Tumor-reactive antibodies evolve from non-binding and autoreactive precursors.

The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC). Patient-derived tumor cells were frequently coated with IgGs. Intratumoral ASCs in HGSOC were both mutated and clonally expanded and produced tumor-reactive antibodies that targeted MMP14, which is abundantly expressed on the tumor cell surface. The reversion of monoclonal antibodies to their germline configuration revealed two types of classes: one dependent on SHMs for tumor binding and a second with germline-encoded autoreactivity. Thus, tumor-reactive autoantibodies are either naturally occurring or evolve through an antigen-driven selection process. These findings highlight the origin and potential applicability of autoantibodies directed at surface antigens for tumor targeting in cancer patients.

Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Acute Adnexal Torsion: Is Immediate Surgical Intervention Associated with a Better Outcome?

OBJECTIVES: We aimed to investigate whether surgery for adnexal detorsion within 6 h from admission to the hospital was associated with less adnexal ischemia. DESIGN: This is a retrospective cohort study. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: This retrospective study was conducted at two university-affiliated medical centers and assessed women aged 18-45 years with adnexal torsion who were hospitalized within 12 h from the pain onset and underwent surgery for detorsion within 24 h. The study group was divided into 2 groups: early, surgical intervention within less than 6 h and late, surgical intervention between 6 and 24 h. The primary outcome was the rate of macroscopic appearance of ischemic adnexa. RESULTS: Two hundred and twenty women fulfilled the inclusion criteria. In 101 women, the adnexa with the torsion appeared macroscopically ischemic. There was no difference in ischemic adnexa between the early and late intervention groups (48% vs. 40%; p = 0.269). No significant association was found between the physical examination or ultrasonographic findings and the rate of ischemic adnexa within each group. LIMITATIONS: The main limitations of our study are its retrospective nature. Much of the clinical and ultrasonographic data are subjective and operator-dependent. The decision to operate may vary from one surgeon to another. CONCLUSION: Immediate surgical intervention in patients with adnexal torsion is not associated with a lower rate of adnexal ischemia. These findings suggest that in acute adnexal torsion, there is a wider time window for a thorough evaluation before surgery.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study.

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.

INTRODUCTION: Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS: In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS: A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001). CONCLUSIONS: Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.

Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection.

High-grade ovarian cancer (HGOC) is the leading cause of mortality from gynecological malignancies, because of diagnosis at a metastatic stage. Current screening options fail to improve mortality because of the absence of early-stage-specific biomarkers. We postulated that a liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Further, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile, is expected to enable earlier detection, as it reveals perturbations in both the tumor as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we applied our method for microvesicle proteomics to the UtL samples. Liquid biopsies from HGOC patients (n = 49) and controls (n = 127) were divided into a discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8578 UtL proteins in total, and on average ∼3000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 70% sensitivity and 76.2% specificity. The signature correctly identified all Stage I lesions. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis.

Neoadjuvant Chemotherapy for Elderly Patients with Advanced Stage Ovarian Carcinoma.

BACKGROUND: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity. OBJECTIVES: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT). METHODS: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001). CONCLUSIONS: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Postoperative radiation rates in stage IIA1 cervical cancer: Is surgical treatment justified? An Israeli Gynecologic Oncology Group Study.

OBJECTIVES: Data on the outcome of stage IIA1 cervical cancer is limited, as these tumors comprise a small percentage of early tumors. NCCN guidelines suggest consideration of surgical management for small tumors with vaginal involvement. Our objective was to evaluate the risk of adjuvant radiotherapy in stage IIA1 cervical cancer and its associated features, in order to improve selection of patients for surgical management. METHODS: A retrospective cohort study comparing surgically treated cervical cancer patients with stage IB1 and stage IIA1 disease. Women treated between 2000 and 2015 in ten Israeli medical centers were included. Patient and disease features were compared between stages. The relative risk (Fisher's exact test) of receiving post-operative radiation was calculated and compared for each risk factor. A general linear model (GLM) was used for multivariable analysis. RESULTS: 199 patients were included, of whom 21 had stage IIA1 disease. Most features were comparable for stage IB1 and stage IIA1 disease, although patients with vaginal involvement were more likely to have close surgical margins (23.8% vs 8.5%, p = 0.03). Patients with stage IIA1 disease were more likely to receive radiation after surgery (76% vs. 46%, RR = 1.65 (1.24-2.2), p = 0.011). Vaginal involvement as well as depth of stromal invasion, LVSI and lymph node metastases were independent predictors of radiation on multivariable general linear modeling. CONCLUSIONS: Cervical cancer patients with vaginal involvement are highly more likely to require postoperative radiation. We recommend careful evaluation of these patients before surgical management is offered.

Is there a survival advantage in diagnosing endometrial cancer in asymptomatic postmenopausal patients? An Israeli Gynecology Oncology Group study.

BACKGROUND: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking. OBJECTIVE: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer. STUDY DESIGN: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared. RESULTS: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37). CONCLUSION: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time.

Malignant Ascites: Validation of a Novel Ascites Symptom Mini-Scale for Use in Patients With Ovarian Cancer.

BACKGROUND: Ascites is a common finding in patients with ovarian cancer. Paracentesis is a relatively simple, safe, and effective procedure for draining fluid from the peritoneum, but valid quality-of-life tools are needed to determine its subjective value for alleviating symptoms and improving patient quality of life. The objective of this study was to prospectively evaluate the performance of a novel Ascites Symptom Mini-Scale (ASmS) and compare it with a previously available questionnaire. METHODS: Patients with ovarian cancer-related ascites presenting for paracentesis were asked to complete the newly devised ASmS before the procedure and 1 and 24 hours after. Patients also completed a pain assessment scale and a previously validated ascites questionnaire at the same time points. RESULTS: The cohort included 28 patients of median age 68 years (range, 51-86 years), 13 (46.4%) with primary ovarian cancer and 15 with recurrent disease. A median of 3300 mL of ascites was drained. The median score on the ASmS decreased significantly from 21.5 before paracentesis to 11.0 at 1 hour after paracentesis (P < 0.001) and remained low at 24 hours. No demographic factor predicted greater benefit from the procedure. Patients with both mild and severe symptoms reported significant relief. CONCLUSIONS: The ASmS is a robust quality-of-life tool for the specific assessment of symptoms of ovarian cancer-related malignant ascites. It can be used in the clinical trial setting assessing interventions aimed at treating ascites and in the clinic to identify those patients with mild symptoms, who may benefit from paracentesis.

Simple Hysterectomy for Residual Cervical Intraepithelial Neoplasm.

OBJECTIVE: Many patients undergo hysterectomy for the treatment of cervical dysplasia. Factors that correlate with residual high-grade squamous intraepithelial lesions (HGSIL) at hysterectomy are not clear. We set out to determine preoperative features that may predict residual disease for patients treated for cervical dysplasia. MATERIALS AND METHODS: A retrospective database was reviewed for women who underwent simple hysterectomy for HGSIL between 1990 and 2013. Clinical data included age, history of dysplasia, initial treatment, follow-up colposcopy, indications for surgery, time elapsed between initial treatments, and pathology findings after hysterectomy. Significant residual disease was defined as HGSIL or cervical carcinoma. Statistical analyses were performed with the SPSS, independent Student t test, and Pearson χ test. Significance was set at p < .05. RESULTS: Eighty-three women met the study criteria. The indication for hysterectomy was residual histological finding at conization pathology in 30 women and patients' request in 53 women. Residual disease was found in 42 hysterectomy specimens: in 16 of 30 with residual histological finding and in 26 of the 53 patients' request. Reason for the hysterectomy was not statistically significant for residual disease (p = .708). Median age of patients with residual disease was 46.5 years versus 44.1 years for those without residua (p = .02). Postmenopausal patients had a higher rate of residual disease, 12 (32.4%) of the 28 premenopausal patients and 25 (67.6%) of the 54 postmenopausal patients (p = .04). Conization margin status was not associated with residual disease (p = .878). CONCLUSIONS: Older women and those in menopause are at significantly higher risk of residual disease at hysterectomy.

[LAPAROSCOPICALLY-ASSISTED ULTRASOUND-GUIDED PERCUTANEOUS TRANSABDOMINAL OOCYTE COLLECTION: FERTILITY PRESERVATION IN A 17-YEARS-OLD GIRL WITH VAGINAL EWING SARCOMA].

INTRODUCTION: Options for preserving fertility in children and adolescents with cancer depend on patient age, the available time frame, and the treatment regimen. Ovarian stimulation with mature oocyte preservation is often the optimal method in post-menarcheal adolescents. We describe a case of a 17-year-old girl with vaginal soft-tissue Ewing sarcoma in whom transvaginal oocyte collection for fertility preservation was ruled out by the large tumor. To overcome the limitations of the transabdominal approach, we applied a novel method of laparoscopically-assisted ultrasound-guided percutaneous transabdominal oocyte collection. In this manner, we were able to both perform oophorectomy and obtain superficial and deep ovarian follicles for cryopreservation.

Diagnosis of deep pelvic masses on a gynaecology service: Trans-vaginal ultrasound-guided needle aspiration of pelvic solid and cystic lesions.

OBJECTIVES: Women with undiagnosed pelvic lesions are often referred for evaluation and treatment. Transvaginal ultrasound-guided fine needle aspiration (TVUS-FNA) biopsy can assist in making management decisions. We describe our experience with this modality. METHODS: We performed a retrospective chart review of all women who had a TVUS-FNA biopsy between January 2004 and December 2014. Charts were reviewed for clinicopathologic information. The pathologic results of the TVUS-FNA were compared with the final diagnosis. RESULTS: Fifty-nine women underwent TVUS-FNA; the median age was 66 years (range 27-85). Thirty-three lesions were evaluated by fine-needle aspiration biopsy of the solid structure and 26 by aspiration of fluid for cytology. Pathologic feasibility rate was 88% (52/59). Of those with evaluable tissue, the sensitivity of the procedure was 100% and the specificity 92%. Considering the seven inconclusive results, the procedure had sensitivity of 88% (29/33) and specificity of 88% (23/26). Overall accuracy of TVUS-FNA for this patient cohort was 85%. No patient characteristics were found to distinguish between accurate and inaccurate or inconclusive TVUS-FNA result. No complications were noted. CONCLUSIONS: TVUS-FNA offers an excellent modality for the diagnosis and management of deep pelvic lesions otherwise not amenable for histologic evaluation.

Structured hands-on workshop decreases the over-detection rate of obstetrical anal sphincter injuries.

PURPOSE: The purpose of this study was to assess the effect of a structured hands-on workshop on the detection rate of obstetric anal sphincter injuries. METHODS: All physicians attending the delivery ward in our institution participated in a structured obstetric anal sphincter injury hands-on workshop developed by Dr. Ranee Thakar and Dr. Abdul Sultan which demonstrated proper identification and techniques for obstetric anal sphincter injury detection and repair. We retrospectively reviewed the electronic records of all singleton-pregnancy women who delivered vaginally (vertex presentation) during the 2 years prior to and 1 year following the workshop to assess the workshop's effect on the rate of detection of obstetric anal sphincter injuries. RESULTS: Overall, 20,484 women met the inclusion criteria during the study period and were eligible for final analysis. There were no significant differences in patient's characteristics between the groups. Women in the pre-workshop group had a higher rate of obstetric anal sphincter injuries than the post-workshop group (0.4 vs. 0.2 %, p = 0.005). On multivariate analysis, factors independently associated with a decreased risk for obstetric anal sphincter injuries were deliveries in the post-workshop period (odds ratio 0.43, 95 % confidence interval 0.24-0.79, p = 0.006), parity (odds ratio 0.37, 95 % confidence interval 0.25-0.54, p < 0.001), and spontaneous vaginal delivery (odds ratio 0.43, 95 % confidence interval 0.26-0.71, p = 0.001). CONCLUSIONS: A proper detection of obstetric anal sphincter injuries may depend on the experience of the assessor. A structured hands-on workshop is important to avoid over diagnosis third-degree perineal tears.

The Use of a Novel Optical Algorithm in the Diagnosis of Cervical Pre-Invasive Pathology - A Preliminary Proof of Principal Study.

OBJECTIVE: To develop a novel optical probe monitoring cervical tissues in real-time and to compare the new imaging technique to actual cervical pathologic findings on resected cone biopsy specimens. METHODS: A loop electro-excisional procedure was performed on 15 women with a biopsy diagnosis of dysplasia. The conization specimen was then assessed with the novel optical system and results recorded. The 'normal' and 'abnormal' areas were tested by the optical setup at several points. Extracted parameters were used as the input of the classifier function of a logistic regression algorithm model to assess for system accuracy vs. clinical examination. RESULTS: Ninety-seven samples were taken - forty-five samples from 'abnormal zones' and 42 samples from 'normal zones', as defined by the surgeon. The pathologist diagnosed 58 samples as dysplastic and 39 samples as normal. The novel optical method predicted 58 sample points as abnormal and 39 points as normal. The sensitivity of the system was 90% with a specificity of 77%. The probability of correct differentiation of dysplastic cervical tissue from normal cervical tissue was 85%. CONCLUSIONS: The optical probe and the algorithms of image processing in combination with the logistic regression algorithm correlated well with pathology results for cervical dysplasia ex-vivo.

A Dedicated Follow-Up Clinic for BRCA Mutation Carriers.

BACKGROUND: Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33-68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a "home" for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer.

OBJECTIVE: Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. METHODS: A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. RESULTS: Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0 months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3 months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. CONCLUSION: The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Endometrial Cancer Surgery for Elderly Women--The Early Postoperative Period.

OBJECTIVE: The aim of this study was to examine the early postoperative period and assess whether elderly patients recuperate differently than do their younger counterparts after surgery for endometrial cancer. METHODS: This retrospective chart review comprised all women older than 75 years who underwent laparotomy for endometrial cancer staging at our center from January 2005 through December 2010 and a consecutive control group of women younger than 74 years. Parameters included demographic variables, surgical procedure/findings, postoperative morbidity, and pathology. RESULTS: Ninety patients older than 75 years and 88 younger patients were identified. The elderly patients had a statistically significant prolonged wait for bowel movement (5.9 vs 3.1 days, P = 0.002) and ambulated later (4.1 vs 1.1 days, P < 0.001). Postoperative hospital stay was similar in both groups (5.8 vs 4.2 days, P = 0.37). Early postoperative complications (fever, bowel, wound, eventration, cardiopulmonary) occurred at a similar rate in both groups. CONCLUSIONS: Elderly patients after laparotomy for endometrial cancer staging ambulated later and recovered bowel function later than did the younger patients. This did not translate into prolonged hospital stay or excessive complications. Earlier intervention with physical therapy and stool softeners can possibly close this gap in recovery.

Uterine papillary serous carcinoma pre-operatively diagnosed as endometrioid carcinoma: Is omentectomy necessary?

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a relatively rare but aggressive uterine malignancy comprising approximately 10% of endometrial cancers. Many women pre-operatively misdiagnosed as having endometrioid carcinoma have ultimately UPSC on final pathology. These women receive inadequate surgical staging without omentectomy. AIM: To assess the value of omentectomy on disease-free interval and overall survival in women with UPSC who had an initial diagnosis of endometrioid carcinoma. METHODS: This retrospective study included all women treated for the final diagnosis of UPSC in our centre from January 2007 to December 2012. Data regarding patient demographics, staging procedures, histology results, adjuvant therapy and follow-up outcomes were recorded. RESULTS: Of the 52 women with a final diagnosis of UPSC, more than 45% had an initial diagnosis of endometrioid carcinoma. All women underwent hysterectomy and removal of the adnexa. Lymph node evaluation was performed in 75% of women. Omentectomy was performed in 30/52 women (58%). Of those, three women (10%) had omental involvement. Mean disease-free interval with omentectomy was 24.5 months versus 30.5 months without (P = 0.29). Mean overall survival was 33 months with an omentectomy and 29 months without (P = 0.32). Recurrence patterns did not differ between groups. CONCLUSION: Women diagnosed pre-operatively with endometrioid carcinoma and eventually found to have UPSC can expect no change in prognosis despite not having undertaken a full staging procedure. Repeat surgery for omentectomy is probably of no benefit.

Liposome-encapsulated doxorubicin citrate (Myocet) for treatment of recurrent epithelial ovarian cancer: a retrospective analysis.

The aim of this study was to assess the clinical activity and toxicity of liposome-encapsulated doxorubicin citrate (Myocet) in a retrospective multicenter cohort of epithelial ovarian, primary peritoneal, and tubal cancer patients. Records of patients with recurrent epithelial ovarian, primary peritoneal, and tubal cancer treated with liposome-encapsulated doxorubicin citrate (60 mg/m on day 1 of a 21-day cycle) after failure of more than one previous regimen were reviewed. Fifty-three patients were evaluated for efficacy and toxicity. The median age of the patients was 59 (range 39-73). The median follow-up was 6 months (range 1-17). One patient (1.9%) showed a complete response and 13 patients (24.5%) showed a partial response, yielding an overall response rate of 26.4% (14/53 patients). Clinical benefit was achieved in 36 patients (67.9%). The median progression-free survival (PFS) for the entire study population was 4.0 months (range 1.0-14.8). The median PFS for platinum-sensitive and platinum-resistant patients was 4.0 months (ranges 1.0-14.8 and 1.0-9.4, respectively; P=0.652). The median overall survival from the start of liposome-encapsulated doxorubicin citrate was 10.0 months. Multivariate survival analysis showed no association between the liposome-encapsulated doxorubicin citrate line of treatment or platinum sensitivity to PFS in age and BRCA status-adjusted models. Only 11.3% of patients experienced grade 3-4 hematologic toxicities, 80% grade-2 alopecia, and 50% grade-1-2 fatigue. No other grade-4 toxicities, no significant cardiac events, or hand and foot syndromes were reported. Liposome-encapsulated doxorubicin citrate was well tolerated, with a good response and high clinical benefit rate. Further evaluation in a larger prospective cohort is warranted.