RESUMO
BACKGROUND: Lymphatic involvement is the most important prognostic factor in early-stage cervical cancer. Sentinel lymph node biopsy is a viable alternative to systematic lymphadenectomy and may identify metastases more precisely. OBJECTIVE: To compare two tracers (indocyanine green and patent blue) to detect sentinel nodes. METHODS: A single-center, retrospective study of women treated due to early-stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 IA1 with lymphovascular invasion, IA2, and IB1). Location and tracer of all detected sentinel nodes had been documented for a prospective, multicenter trial (SENTIX trial). All sentinel nodes were sent to frozen section and final analysis through ultrastaging using a standard protocol. RESULTS: Overall, 103 patients were included. Bilateral detection rate for indocyanine green (93.2%) was significantly higher than for blue dye (77.7%; p=0.004). Their combined use significantly increased the bilateral detection to 99.0% (p=0.031). While 97.4% of all sentinel nodes were located below the common iliac vessels, no para-aortic nodes were labeled. Simultaneous bilateral detection with both tracers was found in 71.8% of the cases, of which the sentinel nodes were identical in 91.9%. Nine positive nodes were detected among seven patients (6.8%), all marked with indocyanine green while patent blue labeled six. Frozen section failed to detect one of three macrometastases and three of four micrometastases (sensitivity 43%; negative prediction value 96%). CONCLUSION: Anatomical distribution and topographic localization of the sentinel nodes obtained with these tracers were not different. Indocyanine green provided a significantly higher bilateral detection rate and had superior sensitivity to detect positive nodes compared with patent blue. Combining indocyanine green and blue dye increased the bilateral detection rate significantly.
Assuntos
Corantes , Verde de Indocianina , Estadiamento de Neoplasias , Corantes de Rosanilina , Biópsia de Linfonodo Sentinela , Neoplasias do Colo do Útero , Humanos , Verde de Indocianina/administração & dosagem , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Corantes/administração & dosagem , Idoso , Linfonodo Sentinela/patologia , Linfonodo Sentinela/diagnóstico por imagem , Metástase Linfática , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Idoso de 80 Anos ou mais , Prognóstico , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico por imagemRESUMO
PURPOSE: This cross-sectional study aims to investigate parameters that predict relevant levels of distress in women in a perioperative setting undergoing treatment for cervical cancer. MATERIALS AND METHODS: Data from 495 patients with cervical cancer that were treated at the university hospital Aachen between 2010 and 2022 were analysed based on their respective National Comprehensive Cancer Network (NCCN) Distress Thermometer score (DT) and Problem List (PL) and their clinical history. 105 patients were enrolled in the study. 18 medical and demographic variables were analysed using multivariate logistic regression. RESULTS: Three variables contributed significantly to the prediction of a DT score ≥ 5. Significant distress was defined as a DT score of ≥ 5, which was observed in 70.5% of the participants (mean: 5.58 ± 2.892). Women who chose to receive psycho-oncological counselling were more likely to have a DT score ≥ 5 (Odds Ratio(OR) = 3.323; Confidence Interval (CI95%): 1.241-8.900; p-value: 0.017). In addition, women who did not receive chemoradiation had significantly higher DT scores (OR = 3.807; CI 95%:1.185-12.236; p-value: 0.025), as did women whose Distress Thermometer was assessed in the first month after their initial diagnosis (OR = 3.967; CI 95%:1.167-13.486; p-value: 0.027). CONCLUSION: Increased distress in women with cervical cancer is common especially in the first month after diagnosis, in patients who do not receive chemoradiation and in patients who seek psycho-oncological counselling. Surgical factors do not play a major role in patient distress.
Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/terapia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Idoso , Estresse Psicológico , Angústia Psicológica , Modelos Logísticos , Quimiorradioterapia/psicologia , AconselhamentoRESUMO
IMPORTANCE: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide. OBJECTIVE: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery. EVIDENCE ACQUISITION: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included. RESULTS: We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0-67%, and 85%, respectively. CONCLUSIONS AND RELEVANCE: Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.
Assuntos
Procedimentos Cirúrgicos em Ginecologia , Complicações Pós-Operatórias , Humanos , Aderências Teciduais/prevenção & controle , Aderências Teciduais/etiologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Cirurgia de Second-Look , Doenças Peritoneais/prevenção & controle , Doenças Peritoneais/etiologiaRESUMO
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
Assuntos
Neoplasias , Fototerapia , Linhagem Celular Tumoral , Fototerapia/métodos , Imunoterapia/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Raios Infravermelhos , Neoplasias/tratamento farmacológicoRESUMO
Traditional immunohistochemistry (IHC) has already become an essential method of diagnosis and therapy in cancer management. However, this antibody-based technique is limited to detecting a single marker per tissue section. Since immunotherapy has revolutionized the antineoplastic therapy, developing new immunohistochemistry strategies to detect multiple markers simultaneously to better understand tumor environment and predict or assess response to immunotherapy is necessary and urgent. Multiplex immunohistochemistry (mIHC)/multiplex immunofluorescence (mIF), such as multiplex chromogenic IHC and multiplex fluorescent immunohistochemistry (mfIHC), is a new and emerging technology to label multiple biomarkers in a single pathological section. The mfIHC shows a higher performance in cancer immunotherapy. This review summarizes the technologies, which are applied for mfIHC, and discusses how they are employed for immunotherapy research.
Assuntos
Neoplasias , Humanos , Imunofluorescência , Imuno-Histoquímica , Biomarcadores , Imunoterapia , Biomarcadores TumoraisRESUMO
BACKGROUND: Postoperative pain remains a common problem in gynecologic laparoscopy, especially in head zone-related regions, triggered by intra-abdominal pressure during capnoperitoneum. Humidified and prewarmed insufflation gas may ameliorate pain and be beneficial. METHODS: This prospective randomized controlled parallel group multi-arm single-center study investigated the effects of temperature and humidity of insufflation gas on postoperative pain during gynecologic laparoscopy with a duration ≥ 60 min. Female participants (18-70 years) were blinded and randomly assigned-computer generated-to either insufflation with dry cold CO2 with forced air warming blanket ("AIR"), humidified warm gas without forced air warming blanket ("HUMI"), or humidified warm gas with forced air warming blanket ("HUMI +"). We hypothesized that using humidified warm gas resulted in lower pain scores and less analgesic consumption. The primary endpoint postoperative pain was assessed for different pain localizations every 12 h during 7 days after surgery. Secondary endpoints were demand for painkillers and epidural anesthetics, length of stay in recovery room, and hospital stay. (Registration: ClinicalTrials.gov NCT02781194-completed). RESULTS: 150 participants were randomized. Compared to group "AIR" (n = 48), there was significantly less pain in group "HUMI +" (n = 48) in the recovery room (- 1.068; 95% CI - 2.08 to - 0.061), as well as significantly less ibuprofen use at day two (- 0.5871 g ± 0.258; p-value = 0.0471). Other variables did not change significantly. Stratification for presence of endometriosis or non-previous abdominal surgery in patient history revealed significantly less pain in both groups "HUMI" (n = 50) and "HUMI +" versus group "AIR." Related side effects were not noted. CONCLUSION: In the overall population, the use of warm, humidified insufflation gas did not yield clinically relevant effects; however, in predisposed patients with endometriosis and who could otherwise expect high pain levels, warm and humidified gas may be beneficial.
Assuntos
Endometriose , Insuflação , Laparoscopia , Dióxido de Carbono , Endometriose/cirurgia , Feminino , Temperatura Alta , Humanos , Umidade , Insuflação/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos ProspectivosRESUMO
Uterine fibroids are one of the most common diseases in female patients, lead mainly to bleeding disorders and lower abdominal pain, and reduce the chance of having children. In recent years we have seen a trend towards more and more pharmacotherapies and minimally invasive organ-preserving treatments. One novel and innovative procedure for an organ-preserving treatment of symptomatic uterine fibroids is the transcervical ultrasound-guided radiofrequency ablation (TRFA). TRFA has been used in Germany since 2013 and later found use in other German-speaking countries as well. There have now been more than 1200 TRFA treatments performed in Germany, Austria, and Switzerland. Experts from these three countries came together for a consensus meeting to analyze the significance of the procedure in the overall concept of the treatment of symptomatic uterine fibroids.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Ablação por Radiofrequência , Neoplasias Uterinas , Criança , Consenso , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Ablação por Radiofrequência/métodos , Resultado do Tratamento , Ultrassonografia de Intervenção , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgiaRESUMO
BACKGROUND: Hypothermia is defined as a decrease in body core temperature to below 36 °C. If intraoperative heat-preserving measures are omitted, a patient's temperature will fall by 1â-â2 °C. Even mild forms of intraoperative hypothermia can lead to a marked increase in morbidity and mortality. Using warm and humidified gas insufflation in laparoscopy may help in the maintenance of intraoperative body temperature. METHODS: In this prospective randomized controlled study, we investigated effects of temperature and humidity of the insufflation gas on intra- and postoperative temperature management. 150 patients undergoing gynecologic laparoscopic surgery were randomly assigned to either insufflation with non-warmed, non-humidified CO2 with forced air warming blanket (AIR), humidified warm gas without forced air warming blanket (HUMI) or humidified warm gas combined with forced air warming blanket (HUMI+). We hypothesized that the use of warmed laparoscopic gas would have benefits in the maintenance of body temperature and reduce the occurrence of hypothermia. RESULTS: The use of warm and humidified gas insufflation alone led to more hypothermia episodes with longer duration and longer recovery times as well as significantly lower core body temperature compared to the other two groups. In the comparison of the AIR group and HUMI + group, HUMI + patients had a significantly higher body temperature at arrival at the PACU (Post Anaesthesia Care Unit), had the least occurrence of hypothermia and suffered from less shivering. CONCLUSION: The use of warm and humidified gas insufflation alone does not sufficiently warm the patients. The optimal temperature management is achieved in the combination of external forced air warming and insufflation of warm and humidified laparoscopy gas.
Assuntos
Hipotermia , Insuflação , Laparoscopia , Temperatura Corporal , Dióxido de Carbono , Feminino , Temperatura Alta , Humanos , Umidade , Hipotermia/etiologia , Hipotermia/prevenção & controle , Estudos ProspectivosRESUMO
RESEARCH QUESTION: How closely related are adenomyotic and endometrial glands? DESIGN: In this study, the mRNA and protein database www.proteinatlas.org was searched for proteins expressed predominantly in the endometrial glands. Specificity was tested with tissue microarrays. Biopsy specimens of endometrial, adenomyotic tissue, or both, were collected after surgery from 21 women without endometriosis, 20 women with endometriosis, 18 women with adenomyosis together with endometriosis and 12 women with adenomyosis alone. Tissue expression was analysed by immunohistochemistry. RESULTS: Two proteins were identified: calcyphosine (CAPS), and msh homeobox 1 (MSX1). A high abundance and good specificity in endometrial glands were found. Both proteins, CAPS and MSX1, showed a high specificity for endometrium and are both localized in the luminal cells and epithelial cells of the glandular and adenomyotic glands. No significant differences were found between CAPS- and MSX1-positive endometrial glands between cases with and without endometriosis. Also, no cycle-specific different expression was found. Furthermore, a close relationship between the adenomyotic glands and the endometrial glands for CAPS (range 63.0-98.3%) and for MSX1 (range 87.1-99.3%) could be demonstrated. Only 11.2% and 6.8% negative glands for CAPS and MSX1 were identified in all tissues from all patients, respectively; none were negative for both proteins. CONCLUSIONS: Taken together, our results show that the protein expression pattern of adenomyosis is nearly identical to those of the endometrium with and without endometriosis, thus suggesting endometrial glands as the main source for adenomyotic glands.
Assuntos
Adenomiose/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Endometriose/metabolismo , Endométrio/metabolismo , Fator de Transcrição MSX1/metabolismo , Adenomiose/patologia , Adenomiose/cirurgia , Adulto , Endometriose/patologia , Endometriose/cirurgia , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Claudins as the major components of tight junctions are important in maintaining cell-cell integrity and thus function as a barrier. Dysregulation of the claudins is often associated with loss of the epithelial phenotype, a process called epithelial-mesenchymal transition (EMT), which most often results in gain of migrative and invasive properties. However, the role of claudins in the endometrium or endometriosis has only rarely been examined. METHODS: In this study, we investigated localization of claudin-2 and claudin-3 in the eutopic and ectopic endometrium with immunohistochemistry. A detailed quantification with HSCORE was performed for claudin-2 and claudin-3 in endometrium without endometriosis and in cases with endometriosis compared to the three endometriotic entities: peritoneal, ovarian, and deep-infiltrating endometriosis. RESULTS: We found a preferential localization of both claudins in the glandular and the luminal epithelial cells in the endometrium with and without endometriosis. Quantification of localization of both claudins showed no differences in eutopic endometrium of control cases compared to cases with endometriosis. Furthermore, both claudins are localized highly similar in the ectopic compared to the eutopic endometrium, which is in clear contrast to previously published data for claudin-3. CONCLUSION: From our results, we conclude that localization of claudin-2 and claudin-3 is highly stable in eutopic and ectopic endometrium without any loss of the epithelial phenotype and thus do not contribute to the pathogenesis of endometriosis.
Assuntos
Claudina-2/metabolismo , Claudina-3/metabolismo , Endometriose/genética , Endométrio/patologia , Estudos de Casos e Controles , Endometriose/patologia , Feminino , HumanosRESUMO
OBJECTIVE: The aim of this study was to report on the use of laparoscopic implantation of leads on the branches of the sacral plexus for neuromodulation in the treatment of chronic pelvic pain (CPP) in a multidisciplinary setting with the help of electrophysiological neuromonitoring. MATERIALS AND METHODS: Between 2012 and 2019, six female patients complaining of chronic pain and bladder and bowel dysfunctions underwent laparoscopic exposure and nerve identification with the help of electrophysiological neuromonitoring. A lead was placed laparoscopically in direct contact with the affected nerve. Pain intensity (numerous ranking scale [NRS]), generic health status (EQ-5D-5L), Becks Depressions Inventory (BDI-V), Pain Catastrophizing Scale (PCS), and Client Satisfaction Questionnaire (CSQ-8) were assessed pre-/postoperatively as well as three and six months after surgery. Statistical analysis was performed using Mann-Whitney U and Wilcoxon rank-sum test. RESULTS: The median age was 36.5 years. NRS improved from a median of 9.5 preoperatively to 3.0 (p < 0.001) at six-month follow-up. Median EQ-5D-5L index value before treatment was 0.18, indicating a notably lowered quality of life and increased up to 0.83 after six months (p < 0.001). Preoperative median BDI-V scores indicated a major depressive mood and improved from a median of 46.0 to 12.0 after six months (p = 0.007). Preoperative PCS was elevated with a median score of 41.0 and decreased to 4.0 after six months (p < 0.001). CSQ showed that patients were satisfied with the treatment. CONCLUSIONS: This unique method is an alternative and effective treatment option for CPP even years after primary endometriosis surgery.
Assuntos
Dor Crônica , Terapia por Estimulação Elétrica , Dor Pélvica , Bexiga Urinaria Neurogênica , Adulto , Dor Crônica/terapia , Transtorno Depressivo Maior , Eletrodos Implantados , Feminino , Humanos , Laparoscopia , Plexo Lombossacral , Dor Pélvica/terapia , Qualidade de Vida , Bexiga Urinaria Neurogênica/terapiaRESUMO
A diagnosis of endometriosis is based upon the histological identification of endometrial tissue at ectopic sites which are commonly located on the pelvic organs, the peritoneum and ovary. In rare cases, ectopic lesions can be found in other organs, such as kidney, bladder, lung or brain. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of endometriotic tissue. Prevalence is estimated at approximately 10% in the general female population with many patients experiencing pain and/or infertility. Currently, the implantation hypothesis by Sampson is the most accepted hypothesis about the pathogenesis of endometriosis. However, the occurrence of endometriosis in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome who sometimes lack a uterus or endometrium seems to suggest metaplasia as a cause of endometriosis. A critical reevaluation of the literature about MRKH does not reveal conclusive evidence of an association of uterus/endometrium agenesis and endometriosis. Most often only MRI diagnoses of uterus/endometrium agenesis and only very rarely conclusive histological evidence of the endometriotic lesions are presented. In contrast, whenever biopsies were performed endometriosis always appeared together with uterus/endometrium remnants. Taken together, we suggest that MRKH patients only develop endometriosis if a uterus/endometrium is present which underscores and not contradicts the implantation hypothesis of Sampson.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/complicações , Endometriose/etiologia , Ductos Paramesonéfricos/anormalidades , Anormalidades Congênitas , Feminino , Humanos , Metaplasia , Útero/anormalidadesRESUMO
Antibody-based diagnostic and therapeutic reagents armed with effector molecules such as dyes and drugs offer hope in the battle against cancer. Several site-specific conjugation methods have been developed to equip antibodies with such effector molecules, but they tend to be expensive and involve multiple reaction steps. The conjugation of two different effector molecules to a single antibody also remains a major challenge. Here we describe a simple, controlled, and robust method for the dual site-specific conjugation of an antibody with two effector molecules in a single-pot reaction using the self-labeling SNAP and CLIP protein tags. We verified the principle of the method by labeling an epidermal growth factor receptor (EGFR)-specific single-chain antibody fragment (scFv-425) simultaneously with IRDye700 and Alexa-Fluor647. This dual-labeled antibody bound to EGFR+ ovarian cancer cell lines and tissue samples with high specificity, and its phototherapeutic efficacy was confirmed by the selective killing of EGFR+ cells in vitro.
Assuntos
Anticorpos de Cadeia Única/química , Linhagem Celular Tumoral , Corantes/química , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunoconjugados/química , Microscopia Confocal , Neoplasias Ovarianas/patologia , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Anticorpos de Cadeia Única/imunologiaRESUMO
PURPOSE: Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells on-demand using an ATC directed to EGFR. METHODS: An ATC with a defined drug-to-antibody ratio was generated by the site-directed conjugation of IRDye®700 to a self-labeling protein (SNAP-tag) fused to an EGFR-specific antibody fragment (scFv-425). RESULTS: In vitro and ex vivo imaging showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR+ ovarian cancer cell, human tissues and ascites samples. The construct was also able to eliminate EGFR+ cells and human ascites cells with IC50 values of 45-66 nM and 40-90 nM, respectively. CONCLUSION: Our experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Receptores ErbB/metabolismo , Imunoconjugados/farmacologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia , Anticorpos Monoclonais/química , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/química , Humanos , Imunoconjugados/química , Região Variável de Imunoglobulina/química , Indóis/química , Concentração Inibidora 50 , Compostos de Organossilício/química , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Anticorpos de Cadeia Única/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Nanomedicina TeranósticaRESUMO
INTRODUCTION: Molecular pathological research has contributed to improving the knowledge of different subtypes of ovarian cancer. In parallel with the implementation of the new FIGO staging classification, the WHO classification was revised. The latter is mainly based on the histopathological findings and defines the actual type of tumor. It has, therefore, also an important impact on prognosis and therapy of the patient. MATERIALS AND METHODS: The new WHO Classification of Ovarian Cancer published 2014 by Robert Kurman and co-authors is summarized. The major changes compared to the hitherto existing classification are presented. RESULTS: The new classification eliminates the previous focus of mesothelial origin of ovarian cancer. Instead, it features a discussion of tubal carcinogenesis of hereditary and some other high-grade serous carcinomas. The previously assumed pathogenesis pathway may be correct for some, but not for all, serous cancers. The new classification was established to classify ovarian cancer in a more consistent way. The earlier transitional cell type of ovarian cancer has been removed while seromucinous tumors have been added as a new entity. The role of some borderline tumors as one possible step in the progression from benign to invasive lesions is incorporated. The article summarizes the essential updates concerning serous, mucinous, seromucinous, endometrioid, clear-cell, and Brenner tumors. CONCLUSION: The new WHO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes. The tubal origin of hereditary and some non-hereditary high-grade serous cancers is mentioned in contrast to the hitherto theory of mesothelial origin of tumors. Seromucinous tumors represent a new entity.
Assuntos
Adenocarcinoma de Células Claras/classificação , Adenocarcinoma Mucinoso/classificação , Cistadenocarcinoma Seroso/classificação , Neoplasias das Tubas Uterinas/classificação , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificação , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Adulto , Animais , Tumor de Brenner/patologia , Carcinogênese , Cistadenocarcinoma Seroso/patologia , Endométrio/patologia , Células Epiteliais/metabolismo , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Lesões Pré-Cancerosas/patologia , Prognóstico , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Organização Mundial da SaúdeRESUMO
BACKGROUND: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production. METHODS: We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition's impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine uptake measurement, respectively. RESULTS: Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. CONCLUSIONS: FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Ácido Graxo Sintases/metabolismo , Terapia de Alvo Molecular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/enzimologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cerulenina/metabolismo , Colina/análogos & derivados , Colina/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Ovarianas/patologia , Ácido Palmítico/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise Serial de TecidosRESUMO
Ovarian tumors comprise a wide variety of entities. The largest group, epithelial ovarian carcinoma, can be classified into two main groups, type I and type II tumors. Recent advances in the understanding of ovarian cancer development have resulted in the finding of 'serous tubal intraepithelial carcinoma', which is believed to represent the precursor lesion in high-grade serous ovarian carcinoma. In this review, lines of evidence for this are discussed and possible future implications for clinical and research settings are outlined.
Assuntos
Carcinoma/etiologia , Neoplasias das Tubas Uterinas/etiologia , Feminino , HumanosRESUMO
The detection of premalignant cells in the epithelium of the fallopian tube has resulted in revolutionary theories regarding the origin of epithelial ovarian cancer (EOC). Serous tubal intra-epithelial carcinomas (STIC) have been detected in patients with BRCA 1 or 2 mutations and are considered as the most likely precursors of the high-grade serous ovarian cancer (HGSOC), which is the most common histological subtype in patients with EOC. A bilateral salpingo-oophorectomy is associated with a significant reduction in risk of developing EOC. According to various national guidelines, prophylactic bilateral salpingo-oophorectomy should be performed in the age group 40-45 years. As in patients with BRCA mutations, the prophylactic removal of the fallopian tubes is also performed in women without an increased genetic risk, for example, in surgical treatments of benign conditions. There is a current debate as to whether prophylactic or so-called opportunistic salpingectomy will influence the overall incidence of EOC in the coming years. Opponents of this theory warn of a higher surgical morbidity and the higher risk of a premature menopause through impaired vascular supply to the ovaries. The value of opportunistic salpingectomies has not yet been clarified since there are currently no systematic risk-benefit evaluations. This review will attempt to give an overview of the current body of evidence regarding the risks and benefits of opportunistic salpingectomies.