ObjectivesThe aim of this study was to evaluate the impact of micrometastasis and isolated tumor cells on disease recurrence in patients with early-stage cervical cancer.MethodsWe included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1 with lymphvascular space invasion, stage IA2, and IB1 who participated in the SENTICOL1 trial. A centralized histologic analysis with re-reading and ultrastaging was performed 3 months after surgery and treatment was not impacted by findings from our study. Patients were followed for 3 years and outcomes were compared according to prognostic factors.ResultsA total of 139 patients were included and 13 recurrences were found. There were two recurrences in patients with positive sentinel lymph node (SLN) (one macrometastases and one micrometastases) and 11 recurrences in patients with negative lymph nodes (sentinel or non-sentinel). Among patients with positive SLN for micrometastases there was only one recurrence. No patient with isolated tumor cells on their lymph nodes experienced a recurrence. There was a significant decrease in disease-free survival in patients aged >50 years (p = 0.01).ConclusionEvidence of micrometastasis or isolated tumor cells in the SLN of untreated patients with early cervical cancer in the SENTICOL1 trial did not impact progression-free survival.

After reading this article, the reader should be able to list clinical disorders related to mutations in the follicle stimulating hormone receptor (FSHR) gene, explain the principles behind the study of FSHR mutations, and state possible future applications of knowledge of mutations in the FSHR gene in reproductive medicine.

Objective Herein we analyzed FSH-R polymorphism at position 307 aiming (a) to assess the prevalence of the three allelic variants (Ala307Ala, Ala307Thr and Thr307Thr) in relation to the type of ovary and (b) to clarify if the allelic variant could influence the responsiveness to exogenous FSH. Study design We prospectively studied a group of 106 Italian women undergoing in vitro fertilization (IVF), among which 40 were subjects with polycystic ovary syndrome (PCOS) and 66 were normo-ovulatory women with a normal ovarian morphology at transvaginal ultrasound. DNA extraction, denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing were used to detect the FSH-R 307 polymorphic genotype and the whole exon 10 was analyzed. Results The heterozygote variant Ala307Thr was significantly more frequent than the homozygote variants in women with PCOS, whereas in normo-ovulatory women with normal ovary the three allelic variants had a comparable prevalence. Women bearing the Ala307Thr variant showed a higher ovarian responsiveness to exogenous FSH than normo-ovulatory subjects. Conclusions The heterozygote FSH-R polymorphism Ala307Thr is significantly more frequent in women with PCOS than in normo-ovulatory subjects and is more frequently associated with a higher ovarian responsiveness to exogenous FSH.

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Background: With the development of the sentinel node technique in early-stage cervical cancer, it is imperative to define the clinical significance of micrometastases (MICs) and isolated tumor cells (ITCs). Methods: We included all patients who participated in the Senticol 1 and Senticol 2 studies. We analyzed the factors associated with the presence of low-volume metastasis, the oncological outcomes of patients with MIC and ITC and the correlation of recurrences and risk factors. Results: Twenty-four patients (7.5%) had low-volume metastasis. The risk factors associated with the presence of low-volume metastasis were a higher stage (p = 0.02) and major stromal invasion (p = 0.01) in the univariate analysis. The maximum specificity and sensitivity were found at a cutoff of 8 mm of stromal invasion. In multivariate analysis, the higher stage (p = 0.02) and the positive lymphovascular space invasion (p = 0.02) were significantly associated with the MIC and ITC. Patients with low-volume metastasis had similar disease-free survival (DFS) (92.7%) to node-negative patients (93.6%). The addition of adjuvant treatment in presence of low-volume metastasis did not modify the DFS. Conclusions: These results confirm our previous analysis of Senticol 1: the presence of low-volume metastasis did not decrease the DFS in early-stage cervical cancer patients.

Background: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. Methods: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. Results: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4–127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). Conclusions: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment.

Ovarian hyperstimulation syndrome (OHSS) is rather frequent (1-5%) in women submitted to superovulation with gonadotropins for in vitro fertilisation (IVF), whereas it is very rare in case of spontaneous ovulation. Spontaneous OHSS (sOHSS) was previously described to be associated to hydatiform mole, multiple conception, hypothyroidism in pregnancy. It may also depend on activating mutations of the FSH receptor (FSHR) gene that cause ovarian hyper-responsiveness to circulating FSH or even cross-responsiveness of FSHR to hormones having a structure similar to FSH, such as hCG or TSH. We report, herein, a case of sOHSS in a woman who conceived spontaneously. We checked the presence of all possible factors that could explain the onset of the syndrome, and we evidenced hypothyroidism and abnormally elevated hCG levels in the second trimester of pregnancy. The thorough molecular biology study of FSHR gene did not detect exonic mutations, but revealed the presence of intronic mutations whose role in the onset of sOHSS is still uncertain.

Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I and II—from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. Results: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86–0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. Conclusion: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping.