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Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature. Compared to their spherical counterparts, nonspherical polymeric MB displayed superior performance in multiple ways, including i) increased margination behavior in blood vessel-like flow chambers, ii) reduced macrophage uptake in vitro, iii) prolonged circulation time in vivo, and iv) enhanced blood-brain barrier (BBB) permeation in vivo upon combination with transcranial focused ultrasound (FUS). Our studies identify shape as a design parameter in the MB landscape, and they provide a rational and robust framework for further exploring the application of anisotropic MB for ultrasound-enhanced drug delivery and imaging applications.
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Barrera Hematoencefálica , Microburbujas , Barrera Hematoencefálica/diagnóstico por imagen , Ultrasonografía , Transporte Biológico , Sistemas de Liberación de MedicamentosRESUMEN
INTRODUCTION: Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. METHODS: Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. RESULTS: Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. CONCLUSION: This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC.
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Radioisótopos , Neoplasias de la Mama Triple Negativas , Humanos , Masculino , Animales , Ratones , Radioisótopos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Radiofármacos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Próstata/metabolismo , Línea Celular Tumoral , Dipéptidos/uso terapéuticoRESUMEN
PURPOSE: This cross-sectional study aims to investigate parameters that predict relevant levels of distress in women in a perioperative setting undergoing treatment for cervical cancer. MATERIALS AND METHODS: Data from 495 patients with cervical cancer that were treated at the university hospital Aachen between 2010 and 2022 were analysed based on their respective National Comprehensive Cancer Network (NCCN) Distress Thermometer score (DT) and Problem List (PL) and their clinical history. 105 patients were enrolled in the study. 18 medical and demographic variables were analysed using multivariate logistic regression. RESULTS: Three variables contributed significantly to the prediction of a DT score ≥ 5. Significant distress was defined as a DT score of ≥ 5, which was observed in 70.5% of the participants (mean: 5.58 ± 2.892). Women who chose to receive psycho-oncological counselling were more likely to have a DT score ≥ 5 (Odds Ratio(OR) = 3.323; Confidence Interval (CI95%): 1.241-8.900; p-value: 0.017). In addition, women who did not receive chemoradiation had significantly higher DT scores (OR = 3.807; CI 95%:1.185-12.236; p-value: 0.025), as did women whose Distress Thermometer was assessed in the first month after their initial diagnosis (OR = 3.967; CI 95%:1.167-13.486; p-value: 0.027). CONCLUSION: Increased distress in women with cervical cancer is common especially in the first month after diagnosis, in patients who do not receive chemoradiation and in patients who seek psycho-oncological counselling. Surgical factors do not play a major role in patient distress.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/psicología , Neoplasias del Cuello Uterino/terapia , Estudios Transversales , Persona de Mediana Edad , Adulto , Anciano , Estrés Psicológico , Distrés Psicológico , Modelos Logísticos , Quimioradioterapia/psicología , ConsejoRESUMEN
OBJECTIVE: Vulvar lichen sclerosus (VLS) is an underestimated chronic disease. It can cause significant symptom burden and sexual dysfunction. This study aimed to evaluate patient satisfaction and current challenges in the management of VLS in a certified dysplasia unit, particularly during the COVID-19 pandemic. METHODS: This survey analyzed patients who had been diagnosed with VLS and treated at our DKG-certified dysplasia unit. The study was conducted during the COVID-19 pandemic in the Department of Gynecology and Obstetrics at the University of Aachen. The questionnaire contained 43 questions on general treatment, diagnostic delays, disease education, psychologic and sexual issues, and specific questions regarding the COVID-19 pandemic. The questionnaires were distributed between January 2021 and September 2023. RESULTS: This study included 103 patients diagnosed with VLS, who were treated at our certified dysplasia unit. Overall, 48% of the patients were satisfied with the success of the therapy. Most participants reported psychologic problems (36.8%), fear of cancer (53.3%), or sexual restrictions (53.3%). Among the patients, 38% were bothered by the regular application of topical cortisone. However, 72% were willing to undergo treatment for more than 24 months. The COVID-19 outbreak in March 2020 had a significant negative impact on general VLS care from the patient's perspective (3.83/5 before vs. 3.67/5 after; p = 0.046). There was a general request for booklets to inform and educate the patients about their disease. Furthermore, the respondents demanded a telephone hotline to answer the questions and wished for follow-up visits via e-mail to cope better with their current situation. CONCLUSION: This study highlights the need for more effective treatments for VLS and an increased awareness of psychologic and sexual distress. To ensure patient well-being and satisfaction, it is imperative to offer individualized care with adequate disease education in a team of specialists from various disciplines.
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COVID-19 , Satisfacción del Paciente , Liquen Escleroso Vulvar , Humanos , Femenino , COVID-19/psicología , COVID-19/epidemiología , Persona de Mediana Edad , Liquen Escleroso Vulvar/psicología , Liquen Escleroso Vulvar/terapia , Adulto , Encuestas y Cuestionarios , Anciano , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Fisiológicas/terapia , Disfunciones Sexuales Fisiológicas/etiología , SARS-CoV-2 , Disfunciones Sexuales Psicológicas/psicología , Disfunciones Sexuales Psicológicas/terapia , Disfunciones Sexuales Psicológicas/etiologíaRESUMEN
Heterotopic pregnancies are a rare phenomenon defined by the simultaneous occurrence of intrauterine and extrauterine pregnancy. The incidence of heterotopic pregnancy occurring through natural fertilization is low but is increased by risk factors such as assisted reproductive techniques or pelvic inflammatory disease increase. We report the case of a 36-year-old female patient in the 6th week of pregnancy who presented to the emergency unit with severe acute lower abdominal pain. Laboratory chemistry and sonography revealed a suspected heterotopic pregnancy. The patient was admitted for observation. The sonographic reevaluation on the next day confirmed the suspicion of extrauterine gravidity with intact intrauterine gravidity with additional decreasing hemoglobin and hematoperitoneum, so that laparoscopy was indicated. Intraoperatively, the mass on the left ovary was removed without complications. The patient could be discharged quickly postoperatively after a complication-free course and gave birth to a healthy child by spontaneous partus in the 38th week of gestation. Due to their rarity, there is limited research related to heterotopic pregnancies, and most scientific articles are case studies. Diagnostically, the most important thing in clinical practice is to think about the possibility of EUG even if there is evidence of an intact IUG. Transvaginal sonography is of particular importance in diagnostics. The performance of prospective cohort studies is desirable for the evidence-based diagnosis and therapy of affected patients in the future.
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Embarazo Heterotópico , Humanos , Femenino , Embarazo , Adulto , Embarazo Heterotópico/diagnóstico por imagen , Embarazo Heterotópico/diagnóstico , Embarazo Heterotópico/cirugía , Ovario/diagnóstico por imagen , Laparoscopía , Ultrasonografía PrenatalRESUMEN
Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array-based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH-probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut-off value has been defined. A first validation of this EC-FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut-off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non-invasive EC-FISH Test to predict EC in women with suspected EC.
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Neoplasias Endometriales , Humanos , Femenino , Sensibilidad y Especificidad , Hibridación Fluorescente in Situ , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Valor Predictivo de las Pruebas , VaginaRESUMEN
PURPOSE: Currently, various techniques are available to mark and selectively remove initially suspicious axillary lymph nodes (target lymph nodes, TLNs) in breast cancer patients receiving neoadjuvant chemotherapy (NACT). To date, limited data are available on whether the use of magnetic seeds (MS) is suitable for localizing TLNs. This study aimed to investigate the feasibility of MS in patients undergoing target lymph node biopsy (TLNB) or targeted axillary dissection (TAD) after NACT. METHODS: Prospective data from the ongoing multicentric AXSANA study were extracted from selected patients in whom the TLN had been marked with an MS before NACT and who were enrolled from June 2020 to June 2023. The endpoints of the analysis were the detection rate, the rate of lost markers, and the potential impairment on magnetic resonance imaging (MRI) assessment. RESULTS: In 187 patients from 27 study sites in seven countries, MS were placed into the TLN before NACT. In 151 of these, post-NACT surgery had been completed at the time of analysis. In 146 patients (96.0%), a TLN could successfully be detected. In three patients, the seed was removed but no lymphoid tissue was detected on histopathology. The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. CONCLUSION: MS show excellent applicability for TLNB/TAD when inserted before NACT with a high DR and a low rate of lost markers. Axillary MS can impair MRI assessment of the breast. TRIAL REGISTRATION NUMBER: NCT04373655 (date of registration May 4, 2020).
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The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. METHODS: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. RESULTS: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. CONCLUSION: RAD201 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic (breast) cancer, regardless of ongoing HER2-targeted antibody treatment.
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Neoplasias de la Mama , Anticuerpos de Dominio Único , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anticuerpos de Dominio Único/metabolismo , Distribución Tisular , Poligelina/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Neoplasias de la Mama/patología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE OF REVIEW: Taxanes in combination with trastuzumab and pertuzumab are the established first-line standard in the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. In the last years, several new HER2-targeted therapies, including antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors, have been approved for therapy after trastuzumab or dual blockade. In this review, the current treatment algorithms are discussed, including these new treatment options. RECENT FINDINGS: The ADC T-DM1 was the established second-line standard based on the results of the EMILIA trial. Recently, the DESTINY-Breast03 trial compared T-DM1 with the new ADC trastuzumab deruxtecan (T-DXd) in patients with disease progression after treatment with taxanes and trastuzumab. T-DXd was associated with an improved progression-free survival and a trend toward improved overall survival, establishing T-DXd as a new second-line standard. The HER2CLIMB trial demonstrated a significant progression-free survival and overall survival benefit for the tyrosine kinase inhibitor tucatinib in combination with trastuzumab and capecitabine after T-DM1 and trastuzumab/pertuzumab. This benefit was also observed in patients with active brain metastases defining this combination as the preferred second or third-line option in these patients. SUMMARY: New treatment strategies in HER2-positive metastatic breast cancer have substantially improved the clinical outcome of these patients, including those with active brain metastases.
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Neoplasias Encefálicas , Neoplasias de la Mama , Femenino , Humanos , Ado-Trastuzumab Emtansina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Taxoides/uso terapéutico , Trastuzumab/uso terapéuticoRESUMEN
PURPOSE: To evaluate the feasibility and diagnostic value of the combination of colposcopy, cytology and hrHPV (high-risk human papilloma virus) PCR (polymerase chain reaction) testing in patients with no or minor cytologic abnormalities and HPV high risk infection and to find the best predictors for the presence of CIN2 + in this patient collective. METHODS: Three hundred and thirty-four hrHPV patients with normal cytology or minor cytologic abnormalities who had a colposcopic examination at the center of colposcopy at the university hospital Aachen in 2021 were enrolled in this retrospective cohort analysis. Multivariate logistic regression and a machine-learning technique (random forests, leave-one-out analysis) were used. RESULTS: The overall risk for CIN2 + in hrHPV-positive patients with normal cytology was 7.7% (N = 18) (5% for CIN3 +), 18% (N = 16) (10.1% for CIN3 +) in patients with PAP IIp (ASC-US) and 62.5% (N = 5) (25% for CIN3 +) in patients with PAP IIg (AGC). Variables that show a statistically significant influence for the CIN-status are 'major change' as the result of colposcopy, transformation zone type T1, PAP IIg upon referral (AGC) and hrHPV category 1a (HPV 16/18) detection. Using machine learning (random forests) techniques, the main influencing variables were confirmed. A monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3 (in accordance to the IACR guidelines) was found. CONCLUSION: In the collective of hrHPV patients with no or minor cytologic abnormalities, the result of colposcopy and HPV PCR status are key predictors for the detection of CIN2 + with a monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Estudios Retrospectivos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Colposcopía , Papillomaviridae , Frotis Vaginal/métodos , Detección Precoz del Cáncer/métodosRESUMEN
PURPOSE: In the last 2 decades, the optimal management of the axilla in breast cancer patients receiving neoadjuvant chemotherapy (NACT) has been one of the most frequently discussed topics. Little is known about the attitudes of surgeons/radiologists towards new developments such as targeted axillary dissection. Therefore, the NOGGO conducted a survey to evaluate the current approach to axillary management. METHODS: A standardized digital questionnaire was sent out to > 200 departments in Germany between 7/2021 and 5/2022. The survey was supported by EUBREAST. RESULTS: In total, 116 physicians completed the survey. In cN0 patients scheduled to receive NACT, 89% of respondents recommended sentinel lymph node biopsy (SLNB) after NACT. In case of ypN1mi(sn), 44% advised no further therapy, while 31% proposed ALND and 25% axillary irradiation. 64% of respondents recommended a minimally invasive axillary biopsy to cN + patients. TAD was used at the departments of 82% of respondents and was offered to all cN + patients converting to ycN0 by 57% and only to selected patients, usually based on the number of suspicious nodes at time of presentation, by 43%. The most common marking technique was a clip/coil. 67% estimated that the detection rate of their marker was very good or good. CONCLUSION: This survey shows a heterogenous approach towards axillary management in the neoadjuvant setting in Germany. Most respondents follow current guidelines. Since only two-thirds of respondents experienced the detection rate of the marker used at their department as (very) good, future studies should focus on the comparative evaluation of different marking techniques.
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Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Femenino , Terapia Neoadyuvante/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Axila/patología , Biopsia del Ganglio Linfático Centinela/métodos , Escisión del Ganglio Linfático/métodos , Encuestas y Cuestionarios , Ganglios Linfáticos/patología , Estadificación de NeoplasiasRESUMEN
PURPOSE: The aim of this study was to investigate the reliability and reproducibility of transperineal ultrasound (TPUS) in the initial phase of labor. As TPUS is a common method, it could supplement vaginal palpation and even replace it in certain situations. In addition, we used a 4-dimensional method for the assessment of cervical effacement. MATERIALS AND METHODS: 54 women in labor were included and underwent TPUS. The resulting images from the acquired 4D volumes were evaluated after the examination for the first time and a second time after 21 days. The measured values were cervical length, dilatation and effacement, the angle of progression (AoP), and head-perineum distance. RESULTS: 54 patients were examined. TPUS images were unable to be evaluated in 12 patients because of cervical dilatation of more than 5 cm or poor image quality. Thus, 42 measurements were included. The concordance correlation coefficients according to Lin are satisfactory overall, with one exception for cervical effacement. The accuracy component of cervical length (CCCLin: 0.93; accuracy: 1.00), dilatation (CCCLin: 0.93; accuracy: 1.00), and AoP (CCCLin: 0.87; accuracy: 1.00) is excellent and still high for the head-perineum distance (CCCLin: 0.89; accuracy: 0.96) and cervical effacement (CCCLin: 0.77; accuracy: 0.97). CONCLUSION: TPUS is a valuable noninvasive tool with good diagnostic accuracy for the AoP, cervical length, and dilatation. Our study provides support for the use of TPUS to complement a vaginal examination. It should not replace a digital examination but should serve as a suitable alternative method for monitoring labor progression in the future.
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Cuello del Útero , Ultrasonografía Prenatal , Embarazo , Humanos , Femenino , Proyectos Piloto , Reproducibilidad de los Resultados , Estudios Prospectivos , Ultrasonografía , Cuello del Útero/diagnóstico por imagen , Ultrasonografía Prenatal/métodosRESUMEN
Breast cancer stem cells (BCSCs) are responsible for tumour recurrence and therapy resistance. We have established primary BCSC cultures from human tumours of triple-negative breast cancer (TNBC), a subgroup of breast cancer likely driven by BCSCs. Primary BCSCs produce xenografts that phenocopy the tumours of origin, making them an ideal model for studying breast cancer treatment options. In the TNBC cell line MDA-MB-468, we previously screened kinases whose depletion elicited a differentiation response, among which IRAK2 was identified. Because primary BCSCs are enriched in IRAK2, we wondered whether IRAK2 downregulation might affect cellular growth. IRAK2 was downregulated in primary BCSCs and MDA-MB-468 by lentiviral delivery of shRNA, causing a decrease in cellular proliferation and sphere-forming capacity. When orthotopically transplanted into immunocompromised mice, IRAK2 knockdown cells produced smaller xenografts than control cells. At the molecular level, IRAK2 downregulation reduced NF-κB and ERK phosphorylation, IL-6 and cyclin D1 expression, ERN1 signalling and autophagy in a cell line-dependent way. Overall, IRAK2 downregulation decreased cellular aggressive growth and pathways often exploited by cancer cells to endure stress; therefore, IRAK2 may be considered an interesting target to compromise TNBC progression.
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Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo , Células Madre Neoplásicas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers. In this study, the proteomic content of 1191 human breast cancer samples was characterized by mass spectrometry imaging and the epithelial regions were employed to train and test machine-learning models to characterize the individual receptor status and to classify TNBC. The classification models presented yielded high accuracies for estrogen and progesterone receptors and over 95% accuracy for classification of TNBC. Analysis of the molecular features revealed that vimentin overexpression is associated with TNBC, supported by immunohistochemistry validation, revealing a new potential target for diagnosis and treatment.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Receptor ErbB-2/metabolismo , Proteómica , Biomarcadores de Tumor/metabolismo , Estrógenos , Receptores de Progesterona/metabolismo , Espectrometría de MasasRESUMEN
BACKGROUND: Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy. METHODS: EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). RESULTS: Of the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5-291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90-2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48-1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44-1.31], log-rank p = 0.314) without reaching statistical significance. CONCLUSION: EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients. TRIAL REGISTRATION: NCT00544765.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Terapia Neoadyuvante , Pronóstico , Receptor ErbB-2/metabolismo , Taxoides , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
BACKGROUND: Postoperative pain remains a common problem in gynecologic laparoscopy, especially in head zone-related regions, triggered by intra-abdominal pressure during capnoperitoneum. Humidified and prewarmed insufflation gas may ameliorate pain and be beneficial. METHODS: This prospective randomized controlled parallel group multi-arm single-center study investigated the effects of temperature and humidity of insufflation gas on postoperative pain during gynecologic laparoscopy with a duration ≥ 60 min. Female participants (18-70 years) were blinded and randomly assigned-computer generated-to either insufflation with dry cold CO2 with forced air warming blanket ("AIR"), humidified warm gas without forced air warming blanket ("HUMI"), or humidified warm gas with forced air warming blanket ("HUMI +"). We hypothesized that using humidified warm gas resulted in lower pain scores and less analgesic consumption. The primary endpoint postoperative pain was assessed for different pain localizations every 12 h during 7 days after surgery. Secondary endpoints were demand for painkillers and epidural anesthetics, length of stay in recovery room, and hospital stay. (Registration: ClinicalTrials.gov NCT02781194-completed). RESULTS: 150 participants were randomized. Compared to group "AIR" (n = 48), there was significantly less pain in group "HUMI +" (n = 48) in the recovery room (- 1.068; 95% CI - 2.08 to - 0.061), as well as significantly less ibuprofen use at day two (- 0.5871 g ± 0.258; p-value = 0.0471). Other variables did not change significantly. Stratification for presence of endometriosis or non-previous abdominal surgery in patient history revealed significantly less pain in both groups "HUMI" (n = 50) and "HUMI +" versus group "AIR." Related side effects were not noted. CONCLUSION: In the overall population, the use of warm, humidified insufflation gas did not yield clinically relevant effects; however, in predisposed patients with endometriosis and who could otherwise expect high pain levels, warm and humidified gas may be beneficial.
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Endometriosis , Insuflación , Laparoscopía , Dióxido de Carbono , Endometriosis/cirugía , Femenino , Calor , Humanos , Humedad , Insuflación/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Estudios ProspectivosRESUMEN
Urinary incontinence (UI) could negatively affect a person's quality of life (QoL). This study investigates the association among gynecological cancers, their treatments, UI, and its effect on the QoL of survivors of gynecological cancer. This cross-sectional questionnaire-based study included 121 cases from 405 patients who had undergone gyneco-oncological therapy. The participants were asked whether they experienced any form of UI and whether it impacted their QoL. The following therapies were used to treat the 12 gynecologic tumor types found in the participants: surgery (n = 116, 95.87%), chemotherapy (CTx) (n = 51, 42.2%), radiotherapy (RTx) (n = 31, 25.6%), and antibody therapy (ABT) (n = 11, 9.1%). No significant association was determined between tumor type and UI. However, body mass index (BMI), radical hysterectomy, vulvar or vaginal surgery, and presence of UI before treatment had significant impacts on the presence of UI. The surgical access routes, CTx, ABT, and hysterectomy had significant impacts on the severity of UI after treatment. Among all patients, 55.4% reported very good QoL. These reports of good QoL by patients could be due to their very good adjustment to the situation, with regard to being diagnosed with and receiving treatment for cancer, or due to the patients considering UI to not be much of an issue. Additionally, 34% of patients reported they had not been informed about the risk of UI before treatment. Informing patients about UI as one of the risks of therapy before initiating the treatment is crucial as patients who had been informed beforehand coped with UI far better than those who were not informed. Hence, the treatment of UI is often successful, so patients should be encouraged to receive urogynecological consultation.
Asunto(s)
Neoplasias Pélvicas , Incontinencia Urinaria , Femenino , Humanos , Calidad de Vida , Estudios Transversales , Incontinencia Urinaria/etiología , Encuestas y CuestionariosRESUMEN
PURPOSE: The aim of this study was to examine whether OASIS, and its extent, can be confirmed or excluded using transperineal ultrasound (TPUS). A further objective of this study was to monitor the healing process over a period of 6 months and to establish a connection between the sonographic appearance of obstetric anal sphincter injury (OASIS) and anal incontinence. MATERIALS AND METHODS: In this retrospective clinical study, women with OASIS who gave birth between March 2014 and August 2019 were enrolled. All the patients underwent TPUS 3 days and 6 months after delivery. A GE E8 Voluson ultrasound system with a 3.5-5 MHz ultrasound probe was used. The ultrasound images showed a third-degree injury, with the measurement of the width of the tear and its extent (superficial, partial, complete, EAS and IAS involvement). A positive contraction effect, a sign of sufficient contraction, was documented. Six months after delivery, a sonographic assessment of the healing (healed, scar or still fully present) was performed. A Wexner score was obtained from each patient. The patients' medical histories, including age, parity, episiotomy and child's weight, were added. RESULTS: Thirty-one of the 55 recruited patients were included in the statistical evaluation. Three patients were excluded from the statistical evaluation because OASIS was excluded on TPUS 3 days after delivery. One patient underwent revision surgery for anal incontinence and an inadequately repaired anal sphincter injury, as shown sonographic assessment, 9 days after delivery. Twenty patients were excluded for other reasons. The results suggest that a tear that appears smaller (in mm) after 3 days implies better healing after 6 months. This effect was statistically significant, with a significance level of alpha = 5% (p = 0.0328). Regarding anal incontinence, women who received an episiotomy had fewer anal incontinence symptoms after 6 months. The effect of episiotomy was statistically significant, with a significance level of alpha = 5% (p = 0.0367). CONCLUSION: TPUS is an accessible, non-invasive method for detecting, quantifying, following-up and monitoring OASIS in patients with third-degree perineal tears. The width, as obtained by sonography, is important with regard to the healing of OASIS. A mediolateral episiotomy seems to prevent anal incontinence after 6 months.
Asunto(s)
Incontinencia Fecal , Laceraciones , Complicaciones del Trabajo de Parto , Canal Anal/diagnóstico por imagen , Canal Anal/lesiones , Parto Obstétrico/efectos adversos , Episiotomía/efectos adversos , Incontinencia Fecal/diagnóstico por imagen , Incontinencia Fecal/etiología , Femenino , Humanos , Recién Nacido , Laceraciones/diagnóstico por imagen , Complicaciones del Trabajo de Parto/diagnóstico por imagen , Complicaciones del Trabajo de Parto/etiología , Perineo/diagnóstico por imagen , Perineo/lesiones , Embarazo , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the occurrence of anxiety in women attending a colposcopic examination within the new cervical cancer screening in Germany. METHODS: One hundred and fifty-six patients were asked to fill out Spielbergers STAI inventory form prior to their colposcopic examination. For the statistical analysis, a two by two between-group design was applied including the following group factors: the repeat factors included patients, who presented to our centre of dysplasia for the first time (new) and patients who have had an examination in our centre before (repeat). Further, the factor diagnosis included two groups: first, patients with cervical dysplasia and second, patients with vulva diseases. RESULTS: The analysis of the STAI results showed that patients presenting with cervical dysplasia for the first time had the highest levels of anxiety, directly followed by new patients in the vulva group. The ANOVA revealed a main effect of the repeat factor, F(1,140) = 7.53, p = 0.007. There was no significant effect of diagnosis. CONCLUSION: Regardless of the diagnosis, patients being transferred for a colposcopy within the cervical cancer screening program for the first time have very high anxiety levels. The prospect of a potentially painful examination seems to be a key factor. Only a scientific evaluation of the new cervical cancer screening will be able to show if the rising numbers of colposcopic examinations is really worth the risk of exposing so many more women to the emotional distress of a colposcopy.
Asunto(s)
Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Ansiedad , Colposcopía , Detección Precoz del Cáncer , Femenino , Humanos , Embarazo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiologíaRESUMEN
BACKGROUND: Hypothermia is defined as a decrease in body core temperature to below 36 °C. If intraoperative heat-preserving measures are omitted, a patient's temperature will fall by 1â-â2 °C. Even mild forms of intraoperative hypothermia can lead to a marked increase in morbidity and mortality. Using warm and humidified gas insufflation in laparoscopy may help in the maintenance of intraoperative body temperature. METHODS: In this prospective randomized controlled study, we investigated effects of temperature and humidity of the insufflation gas on intra- and postoperative temperature management. 150 patients undergoing gynecologic laparoscopic surgery were randomly assigned to either insufflation with non-warmed, non-humidified CO2 with forced air warming blanket (AIR), humidified warm gas without forced air warming blanket (HUMI) or humidified warm gas combined with forced air warming blanket (HUMI+). We hypothesized that the use of warmed laparoscopic gas would have benefits in the maintenance of body temperature and reduce the occurrence of hypothermia. RESULTS: The use of warm and humidified gas insufflation alone led to more hypothermia episodes with longer duration and longer recovery times as well as significantly lower core body temperature compared to the other two groups. In the comparison of the AIR group and HUMI + group, HUMI + patients had a significantly higher body temperature at arrival at the PACU (Post Anaesthesia Care Unit), had the least occurrence of hypothermia and suffered from less shivering. CONCLUSION: The use of warm and humidified gas insufflation alone does not sufficiently warm the patients. The optimal temperature management is achieved in the combination of external forced air warming and insufflation of warm and humidified laparoscopy gas.