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Introduction: Artificial intelligence (AI) is revolutionizing medical workflows, with self-learning systems like ChatGPT showing promise in therapy recommendations. Our study evaluated ChatGPT's performance in suggesting treatments for 30 breast cancer cases. AI's role in healthcare is expanding, particularly with tools like ChatGPT becoming accessible. However, understanding its limitations is vital for safe implementation. Material and Methods: We used 30 breast cancer cases from our medical board, assessing ChatGPT's suggestions. The input was standardized, incorporating relevant patient details and treatment options. ChatGPT's output was evaluated by oncologists based on a given questionnaire. Results: Treatment recommendations by ChatGPT were overall rated sufficient with minor limitations by the oncologists. The HER2 treatment category was the best-rated therapy option, with the most accurate recommendations. Primary cases received more accurate recommendations, especially regarding chemotherapy. Conclusions: While ChatGPT demonstrated potential, difficulties were shown in intricate cases and postoperative scenarios. Challenges arose in offering chronological treatment sequences and partially lacked precision. Refining inputs, addressing ethical intricacies, and ensuring chronological treatment suggestions are essential. Ongoing research is vital to improving AI's accuracy, balancing AI-driven suggestions with expert insights and ensuring safe and reliable AI integration into patient care.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Inteligência Artificial , Ginecologia/métodosRESUMO
Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, as well as urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. The present study aimed to decipher the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of a third-generation natural killer (NK) cell chimeric antigen receptor (CAR) against CD24 in urologic tumour cell lines. Up to 20 urologic tumour cell lines and several non-malignant control cells were included. XTT viability assays and annexin V/propidium iodide flow cytometry analyses were performed to measure cell viability and apoptosis rates, respectively. Co-immunoprecipitation followed by mass spectrometry analyses identified direct interaction partners of CD24. Luciferase reporter assays were used to functionally validate transactivation of CD24 expression by SOX2. N- and O-glycosylation of CD24 were evaluated by enzymatic digestion and mass spectrometry. The study demonstrates that SOX2 transactivates CD24 expression in embryonal carcinoma cells. In cells of different urological origins, CD24 interacted with proteins involved in cell adhesion, ATP binding, phosphoprotein binding and post-translational modifications, such as histone acetylation and ubiquitination. Treatment of urological tumour cells with NK-CD24-CAR cells resulted in a decreased cell viability and apoptosis induction specifically in CD24+ tumour cells. Limitations of the study include the in vitro setting, which still has to be confirmed in vivo. In conclusion, we show that CD24 is a promising novel target for immune therapeutic approaches targeting urologic malignancies.
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Receptores de Antígenos Quiméricos , Neoplasias Urogenitais , Humanos , Masculino , Antígeno CD24/genética , Antígeno CD24/metabolismo , Linhagem Celular Tumoral , Imunoterapia/métodos , Células Matadoras Naturais , Próstata , Receptores de Células Matadoras Naturais/metabolismo , Testículo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias Urológicas/metabolismo , Neoplasias Urogenitais/imunologia , Neoplasias Urogenitais/terapiaRESUMO
Cervical cancer is one of the most common malignant diseases in women worldwide. Despite the global introduction of a preventive vaccine against the leading cause of cervical cancer, human papillomavirus (HPV) infection, the incidence of this malignant disease is still very high, especially in economically challenged areas. New advances in cancer therapy, especially the rapid development and application of different immunotherapy strategies, have shown promising pre-clinical and clinical results. However, mortality from advanced stages of cervical cancer remains a significant concern. Precise and thorough evaluation of potential novel anti-cancer therapies in pre-clinical phases is indispensable for efficient development of new, more successful treatment options for cancer patients. Recently, 3D tumor models have become the gold standard in pre-clinical cancer research due to their capacity to better mimic the architecture and microenvironment of tumor tissue as compared to standard two-dimensional (2D) cell cultures. This review will focus on the application of spheroids and patient-derived organoids (PDOs) as tumor models to develop novel therapies against cervical cancer, with an emphasis on the immunotherapies that specifically target cancer cells and modulate the tumor microenvironment (TME).
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Purpose: For adjuvant radiotherapy of low-risk breast cancer after breast-conserving surgery, there have been many trials of hypofractionation and partial breast irradiation (PBI) over the years, with proven mild long-term toxicity. The aim of this study was to introduce a short-course dose-adapted concept, proven in whole breast irradiation (WBI) for use in accelerated partial breast irradiation (APBI), while monitoring dosimetric data and toxicity. Methods: From April 2020 to March 2022, 61 patients with low-risk breast cancer or ductal carcinoma in situ (DCIS) were treated at a single institution with percutaneous APBI of 26 Gy in five fractions every other day after breast-conserving surgery. Dosimetric data for target volume and organs at risk were determined retrospectively. Acute toxicity was evaluated. Results: The target volume of radiotherapy comprised an average of 19% of the ipsilateral mamma. The burden on the heart and lungs was very low. The mean cardiac dose during irradiation of the left breast was only 0.6 Gy. Two out of three patients remained without any acute side effects. Conclusions: Linac-based APBI is an attractive treatment option for patients with low-risk breast cancer in whom neither WBI nor complete omission of radiotherapy appears to be an adequate alternative.
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Background: Although quantification of tumor infiltrating lymphocytes (TILs) has become of increasing interest in immuno-oncology, only little is known about TILs infiltration in the tumor microenvironment and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3+ (DAKO, #IR503) and CD8+ (DAKO, #IR623) TILs at the invasive margin and in the center of 530 vulvar squamous cell cancers. Results: An elevated density of CD3+ T-cell at the invasive margin was significantly associated with low tumor stage (p = 0.0012) and prolonged survival (overall survival [OS] p = 0.0027, progression free survival [PFS] p = 0.024) and was independent from tumor stage, nodal stage, grade, and HPV-status in multivariate analysis (p < 0.05). The prognostic impact of CD3+ cells in the center of the tumor was weaker compared to the invasive margin (OS p = 0.046, PFS p = 0.031) and lacking for CD8+ T-cell densities at any location (p ≥ 0.14 each). Unsupervised clustering of CD3+ and CD8+ T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (p = 0.0071) and PFS (p = 0.0027). Conclusion: Our data demonstrate a high prognostic value of CD3+ T-cells at the invasive margin and immune phenotypes in vulvar squamous cell cancer.
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Surgical disciplines are affected by an increasing shortage of young doctors. Studies show that formerly interested students decide against a career in surgical disciplines at the end of their studies or during practical year. Measures to counteract this development are urgently needed. As a joint project between gynecology, urology, and general surgery, SOCIUS mentoring was designed to prepare and encourage students for a career in surgical oncology. The structured curriculum of SOCIUS mentoring contains six modules, including surgical skills, soft skills, mentoring, theory, clinical visitation, and congress participation and runs over one year. Effects on confidence towards physician skills and plans for a future career were evaluated with questionnaires. After participation, students reported increased confidence in surgical and soft skills. In addition, participants noted that they have specified their career goals and gained more confidence in surgery, as well as seeing more development potential for a career in surgery. We describe the implementation of a novel extracurricular program for motivated students that combines individual mentoring with surgical and soft skills training. Due to its modular structure, this concept can easily be transferred to other disciplines. SOCIUS mentoring, with its combination of mentoring and skills training, is a promising measure to prepare and motivate students for their surgical career and thus counteract the shortage of young talent.
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Tutoria , Oncologistas , Estudantes de Medicina , Escolha da Profissão , Currículo , HumanosRESUMO
Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases, immunotherapies may be useful based on promising preclinical work, some of which has been successfully translated to the clinic. For example, approaches using monoclonal antibodies directed against surface proteins important for control of immune checkpoints (i.e., immune checkpoint inhibitors) were shown to improve outcome in many cancer settings, including cervical cancer. Additionally, initial clinical studies showed that application of cytotoxic immune cells modified to express chimeric antigen receptors (CAR) or T cell receptors (TCR) for better recognition and elimination of tumor cells may be useful to control cervical cancer. This review explores these important topics, including strengths and limitations of standard and developing approaches, and how some novel treatment strategies may be optimally used to offer the best possible treatment for cervical cancer patients.
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OBJECTIVE: To evaluate association of preoperative cone biopsy with the probability of recurrent disease after radical hysterectomy for cervical cancer. METHODS: This is a retrospective single-center study. Patients with cervical cancer stage IA1 with LVSI to IIA2 and squamous, adenosquamous and adenocarcinoma subtype were included. Patients were analyzed for general characteristics and recurrence-free survival (RFS). RESULTS: In total, of 480 patients with cervical cancer, 183 patients met the inclusion criteria (117 with laparoscopic and 66 with open surgery). The median tumor diameter was 25.0 mm (range 4.6-70.0 mm) with 66 (36.2%) patients having tumors smaller than 2 cm. During median follow-up of 54.0 months (range 0-166.0 months), the RFS for the laparoscopic cohort was 93.2% and 87.5% at 3 and 4.5 years, and 79.3% for the open cohort after 3 and 4.5 years, respectively. In total, 17 (9.3%) patients developed recurrent disease, 9 (7.3%) after laparoscopic, and 8 (12.1%) after open surgery. No preoperative cone biopsy (OR 9.60, 95% CI 2.14-43.09) as well as tumor diameter > 2 cm (OR 5.39, 95% CI 1.20-24.25) were significantly associated with increased risk for recurrence. In multivariate analysis, only missing preoperative cone biopsy was significantly associated with increased risk for recurrence (OR 5.90, 95% CI 1.11-31.29) CONCLUSION: There appears to be a subgroup of patients (preoperative cone biopsy, tumor diameter < 2 cm) with excellent survival and low risk for recurrence after radical hysterectomy which might benefit from the advantages of laparoscopic surgery.
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Laparoscopia , Neoplasias do Colo do Útero , Conização , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Recidiva , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Ovarian cancer is the most common cause of gynecological cancer-related death in the developed world. Disease recurrence and chemoresistance are major causes of poor survival rates in ovarian cancer patients. Ovarian cancer stem cells (CSCs) were shown to represent a source of tumor recurrence owing to the high resistance to chemotherapy and enhanced tumorigenicity. Chimeric antigen receptor (CAR)-based adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease. In this study, we developed a codon-optimized third-generation CAR to specifically target CD44, a marker widely expressed on ovarian cancer cells and associated with CSC-like properties and intraperitoneal tumor spread. We equipped NK-92 cells with the anti-CD44 CAR (CD44NK) and an anti-CD19 control CAR (CD19NK) using lentiviral SIN vectors. Compared to CD19NK and untransduced NK-92 cells, CD44NK showed potent and specific cytotoxic activity against CD44-positive ovarian cancer cell lines (SKOV3 and OVCAR3) and primary ovarian cancer cells harvested from ascites. In contrast, CD44NK had less cytotoxic activity against CD44-negative A2780 cells. Specific activation of engineered NK cells was also demonstrated by interferon-γ (IFNγ) secretion assays. Furthermore, CD44NK cells still demonstrated cytotoxic activity under cisplatin treatment. Most importantly, the simultaneous treatment with CD44NK and cisplatin showed higher anti-tumor activity than sequential treatment.
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Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
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BACKGROUND: Prophylactic mastectomy is an effective approach to breast cancer risk reduction in patients at high risk. Further studies using standardized measures for quality of life are needed to better understand the effect of prophylactic mastectomy on individual patients and, thereby, allow for better patient counseling and selection. METHODS: In this prospective study patients undergoing bilateral mastectomy were asked to complete the BREAST-Q questionnaire before and 1 year after surgery. All patients underwent bilateral mastectomy with implant-based breast reconstruction. Patient- and surgery-related information was collected in a database. RESULTS: In total, 48 patients underwent bilateral skin-sparing mastectomy. Of these, 29 (60.4%) suffered from breast cancer. A 2-stage reconstruction with intermediate expander implantation was conducted in 19 (39.6%) patients. All patients completed the BREAST-Q questionnaire. The domain "psychosocial well-being" was significantly improved from a mean score of 74.98 preoperatively to a postoperative score of 81.56 (p = 0.021). In contrast, the domain "physical well-being" dropped -8.38 points on average to a postoperative score of 74.96 (p < 0.001). Interestingly, patients with the lowest preoperative score in the domain "satisfaction with breast" showed the greatest increase after surgery (50.31 vs. 67.25, p < 0.001). On the contrary, patients with the highest preoperative values experienced the strongest decrease in satisfaction (91.60 vs. 75.27, p = 0.012). CONCLUSION: Implant-based prophylactic mastectomy leads to good quality-of-life results in patients at high risk for breast cancer. Especially, patients with a low preoperative satisfaction with their breasts have a significantly higher chance of experiencing substantial improvements in their quality of life.
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PURPOSE: Evaluating the counseling of patients with vulvar cancer in outpatient setting regarding the application of sentinel lymph node dissection (SLND), the selection of hospitals for further treatment, and level of knowledge. METHODS: A questionnaire containing 29 questions about SLND in vulvar cancer was sent to gynecologists in Lower Saxony. The questionnaire contained multiple choice questions and open questions. The study was approved by the local ethics committee. RESULTS: The median age of the 86 respondents was 54 (26-66) years. Most participants (83.1%) reported to only treat one to five patients with vulvar cancer per year. Interestingly, 70.5% of the gynecologists send their patients to university hospitals and 64.1% to hospitals offering maximum care, respectively. Of all, 32.7% replied that SLND was performed rarely or never in their patients. The gynecologists answered that only 36.7% of the patients are well informed about advantages and possible disadvantages of SLND. Most (84%) felt responsible to counsel patients on treatment decisions independently from or additionally to the hospital. Of all, 72% replied that they are not completely sure about the exact recurrence rates after SLND. Of notice, 66% believe that SLND for vulvar cancer is safe if applied in specialized centers and 92% stated that focusing treatment on specialized centers is required for best results. CONCLUSION: SLND for vulvar cancer is widely accepted and regularly recommended among gynecologists. Outpatient doctors report to send most patients to specialized centers. However, it appears that patients remain uninformed after counseling in the clinics and that there is a lack of detailed knowledge about risks and complication rates of groin treatment in the outpatient setting.
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Aconselhamento/métodos , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/cirurgia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Neoplasias Vulvares/patologiaRESUMO
Surgical treatment of cervical cancer has led to one of the greatest controversies in gynecological oncology in recent years. After laparoscopic radical hysterectomy became increasingly widespread worldwide, it lost its importance dramatically when the data from the LACC study were published. In contrast to previous assumptions, there was a significantly reduced survival after laparoscopic hysterectomy compared to the open abdominal procedure. Multiple studies were subsequently published. Some confirm these results some do not. Some consider further studies to be unethical, others point to their own non-randomized results and call for a new LACC study. This article gives an overview of the current data situation and the possible criticisms of the individual studies. And, finally, calls for new RCT's under defined criteria.
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Histerectomia/métodos , Neoplasias do Colo do Útero/cirurgia , Feminino , Humanos , Histerectomia/efeitos adversos , Laparoscopia/métodos , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Robóticos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: Obesity is associated with worse survival and an increased risk of relapse in several malignancies. The influence of obesity on vulvar cancer recurrence has not been previously described. The primary objective of this study was to evaluate the association between obesity and tumor recurrence in patients with vulvar cancer. METHODS: This is an analysis of the AGO-CaRE-1 study. Patients diagnosed with squamous cell vulvar cancer (stage IB and higher), treated in 29 cancer centers between January 1998 and December 2008, were registered in a centralized database. The cohort was divided into two gropus depending on the body mass index (BMI) (<30 vs ≥30 kg/m²). Descriptive statistics, survival analyses, and multivariate Cox regression analyses were performed in order to evaluate the association between obesity and progression-free and overall survival. RESULTS: In 849 (52.4%) of 1618 patients in the database, the BMI was documented. Patients were grouped according to their BMI (<30 vs ≥30 kg/m²). There were 621 patients with a BMI <30 kg/m² and 228 patients with a BMI ≥30 kg/m². Besides age, there was no difference in baseline variables (tumor diameter, depth of infiltration, tumor stage, nodal metastasis, tumor grade). Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ between groups. However, patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1% vs 51.8%, p=0.04). During follow-up there was a higher recurrence rate in the group with BMI ≥30 kg/m² (43.4% vs 28.3%, p<0.01) due to an increased rate of local recurrences (33.3% vs 18.5%, p<0.01). There was a significantly shorter time to recurrence in obese patients on univariate analysis (BMI ≥30 kg/m² vs <30 kg/m²: 43.8 months (95% CI 23.3 to 64.3) vs 102.3 months (95% CI 72.6 to 131.9), p=0.001) and on multivariate Cox regression analysis (HR 1.94 (95% CI 1.4 to 2.8), p<0.001). CONCLUSIONS: In this study a BMI ≥30 kg/m² was associated with a shorter time to recurrence in patients with vulvar cancer and this was mainly attributed to a higher risk of local recurrence.
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Carcinoma de Células Escamosas/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Obesidade/epidemiologia , Neoplasias Vulvares/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapia , Adulto JovemRESUMO
BACKGROUND: Lymph node (LN) metastasis is the most important prognostic factor in primary vulvar cancer. Assessing risk factors for the incidence and extent of LN metastases may help to select the optimal treatment strategy for each individual patient. METHODS: In a subgroup analysis of the large multicenter AGO-CaRE-1 study we included all patients treated with radical groin dissection. Univariate and multivariate regression analyses were performed in order to detect factors associated with the prevalence and extent of nodal involvement. RESULTS: In total, 1162 patients were analyzed. Univariate analyses detected age, ECOG as well as multiple tumor characteristics such as FIGO stage, grading, depth of invasion, tumor diameter, and (lymph)vascular space invasion to be related with the prevalence of LN metastases. Interestingly, only tumor stage, tumor diameter and depth of infiltration were found to be significantly associated with the number of LN metastases. In multivariate analysis, age (OR 1.03), lymphvascular space invasion (OR 4.97), tumor stage (OR 2.22) and depth of infiltration (OR 1.08) showed an association with the prevalence of LN metastases. Regarding the number of metastatic LNs, only tumor stage (OR 2.21) or, if excluded, tumor diameter (OR 1.02) were tested significant. CONCLUSION: This large analysis of the multicenter AGO-CaRE-1-study identified lymphvascular space invasion, tumor stage, and depth of infiltration as factors with the strongest association regarding the prevalence of LN metastasis. Interestingly, tumor stage or, if excluded, tumor diameter were the only factors associated with the prevalence as well as the extent of LN metastases.
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Linfonodos/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Coortes , Feminino , Virilha/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Vulvares/cirurgiaRESUMO
INTRODUCTION: Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. MATERIAL AND METHODS: In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. RESULTS: By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. CONCLUSIONS: Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.
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Colpotomia/efeitos adversos , Histerectomia/métodos , Verde de Indocianina/efeitos adversos , Laparoscopia/métodos , Cavidade Peritoneal/fisiopatologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Estudos de Coortes , Colpotomia/métodos , Feminino , Seguimentos , Humanos , Histerectomia/efeitos adversos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/fisiopatologia , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologiaRESUMO
Novel therapeutic approaches against ovarian cancer (OC) are urgently needed because of its high rate of recurrence even after extensive surgery and multi-agent chemotherapy. We aimed to develop a novel anti-CD24 chimeric antigen receptor (CAR) as an immunotherapeutic approach against OC cells and cancer stem cells (CSC). CSC represents a subpopulation of the tumor characterized by enhanced chemoresistance as well as the increased capability of self-renewal and metastasis. We designed a codon-optimized third-generation CAR containing the highly active single chain variable fragment (scFv) "SWA11" against CD24. We equipped the human NK-cell line NK-92 with the anti-CD24 CAR and an anti-CD19 control CAR using lentiviral transduction. Engineered NK-92 cells showed high cytotoxic activity against CD24-positive OC cell lines (SKOV3, OVCAR3). This effect was restricted to CD24-expressing cells as shown after lentiviral transduction of CD24-negative cell lines (A2780, HEK-293T) with CD24 transmembrane proteins. Additionally, NK-92 cells equipped with our novel anti-CD24 CAR were highly effective against patient-derived primary ovarian cancer cells. The activation of NK cells was shown by specific IFNγ secretion upon antigen stimulation. To further reduce possible off-target effects in vivo, we applied a dual-CAR approach using an anti-CD24-CD28-41BB fusion protein linked via a 2A sequence to an anti-mesothelin-CD3ζ-CAR. The dual-CAR was simultaneously active against CD24 and mesothelin expressing cells. Our novel anti-CD24-CAR showed a highly cytotoxic effect against OC cell lines and primary OC cells and will be evaluated in future in vivo trials as a promising immunotherapeutic approach against OC.
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Antígeno CD24/imunologia , Imunoterapia Adotiva , Neoplasias Ovarianas/terapia , Receptores de Antígenos Quiméricos , Linhagem Celular Tumoral , Feminino , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismoAssuntos
Linfonodo Sentinela , Neoplasias Vulvares , Abdome , Feminino , Humanos , Excisão de Linfonodo , LinfonodosRESUMO
OBJECTIVE: Sentinel diagnostic in cervical cancer is performed using Technetium-99m-nanocolloid as a radioactive marker with or without patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule which emits a light signal in the near infrared band after excitation. Our study aims to evaluate indocyanine green compared to the gold standard Tc-99m-nanocolloid. MATERIALS AND METHODS: We included patients with early cervical cancer up to FIGO stage IIA with clinically node-negative pelvic sites and the indication for nodal staging in this prospective trial. Sentinel diagnostic was carried out using Tc-99m-nanocolloid, indocyanine green and patent blue. We examined each pelvic site for light signals from the near infrared band, for radioactivity and for blue staining. A sentinel lymph node was defined as a Tc-99m-nanocolloid positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested; then sent to histologic examination. RESULTS: Thirty-three patients were included in which we found 211 Tc-99m-nanocolloid-positive sentinel lymph nodes in 66 pelvic sites. Two hundred and seven of these lymph nodes were positive for indocyanine green, too, giving a sensitivity of 98.1% (95%CI 94.9-99.4%) compared to Tc-99m-nanocolloid. One hundred and sixty additional lymph nodes showed indocyanine green fluorescence but no Tc-99m-positivity, so that the sensitivity was 79.6% (95%CI 76.6-82.3%). In one patient, a pelvic site was only identified to be tumor infiltrated due to an ICG-positive, but Tc-99m-negative lymph node. CONCLUSION: Our results show that indocyanine green is a promising approach for pelvic sentinel identification in cervical cancer. ICG has a similar sensitivity as radioactive Tc-99m-nanocolloid and may enhance both patient safety and surgeons' comfort. Lasers Surg. Med. 50:994-1001, 2018. © 2018 Wiley Periodicals, Inc.
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Corantes , Verde de Indocianina , Excisão de Linfonodo , Metástase Linfática/patologia , Linfocintigrafia/métodos , Compostos Radiofarmacêuticos , Corantes de Rosanilina , Biópsia de Linfonodo Sentinela/métodos , Agregado de Albumina Marcado com Tecnécio Tc 99m , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. RESULTS: Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. CONCLUSIONS: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.