Abstract Objectives Our primary objective was to assess the detection rate of sentinel lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for uterine and ...cervical malignancies. Methods NIR fluorescence imaging for the robotic platform was obtained at our institution in 12/2011. We identified all cases planned for SLN mapping using fluorescence imaging from 12/2011–4/2013. Intracervical ICG was the fluorophobe in all cases. Four cc (1.25 mg/mL) of ICG was injected into the cervix alone divided into the 3- and 9-o'clock positions, with 1 cc deep into the stroma and 1 cc submucosally before initiating laparoscopic entry. Blue dye was concurrently injected in some cases. Results Two hundred twenty-seven cases were performed. Median age was 60 years (range, 28–90 years). Median BMI was 30.2 kg/m2 (range, 18–60 kg/m2 ). The median SLN count was 3 (range, 1–23 ). An SLN was identified in 216 cases (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases, 188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in cases in which both dyes were used ( P = NS). Bilateral mapping was seen in 156/197 (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases ( P = NS). Conclusions NIR fluorescence imaging with intracervical ICG injection using the robotic platform has a high bilateral SLN detection rate and appears favorable to using blue dye alone and/or other modalities. Combined use of ICG and blue dye appears unnecessary.
Abstract Objective To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial ...cancer. Methods A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied. Results From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND. Conclusions Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.
Purpose
To assess sexual/vaginal health issues and educational intervention preferences in women with a history of breast or gynecologic cancer.
Methods
Patients/survivors completed a cross-sectional ...survey at their outpatient visits. Main outcome measures were sexual dysfunction prevalence, type of sexual/vaginal issues, awareness of treatments, and preferred intervention modalities. Descriptive frequencies were performed, and results were dichotomized by age, treatment status, and disease site.
Results
Of 218 eligible participants, 109 (50%) had a history of gynecologic and 109 (50%) a history of breast cancer. Median age was 49 years (range 21–75); 61% were married/cohabitating. Seventy percent (
n
= 153) were somewhat-to-very concerned about sexual function/vaginal health, 55% (
n
= 120) reported vaginal dryness, 39% (
n
= 84) vaginal pain, and 51% (
n
= 112) libido loss. Many had heard of vaginal lubricants, moisturizers, and pelvic floor exercises (97, 72, and 57%, respectively). Seventy-four percent (
n
= 161) had used lubricants, 28% moisturizers (
n
= 61), and 28% pelvic floor exercises (
n
= 60). Seventy percent (
n
= 152) preferred the topic to be raised by the medical team; 48% (
n
= 105) raised the topic themselves. Most preferred written educational material followed by expert discussion (66%,
n
= 144/218). Compared to women ≥50 years old (41%,
n
= 43/105), younger women (54%,
n
= 61/113) preferred to discuss their concerns face-to-face (
p
= 0.054). Older women were less interested in online interventions (52%,
p
< 0.001), despite 94% having computer access.
Conclusion
Female cancer patients/survivors have unmet sexual/vaginal health needs. Preferences for receiving sexual health information vary by age. Improved physician–patient communication, awareness, and educational resources using proven sexual health promotion strategies can help women cope with treatment side effects.
To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244.
The prospective, national, ...cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012–11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy FACT), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%.
In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms.
LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.
•This prospective cooperative group study demonstrated LLE symptoms were associated with poorer outcomes on PRO/QOL measures•Women with LLE symptoms reported lower health-related QOL, higher cancer distress (IES), and negative impact on daily life•Prospective trial to collect and follow sexual partner/activity status in newly diagnosed gynecologic cancer patients
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.
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.
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.
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.
Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of ...all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.
A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.
During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio HR = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.
The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.
Purpose: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival,
and motility, is believed to play an oncogenic role in many cancer ...types. The PIK3CA gene encodes the p110α catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K -like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain
cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers.
Experimental Design: Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA , were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas
(48 of ductal histology and 24 of lobular histology).
Results: Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas.
Conclusions: These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other
components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast
carcinomas.
To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244.
Women undergoing a lymph node dissection for endometrial, cervical, or ...vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4–6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined as a limb volume change (LVC) ≥10% from baseline and categorized as mild: 10–19% LVC; moderate: 20–40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed.
Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28–91) in the endometrial, 44 years (range, 25–83) in the cervical, and 58 years (range, 35–88) in the vulvar group. The incidence of LVC ≥10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4–6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033).
For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors.
•Lymphedema as defined by volume change ≥10% was found in 34% of endometrial, 35% of cervical, and 43% of vulvar patients.•Regression analysis showed risk decreased with advanced age (p = 0.0467) and increased with a node count >8 (p = 0.033).•Increase risk of lymphedema was not associated with radiation, advanced stage or other commonly reported risk factors.•Final conclusions were weakened by 50% lost to follow-up and discrepancies in measurements identified in 32% of patients.
To describe the incidence of symptomatic postoperative lower-extremity lymphedema in women treated for uterine corpus cancer, and to evaluate its relationship to regional lymph node removal and ...postoperative therapy.
A retrospective chart review of all patients with uterine corpus cancer managed over a 12-year period (1/93-12/04). All patients had a hysterectomy as part of their therapy. We identified patients with leg lymphedema - as described by the physician or reported by the patient - through medical records. We excluded cases of leg edema that developed secondary to medical conditions such as cardiovascular and renal disease, venous thrombosis, and end-stage recurrent malignancy. Lymphedema dermal changes and related fibrosis were graded using the common terminology criteria for adverse events.
In all, 1,289 patients with uterine corpus malignancy were evaluated. We excluded other chronic lower-extremity edema that was related to a variety of medical conditions in 74 patients (5.7%). With a median follow-up of 3 years (interquartile range, 1.1-5.4 years), new symptomatic post-treatment lower-extremity lymphedema was noted in 16 patients. Patients who had lymph nodes removed at initial surgery had a higher rate of developing lymphedema (16/670, 2.4%) than those who did not (0/619, 0%) (P = 0.0001). Furthermore, symptomatic lymphedema was limited to patients who had 10 or more regional lymph nodes removed 16/469 (3.4%). Lymphedema was noted at a median of 5.3 months after surgery (range, 1-32 months). Lymphedema was unilateral in 11 patients (69%) and bilateral in 5 (31%); moreover, it was considered grade 1 in 12 patients (75%) and grade 2 in 4 (25%). Age, weight, stage, type of hysterectomy, and type of postoperative adjuvant therapy were not associated with lymphedema.
To date, this is the largest series evaluating symptomatic lower-extremity lymphedema in women with uterine corpus cancer. Patients who had 10 or more regional lymph nodes removed at initial surgery appeared to be at higher risk for developing new symptomatic leg lymphedema. Patients undergoing surgery with lymphadenectomy for uterine corpus malignancy should be informed about the possibility of postoperative new symptomatic leg lymphedema. A prospective evaluation of leg lymphedema is needed to accurately determine the incidence, severity, and risk factors of this complication.
Women with mutations in BRCA1 or BRCA2 are at tremendously increased lifetime risk of both breast and BRCA-associated gynecologic (ovarian, fallopian tube, and primary peritoneal) cancer. Because of ...limitations in the efficacy of available screening and chemopreventive approaches for women with a mutation in one of these genes, surgical risk reduction, particularly risk-reducing salpingo-oophorectomy (RRSO), has become an important component of the management options in hereditary breast-ovarian cancer syndrome. This article will review the rationale and efficacy of RRSO for prevention of breast and BRCA-associated gynecologic cancer. Surgical technique and methods of pathologic evaluation will be presented. Controversies regarding uterine preservation and post-RRSO hormone replacement therapy will be addressed. Considerations that may impact the appropriate timing of the procedure will be reviewed, and the potential role of RRSO in BRCA-negative hereditary breast cancer families will also be discussed.
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