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).

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.

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.

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.

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.

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.

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.

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 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.

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.

Minilaparoscopy vs Standard Laparoscopy for Sentinel Node Dissection: A Pilot Study.

OBJECTIVE: To compare 3-mm minilaparoscopy and standard 5-mm laparoscopy for sentinel lymph node (SLN) detection in apparent early-stage endometrial cancer (EC). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Two academic research centers. PATIENTS: Consecutive women with apparent early-stage EC who underwent surgical staging with SLN detection between November 2015 and April 2016. INTERVENTIONS: The surgical approach was a total laparoscopic extrafascial hysterectomy plus bilateral salpingo-oophorectomy and SLN detection. Systematic lymphadenectomy was performed in selected cases. In all patients, SLN detection was performed with cervical injection of indocyanine green and the use of an optical camera with a near-infrared high-intensity light source for detection of fluorescence imaging. All patients who underwent a minilaparoscopic approach (using one 5-mm scope and three 3-mm ancillary trocars) have been enrolled at the University of Insubria, whereas at the San Gerardo Hospital, standard laparoscopy was performed with one 10-mm scope and three 5-mm ancillary trocars. MEASUREMENTS AD MAIN RESULTS: A total of 38 patients were enrolled, including 15 (39.5%) in the 3-mm group and 23 (60.5%) in the 5-mm group. No between-group differences were found in terms of demographic and tumor characteristics. Bilateral SLNs were detected in 73.3% of the patients in the 3-mm group and in 73.9% in the 5-mm group. Operative time, blood loss, hemoglobin drop, hospital stay, and the incidence and severity of complications were similar in the 2 groups. One patient (4.3%) in the standard 5-mm group had a positive SLN result (a micrometastasis in the left external iliac SLN). No positive SLNs were detected in the 3-mm group. CONCLUSION: Minilaparoscopic SLN biopsy appears to be a promising and feasible technique for EC staging. Further research is warranted to investigate the possible benefits of 3-mm instruments in this specific setting.

Real-Time Fluorescent Sentinel Lymph Node Mapping with Indocyanine Green in Women with Previous Conization Undergoing Laparoscopic Surgery for Early Invasive Cervical Cancer: Comparison with Radiotracer ± Blue Dye.

STUDY OBJECTIVE: To evaluate the added value of the fluorescence dye indocyanine green (ICG) for sentinel lymph node (SLN) mapping in women with cervical cancer who had undergone previous conization (stage 1A-1B1) by comparing ICG versus Tc99m radiotracer + blue dye (BD). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Two European academic medical centers, San Gerardo Hospital, Italy and University of Berne, Switzerland. PATIENTS: Sixty-five women with early stage (IA-IB1) cervical cancer who had undergone previous conization and who underwent SLN mapping with Tc99m ± BD (n = 23) or ICG (n = 42) followed by pelvic lymphadenectomy and fertility-sparing surgery or hysterectomy were included in this analysis. INTERVENTION: Overall detection rate and bilateral SLN mapping rates of ICG were compared with those obtained using the standard Tc99m radiocolloid and BD. MEASUREMENT AND MAIN RESULTS: Overall, 220 SLNs were detected. The median number of SLNs per patient in the Tc99m ± BD group was 2 (range, 1-5) and in the ICG group, 3 (range, 2-15). The detection rate of SLNs was 95.7% in Tc99m ± BD group and 100% in the ICG group (p = .354). The women injected with ICG had a higher rate of bilateral mapping of the SLNs as compared with the Tc99m ± BD group (95.2% vs 69.6%, p = .016%). Only 12% of the patients (8/65) presented metastatic nodes, 2 in the Tc99m ± BD group and 6 in the ICG group. CONCLUSION: In early-stage cervical cancer patients conization had no significant impact on the SLN detection rate using both techniques (ICG and radiotracer ± BD). In this scenario a higher bilateral mapping rate was confirmed using the fluorescent dye ICG rather than the standard techniques.

The impact on survival of two different staging strategies in apparent early stage endometrial cancer comparing sentinel lymph nodes mapping algorithm and selective lymphadenectomy: An Italian retrospective analysis of two reference centers.

OBJECTIVE: The role of lymphadenectomy in endometrial cancer is still uncertain. We aimed to evaluate the survival outcomes of two different strategies in apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping and selective lymphadenectomy (LD). METHODS: We retrospectively reviewed women with preoperative stage I endometrial cancer underwent surgical staging with either SLN mapping, or LD in two Italian centers. RESULTS: Eight hundred and two women underwent surgical staging for preoperative stage I endometrial cancer were revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome, respectively (p<0.001). Patients with positive pelvic LN were 16.7% and 7.3%, in SLN and LD groups, respectively (p=0.002). Disease-free survival (DFS) curves did not showed a statistically significant difference between centers and strategies adopted (SLN mapping, LD, SLN+LD) with a HR of 0.87 (95% CI 0.63-2.16; p=0.475). CONCLUSIONS: Survival outcomes were similar for both strategies. The SLN strategy allowed to identify a higher rate of stage IIIC1 disease even with a lower median number of lymph node removed in SLN group. Applying a SLN algorithm does not impair the prognosis of endometrial cancer patients. The clinical impact and management of low volume metastasis in high-risk patients should be further clarify.

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

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

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PURPOSE: To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. METHODS: From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. RESULTS: SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. CONCLUSIONS: SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

Quality of Care for Cervical and Endometrial Cancer Patients: The Impact of Different Techniques of Sentinel Lymph Node Mapping on Patient Satisfaction.

OBJECTIVES: The purpose of this study was to assess the quality of care in patients who underwent sentinel lymph node (SLN) mapping for endometrial and cervical cancer staging, and evaluate the impact of different techniques on patient satisfaction, i.e. radiotracer Tc99m versus indocyanine green (ICG) or methylene blue injection. METHOD: Women with preoperative stage I endometrial cancer or stage I (1A2-1B1) cervical cancer who underwent surgical staging, including SLN mapping, were considered for this study. Patient satisfaction was assessed using the European Organisation for Research and Treatment of Cancer IN-PATSAT32 questionnaire. Women were classified into two groups according to the different nodal mapping techniques: intracervical preoperative injection of Tc99m nanocolloid + intraoperative blue dye (Group 1) versus intraoperative cervical injection of ICG or blue dye (Group 2). Differences in patient satisfaction scores between the groups were analyzed. RESULTS: Of the 178 eligible women, 143 were included in the study (endometrial cancer n = 106, cervical cancer n = 37): 57 underwent SLN mapping with Tc99m and blue dye (Group 1), and 86 women were mapped intraoperatively with blue dye alone or ICG (Group 2). Analysis of IN-PATSAT32 questionnaire scores showed a higher patient satisfaction score for patients in Group 2 (p = 0.001), which was independent of the physician and surgical outcomes evaluated. The scores were statistically better for Group 2, and also in rating doctors (p = 0.0001), nurses (p = 0.006), and care and services organizations (p = 0.001). CONCLUSIONS: Cervical and endometrial cancer patients who underwent SLN mapping by ICG or blue dye perceived a better quality of care when compared with those patients who underwent the combined radiocolloid and blue dye technique.

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

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

Sentinel Lymph Node Mapping With Near-Infrared Fluorescent Imaging Using Indocyanine Green: A New Tool for Laparoscopic Platform in Patients With Endometrial and Cervical Cancer.

Indocyanine green (ICG) represents a feasible alternative to the more traditional methods of sentinel lymph node (SLN) mapping, and interest in this promising tracer is growing. This report outlines our experience with ICG in a minimally invasive laparoscopic approach in women with endometrial cancer and cervical cancer using the Storz SPIES ICG near-infrared fluorescence imaging technology. A total of 49 patients with clinical stage I endometrial cancer (n = 40) or stage I cervical cancer (n = 9) were retrospectively reviewed. All patients had undergone simple or radical laparoscopic hysterectomy with pelvic and/or aortic lymphadenectomy and SLN mapping by means of an intracervical injection of ICG dye at the 3 o'clock and 9 o'clock locations after the induction of general anesthesia. The detection rate of ICG was 100% (49 of 49). The rate of bilateral SLN detection was 86% (42 of 49). Positive lymph nodes were found in 6 patients (12%), with at least 1 positive SLN. The sensitivity and negative predictive value of SLN detection were 100%. All procedures were successfully completed without conversion to open laparotomy, and no intraoperative or postoperative complications occurred. In our preliminary experience, ICG showed a high overall detection rate, and bilateral mapping appears to be a feasible alternative to the more traditional methods of SLN mapping in patients with endometrial cancer and cervical cancer. Laparoscopic SLN mapping with ICG appears to be safe, easy, and reproducible, with a positive impact on patient management.

Near-Infrared Sentinel Lymph Node Mapping With Indocyanine Green Using the VITOM II ICG Exoscope for Open Surgery for Gynecologic Malignancies.

Sentinel lymph node (SLN) mapping is emerging as an effective method for surgical staging of different gynecologic malignancies. Near-infrared (NIR) technology using a fluorescent dye such as indocyanine green (ICG) represents an interesting and feasible method for SLN mapping even in traditional open surgeries by applying video telescope operating microscope (VITOM) system technology. We report our preliminary experience in 12 women who underwent surgical nodal staging for early-stage vulvar and uterine or cervical cancer. Surgical and pathological outcomes are described, and the VITOM II ICG system's intraoperative image quality, handling and docking, and teaching value are assessed. The general impression of the surgical staff was that the VITOM II system is easy to use, and that the image quality of the anatomic structures is impressive. Traditional open SLN mapping with ICG appears to be easy to perform and reproducible, providing a new tool in the management of patients with gynecologic malignancies. Moreover, we believe that this technology has great potential as an operative teaching and learning modality for trainers for open surgical cases. Additional studies involving the VITOM system with a large sample size of patients are needed to confirm these promising results.