Detection of sentinel lymph node in vulvar cancer using 99mTc-labeled colloid lymphoscintigraphy, blue dye, and indocyanine-green fluorescence: a meta-analysis of studies published in 2010-2020.

OBJECTIVES: Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence. METHODS: The meta-analysis was conducted according to the PRISMA guideline. The search string was: "sentinel" and "vulv*", with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history. RESULTS: A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference. CONCLUSIONS: This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer.

Laparoscopic Ultra-radical Lymph Node Debulking Using Yasargil Clamps for Gynecological Malignancies: Results from a Large, Multicenter, Retrospective Analysis.

STUDY OBJECTIVE: Resection of bulky lymph nodes in gynecologic oncology is a challenging procedure. Considering the risk of intraoperative vascular injury, a technique to avoid severe complications is mandatory. In this study, we aimed to analyze the feasibility of laparoscopic ultraradical lymph node debulking using Yasargil clamps in patients with gynecologic cancer with bulky lymph node metastases. DESIGN: Multicenter retrospective case series (ClinicalTrialg.gov ID: NCT05318170), between September 2010 and April 2020. SETTING: Units of Gynecologic Oncology. PATIENTS: Patients with gynecologic cancer with bulky lymph node metastases. INTERVENTIONS: Laparoscopic ultraradical lymph node debulking using Yasargil clamps. MEASUREMENTS AND MAIN RESULTS: Forty-three patients with gynecologic cancer with bulky pelvic and/or aortic lymph nodes metastases undergoing laparoscopic lymph node debulking surgery using Yasargil clamps were included. Median surgical time was 300 minutes (range, 120-550 minutes); median estimated blood loss was 170 mL (range, 0-700 mL). Median size of lymph nodes was 50 mm (range, 25-100). R0 resection was achieved in all cases. Four intraoperative complications (9.3%) occurred. No conversion to open surgery was required. There were 8 postoperative complications, classified grade 2 or worse. There were no cases with intra- or postoperative mortality. CONCLUSION: In our experience, in carefully selected patients with gynecologic cancer with bulky lymph nodes, laparoscopic lymph node debulking using Yasargil clamps could be considered a valid option to avoid potential severe vascular intraoperative complications.

Laparoscopic sentinel node mapping with intracervical indocyanine green injection for endometrial cancer: the SENTIFAIL study - a multicentric analysis of predictors of failed mapping.

OBJECTIVES: Laparoscopy is commonly used for endometrial cancer treatment, and sentinel lymph node (SLN) mapping has become the standard procedure for nodal assessment. Despite the standardization of the technique, there is no definitive data regarding its failure rate. The objective of this study is to identify factors associated with unsuccessful SLN mapping in endometrial cancer patients undergoing laparoscopic SLN mapping after intracervical indocyanine green (ICG) injection. METHODS: We retrospectively evaluated a consecutive series of endometrial cancer patients who underwent laparoscopic SLN mapping with intracervical ICG injection, in four oncological referral centers from January 2016 to July 2019. Inclusion criteria were biopsy-proven endometrial cancer, total laparoscopic approach, and intracervical ICG injection. Exclusion criteria were evidence of lymph node involvement or extrauterine disease at pre-operative imaging, synchronous invasive cancer, the use of tracers different from ICG, and the use of neoadjuvant treatment. Bilateral and failed bilateral SLN mapping groups were compared for clinical and pathological features. In patients with an unsuccessful procedure, side-specific lymphadenectomy was performed. Logistic regression was used to identify predictors of failure. RESULTS: A total of 376 patients were included in the study. The overall bilateral and unilateral SLN detection rates were 96.3%, 76.3%, and 20.0% respectively. The failed bilateral mapping detection rate was 23.7%. The median number of sentinel nodes removed was 2.2 (range, 0-5). After multivariate analysis, lymph vascular space involvement [OR 2.4 (1.04-1.12), P=0.003], non-endometrioid histology [OR 3.0 (1.43-6.29), P=0.004], and intraoperative finding of enlarged lymph node [OR 2.3 (1.01-5.31), P=0.045] were identified as independent predictors of failure of SLN mapping. CONCLUSION: Lymph vascular space involvement, non-endometrioid histology, and intra-operative finding of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping.

Integrated pre-surgical diagnostic algorithm to define extent of disease in cervical cancer.

OBJECTIVES: Survival of patients with cervical cancer is strongly associated with the local extent of the primary disease. The aim of the study was to develop an integrated diagnostic algorithm, including ultrasonography (USG), magnetic resonance imaging (MRI), and examination under anesthesia, to define the local extent of disease in patients with newly diagnosed cervical cancer. METHODS: Patients with biopsy proven cervical cancer who underwent primary surgery from January 2013 to December 2018 in four participating centers were recruited. Patients who underwent USG, MRI, and examination under anesthesia prior to surgery were included in the study. Those for whom complete data were not available were excluded. Data regarding tumor size, parametrial invasion, and vaginal involvement obtained by USG, MRI, and examination under anesthesia were retrieved and compared with final histology. Specificity and sensitivity of the three methods were calculated for each parameter and the methods were compared with each other. An integrated pre-surgical algorithm was constructed considering the accuracy of each diagnostic method for each parameter. RESULTS: A total of 79 consecutive patients were included in the study. Median age was 53 years (range 28-87) and median body mass index was 24.6 kg/m2 (range 16-43). Fifty-five (69.6%) patients had squamous carcinoma, 18 (22.8%) patients had adenocarcinoma, and six (7.6%) patients had other histological subtypes. A statistically significant difference among the three methods was found for detecting tumor size (p=0.002 for tumors >2 cm and p=0.006 for tumors >4 cm) and vaginal involvement (p=0.01). There was no difference in detection of parametrial invasion between USG, MRI, and examination under anesthesia (p=0.26). Furthermore, regarding tumor size assessment, USG was found to be the significantly better method (p<0.01 for tumors >2 cm and p=0.02 for tumors >4 cm). Examination under anesthesia was the most accurate method for detection of vaginal involvement (p=0.01). Examination under anesthesia and MRI had higher accuracy than USG for identification of parametrial invasion. Application of the algorithm provided the correct definition of local extent of disease in 77.2% of patients (p=0.04). USG was the most accurate method to determine tumor size, while examination under anesthesia was found to be more accurate in prediction of vaginal involvement. CONCLUSION: Our integrated diagnostic algorithm allows a higher accuracy in defining the local extent of disease and may be used as a tool to determine the therapeutic approach in women with cervical cancer.

Laterally extended endopelvic resection for gynecological malignancies, a comparison between laparoscopic and laparotomic approach.

INTRODUCTION: The historical approach to LEER is laparotomic, but recently laparoscopy has been proposed. The objective of this study was to compare surgical and oncological outcomes between the two approaches and to assess the overall quality of life (QoL). MATERIALS AND METHODS: Women submitted to LEER between October 2012 and March 2020 were retrospectively recruited. Peri-operative data were analyzed and compared. Recurrence-free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-CX24, and QLQ-OV28 questionnaires were administered 6 months after surgery in women with no evidence of recurrence after LEER. RESULTS: Of the included 41 patients, 20 were submitted to laparoscopic LEER (L-LEER) and 21 to open LEER (O-LEER). Median operating time (442 vs 630 min, p = 0.001), median blood loss (275 vs 800 ml, p < 0.001), and median length of hospital stays (10 vs 16 days, p = 0.002) were shorter in the laparoscopic group, while tumor resection rate and peri-operative complications were similar. After a median follow-up of 27.5 months, no differences, in terms of DFS (p = 0.83) and OS (p = 0.96) were observed between the two approaches. High functional scores and low levels of adverse symptoms were observed on the surviving women. CONCLUSION: QoL after LEER is acceptable, and laparoscopy provides better surgical and similar oncological outcomes when compared to laparotomy. L-LEER can be considered a further option of treatment for women with gynecological tumors infiltrating the pelvic sidewall.

Concordance of Radiological, Laparoscopic and Laparotomic Scoring to Predict Complete Cytoreduction in Women with Advanced Ovarian Cancer.

OBJECTIVE: To identify the best method among the radiologic, laparoscopic and laparotomic scoring assessment to predict the outcomes of cytoreductive surgery in patients with advanced ovarian cancer (AOC). METHODS: Patients with AOC who underwent pre-operative computed tomography (CT) scan, laparoscopic evaluation, and cytoreductive surgery between August 2016 and February 2021 were retrospectively reviewed. Predictive Index (PI) score and Peritoneal Cancer Index (PCI) scores were used to estimate the tumor load and predict the residual disease in the primary debulking surgery (PDS) and interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) groups. Concordance percentages were calculated between the two scores. RESULTS: Among 100 eligible patients, 69 underwent PDS, and 31 underwent NACT and IDS. Complete cytoreduction was achieved in 72.5% of patients in the PDS group and 77.4% in the IDS. In patients undergoing PDS, the laparoscopic PI and the laparotomic PCI had the best accuracies for complete cytoreduction (R0) [area under the curve (AUC) = 0.78 and AUC = 0.83, respectively]. In the IDS group, the laparotomic PI (AUC = 0.75) and the laparoscopic PCI (AUC= 0.87) were associated with the best accuracy in R0 prediction. Furthermore, radiological assessment, through PI and PCI, was associated with the worst accuracy in either PDS or IDS group (PI in PDS: AUC = 0.64; PCI in PDS: AUC = 0.64; PI in IDS: AUC = 0.46; PCI in IDS: AUC = 0.47). CONCLUSION: The laparoscopic score assessment had high accuracy for optimal cytoreduction in AOC patients undergoing PDS or IDS. Integrating diagnostic laparoscopy in the decision-making algorithm to accurately triage AOC patients to different treatment strategies seems necessary.

Urinary, Gastrointestinal, and Sexual Dysfunctions after Chemotherapy, Radiotherapy, Radical Surgery or Multimodal Treatment in Women with Locally Advanced Cervical Cancer: A Multicenter Retrospective Study.

BACKGROUND: Different strategies have been proposed for the treatment of locally advanced cervical cancer (LACC), with different impacts on patient's quality of life (QoL). This study aimed to analyze urinary, bowel, and sexual dysfunctions in a series of LACC patients who underwent chemotherapy, radiotherapy, radical surgery, or a combination of these treatments. METHODS: Patients with LACC who underwent neoadjuvant radio-chemotherapy (NART/CT; n = 35), neoadjuvant chemotherapy (NACT; n = 17), exclusive radio-chemotherapy (ERT/CT; n = 28), or upfront surgery (UPS; n = 10) from November 2010 to September 2019 were identified from five oncological referral centers. A customized questionnaire was used for the valuation of urinary, gastrointestinal, and sexual dysfunctions. RESULTS: A total of 90 patients were included. Increased urinary frequency (>8 times/day) was higher in ERT/CT compared with NACT/RT (57.1% vs. 28.6%; p = 0.02) and NACT (57.1% vs. 17.6%; p = 0.01). The use of sanitary pads for urinary leakage was higher in ERT/CT compared with NACT/RT (42.9% vs. 14.3%; p = 0.01) and NACT (42.9% vs. 11.8%; p = 0.03). The rate of reduced evacuations (<3 times a week) was less in UPS compared with NACT/RT (50% vs. 97.1%; p < 0.01), NACT (50% vs. 88.2, p < 0.01), and ERT/CT (50% vs. 96.4%; p < 0.01). A total of 52 women were not sexually active after therapy, and pain was the principal reason for the avoidance of sexual activity. CONCLUSIONS: The rate and severity of urinary, gastrointestinal, and sexual dysfunction were similar in the four groups of treatment. Nevertheless, ERT/CT was associated with worse sexual and urinary outcomes.

Attitudes of mothers of pre-adolescent girls on HPV vaccine in Italy. Do we need a turning point?

BACKGROUND: To investigate the knowledge, awareness and attitude of mothers of preadolescent girls regarding the HPV vaccination and cervical cancer, and to understand how to improve the efficacy of the Italian vaccination campaign through the gathered data. METHODS: A questionnaire-based survey was conducted in mothers of unvaccinated 9 to 12-year-old (yo) girls in Italy from November 2018 to July 2019, to evaluate their awareness and the attitude toward HPV, its vaccination and the information sources of the vaccination campaign. The selection of the distribution sites of the questionnaire was performed with randomization of 50 major places of aggregation located throughout the Italian territory. RESULTS: Three hundred mothers of unvaccinated girls were included in the study and divided into two groups (191 subjects <45yo, 109 subjects >45yo). Results showed that 79.6% of <45yo knew what HPV is, compared to 60.6% of >45yo (p-value <0.001); only 60.2% (<45yo) and 54.1% (>45yo) showed awareness about the HPV vaccine (p-value 0.03). The percentage of parents against vaccination in pre-adolescent was higher in the >45yo (29.4%); however, most of them appeared favorable to the information campaigns regarding the vaccine (p-value <0.001). CONCLUSIONS: Our study showed that mothers of unvaccinated pre-adolescent girls have suboptimal knowledge on the topic. Moreover, the implementation of communication strategies dedicated to the population segment appears as a central aspect. As HPV vaccination keeps being a public health concern, it is fundamental to understand which trigger should be managed by healthcare decision makers in order to boost the vaccination campaigns.

Conventional Laparoscopy versus Robotic-Assisted Aortic Lymph-Nodal Staging for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis.

Aortic lymph node metastases are a relative common finding in locally advanced cervical cancer. Minimally invasive surgery is the preferred approach to perform para-aortic lymph nodal staging to reduce complications, hospital stay, and the time to primary treatment. This meta-analysis (CRD42022335095) aimed to compare the surgical outcomes of the two most advanced approaches for the aortic staging procedure: conventional laparoscopy (CL) versus robotic-assisted laparoscopy (RAL). The meta-analysis was conducted according to the PRISMA guideline. The search string included the following keywords: "Laparoscopy" (MeSH Unique ID: D010535), "Robotic Surgical Procedures" (MeSH Unique ID: D065287), "Lymph Node Excision" (MeSH Unique ID: D008197) and "Aorta" (MeSH Unique ID: D001011), and "Uterine Cervical Neoplasms" (MeSH Unique ID: D002583). A total of 1324 patients were included in the analysis. Overall, 1200 patients were included in the CL group and 124 patients in the RAL group. Estimated blood loss was significantly higher in CL compared with RAL (p = 0.02), whereas hospital stay was longer in RAL compared with CL (p = 0.02). We did not find significant difference for all the other parameters, including operative time, intra- and postoperative complication rate, and number of lymph nodes excised. Based on our data analysis, both CL and RAL are valid options for para-aortic staging lymphadenectomy in locally advanced cervical cancer.

Transperitoneal versus extraperitoneal laparoscopic aortic lymph nodal staging for locally advanced cervical cancer: A systematic review and meta-analysis.

Cervical cancer is the fourth most common neoplasm in women. In locally advanced cervical cancers, the international guidelines recommend nodal aortic assessment. Two techniques have been described to perform laparoscopic aortic lymphadenectomy: transperitoneal laparoscopic lymphadenectomy (TLL) and extraperitoneal laparoscopic lymphadenectomy (ELL). This meta-analysis aims to compare the surgical outcomes of TLL and ELL for staging purposes. The systematic review was carried out in agreement with the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Two hundred and twenty studies were analyzed, and 19 studies were included in the review (7 for TLL and 12 for ELL group). 1112 patients were included in the analysis: 390 patients were included in group 1 and 722 patients in group 2.38 patients (9.7%) in the TLL group and 69 (9.5%) patients in the ELL group developed major complications. The analysis of all complications (intraoperative and postoperative) rate through pooled analysis did not show a significant difference between the two groups (p = 0.979), although a significantly higher intraoperative complication rate (p = 0.018) occurred in the TLL group compared to ELL. No significant differences were found between groups for BMI (p = 0.659), estimated blood loss (p = 0.889), length of stay (p = 0.932), intraoperative time (p = 0.932), conversion to laparotomy rate (p = 0.404), number of lymph node excised (p = 0.461) and postoperative complication (p = 0.291). TLL approach shows a higher rate of intraoperative complications, while no significant difference was found between the two techniques when postoperative complications were analyzed.