Summary Background Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative ...predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. Methods In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov , number NCT01673022 and is completed and closed. Findings Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12%) patients had positive nodes, 36 of whom had at least one mapped sentinel lymph node. Nodal metastases were identified in the sentinel lymph nodes of 35 (97%) of these 36 patients, yielding a sensitivity to detect node-positive disease of 97·2% (95% CI 85·0–100), and a negative predictive value of 99·6% (97·9–100). The most common grade 3–4 adverse events or serious adverse events were postoperative neurological disorders (4 patients) and postoperative respiratory distress or failure (4 patients). 22 patients had serious adverse events, with one related to the study intervention: a ureteral injury incurred during sentinel-lymph-node dissection. Interpretation Sentinel lymph nodes identified with indocyanine green have a high degree of diagnostic accuracy in detecting endometrial cancer metastases and can safely replace lymphadenectomy in the staging of endometrial cancer. Sentinel lymph node biopsy will not identify metastases in 3% of patients with node-positive disease, but has the potential to expose fewer patients to the morbidity of a complete lymphadenectomy. Funding Indiana University Health, Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology.
Abstract Objective Traditional techniques of sentinel lymph node (SLN) mapping for endometrial and cervical cancer present challenges which may be overcome with newer technologies such as near ...infrared (NIR) imaging of the fluorescent dye Indocyanine green (ICG). We performed a feasibility and dose-finding study to define the dose of ICG required to identify pelvic and para-aortic sentinel lymph nodes with robotically assisted endoscopic NIR imaging after cervical injection. Methods 20 subjects with cervical or endometrial carcinoma were prospectively enrolled for SLN mapping. ICG was injected into the cervical stroma at 3 o'clock and 9 o'clock Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared to the non-sentinel lymph nodes. Results 20 subjects received cervical injection with at least one SLN observed in 17 subjects. 15 of the 17 subjects who received 1 mg injections of ICG mapped a SLN for an observed detection rate of 88% (95% CI is (64%,99%)). A median of 4.5 SLN's was identified per patient. Three patients had lymphatic metastases, one of whom had a positive SLN. No adverse events were identified. Conclusions A 1 mg cervical injection of ICG identified a SLN in 88% of patients (95% CI is (64%, 99%)). Robotically assisted fluorescence imaging is a feasible, safe, time efficient and reliable method for lymphatic mapping in early stage cervical and endometrial cancer.
Abstract The emphasis in contemporary medical oncology has been “precision” or “personalized” medicine, terms that imply a strategy to improve efficacy through targeted therapies. Similar attempts at ...precision are occurring in surgical oncology. Sentinel lymph node (SLN) mapping has recently been introduced into the surgical staging of endometrial cancer with the goal to reduce morbidity associated with comprehensive lymphadenectomy, yet obtain prognostic information from lymph node status. The Society of Gynecologic Oncology's (SGO) Clinical Practice Committee and SLN Working Group reviewed the current literature for preparation of this document. Literature-based recommendations for the inclusion of SLN assessment in the treatment of patients with endometrial cancer are presented. This article examines: • History and various techniques of SLN mapping in endometrial cancer • Pathology and clinical outcomes from SLN assessment • Controversies and future directions for research in SLN assessment in endometrial cancer.
To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or ...persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle.
Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.
Objective The purpose of this study was to compare outcomes in women who underwent endometrial cancer staging by different surgical techniques. Study Design Three hundred twenty-two women underwent ...endometrial cancer staging: 138 by laparotomy (TAH); 81 by laparoscopy (TLH) and 103 by robotic technique (TRH). Results The TRH cohort had a higher body mass index than the TLH cohort ( P = .0008). Lymph node yield was highest for TRH ( P < .0001); hospital stay ( P < .0001) and estimated blood loss ( P < .0001) were lowest for this cohort. Operative time was longest for TLH (213.4 minutes) followed by TRH (191.2 minutes) and TAH (146.5 minutes; P < .0001. Postoperative complication rates were lower for TRH, compared with TAH (5.9% vs 29.7%; P < .0001). Conversion rates for the robotic and laparoscopic groups were similar. Conclusion TRH with staging is feasible and preferable over TAH and may be preferable over TLH in women with endometrial cancer. Further study is necessary to determine long-term oncologic outcomes.
Sentinel lymph node (SLN) mapping with indocyanine green (ICG) detected by robotic near infrared (NIR) imaging is a feasible technique. The optimal site of injection (cervical or endometrial) for ...endometrial cancer has yet to be determined. We prospectively evaluated SLN mapping after cervical and endometrial injections of ICG to compare the detection rates and patterns of nodal distribution.
Twenty-nine subjects with endometrial cancer undergoing robotic hysterectomy with lymphadenectomy by a single surgeon received SLN mapping with robotic fluorescence imaging. Seventeen patients received cervical injections of 1 mg of ICG and 12 patients received hysteroscopic endometrial injections of 0.5-mg ICG. Detection rates between the 2 groups were compared using Fisher exact tests. Continuous variables such as operating room times and body mass index were compared using t tests.
The SLN detection rate was 82% (14/17) for cervical and 33% (4/12) for hysteroscopic injection (P = 0.027). Sentinel lymph nodes were seen bilaterally in 57% (8/14) of the cervical injection group and 50% (2/4) of the hysteroscopic group. Para-aortic SLNs were seen in 71% (10/14) of patients who mapped after cervical injection and 75% (3/4) patients who mapped after hysteroscopic injection. There was 1 false-negative SLN in the cervical injection group.
Cervical ICG injection achieves a higher SLN detection rate and a similar anatomic nodal distribution as hysteroscopic endometrial injection for SLN mapping in patients with endometrial cancer.
Objective The purpose of this study was to compare robotically assisted hysterectomy (RAH) with open (ORH) type III radical hysterectomy in the treatment of early-stage cervical cancer. Study Design ...The outcomes of 51 consecutive patients who underwent RAH were compared with the outcomes of 49 patients who underwent ORH. Results There were no differences with regard to patient demographics. There were significant differences between the groups with regard to operative blood loss ( P < .0001), operative time ( P = .0002), and lymph node retrieval ( P = .0003), all of which were in favor of the RAH cohort. All patients with RAH were discharged on postoperative day 1, compared with a 3.2-day average hospitalization for the cohort with ORH. The incidence of postoperative complications was 7.8% and 16.3% for the RAH and ORH cohorts, respectively ( P = .35). Conclusion Robotic type III radical hysterectomy with pelvic node dissection is feasible and may be preferable over open radical hysterectomy in patients with early-stage cervical cancer. Further study will determine procedure generalizability and long-term oncologic outcomes.
Given that prolonged exposure to estrogen and increased telomerase activity are associated with endometrial carcinogenesis, our objective was to evaluate the interaction between the MAPK pathway and ...estrogen induction of telomerase activity in endometrial cancer cells. Estradiol (E2) induced telomerase activity and hTERT mRNA expression in the estrogen receptor (ER)-α positive, Ishikawa endometrial cancer cell line. UO126, a highly selective inhibitor of MEK1/MEK2, inhibited telomerase activity and hTERT mRNA expression induced by E2. Similar results were also found after transfection with ERK 1/2-specific siRNA. Treatment with E2 resulted in rapid phosphorylation of p44/42 MAPK and increased MAPK activity which was abolished by UO126. The hTERT promoter contains two estrogen response elements (EREs), and luciferase assays demonstrate that these EREs are activated by E2. Exposure to UO126 or ERK 1/2-specific siRNA in combination with E2 counteracted the stimulatory effect of E2 on luciferase activity from these EREs. These findings suggest that E2-induction of telomerase activity is mediated via the MAPK pathway in human endometrial cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective Thirty-three percent of U.S. women are either obese or morbidly obese. This is associated with an increased risk of death from all causes and is also associated with an increased ...risk of endometrial carcinoma. We sought to compare minimally invasive surgical techniques for staging the obese and morbidly obese woman with endometrial cancer. Materials and methods Consecutive robotic endometrial cancer staging procedures were collected from 2005–2007 and were compared to consecutive laparoscopic cases (2000–2004). Demographics including age, weight, body mass index (BMI), operative time, estimated blood loss, lymph node retrieval, hospital stay and complications were collected and compared. Results During the study period, there were 36 obese and 13 morbidly obese women who underwent surgery with the DaVinci® robotic system and 25 obese and 7 morbidly obese women who underwent traditional laparoscopy. For both the obese and morbidly obese patient, robotic surgery was associated with shorter operative time ( p = 0.0004), less blood loss ( p < 0.0001), increased lymph node retrieval ( p = 0.004) and shorter hospital stay ( p = 0.0119). Conclusions Robotic surgery is a useful minimally invasive tool for the comprehensive surgical staging of the obese and morbidly obese woman with endometrial cancer. As this patient population is at increased risk of death from all causes, including post-operative complications, all efforts should be made to improve their outcomes and minimally invasive surgery provides a useful platform by which this can occur.
Abstract Objective To report clinical and pathologic relationships with disease spread in endometrial cancer patients. Methods Surgical candidates with uterine cancer (adenocarcinoma or ...carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003–2007, open eligibility enrollment was conducted, and from 2007–2011, eligibility was restricted to enrich underrepresented patients or those at high risk. Results This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease. Conclusions This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.
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