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A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
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Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Anotação de Sequência Molecular , Regiões Promotoras Genéticas , Neoplasias da Mama/genética , Sistemas CRISPR-Cas , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 2 , Feminino , Estudos de Associação Genética , Variação Genética , Humanos , Fatores de Risco , Deleção de SequênciaRESUMO
PURPOSE: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.
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Neoplasias da Mama , Neoplasias da Mama/radioterapia , Humanos , Feminino , Alemanha , Guias de Prática Clínica como Assunto , Metástase Linfática/radioterapia , Metástase Linfática/patologia , Radioterapia (Especialidade)/normas , Radioterapia AdjuvanteRESUMO
After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.
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Endométrio , Neovascularização Patológica , Fator de Crescimento Placentário , Pré-Eclâmpsia , Proteínas Serina-Treonina Quinases , Fatores de Transcrição , Feminino , Humanos , Gravidez , Endométrio/metabolismo , Endométrio/irrigação sanguínea , Ensaio de Imunoadsorção Enzimática , Proteínas Imediatamente Precoces/metabolismo , Neovascularização Patológica/metabolismo , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: The goal of breast-conserving surgery is to achieve negative tumor margins, since insufficient marginal distance is associated with more local and distant recurrences. This study investigates whether IOUS (intraoperative ultrasound) can reduce the re-resection rate compared to standard breast surgery, regardless of tumor biology and focality. MATERIALS AND METHODS: The present study is a monocentric, prospective, randomized, and non-blinded parallel group study conducted between 7/2015 and 2/2018. Patients with sonographically visible breast cancer were randomized into two study arms: 1) breast-conserving surgery with IOUS; 2) conventional arm. RESULTS: 364 patients were included in the study and underwent surgery. Tumor biology, size, and focality were equally distributed in both groups (p = 0.497). The study arms did not differ significantly in the proportion of preoperative wire markings (p= 0.084), specimen weight (p = 0.225), surgery duration (p = 0.849), and the proportion of shavings taken intraoperatively (p = 0.903). Positive margins were present in 16.6% of the cases in the IOUS arm and in 20.8% in the conventional arm (p = 0.347). Re-operation was necessary after intraoperative shavings in 14.4% of cases in the US arm and in 21.3% in the conventional arm (p = 0.100). CONCLUSION: Although the present study showed a clear difference in the rate of positive tumor margins with IOUS compared to conventional breast surgery without IOUS, this was not statistically significant in contrast to the current literature. This could be due to the high expertise of the breast surgeons, the precise wire marking, or the fact that the IOUS technique was not standardized.
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Breast cancer remains a leading cause of cancer mortality in women globally. Despite advancements in systemic therapy, the risk of distant recurrence persists even after such treatment and may be linked to disseminated tumor cells (DTCs). Variability in molecular characteristics between primary tumors (PTs) and distant metastases underscores the need to comprehensively understand metastatic pathways. This retrospective study investigated discrepancies between HER2 expression in PTs and DTCs and their implications for survival outcomes in 201 early breast cancer (EBC) patients. We found a significant association between HER2 expression in PTs and DTCs when classifying tumors as HER2-high/low/negative. Patients whose HER2 status was discordant between PTs and DTCs exhibited worse distant disease-free survival than those with concordant status. Multivariate analysis confirmed the HER2 status of DTCs as an independent prognostic factor for distant DFS. These findings emphasize the importance of assessing HER2 expression in DTCs and its potential implications for tailored therapy strategies in EBC. Furthermore, prospective trials are needed to validate these findings and explore targeted therapies based on the molecular characteristics of DTCs.
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Neoplasias da Mama , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Prognóstico , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Metástase NeoplásicaRESUMO
Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5-HIF-1α-COX2 axis could promote endometrial cancer progression.
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Neoplasias do Endométrio , Regulação da Expressão Gênica , Humanos , Feminino , Ciclo-Oxigenase 2/genética , Neoplasias do Endométrio/genética , Fatores de Transcrição NFATC , Transdução de Sinais , Dinoprostona , Fator V , Fatores de TranscriçãoRESUMO
Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Pesquisadores , Ensaio de Imunoadsorção Enzimática , Nível de SaúdeRESUMO
BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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Carcinoma , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genética , RNA Mensageiro , Cistadenocarcinoma Seroso/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/uso terapêutico , Ciclina E/genéticaRESUMO
Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
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Neoplasias da Mama/genética , Predisposição Genética para Doença , Genoma Humano , Herança Multifatorial , Segunda Neoplasia Primária/genética , Adulto , Idoso , Povo Asiático , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Neoplasias da Mama/terapia , Estudos de Coortes , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etnologia , Segunda Neoplasia Primária/terapia , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Medição de Risco , População BrancaRESUMO
PURPOSE: Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. METHODS: DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. RESULTS: Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047). CONCLUSION: We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Prognóstico , Estudos Retrospectivos , Alemanha , Recidiva Local de Neoplasia/patologiaRESUMO
PURPOSE: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient's quality of life) using a questionnaire. METHODS: 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient's quality of life. RESULTS: 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients' health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. CONCLUSION: This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Qualidade de Vida , Genômica , Revelação , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.
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Neoplasias do Endométrio , Ginecologia , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Sarcoma/epidemiologia , Sarcoma/terapia , Sarcoma/patologia , Histerectomia , Alemanha/epidemiologia , Neoplasias do Endométrio/patologia , Neoplasias Uterinas/patologia , Estudos RetrospectivosRESUMO
PURPOSE: Cervical cancer screening by visual inspection with acetic acid (VIA) during colposcopy can be challenging and is highly dependent on the clinical experience of the examiner. Health-care systems lack qualified physicians able to perform the examination in both industrialized and low- and middle-income countries. Previous work has shown the general potential of hyperspectral imaging (HSI) to discriminate CIN from normal tissue, but clinical translation has been limited due to the lack of medically approved HSI systems. METHODS: In this study, we evaluate the feasibility of a commercially available HSI system for CIN detection in a prospective monocentric clinical trial. RESULTS: By obtaining spectral fingerprints of 41 patients with CIN 1-3 we show that HSI-based differentiation between CIN and normal tissue is possible with high statistical significance. Major spectral differences were seen in the 555-585 wavelength area. CONCLUSION: HSI advances tissue differentiation by associating each pixel with high-dimensional spectra and thereby obtains morphological and biochemical information of the observed tissue. Currently available and medically approved HSI systems may represent a contact- and marker-free examiner-independent method for the diagnosis of CIN.
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Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Colposcopia , Detecção Precoce de Câncer , Imageamento Hiperespectral , Estudos Prospectivos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/prevenção & controleRESUMO
PURPOSE: Conventional laparoscopic surgery (CLS) imposes an increased risk of work-related musculoskeletal disorders. Technical innovations, such as robotic-assisted laparoscopic surgery (RALS), may provide ergonomic benefits. We compare the surgeon`s work-related demands of CLS vs RALS for benign hysterectomies. METHODS: Five specialists (3 females, 2 males) each performed four RALS and four CLS as part of their daily clinical routine. During the surgical procedures, muscular demands were assessed by bipolar surface electromyograms of the descendent trapezius, extensor digitorum and flexor carpi radialis muscles as well as cardio-vascular demands by electrocardiography, and neck, arm and torso posture by gravimetrical position sensors. Additionally, the subjects rated their level of perceived workload (NASA TLX questionnaire with 6 dimension) and musculoskeletal discomfort (11-point Likert-scale, 0-10). RESULTS: Muscular demands of the trapezius and flexor carpi radialis muscles were lower with RALS but extensor digitorum demands increased. Cardiovascular demands were about 9 heart beats per minute (bpm) lower for RALS compared to CLS with a rather low median level for both surgical techniques (RALS = 84 bpm; CLS 90 bpm). The posture changed in RALS with an increase in neck and torso flexion, and a reduction in abduction and anteversion position of the right arm. The perceived workload was lower in the physical demands dimension but higher in the mental demands dimension during RALS. Subjective musculoskeletal discomfort was rare during both surgical techniques. CONCLUSIONS: This explorative study identified several potential ergonomic benefits related to RALS which now can be verified by studies using hypothesis testing designs. However, potential effects on muscular demands in the lower arm extensor muscles also have to be addressed in such studies.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Cirurgiões , Masculino , Feminino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Carga de Trabalho , Eletromiografia , Laparoscopia/métodos , PosturaRESUMO
PURPOSE: Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS). METHODS: Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL. RESULTS: The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training-the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time. CONCLUSION: PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.
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Neoplasias da Mama , Linfedema , Humanos , Feminino , Qualidade de Vida , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Nível de Saúde , Linfedema/etiologiaRESUMO
PURPOSE: Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. METHODS: Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. RESULTS: The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). CONCLUSION: Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account.
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Doenças Cardiovasculares , Hipertensão , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Fatores de Risco , Período Pós-Parto , Atenção Primária à SaúdeRESUMO
PURPOSE: Endometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC. METHODS: In this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate. RESULTS: The eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p < .05). No intra- and postoperative complications were registered. CONCLUSION: This clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis.
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Endometriose , Laparoscopia , Feminino , Humanos , Endometriose/cirurgia , Endometriose/patologia , Coagulação com Plasma de Argônio , Estudos Prospectivos , Peritônio/patologia , Laparoscopia/métodos , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Aderências Teciduais/patologiaRESUMO
PURPOSE: To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). PATIENT: A 37-year-old woman with uterovaginal agenesis due to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. METHODS: Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. RESULTS: TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. CONCLUSIONS: To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.
Assuntos
Cesárea , Laparoscopia , Masculino , Humanos , Feminino , Gravidez , Adulto Jovem , Adulto , Doadores Vivos , Útero/anormalidades , Histerectomia , Laparoscopia/métodos , AloenxertosRESUMO
Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a clinical routine level, the characterization of DTCs and in vitro drug testing on DTCs are of great interest. Therefore, biobanking methods, as well as novel approaches to DTC isolation, need to be developed. In this study, we established a protocol for the biobanking of BM samples and evaluated a microfluidic-based separation system (Parsortix®) for the enrichment of cryopreserved DTCs. We were able to successfully isolate viable DTCs after the prior cryopreservation of BM samples. We calculated a significant increase of up to 90-fold in harvested DTCs with the proposed method compared to the current standard techniques, opening up new analysis possibilities for DTCs. Our advanced method further presents options for 3D DTC cultures, enabling the individualized testing of targeted therapies for BC patients. In conclusion, we present a novel approach for DTC enrichment, with possibilities for future clinical implications.
RESUMO
The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.