Faculty Bibliography

Group A streptococcal (GAS) toxic shock syndrome (TSS) is a rare life-threatening illness. Most reported cases have occurred in the post-partum period. Here, we report a rare case of a primigravid who developed GAS TSS in the third trimester. We also review the potential preventive measures and treatment modalities for this syndrome. A 29-year-old primigravid presented at 36 weeks' gestation with diarrhea, abdominal pain, fever, and fetal bradycardia. She underwent an emergency cesarean section and was subsequently diagnosed with GAS TSS. She had a complicated post-partum course marked by a 3-month hospital stay and major sequelae. Her infant died on post-partum day 4. GAS TSS should be considered in the differential diagnosis of pregnant patients presenting with fever and rapid onset of septic shock. A consideration to treat GAS that is detected incidentally during routine screening for group B streptococcus is suggested.

UNLABELLED:: Lymph node removal for staging, as part of the initial surgical management of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. There is currently wide variability among clinical practices, with surgical approaches ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. Lymphatic mapping has emerged as an increasingly popular option over the past few years, with several attractive features in its concept, innovative surgical approach, and encouraging preliminary results. At this time, however, several different techniques have been described and used for lymphatic mapping in endometrial cancer, incorporating a variety of mapping agents and injection sites. Although recently published results are encouraging, they are limited to single-institution series or multi-institutional collaborations undertaken without the aegis of a prospective randomized controlled trial. However, the surgical staging of endometrial cancer with lymphadenectomy was historically established based not on randomized trial data but on prospective clinicopathologic studies. Another evolving field in endometrial cancer staging is the interpretation of pathologic ultrastaging of sentinel lymph nodes (SLNs), which can identify low-volume metastases for which the clinical significance and the ideal management remain uncertain. This is particularly an issue with extremely low-volume nodal metastasis and isolated tumor cells. Furthermore, it has become apparent that applying a predefined SLN algorithm can decrease false-negative rates. The Memorial Sloan Kettering Cancer Center SLN algorithm can be used as a checklist to ensure standardization of care and to reduce the chance of missing nodal disease. Prospective trials are under way at many institutions to help establish the definitive role of SLN mapping for staging of endometrial cancer. The objective of this study was to provide an update on the latest clinical data related to lymphatic mapping for the staging and management of endometrial cancer and its role in clinical practice. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Lymphatic mapping is an increasingly popular option in the surgical treatment of endometrial cancer. The aim of using this tool is to target the lymph nodes that are the most likely to be involved with metastatic cancer cells (sentinel lymph nodes) and thereby limit the extent of surgery needed and decrease surgical complications and long-term side effects associated with extensive lymph node removal. By examining a limited number of sentinel lymph nodes, a more detailed examination of the node can be done (ultrastaging). This allows for the detection of a small number of cancer cells (low-volume metastasis) that can be missed with standard techniques.

While there is an ongoing debate regarding the timing of the maximal surgical effort in epithelial ovarian cancer, it is well established that patients with suboptimal tumor debulking derive no benefit from the surgical procedure. The amount of residual disease after cytoreductive surgery has been repeatedly identified as a strong predictor of survival, and accordingly, the surgical effort to achieve the goal of complete gross tumor resection has been constantly evolving. Centers that have adopted the concept of radical surgery in patients with advanced ovarian cancer have reported improvements in their patients' survival. In addition to the expected improvements in the pharmacologic treatment of this disease, some of the next challenges in the surgical management of ovarian cancer include the preoperative prediction of suboptimal debulking, improving the drug delivery to the tumor, and increasing access to centers of excellence in ovarian cancer regardless of geographical, financial, or other social barriers. This review will discuss an update on the role of surgery in the treatment of primary epithelial ovarian cancer as it has evolved since the emergence of the concept of surgical cytoreduction.

OBJECTIVES/OBJECTIVE: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.

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.

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.

OBJECTIVE:It is well documented that recurrence after pelvic exenteration remains high (up to 50%), and patients may require a prolonged period of recuperation following this aggressive surgery. We conducted a retrospective review to evaluate the feasibility of administering adjuvant chemotherapy after pelvic exenteration for gynecologic malignancies. METHODS:We reviewed the medical records of patients with any gynecologic cancer who underwent exenterative surgery between January 2005 and February 2011 at our institution. Patients were referred for postexenteration adjuvant chemotherapy based on surgeon's discretion and/or presence of high-risk features: positive margins, positive lymph nodes, and/or lymphovascular space invasion. Suitability for chemotherapy was assessed by a gynecologic medical oncologist. Regimens consisted of 4 to 6 cycles of platinum-based doublet chemotherapy. Chemotherapy-related toxicities were assessed using the Common Terminology Criteria for Adverse Events version 4. RESULTS:We identified 42 patients who underwent pelvic exenteration during the study period. Eleven (26%) were referred for adjuvant chemotherapy. Three (27%) of the 11 patients did not receive chemotherapy because of delayed postoperative recovery or physician choice. Seven (88%) of the remaining 8 patients completed all scheduled chemotherapy. Grade 2 toxicities or greater were documented in 6 patients (75%), the most common being neutropenia, neuropathy, and fatigue. Median follow-up time was 25 months (range, 6-56 months). The 3-year progression-free and overall survival rates of the 8 patients who received chemotherapy were 58% (95% confidence interval, 18%-84%) and 54% (95% confidence interval, 13%- 83%), respectively. CONCLUSIONS:The administration of adjuvant chemotherapy is feasible for a select group of patients after pelvic exenteration for gynecologic malignancies. Our results need to be interpreted with caution because of the small and heterogeneous cohort of patients included.

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.

OBJECTIVE:The objective of this study was to compare morbidity and outcome following radical surgery with or without adjuvant radiation therapy (RT) in the treatment of stages IB1-IB2 cervical carcinoma. METHODS:We retrospectively identified 222 patients with stages IB1-IB2 cervical carcinoma treated initially with radical hysterectomy or radical trachelectomy with or without adjuvant RT from February 2000 to November 2009. All grade 3 or higher complications-those requiring interventional radiology, endoscopic evaluation, or operative intervention-were documented. RESULTS:One hundred fifty-eight patients (71%) underwent radical hysterectomy; 64 (29%) underwent radical trachelectomy. One hundred fifty-three patients (69%) underwent surgery alone; 69 (31%) received adjuvant radiation with or without chemosensitization. There was a statistically significant difference in the rate of total grades 1 to 5 late complications between the surgery-alone and surgery + RT groups (12% vs 32%, respectively; P < 0.001); however, the rate of grade 3 or higher complications was similar (5% vs 4%, respectively; P = 0.999). The progression-free and overall survival rates of the entire cohort were both 95%. The 5-year progression-free survival rates for the surgery-alone and surgery + RT groups were 93% and 90% (P = 0.172). The overall survival rates were 96% and 91%, respectively (P = 0.332). CONCLUSIONS:The majority of women with stages IB1-IB2 cervical cancer undergoing radical surgery do not require adjuvant RT, have excellent oncologic outcome, and have low severe complication rates. Nearly one third of our patients required postoperative radiation, with no statistically significant increase in severe complication rate and with similar oncologic outcomes compared with the surgery-only cohort. These data support the continued practice of radical surgery with individualized postoperative radiation for these patients.

OBJECTIVE:The purpose of this study was to describe the location of disease at the time of death of patients with endometrial cancer who died of their disease. METHODS:All patients with a diagnosis of endometrial cancer from January 1993 through December 2010 were included. Histologic classification was either endometrioid or high-risk (HR) endometrial cancer. Patients who died were divided into 3 groups: dead of disease (DOD), dead of other causes (DOO), and dead lost to follow-up. Patterns of disease spread at death were documented from the most recent examination and imaging studies. RESULTS:We identified 2513 patients. The median age at diagnosis was 62 years. Histologic findings were endometrioid endometrial cancer, 1949 patients (78%); and HR endometrial cancer, 54 patients (22%). The 1988 International Federation of Gynecology and Obstetrics stages were: stage I, 1763 patients (70%); stage II, 145 patients (6%); stage III, 416 patients (17%); and stage IV, 189 patients (8%). At the time of this study, 1867 patients (74%) had no evidence of disease, 232 patients (9%) were alive with disease, and 414 patients (16%) were dead. Of the 16% of patients who were dead, 224 (9%) of the 2513 patients were DOD, 84 (3%) of the 2513 patients were dead of other disease, and 106 (4%) of the 2513 patients were dead lost to follow-up. Of the 224 patients who were DOD, the locations of the disease at the time of death were pelvic, 23 patients (10%); abdominal, 83 patients (37%); and distant, 118 patients (53%). There was no significant difference in the pattern of location of disease between the endometrioid and HR histologies (P = 0.36). CONCLUSIONS:These data suggest that death from endometrial cancer is largely due to abdominal (liver) and distant (lung) metastases, and this pattern of disease seems similar in the endometrioid and HR histologies. Most of the patients who died of their disease had metastases beyond the pelvis at the time of death.