What is the role of lymphadenectomy in surgical management of patients with endometrial carcinoma?

The role of lymphadenectomy in the management of endometrial carcinoma remains controversial in gynecologic oncology. Comprehensive pelvic and paraaortic lymphadenectomy should be performed in patients with intermediate- and high-risk endometrial cancer.     

Is selective lymphadenectomy more cost-effective than routine lymphadenectomy in patients with endometrial cancer?

ObjectiveThe objective of this study is to determine the cost-effectiveness of two strategies in women undergoing surgery for newly diagnosed endometrial cancer.MethodsA decision analysis model compared two surgical strategies: 1) routine lymphadenectomy independent of intraoperative risk factors or 2) selective lymphadenectomy for women with high or intermediate risk tumors based on intraoperative assessment including tumor grade, depth of invasion, and tumor size. Published data were used to estimate the outcomes of stage, adjuvant therapy, and recurrence. Costs of surgery, radiation, and chemotherapy were estimated using Medicare Current Procedural Technology codes and Physician Fee Schedule. Cost-effectiveness ratios were estimated for each strategy. Sensitivity analyses were performed including an estimate for lymphedema for patients that underwent a lymphadenectomy.ResultsFor 40,000 women diagnosed annually with endometrial cancer in the United States, the annual cost of selective lymphadenectomy is $1.14 billion compared to $1.02 billion for routine lymphadenectomy. The selective lymphadenectomy strategy cost an additional $123.3 million. Five-year progression-free survival was 85.9% in the routine strategy compared to 79.3% in the selective strategy. Treatment cost $6349 more per survivor in the selective strategy compared to routine strategy ($36,078 vs. $29,729). These results held up under a variety of sensitivity analyses including costs due to lymphedema which were higher in the routine lymphadenectomy strategy compared to the selective lymphadenectomy strategy ($10 million vs. $7.75 million).ConclusionsA strategy of selective lymphadenectomy based on intraoperative risk factors for patients with endometrial cancer was less cost-effective than routine lymphadenectomy even when the impact of lymphedema was considered.     

Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic activity in the breast and oestrogenic effects in various tissues such as the endometrium, bone and cardiovascular territory. As adjuvant hormone therapy, it has a clear beneficial effect in patients with breast cancer, reducing relapses, contralateral breast cancer and mortality. Its most important secondary effect is a greater rate of occurrence of endometrial cancer. Although the risk/benefit ratio is clearly positive, the follow-up on these patients is still an issue. In women with metrorrhagia, it is clear that an endometrial sample must be obtained for histological examination and the best procedure today is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic patients is not universally accepted. The vaginal ultrasound scan gives a great number of false positives. This entails more aggressive and more expensive procedures such as hysteroscopic-directed biopsy, meaning greater expense and more complications. As a result, the cost/benefit ratio is not very favourable. The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases were diagnosed in asymptomatic patients. In this article, we analyse the literature on the need to screen patients on tamoxifen and about the most appropriate diagnostic protocol.     

Is tocolysis safe in the management of third-trimester bleeding?

Objective: Expectant management is among the current treatment options for pregnancies complicated by third-trimester bleeding at <36 weeks’ gestation. The use of tocolytic agents to stop associated contractions is still somewhat controversial, however, and the number of cases reported to date is small. The purpose of our study was to find a large number of cases of preterm third-trimester bleeding that was treated with tocolytic agents and evaluate them for any evidence of potential harm related to the use of these agents. Study Design: Every case of third-trimester bleeding for a 6-year period was obtained from a perinatal database that was created as patients were hospitalized. Only cases of patients with onset of bleeding between 23 and 36 weeks’ gestation were analyzed. Data collected included the gestational age at the time of first bleeding, the gestational age at delivery, whether tocolytic agents were used, the need for transfusion, maternal morbidity, and neonatal outcome. Results: A total of 236 cases, consisting of 131 cases of abruptio placentae and 105 cases of placenta previa, met the study criteria. In the abruptio placentae group 95 women (73%) were treated with tocolytic agents. In this group the mean gestational age at the time of first bleeding was 28.9 weeks, the mean time from bleeding until delivery was 18.9 days, the median time from bleeding until delivery was 7 days, and the neonatal mortality rate was 51 deaths/1000 live births. In the placenta previa group 76 patients (72%) were treated with tocolytic agents. In this group the mean gestational age at first bleeding was 29.5 weeks, the mean time from bleeding until delivery was 29.3 days, the median time from bleeding until delivery was 22 days, and the neonatal mortality rate was 39 deaths/1000 live births. In both groups the need for transfusion and the incidence of fetal distress were not increased by the use of tocolytic agents. Among the 171 combined patients who underwent tocolysis, no maternal morbidity related to the tocolytic agents was found and no stillbirths occurred after admission. The neonatal deaths were all related to complications of prematurity. Conclusions: This is the largest series to date evaluating the use of tocolytic agents in preterm patients with third-trimester bleeding. From these data there does not appear to be any increased morbidity or mortality associated with tocolytic agent use in a controlled tertiary setting. A prospective randomized trial would be necessary to determine whether tocolytic use carries any benefits. (Am J Obstet Gynecol 1999;180:1572-8.)     

Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary? An analysis from Gynecologic Oncology Group (GOG) 173

ObjectiveTo determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results.MethodsPatients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal–femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (> 2 cm from midline), midline, or lateral ambiguous (LA) if located within 2 cm, but not involving the midline.ResultsTwo-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N = 65) and midline (N = 105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors.ConclusionThe likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.     

Can a lymphadenectomy be avoided in early-stage endometrial adenocarcinoma?

Purpose

Determination of early disease recurrence in patients with early-stage endometrial cancer operated laparoscopically without pelvic or paraaortic lymphadenectomy.

Methods

Retrospective chart review of all patients with endometrial carcinoma operated with laparoscopic-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy between 2004 and 2008.

Results

81 patients were eligible for data analysis. The operation time varied between 32 and 284 min. None of the patients suffered serious intraoperative complications. All patients had endometrial carcinoma of endometrioid type. As adjuvant therapy, patients received no further therapy (n = 30), radiation with brachytherapy with an afterloading technique alone (n = 36) or brachytherapy in combination with percutaneous radiation (n = 15). The observation period varied between 19 and 28 months (median 26 months). No patients were lost to follow-up. During the observation period, none of the patients had recurrence of disease or died.

Conclusions

Laparoscopic-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy without pelvic or paraaortic lymphadenectomy combined with stage-adapted postoperative irradiation is a safe and efficient treatment option for patients with early-stage endometrial cancer of the endometriod type regarding early disease recurrence.     

What is the incidence of isolated paraaortic nodal recurrence in grade 1 endometrial carcinoma?

ObjectivesTo describe the incidence of isolated paraaortic nodal recurrences in patients with a final diagnosis of grade 1 endometrial carcinoma initially treated with surgery.MethodsRecords from a prospectively maintained endometrial carcinoma database were reviewed to identify sites of recurrence. Patients with any papillary serous or clear cell carcinoma, leiomyosarcoma, endometrial stromal sarcoma, squamous carcinoma, or adenosarcoma were excluded. Recurrence sites were classified into 4 main categories: 1) pelvic (including vaginal and other soft tissue pelvic sites); 2) abdominal (including peritoneum, omentum and liver); 3) distant (including lung, brain, supraclavicular, and groins); and 4) isolated paraaortic nodal recurrence (including any nodal recurrence between the midcommon iliac to renal vessels).ResultsBetween 1/93 and 5/06, 1453 patients with endometrial carcinoma met the study inclusion criteria. Final grade distribution included: grade 1 endometrial adenocarcinoma, 310 (21%); grade 2, 578 (40%); grade 3, 481 (33%); and incomplete, 84 (5.8%). In all, 154 patients (11%) had documented recurrences. Recurrence sites for all patients/all grades included: pelvis, 52 (34%); abdomen, 51 (33%); distant, 41 (27%), and isolated paraaortic, 10 (6%). None of the isolated paraaortic recurrences occurred in patients with a final diagnosis of grade 1 carcinoma. Furthermore, 9/10 (90%) isolated paraaortic nodal recurrences were in grade 3 tumors. Only 8 (2.6%) of 310 patients with grade 1 tumors recurred. Sites of recurrence for grade 1 tumors included: abdomen, 3; pelvis, 3; and distant, 2.ConclusionsThis large series of endometrial carcinoma patients initially treated with surgery confirms that isolated paraaortic nodal recurrence in women with a final diagnosis of grade 1 endometrial carcinoma is extremely rare. These rare isolated paraaortic nodal recurrences appear to be limited to high-grade endometrial carcinomas.     

Is endometrial apoptosis evidence of endometrial aging in unexplained infertility? a preliminary report

OBJECTIVE: To investigate spontaneous endometrial apoptosis in women with unexplained infertility and to find out whether there is a possible relationship between endometrial apoptosis, age, and hormonal parameters. STUDY DESIGN: This study was designed as a prospective, case-controlled study in a University Hospital setting. A total of 34 endometrial biopsies were performed from 17 women with unexplained infertility and 17 fertile controls, who were admitted for tubal ligation. Endometrium was sampled on the seventh post-ovulatory day. On the same day of endometrial sampling, serum levels of FSH, LH, PRL, TSH, E2, progesterone, 17alpha-hydroxyprogesterone, testosterone and DHEA-S were determined. Endometrial glandular and stromal apoptosis were investigated by DNA nick end labeling (TUNEL) method on each sample. Endometrial apoptotic index was calculated and correlated with age and hormonal parameters. RESULTS: There was no difference in either endometrial glandular apoptotic index (AI) or stromal AI between the groups. However, the mean glandular AI was significantly higher than the mean stromal AI (p = 0.0001). There was a strong correlation between endometrial AI and age (r = 0.91, p = 0.02). Serum T levels were significantly found to be decreased in the unexplained infertility group (p = 0.0001). In addition, serum TSH levels were positively correlated with AI in the glandular endometrium in women with unexplained infertility (r = 0.611, p = 0.009). CONCLUSION: Endometrial apoptosis increases with age. Serum levels of testosterone were lower in unexplained infertility. The effect of serum TSH levels on apoptosis in the glandular epithelium of the endometrium needs further studies.     

Is time to recurrence after hysterectomy predictive of survival in patients with early stage endometrial carcinoma?

Purpose/objective(s)

To determine the prognostic significance of time to recurrence (TTR) on overall survival (OS) and disease-specific survival (DSS) following recurrence in patients with stage I-II uterine endometrioid carcinoma.

Materials/methods

After IRB approval, we retrospectively identified 57 patients with recurrent endometrioid carcinoma who were initially treated for FIGO 1988 stages I-II between 1987 and 2009. The Kaplan-Meier approach and Cox regression analysis were used to estimate OS and DSS following recurrence and identify factors impacting outcomes.

Results

Median follow-up times were 54.8 months from hysterectomy and 19.8 months after recurrence. Median time to recurrence was 20.2 months. Twenty-eight (47%) patients had a recurrence < 18 months after hysterectomy and 29 (53%) had a recurrence ≥ 18 months. Both groups were evenly matched regarding initial pathological features and adjuvant treatments. The median OS and DSS in patients with TTR < 18 months was shorter than those with TTR ≥ 18 months, but not statistically significant (p = 0.216). TTR did not impact outcomes after loco-regional recurrence, but for extrapelvic recurrence, a shorter TTR resulted in worse OS and DSS (p = 0.03). On multivariate analysis, isolated loco-regional recurrence (HR 0.28, p = 0.001) and salvage radiation therapy (HR 0.47, p = 0.045) were statistically significant independent predictors of longer OS following recurrence. TTR as a continuous variable or dichotomized was not predictive of OS or DSS.

Conclusions

In our study, the prognostic impact of time to recurrence was less important than the site of recurrence. While not prognostic for the entire cohort or for patients with loco-regional recurrence, TTR < 18 months was associated with shorter OS and DSS after extrapelvic recurrence.     

Is the monitoring of anti-Xa activity necessary in pregnant women undergoing thromboprophylaxis?

Thromboprophylaxis is increasingly advocated in pregnancy for certain clinical conditions. Low molecular weight heparins offer potential benefit over unfractionated heparins with increased bioavailability and a longer half-life, thus allowing for once daily administration. This study aims to determine if monitoring of anti-Xa activity is necessary in pregnant women undergoing thromboprophylaxis. Twenty-five pregnancies were prospectively followed where either tinzaparin or enoxparin was employed for thromboprophylaxis. Once the anti-Xa levels were in the thromboprophylactic range (0.03-0.5 U/ml) no patient required a change of dose. Frequent monitoring of Anti-Xa levels, once in the thromboprophylactic range, may not be required.     

Is common iliac lymph node dissection necessary in early stage cervical carcinoma?

OBJECTIVES: Nodal metastasis is one of the most important prognostic factors in early stage cervical carcinoma and has an immense impact on the subsequent management. Thus, searching for nodal metastasis by pelvic lymphadenectomy is an integral part in the surgical management of cervical carcinoma. Complete nodal clearance of lymphatic tissue up to 2 cm above the bifurcation of common iliac vessels is therefore performed as a routine in our unit. The aim of this study is to investigate the incidence and pattern of pelvic lymph node metastases in patients with early stage cervical carcinoma to determine the role of common iliac node dissection in the surgery. METHODS: We retrospectively reviewed 174 operation and histopathology reports of patients who underwent pelvic lymphadenectomy because of stage IA2 to IIA cervical carcinoma. Lymph nodes collected below and above the bifurcation of common iliac vessels were labeled as pelvic nodes and common iliac nodes, respectively. The incidence and distribution of nodal metastases were analyzed. RESULTS: Complete and selective pelvic lymphadenectomy was performed in 163 and 11 patients, respectively. Nodal metastasis was documented in 35 (20.1%) patients. Pelvic and common iliac nodes were involved in 34 and 8 cases, respectively. All except one patient with common iliac node metastases were also found to have pelvic node metastasis. CONCLUSIONS: In early stage cervical carcinoma, isolated common iliac lymph node metastasis is rare, especially in cases without associated high risk factors. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operation morbidity and time.     

Is sonographic assessment of the cervix necessary and helpful?

Transvaginal sonography of the cervix has emerged as a useful window into preterm parturition. Cervical sonography allows measurements of cervical length (CL), which can aid clinicians in identifying women at risk for preterm birth. The use of transvaginal assessments of CL can assist in the triage of patients with possible preterm labor. Recent studies also support the use of CL measurements as a means of determining appropriate candidates for cerclage placement and progesterone supplementation to reduce the risk of premature birth, further highlighting the importance of this modality in modern obstetric management.