SUrgical Access and Pattern of Recurrence of Endometrial Cancer: The SUPeR Study, a Multicenter Retrospective Observational Study.

STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.

Successful laparoscopic surgical removal of a caesarean scar pregnancy (CSP) using temporary uterine artery ligation.

STUDY OBJECTIVE: To demonstrate a laparoscopic technique to remove a scar pregnancy. DESIGN: Stepwise demonstration of the surgical technique. SETTING: Santa Croce and Carle Hospital, Cuneo. INTERVENTION: Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial-pregnancy interface. (4) Double layer suture on the anterior uterine wall. CONCLUSION: Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively.

Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review.

Nowadays, the optimal management of patients with cervical cancers measuring 2-4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients.

Intraoperative Ultrasound for Bowel Deep Infiltrating Endometriosis: A Preliminary Report.

The decision to perform either conservative surgery or segmental bowel resection for bowel deep infiltrating endometriosis (DIE) is made intraoperatively, after a preoperative assessment, based on the nodule's features. We introduce a technique to evaluate DIE bowel nodules using laparoscopic intraoperative ultrasound (US) during laparoscopic radical treatment of 9 cases of DIE invading the bowel. Once the bowel lesion was isolated, an intraoperative 12-4-MHz US transducer was placed on the surface of the nodules to study their US features and to gain measurements. Deep infiltrating endometriosis nodules appear at intraoperative US as hypoechoic elliptical lesions with a clear definition of margins and the depth of infiltration of the rectal wall.

Traditional McCall culdoplasty compared to a modified McCall technique with double ligament suspension: anatomical and clinical outcomes.

INTRODUCTION AND HYPOTHESIS: This study compared anatomical and clinical outcomes of traditional McCall culdoplasty versus a modified McCall technique with double ligament suspension (DLS). METHODS: This retrospective study presents outcomes of 68 patients who underwent vaginal hysterectomy and vaginal suspension for apical prolapse ≥ stage II according to the POP-Q score system, at, between January 2016 and February 2018. In 34 women vaginal cuff suspension was obtained with traditional McCall culdoplasty (McCall group), while in 34 women we performed a modified McCall, which consists of a double ligament suspension (DLS group), suspending the vaginal cuff to uterosacral ligaments and also to adnexal peduncles. Primary outcome was prolapse recurrence ≥ stage II according to the POP-Q system. Fisher's, Mann-Whitney U and Student's t tests were used for statistical analysis. RESULTS: There were no statistical differences among patients' preoperative characteristics, operative time, blood loss or postoperative complications. Follow-up mean duration was 23.2 ± 6.7 and 22.4 ± 8.7 months in the McCall and DLS group, respectively. Prolapse recurrence occurred in 11 (32.3%) women in the McCall group versus 2 (5.9%) women in the DLS group (p < 0.05): among them, 2 patients (5.9%) in the McCall group and 1 (2.9%) in the DLS group required further treatment. Total vaginal length was 6.1 ± 0.9 cm in the McCall group versus 6.9 ± 0.7 cm in the DLS group (p < 0.001). No statistical difference in quality of life assessment was observed. CONCLUSIONS: DLS group patients had better anatomical outcomes and lower recurrence rates than McCall group patients, without increasing operative time or complications. A prospective study with more cases is needed to confirm our data.

Simplified laparoscopic sacropexy avoiding deep vaginal dissection.

OBJECTIVE: To evaluate the safety and efficacy of a "simplified" laparoscopic sacropexy approach. METHODS: Data were retrospectively assessed from women with apical prolapse of stage 2 or higher who underwent "simplified" laparoscopic sacropexy between October 1, 2010, and May 31, 2017 at the St Anna Hospital, City of Health and Science, Torino, Italy. Patients were treated with the "simplified" laparoscopic sacropexy, where meshes were anchored solely to the vaginal apex, even in the presence of advanced multi-compartment vaginal prolapse. Data on prolapse stage and urogenital functions collected through clinical examinations, and questionnaires at baseline, 6 months, 12 months, and annually thereafter were examined. RESULTS: Overall, 121 women were included in the analysis; the mean follow-up was 33.2 months. Mean operative time was 135.1 minutes; there were no intraoperative visceral or vascular injuries. There was 1 (0.8%) patient who experienced recurrence, and 2 (1.7%) who experienced vaginal erosion. Both urogenital symptom scores (all P<0.05) and quality of life scores (all P<0.05) improved significantly. CONCLUSION: Adequate re-suspension of only the apex was sufficient to correct other vaginal compartments, even for women with preoperative multi-compartment prolapse higher than POP-Q stage 2. The "simplified" laparoscopic sacropexy was an efficacious intraoperative time-saving technique; it could reduce adverse events caused by deep vaginal dissection up to puborectal muscles and the bladder trigone.

In Vitro Human Placental Studies to Support Adenovirus-Mediated VEGF-DΔNΔC Maternal Gene Therapy for the Treatment of Severe Early-Onset Fetal Growth Restriction.

Severe fetal growth restriction (FGR) affects 1 in 500 pregnancies, is untreatable, and causes serious neonatal morbidity and death. Reduced uterine blood flow (UBF) is one cause. Transduction of uterine arteries in normal and FGR animal models using an adenovirus (Ad) encoding VEGF isoforms increases UBF and improves fetal growth in utero. Understanding potential adverse consequences of this therapy before first-in-woman clinical application is essential. The aims of this study were to determine whether Ad.VEGF-DΔNΔC (1) transfers across the human placental barrier and (2) affects human placental morphology, permeability and primary indicators of placental function, and trophoblast integrity. Villous explants from normal term human placentas were treated with Ad.VEGF-DΔNΔC (5 × 107-10 virus particles [vp]/mL), or virus formulation buffer (FB). Villous structural integrity (hematoxylin and eosin staining) and tissue accessibility (LacZ immunostaining) were determined. Markers of endocrine function (human chorionic gonadotropin [hCG] secretion) and cell death (lactate dehydrogenase [LDH] release) were assayed. Lobules from normal and FGR pregnancies underwent ex vivo dual perfusion with exposure to 5 × 1010 vp/mL Ad.VEGF-DΔNΔC or FB. Perfusion resistance, para-cellular permeability, hCG, alkaline phosphatase, and LDH release were measured. Ad.VEGF-DΔNΔC transfer across the placental barrier was assessed by quantitative polymerase chain reaction in DNA extracted from fetal-side venous perfusate, and by immunohistochemistry in fixed tissue. Villous explant structural integrity and hCG secretion was maintained at all Ad.VEGF-DΔNΔC doses. Ad.VEGF-DΔNΔC perfusion revealed no effect on placental permeability, fetoplacental vascular resistance, hCG secretion, or alkaline phosphatase release, but there was a minor elevation in maternal-side LDH release. Viral vector tissue access in both explant and perfused models was minimal, and the vector was rarely detected in the fetal venous perfusate and at low titer. Ad.VEGF-DΔNΔC did not markedly affect human placental integrity and function in vitro. There was limited tissue access and transfer of vector across the placental barrier. Except for a minor elevation in LDH release, these test data did not reveal any toxic effects of Ad.VEGF-DΔNΔC on the human placenta.

Cervical pessary for preventing preterm birth in twin pregnancies with short cervical length: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in twin pregnancies with an asymptomatic transvaginal ultrasound cervical length (TVU CL) in the second trimester. METHODS: We performed a meta-analysis including all randomized clinical trials (RCTs) comparing the use of cervical pessary (i.e. intervention group) with expectant management (i.e. control group). The primary outcome was incidence of SPTB <34 weeks. RESULTS: Three trials, including 481 twin pregnancies with short cervix, were analyzed. Two RCTs defined short cervix as TVU CL ≤25 mm and one as TVU CL ≤38 mm. Pessary was not associated with prevention of SPTB, and the mean gestational age at delivery and the mean latency were similar in the pessary group compared to the control group. Moreover, no benefits were noticed in neonatal outcomes. CONCLUSIONS: Use of the Arabin pessary in twin pregnancies with short TVU CL at 16-24 weeks does not prevent SPTB or improve perinatal outcome.

Pre-eclampsia or chronic kidney disease? The flow hypothesis.

BACKGROUND: Chronic kidney disease (CKD) and pre-eclampsia (PE) occur in 3-5% of pregnancies. They often share hypertension and proteinuria and a differential diagnosis may be impossible. However, in PE, the pathogenesis is related to abnormal placentation, which can be detected by abnormal uterine and umbilical Doppler flow velocities, while in CKD, an intrinsic kidney disease is present. We hypothesize that Doppler studies can help to differentiate PE from CKD, as the flow velocities are altered in PE and normal in CKD. METHODS: We retrospectively selected patients who were followed in our Materno-Foetal Unit (2005-10) and had at least one flow measurement in our setting. CKD patients were included in the presence of proteinuria (≥ 300 mg/day) and hypertension, mimicking PE. The clinical charts were reviewed by the same operators; the clinical diagnoses were taken as reference. Three flow patterns were considered: alteration of both flow velocity waveforms (FVWs) (uterine and umbilical arteries), hypothesized as predictive of PE; normal FVWs at both levels, hypothesized as predictive of CKD; altered FVW in either artery, considered 'mixed'. Uterine FVWs were considered pathological according to the classical cut-point (RI > 0.58). Umbilical flows were evaluated according to standards adjusted for gestational age. Statistical analysis was performed in SPSS. RESULTS: The analysis included 61 cases. The presence of normal FVWs was significantly associated with the diagnosis of CKD (P = 0.0018). Conversely, the presence of both altered flows was significantly associated with PE (P = 0.0233). CONCLUSIONS: In the presence of proteinuria and hypertension, normal flows suggest CKD altered flows PE. Prospective studies are needed to refine this hypothesis based on the first Doppler criteria supporting the differential diagnosis between CKD and PE.

Thymic volume in healthy, small for gestational age and growth restricted fetuses.

OBJECTIVE: The aim of this study was to verify the hypothesis that a difference in thymic size exists between small for gestational age (SGA) fetuses, likely constitutional, and intrauterine growth restricted (IUGR) fetuses because of placental causes. METHODS: We studied 27 SGA and 36 control fetuses. SGA was defined as fetal abdominal circumference (AC) and birthweight <10th percentile for gestational age. We defined as constitutional SGA those with normal uterine and umbilical artery Doppler flow velocity waveforms (FVW), and as IUGR those with abnormal uterine FVW. IUGR were further divided based on normal or abnormal umbilical FVW. Fetal thymic volume (TV) was acquired by three-dimensional ultrasound and reconstructed with virtual organ computer-aided analysis. To correct for the influence of fetal size on thymic dimension, TV/AC ratio was calculated. RESULTS: Controls presented a higher TV/AC compared with each group of SGA (p < 0.001). TV/AC was significantly lower in IUGR with abnormal umbilical FVW compared with both constitutional SGA (p = 0.01) and IUGR with normal umbilical FVW (p = 0.01). CONCLUSIONS: The differences in TV/AC between constitutional SGA and IUGR with abnormal umbilical FVW suggest that, in the latter, a specific 'trigger' might compromise trophoblastic invasion and thymic development; however, some kind of alteration of the immune system might occur in all SGA fetuses.