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1.
Strahlenther Onkol ; 200(6): 461-467, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38393398

RESUMO

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.


Assuntos
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 Adjuvante
2.
Anal Bioanal Chem ; 416(12): 2969-2981, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38488952

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 Testes
3.
Int J Mol Sci ; 24(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298528

RESUMO

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Oncogenes , Movimento Celular/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Membrana Transportadoras/metabolismo
4.
BMC Cancer ; 19(1): 520, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146706

RESUMO

BACKGROUND: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis. METHODS: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk. RESULTS: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively. CONCLUSIONS: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Sistema de Registros/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Metástase Neoplásica , Recidiva Local de Neoplasia , Fatores de Risco
5.
Arch Gynecol Obstet ; 299(5): 1481-1485, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30737584

RESUMO

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 Jovem
6.
Arch Gynecol Obstet ; 298(4): 773-779, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30116930

RESUMO

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 Jovem
7.
Ann Surg Oncol ; 24(3): 698-704, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27783163

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) subtype and young patient age are both associated with an increased risk of local recurrence (LR) and distant recurrence (DR). In young women with TNBC, it is unclear whether subtype or patient age is driving prognosis. METHODS: Patients treated for primary TNBC from 1998 to 2011 were identified from the breast surgery database. Clinicopathologic characteristics, treatment, and outcomes were compared between patients <40 and ≥40 years of age at diagnosis. Multivariate models were used to identify factors independently associated with LR and DR. RESULTS: Among 1930 patients with TNBC, 289 (15 %) were <40 and 1641 (85 %) were ≥40 years of age at diagnosis. Younger patients were more likely to present with higher stage disease and more likely to receive mastectomy (p < 0.01), axillary node dissection (p < 0.01), and chemotherapy (p < 0.01). At a median follow-up of 74 (0-201.1) months, there was no difference in LR or disease-free survival (DFS) by age group [5-year LR = 3.9 % (95 % confidence interval (CI) 1.5-6.2) vs. 4.5 % (95 % CI 3.5-5.6) and 5-year DFS = 75.3 % (95 % CI 70.2-80.7) vs. 77.7 % (95 % CI 75.6-79.8), p = 0.94] in patients aged <40 and ≥40 years, respectively. On multivariate analysis, larger tumor size, lymphovascular invasion, and nodal positivity were associated with increased risk of DR. Age and type of surgery were not significantly associated with either outcome. CONCLUSIONS: Young age at diagnosis is not an independent risk factor for LR or DR in patients with TNBC.


Assuntos
Excisão de Linfonodo , Recidiva Local de Neoplasia/patologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Axila , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Seguimentos , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
8.
J Sex Med ; 11(9): 2342-50, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25042204

RESUMO

INTRODUCTION: Hysterectomy ranks among the most frequently performed gynecological surgical procedures. At the time of operation, the majority of patients are premenopausal and sexually active. Hence, detailed counseling about the effects of hysterectomy on postoperative sexuality and quality of life can be regarded as an integral part of preoperative counseling. However, available data on these subjects are limited and contradictory. AIM: The aim of this study was to assess quality of life and sexuality following three common hysterectomy procedures-total laparoscopic hysterectomy (TLH), supracervical laparoscopic hysterectomy (SLH), and vaginal hysterectomy (VH)-in premenopausal patients using the European Quality of Life Five-Dimension Scale (EQ-5D) and Female Sexual Function Index (FSFI). MAIN OUTCOME MEASURES: Preoperative and postoperative EQ-5D and FSFI scores were compared using the Wilcoxon signed-rank test. Kruskal-Wallis analysis and Mann-Whitney U-test with post hoc Bonferroni correction were used to assess differences among the three subgroups. METHODS: All premenopausal patients who underwent TLH, SLH, or VH without adnexectomy due to benign uterine disorders between April 2011 and June 2013 at the Department of Gynaecology and Obstetrics of Saarland University Hospital were enrolled in this observational cohort study. Sexuality and quality of life status were assessed preoperatively and 6 months postoperatively using two standardized validated questionnaires: the FSFI, a multidimensional, self-reported instrument for the assessment of female sexual function, and the EQ-5D, a standardized, validated instrument to measure an individual's health status. RESULTS: Of 402 eligible patients, 237 completed the study. Patient characteristics and preoperative FSFI and EQ-5D scores did not differ among the three hysterectomy subgroups. Postoperative FSFI and EQ-5D scores were significantly higher (P ≤ 0.01) than preoperative scores for all procedures but did not differ among the groups. CONCLUSIONS: In this cohort of premenopausal women, hysterectomy without adnexectomy performed due to benign uterine pathologies had significant positive effects on postoperative sexual function and quality of life, regardless of the surgical technique used.


Assuntos
Histerectomia/métodos , Qualidade de Vida , Sexualidade , Adulto , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade
9.
Cancers (Basel) ; 16(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254908

RESUMO

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.

10.
Arch Gynecol Obstet ; 287(4): 715-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23179797

RESUMO

PURPOSE: We evaluated the long-term results and patient's satisfaction in reduction mammaplasties for symptomatic mammary hypertrophy. METHODS: From 2002 to 2008 a total of 92 women underwent bilateral mammaplasty for a symptomatic macromastia at our department. Three different surgical techniques for reduction mammaplasty were used (Bostwick, Stroembeck, Ribeiro). Patients were re-contacted in 2009 and asked to complete a self-assessment survey in order to asses their satisfaction with the post-operative symptom-relief and the overall outcome. RESULTS: 90.5 % of all patients stated, that they would retrospectively re-opt for a reduction mammaplasty. Preoperative patients' age, BMI and severity of macromasty-related symptoms were found to be factors positively correlated with a high post-interventional satisfaction with the achieved symptom-relief and the overall outcome. No correlation was found between the amount of intra-operatively resected breast tissue and the post-operative patients' assessment. Patients' assessment regarding the achieved post-operative symptom relief was comparable for all three surgical techniques, however the overall outcome rating for both bi-pedicled approaches (Stroembeck and Ribeiro) was higher compared to the mono-pedicled Bostwick technique. CONCLUSIONS: Reduction mammaplasty for patients with a mammary hypertrophy and somatic symptoms could offer a causal and effective treatment. The predictive factors for a high patients' satisfaction identified in this study could become a valuable tool in the pre-operative patients counceling and their role should be further evaluated prospectively. The use of bi-pedicled surgical techniques seems to favor a high post-operative patients' assessment.


Assuntos
Hipertrofia/cirurgia , Mamoplastia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Mama/anormalidades , Mama/cirurgia , Feminino , Humanos , Hipertrofia/complicações , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
11.
Int J Gynaecol Obstet ; 160(2): 548-553, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35965372

RESUMO

OBJECTIVE: To evaluate how hysterectomy performed for benign gynecologic pathologies affects the quality of life and sexual function of patients aged 35 years or younger, and if outcomes differ according to the surgical technique. METHODS: Seventy-three patients who underwent total laparoscopic hysterectomy (TLH), supracervical laparoscopic hysterectomy (SLH), or vaginal hysterectomy (VH) for benign uterine disorders between April 2014 and June 2020 at the Department of Gynecology and Obstetrics, Saarland University Hospital, Homburg, Germany, were enrolled in this prospective observational cohort study. Quality of life and sexual function were assessed preoperatively and 6 months postoperatively using standardized validated questionnaires: the European Quality of Life Five-Dimension Scale (EQ-5D) and the Female Sexual Function Index (FSFI). RESULTS: Thirty-three (45%) patients underwent TLH, 25 (34%) underwent SLH, and 15 (21%) patients underwent VH. The median preoperative EQ-5D score, FSFI score, and EQ-5D visual analog scale were 0.9 (range 0.62-1), 19.25 (range 2.4-27.4), and 50 (range 0-100); postoperative scores were 1 (range 0.61-1), 24.15 (range 3.9-29.3), and 90 (range 30-100), respectively (P ≤ 0.001). Postoperative scores were significantly higher than preoperative scores, with no significant difference according to the surgical technique. CONCLUSION: Hysterectomy for benign indication in women aged 35 years or less significantly improved the patients' quality of life and sexual function with no differences regarding the surgical technique. CLINICAL TRIAL REGISTRATION: The study was registered in the German trial registry (no. DRKS00005622).


Assuntos
Laparoscopia , Doenças Uterinas , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Histerectomia/métodos , Histerectomia Vaginal/métodos , Doenças Uterinas/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia
12.
J Clin Med ; 12(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36983206

RESUMO

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients-indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.

13.
Cancers (Basel) ; 15(20)2023 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-37894466

RESUMO

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case-control (n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3-150) and 150 (5-150) months; p = 0.61] and overall survival [36 (3-150) and 50 (1-275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes.

14.
Geburtshilfe Frauenheilkd ; 83(9): 1102-1116, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37706057

RESUMO

This year's 18th St. Gallen (SG) consensus conference on the treatment of early breast cancer (SGBCC: St. Gallen International Breast Cancer Conference) focused on practice-oriented questions. The individual situation and risk-benefit assessment were discussed in great detail. As in previous years, a German working group of leading breast cancer experts presented the results of the international SGBCC 2023 against the background of German treatment recommendations - especially the updated treatment recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) - for everyday clinical practice in Germany. The German treatment recommendations of AGO are based on the current evidence. The comparison with the clinical approach in Germany has proven useful, as the SGBCC panel consists of experts from different countries and disciplines. That is why country-specific characteristics can be incorporated into the SGBCC recommendations.

15.
Front Physiol ; 13: 1014271, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262254

RESUMO

The human SEC62 gene is located on chromosome 3q, was characterized as a tumor driver gene and is found to be overexpressed in an ever-growing number of tumors, particularly those with 3q26 amplification. Where analyzed, SEC62 overexpression was associated with poor prognosis. Sec62 protein is a membrane protein of the endoplasmic reticulum (ER) and has functions in endoplasmic reticulum protein import, endoplasmic reticulum-phagy and -in cooperation with the cytosolic protein calmodulin- the maintenance of cellular calcium homeostasis. Various human tumors show SEC62 overexpression in immunohistochemistry and corresponding cell lines confirm this phenomenon in western blots and immunofluorescence. Furthermore, these tumor cells are characterized by increased stress tolerance and migratory as well as invasive potential, three hallmarks of cancer cells. Strikingly, plasmid-driven overexpression of SEC62 in non-SEC62 overexpressing cells introduces the same three hallmarks of cancer into the transfected cells. Depletion of Sec62 from either type of SEC62 overexpressing tumor cells by treatment with SEC62-targeting siRNAs leads to reduced stress tolerance and reduced migratory as well as invasive potential. Where tested, treatment of SEC62 overexpressing tumor cells with the small molecule/calmodulin antagonist trifluoperazine (TFP) phenocopied the effect of SEC62-targeting siRNAs. Recently, first phase II clinical trials with the prodrug mipsagargin/G202, which targets cellular calcium homeostasis in prostate cells as well as neovascular tissue in various tumors were started. According to experiments with tumor cell lines, however, SEC62 overexpressing tumor cells may be less responsive or resistant against such treatment. Therefore, murine tumor models for tumor growth or metastasis were evaluated with respect to their responsiveness to treatment with a mipsagargin analog (thapsigargin), or trifluoperazine, which had previously been in clinical use for the treatment of schizophrenia, or with the combination of both drugs. So far, no additive effect of the two drugs was observed but trifluoperazine had an inhibitory effect on tumor growth and metastatic potential in the models. Here, we review the state of affairs.

16.
Front Physiol ; 13: 1054508, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685175

RESUMO

With approximately 220,000 newly diagnosed cases per year, ovarian cancer is among the most frequently occurring cancers among women and the second leading cause of death from gynecological malignancies worldwide. About 70% of these cancers are diagnosed in advanced stages (FIGO IIB-IV), with a 5-year survival rate of 20-30%. Due to the poor prognosis of this disease, research has focused on its pathogenesis and the identification of prognostic factors. One possible approach for the identification of biological markers is the identification of tumor entity-specific genetic "driver mutations". One such mutation is 3q26 amplification in the tumor driver SEC62, which has been identified as relevant to the pathogenesis of ovarian cancer. This study was conducted to investigate the role of SEC62 in ovarian malignancies. Patients with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who were treated between January 2007 and April 2019 at the Department of Gynecology and Obstetrics, Saarland University Hospital, were included in this retrospective study. SEC62 expression in tumor tissue samples taken during clinical treatment was assessed immunohistochemically, with the calculation of immunoreactivity scores according to Remmele and Stegner, Pathologe, 1987, 8, 138-140. Correlations of SEC62 expression with the TNM stage, histological subtype, tumor entity, and oncological outcomes (progression-free and overall survival) were examined. The sample comprised 167 patients (123 with ovarian cancer and 44 with borderline tumors of the ovary) with a median age of 60 (range, 15-87) years. At the time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed SEC62 overexpression in tumor cells and no SEC62 expression in other cells. Median immunoreactivity scores were 8 (range, 2-12) for ovarian cancer and 9 (range, 4-12) for borderline tumors of the ovary. Patients with borderline tumors of the ovary as well as patients with ovarian cancer and an immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to be a prognostic biomarker for the overall survival of patients with ovarian malignancies.

17.
Laryngoscope Investig Otolaryngol ; 5(4): 621-629, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32864433

RESUMO

OBJECTIVE: Endoscopic sinus surgery represents the gold standard for surgical treatment of chronic sinus diseases. Thereby, navigation systems can be of distinct use. In our study, we tested the recently developed KARL STORZ NAV1 SinusTracker navigation software that incorporates elements of augmented reality (AR) to provide a better preoperative planning and guidance during the surgical procedure. METHODS: One hundred patients with chronic sinus disease were operated on using either a conventional navigation software (n = 52, non-AR, control group) or a navigation software incorporating AR elements (n = 48, AR, intervention group). Incidence of postoperative complications, duration of surgery, surgeon-reported benefit from the navigation system and patient-reported postoperative rehabilitation were assessed. RESULTS: The surgeons reported a higher benefit during surgery, used the navigation system for more surgical steps and spent longer time with preoperative image analysis when using the AR system as compared with the non-AR system. No significant differences were seen in terms of postoperative complications, target registration error, operation time and postoperative rehabilitation. CONCLUSION: The AR enhanced navigation software shows a high acceptance by sinus surgeons in different stages of surgical training and offers potential benefits during surgery without affecting the duration of the operation or the incidence of postoperative complications. LEVEL OF EVIDENCE: 1b.

18.
Abdom Radiol (NY) ; 45(9): 2871-2878, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32671442

RESUMO

PURPOSE: Characterization of intraabdominal fluid collections as postoperative complication is a challenging task. The aim was to develop and validate a new score to differentiate infected from sterile postoperative abdominal fluid collections and to compare it with a published score. MATERIALS AND METHODS: From May to November 2015, all patients with postoperative CT and C-reactive protein (CRP) 24 hours before CT-guided drainage were retrospectively included (Group A). HU, gas entrapment and wall enhancement of fluid collections were evaluated in the CT. All parameters were correlated with microbiology. To validate the score and to compare it with a published score, a second patient cohort was retrospectively recruited (Group B; January 2013-April 2015; December 2015-September 2016). RESULTS: In Group A (50 patients), univariate analysis confirmed that the four parameters were significantly associated with infected fluid collections. Based on binary logistic regression analysis, a score from 0 to 11 was developed (CRP

Assuntos
Drenagem , Tomografia Computadorizada por Raios X , Proteína C-Reativa , Humanos , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos
19.
Minerva Ginecol ; 72(1): 43-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32153163

RESUMO

INTRODUCTION: Endometriosis is a chronic hormone-dependent disease affecting approximately 25-30% of women in the third and fourth decade. Despite its frequency, it is often detected late. The aim of this overview article was to present a standardized treatment algorithm for an interdisciplinary endometriosis consultation considering conservative and surgical approaches. EVIDENCE ACQUISITION: Despite the frequency of endometriosis and a high number of publications dealing with the disease there is a lack of evidence in literature for standardized treatment algorithms allowing a rational diagnostic and therapeutic approach. In May 2019 we did a literature search in Medline. While finding 26702 publications under the term "endometriosis" there was only one publication for the search term "endometriosis consultation treatment algorithm." After screening the abstracts 144 publications in English, French or German language had been assessed as relevant for the diagnosis and therapy of endometriosis (143 overview articles and one guideline). EVIDENCE SYNTHESIS: Based on clinical evidence, we have developed a treatment algorithm for women with suspected endometriosis. The diagnosis includes a structured medical history with the identification of endometriosis-typical symptoms and a gynecological examination, if necessary additional examinations. The treatment algorithm is essentially divided into the phase of diagnosis and the phase of therapy as well as the prevention of recurrence or long-term treatment. A multi-professional team of visceral surgery, urology, nutritional medicine, physiotherapy and psychology can be consulted for support. CONCLUSIONS: The treatment of endometriosis should be multiprofessional, standardized and reproducible during specialized consultations at certified centers. So far, there are few publications on a standardized and clinically proven treatment algorithm for women with suspected endometriosis. The presented treatment algorithm could be helpful in the diagnosis and treatment of endometriosis patients, even at other centers.


Assuntos
Algoritmos , Endometriose/diagnóstico , Endometriose/terapia , Adulto , Tratamento Conservador , Endometriose/cirurgia , Feminino , Humanos , Anamnese , Equipe de Assistência ao Paciente , Recidiva , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Prevenção Secundária
20.
Minerva Ginecol ; 71(4): 298-305, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30993959

RESUMO

INTRODUCTION: Protecting fertility in the presence of cancer has become highly significant, as the desire to give birth to a child is increasingly postponed to later in life, and long-term survival with cancer has increased. A variety of fertility-preserving methods have been developed. EVIDENCE ACQUISITION: To find them, we performed a literature search in Medline using the key words "female fertility preservation in cancer" in December 2017. A total of 2381 different publications were found. EVIDENCE SYNTHESIS: After screening the abstracts 78 publications in English, French, or German language had been assessed as relevant (17 dealing with medical approaches, six with surgical approaches, 15 with oocyte cryopreservation, 11 with ovarian tissue cryopreservation and 29 were review articles). In general, there are medical (non-surgical) and surgical approaches. Medical approaches comprise administration of GnRH-analogues during gonad toxic oncologic treatment, and cryopreservation of oocytes after ovarian stimulation. Surgical approaches comprise traditional methods of organ-saving surgery and ovarian transposition outside of the radiation portal as well as ovary cryopreservation as standard. CONCLUSIONS: It is important to inquire about a prospective desire to have children with premenopausal women with cancer and comprehensively explain the fertility conserving methods available. Every premenopausal woman with cancer should be counseled about the methods of fertility protection currently available at a multiprofessional center.


Assuntos
Criopreservação/métodos , Preservação da Fertilidade/métodos , Neoplasias/terapia , Feminino , Humanos , Oócitos/metabolismo , Ovário/metabolismo
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