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Article ; Online: Sentinel lymph node identification in early stage ovarian cancer: is it still possible after prior tumor resection?

Laven, Pim / Kruitwagen, Roy / Zusterzeel, Petra / Slangen, Brigitte / van Gorp, Toon / van der Pol, Jochem / Lambrechts, Sandrina

Journal of ovarian research

2021 Volume 14, Issue 1, Page(s) 132

Abstract: Objective: Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian ... ...

Abstract	Objective: Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy. Methods: Patients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-min, the sentinel node(s) were identified using either the gamma-probe and / or blue dye. Results: A total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%. Conclusion: In this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection. Trial registration: NCT02540551.
MeSH term(s)	Adult ; Aged ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/pathology ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node/surgery ; Sentinel Lymph Node Biopsy/methods
Language	English
Publishing date	2021-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2455679-8
ISSN	1757-2215 ; 1757-2215
ISSN (online)	1757-2215
ISSN	1757-2215
DOI	10.1186/s13048-021-00887-w
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Article ; Online: Feasibility of sentinel lymph node mapping of the ovary: a systematic review.

Dell'Orto, Federica / Laven, Pim / Delle Marchette, Martina / Lambrechts, Sandrina / Kruitwagen, Roy / Buda, Alessandro

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2019 Volume 29, Issue 7, Page(s) 1209–1215

Abstract: Pelvic and para-aortic lymphadenectomy is routinely performed in early ovarian cancer to define the stage of the disease. However, it may be associated with increased blood loss, operative time, and length of hospitalization. The sentinel lymph node ... ...

Abstract	Pelvic and para-aortic lymphadenectomy is routinely performed in early ovarian cancer to define the stage of the disease. However, it may be associated with increased blood loss, operative time, and length of hospitalization. The sentinel lymph node technique has been shown to be safe and feasible in vulvar, uterine, and cervical cancer. Data detailing feasibility and outcomes of sentinel lymph node mapping in ovarian cancer are scarce.To summarize the studies evaluating the feasibility of sentinel lymph node detection from the ovary, examining the technique and detection rate.A systematic search of the literature was performed using PubMed and Embase from June 1991 to February 2019. Studies describing the sentinel lymph node technique and lymphatic drainage of the ovaries were incorporated in this review. Ten articles were selected, comprising a total of 145 patients. A variety of agents were used, but the primary markers were technetium-99m radiocolloid (Tc-99m), patent blue, or indocyanine green, and the most common injection site was the ovarian ligaments.The overall sentinel lymph node detection rate was 90.3%.We propose a standardized technique sentinel lymph node mapping in ovarian cancer, using indocyanine green, or Tc-99m and blue dye as alternative tracers, injected in both the suspensory and the infundibulopelvic ligament of the ovary.
MeSH term(s)	Coloring Agents/administration & dosage ; Female ; Humans ; Indocyanine Green/administration & dosage ; Lymph Node Excision/methods ; Lymph Nodes/pathology ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Organotechnetium Compounds/administration & dosage ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/surgery ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node/surgery ; Sentinel Lymph Node Biopsy/methods
Chemical Substances	Coloring Agents ; Organotechnetium Compounds ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2019-08-07
Publishing country	England
Document type	Journal Article ; Systematic Review
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1136/ijgc-2019-000606
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Article ; Online: Signal transduction pathway activity in high-grade serous carcinoma, its precursors and Fallopian tube epithelium.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Bosch, Steven L / van Diest, Paul J / Wesseling-Rozendaal, Yvonne J W / van de Stolpe, Anja / Lambrechts, Sandrina / Bekkers, Ruud L M / Piek, Jurgen M J

Gynecologic oncology

2022 Volume 165, Issue 1, Page(s) 114–120

Abstract: Objective: To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE).!## ...

Abstract	Objective: To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE). Methods: We assessed mRNA expression levels of pathway-specific target genes with RT-qPCR in STIC and concurrent HGSC (n = 8) and normal FTE (n = 8). Subsequently, signal transduction pathway assays were used to assess functional activity of the androgen (AR) and estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathways. Results: There were no statistically significant differences in pathway activity between STIC and HGSC, but STIC and HGSC demonstrated significantly lower ER and higher PI3K and HH pathway activity in comparison to normal FTE, suggesting these pathways as putative early drivers. In addition, we determined FOXO3a protein expression by immunohistochemistry and found loss of FOXO3a protein expression in STIC and HGSC compared to normal FTE. This observation confirmed that activation of PI3K signaling by loss of FOXO is an early hallmark of serous carcinogenesis. Furthermore, HGSC demonstrated significant loss of AR and Wnt pathway activity in relation to FTE, suggesting these pathways contribute to disease progression. Conclusion: Our observations, together with the previously described associations between p53 signaling and both PI3K and HH pathway activity, provide evidence that increased PI3K and HH pathway activity and loss of ER pathway activity may be underlying events contributing to neoplastic transformation of FTE into STIC.
MeSH term(s)	Adenocarcinoma in Situ/pathology ; Carcinoma in Situ/pathology ; Cystadenocarcinoma, Serous/pathology ; Epithelium/metabolism ; Fallopian Tube Neoplasms/pathology ; Fallopian Tubes/pathology ; Female ; Hedgehog Proteins ; Humans ; Ovarian Neoplasms/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2022.01.027
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Article ; Online: Positive DESKTOP and Tian Scores Systems Are Adequate to Predict Optimal (R0) Secondary Debulking Surgery in Ovarian Cancer, But a Negative Score Does Not Preclude Secondary Surgery.

Laga, Tina / Lambrechts, Sandrina / Laenen, Annouschka / Van Nieuwenhuysen, Els / Han, Sileny N / Vergote, Ignace

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2018 Volume 28, Issue 4, Page(s) 721–728

Abstract: Objective: The aim of this study was to assess the safety and feasibility of macroscopically complete (R0) secondary debulking surgery (SDS) in a single-center cohort of patients with recurrent ovarian cancer. The performances of existing prediction ... ...

Abstract	Objective: The aim of this study was to assess the safety and feasibility of macroscopically complete (R0) secondary debulking surgery (SDS) in a single-center cohort of patients with recurrent ovarian cancer. The performances of existing prediction models (DESKTOP score, Tian model) for R0 SDS were evaluated in this cohort. Methods: Patient, disease, and treatment characteristics of 102 patients undergoing SDS for recurrent ovarian cancer at the University Hospitals Leuven between 1997 and 2014 were collected. Results: R0 SDS was achieved in 73% of patients and associated with improved progression-free survival (P = 0.0002) and overall survival (P = 0.0003) compared with non-R0 resection. Variables associated with R0 SDS were site of relapse (P = 0.046) and absence of ascites (P = 0.045). The DESKTOP score and Tian model showed positive predictive values for R0 SDS of 80% and 73%, respectively. However, a false-negative rate for R0 resection of 61% and 70% was observed in our study. Progression-free survival and overall survival did not significantly differ between DESKTOP score-positive and -negative patients with R0 SDS. Conclusions: We confirmed a high positive predictive value in the selection of candidates for R0 SDS with the DESKTOP score and the Tian model. However, because 61% and 70% of the patients with a negative score were debulked to R0, we suggest that other selection criteria based on anatomic and metabolic imaging such as whole-body diffusion-weighted magnetic resonance imaging should be evaluated when selecting patients for SDS.
MeSH term(s)	Carcinoma, Ovarian Epithelial/mortality ; Carcinoma, Ovarian Epithelial/surgery ; Cytoreduction Surgical Procedures ; Decision Support Techniques ; Feasibility Studies ; Female ; Gynecologic Surgical Procedures ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/surgery ; Retrospective Studies
Language	English
Publishing date	2018-03-21
Publishing country	England
Document type	Journal Article ; Validation Studies
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1097/IGC.0000000000001219
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Zs.A 3198: Show issues

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Article: Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

van der Ploeg, Phyllis / Hendrikse, Cynthia Se / Thijs, Anna Mj / Westgeest, Hans M / Smedts, Huberdina Pm / Vos, M Caroline / Jalving, Mathilde / Lok, Christianne Ar / Boere, Ingrid A / van Ham, Maaike Apc / Ottevanger, Petronella B / Westermann, Anneke M / Mom, Constantijne H / Lalisang, Roy I / Lambrechts, Sandrina / Bekkers, Ruud Lm / Piek, Jurgen Mj

Heliyon

2023 Volume 10, Issue 1, Page(s) e23170

Abstract: Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for ... ...

Abstract	Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.
Language	English
Publishing date	2023-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e23170
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Article ; Online: The effectiveness of monotherapy with PI3K/AKT/mTOR pathway inhibitors in ovarian cancer: A meta-analysis.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Thijs, Anna M J / Westgeest, Hans M / Boere, Ingrid A / Lambrechts, Sandrina / van de Stolpe, Anja / Bekkers, Ruud L M / Piek, Jurgen M J

Gynecologic oncology

2021 Volume 163, Issue 2, Page(s) 433–444

Abstract: Objective: To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response.: ...

Abstract	Objective: To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response. Methods: A systematic search was conducted in PubMed, Embase and the Cochrane Library for articles reporting on treatment with PI3K/AKT/mTOR inhibitors in ovarian cancer. The primary endpoint was defined as the clinical benefit rate (CBR), including the proportion of patients with complete (CR) and partial response (PR) and stable disease (SD). Secondary endpoints included the overall response rate (ORR, including CR and PR) and drug-related grade 3 and 4 adverse events. Results: We included 233 patients from 19 studies and observed a pooled CBR of 32% (95% CI 20-44%) and ORR of 3% (95% CI 0-6%) in advanced or recurrent ovarian cancer patients treated with PI3K/AKT/mTOR inhibitors. Subgroup analysis tended to favor the studies who selected patients based on current PI3K/AKT/mTOR biomarker criteria (e.g. genomic alterations or loss of PTEN protein expression), but the difference in CBR was not statistically significant from studies with unselected populations (respectively, CBR of 42% (95% CI 23-62%) and 27% (95% CI 14-42%), P = 0.217). To better reflect true patient benefit, we excluded SD <6 months as a beneficial outcome which resulted in a pooled CBR of 7% (95% CI 2-13%). The overall proportion of patients with drug-related grade 3 and 4 adverse events was 36%. Conclusions: The efficacy of monotherapy with PI3K/AKT/mTOR inhibitors in advanced recurrent ovarian cancer patients is limited to a small subgroup and selection of patients with the use of current biomarkers did not improved the CBR significantly. Given the toxicity profile, we suggest that current treatment with PI3K/AKT/mTOR inhibitors should not be initiated unless in clinical trials. Furthermore, improved biomarkers to measure functional PI3K/AKT/mTOR pathway activity are needed to optimize patient selection.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Clinical Decision-Making ; Female ; Humans ; MTOR Inhibitors/administration & dosage ; MTOR Inhibitors/adverse effects ; Neoplasm Staging ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/mortality ; Patient Selection ; Phosphatidylinositol 3-Kinases/analysis ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/administration & dosage ; Phosphoinositide-3 Kinase Inhibitors/adverse effects ; Predictive Value of Tests ; Proto-Oncogene Proteins c-akt/analysis ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/analysis ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; MTOR Inhibitors ; Phosphoinositide-3 Kinase Inhibitors ; MTOR protein, human (EC 2.7.1.1) ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-07-10
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.07.008
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Article ; Online: Use of PlasmaJet for Peritoneal Carcinomatosis in Ovarian Cancer.

Panuccio, Enrico / Leunen, Karin / Van Nieuwenhuysen, Els / Neven, Patrick / Lambrechts, Sandrina / Vergote, Ignace

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2016 Volume 26, Issue 8, Page(s) 1521–1524

Abstract: Objective: This study aimed to assess the role and complications of extensive cytoreduction with PlasmaJet (Plasma Surgical, Roswell, Ga) in ovarian cancer with peritoneal carcinomatosis.: Materials: All patients undergoing primary, secondary, or ... ...

Abstract	Objective: This study aimed to assess the role and complications of extensive cytoreduction with PlasmaJet (Plasma Surgical, Roswell, Ga) in ovarian cancer with peritoneal carcinomatosis. Materials: All patients undergoing primary, secondary, or interval debulking surgery for ovarian cancer and treated with PlasmaJet between October 2013 and February 2015 were analyzed. Results: Nineteen patients were enrolled. The median operative time was 270 minutes, median blood loss was 700 mL, and median length of stay was 9 days. In all patients, complete resection of all macroscopic disease was achieved.We used PlasmaJet to remove peritoneal carcinomatosis on the abdominal peritoneum, intestinal mesentery, bowel serosa, and diaphragmatic region. Overall, we treated 66 organs with PlasmaJet in our series. No bowel or urological fistulas were observed. According to the Clavien-Dindo classification, 13 adverse events were recorded at grade 2 or lesser. We observed only 1 grade 3 adverse event. No postoperative mortality was recorded. Conclusions: In our series, the PlasmaJet seems to be an efficient device for tumor ablation or dissection to obtain complete resection of all macroscopic disease in patients with peritoneal carcinomatosis.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Argon Plasma Coagulation/methods ; Carcinoma/surgery ; Cytoreduction Surgical Procedures/methods ; Female ; Humans ; Laparotomy/methods ; Middle Aged ; Ovarian Neoplasms/surgery ; Peritoneal Neoplasms/surgery
Language	English
Publishing date	2016-07-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1097/IGC.0000000000000788
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Article ; Online: Ovarian cancer ascites induces skeletal muscle wasting in vitro and reflects sarcopenia in patients.

Ubachs, Jorne / van de Worp, Wouter R P H / Vaes, Rianne D W / Pasmans, Kenneth / Langen, Ramon C / Meex, Ruth C R / van Bijnen, Annemarie A J H M / Lambrechts, Sandrina / Van Gorp, Toon / Kruitwagen, Roy F P M / Olde Damink, Steven W M / Rensen, Sander S

Journal of cachexia, sarcopenia and muscle

2021 Volume 13, Issue 1, Page(s) 311–324

Abstract: Background: Cachexia-associated skeletal muscle wasting or 'sarcopenia' is highly prevalent in ovarian cancer and contributes to poor outcome. Drivers of cachexia-associated sarcopenia in ovarian cancer remain elusive, underscoring the need for novel ... ...

Abstract	Background: Cachexia-associated skeletal muscle wasting or 'sarcopenia' is highly prevalent in ovarian cancer and contributes to poor outcome. Drivers of cachexia-associated sarcopenia in ovarian cancer remain elusive, underscoring the need for novel and better models to identify tumour factors inducing sarcopenia. We aimed to assess whether factors present in ascites of sarcopenic vs. non-sarcopenic ovarian cancer patients differentially affect protein metabolism in skeletal muscle cells and to determine if these effects are correlated to cachexia-related patient characteristics. Methods: Fifteen patients with an ovarian mass and ascites underwent extensive physical screening focusing on cachexia-related parameters. Based on computed tomography-based body composition imaging, six cancer patients were classified as sarcopenic and six were not; three patients with a benign condition served as an additional non-sarcopenic control group. Ascites was collected, and concentrations of cachexia-associated factors were assessed by enzyme-linked immunosorbent assay. Subsequently, ascites was used for in vitro exposure of C2C12 myotubes followed by measurements of protein synthesis and breakdown by radioactive isotope tracing, qPCR-based analysis of atrophy-related gene expression, and NF-κB activity reporter assays. Results: C2C12 protein synthesis was lower after exposure to ascites from sarcopenic patients (sarcopenia 3.1 ± 0.1 nmol/h/mg protein vs. non-sarcopenia 5.5 ± 0.2 nmol/h/mg protein, P < 0.01), and protein breakdown rates tended to be higher (sarcopenia 31.2 ± 5.2% vs. non-sarcopenia 20.9 ± 1.9%, P = 0.08). Ascites did not affect MuRF1, Atrogin-1, or REDD1 expression of C2C12 myotubes, but NF-κB activity was specifically increased in cells exposed to ascites from sarcopenic patients (sarcopenia 2.2 ± 0.4-fold compared with control vs. non-sarcopenia 1.2 ± 0.2-fold compared with control, P = 0.01). Protein synthesis and breakdown correlated with NF-κB activity (r Conclusions: Ascites of sarcopenic ovarian cancer patients induces pronounced skeletal muscle protein metabolism changes in C2C12 cells that correlate with clinical muscle measures of the patient and that are characteristic of cachexia. The use of ascites offers a new experimental tool to study the impact of both tumour-derived and systemic factors in various cachexia model systems, enabling identification of novel drivers of tissue wasting in ovarian cancer.
MeSH term(s)	Ascites/etiology ; Ascites/metabolism ; Ascites/pathology ; Cachexia/diagnosis ; Humans ; Muscle, Skeletal/pathology ; Ovarian Neoplasms/pathology ; Sarcopenia/diagnosis ; Sarcopenia/etiology ; Sarcopenia/metabolism
Language	English
Publishing date	2021-12-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12885
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Article ; Online: Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Bucks, Karlijn M M / Lentjes-Beer, Marjolein H F M / Bosch, Steven L / van Rumste, Minouche M E / Vos, M Caroline / van Diest, Paul J / Lambrechts, Sandrina / van de Stolpe, Anja / Bekkers, Ruud L M / Piek, Jurgen M J

Acta obstetricia et gynecologica Scandinavica

2021 Volume 101, Issue 2, Page(s) 256–264

Abstract: Introduction: The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of ... ...

Abstract	Introduction: The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant signal transduction pathway activity leading to female subfertility and other tubal diseases. Therefore, in this study we investigate the influence of the hormonal cycle on the activity of key signal transduction pathways in the fimbrial epithelium of morphologically normal fallopian tubes. Material and methods: We included healthy pre- (n = 17) and postmenopausal (n = 8) patients who had surgical interventions for benign gynecologic conditions. Histologic sections of the fallopian tubes were reviewed by two pathologists and, for the premenopausal patients, hormone serum levels and sections of the endometrium were examined to determine the hormonal phase (early follicular [n = 4], late follicular [n = 3], early luteal [n = 5], late luteal [n = 5]). After laser capture microdissection, total mRNA was extracted from the fimbrial epithelium and real-time quantitative reverse transcription-PCR was performed to determine functional signal transduction pathway activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor-beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathways. Results: The early luteal phase demonstrated high AR and ER pathway activity in comparison with the late luteal phase (p = 0.016 and p = 0.032, respectively) and low PI3K activity compared with the late follicular phase (p = 0.036), whereas the late luteal phase showed low activity of HH and Wnt compared with the early follicular phase (both p = 0.016). Signal transduction pathway activity in fimbrial epithelium from postmenopausal patients was most similar to the early follicular and/or late luteal phase with regard to the AR, ER and PI3K pathways. Wnt pathway activity in postmenopausal patients was comparable to the late follicular and early luteal phase. We observed no differences in HH and TGF-β pathway activity between pre- and postmenopausal samples. The cyclic changes in signal transduction pathway activity suggest a stage-specific function which may affect the morphology and physiology of the human fallopian tube. Conclusions: We demonstrated cyclic changes in activity of the AR, ER, PI3K, HH and Wnt pathways throughout the hormonal cycle.
MeSH term(s)	Aged ; Epithelium/physiology ; Fallopian Tubes/physiology ; Female ; Hedgehog Proteins/metabolism ; Humans ; Menopause ; Menstrual Cycle ; Middle Aged ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Wnt/metabolism ; Reference Values ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction
Chemical Substances	Hedgehog Proteins ; Receptors, Androgen ; Receptors, Estrogen ; Receptors, Wnt
Language	English
Publishing date	2021-12-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80019-3
ISSN	1600-0412 ; 0001-6349
ISSN (online)	1600-0412
ISSN	0001-6349
DOI	10.1111/aogs.14306
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Article ; Online: Simple Rules, Not So Simple: The Use of International Ovarian Tumor Analysis (IOTA) Terminology and Simple Rules in Inexperienced Hands in a Prospective Multicenter Cohort Study.

Meys, Evelyne / Rutten, Iris / Kruitwagen, Roy / Slangen, Brigitte / Lambrechts, Sandrina / Mertens, Helen / Nolting, Ernst / Boskamp, Dieuwke / Van Gorp, Toon

Ultraschall in der Medizin (Stuttgart, Germany : 1980)

2017 Volume 38, Issue 6, Page(s) 633–641

Abstract: Objectives: To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to ... ...

Title translation	„Simple Rules“ – nicht so einfach: Anwendung der „International Ovarian Tumor Analysis“ (IOTA)- Terminologie und der „Simple Rules“ in unerfahrenen Händen in einer prospektiven multizentrischen Kohortenstudie.
Abstract	Objectives: To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert. Methods: This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert. Ultrasound features were recorded using IOTA nomenclature, and used for classifying the mass by simple rules. Interobserver agreement was evaluated with Fleiss' kappa and percentage agreement between observers. Results: 50 consecutive women were included. We observed 46 discrepancies in the description of ovarian masses when non-experts utilized IOTA terminology. Tumor type was misclassified often (n = 22), resulting in poor interobserver agreement between the non-experts and the expert (kappa = 0.39, 95 %-CI 0.244 - 0.529, percentage of agreement = 52.0 %). Misinterpretation of simple rules by non-experts was observed 57 times, resulting in an erroneous diagnosis in 15 patients (30 %). The agreement for classifying the mass as benign, malignant or inconclusive by simple rules was only moderate between the non-experts and the expert (kappa = 0.50, 95 %-CI 0.300 - 0.704, percentage of agreement = 70.0 %). The level of agreement for all 10 simple rules features varied greatly (kappa index range: -0.08 - 0.74, percentage of agreement 66 - 94 %). Conclusion: Although simple rules are useful to distinguish benign from malignant adnexal masses, they are not that simple for untrained examiners. Training with both IOTA terminology and simple rules is necessary before simple rules can be introduced into guidelines and daily clinical practice.
MeSH term(s)	Adnexal Diseases/diagnostic imaging ; Cohort Studies ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms/diagnostic imaging ; Prospective Studies ; Sensitivity and Specificity ; Terminology as Topic
Language	English
Publishing date	2017-08-23
Publishing country	Germany
Document type	Journal Article ; Multicenter Study
ZDB-ID	801064-x
ISSN	1438-8782 ; 1439-0914 ; 1431-4894 ; 0172-4614
ISSN (online)	1438-8782
ISSN	1439-0914 ; 1431-4894 ; 0172-4614
DOI	10.1055/s-0043-113819
Database	MEDical Literature Analysis and Retrieval System OnLINE

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