Fady Khoury-Collado

Sentinel lymph node mapping for grade 1 endometrial cancer: Is it the answer to the surgical staging dilemma?

OBJECTIVE To describe the accuracy of SLN mapping in patients with a preoperative diagnosis of grade 1 endometrial cancer. METHODS A prospective, non-randomized study of women with a preoperative diagnosis of endometrial cancer and clinical stage I disease was conducted. A subset analysis of patients with a preoperative diagnosis of grade 1 endometrial endometrioid cancer was performed. All patients had preoperative lymphoscintigraphy with Tc99m on the day of or day before surgery followed by an intraoperative injection of 2 cm(3) of isosulfan or methylene blue dye deep into the cervix or both cervix and fundus. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and regional nodal dissection. Hot and/or blue nodes were labeled as SLNs and sent for histopathological analysis. RESULTS Forty-two patients with a preoperative diagnosis of grade 1 endometrial carcinoma treated from 3/06 to 8/08 were identified. Twenty-five (60%) had laparoscopic surgery; 17 (40%) were treated by laparotomy. Preoperative lymphoscintigraphy visualized SLNs in 30 patients (71%); intraoperative localization of the SLN was possible in 36 patients (86%). A median of 3 SLNs (range, 1-14) and 14.5 non-SLNs (range, 4-55) were examined. In all, 4/36 (11%) had positive SLNs-3 seen on H&E and 1 as cytokeratin-positive cells on IHC. All node-positive cases were picked up by the SLN; there were no false-negative cases. The sensitivity of the SLN procedure in the 36 patients who had an SLN identified was 100%. CONCLUSION Sentinel lymph node mapping using a cervical injection with combined Tc and blue dye is feasible and accurate in patients with grade 1 endometrial cancer and may be a reasonable option for this select group of patients. Regional lymphadenectomy remains the gold standard in many practices, particularly for the approximately 15% of cases with failed SLN mapping.

Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes

OBJECTIVE To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate. METHODS All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC). RESULTS Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003). CONCLUSION Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.

Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging.

Objective To describe the incidence of low-volume ultrastage-detected metastases in sentinel lymph nodes (SLNs) identified at surgical staging for endometrial carcinoma and to correlate it with depth of myoinvasion and tumor grade. Methods We reviewed all patients who underwent primary surgery for endometrial carcinoma with successful mapping of at least one SLN at our institution from September 2005 to December 2011. All patients underwent a cervical injection for mapping. The SLN ultrastaging protocol involved cutting an additional 2 adjacent 5-μm sections at each of 2 levels, 50-μm apart, from each paraffin block lacking metastatic carcinoma on routine hematoxylin and eosin (H&E) staining. At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anticytokeratin AE1:AE3. Micrometastases (tumor deposits >0.2 mm and ≤2 mm) and isolated tumor cells (≤0.2 mm) were classified as low-volume ultrastage-detected metastases if pathologic ultrastaging was the only method allowing detection of such nodal disease. Results Of 508 patients with successful mapping, 413 patients (81.3%) had endometrioid carcinoma. Sixty-four (12.6%) of the 508 patients had positive nodes: routine H&E detected 35 patients (6.9%), ultrastaging detected an additional 23 patients (4.5%) who would have otherwise been missed (4 micrometastases and 19 isolated tumor cells), and 6 patients (1.2%) had metastatic disease in their non-SLNs. The incidence rates of low-volume ultrastage-detected nodal metastases in patients with grades 1, 2, and 3 tumors were 3.8%, 3.4%, and 6.9%, respectively. The frequency rates of low-volume ultrastage-detected metastases in patients with a depth of myoinvasion of 0, less than 50%, and 50% or more were 0.8%, 8.0%, and 7.4%, respectively. Lymphovascular invasion was present in 20 (87%) of the cases containing low-volume ultrastage-detected metastases in the lymph nodes. Conclusions Sentinel lymph node mapping with pathologic ultrastaging in endometrial carcinoma detects additional low-volume metastases (4.5%) that would otherwise go undetected with routine evaluations. Our data support the incorporation of pathologic ultrastaging of SLNs in endometrial carcinoma with any degree of myoinvasion. The oncologic significance of low-volume nodal metastases requires long-term follow-up.

Lymphatic mapping in endometrial cancer: a literature review of current techniques and results.

The objective of this study was to review available literature pertaining to lymphatic mapping in endometrial cancer. We reviewed all published series of lymphatic mapping in endometrial cancer available through a PubMed search. Techniques used for identification of sentinel lymph nodes fell into three main categories in relation to the site of injection: 1) uterine subserosal, 2) cervical, and 3) endometrial via hysteroscopy. High detection rates may be achieved in all three categories. The use of both radiolabeled technetium and blue dye has been reported. A combination of cervical and uterine corpus injections appears feasible and less technically demanding than hysteroscopic injections. Immunohistochemistry staining of sentinel nodes coupled with step-serial section may improve the detection of micrometastasis in sentinel nodes. Meaningful sensitivity and false-negative rates cannot be calculated from current series due to their small numbers. The role of lymphatic mapping in endometrial carcinoma and the optimal injection site remains to be determined. A combination of cervical and uterine fundal injections may result in acceptable detection rates. Large-scale validation trials requiring complete pelvic and para-aortic lymphadenectomy are needed to evaluate its role in future clinical practice.

Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer

OBJECTIVE To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment. METHODS Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used. RESULTS We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0). CONCLUSIONS The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection.

Techniques of sentinel lymph node identification for early-stage cervical and uterine cancer

Techniques for sentinel lymph node injections have varied over the years in both cervical and uterine malignancy lymph node mapping. There remains considerable variation in techniques, particularly for uterine malignancies. This review summarizes some of the techniques that have been published and are currently utilized in sentinel lymph node mapping for cervical and uterine malignancies.

Pelvic exenteration with curative intent for recurrent uterine malignancies

OBJECTIVE To evaluate the outcomes observed with pelvic exenteration with curative intent for recurrent uterine malignancies in the modern era. METHODS We reviewed the records of all patients who underwent this procedure at our institution between 1/1997 and 03/2011. Postoperative complications up to 90 days after surgery were analyzed and graded as per our institution grading system. Survivals were estimated using the Kaplan-Meier method. RESULTS During the study period, 21 patients were identified. Median age at the time of exenteration was 57 years (range, 36-75). Median tumor size was 6 cm (range, microscopic - 14.5). Tumor histology was: endometrioid, 10 cases; mixed, serous, and carcinosarcoma, 7 cases; and sarcomas, 4 cases. The type of exenteration was: total, 14 cases; anterior, 6 cases and posterior, 1 case. There were no intra- or postoperative mortalities. Seven patients (33%) developed at least one grade 2 complication, and 10 patients (48%) developed at least one grade 3 complication. Five (24%) patients had to be re-operated on in the first 90 days post surgery. The median follow up time after exenteration was 39 months (range, 5-112). The 5-year survival of the entire cohort was 40% (95% CI: 18-63). An improved survival was observed in patients with endometrioid tumors and sarcomas (5-year survival rates of 50% and 66%, respectively). The presence of pelvic sidewall involvement and/or hydronephrosis did not negatively affect survival. CONCLUSION Pelvic exenteration for recurrent uterine malignancies can be associated with long-term survival in properly selected patients. A high rate of postoperative complications remains a hallmark of this procedure and should be discussed carefully with patients facing this decision.

Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion

OBJECTIVE To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging. METHODS All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells. RESULTS Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion. CONCLUSIONS Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.

Sentinel Lymph Node Biopsy in the Management of Vulvar Carcinoma, Cervical Cancer, and Endometrial Cancer

The treatment of gynecologic malignancies can include surgery, systemic therapy, and radiation. Depending on the primary site of disease and the extent of the disease, these treatment strategies are applied alone or in combination. Trends over the past few decades have concentrated on performing more comprehensive staging procedures for a large percentage of patients with gynecologic malignancies. The surgical techniques available for comprehensive staging have facilitated a greater understanding of stage and prognosis overall, and better tailoring of postsurgical treatment. One such technique is regional lymphadenectomy. Although the role of regional lymphadenectomy as a therapeutic procedure in some gynecologic cancers is debated and challenged (regional lymphadenectomy and multimodality therapy increases adverse side effects and long-term sequelae without proven survival benefit), there is no controversy regarding the staging and prognostic benefit of the evaluation of regional lymph nodes. The sentinel lymph node (SLN) concept was successfully introduced in melanoma. It has since become the standard of care in breast cancer and has had a significant impact on postoperative morbidity for a large percentage of breast cancer patients. Interest in using SLN techniques in gynecologic cancers was thus a natural progression. In light of the growing body of evidence in the literature opposing the therapeutic benefit of systematic lymphadenectomy, the SLN concept will continue to play an important role in the treatment of gynecologic malignancies. This technique can provide accurate staging information in some gynecologic cancers. Increased use of this technique could potentially impact the quality of life of gynecologic cancer survivors while still providing important staging information without compromising oncologic safety. In this review, we examine the body of literature related to gynecologic cancer malignancies and SLN biopsy.

Cervical conization and sentinel lymph node mapping in the treatment of stage I cervical cancer: is less enough?

Objectives This study aimed to determine the feasibility of cervical conization and sentinel lymph node (SLN) mapping as a fertility-sparing strategy to treat stage I cervical cancer and to estimate the tumor margin status needed to achieve no residual carcinoma in the cervix. Methods We identified all patients who desired fertility preservation and underwent SLN mapping with cervical conization for stage I cervical cancer from September 2005 to August 2012. Relevant demographic, clinical, and pathologic information was collected. Results Ten patients were identified. Median age was 28 years (range, 18–36 years). None of the patients had a grossly visible tumor. The initial diagnosis of invasive carcinoma was made either on a loop electrosurgical excision procedure or cone biopsy. All patients underwent preoperative radiologic evaluation (magnetic resonance imaging and positron emission tomography–computed tomography). None of the patients had evidence of gross tumor or suspicion of lymph node metastasis on imaging. Stage distribution included 7 (70%) patients with stage IA1 cervical cancer with lymphovascular invasion and 3 (30%) patients with microscopic IB1. Histologic diagnosis included 8 (80%) patients with squamous cell carcinoma, 1 (10%) patient with adenocarcinoma, and 1 (10%) patient with clear cell carcinoma. Nine patients underwent repeat cervical conization with SLN mapping, and 1 patient underwent postconization cervical biopsies and SLN mapping. None of the patients had residual tumor identified on the final specimen. The median distance from the invasive carcinoma to the endocervical margin was 2.25 mm, and the distance from the invasive carcinoma to the ectocervical margin was 1.9 mm. All collected lymph nodes were negative for metastasis. After a median follow-up of 17 months (range, 1–83 months), none of the patients’ conditions were diagnosed with recurrent disease and 3 (30%) patients achieved pregnancy. Conclusions Cervical conization and SLN mapping seems to be an acceptable treatment strategy for selected patients with small-volume stage I cervical cancer. Tumor clearance of 2 mm and above seems to correlate well with no residual on repeat conization. A larger sample size and longer follow-up is needed to establish the long-term outcomes of this procedure.