Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-µm intervals/levels). SLNs from each site were submitted for central quality control. RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). CONCLUSION: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging. STUDY REGISTRATION: NCT02494063 (ClinicalTrials.gov).

Low-Volume Metastases in Cervical Cancer: Does Size Matter?

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.

Assessment of sentinel Lymph node mapping with different volumes of Indocyanine green in early-stage ENdometrial cancer: the ALIEN study.

OBJECTIVE: To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. METHODS: All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. RESULTS: Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (97.8% vs 92.4%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m2 (p=0.05). CONCLUSIONS: In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

Radical Hysterectomy in Early-Stage Cervical Cancer: Abandoning the One-Fits-All Concept.

Two pillars in modern oncology are treatment personalization and the reduction in treatment-related morbidity. For decades, the one-fits-all concept of radical hysterectomy has been the cornerstone of early-stage cervical cancer surgical treatment. However, no agreement exists about the prevalent method of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Therefore, authors started investigating if less radical surgery was feasible and oncologically safe in these patients. Two historical randomized controlled trials (RCTs) compared classical radical hysterectomy (RH) to modified RH and simple hysterectomy. Less radical surgery showed a drastic reduction in morbidity without jeopardizing oncological outcomes. However, given the high frequency of adjuvant radiotherapy, the real impact of reduced radicality could not be estimated. Subsequently, several retrospective studies investigated the chance of tailoring parametrectomy according to the tumor's characteristics. Parametrial involvement was shown to be negligible in early-stage low-risk cervical cancer. An observational prospective study and a phase II exploratory RCT have recently confirmed the feasibility and safety of simple hysterectomy in this subgroup of patients. The preliminary results of a large prospective RCT comparing simple vs. radical surgery for early-stage low-risk cervical cancer show strong probability of giving a final answer on this topic.

Role of adjuvant therapy in intermediate-risk cervical cancer patients - Subanalyses of the SCCAN study.

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers.

Simple summary: Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III-IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved. Background: Low-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence. Methods: We retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan-Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula. Results: A total of 92 patients were included (median age was 47 years, IQR 35-64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1-10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1-10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1-10 mm (HR = 2.30, 95% CI 1.30-4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92-7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52-6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS. Conclusions: Optimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Evaluating long-term outcomes of three approaches to retroperitoneal staging in endometrial cancer.

OBJECTIVE: Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS: This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS: Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION: Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Low-Pressure Laparoscopy Using the AirSeal System versus Standard Insufflation in Early-Stage Endometrial Cancer: A Multicenter, Retrospective Study (ARIEL Study).

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists' parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8−10 mmHg, n = 84) or standard laparoscopic insufflation (10−12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Factors predicting morbidity in surgically-staged high-risk endometrial cancer patients.

OBJECTIVE: To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. METHODS: This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. RESULTS: Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001). CONCLUSION: The adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery.

Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer.

OBJECTIVE: Conization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization. METHODS: Patients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma. RESULTS: A total of 42 patients were included. The median age was 32 years (range 19-44) and median tumor size was 11 mm (range 8-20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1-185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss. CONCLUSIONS: Our study showed that conization is feasible for the conservative management of women with stage IB1 cervical cancer desiring fertility. Oncologic outcomes appear favorable in this series of patients. Future prospective studies will hopefully provide further insight into this important question.

Dose-dense Neoadjuvant Chemotherapy With Paclitaxel and Carboplatin in Cervical Cancer: Efficacy on Pathological Response.

BACKGROUND/AIM: The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). PATIENTS AND METHODS: A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. RESULTS: A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. CONCLUSION: Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients.

OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.

Correction to: The impact of different doses of indocyanine green on the sentinel lymph-node mapping in early stage endometrial cancer.

Unfortunately, the P value at multivariate analysis for ICG concentration in Table 3 was incorrectly published.

The impact of the type of nodal assessment on prognosis in patients with high-intermediate and high-risk ESMO/ESGO/ESTRO group endometrial cancer. A multicenter Italian study.

OBJECTIVES: The majority of endometrial cancers (EC) are discovered while the disease is confined to the uterine body. The presence of lymph nodes metastases impairs the prognosis. In this study, we evaluated the possible impact on survival of sentinel lymph node (SLN) mapping algorithm and selective lymphadenectomy (LD) in early stage EC, according to the ESMO-ESGO-ESTRO risk subgroup classification. METHODS: We retrospectively analyzed the database from two collaborative institutions including women with high-intermediate (HI) and high-risk (HR) ESMO/ESGO/ESTRO groups that underwent surgical staging with either SLN mapping, or selective LD. RESULTS: Two-hundred and sixty-six women were overall identified, 121 in HI and 145 in HR group, respectively. LD was performed in 139 patients (52.5%), whereas SLN mapping algorithm in 61 patients (23%). Sixty-six patients in Rome center were not staged (24.8%). Aortic dissection was performed in 29 women (10.9%). The 3-year comparison did not show a significant difference between strategy adopted for nodal staging (SLN mapping, LD, and SLN + LD) on both disease-free survival [HR: 0.82; 95% CI 0.53-1.28; p = 0.390], and overall survival [HR: 0.78; 95% CI 0.47-1.31; p = 0.355]. CONCLUSIONS: In this study focused on women in the HI and HR groups we did not find difference in the 3-years DFS and OS when comparing the SLN strategy with selective lymphadenectomy, or the SLN algorithm. The SLN strategy did not seem to not compromise the prognosis of high risk patients.

The impact of different doses of indocyanine green on the sentinel lymph-node mapping in early stage endometrial cancer.

INTRODUCTION: Aim of the study is to evaluate the impact of different doses of indocyanine green (ICG) on the sentinel lymph-node (SLN) mapping in endometrial cancer (EC). MATERIALS AND METHODS: A retrospective analysis of EC patients undergoing a laparoscopic SLN mapping at two institutions was performed. Two different injection protocols were used (protocol # 1: 5 mg/ml and a volume of 8 ml; protocol # 2: 1.25 mg/ml and a volume of 4 ml). In every case, the injection was intracervical. The laparoscopic equipment adopted was the same among both institutions. Overall and bilateral detection rates (DR) and median number of retrieved SLNs were calculated. At uni- and multivariate analysis factors (including ICG dose) associated with DR and number of detected SLNs were investigated. RESULTS: Overall, 168 patients were included. The overall and bilateral DR were 96.3 and 84.5%. Median number of removed SLNs was 3 (0-18). In 56% of the patients, a median number of 6 (1-93) non-SLNs (NSLNs) were removed. Seventeen (10.1%) patients had metastatic SLNs. At multivariate analysis, no factors were associated with bilateral DR. ICG dose was the only factor associated with number of removed SLNs at multivariate analysis. CONCLUSION: A larger dose of ICG is associated with a higher number of retrieved SLNs but not with an increased bilateral DR.

Lymph node evaluation in high-risk early stage endometrial cancer: A multi-institutional retrospective analysis comparing the sentinel lymph node (SLN) algorithm and SLN with selective lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). METHODS: We retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. RESULTS: One-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53-1.28; p = 0.390]. CONCLUSIONS: In this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Laparoscopic Typical and Atypical Locations of Sentinel Node Mapping with Indocyanine Green: Comparison of 2 Near-Infrared Fluorescence Systems.

STUDY OBJECTIVE: To present our minimally invasive laparoscopic approach for sentinel lymph node (SLN) mapping with indocyanine green (ICG) using 2 fluorescence systems. DESIGN: A step-by-step video description of the technique showing the most frequent typical and atypical location of SLNs (educational video). SETTING: Lymph node staging in apparent confined endometrial cancer. PATIENTS: Women underwent SLN mapping in a minimally invasive setting. INTERVENTIONS: Laparoscopic SLN mapping before comprehensive staging including simple hysterectomy, bilateral salpingo-oophorectomy, and pelvic and aortic bilateral lymphadenectomy in case of unilateral or no identification of SLNs. The PINPOINT 0 degree HD S1 SPY camera (PINPOINT Endoscopic Fluorescence Imaging System; NOVADAQ, Mississauga, ON, Canada) or the Full HD Image 1S with ICG camera (Karl Storz Endoscopy, Tuttlingen, Germany) were used for SLN detection [1,2]. The ICG powder was diluted to a final solution of 1.25 mg/mL of fluorescent dye. After the induction of general anesthesia, a total of 4 mL of the ICG solution was injected into the cervix at the 3 and 9 o'clock positions. Attention to the technical details is crucial to correctly identify SLNs that sometimes are located in atypical locations [3]. CONCLUSION: Both fluorescence systems are valid and applicable for SLN mapping in the case of apparent confined endometrial cancer. In our experience, the PINPOINT system seems to allow surgeons easier and faster nodal staging of the SLNs, particularly with the color-segmented fluorescence function activated, which can better discriminate between the lymphatic channels and the real SLNs [4,5].

Laparoscopic Sentinel Node Mapping in Cervical and Endometrial Malignancies: A Case-Control Study Comparing Two Near-Infrared Fluorescence Systems.

STUDY OBJECTIVE: The goal of this study was to evaluate the intraoperative and perioperative surgical outcomes of 2 different florescence systems commonly used for sentinel lymph node (SLN) mapping in women with early-stage cervical cancer or endometrial cancer. DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: The Gynecology Oncology Surgical Unit of the San Gerardo Hospital, Italy. PATIENTS: Thirty-four consecutive women with early stage-cervical cancer (stage IA-1B1) or apparent confined stage I endometrial cancer were included in the study. INTERVENTIONS: Between October 2016 and May 2017, 34 patients underwent laparoscopic surgery with SLN mapping using indocyanine green dye: 22 women were mapped with the Storz 1S system (Karl Storz Endoscopy, Tuttlingen, Germany; Group A), whereas 12 women underwent planned surgery with the Novadaq PinPoint system (Novadaq, Mississauga, Ontario, Canada; Group B). MEASUREMENT AND MAIN RESULTS: We compared the surgical and perioperative outcomes of Group A and Group B. Patients in Group B had a shorter duration of the SLN mapping time than those in Group A (p = .0003). The median number of SLNs removed was 2 (range, 0-5) in Group A and 2 (range, 1-3) in Group B (p = .501). Bilateral mapping was 77.3% in Group A and 83.3% in Group B (p = .334), respectively. No differences were recorded in terms of body mass index, length of hospital stay, type of tumor, bilateral mapping, or number of lymph nodes removed. Body mass index was found to have no impact on the duration of the mapping (p = .353). CONCLUSION: From our preliminary experience we can conclude that both fluorescence systems are valid and applicable for SLN detection in the case of early-stage cervical or endometrial cancer. The PinPoint system seems to allow surgeons easier and faster identification of the SLNs, particularly in endometrial cancer patients.

Laparoscopic Minimally Invasive Approach to Sentinel Lymph Node Mapping of the Ovary Using the Near-infrared Fluorescent S1 HD Pinpoint System with Indocyanine Green Dye.

STUDY OBJECTIVE: To show a novel minimally invasive approach to sentinel lymph node (SLN) detection of the ovary with near-infrared-guided surgery using indocyanine green (ICG). DESIGN: A step by step description of the technique with video and figures (educational video). SETTING: The standard surgical staging of early-stage I-II ovarian cancer includes systematic pelvic and aortic lymphadenectomy even in the absence of clear evidence regarding the survival benefits associated with comprehensive retroperitoneal staging. The ideal candidates are all women undergoing a surgical approach with frozen section analysis for highly suspicious ovarian masses or patients in whom an adnexal mass has been removed that appeared to be malignant and an open or laparoscopic surgical staging procedure is planned. PATIENT: A 31-year-old woman with occult ovarian cancer after simple left ovarian cystectomy. INTERVENTIONS: Laparoscopic surgical staging including simple hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and aortic bilateral lymphadenectomy, and sentinel node biopsy from the left ovary. MEASUREMENTS AND MAIN RESULTS: The surgical intervention was performed with the PinPoint 0 degree HD S1 SPY fluorescence camera (PinPoint Endoscopic Fluorescence Imaging System; NOVADAQ, Mississauga, ON, Canada). After the induction of the pneumoperitoneum, ICG was injected with 2 separate injections in the proper ovarian ligament and the infundibulopelvic ligament, just below the peritoneum, at a concentration of 1.25 mg/mL. A total amount of 0.4 mL ICG solution was injected using a percutaneous abdominal approach with a 12-cm-long 22-G spinal needle. SLN mapping should be preceded by the exposure of the aortic region with a gentle dissection on both sides along the Toldt fascia up to the left renal vein. Two SLNs were identified in the left inframesenteric para-aortic and superficial left common areas. Both SLNs were negative. CONCLUSION: The minimally invasive approach in combination with the ICG near-infrared fluorescence S1 PinPoint fluorescence system seems feasible, and, in our opinion, even if preliminary, this approach can further extend the range of indications of SLN mapping. In the future, this combined approach can prospectively involve ovarian SLN detection.