Temporal trends of failure-to-rescue following perioperative complications in vulvar cancer surgery in the United States.

OBJECTIVE: Failure-to-rescue, defined as mortality following a perioperative complication, is a perioperative quality indicator studied in various surgeries, but not in vulvar cancer surgery. The objective of this study was to assess failure-to-rescue in patients undergoing surgical therapy for vulvar cancer. METHODS: This cross-section study queried the National Inpatient Sample. The study population was 31,077 patients who had surgical therapy for vulvar cancer from 1/2001-9/2015. The main outcomes were (i) perioperative morbidity (29 indicators) and (ii) mortality following a perioperative complication during the index admission for vulvar surgery (failure-to-rescue), assessed with a multivariable binary logistic regression model. RESULTS: The cohort-level median age was 69 years, and 14,337 (46.1%) had medical comorbidity. Perioperative complications were reported in 4736 (15.2%) patients during the hospital admission for vulvar surgery. In multivariable analysis, patient factors including older age, medical comorbidity, and morbid obesity, and treatment factors with prior radiotherapy and radical vulvectomy were associated with perioperative complications (P < 0.05). The number of patients with morbid obesity, higher comorbidity index, and prior radiotherapy increased over time (P-trends < 0.001). Among 4736 patients who developed perioperative complications, 55 patients died during the hospital admission for vulvar surgery (failure-to-rescue rate, 1.2%). In multivariable analysis, cardiac arrest (adjusted-odds ratio [aOR] 27.25), sepsis or systemic inflammatory response syndrome (aOR 11.54), pneumonia (aOR 6.03), shock (aOR 4.37), and respiratory failure (aOR 3.10) were associated with failure-to-rescue (high-risk morbidities). There was an increasing trend of high-risk morbidities from 2.0% to 3.7% over time, but the failure-to-rescue from high-risk morbidities decreased from 9.1% to 2.8% (P-trend < 0.05). CONCLUSION: Vulvar cancer patients undergoing surgical treatment had increased comorbidity over time with an increase in high-risk complications. However, failure-to-rescue rate has decreased significantly.

Two staged phase II clinical trial of Eribulin monotherapy in advanced or recurrent cervical cancer.

BACKGROUND: Eribulin a microtubule targeting agent and analog of Halichondrin B, a natural product isolated from marine sponge H. okadai, has proven clinical efficacy in metastatic pretreated breast cancer and liposarcoma. We conducted a 2-stage Phase II study of eribulin in patients with advanced/recurrent cervical cancer to examine its clinical activity and evaluate biomarkers for predictors of response. METHODS: Women with advanced/recurrent cervical cancer after ≤1 prior chemotherapy regimen, measurable disease and ECOG performance status ≤2 were treated with eribulin (1.4 mg/m2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival (PFS6); secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS). Exploratory endpoints were associations of biomarkers with clinical activity. Immunohistochemistry was performed on archival tumor samples. Overexpression was defined when both intensity and distribution scores were ≥ 2. RESULTS: 32 patients enrolled from 11/2012-5/2017. 29/32 patients had prior chemotherapy with cisplatin/paclitaxel/bevacizumab (n = 12) or cisplatin/gemcitabine (n = 12) as the most common regimens. 14 patients received prior paclitaxel. 1 (3%) had a complete response, 5 (16%) had a partial response and 13 (41%) had stable disease for ORR of 19% (95% CI 8, 37). Those who are paclitaxel naïve experienced the greatest benefit with a 29% ORR (95% CI 12, 54). Patients who received prior paclitaxel responded less favorably than those who did not (p = .002) and had a shorter PFS and OS. Grade 3/4 adverse events occurring in >10% of patients were anemia (n = 12, 38%), neutropenia (n = 7, 22%) and leukopenia (n = 6, 19%). Analysis of correlative predictors of response revealed that patients who did not overexpress ßII and BAX were significantly more likely to respond to e`ribulin. PFS was significantly shorter in patients with ßII and BAX overexpression, OS was significantly shorter in those with ßIII and BAX overexpression. These associations remained after multivariate analysis. CONCLUSIONS: Eribulin shows modest activity in patients with recurrent/advanced cervical cancer with a favorable toxicity profile. Prior paclitaxel exposure is associated with decreased eribulin response. ßII, ßIII tubulin subtypes and BAX are predictors of response and survival. Eribulin may be an option for women with paclitaxel-naïve recurrent/advanced cervical cancer.

Association between sentinel lymph node biopsy and micrometastasis in endometrial cancer.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is increasingly utilized at surgical staging for early endometrial cancer. This study examined the association between SLN biopsy and micrometastasis in endometrial cancer. METHODS: This is a retrospective cohort study examining the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study population was 6,414 women with T1-2 endometrial cancer who underwent primary hysterectomy and surgical nodal evaluation. Exclusion criteria included cases with isolated tumor cells. Exposure assignment was surgical nodal evaluation (SLN biopsy or lymphadenectomy). Main outcome measure was micrometastasis, assessed by inverse probability of treatment weighting propensity score in a stage-specific fashion. RESULTS: In T1a disease (n = 4,608), SLN biopsy was performed in 1,164 (25.3%) cases. SLN biopsy was associated with a 90% increased likeliness of identifying micrometastasis compared to lymphadenectomy (1.3% versus 0.7%, odds ratio 1.90, 95% confidence interval 1.02-3.55, P = 0.040). In T1b disease (n = 1,369), 270 (19.7%) cases had SLN biopsy. The incidence of micrometastasis was significantly higher in the SLN biopsy group compared to the lymphadenectomy group (8.4% versus 5.0%, odds ratio 1.74, 95% confidence interval 1.06-2.86, P = 0.028). In T2 disease (SLN biopsy in 57 [13.0%] of 437 cases), the incidence of micrometastasis was similar between the two groups (7.9% versus 7.0%, odds ratio 0.88, 95% confidence interval 0.30-2.60, P = 0.818). CONCLUSION: This study suggests that SLN biopsy protocol may identify more micrometastasis in the regional lymph nodes of T1 endometrial cancer. Whether national-level increase in the utilization of SLN biopsy for early endometrial cancer results in a stage-shifting to advanced disease on a population-basis warrants further investigation.

Population-level uptake of neoadjuvant chemotherapy for stage IVB endometrial cancer.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes of patients with stage IVB endometrial cancer who received neoadjuvant chemotherapy (NACT) prior to surgery. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried by examining 5505 patients with stage IVB endometrial cancer from 2010 to 2018. Exposure allocation was per treatment: primary surgery followed by chemotherapy (n = 3052, 55.4%), NACT followed by surgery (n = 930, 16.9%), and chemotherapy alone (n = 1523, 27.7%). Main outcomes measured were (i) the trend of utilization of NACT and patient characteristics related to NACT assessed with multinomial regression analysis and (ii) overall survival (OS) assessed with multivariable Cox proportional hazards regression model. RESULTS: The number of patients receiving NACT prior to surgery increased from 11.6% to 21.7% whereas those undergoing primary surgery followed by chemotherapy decreased from 62.7% to 48.3% (P < 0.001). Increasing utilization of NACT remained independent in multivariable analysis (adjusted-odds ratio per one-year increments 1.11, 95% confidence interval [CI] 1.08-1.15). Increasing utilization of NACT was observed in several sub-cohorts including patients aged <65 years, ≥65 years, White, non-White, endometrioid, non-endometrioid, and cases with non-distant organ metastasis (P < 0.05). In a multivariable analysis, NACT followed by surgery and primary surgery followed by chemotherapy had comparable OS (median 25 versus 26 months, adjusted-hazard ratio [HR] 1.03, 95%CI 0.93-1.15). When examined for metastatic extent, NACT followed by surgery was associated with decreased OS compared to primary surgery followed by chemotherapy in the non-distant organ metastasis group (adjusted-HR 1.20, 95%CI 1.05-1.36) whereas it was associated with improved OS in the distant organ metastasis group (adjusted-HR 0.79, 95%CI 0.66-0.95). CONCLUSION: The treatment of stage IVB endometrial cancer is shifting from primary surgery to NACT in the United States.

Trends and characteristics of ovarian conservation at hysterectomy for young women with cervical cancer.

OBJECTIVE: The association between early surgical menopause and increased mortality has been well demonstrated. Prior studies have also demonstrated that ovarian conservation is not associated with worse oncologic outcomes in early-stage cervical cancer. This study examined the contemporary trends and characteristics of ovarian conservation at time of hysterectomy in young women with cervical cancer. METHODS: This is a retrospective cohort study examining the National Inpatient Sample. The study population was 4900 women aged ≤50 years with cervical cancer who had hysterectomy-based surgical treatment from 10/2015 to 12/2018. The exposure allocation was the adnexal procedure status (ovarian conservation versus oophorectomy). The main outcome measures were temporal trends of ovarian conservation over time and per patient age. Multivariable binary logistic regression model was fitted to identify independent characteristics associated with ovarian conservation. A classification-tree was constructed by recursive partitioning analysis to examine the utilization patterns of ovarian conservation. RESULTS: A total of 2,940 (60.0%) women underwent ovarian conservation at hysterectomy. Ovarian conservation rates remained stable until age 37 years, ranging from 82.5% to 77.9% (P = 0.502), after which time the rate sharply and significantly decreased by 7.4% (95% confidence interval 5.4-9.3, P < 0.001) in one-year age increments from 77.9% at age 37 years to 28.7% at age 50 years. The rate of ovarian conservation increased from 54.7% in Q4/2015 to 64.4% in Q4/2018 (P = 0.002). In multivariable analysis, recent surgery remained an independent factor for ovarian conservation (adjusted-odds ratio per year-quarter 1.04, 95% confidence interval 1.03-1.06). A classification-tree model identified 24 unique patterns of ovarian conservation based on patient factor (age, race/ethnicity, primary expected payer, and year of surgery), surgical factor (minimally invasive hysterectomy), and facility factor (hospital bed capacity and region), ranging from <20% to 90% (absolute percentage difference, >80%). CONCLUSION: Increasing rates of ovarian conservation at the time of hysterectomy in women undergoing surgical management of cervical cancer is encouraging; however, the marked decrease noted in patients in their mid-30s as well as substantial variability in ovarian conservation based on patient, surgical, and hospital factors are striking and warrant further consideration in clinical practice guidelines.

Side-to-end reanastomosis after low-anterior resection (STELAR): Outcomes, feasibility, and description of procedure performed by a gynecologic oncology service.

BACKGROUND AND OBJECTIVES: Low anterior rectosigmoid resection for a gynecologic disease is usually performed in concert with other procedures and can result in significant morbidity should anastomotic complication occur. This study examined surgical outcomes of side-to-end reanastomosis after low anterior resection (STELAR) performed by gynecologic oncology service. METHODS: This is a case series examining consecutive patients who underwent STELAR for gynecologic indications by a single gynecologic oncology group from 2009 to 2018. Prospectively collected institutional surgical database was searched for STELAR, and standard descriptive statistics were used to describe intraoperative and postoperative complications specific to reanastomosis. RESULTS: A total of 69 women underwent STELAR, with median age and body mass index of 54 years and 24 kg/m2 , respectively. 63.8% of patients had ovarian cancer and 84.4% had stage III-IV disease. The median estimated blood loss was 875 ml. Four (5.8%) women underwent protective loop colostomy at the time of STELAR. Postoperatively, there was 1 (1.4%) case of abscess formation within 30 days and 1 (1.4%) case of anastomotic leak 5 weeks after STELAR that required reoperation and diversion. No cases of fistula were clinically identified. CONCLUSION: Side-to-end reanastomosis may be a safe and feasible procedure to accomplish low rectosigmoid anastomosis in women with gynecologic disease.

Adjuvant hysterectomy following primary chemoradiation for stage IB2 and IIA2 cervical cancer: a retrospective comparison of complications for open versus minimally invasive surgery.

BACKGROUND: Adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer has been shown to decrease local relapse rate. The objective of this study is to compare complications and recurrences between minimally invasive and open adjuvant hysterectomy for early stage cervical cancer. METHODS: Patients were identified who had undergone adjuvant hysterectomy following chemoradiation for 2009 FIGO stage IB2 and IIA2 cervical cancer from August 2006 to June 2018. Demographic information, treatment course, complications, recurrence data were retrospectively extracted from the medical record. Frequency of complications was compared with Fisher exact test or chi-square test as appropriate and inverse probability of treatment propensity score weighting was used to calculate the disease-free survival. RESULTS: Fifty-four patients met inclusion criteria with a median follow up time of 60.4 months (interquartile range 28.0-98.1 months). There were 24 (44%) open versus 30 (56%) minimally invasive hysterectomies performed. The overall grade 2 or worse complication rate was 43%. There were 8 (27%) patients with complications in the minimally invasive group compared to 4 (17%) in the open group (OR 1.82 (95% CI 0.5-7.0)). There were 9 vaginal cuff defects, dehiscences and/or fistulas in the minimally invasive group compared to 3 in the open group (OR 3.0 (95% CI 0.8-11.2)). There was no statistically significant difference between disease free survival and overall survival among the two groups, however there was a trend towards decreased disease-free survival in the minimally invasive group. CONCLUSIONS: Among women undergoing adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer, there was no difference in complication rates between an open or minimally invasive surgical approach. However, the overall complication rate was high, including a high rate of vaginal cuff defect, dehiscence and/or fistulas. Our findings suggest that an adjuvant hysterectomy should be reserved for patients in which chemoradiation is not anticipated to successfully treat the primary tumor and, if performed, an open approach should be considered.

Non-prescription cannabis use for symptom management amongst women with gynecologic malignancies.

OBJECTIVES: To evaluate interest in and patterns of use of non-prescription cannabis products for symptom management amongst gynecologic cancer patients living in states with legal access to medical and recreational marijuana. METHODS: Cross-sectional study using a novel 35-question survey distributed to women diagnosed with gynecologic cancer within two academic centers in California and Colorado. The survey queries demographic and disease traits, and both objective and subjective issues surrounding use of cannabis products for symptom management. Surveys were distributed to patients actively receiving treatment or under surveillance. RESULTS: Enrollment began July 16, 2018 and was completed December 1, 2018. Survey return rate was 52.7%. A total of 225 participants met inclusion criteria.Sixty-two percent reported that they have used or would be interested in using cannabis products for symptom management; 60 (26.7%) are using non-prescription cannabis for treatment of cancer related symptoms, and 80 (35.6%) are interested in using cannabis derivatives under direction of their oncologist. Reasons cited for use of cannabis included: pain control (n = 41, 68.3), insomnia (n = 33, 55.0%), anxiety (n = 29, 48.3%), nausea (n = 26, 43.3%), and appetite stimulation (n = 21, 35.0%). Of the women using cannabis products, almost half report decreased prescription narcotic use after initiation of cannabis products (n = 27, 45.0%). CONCLUSIONS: Women with gynecologic cancer report a strong interest in the use of non-prescription cannabis products for management of cancer-related symptoms. Practitioners in the field of gynecologic oncology should be aware of the frequency of use of non-prescription cannabis amongst their patients as well as the growing desire for guidance about the use of cannabis derivatives. A substantial number of patients report decreased reliance on opioids when using cannabis derivatives for pain control.

Overexpression of HOMER2 predicts better outcome in low-grade endometrioid endometrial adenocarcinoma.

We have previously shown that HOMER2 (Homer scaffolding protein 2), a protein coding gene, was highly expressed in low grade (LG) endometrioid adenocarcinoma (EAC) of the uterus. The role of HOMER2 in endometrial cancer (EC) is widely unknown; therefore, the aim of this study was to determine the expression and the predictive value of HOMER2 protein expression in series of patients with EC. HOMER2 protein expression was detected on paraffin-embedded tissues from 336 cases using immunohistochemistry (IHC). Tumours were categorised in two groups; group 1 (EAC, FIGO grade 1 and 2; n = 191) and group 2 (all other subtypes including grade 3 EAC; n = 145). Statistical analysis was performed to evaluate associations between HOMER2 protein expression and pathological parameters (histological type, grade, stage, lymphovascular invasion, myometrial depth of invasion) and patient outcome [progression-free survival (PFS) and cancer-specific survival (CSS)]. HOMER2 was significantly overexpressed in group 1 compared to group 2 cancers (67% versus 30%; p < 0.001) and with low tumour grade (p < 0.001). In group 1, HOMER2 overexpression was an independent prognostic factor for improved CSS (adjusted-hazard ratio 0.28; 95% confidence interval 0.08-0.96; p = 0.042). HOMER2 expression was not associated with survival in group 2 (p > 0.05). This is the first study of HOMER2 protein expression in EC. We speculate that HOMER2 may be involved in tumourigenesis of endometrioid uterine tumours and suggest that HOMER2 should be studied further for potential clinical and therapeutic applications.

Patient compliance for postoperative radiotherapy and survival outcome of women with stage I endometrioid endometrial cancer.

BACKGROUND AND OBJECTIVES: To examine characteristics and survival outcome of women with endometrial cancer who declined postoperative radiotherapy. METHODS: A retrospective study was conducted to examine surgically-treated grade 1-2 stage IB and grade 3 stage IA-IB endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results Program between 1983 and 2013 (n = 10 613). Associations of patient declination for guideline-based postoperative radiotherapy and clinico-pathological demographics or survival outcome were examined on multivariable analysis. RESULTS: There were 323 (3.0%) women who declined adjuvant radiotherapy. Women who declined postoperative radiotherapy were more likely to be older, White, Western U.S. residents, and register in recent years (all, adjusted-P < 0.05). On multivariable analysis, patient declination for guideline-based postoperative radiotherapy remained an independent prognostic factor for decreased endometrial cancer-specific survival in unstaged grade 1-2 stage IB or staged/unstated grade 3 stage IA-IB diseases (adjusted-hazard ratio 1.84, 95% confidence interval 1.34-2.51, P = 0.001). Association of patient declination for guideline-based postoperative radiotherapy and decreased overall survival remained independent in the entire cohort on multivariable analysis (adjuvant-hazard ratio 1.71, 95% confidence interval 1.44-2.02, P < 0.001). CONCLUSIONS: Our study suggested that patient compliance to guideline-based postoperative radiotherapy is a prognostic factor for women with stage I endometrioid endometrial cancer.

Prognosis of women with apparent stage I endometrial cancer who had supracervical hysterectomy.

OBJECTIVE: To examine characteristics and survival outcomes of women with apparent early-stage endometrial cancer who had a supracervical hysterectomy. METHODS: The Surveillance, Epidemiology, and End Results Program was used to identify women with presumed stage I endometrial cancer who underwent supracervical hysterectomy between 1983 and 2012. Propensity score matching was performed to adjust background difference between supracervical hysterectomy (n=1,339) and total hysterectomy (n=110,523) cases. Endometrial cancer-specific survival (CSS) was examined by multivariable analysis expressed with adjusted-hazard ratio [HR] and 95% confidence interval [CI]. RESULTS: Supracervical hysterectomy was independently associated with younger age, low-grade disease, and small tumor size on multivariable analysis (all, P<0.001). After propensity score matching, supracervical hysterectomy remained an independent prognostic factor for decreased CSS compared to total hysterectomy (10-year rates, 91.0% versus 94.9%, adjusted-HR 1.72, 95%CI 1.20-2.47, P=0.003). Among women who received postoperative radiotherapy, 10-year CSS rates were similar between supracervical and total hysterectomy cases (84.7% versus 80.3%, P=0.40). Contrary, in the absence of postoperative radiotherapy, women undergoing supracervical hysterectomy had a significantly lower 10-year CSS rate compared to those undergoing total hysterectomy (92.1% versus 97.2%, P<0.001). Moreover, with lack of lymphadenectomy, supracervical hysterectomy was associated with decreased CSS compared to those who had total hysterectomy (91.6% versus 94.3%, P=0.018) but had similar CSS rates with lymphadenectomy (92.7% versus 91.8%, P=0.91). CONCLUSION: Although rarely performed, supracervical hysterectomy is associated with decreased survival outcome among women with apparent stage I endometrial cancer supporting the importance of avoiding this procedure in women with or at risk of endometrial cancer.

Endoplasmic reticulum stress in complex atypical hyperplasia as a possible predictor of occult carcinoma and progestin response.

Glucose-regulated protein (GRP)-78, the key regulator of endoplasmic reticulum (ER) stress, is associated with endometrial cancer (EC) development and progression. However, its role in the continuum from complex atypical hyperplasia (CAH) to EC is unknown and the focus of this study. METHODS: 252 formalin-fixed, paraffin-embedded endometrial biopsies from patients with CAH diagnosed between 2003 and 2011 were evaluated for GRP78 expression by immunohistochemistry. Expression was also evaluated in subsequent biopsies from those patients treated with progestins. Differences in GRP78 expression were assessed using standard statistical methods. RESULTS: GRP78 expression was undetectable in 45(18%) patients with CAH, while 120(48%) CAH cases showed moderate/strong expression. Among women who ultimately underwent hysterectomy for CAH (n=134), 54(40%) had occult EC while 57(43%) had persistent CAH. Those with occult EC upon hysterectomy had significantly stronger GRP78 expression than those who did not have occult EC (p=0.007). Greater GRP78 expression within CAH remained independently associated with the presence of an occult EC (p=0.017). Thirty-four of 54 (63%) patients with occult EC had moderate/strong GRP78 expression compared to 36 of 80 (45%) patients with persistent CAH, benign or non-atypical hyperplastic endometrium. In those treated with progestins, samples with persistent CAH and EC were more likely to have high levels of GRP78 expression in the initial biopsies than those who responded (p=0.014). CONCLUSIONS: Increased GRP78 expression in untreated CAH correlates with the presence of an occult EC. In addition, CAH specimens with greater GRP78 expression may identify patients who are less likely to respond to progestin therapy.

Predictive Factor of Conversion to Laparotomy in Minimally Invasive Surgical Staging for Endometrial Cancer.

OBJECTIVE: The aim of the study was to identify risk factors associated with laparotomy conversion during total laparoscopic hysterectomy for endometrial cancer. METHODS: This is a retrospective study examining endometrial cancer cases that underwent hysterectomy-based surgical staging initiated via conventional laparoscopic approach. Factors related to patient, tumor, and surgeon were examined to establish risk of laparotomy conversion using a multivariate logistic regression model. RESULTS: There were 251 cases identified including 30 cases (12.0%) of laparotomy conversion. The most common indication for laparotomy conversion was a large uterus (27.0%), followed by extensive adhesions (24.3%) and surgical complications (18.9%). Outcomes of cases resulting in laparotomy conversion include longer surgical time (333 vs 224 minutes, P < 0.001), larger blood loss (350 vs 100 mL, P < 0.001), longer hospital stay (4 vs 2 days, P < 0.001), and increased risk of hospital readmission (10% vs 1.4%, P = 0.024). In multivariate analysis, morbid obesity (odds ratio [OR], 4.51; P = 0.011), suboptimal pelvic examination or enlarged uterus during preoperative evaluation (OR, 3.55; P = 0.034), para-aortic lymphadenectomy (OR, 10.5; P = 0.001), uterine size 250 g or greater (OR, 3.49; P = 0.026), and extrauterine disease (OR, 4.68; P = 0.012) remained the independent predictors for laparotomy conversion. The following numbers of risk factors were significantly correlated with laparotomy-conversion rate: none, 1.1%; single risk factor, 5.3% (OR, 5.00; P = 0.15); double risk factors, 21.7% (OR, 24.9; P = 0.002); and triple or more risk factors, 50% (OR, 90.0; P < 0.001). Ultrasonographic 3-dimensional volumes of 496 cm in preoperative uterine size correlate with actual uterine weight of 250 g (Y = 61.5 + 0.38X, P < 0.001). CONCLUSIONS: Laparotomy conversion significantly impacts outcomes of patients with endometrial cancer. In this setting, our predictive model for laparotomy conversion will be useful to guide the surgical management of endometrial cancer.

Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal.

Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C.

Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection.

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy.

Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and α-smooth muscle actin (αSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and αSMA antibodies were performed on paraffin-embedded tissue. Fisher's exact test was performed to test the association between FAP and αSMA expression and disease status. Kaplan-Meier method with log-rank test was used to check the survival difference between different FAP tumor/stroma expressions. FAP stroma (pos) . expression was strongly associated with higher recurrences rate [OR: 15.95; 95 % CI: 1.521-835.206; p = 0.0072]. Cases with combined FAP stroma (pos) and FAP tumor (neg) had higher death rate [OR: 4.845; 95 % CI: 1.53-16.61; p = 0.0046] and higher recurrence rate [OR: 5.12; 95 % CI: 0.91-54.42; p = 0.0487] compared to all the others. Cases with combined FAP stroma (neg) and FAP tumor (neg) were more likely to have lower recurrence rates [OR: 0.086; 95 % CI: 0.001-0.997; p = 0.0248]. αSMA was expressed by tumor-associated stroma in 95 % of cases and by tumor cells in 9 % of cases. No statistical power was found for αSMA and disease status. Our data indicate that FAP plays an important role in predicting tumor aggressiveness in patients with EOC post-neoadjuvant therapy, and its frequent expression in this malignancy implicates that FAP targeted therapy could be a very attractive strategy.

Predictive model of venous thromboembolism in endometrial cancer.

OBJECTIVE: To profile characteristics and survival of endometrial cancer patients who develop venous thromboembolism (VTE) and to establish a predictive model of VTE in endometrial cancer. METHODS: Cases were identified using an institutional database between 2000 and 2011. VTE was correlated to clinico-pathological information and survival outcomes. Frequency and odds ratio (OR) of VTE were examined in a predictive model based on combination patterns of independent risk factors for VTE. RESULTS: VTE was seen in 42 (8.1%, 95% CI 5.8-10.5) out of 516 cases subsequent to the diagnosis of endometrial cancer. Multivariate analysis identified 4 independent risk factors for VTE: elevated CA-125 (hazard ratio [HR] 5.38, p<0.001), extrauterine disease (HR 2.87, p=0.019), thrombocytosis (HR 2.11, p=0.04), and high risk histology (serous and clear cell, HR 2.09, p=0.049). VTE was the strongest variable for decreased progression-free survival (HR 4.28) and the second strongest variable for decreased overall survival (HR 5.65) in multivariate analysis. In a predictive model of VTE, the presence of multiple risk factors was associated with significantly increased risk of VTE: frequency of VTE, 1.4% if no risk factors, 0-9.3% (OR 1.0-4.2) if a single risk factor, 11.1-25.0% (OR 9.0-24.0) if two risk factors, and 42.9-46.2% (OR 54.0-61.7) if ≥3 risk factors. CONCLUSION: VTE represents a surrogate for aggressive disease in endometrial cancer. Multiple risk factors of VTE in our predictive model demonstrated exceedingly high risk of VTE, suggesting that there may be a certain population of endometrial cancer patients who would benefit from long-term anti-coagulant prophylaxis to improve survival outcome.