150 research outputs found
Comparison of two surgical methods for the treatment of CIN: classical LLETZ (large-loop excision of the transformation zone) versus isolated resection of the colposcopic apparent lesion - study protocol for a randomized controlled trial.
Background
In compliance with national and international guidelines, non-pregnant women with cervical intraepithelial neoplasia grade 3 should be treated by cervical conization. According to the definition of the large loop excision of the transformation zone (LLETZ) operation, the lesion needs to be resected, including the transformation zone. It is well known from the literature that the cone size directly correlates with the risk of preterm delivery in the course of a future pregnancy. Thus, it would be highly desirable to keep the cone dimension as small as possible while maintaining the same level of oncological safety.
Methods/Design
The aim of this study is to analyze whether resection of the lesion only, without additional excision of the transformation zone, is equally as effective as the classical LLETZ operation regarding oncological outcome. We are performing this prospective, patient-blinded multicenter trial by randomly assigning women who need to undergo a LLETZ operation for cervical intraepithelial neoplasia grade 3 to either of the following two groups at a ratio of 1:1: (1) additional resection of the transformation zone or (2) resection of the lesion only. To evaluate equal oncological outcome, we are performing human papillomavirus (HPV) tests 6 and 12 months postoperatively. The study is designed to consider the lesion-only operation as oncologically not inferior if the rate of HPV high-risk test results is not higher than 5 % compared with the HPV high-risk rate of women undergoing the classical LLETZ operation.
Discussion
In case that non-inferiority of the “lesion-only” method can be demonstrated, this operation should eventually become standard treatment for all women at childbearing age due to the reduction in risk of preterm delivery.
Trial registration
German Clinical Trials Register (DRKS) Identifier: DRKS00006169 webcite. Date of registration: 30 July 2014
Thyroid Hormone Receptors Predict Prognosis in BRCA1 Associated Breast Cancer in Opposing Ways
Since BRCA1 associated breast cancers are frequently classified as hormone receptor negative or even triple negative, the application of endocrine therapies is rather limited in these patients. Like hormone receptors that bind to estrogen or progesterone, thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily. TRs might be interesting biomarkers-especially in the absence of classical hormone receptors. The current study aimed to investigate whether TRs may be specifically expressed in BRCA1 associated cancer cases and whether they are of prognostic significance in these patients as compared to sporadic breast cancer cases. This study analyzed TR alpha and TR beta immunopositivity in BRCA1 associated (n = 38) and sporadic breast cancer (n = 86). Further, TRs were studied in MCF7 (BRCA1 wildtype) and HCC3153 (BRCA1 mutated) cells. TR beta positivity rate was significantly higher in BRCA1 associated as compared to sporadic breast cancers (p = 0.001). The latter observation remained to be significant when cases that had been matched for clinicopathological criteria were compared (p = 0.037). Regarding BRCA1 associated breast cancer cases TR beta positivity turned out to be a positive prognostic factor for five-year (p = 0.007) and overall survival (p = 0.026) while TR alpha positivity predicted reduced five-year survival (p = 0.030). Activation of TR beta resulted in down-modulation of CTNNB1 while TR alpha inhibition reduced cell viability in HCC3153. However, only BRCA1 wildtype MCF7 cells were capable of rapidly degrading TR alpha 1 in response to T3 stimulation. Significantly, this study identified TR beta to be up-regulated in BRCA1 associated breast cancer and revealed TRs to be associated with patients' prognosis. TRs were also found to be expressed in triple negative BRCA1 associated breast cancer. Further studies need to be done in order to evaluate whether TRs may become interesting targets of endocrine therapeutic approaches, especially when tumors are triple-negative
Thyroid Hormone Receptors Predict Prognosis in BRCA1 Associated Breast Cancer in Opposing Ways
Since BRCA1 associated breast cancers are frequently classified as hormone receptor negative or even triple negative, the application of endocrine therapies is rather limited in these patients. Like hormone receptors that bind to estrogen or progesterone, thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily. TRs might be interesting biomarkers-especially in the absence of classical hormone receptors. The current study aimed to investigate whether TRs may be specifically expressed in BRCA1 associated cancer cases and whether they are of prognostic significance in these patients as compared to sporadic breast cancer cases. This study analyzed TR alpha and TR beta immunopositivity in BRCA1 associated (n = 38) and sporadic breast cancer (n = 86). Further, TRs were studied in MCF7 (BRCA1 wildtype) and HCC3153 (BRCA1 mutated) cells. TR beta positivity rate was significantly higher in BRCA1 associated as compared to sporadic breast cancers (p = 0.001). The latter observation remained to be significant when cases that had been matched for clinicopathological criteria were compared (p = 0.037). Regarding BRCA1 associated breast cancer cases TR beta positivity turned out to be a positive prognostic factor for five-year (p = 0.007) and overall survival (p = 0.026) while TR alpha positivity predicted reduced five-year survival (p = 0.030). Activation of TR beta resulted in down-modulation of CTNNB1 while TR alpha inhibition reduced cell viability in HCC3153. However, only BRCA1 wildtype MCF7 cells were capable of rapidly degrading TR alpha 1 in response to T3 stimulation. Significantly, this study identified TR beta to be up-regulated in BRCA1 associated breast cancer and revealed TRs to be associated with patients' prognosis. TRs were also found to be expressed in triple negative BRCA1 associated breast cancer. Further studies need to be done in order to evaluate whether TRs may become interesting targets of endocrine therapeutic approaches, especially when tumors are triple-negative
Brief Distress Screening in Clinical Practice: Does it Help to Effectively Allocate Psycho-Oncological Support to Female Cancer Inpatients?
BACKGROUND The usefulness of distress screening in cancer inpatient settings has rarely been investigated. This study evaluated a brief distress screening of inpatients in a breast cancer centre and a gynaecological cancer centre. PATIENTS AND METHODS Hospitalised patients with breast or gynaecological cancers were screened with the Distress Thermometer. Patients who scored above the cut-off, were referred by the medical staff, or self-referred were offered bedside psycho-oncological counselling. RESULTS Of 125 patients, 68 (54.4%) received an offer of counselling, and 62 patients (49.6%) accepted. Most of the counselling was induced by distress screening. Only 4 (3.2%) patients self-referred to the counselling service. Of the counselled patients, 65.8% stated that they had substantially benefited from psycho-oncological support; only 5.6% of the non-counselled patients indicated that they might have benefited from psycho-oncological support. CONCLUSION Almost all patients who will accept and benefit from psycho-oncological counselling can be identified if distress screening is used in conjunction with referrals by physicians and nurses. Distress screening is a worthwhile component in a framework of psycho-oncological support in a cancer inpatient setting. It paves the way to counselling for cancer inpatients who need it and are willing to accept it but hesitate to self-refer to psycho-oncological services
Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients
Background
Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients.
Methods
Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score.
Results
TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival.
Conclusions
This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols
Intraoperative Near-Infrared Autofluorescence and Indocyanine Green Imaging to Identify Parathyroid Glands: A Comparison
Objective. To investigate the feasibility of near-infrared autofluorescence (AF) and indocyanine green (ICG) fluorescence to identify parathyroid glands intraoperatively. Methods. Fluorescence imaging was carried out during open parathyroid and thyroid surgery. After visual identification, parathyroid glands were exposed to near-infrared (NIR) light with a wavelength between 690 and 770 nm. The camera of the Storz (R) NIR/ICG endoscopic system used detects NIR light as a blue signal. Therefore, parathyroid AF was expected to be displayed in the blue color channel in contrast to the surrounding tissue. Following AF imaging, a bolus of 5 mg ICG was applied intravenously. ICG fluorescence was detected using the same NIR/ICG imaging system. Well-vascularized parathyroid glands were expected to show a strong fluorescence in contrast to surrounding lymphatic and adipose tissue. Results. We investigated 78 parathyroid glands from 50 patients. 64 parathyroid glands (82%) displayed AF showing the typical bluish violet color. 63 parathyroid glands (81%) showed a strong and persistent fluorescence after application of ICG. The sensitivity of identifying a parathyroid gland by AF was 82% (64 true positive and 14 false negative results), while ICG imaging showed a sensitivity of 81% (63 true positive and 15 false negative results). The Fisher exact test revealed no significant difference between both groups at p < 0.05. Neither lymph nodes nor adipose tissue revealed substantial AF or ICG fluorescence. Conclusion. AF and ICG fluorescence reveal a high degree of sensitivity in identifying parathyroid glands. Further, ICG imaging facilitates the assessment of parathyroid perfusion. However, in the current setting both techniques are not suitable as screening tools to identify parathyroid glands at an early stage of the operation
Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients
Background
Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients.
Methods
Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score.
Results
TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival.
Conclusions
This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols
The prostaglandin receptor EP2 determines prognosis in EP3-negative and galectin-3-high cervical cancer cases
Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the IRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score >= 2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS >= 2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations
German evidence and consensus‐based (S3) guideline: Vaccination recommendations for the prevention of HPV‐associated lesions
Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view
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