Bilateral Singapore fasciocutaneous flap after anterior vulvectomy and distal urethrectomy for localized recurrent vulvar carcinoma.

Introduction: Vulvar cancer has an overall low incidence, accounting for approximately 3-5% of all gynecological malignancies.Case: We present a case of locally recurrent Stage IIIA squamous cell carcinoma of the vulva in a 51-year-old healthy African American female. She was initially treated with primary chemoradiation with cisplatin sensitization and boost to primary tumor up to 70 Gray. Post-treatment biopsies revealed complete pathologic response. She later presented with local recurrence to the primary site of the clitoris and vulva, with no evidence of metastasis on imaging, with progressive disease despite treatment with immunotherapy. Methods: Biopsy-proven disease progression was present on the clitoris, entire left labia minora, and a portion of the right labia minora with no evidence of metastasis on imaging. Surgical resection for localized recurrence was recommended, and she underwent radical anterior vulvectomy, distal urethrectomy, and vulvar reconstruction with bilateral Singapore fasciocutaneous flap as part of a multidisciplinary team. Patient underwent several prophylactic hyperbaric oxygen treatments. There were no issues with postoperative wound healing. Conclusion: Treatment with radical excision often requires multidisciplinary teams for complex reconstructions to restore vulvar anatomy in the setting of prior radiation, especially for those patients desiring the ability to have penetrative intercourse in the future. There are few surgical videos that describe these types of vulvar excisions and subsequent reconstructions. This video provides a unique approach to vulvar reconstruction in a previously irradiated field.

Underserved Pacific Islanders With Locally Advanced Cervical Cancer Receive Higher Rates of Standard-of-Care Radiation Treatment Through the Pacific Island Health Care Project and Military Health System Compared to the Average U.S. Population.

INTRODUCTION: Brachytherapy, with external beam radiation, increases survival in the treatment of locally advanced cervical cancer (LACC). In 2016, Robin et al. reported only 44% of patients received standard-of-care (SOC) brachytherapy in the USA. The Pacific Island Health Care Project has provided humanitarian medical care to women from the U.S. Associated Pacific Islands (USAPI) for three decades at Tripler Army Medical Center (TAMC), a military health care system (MHS) facility. We evaluated whether this underserved and understudied patient population received SOC treatment for LACC at TAMC. MATERIALS AND METHODS: The TAMC tumor registry was searched for all cervical cancer cases from 1997 to 2019. Subjects were excluded if they did not have stage IB2-IVA disease and were not from USAPI. The primary outcome was the overall utilization of brachytherapy, and statistical analysis was performed using the chi-square test. RESULTS: We identified 214 women with cervical cancer treated at TAMC, of which 67 met the study criteria. Ninety-two percent had squamous cell carcinoma on histology. Of the patients identified, 48 (71.6%, P < .001) were treated with brachytherapy. Fifteen (22.4%) patients received external radiation alone, and four (6.0%) received chemoradiation without brachytherapy. A post-hoc power analysis was conducted with a power of 91.3%. CONCLUSIONS: Women with cervical cancer from USAPI in the PIHCP program treated at TAMC received significantly higher rates of SOC radiation treatment than the U.S. population on average. This highlights the ability of PIHCP, through the MHS, to deliver SOC treatment for cervical cancer to an otherwise underserved patient population.

Analyzing trends in obstetrics and gynecology fellowship training over the last decade using the normalized competitive index.

BACKGROUND: The objective and relative competitiveness of obstetrical and gynecologic subspecialty training programs remain understudied. Traditional metrics, such as match rate or program fill rate, fail to standardize the application environment. This limits their applicability when examining demographic trends or when comparing data between different fellowship matches. The normalized competitive index was introduced to serve as a comprehensive metric of competitiveness by incorporating disparate indicators and normalizing to enable more detailed analyses. OBJECTIVE: This study aimed to analyze trends in the competitiveness across obstetrical and gynecologic subspecialty fellowship matches during the last decade. STUDY DESIGN: The results and data reports from the National Resident Match Program fellowship for 2010 to 2019 were used to collect data on multiple metrics of competitiveness for 6 obstetrical and gynecologic subspecialties. These data were used to determine the normalized competitive index. Subanalyses were conducted to identify trends over the last decade. RESULTS: Among fellowship programs in obstetrics and gynecology, the overall specialty match rate was 67.6%. The overall specialty program fill rate was 95.7%. According to the normalized competitive index metric, minimally invasive gynecologic surgery was the most competitive fellowship match (normalized competitive index=1.31; P=.002). Maternal-fetal medicine was the least competitive (normalized competitive index=0.94; P≤.005). When comparing the first and second half of the decade, no specialty experienced a significant decrease in match rate. The only significant increase in match rates occurred for female pelvic medicine and reconstructive surgery (P=.035). Subanalyses of the normalized competitive index metric and other indicators of competitiveness demonstrated a strong negative correlation between the normalized competitive index and the subspecialty match rate (r=-0.9444) and a moderately positive correlation between the normalized competitive index and the program fill rate (r=0.4047). CONCLUSION: The normalized competitive index offers trainees a more quantitative understanding of the fellowship application environment. By incorporating multiple metrics and normalizing the result, it uniquely enables comparison between the subspecialty matches and the match process over time. The same standardization offers the potential for future comparisons of competitiveness within a single subspecialty match based on geographic region, applicant demographics, and other important determinants of a diverse and vibrant training environment.

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study.

Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves. Results: Seven metastasis-associated transcripts were selected from analysis in the training cohorts using 10-fold cross validation and incorporated into an MS7 classifier using platform-specific coefficients. The predictive accuracy of the MS7 classifier in Training-1 was superior to that of other clinical and molecular features, with an area under the curve (95% confidence interval) of 0.89 (0.80-0.98) for MS7 compared with 0.69 (0.59-0.80) and 0.71 (0.58-0.83) for the top evaluated clinical and molecular features, respectively. The performance of MS7 was independently validated in 245 patients using RNA sequencing and in 81 patients using microarray-based data. MS7 + MI (myometrial invasion) was preferrable to individual features and exhibited 100% sensitivity and negative predictive value. The MS7 classifier was associated with lower progression-free and overall survival (p ≤ 0.003). Conclusion: A risk assessment classifier for metastasis and prognosis in EEC patients with primary tumor derived MS7 + MI is available for further development and optimization as a companion clinical support tool.

Validation of an Endometrial Tumor Diameter Model for Risk Assessment in the Absence of Lymph Node Mapping.

PURPOSE: This study aimed to assess the optimal tumor diameter for predicting lymphatic metastasis and to determine intraoperatively the need for lymph node dissection in patients with endometrioid endometrial cancer. METHODS: Military beneficiaries diagnosed with stage I-III endometrioid endometrial cancer during 2003-2016 who had at least 7 pelvic and/or paraaortic lymph nodes removed during the time of hysterectomy were studied. Tumor diameter was compared against the presence of positive nodes, using the prior models of 20 mm (ie, Mayo model) and 50 mm (ie, Milwaukee model), to determine the false-negative rate of each threshold. A separate analysis was completed to determine the optimal diameter for our population. Receiver operating characteristic curve analysis models of tumor diameter were evaluated for model fit and predictive power of lymph node involvement. RESULTS: Of the 1224 patients with endometrioid endometrial cancer included, 13% (n=160) had positive lymph node involvement. Tumor sizes ranged from 1 mm to 100 mm. In contrast to Mayo and Milwaukee models (ie, Mayo, Milwaukee), the optimal tumor diameter independent of myometrial invasion and grade of tumor to predict lymph node metastasis was found to be 35 mm. CONCLUSIONS: Endometrioid endometrial cancer tumor diameter of 35 mm was found to be the optimal threshold for lymphadenectomy when the operating surgeon has no knowledge of tumor invasion.

Extraovarian sex cord tumor with annular tubules discovered arising from a leiomyoma.

BACKGROUND: Sex cord tumors with annular tubules (SCTAT) are a rare (2%) subtype of ovarian sex cord-stromal tumor. SCTATs are usually cured at time of diagnosis by surgical resection with an oophorectomy. SCTATs have a 100%(disease related) five-year survival. One third of SCTAT tumors are associated with Peutz-Jeghers syndrome. Literature review discovered only two published cases of extra-ovarian SCTAT. Due to the rarity there is no standard treatment for extraovarian SCTATs. CASE: A 39-year-old para-1 female with a symptomatic fibroid uterus, heavy menstrual bleeding, and a history of a uterine myomectomy, underwent an elective total abdominal hysterectomy. Intraoperative findings showed a 7.5 cm retroperitoneal mass adhered between the uterus and the right pelvic sidewall that on frozen section was found to be a degenerating leiomyoma. Final pathology demonstrated a 2 mm focus of incidental SCTAT adjacent to the serosal surface of the leiomyoma. The SCTAT was not associated with ectopic ovarian tissue or endometriosis. The patient's ovaries were normal on direct intraoperative examination, preoperative ultrasound and MRI. Six month postoperative surveillance ultrasound also demonstrated normal premenopausal ovaries. CONCLUSION: This is the first extraovarian SCTAT in the published literature arising from a leiomyoma. Our patient had no family history and displayed no syndromic features for Peutz-Jeghers Syndrome. Ultimately, she declined genetic testing. The lack of evidence of ovarian involvement on both imaging and on intraoperative examination made localization to either ovary impossible. The patient is currently being managed with surveillance since the morbidity associated with bilateral oophorectomy in the 4th decade of life exceeds the theoretical risk of SCTAT.

A randomized controlled trial to determine whether a video presentation improves informed consent for hysterectomy.

BACKGROUND: Informed consent is an integral part of the preoperative counseling process. It is important that we know the best way to relay this information to patients undergoing surgery, specifically, hysterectomy. OBJECTIVE: We sought to determine whether supplementing normal physician counseling with a video presentation improves patient comprehension during the informed consent process for hysterectomy. STUDY DESIGN: In a randomized, mixed factorial controlled trial, standard physician counseling (control arm) was compared to physician counseling plus video presentation (video arm) during the prehysterectomy informed consent process. Primary outcome was improvement in patient comprehension measured by assessments at baseline, postcounseling, day of surgery, and postsurgery. Patient satisfaction was measured by a validated questionnaire. Audiotaped patient-physician interactions were analyzed to determine time spent counseling, number of patient questions, and whether standard counseling included 11 predetermined critical components included in the video. A sample size of 60 per group (N = 120) was planned to compare both groups. RESULTS: From May 2014 through June 2015, 120 patients were enrolled and 116 randomized: 59 to the video arm and 57 to the control arm. All characteristics were similar between groups. Video arm subjects demonstrated greater improvement in comprehension scores in both postcounseling (9.9% improvement; 95% confidence interval, 4.2-15.7%; P = .0009) and day-of-surgery questionnaires (7.2% improvement; 95% confidence interval, 0.96-13.4%; P = .02). Scores 4-6 weeks after surgery returned to baseline for both groups. Control subjects were less likely to be counseled about risk of thrombosis (P < .0001), colostomy (P < .0001), further medical/surgical therapy (P = .002), hormone replacement therapy (P < .0001), or postoperative expectations (P < .0001). Physicians spent more time counseling patients who did not watch the video (8 vs 12 minutes, P = .003) but number of questions asked by patients in each group was similar. CONCLUSION: Enhancing prehysterectomy counseling with a video improves patient comprehension through day of surgery, increases thoroughness of counseling, and reduces physician time.

Management of highly differentiated thyroid follicular carcinoma of ovarian origin with a minimally invasive approach.

•Peritoneal strumosis is highly differentiated thyroid follicular carcinoma of ovarian origin.•Minimally invasive surgical techniques for peritonectomy can resect extra-ovarian disease.•Multi-disciplinary collaboration allowed avoidance of thyroid ablation and thyroidectomy.

Apparent ectopic pregnancy with unexpected finding of a germ cell tumor: A case report.

•Ovarian germ cell tumors can produce hCG and be confused with ectopic pregnancy.•Ovarian germ cell tumors can present with subacute pelvic pain.•Ectopic pregnancy should be the primary differential diagnosis due to its acuity.

Actinomyces-Related Tubo-Ovarian Abscess in a Poorly Controlled Type II Diabetic With a Copper Intrauterine Device.

BACKGROUND: The historic association of Actinomyces israelii infection with intrauterine devices (IUDs) has long been recognized. In recent years, the risk of developing pelvic inflammatory disease with a copper or levonorgestrel IUD has been less than 1% in women who are low risk for sexually transmitted infections. IUD-related pelvic infections secondary to actinomyces have largely vanished from contemporary practice. CASE: A 49-year-old using a copper IUD for contraception with poorly controlled type II diabetes mellitus was admitted for suspected tubo-ovarian abscess on the basis of abdominopelvic pain, leukocytosis, and computed tomography findings. After she was treated with intravenous and outpatient antibiotics with clinical improvement, repeat imaging 1 month later revealed a persistent complex left adnexal mass. Tumor markers were negative but given the persistence and complex nature of the mass, surgical management was recommended. A robotic-assisted hysterectomy with bilateral salpingo-oophorectomy was performed. Adhesiolysis, profuse irrigation, and ureteral stenting were required. Pathology revealed bilateral tubo-ovarian abscesses with actinomyces species identified on intraoperative culture. The patient had a total of 10 days of postoperative antibiotics and improved glucose control with no further signs of infection. CONCLUSION: Although actinomyces-related IUD PID is considered an outdated diagnosis, there are intermittent case reports of bizarre presentations in older women, often mimicking malignancy. Actinomyces should be a consideration in tubo-ovarian abscesses or pelvic inflammatory disease in patients with an IUD in place, particularly those who have poor glucose control or are otherwise immunosuppressed. Early identification and treatment of actinomyces tubo-ovarian abscesses may reduce surgical morbidity and overall improve patient outcomes and safety.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

OBJECTIVES: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens. METHODS: A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens. RESULTS: Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective. CONCLUSIONS: With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Is FDA-Approved Bevacizumab Cost-Effective When Included in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer?

PURPOSE: Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. METHODS: A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. RESULTS: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. CONCLUSION: Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.

MEK1/2 inhibitors in the treatment of gynecologic malignancies.

Mitogen-activated protein kinases (MAPKs) are a family of ubiquitous eukaryotic signal transduction enzymes which link extracellular stimuli to intracellular gene expression pathways. While several three-tiered MAPK cascades have been elucidated in mammals, the prototypical pathway involves a network of proteins and kinases including the Rat sarcoma protein (Ras), mitogen-activated protein kinase kinase kinase (Raf or MAP3K), mitogen-activated protein kinase kinase (MEK or MAP2K), and extracellular signal regulated protein kinase (ERK or MAPK). This MAPK cascade (the Ras/Raf/MEK/ERK pathway) is a receptor tyrosine kinase mediated signaling pathway that regulates cell proliferation, cell cycle progression, and cell migration. There are multiple molecular mechanisms of interaction and activation between the upstream nodes of the Ras/Raf/MEK/ERK cascade and other cell signaling pathways, all ultimately leading to the activation of the nuclear transcription factor ERK. Important downstream targets include MEK1/2, which comprise the final step leading to ERK transcription factor activation. While multiple conduits exist to activate ERK upstream of MEK, there is little redundancy downstream. Located at this pivotal intersection between a limited number of upstream activators and its exclusive downstream targets, MEK is an appealing molecular target of novel cancer therapies. MEK inhibitors are small molecules that inhibit MEK phosphorylation by binding to a pocket adjacent to the ATP binding site, decreasing both the amount of MEK activity, and the quantity of activated ERK in the cell. Unique allosteric noncompetitive binding sites of MEK inhibitors allow specific targeting of MEK enzymes and prevent cross-activation of other serine/threonine protein kinases through the conserved ATP binding site. This paper reviews the translational evidence in favor of MEK inhibitors in cancer, their role in gynecologic malignancies, and details regarding the status of the fourteen MEK inhibitors currently being clinically tested: trametinib, selumetinib, pimasertib, refametinib, PD-0325901, MEK162, TAK733, RO5126766, WX-554, RO4987655, cobimetinib, AZD8330, MSC2015103B, and ARRY-300.

Surgical outcomes and national comprehensive cancer network compliance in advanced ovarian cancer surgery in a low volume military treatment facility.

OBJECTIVE: To evaluate the optimal cytoreduction (OPT) rate, National Comprehensive Cancer Network (NCCN) treatment guideline compliance rate and patient outcomes for advanced stage epithelial ovarian cancer (EOC) patients at our low volume institution. METHODS: Following IRB approval, records of patients with Stage III-IV EOC, primary peritoneal, or fallopian tube carcinoma completing both primary surgery and adjuvant chemotherapy were reviewed. Patient demographics, clinicopathologic variables, cytoreduction status (optimal or suboptimal), NCCN treatment guideline compliance, and survival were reviewed. Standard statistical tests including the t-test, Chi-square or Fisher's exact test and Kaplan-Meier Survival curves were utilized. RESULTS: Overall, 48 patients met all inclusion criteria. 35(73%) and 13 (27%) achieved optimal and suboptimal cytoreduction, respectively. Median overall survival (OS) for all patients was 37.1 months (95% CI 23.2 - 51.1 months) and NCCN treatment guideline compliance was 85.4%. Compared to sub-optimally cytoreduced patients the optimally cytoreduced patients were significantly older (62.2 vs. 53.5 yrs; p=0.015); no other significant clinicopathologic differences were observed between the two groups. 19 of 48 (39.6%) patients enrolled in an upfront cooperative group trial. Median OS was 43.4 months for optimally compared to 15.6 months in sub-optimally cytoreduced patients (p=0.012). CONCLUSIONS: NCCN treatment guideline compliance, OPT, and median OS rates in our low volume institution are similar to those reported nationally, and argue against using volume alone as a rationale for centralization of care.

Gene expression analysis of early stage endometrial cancers reveals unique transcripts associated with grade and histology but not depth of invasion.

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?

OBJECTIVE: Recurrent cervical cancer has a poor prognosis despite aggressive treatment. We evaluate the comparative-effectiveness of four management strategies in recurrent cervix cancer incorporating risk prognostication categories derived from pooled collaborative group trials: 1) standard doublet chemotherapy; 2) selective chemotherapy (home hospice with no chemotherapy for poorest prognosis patients with remainder receiving standard doublet chemotherapy); 3) single-agent chemotherapy with home hospice; and 4) home hospice. METHODS: A cost-effectiveness decision model was constructed. Survival reduction of 24% was assumed for single-agent chemotherapy and 40% for hospice only compared to standard doublet chemotherapy. Overall survival and strategy cost for each arm were modeled as follows: standard doublet chemotherapy 8.9 months ($33K); selective chemotherapy 8.7 months ($29K); single-agent chemotherapy with home hospice 6.7 months ($16K); and home hospice alone 5.3 months ($11K). Base case analysis assumed equal quality of life (QOL). Sensitivity analyses assessed model uncertainties. RESULTS: Standard doublet chemotherapy for all is not cost-effective compared to selective chemotherapy with an incremental cost-effectiveness ratio (ICER) of $276K per quality-adjusted life-year (QALY). Sensitivity analysis predicted that a 90% improvement in survival is required before standard doublet chemotherapy is cost-effective in the poorest prognosis patients. Selective chemotherapy is the most cost-effective strategy compared to single-agent chemotherapy with home hospice with an ICER of $78K/QALY. Chemotherapy containing regimens become cost-prohibitive with small decreases in QOL. CONCLUSIONS: Supportive care based treatment strategies are potentially more cost-effective than the current standard of doublet chemotherapy for all patients with recurrent cervical cancer and warrant prospective evaluation.

Takotsubo cardiomyopathy following laparoscopic port placement in a patient with ovarian cancer.

► Gynecologic oncology patients can be exposed to both chronic and acute physical and emotional stress. ► Gynecologic oncology patients appear to represent an at-risk population for the development of Takotsubo's cardiomyopathy.

The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: a Gynecologic Oncology Group study.

OBJECTIVE: To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual. METHODS: We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves. RESULTS: The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD). CONCLUSION: Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.

Proteomic analysis of stage I endometrial cancer tissue: identification of proteins associated with oxidative processes and inflammation.

OBJECTIVE: The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection. METHODS: A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins. RESULTS: 209 differentially expressed proteins were identified in a comparison of stage I endometrial cancers and normal post-menopausal endometrium controls (Q<0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q=0.008 and Q=0.00002 respectively). CONCLUSIONS: These data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.

The ability of endometrial biopsies with atypical complex hyperplasia to guide surgical management.

OBJECTIVE: This study was undertaken to determine the clinical relevance of "qualifying comments" on pathology reports of complex atypical endometrial hyperplasia. STUDY DESIGN: A retrospective review of endometrial biopsy specimens with atypical hyperplasia at our institutions was performed if subsequent hysterectomy results were available for review. Endometrial biopsy results were graded on an ordinal scale (complex atypical endometrial hyperplasia vs atypical endometrial hyperplasia "cannot rule out a more severe lesion") and compared with pathology obtained at hysterectomy. Data were analyzed by using Fisher's exact test. RESULTS: Endometrial biopsy specimens were associated with carcinoma in 37.5% (18/48) of complex atypical endometrial hyperplasia cases and in 60% (18/30) of atypical endometrial hyperplasia-cancer cases. Atypical endometrial hyperplasia-cancer on biopsy was associated with an increased risk of discovering a malignancy at intermediate/high-risk for lymph node involvement (odds ratio 4.71, P = .0256). CONCLUSION: Biopsy specimens that show atypical endometrial hyperplasia-cancer are associated with an increased risk of finding a cancer at intermediate or high risk for nodal metastasis.