Annie A. Yessaian

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.

Significance of perioperative infection in survival of patients with ovarian cancer.

Objectives Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer. Methods Patients who underwent primary cytoreductive surgery were included in the analysis (n = 276). The enumeration and speciation of pathogens, antimicrobial agents used, and sensitivity assay results were culled from medical records and correlated to clinicopathologic demographics and survival outcomes. Perioperative infection was determined as a positive microbiology result obtained within a 6-week postoperative period. Results The incidence of perioperative infection was 15.9% (common sites: urinary tract, 57.3%, and surgical wound, 21.4%). Commonly isolated pathogens were Enterococcus species (22.4%) and Escherichia coli (19.4%) in urinary tract infection, and Bacteroides fragilis, E. coli, and Klebsiella pneumoniae (all, 16%) in surgical wound infection. Imipenem represents one of the least resistant antimicrobial agents commonly seen in urinary tract and surgical wound infections in our institution. Perioperative infection was associated with diabetes, serous histology, lymph node metastasis, bowel resection, decreased bicarbonate, and elevated serum urea nitrogen in multivariate analysis. Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival (median time, 8.4 vs 17.6 months; P < 0.001), and decreased overall survival (29.0 vs 51.8 months; P = 0.011). Multivariate analysis showed that perioperative infections other than urinary tract infection remained a significant risk factor for decreased survival (progression-free survival, P = 0.02; and overall survival, P = 0.019). Conclusion Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

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.

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 cm3 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.

Long-Term Pegylated Liposomal Doxorubicin Use and Oromaxillary Squamous Cell Carcinoma in Endometrial Cancer

A case of primary buccal squamous cell carcinoma arising in a patient with uterine papillary serous carcinoma after long-term pegylated liposomal doxorubicin treatment is presented.

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.

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

To examine characteristics and survival outcome of women with endometrial cancer who declined postoperative radiotherapy.

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.

The role of adjuvant chemotherapy in early-stage high-grade uterine leiomyosarcoma: A retrospective review.

e15500 Background: Although the majority of patients with uterine leiomyosarcoma (ULMS) present with early stage disease, the risk of recurrence is high. Because ULMS is a rare disease, standardized adjuvant treatment options do not exist. Therefore, the goal of this study is to determine the role of adjuvant chemotherapy in patients with stages I-II high grade ULMS. METHODS Women with stages I-II ULMS treated at our institution from 1988-2008 were retrospectively identified and included in this study (N=44). Data was collected on patient age, stage of disease, surgical procedure, adjuvant treatment, recurrence, and survival. RESULTS In this population, 24 (55%) patients received cytotoxic chemotherapy, 3 (7%) received concurrent chemoradiation, 2 (4.5%) patients received radiation alone, and 15 (34%) received no further treatment. Median follow up for survivors was 71 months. In the no treatment and radiation alone groups, 71% of patients recurred and 29% were alive at last follow up. In the chemotherapy and chemoradiation groups, 63% of patients recurred and 48% were alive at last follow-up. There was also a difference noted based on type of chemotherapy received. Patients who received adriamycin and ifosfamide had a recurrence rate of 25%, and 63% were alive at last follow up. In the gemcitabine and docetaxel group, while 75% of these patients recurred, many of these recurrences were salvageable, thus 75% of patients were alive at last follow up. The five year survival rate for patients who received chemotherapy was 58% compared to 48% for those who did not receive chemotherapy (p=0.09). The five year survival rate for patients who received combination chemotherapy was 91% compared to 39% for patients who received single agent chemotherapy (p=0.07). CONCLUSIONS Adjuvant chemotherapy, especially combination chemotherapy for early stage high grade ULMS in this series demonstrates a benefit and even a trend towards improved outcome.