Impact of fetal umbilical cord blood CD34+ cells on breast cancer cell lines: a mechanism of fetal microchimerism?

Introduction Fetal microchimerism could be involved in the regulation of breast cancer oncogenesis. CD34+ cells could be of a particular interest as up to 12% of the CD34+ population in maternal blood are of fetal origin. The aim of this research was to analyze the impact of umbilical cord blood (UCB) CD34+ on MCF-7 and MDA-MB-231 breast cancer cell lines, in order to uncover novel biological mechanisms and suggest novel treatment options for breast cancer. Methods UCB CD34+ cells were obtained from healthy women at full-term delivery. Direct cultures were grown with MCF-7 and MDA-MB-231 cells. Proliferation, migration, invasion, and transcriptomic analysis of breast cancer cells were compared between cultures exposed and non-exposed to UCB CD34+ cells. Interactions between UCB CD34+ and breast cancer cells were analyzed under fluorescent microscopy. Functional analyses were generated with QIAGEN's Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Results Direct contact between UCB CD34+ and breast cancer cell lines induced a reduction in the proliferative capacities of MCF-7 and MDA-MB-231 and diminished the migration abilities of MDA-MB-231 cells. In 3D co-culture, UCB CD34+ cells were attracted by tumor spheroids and incorporated into tumor cells. These cell-to-cell interactions were responsible for transcriptome modifications coherent with observed functional modifications. Among the cytokines secreted by UCB CD34+, IFN was identified as a potential upstream regulator responsible for the molecular modifications observed in transcriptomic analysis of MCF-7 breast cancer cells exposed to UCB CD34+ cells, as was IL-17A in MDA-MB-231 cells. Conclusion Direct cell-to-cell contact induced functional modifications in breast cancer cells. Interactions between UCB CD34+ and breast cancer cells could induce cell fusion and signal transmission via cytokines. Further analysis of direct cell-to-cell interactions should be performed at a molecular level to further understand the potential role of fetal CD34+ cells in breast cancer.

Outcomes of discoid excision and segmental resection for colorectal endometriosis: robotic versus conventional laparoscopy.

Surgery for deep endometriosis with colorectal involvement is an option after medical treatment failure. Over the past decade, robotic laparoscopy has emerged as an alternative to conventional laparoscopy. We aimed to evaluate surgical outcomes of robotic versus conventional laparoscopy for discoid excision and segmental resection. From 2019 to 2023, we conducted a retrospective cohort study of 152 consecutive patients with colorectal endometriosis who underwent robotic or conventional laparoscopy for discoid excision and colorectal resection. Ninety of the patients 152 underwent robotic surgery and 62 conventional laparoscopy. The mean total surgical room occupancy and operating times were longer in the robotic group: 270 ± 81 min vs 240 ± 79 min, p = 0.010, and 216 ± 78 min vs 190 ± 76, p = 0.027, respectively. The mean intraoperative blood loss, and the incidence of intra- and postoperative complications (according to Clavien-Dindo classification) were similar in the two groups. The mean hospital stay was greater after conventional laparoscopy (8 ± 5 vs 7 ± 4 days; p = 0.03), and the rate of persistent voiding dysfunction was higher in the conventional group (9/11, 25% vs 2/11, 5%; p = 0.01). A higher incidence of persistent voiding dysfunction was also observed after segmental resection by conventional laparoscopy (25% vs 4.8%, p = 0.01). Our results support the use of robotic surgery as an alternative to conventional laparoscopy for discoid excision and segmental resection for colorectal endometriosis.

To drain or not to drain: A propensity score analysis of abdominal drainage after colorectal surgery for endometriosis.

AIM: To assess the benefit of prophylactic abdominal drainage (AD) after colorectal surgery for endometriosis. METHODS: We conducted a retrospective study of 215 patients who underwent colorectal surgery for endometriosis using a mini-invasive approach in our center from February 2019 to July 2023. A propensity score matched (PSM) analysis (1:1 ratio) identified two groups of patients with similar characteristics. Postoperative outcomes were then compared. RESULTS: In the unmatched cohort, 151 patients (70 %) had AD at the end of surgery and 64 (30 %) did not. Clinical characteristics and surgical procedures were comparable between the groups after PSM. After PSM, AD was associated with a longer hospital stay (p < 0.001) and a greater number of postoperative complications (p = 0.03). There were no differences for readmission, repeat surgery, or severe postoperative complications. CONCLUSION: In this retrospective cohort of patients undergoing colorectal resection for endometriosis using a mini-invasive approach, prophylactic AD was not found to be beneficial.

Exploring uterine involvement in hysterectomy samples following conization for adenocarcinoma in situ of the uterine cervix: Insights from a multicenter study by the FRANCOGYN group.

BACKGROUND: Adenocarcinoma in situ (AIS) of the cervix can progress to invasive adenocarcinoma. While hysterectomy is standard, conservative management may be considered for women desiring future pregnancies. This study aimed to determine the prevalence of residual disease in hysterectomy specimens following excisional therapy with clear margins for AIS. METHODS: A retrospective FRANCOGYN cohort study was conducted on patients who underwent a hysterectomy after conization with clear margins for AIS between 2008 and 2021. The primary goal was to assess the prevalence of residual disease in the hysterectomy specimens. Secondary objectives included identifying preoperative predictors of residual disease and comparing recurrence rates between patients with and without residual disease. RESULTS: Of 53 hysterectomies performed after conization with negative margins for AIS, 20.8% (11/53) showed residual disease in the final histology. None of the patients had invasive cancer. In the residual disease group, 18% (2/11) had persistent CIN 3, and 82% (9/11) had persistent AIS. These patients tended to have higher BMI (27.5 kg/m² vs. 23.6 kg/m², p=0.04) and shorter endocervical margins (2mm vs. 5mm, p=0.01). No recurrences were observed during follow-up. CONCLUSION: Despite clear margins on the initial conization for AIS, 20% of patients had residual disease in their hysterectomy samples, though no invasive cancer was found. A hysterectomy should be considered after completing childbearing, even if initial margins are clear.

Changes in hospital consumption of opioid and non-opioid analgesics after colorectal endometriosis surgery.

The aim of this study was to analyze postoperative consumption of analgesics during hospitalization following colorectal surgery for endometriosis. We conducted a retrospective study at Tenon University Hospital, Paris, France from February 2019 to December 2021. One hundred sixty-two patients underwent colorectal surgery: eighty-nine (55%) by robotic and seventy-three (45%) by conventional laparoscopy. The type of procedure had an impact on acetaminophen and nefopam consumed per day: consumption for colorectal shaving, discoid resection, and segmental resection was, respectively, 2(0.5), 2.1(0.6), 2.4(0.6) g/day (p = 10-3), and 25(7), 30(14), 31(11) mg/day (p = 0.03). The total amount of tramadol consumed was greater following robotic surgery compared with conventional laparoscopy (322(222) mg vs 242(292) mg, p = 0.04). We observed a switch in analgesic consumption over the years: tramadol was used by 70% of patients in 2019 but only by 7.1% in 2021 (p < 10-3); conversely, ketoprofen was not used in 2019, but was consumed by 57% of patients in 2021 (p < 10-3). A history of abdominal surgery (OR = 0.37 (0.16-0.78, p = 0.011) and having surgery in 2020 rather than in 2019 (OR = 0.10 (0.04-0.24, p < 10-3)) and in 2021 than in 2019 (OR = 0.08 (0.03-0.20, p < 10-3)) were the only variables independently associated with the risk of opioid use. We found that neither clinical characteristics nor intraoperative findings had an impact on opioid consumption in this setting, and that it was possible to rapidly modify in-hospital analgesic consumption modalities by significantly reducing opioid consumption in favor of NSAIDS or nefopam.

Identification of patients with ductal carcinoma in situ at high risk of postoperative upstaging: A comprehensive review and an external (un)validation of predictive models developed.

BACKGROUND: Between 8% and 56% of pure ductal carcinoma in situ are upstaged to microinvasive or invasive carcinoma on definitive pathological examination. The first objective of this study was to perform a comprehensive review of the literature on factors associated with increased risk of pre-operative underestimation. The second objective was to perform an external validation of the predictive models developed to enable their use in daily practice if relevant. MATERIALS AND METHODS: A literature search using Medline was undertaken. For each model selected, external validation within the study cohort was undertaken. The study cohort consisted of patients with histologically proven ductal carcinoma in situ who underwent surgical treatment at a French referral centre for cancer treatment between January 2007 and November 2018. RESULTS: Two hundred and thirteen articles were identified; of these, 34 articles focused on factors associated with pre-operative underestimation of invasive carcinoma, 11 studies were identified as predictive models, and three studies were selected for external validation within the study cohort. Four hundred and eighty-eight eligible patients were identified in the study cohort, with an underestimation rate of 9.2%. The Jakub nomogram concordance index was 0.45 [95% confidence interval (CI) 0.39-0.51], the Park nomogram concordance index was 0.57 (95% CI 0.48-0.55), and the Coufal nomogram concordance index was 0.52 (95% CI 0.48-0.55). CONCLUSION: While the literature is rich on this topic, this review clearly highlights the lack of consensus regarding parameters associated with underestimation. It was not possible to validate previously published models for use in daily practice.

Comparison of robot-assisted and conventional laparoscopy for colorectal surgery for endometriosis: A prospective cohort study.

BACKGROUND: Our objective was to evaluate surgical outcomes of robotic compared to conventional laparoscopy for colorectal surgery for endometriosis. METHODS: We conducted a prospective cohort study comparing robotic to conventional laparoscopy for colorectal endometriosis during an 18-month period. We included 61 patients in the robotic group and 61 patients in the conventional laparoscopy group. RESULTS: Regardless of the colorectal procedure, no differences were found between the groups for complications, blood loss, re-hospitalisation, surgical revision. Robotic surgery was associated with a higher operating time (208 ± 90 min vs. 169 ± 81 min, p = 0.01) and a higher rate of healthy margins (91% vs. 76%; p = 0.01). For the patients undergoing discoid or segmental resections, robotic surgery was associated with a lower intraoperative complication rate (2% vs. 14%; p = 0.04) without difference in operating time or in postoperative complication rates, including voiding dysfunction. CONCLUSION: Our results suggest that the robotic route confer advantages for discoid and segmental resections.

[Place of PARP inhibitors in the treatment of endometrial and cervical cancers]. / Place des inhibiteurs de PARP dans le traitement des cancers de l'endomètre et du col de l'utérus.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

Comparison of robotic versus conventional laparoscopy for the treatment of colorectal endometriosis: Pilot study of an expert center.

INTRODUCTION: Surgical management of deep endometriosis with colorectal involvement remains an option after failure of medical treatments. Conventional laparoscopy is currently considered the standard approach for surgical treatment. Recently, assisted-robotic laparoscopy emerged as an alternative to conventional laparoscopy but with low evidence. METHODS: From March 2019 to September 2019, we conducted a prospective cohort study of 48 patients undergoing a surgical treatment for colorectal endometriosis (rectal shaving, discoid excision or segmental resection). The interventions were either performed by robotic or conventional laparoscopy. Patients' characteristics, operative and post-operative data were compared between the robotic and the conventional laparoscopic group. RESULTS: 48 patients were included, 25 in the conventional laparoscopy group and 23 in the robotic group. Patients' characteristics and operative findings were similar between the two groups, except for a trend in a higher incidence of associated surgical urinary or digestive procedures in the robotic group (p = 0.06). The mean total surgical room occupancy time and operating time were longer in the in the robotic group (281 ± 97 min vs 208 ± 85 min; p = 0.008) and (221 ± 94 min vs 163 ± 83 min (p = 0.03), respectively. The mean intra operative blood loss, the incidence of intra operative, post-operative complication (according to Clavien-Dindo classification) rates and voiding dysfunction were similar in the two groups. The rate of grade III complication was higher in the robotic group (13 % vs 0%) without reaching a significance (p = 0.17). The mean hospital stay was 8 ± 4.4 days in the robotic group and 6.5 ± 2.6 days in the conventional laparoscopy group (p = 0.18). CONCLUSION: Despite our initial experience in robotic surgery, our results support that robotic surgery is an adequate alternative to conventional laparoscopy for endometriosis colorectal resection.