A.K. Sinno

A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer

OBJECTIVE The study objective was to compare the ability to detect sentinel lymph nodes (SLNs) in women with endometrial cancer (EC) or complex atypical hyperplasia (CAH) using fluorometric imaging with indocyanine green (ICG) versus colorimetric imaging with isosulfan blue (ISB). METHODS Women underwent SLN mapping, with either ISB or ICG, during robotic-assisted total laparoscopic hysterectomy (RA-TLH) from September 2012 to March 2014. SLNs were submitted for permanent pathologic analysis. Completion lymphadenectomy and ultrastaging were performed according to institutional protocols. RESULTS RA-TLH and SLN mapping was performed in 71 women; 64 had EC (64) and 7 had CAH. Age, body mass index (BMI), stage and tumor characteristics were similar in the ICG versus the ISB cohorts. Overall, SLNs were identified bilaterally (62.0%), unilaterally (21.1%), or neither (16.9%), and in 103 of 142 hemi-pelvises (72.5%). The mean number of SLNs retrieved per hemipelvis was 2.23(SD 1.7). SLNs were identified in the hypogastric (76.8%), external iliac (14.2%), common iliac (4.5%) and paraaortic (4.5%) regions. ICG mapped bilaterally in 78.9% of women compared with 42.4% of those injected with ISB (p=0.02). Five women (7%) had positive lymph nodes, all identified by the SLN protocol (false negative rate: 0%). On multivariate analysis, BMI was negatively correlated with bilateral mapping success (p=0.02). When stratified by dye type, the association with BMI was only significant for ISB (p=0.03). CONCLUSIONS Fluorescence imaging with ICG may be superior to colorimetric imaging with ISB in women undergoing SLN mapping for endometrial cancer. SLN mapping success is negatively associated with increasing patient BMI only when ISB is used.

Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer

OBJECTIVE As our understanding of sentinel lymph node (SLN) mapping for endometrial cancer (EC) evolves, tailoring the technique to individual patients at high risk for failed mapping may result in a higher rate of successful bilateral mapping (SBM). The study objective is to identify patient, tumor, and surgeon factors associated with successful SBM in patients with EC and complex atypical hyperplasia (CAH). METHODS From September 2012 to November 2014, women with EC or CAH underwent SLN mapping via cervical injection followed by robot-assisted total laparoscopic hysterectomy (RA-TLH) at a tertiary care academic center. Completion lymphadenectomy and ultrastaging were performed according to an institutional protocol. Patient demographics, tumor and surgeon/intraoperative variables were prospectively collected and analyzed. Univariate and multivariate analyses were performed evaluating factors known or hypothesized to impact the rate of successful lymphatic mapping. RESULTS RA-TLH and SLN mapping was performed in 111 women; 93 had EC and 18 had CAH. Eighty women had low grade and 31 had high grade disease. Overall, at least one SLN was identified in 85.6% of patients with SBM in 62.2% of patients. Dye choice (indocyanine green versus isosulfan blue), odds ratio (OR: 4.5), body mass index (OR: 0.95), and clinically enlarged lymph nodes (OR: 0.24) were associated with SBM rate on multivariate analyses. The use of indocyanine green dye was particularly beneficial in patients with a body mass index greater than 30. CONCLUSION Injection dye, BMI, and clinically enlarged lymph nodes are important considerations when performing sentinel lymph node mapping for EC.

Robotic-assisted surgery in gynecologic oncology

The quest for improved patient outcomes has been a driving force for adoption of novel surgical innovations across surgical subspecialties. Gynecologic oncology is one such surgical discipline in which minimally invasive surgery has had a robust and evolving role in defining standards of care. Robotic-assisted surgery has developed during the past two decades as a more technologically advanced form of minimally invasive surgery in an effort to mitigate the limitations of conventional laparoscopy and improved patient outcomes. Robotically assisted technology offers potential advantages that include improved three-dimensional stereoscopic vision, wristed instruments that improve surgeon dexterity, and tremor canceling software that improves surgical precision. These technological advances may allow the gynecologic oncology surgeon to perform increasingly radical oncologic surgeries in complex patients. However, the platform is not without limitations, including high cost, lack of haptic feedback, and the requirement for additional training to achieve competence. This review describes the role of robotic-assisted surgery in the management of endometrial, cervical, and ovarian cancer, with an emphasis on comparison with laparotomy and conventional laparoscopy. The literature on novel robotic innovations, special patient populations, cost effectiveness, and fellowship training is also appraised critically in this regard.

Sentinel lymph node detection rates using indocyanine green in women with early-stage cervical cancer

OBJECTIVE Our study objective was to determine feasibility and mapping rates using indocyanine green (ICG) for sentinel lymph node (SLN) mapping in early-stage cervical cancer. METHODS We performed a retrospective review of all women who underwent SLN mapping with ICG during primary surgical management of early-stage cervical cancer by robotic-assisted radical hysterectomy (RA-RH) or fertility-sparing surgery. Patients were treated at two high-volume centers from 10/2012 to 02/2016. Completion pelvic lymphadenectomy was performed after SLN biopsy; additionally, removal of clinically enlarged/suspicious nodes was part of the SLN treatment algorithm. RESULTS Thirty women with a median age of 42.5 and BMI of 26.5 were included. Most (90%) had stage IB disease, and 67% had squamous histology. RA-RH was performed in 86.7% of cases. One patient underwent fertility-sparing surgery. Median cervical tumor size was 2.0cm. At least one SLN was detected in all cases (100%), with bilateral mapping achieved in 87%. SLN detection was not impacted by tumor size and was most commonly identified in the hypogastric (40.3%), obturator (26.0%), and external iliac (20.8%) regions. Five cases of lymphatic metastasis were identified (16.7%): three in clinically enlarged SLNs, one in a clinically enlarged non-SLN, and one case with cytokeratin positive cells in an SLN. All metastatic disease would have been detected even if full lymphadenectomy had been omitted from our treatment algorithm, CONCLUSIONS: SLN mapping with ICG is feasible and results in high detection rates in women with early-stage cervical cancer. Prospective studies are needed to determine if SLN mapping can replace lymphadenectomy in this setting.

Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population.

OBJECTIVE: To describe the human papillomavirus (HPV) genotype distribution in invasive vaginal cancers diagnosed before the introduction of the HPV vaccine and evaluate if survival differed by HPV status. METHODS: Four population-based registries and three residual tissue repositories provided formalin-fixed, paraffin-embedded tissue from microscopically confirmed primary vaginal cancer cases diagnosed between 1994 and 2005 that were tested by L1 consensus polymerase chain reaction with type-specific hybridization in a central laboratory. Clinical, demographic, and all-cause survival data were assessed by HPV status. RESULTS: Sixty cases of invasive vaginal cancer were included. Human papillomavirus was detected in 75% (45) and 25% (15) were HPV-negative. HPV 16 was most frequently detected (55% [33/60]) followed by HPV 33 (18.3% [11/60]). Only one case was positive for HPV 18 (1.7%) Multiple types were detected in 15% of the cases. Vaginal cancers in women younger than 60 years were more likely to be HPV 16– or HPV 18–positive (HPV 16 and 18) than older women, 77.3% compared with 44.7% (P=.038). The median age at diagnosis was younger in the HPV 16 and 18 (59 years) group compared with other HPV-positive (68 years) and no HPV (77 years) (P=.003). The HPV distribution did not significantly vary by race or ethnicity or place of residence. The 5-year unadjusted all-cause survival was 57.4% for women with HPV-positive vaginal cancers compared with 35.7% among those with HPV-negative tumors (P=.243). CONCLUSION: Three fourths of all vaginal cancers in the United States had HPV detected, much higher than previously found, and 57% could be prevented by current HPV vaccines. LEVEL OF EVIDENCE: III

Reducing overtreatment: A comparison of lymph node assessment strategies for endometrial cancer

OBJECTIVES To compare the utility of three lymph node (LN) assessment strategies to identify lymphatic metastases while minimizing complete lymphadenectomy rates in women with low-grade endometrial cancer (EC). METHODS Using our institutional standard protocol (SP), patients with complex atypical hyperplasia (CAH) or grade 1/2 EC underwent sentinel lymph node (SLN) mapping, hysterectomy, and intraoperative frozen section (FS). Lymphadenectomy was performed if high-risk uterine features were identified on FS. Utilizing SP data, two alternative strategies were applied: a Universal FS Strategy (UFS), omitting SLN mapping and performing lymphadenectomy based on FS results, and a SLN-Restrictive FS Strategy (SLN-RFS) in which FS and lymphadenectomy are performed only if bilateral SLN mapping fails. RESULTS Of 114 patients managed on the SP, SLNs were identified in 86%, with lymphatic metastases detected in eight patients. Six patients recurred after a median follow up of 15months. Most (83%) developed in those who had a negative systematic lymphadenectomy (n=4; mean LNs: 18) or no lymphadenectomy indication. When applying the alternative lymphatic assessment strategies, the SLN-RFS approach would theoretically result in lower lymphadenectomy rates compared to both the SP and the alternative UFS strategies (9.2% versus 36.8% and 36.8%, respectively; p=0.004), without a reduction in detection of LN metastases (8/8 versus 8/8 and 5/8, respectively). CONCLUSION In this modeling analysis, an operative strategy omitting universal frozen section and restricting its use to cases with failed SLN mapping may result in lower lymphadenectomy rates and reduce the risk of overtreatment without compromising oncologic outcome for patients with EC.

Patient, surgeon, and hospital disparities associated with benign hysterectomy approach and perioperative complications

BACKGROUND: Hysterectomy is among the most common major surgical procedures performed in women. Approximately 450,000 hysterectomy procedures are performed each year in the United States for benign indications. However, little is known regarding contemporary US hysterectomy trends for women with benign disease with respect to operative technique and perioperative complications, and the association between these 2 factors with patient, surgeon, and hospital characteristics. OBJECTIVE: We sought to describe contemporary hysterectomy trends and explore associations between patient, surgeon, and hospital characteristics with surgical approach and perioperative complications. STUDY DESIGN: Hysterectomies performed for benign indications by general gynecologists from July 2012 through September 2014 were analyzed in the all‐payer Maryland Health Services Cost Review Commission database. We excluded hysterectomies performed by gynecologic oncologists, reproductive endocrinologists, and female pelvic medicine and reconstructive surgeons. We included both open hysterectomies and those performed by minimally invasive surgery, which included vaginal hysterectomies. Perioperative complications were defined using the Agency for Healthcare Research and Quality patient safety indicators. Surgeon hysterectomy volume during the 2‐year study period was analyzed (0‐5 cases annually = very low, 6‐10 = low, 11‐20 = medium, and ≥21 = high). We utilized logistic regression and negative binomial regression to identify patient, surgeon, and hospital characteristics associated with minimally invasive surgery utilization and perioperative complications, respectively. RESULTS: A total of 5660 hospitalizations were identified during the study period. Most patients (61.5%) had an open hysterectomy; 38.5% underwent a minimally invasive surgery procedure (25.1% robotic, 46.6% laparoscopic, 28.3% vaginal). Most surgeons (68.2%) were very low– or low‐volume surgeons. Factors associated with a lower likelihood of undergoing minimally invasive surgery included older patient age (reference 45‐64 years; 20‐44 years: adjusted odds ratio, 1.16; 95% confidence interval, 1.05–1.28), black race (reference white; adjusted odds ratio, 0.70; 95% confidence interval, 0.63–0.78), Hispanic ethnicity (adjusted odds ratio, 0.62; 95% confidence interval, 0.48–0.80), smaller hospital (reference large; small: adjusted odds ratio, 0.26; 95% confidence interval, 0.15–0.45; medium: adjusted odds ratio, 0.87; 95% confidence interval, 0.79–0.96), medium hospital hysterectomy volume (reference ≥200 hysterectomies; 100‐200: adjusted odds ratio, 0.78; 95% confidence interval, 0.71–0.87), and medium vs high surgeon volume (reference high; medium: adjusted odds ratio, 0.87; 95% confidence interval, 0.78–0.97). Complications occurred in 25.8% of open and 8.2% of minimally invasive hysterectomies (P < .0001). Minimally invasive hysterectomy (adjusted odds ratio, 0.22; 95% confidence interval, 0.17–0.27) and large hysterectomy volume hospitals (reference ≥200 hysterectomies; 1‐100: adjusted odds ratio, 2.26; 95% confidence interval, 1.60–3.20; 101‐200: adjusted odds ratio, 1.63; 95% confidence interval, 1.23–2.16) were associated with fewer complications, while patient payer, including Medicare (reference private; adjusted odds ratio, 1.86; 95% confidence interval, 1.33–2.61), Medicaid (adjusted odds ratio, 1.63; 95% confidence interval, 1.30–2.04), and self‐pay status (adjusted odds ratio, 2.41; 95% confidence interval, 1.40–4.12), and very‐low and low surgeon hysterectomy volume (reference ≥21 cases; 1‐5 cases: adjusted odds ratio, 1.73; 95% confidence interval, 1.22–2.47; 6‐10 cases: adjusted odds ratio, 1.60; 95% confidence interval, 1.11–2.23) were associated with perioperative complications. CONCLUSION: Use of minimally invasive hysterectomy for benign indications remains variable, with most patients undergoing open, more morbid procedures. Older and black patients and smaller hospitals are associated with open hysterectomy. Patient race and payer status, hysterectomy approach, and surgeon volume were associated with perioperative complications. Hysterectomies performed for benign indications by high‐volume surgeons or by minimally invasive techniques may represent an opportunity to reduce preventable harm.

Single site robotic sentinel lymph node biopsy and hysterectomy in endometrial cancer

OBJECTIVE Sentinel lymph node (SLN) biopsy has been proposed as a safe and less morbid approach to full lymphadenectomy in endometrial cancer (EC) [1,2]. The role of single incision robotic surgery (SIRS) remains unclear in this setting [3,4]. The aim of this video is to demonstrate the feasibility of SLN biopsy utilizing the SIRS platform and near infrared imaging in EC. METHODS The patient was a 67 year old with FIGO grade I endometrial adenocarcinoma. Body mass index was 23.6 kg/m2 and the uterus was 10 cm on bimanual exam. Two milliliters of ICG was diluted to 1.25 mg/mL and was injected into the cervical stroma. The patient underwent pelvic washings, SLN biopsy, and extra fascial hysterectomy utilizing the daVinci Si Surgical System (Intuitive Surgical, Sunnyvale, CA) through a single multichannel port inserted through a 2.5 cm umbilical incision. RESULTS SLNs were mapped bilaterally to the hypogastric lymph node chains.Total operative time was 88 min and estimated blood loss was 50 mL. The patient was discharged home from the recovery room and no postoperative complications were noted. Swapping instruments to keep graspers on the medial aspect of the field improved visualization and minimized instrument clash while utilizing a vertical pexy of the vaginal cuff allowed for a more rapid cuff closure. CONCLUSION SLN biopsy and hysterectomy utilizing the SIRS are feasible and may offer some benefits over traditional robotic surgery. However, patients need to be carefully selected to minimize the risk of requiring complete lymphadenectomy and injury due to poor visualization.

Laminin C1 expression by uterine carcinoma cells is associated with tumor progression

OBJECTIVES Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin γ1, is associated with various uterine carcinoma subtypes and stages of tumor progression. METHODS An analysis of the immunostaining patterns of laminin γ1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high-grade endometrioid carcinomas, uterine serous and clear cell carcinoma, was performed. Clinicopathological correlation was performed to determine biological significance. The Cancer Genome Atlas (TCGA) data set was used to validate our results. RESULTS As compared to normal proliferative and secretory endometrium, for which laminin γ1 immunoreactivity was almost undetectable, increasing laminin C1 staining intensity was observed in epithelial cells from atypical hyperplasia to low-grade endometrioid to high-grade endometrioid carcinoma, respectively. Laminin γ1 expression was significantly associated with FIGO stage, myometrial invasion, cervical/adnexal involvement, angiolymphatic invasion and lymph node metastasis. Similarly, analysis of the endometrial carcinoma data set from TCGA revealed that LAMC1 transcript levels were higher in high-grade than those in low-grade endometrioid carcinoma. Silencing LAMC1 expression by siRNAs in a high-grade endometrioid carcinoma cell line did not affect its proliferative activity but significantly suppressed cell motility and invasion in vitro. CONCLUSIONS These data suggest that laminin γ1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. Laminin γ1 warrants further investigation regarding its role as a biomarker and therapeutic target in uterine carcinoma.

Robotic laparoendoscopic single site radical hysterectomy with sentinel lymph node mapping and pelvic lymphadenectomy for cervical cancer

Objective. Laparoendoscopic single site (LESS) radical hysterectomy has been previously described but has not gained wide acceptance [1,2]. The role of sentinel lymph node (SLN) mapping in cervical cancer continues to evolve [3]. Recent advances in the single site robotic platform have made the performance of robotic LESS radical hysterectomy feasible [4]. The aim of this video is to demonstrate the feasibility of robotic LESS radical hysterectomy, with sentinel lymph node mapping and complete lymphadenectomy.