RESUMO
Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations.
Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Monitoramento de Medicamentos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/urina , Monitoramento de Medicamentos/métodos , Cromatografia Líquida/métodos , Administração Oral , Espectrometria de Massas/métodos , Letrozol/sangue , Adesão à Medicação , Limite de Detecção , Tamoxifeno/uso terapêutico , Tamoxifeno/sangue , Tamoxifeno/análise , Tamoxifeno/urina , Saliva/química , Androstadienos/urina , Androstadienos/análise , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/sangue , Anastrozol , Reprodutibilidade dos TestesRESUMO
PURPOSE: To assess the accuracy of preoperative sonographic staging in patients with primary invasive breast cancer. METHODS: We retrospectively analyzed a prospectively kept service database of patients with newly diagnosed, unifocal, cT1-3, invasive breast cancer. All patients were diagnosed at a single center institution between January 2013 and December 2021. Clinical T stage was assessed preoperatively by ultrasound and correlated with the definite postoperative pathologic T stage. Demographics, clinical and pathological characteristics were collected. Factors influencing accuracy, over- and underdiagnosis of sonographic staging were analyzed with multivariable regression analysis. RESULTS: A total of 2478 patients were included in the analysis. Median patients' age was 65 years. 1577 patients (63.6%) had clinical T1 stage, 864 (34.9%) T2 and 37 (1.5%) T3 stage. The overall accuracy of sonography and histology was 76.5% (n = 1896), overestimation was observed in 9.1% (n = 225) of all cases, while underestimation occurred in 14.4% (n = 357) of all cases. Accuracy increased when clinical tumor stage cT was higher (OR 1.23; 95% CI 1.10-1.38, p ≤ 0.001). The highest accuracy was seen for patients with T2 stage (82.8%). The accuracy was lower in Luminal B tumors compared to Luminal A tumors (OR 0.71; 95% CI 0.59-0.87, p ≤ 0.001). We could not find any association between sonographic accuracy in HER2 positive patients, and demographic characteristics, or tumor-related factors. CONCLUSION: Our unicentric study showed a high accuracy of sonography in predicting T stage, especially for tumors with clinical T2 stage. Tumor stage and biological tumor factors do affect the accuracy of sonographic staging.
RESUMO
PURPOSE: To assess the accuracy of preoperative sonographic staging for prediction of limited axillary disease (LAD, one or two metastatic lymph nodes) and to identify factors associated with high prediction-pathology concordance in patients with early-stage breast cancer meeting the Z0011 criteria. MATERIALS AND METHODS: Patients treated between January 2015 and January 2020 were included in this retrospective, multicentric analysis of prospectively acquired service databases. The accuracy of LAD prediction was assessed separately for patients with one and two suspicious lymph nodes on preoperative sonography. Test validity outcomes for LAD prediction were calculated for both groups, and a multivariate model was used to identify factors associated with high accuracy of LAD prediction. RESULTS: Of 2059 enrolled patients, 1513 underwent sentinel node biopsy, 436 primary and 110 secondary axillary dissection. For LAD prediction in patients with one suspicious lymph node on preoperative ultrasound, sensitivity was 92% (95% CI 87-95%), negative predictive value (NPV) was 92% (95% CI 87-95%), and the false-negative rate (FNR) was 8% (95% CI 5-13%). For patients with two preoperatively suspicious nodes, the sensitivity, NPV, and FNR were 89% (95% CI 84-93%), 73% (62-83%), and 11% (95% CI 7-16%), respectively. On multivariate analysis, the number of suspicious lymph nodes was associated inversely with correct LAD prediction ([OR 0.01 (95% CI 0.01-0.93), p ≤ 0.01]. CONCLUSIONS: Sonographic axillary staging in patients with one metastatic lymph node predicted by preoperative ultrasound showed high accuracy and a false-negative rate comparable to sentinel node biopsy for prediction of limited axillary disease.
Assuntos
Neoplasias da Mama , Axila/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
PURPOSE: The purpose of this survey was to assess medical students' opinions about online learning programs and their preferences for specific teaching formats during COVID 19 pandemic. METHODS: Between May and July 2020, medical students who took an online gynecology and obstetrics course were asked to fill in a questionnaire anonymously. The questionnaire solicited their opinions about the course, the teaching formats used (online lectures, video tutorials featuring real patient scenarios, and online practical skills training), and digital learning in general. RESULTS: Of 103 students, 98 (95%) submitted questionnaires that were included in the analysis. 84 (86%) students had no problem with the online course and 70 (72%) desired more online teaching in the future. 37 (38%) respondents preferred online to traditional lectures. 72 (74%) students missed learning with real patients. All digital teaching formats received good and excellent ratings from > 80% of the students. CONCLUSION: The survey results show medical students' broad acceptance of the online course during COVID 19 pandemic and indicates that digital learning options can partially replace conventional face-to-face teaching. For content taught by lecture, online teaching might be an alternative or complement to traditional education. However, bedside-teaching remains a key pillar of medical education.
Assuntos
COVID-19 , Educação a Distância/métodos , Educação de Graduação em Medicina/métodos , Ginecologia/educação , Obstetrícia/educação , Estudantes de Medicina/psicologia , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
PURPOSE: Vaginal cuff dehiscence (VCD) is one of the major surgical complications following hysterectomy with data on incidence rates varying largely and studies assessing risk factors being sparse with contradictive results. The aim of this study was to assess the incidence rate of and risk factors for VCD in a homogenous cohort of women treated for benign uterine pathologies via total laparoscopic hysterectomy (TLH) with standardized follow-up. METHODS: All patients undergoing TLH at the Department of Gynecology and Obstetrics, Saarland University Hospital between November 2010 and February 2019 were retrospectively identified from a prospectively maintained service database. RESULTS: VCD occurred in 18 (2.9%) of 617 patients included. In univariate and multivariate analyses, a lower level of surgeon laparoscopic expertise (odds ratio 3.19, 95% confidence interval (CI) 1.0-9.38; p = 0.03) and lower weight of removed uterus (odds ratio 0.99, 95% CI 0.98-0.99; p = 0.02) were associated positively with the risk of VCD. CONCLUSION: In this homogenous cohort undergoing TLH, laparoscopic expertise and uterine weight influenced the risk of postoperative VCD. These findings might help to further reduce the rate of this complication.
Assuntos
Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Deiscência da Ferida Operatória/epidemiologia , Feminino , Alemanha/epidemiologia , Hospitais , Humanos , Histerectomia Vaginal , Incidência , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Deiscência da Ferida Operatória/etiologiaRESUMO
PURPOSE: The aim of this retrospective cohort study was to validate patient's satisfaction and surgical complication rate in patients treated at a certified endometriosis centre with personal patient care (PPC). METHODS: The implementation of PPC at a gynaecologic treatment centre was retrospectively evaluated by analysing perioperative complications using the Clavien Dindo (CD) classification and patient satisfaction utilizing the Picker Patient Experience Questionnaire (PPE-15) for a total of 219 symptomatic endometriosis patients treated surgically at a certified endometriosis centre (Agaplesion Diakonie Hospital, Kassel, Germany) between November 2018 and April 2019. Data from our sample on complication rates and satisfaction were compared with those from reference samples published by Radosa et al. and Jenkinson et al. RESULTS: An overall complication rate of 10.96% (24 out of 219 patients) was observed. Four endometriosis patients (1.83%) had major complications with complications grade III according to the CD classification system. 155 patients out of 219 chose to answer the PPE-15 (return rate 70.78%). 92 patients (59.35%) reported about problems during their treatment in our hospital in their PPE-15. "Doctors sometimes talked as if I was not here" was the best rated item (1.2%) in our cohort. "Staff gave conflicting information" was the most mentioned item (33.55%) by patients during their hospital stay in relation to patient dissatisfaction. CONCLUSION: Incorporation of PPC in the surgical inpatient treatment of endometriosis patients resulted in a low postoperative complication rate and a high patient satisfaction in our study cohort. Furthermore, nursing staff of endometriosis patients also needs particular attention.
Assuntos
Endometriose/terapia , Adulto , Endometriose/patologia , Feminino , Humanos , Pacientes Internados , Satisfação do Paciente , Estudos RetrospectivosRESUMO
PURPOSE: Primary and secondary sterility have become an issue of increasing importance due to demographic and social changes in society. Data regarding the association between female androgen levels and the probability of successful conception after fertility treatment are sparse and contradictive. This study was designed to assess this clinical question. METHODS: In this retrospective single-center cohort study concentrations of androgens androstenedione, dehydroepiandrosteronsulfat (DHEAS) and testosterone (ng/ml) were investigated in the serum of patients presenting for sterility at the department of reproductive medicine of Saarland University hospital Homburg between January 2015 and December 2017. Androgen levels were correlated with reproductive outcomes. Statistical analysis was performed with the aid of SPSS version 24. Significance for conception rates in dependence of androgen concentration was assessed using Kruskal-Wallis test (significance was estimated with p < 0.05). RESULTS: The laboratory values of a total of 301 patients were examined (64% primary, 36% secondary sterility). Median age at first visit at the fertility department was 32.7 years (range 20-47 years). 64 pregnancies were observed during the study period (conception rate 21.3%). 23 out of 301 patients (7.6%) suffered from hypoandrogenaemia, 248 (82.4%) had normal androgen levels and 30 (10%) showed hyperandrogenaemia (p = 0.25). Regarding patients in whom fertility treatment was successful 3 (4.7%) showed hypoandrogenaemia, 54 (84.4%) were normoandrogenaemic and 7 (10.9%) had hyperandrogenaemia (p = 0.40 Kruskal-Wallis test). CONCLUSIONS: We found no association between female androgen levels and sterility and reproductive outcomes.
Assuntos
Androgênios/sangue , Fertilização , Infertilidade Feminina/terapia , Adulto , Feminino , Humanos , Hiperandrogenismo/fisiopatologia , Pessoa de Meia-Idade , Gravidez , Probabilidade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To evaluate instrumental usage in laparoscopic gynecological surgeries and to develop key timesets of a laparoscopic operation, which allows categorization of the operation time into different sections. METHODS: In this prospective clinical observational study, frequency of instrument usage, time for instrument switches, and instrument utilization time were recorded in a standardized manner for laparoscopic surgeries in 103 endoscopic surgeries. RESULTS: A standard equipment (including atraumatic grasping forceps, irrigation and suction device, bipolar clamp, and laparoscopic scissors) was used for nearly all interventions. Bipolar clamps and scissors were changed most frequently. The tool used for the longest amount of time was the atraumatic grasping forceps. Laparoscopic instruments were switched 51 times per surgery (range 2-250 times). One instrument switch lasted for a median of 0.13 min (0.08-1.2 min). Median time for instrument switch for a single surgery added up to 6.83 min. Instrument switches required 10.5% of the overall operation time. CONCLUSION: We analyzed the current instrument usage in laparoscopic gynecological surgeries. The results of our standardized investigation suggest ways to reduce the time required for surgery and provide starting points for the standardization of the work routine.
Assuntos
Procedimentos Cirúrgicos em Ginecologia/instrumentação , Laparoscopia/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: To investigate the role of Dkk1 as a predictor of response to NACT in BC patients. METHODS: This retrospective monocentric study included 145 women who had undergone NACT followed by breast surgery. Dkk1 protein expression was assessed using immunohistochemistry staining in core needle biopsies and mammary carcinoma specimens. RESULTS: Dkk1 levels were lower in treated BC tumours than in untreated tumours. The outcomes of 68 matched pre- and post-therapy tissues showed that Dkk1 levels in mammary carcinoma tissues were significantly predicted by levels in core needle biopsies and that Dkk1 expression was reduced in 83% of cases. Smaller cT stage, positive Her2 expression, and decreased Dkk1-IRS in core needle biopsy tissues were all independent predictors of regression grade (R4), according to Sinn. However, the percentage of Dkk1 expression differences prior to and following NACT had no effect on PFS or OS. CONCLUSIONS: In this study, we demonstrated for the first time that Dkk1 could be identified as an independent predictor of NACT response in BC patients, particularly those with TNBC. Further research with a multicentric expanded (pre-/post-therapy) sample set and better-defined populations in terms of molecular subtypes, therapy modality, and long-term follow-up is recommended to obtain more solid evidence.
RESUMO
Treating estrogen-dependent diseases like endometriosis with drugs suppressing local estrogen activation may be superior to existing endocrine therapies. Steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1) are key enzymes of local estrogen activation. We describe the rational design, synthesis, and biological profilation of furan-based compounds as a novel class of dual STS/17ß-HSD1 inhibitors (DSHIs). In T47D cells, compound 5 showed irreversible inhibition of STS and potent, reversible inhibition of 17ß-HSD1. It was selective over 17ß-HSD2 and displayed high metabolic stabilities in human and mouse liver S9 fractions. No effect on cell viability was detected up to 31 µM (HEK293) and 23 µM (HepG2), respectively, and there was no activation of the aryl hydrocarbon receptor (AhR) up to 3.16 µM. Single daily application to mice revealed steady-state plasma levels high enough to make this compound eligible for an in vivo proof-of-principle study in a mouse endometriosis model.
Assuntos
Endometriose , Esteril-Sulfatase , Feminino , Humanos , Camundongos , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/metabolismo , Endometriose/tratamento farmacológico , Células HEK293 , 17-Hidroxiesteroide Desidrogenases , Estrogênios/metabolismoRESUMO
BACKGROUND: Breast cancer has traditionally been considered to have a low immunogenic potential compared to other tumor entities. SUMMARY: The most extensively studied immunotherapeutic agents for breast cancer to date are immune checkpoint inhibitors, with the results of the IMpassion130 trial leading to the approval of atezolizumab plus nab-paclitaxel for first-line treatment of programmed cell death ligand 1-positive, metastatic, triple-negative breast cancer, and studies in earlier stages have yielded promising results. Other immunotherapeutic options being assessed in phases 2 and 3 trials include vaccine-based therapies and treatment with anti-human epidermal growth factor receptor 2 (H-directed immune-linked antibodies) and substances evaluated in early clinical trials as cellular therapies (adoptive cell therapy and chimeric antigen receptor T cells). KEY MESSAGES: Immunotherapy is an emerging modality for the treatment of breast cancer, as evidenced by the plethora of preclinical and clinical concepts and ongoing trials. Early studies established the role of immunotherapeutic agents in the metastatic setting. Ongoing studies will expand our knowledge about the timing of administration, best partners for combination therapy, and predictive biomarkers to guide immunotherapy for breast cancer.