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Objective: The objective of the study was to evaluate clinical outcomes in patients with stage I endometrial cancer undergoing surgical management without lymphadenectomy based on intra-operative assessment for low-risk disease., Methods: Between 2000 and 2009, a total of 179 patients were surgically staged without lymphadenectomy for low-risk stage I endometrial cancer. Low-risk cancer was defined by intra-operative criteria based on both gross and frozen tissue microscopic evaluation: 1) G1 or G2 endometrioid histology; 2) myoinvasion <50%; 3) no cervical disease, and 4) no intra-abdominal metastasis. Records were reviewed for postoperative complications, pathological diagnoses, adjuvant radiation treatment, cancer recurrence, and mortality., Results: Morbidity, cancer recurrence, and disease-specific mortality were low. Postoperative complications occurred in 5 patients (2.8%). Nine patients (5.0%) were offered adjuvant radiation for higher risk disease diagnosed on final pathology. Radiation morbidity was minimal: grade 1 vaginal toxicity in 2 patients. Three patients (1.7%) experienced recurrent cancer with mean time to recurrence of 43.7 months. Five year overall survival was 95.8%. The five year probability of disease-specific death was 1.1%., Conclusion: In an institution with reliable capability of pathological frozen tissue diagnosis, omission of lymph node dissection is a reasonable option in the surgical management of those patients with low-risk disease diagnosed by intra-operative factors., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Female patients with gynecological malignancies can harbor peritoneal pelvic or abdominal lesions; however, other primary tumors can involve the peritoneum as well. Since sampling of the peritoneum now can be easily performed by fine needle aspiration or percutaneous biopsy, we have noticed an increase in such procedures as initial attempts to establish a diagnosis. PAX8 has been used alone or in combination with other tumor markers to accurately classify these lesions and determine primary site of origin; however, prior published studies determined expression of PAX8 within historically diagnosed cases. We reviewed the reliability of PAX8 to determine tumor type or primary site in 135 current clinical pelvic or abdominal lesions and highlight several pitfalls in its routine use, in particular, relying on the presumed expression pattern (positive or negative) within a given primary tumor and that poorly differentiated endometrial endometrioid carcinomas or undifferentiated carcinomas may have patchy PAX8 expression or even lose expression within the primary tumor or the metastasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.

Available data on appropriate follow-up in endometrial cancer highlight the need of well-conducted studies. Most recurrences tend to occur within three years and involve symptoms. Routine tests are not advocated without symptoms. In case of suspicious recurrence, TEP/CT seems to be the most sensitive and specific method. There is limited evidence to decide whether follow-up schedules with multiple visits result in survival benefits. An appropriate follow-up should be discussed based upon the risk of recurrence. Counselling on the potential symptoms of recurrence should be a major aim.

Objectives: The mechanistic (mammalian) targets of rapamycin (mTOR) inhibitors with known growth Inhibitory effect are currently in clinical trial for treatment of human cancer. The aim of this review is to present current incorporating these new drugs as single agents or in combination with other therapeutic modalities for treatment of gynecologic cancer., Methods: A PubMed search was conducted on "mTOR inhibitors" and "human cancer". The relevant studies published between the year 2000 to present were reviewed. Those related to gynecologic cancer (cervical, endometrial and ovarian) were selected for this manuscript. The result of published data and their clinical application in gynecologic malignancies are presented., Results: mTOR is directly involved in many cell signaling pathways, and mTOR inhibitors have demonstrated anti-tumor activity against a variety of human malignancies, including gynecologic cancers. Combinations of mTOR inhibitors with other treatment modalities, e.g. cytotoxic chemotherapy, hormonal therapies, and other targeted molecular agents, have shown encouraging results particularly in endometrial and ovarian cancer., Conclusions: Patients with advanced or recurrent gynecologic cancers who have failed initial treatment are need of new treatment modalities. There is strong evidence that mTOR inhibitors limit tumor proliferation and progression. The PI3k/AKT/mTOR pathway is often deregulated in gynecologic cancer. Patients with PIK3CA mutations are more responsive to PI3K/AKT/mTOR inhibitors than patients without these mutations. Routine screening for PIK3CA mutations warrants further investigation when PI3K/AKT/mTOR inhibitors are considered in treatment of patients with gynecologic cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This case involved a 69-year-old woman who had been taking tamoxifen for 5 years after breast cancer surgery. She was referred to our clinic for endometrial cancer screening when tamoxifen was first prescribed. Subsequently, transvaginal ultrasonography and endometrial cytology were performed every 6 months. Despite these regular examinations, stage IVb papillary serous carcinoma was detected 8 months after the end of tamoxifen administration. Total abdominal hysterectomy was performed, but only a small polyp was seen upon macroscopic examination of the uterus. However, papillary serous carcinoma was found microscopically in almost all lymphovascular spaces in the uterus from the endometrium to the serosa. On the surface of the polyp, only endometrial intraepithelial carcinoma with positive immunostaining for p53 was detected. Chemotherapy, including a platinum compound, was administrated, but unfortunately it was ineffective and the patient died of her disease 14 months after the operation., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Objective: Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer., Methods: We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival., Results: The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local-regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local-regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p=0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p=0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value=0.018) was associated with a significant increase in local relapse free survival., Conclusions: Adjuvant radiation therapy was significantly associated with an improvement in local-regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes., Methods: A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS)., Results: Type I EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001) and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group., Conclusions: Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Endometrial stromal sarcoma are rare malignant tumors of the uterus and has been described as the second most common malignant uterine mesenchymal tumor. The diagnosis is confirmed on hysterectomy for a presumed benign disease. In the latest World Health Organization (WHO) classification (2003), the term endometrial stromal tumor is applied to neoplasms typically composed of cells that morphologically resemble endometrial stromal cells of the nonneoplastic proliferative phase endometrium. The WHO recognizes three categories of endometrial stromal tumors: Endometrial stromal nodule, low-grade endometrial stromal sarcomas (LGESS), and undifferentiated endometrial sarcoma. We report here an interesting case of a 39-year-old female who presented with irregular bleeding per vaginum and urinary retention with a clinical impression of a leiomyomatous polyp, which on histological examination showed a LGESS.

Objectives: To determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer., Methods: After IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I-II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0-1 (n=204), 2-3 (n=293) and >3 (n=174). Kaplan-Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint., Results: After a median follow-up of 85 months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0-1; 81.7%, 95.3%, and 89.8% for AAC 2-3: and 56%, 88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not., Conclusions: Comorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma., (© 2013.)

Background: For select women with early endometrial cancer, particularly nulliparous women, nonsurgical options may be considered. There is increasing experience using progestogens, but little is known about the long-term outcomes and safety of such treatment., Aims: To present the cancer and pregnancy outcomes of women with greater than five years follow-up after progestogen treatment for early endometrial cancer., Methods: Ten women who underwent greater than six months of continuous progestogen therapy for early endometrial cancer were included in the study. All were managed by a gynaecological oncologist at a major tertiary centre in Melbourne, Australia. The histology of each subsequent curette was recorded, as was the timing and histology of hysterectomy (if relevant), and the results of any subsequent pregnancies., Results: All ten women showed histological regression of cancer with no cases of recurrence on follow-up curette. Four of ten women have undergone hysterectomy with one case of occult disease persistence in a woman noncompliant with therapy. The mean follow-up time was 89 months (range 62-142 months), there were no deaths and no woman was lost to follow-up. All four women attempting pregnancy were successful. There were eight pregnancies and five live births., Conclusions: This form of treatment appears to be successful and safe in the long term with good pregnancy outcomes. However, it is not standard and should be supervised in a specialised gynaecological oncology unit., (© 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Recent findings in stem cell biology have presented new perspectives and opportunities for the treatment of reproductive disease. In a departure from the long held dogma of embryologically fixed numbers of oocytes, current literature suggests that human ovaries contain stem cells which form new oocytes even in adulthood and that these stem cells can be cultured in vitro to develop into mature oocytes. These findings have provided new hope and broader options for fertility preservation. Evidence of endometrial regeneration by bone marrow stem cells in endometrial tissue of women who received bone marrow transplant highlight potential for the novel treatments of uterine disorders and supports new theories for the etiology of endometriosis - ectopic transdifferentiation of stem cells. Further, endometrial derived stem cells have been demonstrated to be useful in the treatment of several chronic and often debilitating diseases, including Parkinson's Disease and Diabetes. Other cells that may present future therapeutic benefits for a myriad of disease states include placental and fetal cells which enter maternal circulation during pregnancy and can later promote parenchymal regeneration in maternal tissue. These findings highlight novel functions of the uterus and ovaries. They demonstrate that the uterus is a dynamic organ permeable to fetal stem cells capable of transdifferentiation as well as a renewable source of multipotent stem cells. While we still have much to understand about stem cells, their potential applications in reproductive biology and medicine are countless., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Endometrial stromal sarcoma is an uncommon tumor representing 0.2% of all uterine neoplasm and 15% to 26% of uterine sarcomas. Endometrial stromal sarcoma has a gross appearance as single nodule, multiple masses, or a poorly demarcated lesion with occasional cystic degeneration; rarely, it shows a cystic multilocular feature. We report 2 cases of endometrial stromal sarcoma with a prominent cystic appearance, forming multilocular cystic mass, detected by ultrasonography. The differential diagnosis among multicystic endometrial stromal sarcoma and cystic uterine tumors might be very difficult.

Resection of liver metastases from gynaecological tumours is uncommon. Endometrial stromal sarcomas (ESS) are low incidence gynecological tumours which can originate in previous sites of endometriosis or following metaplasia of the pelvic peritoneal wall, and which are exceptionally associated with liver metastasis. We present a 68-year-old woman with a ESS and metachronic liver metastasis treated by liver resection. There is very little literature on clinical management about liver metastasis from ESS, but extrapolating the data obtained with liver metastasis from sarcomas and uterine tumours, we should recommend resection as this is considered a resectable extrauterine metastasis. In cases with more sites of extrauterine disease, liver resection should also be performed if the other sites are resectable.

Background: The purpose of this study was to examine the rate and clinico-Pathological characteristics of ovarian metastasis of endometriod type endometrial cancer., Materials and Methods: A retrospective study of all patients with endometriod type endometrial cancer was carried out during 1990-2009. Chi-square and Fisher's Exact tests were used to analyze all the variables. P ≤ 0.05 was considered statistically significant. SPSS software (version 18), was used for statistical analysis of the data obtained., Results: Two hundred and ten patients fulfilled the inclusion criteria. Only 17 (8%) cases were identified to have ovarian metastasis. Fisher's Exact test showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included pathologic grading and depth of myometrial invasion (p<0.001 and p<0.02, respectively)., Conclusion: The risk of ovarian metastasis in the patients with well to moderately differentiated endometriod type endometrial cancer and myometrial invasion limited to less than one half of the myometrium is minimal. Therefore, it is possible to preserve ovaries in young women with early stage endometrioid type endometrial carcinoma, but it is better to remove and freeze ovarian tissue to save fertility without the recurrence risk of ovarian cancer.

Purpose: The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESSs) in relation to their clinical and pathogenic features, and to determine the optimal treatment strategy., Materials and Methods: A retrospective analysis was performed involving 28 patients with histologic-proven ESSs treated at our institution between 1987 and 2006., Results: The median follow-up was 54.7+/-63.1 months and the 5-year survival rate was 82.0%. Twenty-two (81.5%) and 5 patients (18.5%) had low- and high-grade disease, respectively. Univariate analysis revealed that the histologic grades, based on mitotic count, were associated with longer survival (p=0.004). However, among those patients with low-grade tumors, 5/20 patients (25%) had a recurrence and 2/21 patients (9.5%) had distant metastasis during the follow-up period. With the exception of 2 patients, 26 patients with ESSs underwent hysterectomy as primary treatment. Adjuvant treatment after surgery was administered to 14/26 patients (53.8%). Hormone therapy with progesterone, chemotherapy, and/or radiotherapy did not influence overall survival. However, the postoperative adjuvant therapy group, regardless of the treatment modality, was associated with relatively increased overall survival when compared to the surgery only group (p=0.054)., Conclusions: The preoperative differential diagnosis of ESSs from other benign gynecologic diseases is often difficult. We recommend adjuvant therapy be administered after hysterectomy in patients with ESS to prevent recurrence or distant metastasis.