was significantly associated with preoperative anemia and perioperative transfusions (p < 0.05). Moreover, in patients preoperatively classified as frail significantly more postoperative complications (G8 Score: frail: 20.7% vs. non-frail: 6.7%, p = 0.028; ECOG: frail: 40.9% vs. non-frail: 2.8%, p = 0.002; and CCI: frail: 25.0% vs. non-frail: 7.4%, p = 0.003) and an increased length of hospitalization were recorded. According to propensity score matching, the risk for developing postoperative complications for frail patients was approximately two-fold higher, depending on which global health assessment tool was used. CONCLUSIONS: Preoperatively assessed frailty significantly predicts post-surgical morbidity rates in contrast to conventionally used single prognostic parameters such as age or BMI. A standardized preoperative assessment of frailty in the routine work-up might be beneficial in older cancer patients before major surgery to include these patients in a prehabilitation program with nutrition counseling and physiotherapy to adequately assess the perioperative risk.

Effects of intermittent fasting on quality of life tolerance of chemotherapy in patients with gynecological cancers: study protocol of a randomized-controlled multi-center trial.

Fatigue is a very common side effect during intravenous chemotherapy. Unfortunately, only few effective therapeutic options are available, mostly based on daily activity. In our pilot trial we were able to demonstrate that intermittent fasting can reduce fatigue in healthy people, thus we aimed to assess the effects of the fasting dietary on quality of life during chemotherapy in patients with gynecological cancer, especially on the domain of fatigue. The IFAST trial is designed as a prospective, randomized-controlled, multi-center trial. Participation will be offered to women with gynecological cancers (breast cancer, ovarian cancer including peritoneal and fallopian tube cancers, endometrial cancer and cervical cancer) who are planned to receive intravenous chemotherapy for at least three months. Eligible patients will be randomized 1:1, stratified by tumor type and study center. Primary endpoint is the difference in mean change in fatigue, assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT- FS©). Exploratory secondary endpoints will include general Quality of Life impairment, tolerance of chemotherapy, immunological changes, peripheral cell damage in blood cells, as well as tumor response to chemotherapy. There is new evidence that prolonged fasting periods of 46-96 hours during chemotherapy can positively influence the quality of life during chemotherapy. However, these fasting regiments are not feasible for many patients. Intermittent fasting could be a feasible (manageable) option for many patients to actively improve their quality of life and tolerance to chemotherapy and possibly even enhance the effectiveness of chemotherapy. Trial Registration: https://drks.de, identifier DRKS00031429.

Discordance of HER2-Low between Primary Tumors and Matched Distant Metastases in Breast Cancer.

We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative primary breast cancer cohort (HER2-low and HER2-zero). The retrospective study included 191 consecutive paired samples of primary breast cancer and distant metastases diagnosed between 1995 and 2019. HER2-negative samples were divided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridization [ISH]-negative). The main objective was to analyze the discordance rate between matched primary and metastatic samples, focusing on the site of distant metastasis, molecular subtype, and de novo metastatic breast cancer. The relationship was determined by cross-tabulation and calculation of Cohen's Kappa coefficient. The final study cohort included 148 paired samples. The largest proportion in the HER2-negative cohort was HER2-low [primary tumor 61.4% (n = 78), metastatic samples 73.5% (n = 86)]. The discordance rate between the HER2 status of primary tumors and corresponding distant metastases was 49.6% (n = 63) (Kappa -0.003, 95%CI -0.15-0.15). Development of a HER2-low phenotype occurred most frequently (n = 52, 40.9%), mostly with a switch from HER2-zero to HER2-low (n = 34, 26.8%). Relevant HER2 discordance rates were observed between different metastatic sites and molecular subtypes. Primary metastatic breast cancer had a significantly lower HER2 discordance rate than secondary metastatic breast cancer [30.2% (Kappa 0.48, 95%CI 0.27-0.69) versus 50.5% (Kappa 0.14, 95% CI -0.03-0.32)]. This highlights the importance of evaluating potentially therapy-relevant discordance rates between a primary tumor and corresponding distant metastases.

Current Approaches to the Management of Sentinel Node Procedures in Early Vulvar Cancer in Germany: A Web-Based Nationwide Analysis of Practices.

BACKGROUND: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected patients with early vulvar cancer. This study aimed to assess current management practices with respect to the sentinel node procedure in women with early vulvar cancer in Germany. METHODS: A Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments. Data were summarized as frequencies and analyzed using the chi-square test. RESULTS: A total of 222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%, respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management. CONCLUSIONS: The majority of German hospitals implement the SN procedure. However, only 79.5% of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest recommendations and clinical evidence. Deviations from state-of-the-art management should only be after a detailed discussion with the concerned patient.

Patients' expectations of preventive measures of medical institutions during the SARS-CoV-2 pandemic in Germany in women with an increased risk of breast and ovarian cancer: a cross-sectional, web-based survey.

OBJECTIVES: To identify patient-approved contingency measures for protection of patients and healthcare workers (HCWs) from COVID-19 infection and to use these findings to improve staff's preparedness to cope with the course of this pandemic or similar situations. METHODS DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS: We conducted a cross-sectional, web-based survey of women with an increased risk of breast or ovarian cancer, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire, developed for this study, was used to assess expectations and opinions about preventive measures within medical institutions. RESULTS: Sixty-four (71.9%) of the 89 potential participants responded to at least one question regarding contingency measures within medical institutions. Approximately 37% of the respondents preferred having information about their facility's hygiene protocols before appointment; 57.8% of the respondents endorsed regular SARS-CoV-2 testing of patients prior to medical appointments and 95.3% endorsed regular testing of HCWs. Additionally, 84.4% of the respondents supported HCWs' use of surgical masks and 68.8% supported HCWs' use of masks with greater protection. Notably, 75.0% of the respondents advocated for the presence of a significant other during medical consultations; 71.9% approved the use of telemedicine and 93.8% endorsed changes in appointment practices to enable social distancing. No significant associations were found between respondents' sociodemographic, disease-specific or pandemic-specific factors and their opinions on hygiene precautions. CONCLUSIONS: Patients at high risk of infection or severe course of COVID-19 approve strict contingency measures designed to lower the transmission of COVID-19 in medical facilities. Moreover, vulnerable groups may profit from contingency plans in healthcare facilities in order to follow preventive measures, avoid diagnostic delay or avoid worsening of pre-existing conditions. However, they also value the presence of a significant other during medical consultations and procedures.