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1.
Hum Reprod ; 38(1): 113-124, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36367834

RESUMO

STUDY QUESTION: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients? SUMMARY ANSWER: No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients. WHAT IS KNOWN ALREADY: Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients. We aimed to address this question in this study to help understand how similar the random start cycles are to the conventional start ones. STUDY DESIGN, SIZE, DURATION: A clinical translational research study conducted in 62 cancer patients undergoing IVF for fertility preservation between the years 2017 and 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty-two patients who were diagnosed with different types of cancer and underwent ovarian stimulation for oocyte (n = 41) and embryo (n = 21) cryopreservation using GnRH antagonist protocol and human menopausal gonadotropins before receiving cancer treatment/surgery were enrolled in the study. For patients with breast cancer and endometrial cancer the aromatase inhibitor letrozole was used with gonadotropin stimulation. Ovarian stimulation was initiated conventionally at EFP in 22 patients and served as control while it was started at LFP in 20, and mid-LP in the other 20 patients. The luteinized granulosa cells (GCs) were recovered from follicular aspirates during oocyte retrieval procedure and used for the experiments separately for each individual patient. The expression of the enzymes involved in sex steroid biosynthesis (StAR, 3ß-HSD, Aromatase) and cholesterol synthesis (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the expression patterns of the steroidogenic enzymes and their relation with mitochondria. In vitro E2 and P4 production by the cells were compared among the groups. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline demographic and IVF characteristics of the patients undergoing the conventional start and random start IVF cycles were similar. Duration of gonadotropin stimulation was significantly longer in LFP and LP start cycles in comparison to the conventional ones. Ovarian response to gonadotropin stimulation, mature and total oocyte yield, fertilization and Day 5 blastulation rates of the embryos were comparable between the conventional versus random start cycles. When the luteal GCs of these random start cycles were analyzed we could not find any gross differences between these cycles in terms of the viability index and gross light microscopic morphologic features. More detailed analysis of the molecular luteal characteristics of the cells using RT-PCR, immunoblotting methods revealed that the expression profiles of the gonadotropin receptors, and the enzymes involved in sex steroid biosynthesis and cholesterol synthesis/utilization, and the steroidogenic activity of the luteal GCs of the random start cycles are almost identical to those of the conventional start cycles. Confocal image analysis demonstrated similar patterns in the signal expression profiles of the steroidogenic enzymes and their co-localization within mitochondria. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Caution should be exercised when interpreting our data and counseling cancer patients seeking fertility preservation because it is still unclear if previous exposure to cancer drugs, different ovarian pathologies or infertility etiologies, previous ovarian surgery and/or any other underlying diseases that are concomitantly present with cancer may cause a difference between conventional and random start stimulation protocols in terms of IVF parameters, luteal function and reproductive outcome. Relatively low number of patients in each stimulation protocol and pooling of luteal GCs for each patient rather than individual analysis of each follicle and oocyte are additional limitations of our study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide reassurance that random start protocol offers cancer patients an equally good prospect of fertility preservation as conventional IVF. STUDY FUNDING/COMPETING INTEREST(S): Funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Infertilidade , Neoplasias , Feminino , Humanos , Gravidez , Fertilização in vitro/métodos , Progesterona/metabolismo , Corpo Lúteo/metabolismo , Indução da Ovulação/métodos , Oxirredutases , Hormônio Liberador de Gonadotropina , Taxa de Gravidez
2.
Gynecol Oncol ; 164(3): 492-497, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35033380

RESUMO

INTRODUCTION: This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. METHODS: Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. RESULTS: Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. CONCLUSION: SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/patologia , Feminino , Humanos , Verde de Indocianina , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
3.
Int J Gynecol Pathol ; 41(5): 447-458, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856570

RESUMO

Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.


Assuntos
Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Papillomaviridae/genética , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia
4.
J Obstet Gynaecol ; 42(5): 1286-1292, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34704523

RESUMO

Our goal was to address the safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era. The databases of seven gynaecologic cancer centres were searched in order to identify all consecutive gynaecologic cancer patients undergoing major surgery between March 11, 2020 and May 15, 2020 for this retrospective, case-control study. The case group consisted of patients with histopathologically confirmed gynaecologic cancers, and each case was matched with two counterparts who had undergone primary surgery before the COVID-19 pandemic. The case and the control groups were compared in terms of length of hospital stay, admission to the intensive care unit (ICU), intraoperative and postoperative complications.During the study period, 154 women with gynaecologic cancer undergoing major surgery were identified. Although the case group had more co-morbidities compared to the control group (103/154 vs. 178/308, respectively; p = .04), the median length of hospital stays, the rate of ICU admission, intraoperative complication rates and postoperative complication rates were similar in the two groups. Gynaecologic cancer surgery may be performed safely in the COVID-19 era with similar rates of ICU admission, intraoperative and postoperative complications compared to the patients operated before the COVID-19 pandemic.IMPACT STATEMENTWhat is already known on this subject? Many societies have announced their guidelines about the surgical management of gynaecologic cancer patients during the COVID-19 pandemic. However, most of them are not evidence-based and mostly on expert opinions.What do the results of this study add? The main findings of this retrospective, case-control study indicate that the short-term (30 day) outcomes of gynaecologic cancer patients undergoing major surgery in the COVID-19 era are similar to those who had been operated before the COVID-19 pandemic. The length of hospital stays, the rates of admission to the ICU, intraoperative and postoperative complications were comparable between women undergoing major gynaecologic cancer surgery in the COVID-19 era and the women who had been operated before the pandemic.What are the implications of these findings for clinical practice and/or further research? We can suggest that definitive surgery may be performed for gynaecologic cancer patients in the COVID-19 era if the resources permit and appropriate precautions such as social distancing, isolation and the use of personal protective equipment are taken.


Assuntos
COVID-19 , Neoplasias dos Genitais Femininos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Estudos de Casos e Controles , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Pandemias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
5.
Minim Invasive Ther Allied Technol ; 31(2): 284-290, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32723200

RESUMO

INTRODUCTION: We aimed to analyze the preliminary experience of a mini-plus percutaneous instrument (MpPc) setting in total laparoscopic hysterectomy (TLH). MATERIAL AND METHODS: Forty-three women who underwent a mini-plus percutaneous total laparoscopic hysterectomy at a tertiary-care university-based teaching hospital and academic affiliated private hospital between May 2017 and 2018 were included. MpPc-TLH was performed through one optical trans-umbilical 5-mm trocar, one 5-mm ancillary port on the right side, either one 2.4-mm percutaneous endoscopic instrument or 3-mm mini-laparoscopic port on the right upper quadrant and if required one 3-mm ancillary port on the left lower quadrant. RESULTS: A total of 43 patients were included, with a median age of 48 years (range, 38-71 years). Indication for surgery included uterine myomas (n = 20), benign adnexal mass (n = 7), endometrial intraepithelial neoplasia (n = 6), endometrial cancer (n = 5), adenomyosis with abnormal bleeding (n = 3), and high-grade cervical dysplasia (n = 2). The median operating time was 100 min (range, 60-180 min), and the median estimated blood loss was 30 ml (range, 20-60ml). The median postoperative abdominal pain Visual Analog Scale score was 3 (range, 0-6). CONCLUSIONS: The preliminary data suggest that MpPc approach is a feasible and safe surgical modality for total laparoscopic hysterectomy.


Assuntos
Neoplasias do Endométrio , Laparoscopia , Leiomioma , Adulto , Idoso , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Leiomioma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Umbigo
6.
J Surg Oncol ; 123(8): 1801-1810, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33657253

RESUMO

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). METHODS: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. RESULTS: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. CONCLUSIONS: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.


Assuntos
Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Turquia , Adulto Jovem
7.
J Surg Oncol ; 123(2): 638-645, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33259650

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. METHODS: Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. RESULTS: Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Although all 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. CONCLUSIONS: Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.


Assuntos
Adenocarcinoma de Células Claras/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/patologia , Linfonodos/patologia , Micrometástase de Neoplasia/diagnóstico , Neoplasias Pélvicas/secundário , Linfonodo Sentinela/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Histerectomia , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pélvicas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
8.
J Surg Oncol ; 123(7): 1495-1503, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33621377

RESUMO

BACKGROUND: We aimed to assess the feasibility and short-term clinical outcomes of surgical procedures for cancer at an institution using a coronavirus disease 2019 (COVID-19)-free surgical pathway during the peak phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. MATERIALS AND METHODS: This was a single-center study, including cancer patients from all surgical departments, who underwent elective surgical procedures during the first peak phase between March 10 and June 30, 2020. The primary outcomes were the rate of postoperative SARS-CoV-2 infection and 30-day pulmonary or non-pulmonary related morbidity and mortality associated with SARS-CoV-2 disease. RESULTS: Four hundred and four cancer patients fulfilling inclusion criteria were analyzed. The rate of patients who underwent open and minimally invasive procedures was 61.9% and 38.1%, respectively. Only one (0.2%) patient died during the study period due to postoperative SARS-CoV2 infection because of acute respiratory distress syndrome. The overall non-SARS-CoV2 related 30-day morbidity and mortality rates were 19.3% and 1.7%, respectively; whereas the overall SARS-CoV2 related 30-day morbidity and mortality rates were 0.2% and 0.2%, respectively. CONCLUSIONS: Under strict institutional policies and measures to establish a COVID-19-free surgical pathway, elective and emergency cancer operations can be performed with acceptable perioperative and postoperative morbidity and mortality.


Assuntos
COVID-19/epidemiologia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Neoplasias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Pandemias , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Turquia/epidemiologia , Adulto Jovem
9.
Int J Gynecol Cancer ; 31(6): 883-887, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33858953

RESUMO

OBJECTIVE: This study aims to evaluate the effect of the COVID-19 pandemic and related restrictions on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer. METHODS: We retrospectively evaluated ovarian cancer patients who underwent HIPEC following complete cytoreductive surgery performed during the outbreak of the COVID-19 pandemic in three different centers specializing in gynecological oncology. All patients who underwent cytoreduction plus HIPEC for a primary, interval, and recurrent surgery were evaluated. Primary outcomes was postoperative 30-day morbidity and mortality. The secondary outcome was infection of patient and/or related staff with COVID-19 during the perioperative or early postoperative period. RESULTS: We performed a total of 35 HIPEC procedures during the pandemic: 15 (42.9%) patients underwent primary/interval surgery, while 20 (57.1%) patients had recurrent disease. Grade 3-4 complications occurred in one patient (2.9%) (chronic renal failure), while mortality did not occur in any patient. Neither the patients nor related staff were infected with the coronavirus during the perioperative or early postoperative period. One patient, who was diagnosed with COVID-19 pneumonia on postoperative day 80 died from the infection. Another patient died on postoperative day 85 due to progressive ovarian cancer, a disorder in vital functions, and organ failure. CONCLUSION: HIPEC during the COVID-19 pandemic seems a safe and feasible procedure, with acceptable morbidity and mortality rates. Careful selection of patients is important and precautions should be taken before the procedure.


Assuntos
COVID-19/epidemiologia , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/isolamento & purificação
10.
J Obstet Gynaecol Can ; 43(2): 242-246, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33153941

RESUMO

BACKGROUND: Primary retroperitoneal Müllerian adenocarcinoma (PRMA) is a very rare type of primary retroperitoneal tumour. CASE 1: A 45-year-old woman presented with left lower extremity swelling and pain. Imaging revealed that the tumour had invaded the left common iliac vein and artery, internal and external iliac arteries, sciatic and obturator nerves, and pelvic wall. CASE 2: A 37-year-old was admitted with pelvic pain. Imaging showed the tumor at the left iliac bifurcation infiltrating the internal iliac artery and left sciatic, obturator, and femoral nerves. Both of these patients were treated with radical surgery that achieved no visible tumour at the end of the operation. CONCLUSION: There is no guideline for the diagnosis and management of this entity due to its rarity. These cases should be managed at highly specialized centres with expertise in radical surgery.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retroperitoneais/cirurgia , Espaço Retroperitoneal/cirurgia , Adenocarcinoma/patologia , Adulto , Artérias , Biópsia , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal/diagnóstico por imagem , Resultado do Tratamento
11.
Mol Biol Rep ; 47(5): 3789-3796, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32277442

RESUMO

We aimed to provide a comparative characterization of DNA damage response elements, survival/apoptosis and cell cycle progression of the malignant granulosa cells exposed to gemcitabine and cisplatin. Malignant granulosa tumor cell lines COV434 and KGN were used for the experiments. Cell viability, proliferation, DNA damage response and apoptosis were investigated. Cell cycle progression was assessed. In vitro estradiol (E2) and AMH productions of the cells were measured. Exposure of asynchronous malignant granulosa cells to gemcitabine caused growth arrest, induced DNA damage and activated cellular stress pathways, cell cycle checkpoint sensors and triggered apoptosis as evidenced by increased expression of phospho-p38, γ-histone H2AX, phospho-Chk-1/phospho-Chk-2, and cleaved forms of PARP and caspase-3 in a dose dependent manner. In vitro E2 and AMH productions of the cells were decreased along with reduction in viable cell mass. Cisplatin treatment produced a similar response but it was associated with JNK activation rather than p38. When the cells were synchronized and treated with gemcitabine at G2/M transition, the degradation of cyclin B1 and dephosphorylation of cdc-2 at Tyr 15 residue did not occur, resulting in cycle arrest. Similar effects on cell cycle progression was also observed in cisplatin. However, it was associated with JNK activation and higher expression of γ-histone H2AX and cleaved forms of caspase-3 and PARP, indicative of more extensive DNA damage and apoptosis in the cells. This descriptive study provides evidence that gemcitabine exerts cytotoxic effects and causes perturbations in cell cycle progression of malignant granulosa cells.


Assuntos
Desoxicitidina/análogos & derivados , Tumor de Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/metabolismo , Cisplatino/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Desoxicitidina/metabolismo , Desoxicitidina/farmacologia , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Tumor de Células da Granulosa/tratamento farmacológico , Células da Granulosa/metabolismo , Humanos , Gencitabina
12.
Int J Gynecol Cancer ; 30(3): 299-304, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31857440

RESUMO

OBJECTIVE: The aim of this multicenter study was to evaluate the feasibility of sentinel lymph node (SLN) mapping in clinically uterine confined endometrial cancer. METHODS: Patients who underwent primary surgery for endometrial cancer with an SLN algorithm were reviewed. Indocyanine green or blue dye was used as a tracer. SLNs and/or suspicious lymph nodes were resected. Side specific lymphadenectomy was performed when mapping was unsuccessful. SLNs were ultrastaged on final pathology. RESULTS: 357 eligible patients were analyzed. Median age was 59 years. Median number of resected SLNs was 2 (range 1-12) per patient. Minimal invasive and open surgeries were performed in 264 (73.9%) and 93 (26.1%) patients, respectively. Indocyanine green was used in 231 (64.7%) and blue dye in 126 (35.3%) patients. The dyes were injected into the cervix in 355 (99.4%) patients. The overall and bilateral SLN detection rates were 91.9% and 71.4%, respectively. The mapping rates using indocyanine green or blue dye were comparable (P=0.526). There were 43 (12%) patients with lymphatic metastasis. The SLN algorithm was not able to detect 3 of 43 patients who had isolated paraaortic metastasis. After SLN biopsy, complete pelvic lymphadenectomy was performed in 286 (80.1%) patients. Sensitivity and negative predictive value were both 100% for the detection of pelvic lymph node metastases. In addition, 117 (32.8%) patients underwent completion paraaortic lymphadenectomy after SLN biopsy. In these patients, sensitivity for detecting metastases to pelvic and/or paraaortic lymph nodes was 90.3% with a negative predictive value of 96.6%. The risk of non-SLN involvement in patients with macrometastatic SLNs, micrometastatic SLNs, and isolated tumor cells in SLNs were 61.2%, 14.3% and 0%, respectively. CONCLUSIONS: SLN biopsy had good accuracy in detecting lymphatic metastasis. However, one-third of cases with metastatic SLNs also had non-SLN involvement and this risk increased to two-thirds of cases with macrometastatic SLNs. The effect of leaving these nodes in situ on survival should be evaluated in further studies.


Assuntos
Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Corantes , Neoplasias do Endométrio/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Verde de Indocianina , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/cirurgia
13.
Int J Gynecol Cancer ; 30(7): 1005-1011, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32474451

RESUMO

OBJECTIVE: This study aimed to find out whether side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy according to "reflex frozen section" analysis of the uterus in case of sentinel lymph node (SLN) mapping failure. METHODS: Patients who underwent surgery for endometrial cancer with an SLN algorithm were stratified as low-risk or high-risk according to the uterine features on the final pathology reports. Two models for low-risk patients were defined to omit side-specific pelvic lymphadenectomy: strategy A included patients with endometrioid histology, grade 1-2, and <50% myometrial invasion irrespective of the tumor diameter; strategy B included all factors of strategy A with the addition of tumor diameter ≤2 cm. Theoretical side-specific pelvic lymphadenectomy rates were calculated for the two strategies, assuming side-specific pelvic lymphadenectomy was omitted if low-risk features were present on reflex uterine frozen examination, and compared with the standard National Comprehensive Cancer Network (NCCN) SLN algorithm. RESULTS: 372 endometrial cancer patients were analyzed. 230 patients (61.8%) had endometrioid grade 1 or 2 tumors with <50% myometrial invasion (strategy A), and in 123 (53.4%) of these patients the tumor diameter was ≤2 cm (strategy B); 8 (3.5%) of the 230 cases had lymphatic metastasis. None of them were detected by side-specific pelvic lymphadenectomy and metastases were limited to SLNs in 7 patients. At least one pelvic side was not mapped in 107 (28.8%) cases in the entire cohort, and all of these cases would require a side-specific pelvic lymphadenectomy based on the NCCN SLN algorithm. This rate could have been significantly decreased to 11.8% and 19.4% by applying reflex frozen section examination of the uterus using strategy A and strategy B, respectively. CONCLUSION: Reflex frozen section examination of the uterus can be a feasible option to decide whether side-specific pelvic lymphadenectomy is necessary for all the patients who failed to map with an SLN algorithm. If low-risk factors are found on frozen section examination, side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy for lymphatic spread.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Feminino , Secções Congeladas , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Pessoa de Meia-Idade , Fatores de Risco , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Turquia
14.
J Minim Invasive Gynecol ; 27(5): 1081-1086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294549

RESUMO

STUDY OBJECTIVE: To determine and categorize the anatomic variations of the uterine artery (UA) as observed during laparoscopic hysterectomy with retroperitoneal dissection for benign conditions. DESIGN: A prospective, observational study. SETTING: A hospital department of obstetrics and gynecology, Uludag University Hospital, Bursa, Turkey. PATIENTS: A total of 378 female patients who presented with indications for laparoscopic hysterectomy for benign disease. INTERVENTIONS: Laparoscopic hysterectomy with retroperitoneal dissection was performed bilaterally in all patients between March 2014 and October 2018. The vascular anatomy beginning at the bifurcation of the common iliac artery down to the crossing of the UA with the ureter was exposed and subsequently studied. The UA was identified, and its variable branching patterns were recorded. The patterns were then categorized into groups adapted from classic vascular anatomy studies. MEASUREMENTS AND MAIN RESULTS: Retroperitoneal dissections of 756 UAs were performed in 378 female patients. The UA was the first anterior branch of the internal iliac artery in 80.9% of the cases (Model 1; Main Model). Three additional models adequately described other variations of the UA as follows: Model 2 (Cross Model), 3.7%; Model 3 (Trifurcation Model), 3.1%; and Model 4 (Inverted-Y Model), 7.4%. The origin of the UA could not be determined in 7.4% of the cases. CONCLUSION: The UA is the first anterior branch of the internal iliac artery in more than 80% of females. Surgeons should be aware of the anatomic variations of the UA to perform safe and efficient procedures.


Assuntos
Laparoscopia/métodos , Modelos Biológicos , Artéria Uterina/anatomia & histologia , Artéria Uterina/embriologia , Adulto , Dissecação , Feminino , Ginecologia , Humanos , Histerectomia/métodos , Artéria Ilíaca/anatomia & histologia , Artéria Ilíaca/patologia , Artéria Ilíaca/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Turquia , Ureter/patologia , Ureter/cirurgia , Artéria Uterina/patologia , Artéria Uterina/cirurgia
15.
Surg Innov ; 27(5): 455-460, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32501743

RESUMO

Objective. The aim of this study was to assess postoperative incisional pain and cosmetic scores in mini-laparoscopic gynecological surgeries undertaken with different port sizes. Material and Method. In this prospective study, all women who underwent mini-laparoscopic gynecological surgery with 2.4-, 3-, and 5-mm lateral ports for benign gynecological conditions between March 2017 and April 2019 were included. The primary outcome was postoperative incisional pain at rest, walking, and after a provoked Valsalva maneuver assessed by numeric rating scale scores at 6 hours, 12 hours, 24 hours, and 3 days and 7 days after surgery. Secondary outcome measures included cosmetic scores of each port site (evaluated by using patient-observer scar assessment scale [POSAS]), operation time, and intra- and postoperative complications. Results. A total of 330 lateral port sites in 110 patients who underwent benign gynecological surgery via mini-laparoscopy were assessed for pain and cosmetic appearance. Pain scores at each time point were significantly lower for 2.4- and 3-mm ports than those for 5-mm ports; however, no significant difference was detected between 2.4-mm and 3-mm port sites (P = .6). The difference was more evident at 24 hours when routine analgesic drugs were stopped (P = .004). For POSAS scores, both 2.4-mm and 3-mm ports were superior to 5-mm port sites (P = .002); however, there was no significant difference between 2.4-mm and 3-mm port sites (P = .2). There were 2 port-related complications: one subcutaneous emphysema and one bleeding from a 5-mm trocar site 1 hour after surgery. Conclusion. Mini-laparoscopic gynecologic surgery using smaller ports resulted in decreased postoperative incisional pain and superior cosmetic appearance.


Assuntos
Cicatriz , Laparoscopia , Cicatriz/prevenção & controle , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos
16.
J Obstet Gynaecol Res ; 45(12): 2470-2473, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31579988

RESUMO

We aimed to report a detection failure of sentinel lymph node (SLN) mapping via indocyanine green in a patient with endometrial cancer with a previous history of chronic lymphocytic leukemia (CLL), which is a potential risk factor to obstruct lymphatic channels. A 64-year-old woman with a 12-year history of CLL presented to the clinic with grade 2 endometrioid carcinoma. The patient underwent laparoscopic surgical staging. Indocyanine green was used intraoperatively to locate the SLN. No lymph node or lymphatic vessels were identified during SLN mapping. At the final pathology, the morphological findings of CLL were detected in the lymph nodes without metastasis of endometrial cancer. Sentinel lymph node mapping failure due to obstruction of lymphatic channels in a patient with CLL was demonstrated in this study. This is the first report to the best of our knowledge showing SLN mapping failure in the presence of lymphoproliferative diseases.


Assuntos
Neoplasias do Endométrio/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Biópsia de Linfonodo Sentinela , Neoplasias do Endométrio/complicações , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Metástase Linfática , Pessoa de Meia-Idade
17.
J Obstet Gynaecol ; 39(2): 253-258, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30372646

RESUMO

This study was conducted to determine the demographic and clinicopathologic characteristics and evaluate the prognostic value of various factors, such as the extensiveness of surgery, related to the tumour itself and the clinical features in the recurrence of borderline ovarian tumours (BOT). We retrospectively evaluated the data of 103 patients with a borderline ovarian tumours treated at our institution between the years 2000 and 2012. The median age was 37 (16-79) years and the majority of the patients were premenopausal (76.7%). During the follow-up, 16 recurrences were observed (15.5%). The multivariate analysis showed that the micropapillary architecture and fertility sparing surgery were the only significant independent predictors for the development of a recurrence amongst all of the demographic and clinicopathological features. In our study group, we identified that the micropapillary architecture itself and the fertility sparing surgery had a significant impact on the development of a BOT recurrence. The patients who possess these features should be followed up more closely for a long time period. Impact statement What is already known on this subject? A borderline ovarian tumour is known as a recurrent disease. The recurrence rate varies between 5 and 20%. It is well known in the literature that patients treated by an oophorectomy have a relatively lower risk of development of a recurrence compared to the patients treated by cystectomy. What do the results of this study add? Although some of the clinicopathological features are shown to be risk factors for the development of a recurrence in many studies, some of the pathological-clinical and the demographic features have not been described as yet, or have been considered to be equivocal regarding the development of a recurrence. In this study, we investigate all possible demographic, pathological, and clinical factors associated with a recurrence. Not only the well-known pathological characteristics but also the new pathological parameters and clinical approaches have been investigated. For instance, microinvasion architecture and lymphadenectomy speculated in the literature as the risk factors for the development of a recurrence, have not been identified as risk factors in our study. On the other hand, our statistical analyses have revealed that micropapillary architecture should be described as a risk factor for the development of a recurrence. What are the implications of these findings for clinical practice and/or further research? We hope our study becomes influential in the literature on the field of a micropapillary architecture and the development of a recurrence. The patients carrying this feature have to be followed up very closely and carefully. Furthermore, our findings have indicated no significant relation between the performing of a lymphadenectomy and the rate of a recurrence. This result might be encouraging for the gynaecological surgeons to refrain from a lymphadenectomy for the borderline ovarian tumours.


Assuntos
Cistadenocarcinoma/patologia , Recidiva Local de Neoplasia/etiologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Adolescente , Adulto , Idoso , Cistadenocarcinoma/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Adulto Jovem
18.
J BUON ; 23(5): 1528-1533, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30570881

RESUMO

PURPOSE: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) or hyperthermic intrapleural chemotherapy (HIC) has been established as the new treatment modality for selected patients with peritoneal and pleural malignancies. The purpose of the study was to compare the development of acute kidney injury (AKI) in patients who received intravenous cisplatin alone, HIPEC and underwent surgery. METHODS: This retrospective study included 104 patients who underwent different therapeutic procedures including systemic cisplatin, surgery and HIPEC or HIC using cisplatin for the treatment of peritoneal carcinomatosis from a variety of primary tumors at Koc University Hospital and American Hospital between January 2015 to December 2017. RESULTS: AKI developed in 18 (17.3%) patients. Baseline creatinine was significantly increased in 3 groups after therapies. The development of AKI was highest in patients treated with HIPEC compared to patients treated with intravenous cisplatin and patients who underwent surgery. AKI developed 31.2% in the HIPEC group (10 of 32 patients), 11.7% in the surgery group (4 of 34 patients) and 10.5% in intravenous cisplatin group (4 of 38 patients), respectively (p 0.04). CONCLUSION: HIPEC may not be so safe with regard to kidney function. Every attempt should be taken to decrease kidney damage during this procedure.


Assuntos
Injúria Renal Aguda/etiologia , Cisplatino/efeitos adversos , Hipertermia Induzida/efeitos adversos , Injúria Renal Aguda/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Gynecol Endocrinol ; 33(2): 119-123, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27690684

RESUMO

OBJECTIVE: To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters. RESULTS: Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels. CONCLUSION: WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.


Assuntos
Hormônio Antimülleriano/sangue , Proteínas de Sinalização Intercelular CCN/sangue , Resistência à Insulina , Obesidade/sangue , Hormônios Peptídicos/sangue , Síndrome do Ovário Policístico/sangue , Proteínas Proto-Oncogênicas/sangue , Adulto , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Estudos Transversais , Feminino , Humanos , Estudos Prospectivos , Adulto Jovem
20.
Gynecol Oncol ; 142(1): 206-207, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27168004

RESUMO

OBJECTIVE: The majority of ovarian cancer patients are initially diagnosed at an advanced-stage [1]. Upper abdominal bulky metastasis cephalad to the greater omentum reported to be present in 42% of patients [2]. Many complex surgical procedures such as splenectomy, pancreatectomy, mobilization and partial resection of liver, porta hepatis dissection, diaphragmatic peritonectomy and resection are frequently performed to achieve complete resection of metastatic disease [3]. Our aim in this surgical film is to show the resection of a left sided diaphragmatic implant located beneath the heart, with dissection from the pericardium after entrance to the pericardial cavity. Additionally, step by step splenectomy with distal pancreatectomy also presented. METHODS: A 67years-old woman referred to our clinic for interval debulking for advanced stage suboptimally debulked high grade serous ovarian carcinoma. The tumor invading distal pancreas, hilum and parenchyma of spleen is clearly seen on magnetic resonance imaging. Another implant was also visible on left side of the diaphragm. We achieved complete cytoreduction with no macroscopic disease at the end of the surgery. RESULTS: She stayed at the intensive care unit for two days and in our clinic for seven days. We did not encounter any grade 3 or 4 adverse event in post-operative period. CONCLUSION: The surgical treatment of ovarian cancer has evolved in time in favor of radical surgery. The surgical team should be highly motivated, skilled and experienced for this complex procedures, since being able to reach complete cytoreduction is the most important predictor of survival in ovarian cancer patients.


Assuntos
Neoplasias Ovarianas/cirurgia , Idoso , Diafragma/cirurgia , Feminino , Humanos , Pancreatectomia , Pericárdio/cirurgia , Esplenectomia
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