Abstract
Loss of epithelial polarity and gain in invasiveness by carcinoma cells are critical events in the aggressive progression of cancers and depend on phenotypic transition programs such as the ...epithelial-to-mesenchymal transition (EMT). Many studies have reported the aberrant expression of voltage-gated sodium channels (Na
V
) in carcinomas and specifically the Na
V
1.5 isoform, encoded by the
SCN5A
gene, in breast cancer. Na
V
1.5 activity, through an entry of sodium ions, in breast cancer cells is associated with increased invasiveness, but its participation to the EMT has to be clarified. In this study, we show that reducing the expression of Na
V
1.5 in highly aggressive human MDA-MB-231 breast cancer cells reverted the mesenchymal phenotype, reduced cancer cell invasiveness and the expression of the EMT-promoting transcription factor
SNAI1
. The heterologous expression of Na
V
1.5 in weakly invasive MCF-7 breast cancer cells induced their expression of both
SNAI1
and
ZEB1
and increased their invasive capacities. In MCF-7 cells the stimulation with the EMT-activator signal TGF-β1 increased the expression of
SCN5A
. Moreover, the reduction of the salt-inducible kinase 1 (SIK1) expression promoted Na
V
1.5-dependent invasiveness and expression of EMT-associated transcription factor SNAI1. Altogether, these results indicated a prominent role of SIK1 in regulating Na
V
1.5-dependent EMT and invasiveness.
Abstract Objectives The purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO ...classification. Methods Data of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test). Results Data from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5 months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients ( p < 0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), ( p < 0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), ( p < 0.001). Conclusions We report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.
Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the ...present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman’s ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients’ RFS was analyzed using Kaplan−Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to <0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.
SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is ...unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9–dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids.
Prolapse of the fallopian tube into the vaginal vault is a rarely reported complication that may occur after hysterectomy. Clinicians can miss the diagnosis of this disregarded complication when ...dealing with post-hysterectomy vaginal bleeding.
We performed a systematic review in order to describe the clinical presentation, therapeutic management and outcome of fallopian tube prolapse occurring after hysterectomy.
A systematic search of MEDLINE and EMBASE references from January 1980 to December 2010 was performed. We included articles that reported cases of fallopian tube prolapse after hysterectomy. Data from eligible studies were independently extracted onto standardized forms by two reviewers.
Twenty-eight articles including 51 cases of fallopian tube prolapse after hysterectomy were included in this systematic review. Clinical presentations included abdominal pain, dyspareunia, post- coital bleeding, and/or vaginal discharge. Two cases were asymptomatic and diagnosed at routine checkup. The surgical management reported comprised partial or total salpingectomy, with vaginal repair in some cases combined with oophorectomy using different approaches (vaginal approach, combined vaginal-laparoscopic approach, laparoscopic approach, or laparotomy). Six patients were initially treated by silver nitrate application without success.
This systematic review provided a precise summary of the clinical characteristics and treatment of patients presenting with fallopian tube prolapse following hysterectomy published in the past 30 years. We anticipate that these results will help inform current investigations and treatment.
Background
Borderline ovarian tumors (BOTs) are tumors with a favorable prognosis but whose management by consensus is essential to limit the risk of invasive recurrence. This study aimed to conduct ...an inventory of surgical practices for BOT in France and to evaluate the conformity of the treatment according to the current French guidelines.
Methods
This retrospective, multicenter cohort study included nine referral centers of France between January 2001 and December 2018. It analyzed all patients with serous and mucinous BOT who had undergone surgery. A peritoneal staging in accordance with the recommendations was defined by performance of a peritoneal cytology, an omentectomy, and at least one peritoneal biopsy.
Results
The study included 332 patients. A laparoscopy was performed in 79.5% of the cases. Treatment was conservative in 31.9% of the cases. The recurrence rate was significantly increased after conservative treatment (17.3% vs 3.1%;
p
< 0.001). Peritoneal cytology was performed for 95.5%, omentectomy for 83.1%, and at least one biopsy for 82.2% of the patients. The overall recurrence rate was 7.8%, and the recurrence was invasive in 1.2% of the cases. No link was found between the recurrence rate and the conformity of peritoneal staging. The overall rate of staging noncompliance was 22.9%.
Conclusion
The current standards for BOT management seem to be well applied.
Since the LACC study in 2018, the use of the uterine manipulator (UM) has been questioned in Oncological surgery. Nowadays, there are few data on UM use in patients eligible for minimally invasive ...surgery for endometrial cancer. Our objective was to evaluate the practices and modalities of UM use by French onco-gynecologic surgeons in the management of endometrial cancer.
We surveyed the practices of 3 French medical societies-affiliated onco-gynecological surgeons with a web questionnaire composed of 16 questions.
A total of 165 responses were collected. In the case of minimally invasive hysterectomy for endometrial cancer, the routine use of UM was 42.7%. Of the 40.9% of surgeons who never used UM, 83.6% justified it with the risk of tumor spillage. When UM was used, surgeons mentioned reducing operating time and reducing complications in 67.0% and 59.8% of cases respectively as its main advantages. UM was set up without laparoscopic control in 54.6% of cases. In 47.4% of cases, the medical student was in charge of UM instrumentation. Tubal obliteration at the beginning of the procedure was performed systematically in 35.4% of cases. For 63.5% of UM users, the adjuvant treatment could be modified in case of uterine perforation.
This survey confirms the heterogeneity of practices regarding the use of UM in endometrial cancer surgery. Prospective data on the benefit (reduction of surgical complications)/risk (impact on survival) balance are needed to recommend or not the use of this device.
The most appropriate management for patients with stage IV ovarian cancer remains unclear. Our objective was to understand the main determinants associated with survival and to discuss best surgical ...management.
Data of 1038 patients with confirmed ovarian cancer treated between 1996 and 2016 were extracted from maintained databases of 7 French referral gynecologic oncology institutions. Patients with stage IV diseases were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariable analysis, was used to account for the influence of multiple variables.
Two hundred and eight patients met our inclusion criteria: 65 (31.3%) never underwent debulking surgery, 52 (25%) underwent primary debulking surgery (PDS) and 91 (43.8%) neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS). Patients not operated had a significantly worse overall survival than patients that underwent PDS or NACT-IDS (p < 0.001). In multivariable analysis, three factors were independent predictors of survival: upfront surgery (HR 0.32 95% CI 0.14-0.71, p = 0.005), postoperative residual disease = 0 (HR 0.37 95% CI 0.18-0.75, p = 0.006) and association of Carboplatin and Paclitaxel regimen (HR 0.45 95% CI 0.25-0.80, p = 0.007).
Presence of distant metastases should not refrain surgeons from performing radical procedures, whenever the patient is able to tolerate. Maximal surgical efforts should be done to minimize residual disease as it is the main determinant of survival.
The aim of this study was to develop a new diagnostic tool to predict lymph node metastasis (LNM) in patients with advanced epithelial ovarian cancer undergoing primary cytoreductive surgery. The ...FRANCOGYN group's multicenter retrospective ovarian cancer cohort furnished the patient population on which we developed a logistic regression model. The prediction model equation enabled us to create LNM risk groups with simple lymphadenectomy decision rules associated with a user-friendly free interactive web application called shinyLNM. 277 patients from the FRANCOGYN cohort were included; 115 with no LNM and 162 with LNM. Three variables were independently and significantly (p<0.05) associated with LNM in multivariate analysis: pelvic and/or para-aortic LNM on CT and/or PET/CT (p<0.00), initial PCI greater than or equal to 10 and/or diaphragmatic carcinosis (p = 0.02), and initial CA125 greater than or equal to 500 (p = 0.02). The ROC-AUC of this prediction model after leave-one-out cross-validation was 0.72. There was no difference between the predicted and the observed probabilities of LNM (p = 0.09). Specificity for the group at high risk of LNM was 83.5%, the LR+ was 2.73, and the observed probability of LNM was 79.3%; sensitivity for the group at low-risk of LNM was 92.0%, the LR- was 0.24, and the observed probability of LNM was 25.0%. This new tool may prove useful for improving surgical planning and provide useful information for patients.
Patterns of distant metastatic failure of endometrial cancer (EC) by specific anatomic site are not well described in the literature. In this manuscript, we evaluated the metastatic patterns of EC ...cancer and analysed the potential distribution of metastatic disease in this malignancy.
A total of 1444 women with EC were identified. Of which we extracted women with locoregional and distant recurrence or with distant recurrence alone. Women were scored based on first site of metastasis: multiple versus one site: bone, brain, lung, liver or sus diaphragmatic lymph nodes.
110 women developed distant metastatic disease with (n = 37(33.6%)) or without (n = 73(66.4%)) locoregional recurrence, including 39 women with exclusive first site of metastatic disease and 34 women with multiple sites of metastatic disease. When considering all women, the most common exclusive first site of metastasis was lung (42.8%). The median time to develop distant metastases was shorter after the completion of treatment for exclusive brain metastatic disease compared with other sites of metastatic− disease (7 months vs, 9 for lung, 10 for liver, 19 for bone and 27 months for sus-diaphragmatic LN; P = 0.004). The rate of 3-year overall survival was higher in the sus-diaphragmatic LN metastase group (83.3% vs 50.6% for lung, 37.3% for bone, 16.7% for brain and 0% for liver; P = 0.0059).
The present study has demonstrated the site-specific patterns of metastases. These data support current clinical practice of screening for site-specific metastatic disease after initial treatment of early stage EC based on concerning women-specific signs or symptoms.
PDF
