Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.

HE4 suppresses the expression of osteopontin in mononuclear cells and compromises their cytotoxicity against ovarian cancer cells.

Ovarian cancers are known to evade immunosurveillance and to orchestrate a suppressive immune microenvironment. Here we examine the role of human epididymis protein 4 (HE4), an ovarian cancer biomarker, in immune evasion. Through modified subtractive hybridization analyses we have characterized the gene targets of HE4 in human peripheral blood mononuclear cells (PBMCs), and established a preliminary mechanism for HE4-mediated immune failure in ovarian tumours. Upon exposure of purified PMBCs to HE4, osteopontin (OPN) and dual-specificity phosphatase 6 (DUSP6) emerged as the most suppressed and up-regulated genes, respectively. SKOV3 and OVCAR8, human ovarian carcinoma cell lines, exhibited enhanced proliferation in conditioned media from HE4-exposed PBMCs, an effect that was attenuated by the addition of recombinant OPN or OPN-inducible cytokines [interleukin (IL)-12 and interferon (IFN)-Ɣ]. Additionally, upon co-culture with PBMCs, HE4-silenced SKOV3 cells were found to be more susceptible to cytotoxic cell death. The relationship between HE4 and OPN was reinforced further through the analysis of serous ovarian cancer patient samples. In these biopsy specimens, the number of OPN+ T cells correlated positively with progression free survival (PFS) and inversely with serum HE4 level. Taken together, these findings show that HE4 enhances ovarian cancer tumorigenesis by compromising OPN-mediated T cell activation.

Cytoreductive surgery for ovarian cancer: quality assessment.

Surgery is the cornerstone of treatment of ovarian cancer. Given the importance of achieving no or minimal macroscopic residual disease at primary surgery, performing an assessment of the quality of ovarian cancer surgery is crucial. Assessing the quality of care and surgical outcome allows us to establish baseline information, set standards of care and clear priorities, enable benchmarking against peers, and sustain quality improvement. We know that suboptimal care exists and variation in outcomes results. One way to monitor variation in outcomes is through a clinical quality registry (CQR). A CQR collects a defined minimum dataset to measure performance of an individual or center against a range of clinical quality indicators and provides risk-adjusted, benchmarked data to participating institutions. CQR's are an excellent quality assurance measure as they capture all cases (an opt out system). They permit detection and analysis of unwarranted variations in care. This can provide indications of a systems or process problem, thereby motivating health care providers to improve services and care. Several groups have either developed quality indicators for advanced ovarian cancer surgery (The Scottish Cancer Taskforce and the European Society of Gynecological Oncology) or are in the process of doing so (Australian Society of Gynaecological Oncologists). Indicators should be evidence-based and determined by extensive discussion with experts and stakeholders to ensure appropriateness and buy-in. The Scottish Cancer Taskforce and European Society of Gynecological Oncology have set targets for their quality performance measures, which should provide a quantitative framework for improving care in the surgical management of ovarian cancer.

Malignant mixed mesodermal tumors of the ovary.

OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.

Urinary symptoms and impact on quality of life in women after treatment for endometrial cancer.

The primary objective of our study is to describe urinary symptoms in women treated for endometrial cancer. We performed a cross-sectional survey of women who had undergone surgical treatment for endometrial cancer. Three validated questionnaires were utilized: the Sandvik Severity Index, the Urinary Distress Inventory-6 (UDI-6), and Incontinence Impact Questionaire-7 (IIQ-7). Our study included 70 women treated for endometrial cancer; 35.7% (25/70) of women reported adjuvant radiation therapy after surgical staging. Urinary incontinence was reported in over 80% of women. Mean UDI-6 and IIQ-7 scores for women treated with adjuvant radiation therapy were higher compared to women with no adjuvant radiation therapy [47(+/-26.8) vs. 35.6(+/-21.7; p = 0.05)] and [24.4(+/-28.5) vs. 8.1(+/-16.4; p = 0.004)], respectively. Treatment with adjuvant radiation therapy was associated with more severe incontinence symptoms and impact on quality of life.

Lower uterine segment involvement as a predictor for lymph node spread in endometrial carcinoma.

OBJECTIVES: Several predictive factors for lymph node spread in endometrial cancer have been identified including tumor grade, depth of invasion, lymphatic or vascular-space invasion, and histologic subtype. Lower uterine segment involvement may also be predictive of lymph node spread. The objective of this study was to investigate the relationship between lower uterine segment involvement in endometrial carcinoma and lymph node spread. METHODS: This was an IRB approved retrospective study. Data were collected for all patients diagnosed with endometrial cancer from June 1999 to December 2004. The primary end point was the presence of nodal involvement. Subset analysis was performed by histologic subtype. Univariate and multivariate nominal logistic regression was performed. Categorical variables were compared using Chi-square and Fischer's Exact Test. RESULTS: Two-hundred and ninety-nine subjects were eligible for review. One-hundred seventy four (58%) had lower uterine segment involvement. Forty-four (25%) of those with lower uterine segment involvement had positive nodes compared to 10 (8%) of those without (p=0.0001). On univariate analysis, lower uterine segment involvement, lymphovascular-space invasion, and deep invasion predicted nodal disease. On multivariate analysis, lower uterine segment remained predictive of nodal spread for the endometrioid subset. For high-risk histologies, only lymphovascular-space invasion and deep myometrial invasion were predictive of nodal spread. CONCLUSIONS: Lower uterine segment involvement in endometrial carcinoma is an important predictor of lymph node involvement for patients with endometrioid histologies. Tumor within the lower uterine segment may be an important factor to consider in intraoperative decision making regarding staging.

Ki-67 Expression in a Cervical Cancer Organotypic Model Correlates with Growth and EGF-R Expression.

OBJECTIVE: The study objective was to measure the effects of retinoid treatment on Ki-67 expression in a cervical carcinoma organotypic culture model and to determine whether a correlation exists between retinoid effects on Ki-67 expression and effects on growth and epidermal growth factor receptor (EGF-R) expression. METHODS: Organotypic cultures of the cervical carcinoma cell line were treated for 7 days with all-trans retinoic acid, 9-cis retinoic acid, or control solvent. Cultures were fixed and embedded in paraffin, and sections were stained with Ki-67 antibodies. Ki-67 expression was determined by light microscopy. RESULTS: Ki-67 expression was inhibited 25% in the organotypic culture treated with 9-cis retinoic acid and 32% in the culture treated with all-frans retinoic acid. Previous data demonstrated a 45% and 44% inhibition of EGF-R expression and a 49% and 63% inhibition of growth, respectively. DISCUSSION: The inhibition of Ki-67 expression by retinoids correlates with inhibition of EGF-R expression and growth as determined by a Pearson correlation (R = 0.88). Inhibition of Ki-67 and EGF-R demonstrates quantifiable effects of retinoids at both the membrane receptor and nuclear protein levels in our organotypic culture model.

Treatment of cervical intraepithelial neoplasia levels 2 and 3 with adapalene, a retinoid-related molecule.

OBJECTIVES: This study examined dose scheduling, safety, and efficacy of adapalene in the treatment of CIN2 and CIN3. METHODS: Patients were instructed on insertion and removal of an adapalene delivery system. Treatment regimens of 4, 8, and 14 days were utilized. Biopsies were performed on day 90 to assess efficacy. Safety was evaluated with toxicity questionnaires and patient interviews. RESULTS: Two patients treated for 4 days had stable disease. Twenty-three patients treated for 8 days demonstrated an overall 61% (14 of 23) response rate. Twenty-four patients treated for 14 days had an overall 38% (9 of 24) response rate. No patient had disease progression. Compared to untreated historical controls, significantly improved efficacy was demonstrated for patients with CIN2. Patients with CIN3 had improved efficacy, though not statistically significant. CONCLUSIONS: The lack of side effects and practicality of home use make adapalene a nontoxic and safe alternative to surgical therapy in patients with CIN2 and CIN3.

Panniculectomy in morbidly obese gynecologic oncology patients.

BACKGROUND: It is clear that morbid obesity presents a serious risk to women undergoing major intra-abdominal gynecologic surgery. Unfortunately, many gynecologic malignancies and benign conditions are best treated surgically. Thus, the gynecologic surgeon must choose an incision that permits adequate exposure with acceptables rates of complications. Panniculectomy as an approach to the peritoneal cavity is becoming increasingly popular. Recent reports suggest that panniculectomy is reasonably straightforward to perform, provides adequate exposure and is associated with an acceptable rate of manageable complications. In these circumstances, panniculectomy is not a cosmetic procedure, but medically necessary to perform indicated major gynecologic intra-abdominal surgery. AIMS: To present our experience with panniculectomy in morbidly obese women undergoing major intra-abdominal surgery on a gynecologic oncology service. METHODS: The medical records of 48 morbidly obese women (Quetelet Index > 40 kg/m2) with a large dependent pannus who underwent major intra-abdominal surgery via a panniculectomy between May 1990 and October 1999 were reviewed. Data regarding demographics, concomitant medical conditions, operative indications and results, and postoperative outcomes were abstracted for analysis. RESULTS: The mean age was 54.9 years, the mean body mass was 130.2 kg, the mean height was 1.63 m and the mean Quetelet Index was 49.3 kg/m2. The mean operating time was 188 min and the mean estimated blood loss was 615 ml. Two patients suffered intraoperative urologic injuries which were repaired without sequelae; there were no bowel, vascular or neurologic injuries. Eighteen patients had a suprafascial wound breakdown (3 complete and 15 superficial) and 15 patients developed an infection. There were no documented deep venous thromboses, pulmonary emboli or fascial dehiscences. Two patients died in the postoperative period; one from a myocardial infarction on Day 2 and one from overwhelming sepsis on Day 76. CONCLUSIONS: Morbid obesity is associated with substantial operative and postoperative risks. Panniculectomy provides operative exposure with acceptable risks of complications.