Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Impact of pattern of recurrence on post-relapse survival according to surgical timing in patients with advanced ovarian cancer.

OBJECTIVE: Our study aimed to evaluate the association between timing of cytoreductive surgery and pattern of presentation of the first recurrence in patients with advanced ovarian cancer. We also aimed to assess the impact of the pattern of recurrence on post-relapse overall survival according to surgical timing. METHODS: This retrospective multicenter study evaluated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer. Patients had undergone either primary debulking surgery, early interval debulking surgery after 3-4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery after 6 cycles, with minimal or no residual disease, between January 2008 and December 2015. Survival analyses were conducted using the Log-rank test and the Cox model. Cumulative incidences of the different patterns of recurrence were estimated using a competing risks methodology. RESULTS: A total of 549 patients were included: 175 (31.9%) patients had primary, 224 (40.8%) early interval, and 150 (27.3%) delayed debulking surgery. The cumulative incidence of peritoneal recurrences at 2 years was higher with increasing neoadjuvant cycles (24.4%, 30.9% and 39.2%; p=0.019). For pleural or pulmonary recurrences, it was higher after early interval surgery (9.9%, 13.0% and 4.1%; p=0.022). Median post-relapse overall survival was 33.5 months (95% confidence interval (CI) (24.3 to 44.2)), 26.8 months (95% CI (22.8 to 32.6)), and 24.5 months (95% CI (18.6 to 29.4)) for primary, early interval, and delayed debulking surgery groups, respectively (p=0.025). The pattern of recurrence in a lymph node (hazard ratio (HR) 0.42, 95% CI (0.27 to 0.64)), delayed surgery (HR 1.53, 95% CI (1.11 to 2.13)) and time to first recurrence (HR 0.95, 95% CI (0.93 to 0.96)) were associated with post-relapse overall survival. For primary and early interval surgery, lymph node recurrences were associated with significantly longer post-relapse overall survival. CONCLUSIONS: The pattern of first recurrence was associated with timing of surgery, with peritoneal recurrences being more frequent with the increasing number of cycles of neoadjuvant chemotherapy. Lymph node recurrences were associated with better prognosis, having higher post-relapse overall survival. This improved prognosis of lymphatic recurrences was not observed in patients who underwent delayed surgery.

Endometrial adenocarcinoma recurring in the lung: impact of molecular profile and role of local therapies on prognosis.

OBJECTIVES: The objective of our study was to describe the characteristics of patients with endometrial cancer diagnosed with a first recurrence involving the lung, and to describe the prognostic role of the molecular profile. We also aimed to describe the prognostic outcomes after local treatment of recurrence (resection of lung metastases or stereotactic body radiation therapy) in a group of patients with isolated lung recurrence. METHODS: This was a retrospective, single-center study between June 1995 and July 2021. The study included patients diagnosed with a first recurrence of endometrial cancer involving the lung. We defined two groups of patients: patients with isolated lung recurrence (confined to the lung) and patients with multisystemic recurrence (in the lung and other locations). RESULTS: Among 1413 patients diagnosed with endometrial cancer in stage IA to IVA of the International Federation of Gynecology and Obstetrics (FIGO) 2009, 64 (4.5%) patients had a first recurrence involving the lung. Of these, 15 (39.1%) were of a non-specific molecular profile, 16 (25%) were p53-abnormal, 15 (23.4%) were mismatch-repair deficient, and 0% POLE-mutated. P53-abnormal patients had the shortest 3 year progression-free survival after recurrence and those with mismatch-repair deficient had the longest 3 year progression-free survival (14.3% (range; 1.6-40.3) and 47.6% (range; 9.1-79.5) respectively, p=0.001). We found no differences on overall survival after recurrence by molecular profile. Thirty-one of 64 (48.4%) patients had an isolated recurrence in the lung, and 16 (25%) patients received local treatment. When comparing patients with isolated lung recurrence, locally treated patients had a longer median progression-free survival than patients treated systemically (41.9 (range, 15.4-NA) vs 7.8 (range, 7.2-10.6) months respectively, p=0.029), a complete response rate of 80% for stereotactic body radiation therapy and a complete resection of 90.9% for surgery. CONCLUSION: Although few patients will benefit from local treatment (stereotactic body radiation therapy or resection) after a recurrence involving the lung, local therapies might be considered as an option in oligometastatic lung recurrences as they achieve high local control rates and better oncological outcomes than systemic treatment alone.

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). METHODS: A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. RESULTS: Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients' age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72-0.92). CONCLUSIONS: We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients' care.

Survival impact of histological response to neoadjuvant chemotherapy according to number of cycles in patients with advanced ovarian cancer.

OBJECTIVE: We sought to evaluate the impact of chemotherapy response score according to the number of cycles of neoadjuvant chemotherapy, on disease-free survival and overall survival, in patients with advanced epithelial ovarian cancer ineligible for primary debulking surgery. METHODS: This multicenter retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV epithelial ovarian cancer who underwent 3-4 or 6 cycles of a platinum and taxane-based neoadjuvant chemotherapy, followed by complete cytoreduction surgery (CC-0) or cytoreduction to minimal residual disease (CC-1), between January 2008 and December 2015, in four institutions. Disease-free survival and overall survival were assessed according to the histological response to chemotherapy defined by the validated chemotherapy response score. RESULTS: A total of 365 patients were included: 219 (60.0%) received 3-4 cycles of neoadjuvant chemotherapy, and 146 (40.0%) had 6 cycles of neoadjuvant chemotherapy before cytoreductive surgery. There were no significant differences in early relapses, disease-free survival, and overall survival according to the number of neoadjuvant chemotherapy cycles. However, regardless of the number cycles of neoadjuvant chemotherapy, persistent extensive histological disease (chemotherapy response score 1-2) was significantly associated with a higher peritoneal cancer index, minimal residual disease (CC-1), and early relapses. Median disease-free survival in patients with complete or near-complete response (score 3) was 28.3 months (95% CI 21.6 to 36.8), whereas it was 16.3 months in patients with chemotherapy response score 1-2 (95% CI 14.7 to 18.0, p<0.001). CONCLUSION: In our cohort, the number of neoadjuvant chemotherapy cycles was not associated with disease-free survival or overall survival. Chemotherapy response score 3 improved oncological outcome regardless of the number of neoadjuvant chemotherapy cycles.

Can We Reduce Overtreatment of Cervical High-Grade Squamous Intraepithelial Lesions?

OBJECTIVE: The aim was to evaluate the cytology, colposcopic, and pathological factors associated with the absence of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2-3 lesion on loop electrosurgical excision procedure (LEEP) specimens in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy and the risk of disease persistence/recurrence. MATERIALS AND METHODS: Two-center retrospective study of women undergoing LEEP for high-grade cervical disease between January 2014 and December 2019. Clinical, cytology, colposcopy, and pathology results were evaluated to identify independent predictive factors associated with CIN 1/negative LEEP results. Univariate and multivariate logistic regression models were performed. Follow-up data was evaluated to assess the risk of HSIL/CIN 2-3 persistence/recurrence. RESULTS: Six hundred thirty-nine of 801 women (79.8%) had high-grade cytology and 631 (78.8%) HSIL/CIN 2-3 biopsy. High-risk human papillomavirus test was positive in 98% of women. Loop electrosurgical excision procedure specimen showing CIN 1 or less was found in 27%-31%. Normal/low-grade colposcopy (odds ratio [OR] = 2.17, CI = 1.39-3.39, p = .001) and CIN 1/negative biopsy (OR = 3.25, CI = 2.12-4.99, p < .001) were predictors of negative/CIN 1 LEEP result in women with high-grade cytology. Normal/low-grade cytology (OR = 1.77, CI = 1.19-2.64, p = .005), normal/low-grade colposcopy (OR = 1.66, CI = 1.11-2.49, p = .013), and CIN 2 biopsy (OR = 2.75, CI = 1.73-4.39, p < .001) were predictors in women with HSIL/CIN 2-3 biopsy. Women with a negative/CIN 1 LEEP had lower recurrence/persistence than those with confirmed HSIL/CIN 2-3(1 vs 31, p = .002). Positive endocervical margin (OR = 2.85, CI = 1.10-7.36, p = .03) and high-risk human papillomavirus persistence (OR = 41.3, CI = 16-106.7, p < .01) were predictors of HSIL/CIN 2-3 persistence/recurrence. CONCLUSIONS: A CIN 1/negative LEEP specimen in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy is associated with negative/low-grade cytology, normal/low-grade colposcopic findings and CIN 2 biopsy result before treatment. The HSIL/CIN 2-3 disease persistence/recurrence is low when LEEP specimen does not confirm HSIL/CIN 2-3.

Surgical complications comparing extraperitoneal vs transperitoneal laparoscopic aortic staging in early stage ovarian and endometrial cancer.

OBJECTIVE: To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. METHODS: Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010-2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. RESULTS: There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs, 14 [10-19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. CONCLUSIONS: The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov.identifier: NCT02676726.

M-TRAP: Safety and performance of metastatic tumor cell trap device in advanced ovarian cancer patients.

OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.

Clinical Challenges in Managing Cervical Intraepithelial Neoplasia 2: A Report From a Cross-sectional Survey.

OBJECTIVES: The aims of the study were to determine the management strategies offered to women with cervical intraepithelial neoplasia 2 (CIN 2) and the attitude of colposcopists toward its histological diagnosis and to identify the criteria used to select women for conservative management. METHODS: Colposcopists working in Spain were invited to participate in an online questionnaire via the Spanish Gynecology and Colposcopy Societies. The survey included 42 questions covering the 3 objectives of the study. One hundred eighty-two colposcopists representing all autonomous regions in Spain responded. The response rate was 26.2%, considering the total number of members. RESULTS: Most colposcopists offer conservative management in selected cases (153/182). The preferred follow-up interval is 6 months (65%), followed by 3-4 months (30%). Observation was considered no longer appropriate after 24 months (29.5%) and 12 months (26.3%), and 24.3% expressed that it depended on women's plan to conceive. During conservative management, 93.9% always perform a cytology, 62.7% human papillomavirus testing, 96.8% colposcopy, 47.9% cervical biopsy, and 28.1% endocervical curettage. Forty-five percent consider that CIN 2 merely represents a misclassified CIN 1 or CIN 3, whereas 46.2% think that CIN 2 lesions are unlikely to regress. Most respondents considered that age older than 40 years (81.3%), human papillomavirus 16 infection (62.1%), HIV infection (76.8%), positive p16 immunostaining (60.2%), a large lesion occupying more than 50% of the cervix (87%), endocervical involvement (91.6%), and previous treatment for CIN 2-3 (77%) are contraindications for conservative management. CONCLUSIONS: Management of CIN 2 remains challenging for colposcopists, and a lack of consensus still exists in clinical practice. A better understanding of the natural history of CIN 2 and its clinical outcomes is still necessary to guide clinicians in its management.

Technetium-99m-indocyanine green versus technetium-99m-methylene blue for sentinel lymph node biopsy in early-stage endometrial cancer.

INTRODUCTION: The low accuracy of pre-operative imaging techniques for prediction of nodal status strengthens the relevance of sentinel lymph node (SLN) biopsy in endometrial cancer, although the optimal method for its detection is still under investigation. The increasing use of indocyanine green (ICG) has aroused concern about its enhanced visualization of lymphatic channels, which could lead to a specimen that is thought to be nodal tissue not subsequently yielding a lymph node on pathologic analysis ('empty node packet'). Our main objective was to compare the overall and bilateral detection rates for SLN biopsy using two combined techniques: technetium-99m-ICG (Tc-99m-ICG) versus technetium-99m-methylene blue (Tc-99m-MB). Our secondary aim was to compare the 'empty node packet' rates between the two cohorts. METHODS: A prospective, non-randomized, single-center trial including patients diagnosed with endometrial cancer (any grade or histology) in pre-operative early stage, and operated on between February 2017 and July 2019. All tracers were injected intracervically. Pelvic and aortic lymphadenectomy were performed on patients at intermediate or high risk of recurrence pre-operatively. All SLNs were sent for intra-operative frozen section and afterwards processed following an ultrastaging protocol. RESULTS: Eighty-four patients were included, 58% (n=49) in the Tc-99m-MB group and 42% (n=35) in the Tc-99m-ICG group. Overall detection rate was 93% and was not statistically different between the two groups. A better bilateral detection rate was observed among Tc-99m-ICG patients (69% vs 41%, p=0.012). The 'empty node packet' rate was 4% in the Tc-99m-ICG cohort and 0% in the Tc-99m-MB cohort (p=0.032). DISCUSSION: Tc-99m-ICG is a feasible, safe technique for SLN biopsy in early-stage endometrial cancer, and appears to be superior in terms of bilateral detection to Tc-99m-MB. The addition of Tc-99m to ICG could decrease the rate of 'empty node packets' and better define the anatomic location of SLNs in patients with endometrial cancer.

Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study.

OBJECTIVES: The human papilloma virus (HPV) test is recommended in the posttreatment follow-up of cervical intraepithelial neoplasia. The aim of the study was to assess whether the intraoperative HPV (IOP-HPV) test had a similar diagnostic accuracy that HPV test performed at 6 months to predict high-grade squamous intraepithelial lesion (HSIL) recurrence. MATERIALS AND METHODS: In a prospective cohort study, 304 women diagnosed with HSIL by biopsy and/or endocervical curettage before treatment and/or confirmation in the histological specimen were included. Immediately after surgery, HPV testing was performed. This test was compared with the test at 6 months and other predictors of recurrence. Patients were followed for 24 months. An economic analysis was performed to compare the costs of IOP-HPV and HPV test at 6 months. RESULTS: Recurrence rate of HSIL was 6.2% (19 patients). The diagnostic accuracy of the IOP-HPV test to predict HSIL recurrence at 24 months was similar to the HPV test at 6 months, with comparative sensitivities of 100% versus 86.7%, specificities of 82.0% versus 77.9%, positive predictive values of 27.1% versus 18.1%, and negative predictive values of 100% versus 99.0%. Direct economic saving per high-grade intraepithelial lesion patient was 172.8 &OV0556;. CONCLUSIONS: The HPV test performed after loop electrosurgical resection procedure predicted recurrence of HSIL at 24 months with a similar diagnostic accuracy than the HPV test at 6 months. The use of the IOP-HPV test in the management of HSIL will allow early detection of the risk of recurrent disease and to save costs because of potential suppression of the need of HPV and follow-up controls at 6 months.

Radical Hysterectomy: Efficacy and Safety in the Dawn of Minimally Invasive Techniques.

STUDY OBJECTIVE: To analyze the effect that the introduction of minimally invasive procedures has had on surgical and oncologic outcomes when compared with conventional open radical hysterectomy (ORH) in a national reference cancer after 17 years of experience in radical hysterectomy. DESIGN: A prospective controlled study (Canadian Task Force classification II-2). SETTING: A university teaching hospital. PATIENTS: All patients who underwent radical hysterectomy as primary treatment for cervical cancer in our institution between May 1999 and June 2016, with a total of 188 patients. INTERVENTIONS: Patients underwent ORH or minimally invasive surgery (MIS) (i.e., laparoscopic or robotically assisted radical hysterectomy). MEASUREMENTS AND MAIN RESULTS: Seventy-six patients underwent ORH, 90 laparoscopic radical hysterectomy, and 22 robotically assisted radical hysterectomy. Blood loss and hospital stay were inferior in the MIS group (p <.0001). The laparotomic group presented shorter operation times (p = .0001). With a median follow-up of 112.4 months, a total of 156 patients (83%) were alive and free of disease at the time of the data analysis. Overall survival was higher in the MIS group when compared with the ORH group (91 vs 78.9, p = .026). There were no differences regarding recurrence rates between the surgical approaches. CONCLUSION: With 1 of the largest follow-up periods in the literature, this study provides added evidence that MIS could become the preferable surgical approach for early-stage cervical cancer since it appears to reduce morbidity without affecting oncologic results.

Impact of Laparoscopy to Assess Resectability in Stage IIIC Epithelial Ovarian, Tubal and Peritoneal Cancer Patients.

AIMS: To evaluate overall survival (OS) and progression-free survival (PFS) in patients with stage IIIC epithelial ovarian, tubal and peritoneal cancer (EOC) who underwent a laparoscopy to assess surgical resectability prior to Primary Debulking Surgery (PDS) or Interval Debulking Surgery (IDS). METHODS: Retrospective cohort study that included all women with stage IIIC EOC treated at our center between 2000 and 2010. Patients were classified in groups: PDS, neoadjuvant chemotherapy (NACT) with IDS, NACT without IDS; and then sub-classified based on residual tumor (RT). A laparoscopy to assess resectability was performed before PDS and IDS. RESULTS: Among 111 patients included, 66 underwent PDS, and 45 were treated with NACT, 80% of them receiving subsequent IDS. OS was 75.6 months in the PDS group, and 52.8 months for IDS group (p = 0.100); the PFS was 30 months and 19.2 months respectively (p = 0.049). Median OS was 104.4 and 52.8 months for patients with optimal cytoreduction (RT = 0) in the PDS and IDS group respectively (p < 0.05). Laparoscopy did not modify the preoperative consideration for PDS; however, 9 laparotomies were avoided based on laparoscopic findings after NACT. CONCLUSION: Laparoscopy for the assessment of surgical resectability in stage IIIC EOC has no impact on survival; but it still could be useful for the reduction of unnecessary laparotomies after NACT.

Nerve-Sparing Technique during Laparoscopic Radical Hysterectomy: Critical Steps.

STUDY OBJECTIVE: To show the feasibility and safety of nerve-preserving laparoscopic radical hysterectomy (type C1 Querleu-Morrow Classification [1]) for the treatment of early cervical cancer. DESIGN: A surgical video article (Canadian Task Force classification III). SETTING: A university hospital (University Hospital of Barcelona, Barcelona, Spain). PATIENTS: Nerve-preserving radical hysterectomy is performed in a patient with Fédération Internationale de Gynécologie et d'Obstétrique stage 1B1 cervical cancer with deep stromal invasion. INTERVENTIONS: Three steps are fundamental for the removal of the cérvix with a safe oncologic margin and preservation of the pelvic autonomic nerves [2]. 1. Step 1: for the correct preservation of the pelvic splanchnic nerves (ventral roots from spinal nerves S2-S4) and the inferior hypogastric plexus during the section of the paracervix, it is essential to identify the deep uterine vein. This vein will correspond with the inferior limit of the dissection. 2. Step 2: during the dissection of the uterosacral ligament and after dissecting the Okabayashi space, the inferior hypogastric nerve is isolated. This nerve runs 2 cm parallel below the uterosacral ligament in the peritoneal leaf of the broad ligament. 3. Step 3: during the section of the vesicouterine ligament, the lateral side must be preserved because it includes the medial and inferior vesical veins that drain to the deep uterine vein. CONCLUSION: Nerve-sparing laparoscopic radical hysterectomy is an attractive surgical approach for early-stage cervical cancer. Direct visualization of the pelvic autonomic nervous system (sympathetic and parasympathetic branches) innervating the bladder and rectum makes the nerve-sparing approach a safe and feasible procedure.

Prospective Randomized Trial Comparing Transperitoneal Versus Extraperitoneal Laparoscopic Aortic Lymphadenectomy for Surgical Staging of Endometrial and Ovarian Cancer: The STELLA Trial.

BACKGROUND: There is an ongoing debate on which approach, transperitoneal or extraperitoneal, is superior for the performance of laparoscopic aortic lymphadenectomy (LPA-LND) for the surgical staging of gynecologic cancer. A prospective randomized trial (STELLA trial) was designed to compare the perioperative outcomes and node retrieval of extraperitoneal versus transperitoneal aortic lymphadenectomy by laparoscopy or robot-assisted laparoscopy. METHODS: Patients with endometrial or ovarian carcinoma requiring aortic lymphadenectomy for surgical staging were randomized to an extraperitoneal or transperitoneal approach by laparoscopy or robot-assisted laparoscopy between June 2012 and July 2014. RESULTS: A total of 60 patients were entered into the study, 48 with endometrial cancer (80 %) and 12 with ovarian cancer (20 %). Thirty-one patients (51.6 %) were randomly assigned to the extraperitoneal group and 29 to the transperitoneal group (48.3 %). The means LPA-LND operating time was 90 min in both group (p = 0.343). The mean (range) blood loss was 105 (10-400) mL for extraperitoneal versus 100 (5-1000) mL for transperitoneal group (p = 0.541). There were no differences in the number of collected lymph nodes between the two groups [median (range) for extraperitoneal 12 (4-41) vs. 13 (4-29) for transperitoneal (p = 0.719)]. CONCLUSIONS: The extraperitoneal and transperitoneal approaches for laparoscopic and robotic aortic lymphadenectomy provide similar perioperative outcomes and nodal yields. TRIAL REGISTRATION: The STELLA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT01810874.

Mucosal Melanoma Clinical Management and Prognostic Implications: A Retrospective Cohort Study.

Mucosal melanoma (MM) is an uncommon melanoma subtype affecting mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. We aimed to present our experience at a tertiary-level hospital regarding MM diagnosis, management, monitoring of progression, mutations, and outcome predictors. We performed a registry-based cohort study including MM cases diagnosed from 2012 to 2022 and retrospectively characterized somatic mutations on BRAF, NRAS and c-KIT. We employed Kaplan-Meier curves, log-rank tests, and Cox regression analysis to explore prognostic factors and survival outcomes in a cohort of 35 patients, mainly women (63%) with a median age of 70 years. Predominantly, MM occurred in the vulvovaginal region (48.6%). At diagnosis, 28.6% had lymph node involvement, and 31.4% also had distant metastasis. Mutations in BRAF and c-KIT were identified in 3/35 (9%) and 2/6 patients (33%), respectively. Surgery was performed in 71.4% of patients, and most received systemic treatment (65.7%). Lower disease stage, thinner Breslow depth, and surgical resection were associated with improved overall survival. Notably, age, sex, radiotherapy, and BRAF mutant status did not affect survival. Standard management typically involves immunotherapy. Cases with BRAF or c-KIT mutations may be considered for targeted therapies. Unfortunately, MM prognosis remains unfavorable, with a less than 50% survival rate at 2 years.

European Enhanced Recovery After Surgery (ERAS) gynecologic oncology survey: Status of ERAS protocol implementation across Europe.

OBJECTIVE: To acquire a comprehensive assessment of the current status of implementation of Enhanced Recovery After Surgery (ERAS) protocols across Europe. METHODS: The survey was launched by The European Network of Young Gynecologic Oncologists (ENYGO). A 45-item survey was disseminated online through the European Society of Gynecological Oncology (ESGO) Network database. RESULTS: A total of 116 ESGO centers participated in the survey between December 2020 and June 2021. Overall, 80 (70%) centers reported that ERAS was implemented at their institution: 63% reported a length of stay (LOS) for advanced ovarian cancer surgery between 5 and 7 days; 57 (81%) centers reported a LOS between 2 and 4 days in patients who underwent an early-stage gynecologic cancer surgery. The ERAS items with high reported compliance (>75% "normally-always") included deep vein thrombosis prophylaxis (89%), antibiotic prophylaxis (79%), prevention of hypothermia (55%), and early mobilization (55%). The ERAS items that were poorly adhered to (less than 50%) included early removal of urinary catheter (33%), and avoidance of drains (25%). CONCLUSION: This survey shows broad implementation of ERAS protocols across Europe; however, a wide variation in adherence to the various ERAS protocol items was reported.

The Effect of Laparoscopic Endometrioma Surgery on Anti-Müllerian Hormone: A Systematic Review of the Literature and Meta-Analysis.

OBJECTIVE: This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels. METHODS: This systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery. RESULTS: Thirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed. CONCLUSIONS: Endometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.