Giampaolo Di Martino

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

AbstractBackground 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-99m) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG).MethodsData 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-99m with BD.ResultsOverall, 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-99m with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99m with BD; this difference was statistically significant (p < 0.0001).ConclusionsThe 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.

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 systems 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.

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.

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.

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.

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.

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.

18F-FDG PET/CT in preoperative staging of vulvar cancer patients: Is it really effective?

Abstract The aim of this study was to assess the role of 18F-FDG PET/CT in preoperative staging of vulvar cancer patients. 29 pts (69 years, range 51–88) with vulvar cancer (clinical apparent stage I-II), underwent preoperative FDG-PET/CT scan followed by radical vulvectomy and bilateral (or monolateral in case of tumor >2 cm from midline) inguinal lymphadenectomy ± sentinel node biopsy. PET/CT images were analyzed in consensus and correlated to histological findings according to a pt-based and a groin-based analyses. SUVmax of the nodal uptake of each inguinal area (if present) was calculated and correlated to histological findings. The presence of distant metastases was also considered and confirmed. PET/CT analysis in consensus resulted negative at the inguinal LN level in 17 pts (10 true negative, 7 false negative) and positive in 12 pts (7 true positive, 5 false positive). Incidence of LN metastases resulted 48%. On pt-based analysis, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT in detecting LN metastases were 50%, 67%, 59%, 59%, and 58%, respectively. On a groin-based analysis, considering overall 50 LN-sites, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT were 53%, 85%, 73%, 67%, and 76%, respectively. The mean value of SUVmax was 6.1 (range 0.7–16.2) for metastatic nodes, whereas 1.6 (range 0.7 – 5.4) for negative lymph-nodes (P = .007). PET/CT detected pelvic (n = 1) and both pelvic/paraortic (n = 1) nodal metastases. In clinical early stage vulvar cancer FDG PET/CT showed low sensitivity and moderate specificity for N-staging; therefore, it is not an accurate tool for the nodal status assessment. PET/CT may not be cost-effective in detecting the rare event of distant metastases, but further studies are needed.

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.