Role of Adjuvant Radiotherapy in Patients with Cervical Cancer Undergoing Radical Hysterectomy.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine adjuvant RT's impact on survival in accordance with Sedlis criteria. Patients with early-stage cervical cancer undergoing radical hysterectomy between 2005 and 2022 at a single tertiary care institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analysed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. 121 patients were included in this retrospective study, of whom 48 (39.7%) received adjuvant RT due to the presence of unfavourable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p = 0.584) or disease-free survival (DFS) (p = 0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate risk factors.

MiR-151a: a robust endogenous control for normalizing small extracellular vesicle cargo in human cancer.

Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions. Their relevance as normalizers was tested in 26 additional human cancer cell lines from nine different tumor types undergoing chemotherapy or radiotherapy treatment. The validation cohorts were comprised of 242 prospective plasma and ascitic fluid samples from three different human tumor types. Variability and normalization properties were tested in comparison to miR-16, the most used control to normalize free-circulating miRNAs in plasma. Our results indicate that miR-151a is consistently represented in small extracellular vesicles with minimal variability compared to miR-16, providing a novel normalizer to measure small extracellular vesicle miRNA content that will benefit liquid biopsy in cancer patients.

Impact of the Covid-19 pandemic on the management of gynecologic cancer: a Spanish survey. Observational, multicenter study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons' perceptions regarding the management of gynecologic cancers". METHODS: Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain. RESULTS: A total of 75 gynecologic oncologists completed the online survey. Of these, 93.2% (69) reported working in public hospitals and 62.5% (45) in tertiary care hospitals. 97.3% (71) were affiliated with hospitals treating patients infected with SARS-CoV-2. 85.1% (63) of the respondents expressed concern about the SARS-CoV-2 pandemic and 52.1% (38) indicated that the pandemic impacted the diagnostic and therapeutic quality of care for oncology patients. SARS-CoV-2 nasopharyngeal swab PCR (Polymerase Chain Reaction) testing was always performed before surgical interventions by 97.3% (71), being considered a best practice in triage by 94.4% (68). 87.5% (63) reported no change in the type of surgical approach during the pandemic. 62.5% (45) experienced limitations in accessing special personal protective equipment for SARS-CoV-2. An impact on the follow-up of patients with gynecologic cancers due to the pandemic was reported by 70.4% (50). CONCLUSIONS: Most of the Spanish gynecologic oncologists who responded to our survey reported that the SARS-CoV-2 pandemic had affected their clinical practice. The primary measures implemented were an increase in telemedicine, restricting outpatient visits to high-risk or symptomatic patients and the use of SARS-CoV-2 screening prior to surgery. No major changes in the surgical approach or management of the treatment of ovarian, endometrial or cervical cancer during the pandemic were reported.

Personalized Sentinel Node Mapping in Endometrial Cancer by the Indocyanine Green Implementation as Single Tracer: A Case Control Study.

The main objective was to analyze the rate of bilateral sentinel lymph node (SLN) detection in endometrial cancer using indocyanine green (ICG) as a unique tracer compared to Technetium99 + ICG. As secondary objectives, we analyzed the drainage pattern and factors that might affect the oncological outcomes. A case-control ambispective study was carried out on consecutive patients at our center. Data on the SLN biopsy with ICG collected prospectively were compared to retrospective data on the use of a double-tracer technique including Technetium99 + ICG. In total, 194 patients were enrolled and assigned to both groups, in which the group with both tracers (controls) included 107 (54.9%) patients and the ICG-alone group (cases) included 87 (45.1%) patients. The rate of bilateral drainage was significantly higher in the ICG group (98.9% vs. 89.7%; p = 0.013). The median number of nodes retrieved was higher in the control group (three vs. two nodes; p < 0.01). We did not find survival differences associated with the tracer used (p = 0.85). We showed significant differences in terms of disease-free survival regarding the SLN location (p < 0.01), and obturator fossa retrieved nodes showed better prognosis compared to external iliac. The use of ICG as a single tracer for SLN detection in endometrial cancer patients seemed to obtain higher rates of bilateral detection with similar oncological outcomes.

One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA).

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 µm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/µL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation.

OBJECTIVE: To evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC). METHODS: A single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green. RESULTS: Eighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0-11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%. CONCLUSIONS: According to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.

Indocyanine Green versus Radiotracer with or without Blue Dye for Sentinel Lymph Node Mapping in Stage >IB1 Cervical Cancer (>2 cm).

STUDY OBJECTIVE: To compare sentinel lymph node (SLN) mapping in women with cervical cancer stage >IB1 (tumor size >2 cm) using indocyanine green (ICG) versus the standard technique using radioisotope technetium 99m radiocolloid (Tc99m) radiotracer with or without blue dye. DESIGN: European multicenter, retrospective observational study (Canadian Task Force classification II-2). SETTING: Four academic medical centers. PATIENTS: Ninety-five women with stage IB1 cervical cancer (>2 cm) who underwent SLN mapping with Tc99m with or without blue dye or ICG and radical hysterectomy. INTERVENTION: The detection rate and bilateral mapping rate were compared between ICG and standard Tc99m radiotracer with or without blue dye. Lymphadenectomy was performed, and the false-negative rate was assessed. MEASUREMENTS AND MAIN RESULTS: Forty-seven patients underwent SLN mapping with Tc99m with or without blue dye, and 48 did so with ICG. All patients underwent radical hysterectomy with or without bilateral salpingo-oophorectomy between 2008 and 2016. The overall detection rate of SLN mapping was 91.5% for Tc99m with or without blue dye and 100% for ICG. A 91.7% rate of bilateral migration was achieved for ICG, significantly higher than the 66% obtained with Tc99m with or without blue dye (p = .025). Nine of the 23 SLN-positive patients (39.1%) were diagnosed exclusively as a result of the ultrastaging used to identify micrometastases or isolated tumor cells only. CONCLUSIONS: In advanced cervical cancer (stage IB1 >2 cm), the detection rate and bilateral migration rate on real-time fluorescent SLN mapping were higher with ICG than with Tc99m radiotracer with or without blue dye. SLN mapping and ultrastaging can provide additional information for nodal staging in advanced cervical cancer. In this setting, ICG is a promising tool for mapping, appearing less affected by higher disease stage compared with traditional methods.

The role of surgery in advanced epithelial ovarian cancer.

Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer.

From Conventional Radiotracer Tc-99(m) with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach.

BACKGROUND: The credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99(m)) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG). METHODS: Data of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99(m) with BD. RESULTS: Overall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99(m) with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99(m) with BD; this difference was statistically significant (p < 0.0001). CONCLUSIONS: The fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

Laparoscopic Removal of an Intramyometrial Fetus After Uterine Curettage.

STUDY OBJECTIVE: To show the removal of an intramyometrial fetus after uterine curettage using laparoscopy as a safe surgical technique that offers excellent results and fewer complications than laparotomy. DESIGN: Presentation of the clinical case and step-by-step explanation of the technique. SETTINGS: Uterine curettage is a frequently performed gynecologic abortion procedure. Dilatation and curettage is considered to be a safe surgical technique, with a low percentage of complications. The most common is uterine perforation, with higher risks in advanced gestational age, retroflexed uterus, or uterine leiomyomas. INTERVENTIONS: After institutional review board approval, we present the case of a 29-year-old women referred to our hospital from another clinic with a suspected uterine perforation after an elective curettage for a 14-week pregnancy. She presented with moderate abdominal pain. Vaginal ultrasound revealed intramyometrial fetal parts on isthmus and right parametrium and minimal free fluid in the pouch of Douglas. A laparoscopic approach was chosen. After a complete revision of the abdominal cavity, the right paravesical space was dissected, confirming no right uterine artery or ureter injury. One cavity was objectified in the posterior leaf of the broad ligament related to a uterine perforation and containing fetal bone parts, which were removed. The myometrial defect and the peritoneum were closed with intracorporeal sutures. The removal of fetal parts was done with a surgical glove thimble. After the procedure, the patient was treated with clindamycin and gentamycin, with a satisfactory recovery. CONCLUSION: The presence of an intramyometrial fetus is not a common complication of curettage. The use of laparoscopy is feasible and offers excellent results and advantages versus laparotomy regarding its treatment.

Vaginal laparoscopically assisted radical trachelectomy in cervical clear cell adenocarcinoma.

Adenocarcinoma of the cervix is a rare condition that has shown an increase in incidence, especially in the 20- to 34-year-old group. Adenocarcinoma represents about 5-10% of all tumours in this area, and, among these, the clear cell type accounts for 4-9%. This type of tumour affects mainly postmenopausal women but also occurs in young women with a history of prenatal exposure to diethylstilbestrol (DES). The prognosis for adenocarcinoma of the cervix is poor overall and worse for the clear cell variety. This article discusses a case of clear cell adenocarcinoma of the cervix, unrelated to intrauterine exposure to DES, in a woman of childbearing age who wished to preserve her fertility and was therefore treated by radical vaginal trachelectomy and pelvic lymphadenectomy.

Prognostic factors associated with local recurrence in squamous cell carcinoma of the vulva.

OBJECTIVE: To analyze the prognostic factors related to the recurrence rate of vulvar cancer. METHODS: Retrospective study of 87 patients diagnosed of vulvar squamous cell carcinoma diagnosed at a tertiary hospital in Madrid between January 2000 and December 2010. RESULTS: The pathological mean tumor size was 35.1±22.8 mm, with stromal invasion of 7.7±6.6 mm. The mean free margin after surgery was 16.8±10.5 mm. Among all patients, 31 (35.6%) presented local recurrence (mean time 10 months; range, 1 to 114 months) and 7 (8%) had distant metastases (mean time, 5 months; range, 1 to 114 months). We found significant differences in the mean tumor size between patients who presented a relapse and those who did not (37.6±21.3 mm vs. 28.9±12.1 mm; p=0.05). Patients with free margins equal or less than 8 mm presented a relapse rate of 52.6% vs. 43.5% of those with free margin greater than 8 mm (p=0.50). However, with a cut-off of 15 mm, we observed a local recurrence rate of 55.6% vs. 34.5%, respectively (p=0.09). When the stromal invasion cut-off was >4 mm, local recurrence rate increased up to 52.9% compared to 37.5% when the stromal invasion was ≤4 mm (p=0.20). CONCLUSION: Tumor size, pathologic margin distance and stromal invasion seem to be the most important predictors of local vulvar recurrence. We consider the cut-off of 35 mm of tumor size, 15 mm tumor-free surgical margin and stromal invasion >4 mm, high risk predictors of local recurrence rate.