Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review.

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study.

OBJECTIVE: Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. METHODS: This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. RESULTS: 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). CONCLUSION: Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study.

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted.

Predicting recurrence and recurrence-free survival in high-grade endometrial cancer using machine learning.

OBJECTIVE: To develop machine-learning models to predict recurrence and time-to-recurrence in high-grade endometrial cancer (HGEC) following surgery and tailored adjuvant treatment. METHODS: Data were retrospectively collected across eight Canadian centers including 1237 patients. Four models were trained to predict recurrence: random forests, boosted trees, and two neural networks. Receiver operating characteristic curves were used to select the best model based on the highest area under the curve (AUC). For time to recurrence, we compared random forests and Least Absolute Shrinkage and Selection Operator (LASSO) model to Cox proportional hazards. RESULTS: The random forest was the best model to predict recurrence in HGEC; the AUCs were 85.2%, 74.1%, and 71.8% in the training, validation, and test sets, respectively. The top five predictors were: stage, uterus height, specimen weight, adjuvant chemotherapy, and preoperative histology. Performance increased to 77% and 80% when stratified by Stage III and IV, respectively. For time to recurrence, there was no difference between the LASSO and Cox proportional hazards models (c-index 71%). The random forest had a c-index of 60.5%. CONCLUSIONS: A bootstrap random forest model may be a more accurate technique to predict recurrence in HGEC using multiple clinicopathologic factors. For time to recurrence, machine-learning methods performed similarly to the Cox proportional hazards model.

Comparison of outcomes between abdominal, minimally invasive and combined vaginal-laparoscopic hysterectomy in patients with stage IAI/IA2 cervical cancer: 4C (Canadian Cervical Cancer Collaborative) study.

OBJECTIVE: Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer. METHODS: A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes. RESULTS: 423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24-81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p < 0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036). CONCLUSION: In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes.

Identifying Borderline Ovarian Tumor Recurrence Using Routine Ultrasound Follow-Up.

Borderline ovarian tumors (BOTs) are non-invasive tumors frequently diagnosed in young patients. Surgical removal of the uterus, fallopian tubes, ovaries, and omentum is considered definitive management, however fertility-sparing approach is a recognized option. Surveillance is important due to known recurrence, but there is controversy over the effectiveness of follow-up modalities. The objective is to determine the efficacy of ultrasound screening in identifying tumor recurrence. This retrospective chart review evaluated all patients consulted and/or treated surgically at our institution from January 2015 to June 2020 diagnosed with BOT. Patients were excluded if concurrently diagnosed with another gynecologic malignancy, did not have yearly ultrasound follow-up, or were lost to follow-up. This study included 56 patients, 17 of whom underwent fertility preserving surgery. The overall rate of recurrence was 10.7%; with recurrence rates of 23.5% for the fertility preserving surgery population and 5.1% for the definitive surgery population. Ultrasound first identified 5 of the 6 (83.3%) recurrences. Overall time to recurrence was 51.5 months. In conclusion, recurrences were identified on routine ultrasound screening prior to symptom onset or detection via physical exam in 83.3% of cases. While the best modality of follow-up remains controversial, this review provides evidence supporting the use of routine ultrasound follow-up for early detection of BOT recurrence.

Factors associated with an increased risk of recurrence in patients diagnosed with high-grade endometrial cancer undergoing minimally invasive surgery: A study of the society of gynecologic oncology of Canada (GOC) community of practice (CoP).

BACKGROUND: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. RESULTS: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. CONCLUSION: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

Same-Day Discharge Among Patients With Obesity Undergoing Laparoscopic Gynaecologic Oncology Surgery.

OBJECTIVES: To determine the likelihood of same-day discharge (SDD) among patients with obesity undergoing laparoscopic gynaecologic oncology surgery and identify predictors of SDD. METHODS: We conducted a retrospective cohort study of gynaecologic oncology patients who underwent laparoscopic procedures between January 2012 and June 2016. Patients were categorized as non-obese, obese class I/II and obese class III (BMI <30, 30-39.9, and ≥40 kg/m2, respectively). We used univariate and multivariable logistic regression to identify variables associated with SDD. RESULTS: Of 496 patients, 288 were non-obese, 161 were obese class I/II, and 47 were obese class III. Overall, 182 patients (36.7%) were discharged same day; 44% of these were non-obese, 30% class I/II and 15% class III. On multivariable analysis, we found negative predictors for SDD to be obesity (OR 0.54; P = 0.03), procedure length (OR 0.51; P < 0.01), and higher American Society of Anesthesiologists (ASA) score (OR 0.63; P < 0.01), while we found being pre-booked for SDD (OR 9.16; P <0.01) was a positive predictor of SDD. Among all patients with obesity, only procedure length (OR 0.47; P < 0.01) and being pre-booked for SDD (OR 9.67; P < 0.01) were associated with SDD when we controlled for BMI, ASA score, intraoperative complications, type of surgery, and surgical start time. Patients discharged same day were less likely to present to the emergency department within 30 days of surgery (OR 0.48; P = 0.01). CONCLUSION: Among the study cohort and after controlling for potential confounders, women with class I, II, and III obesity had a much lower likelihood of SDD than non-obese women. The only significant predictors of SDD among patients with obesity were duration of procedure and pre-booking for SDD. Further study is needed to identify strategies to improve SDD rates among patients with obesity.

Correlation of differential ascites volume with primary cytoreductive surgery outcome, lymph node involvement, and disease recurrence in advanced ovarian cancer.

OBJECTIVE: High-grade serous ovarian cancer accounts for a disproportionate number of deaths from gynecologic malignancies. It typically presents at an advanced stage and with a high volume of ascites a common presenting feature. The aims of this study is to evaluate the association between ascites volume at the time of primary surgery for advanced stage ovarian cancer with surgical outcomes and patterns of recurrence. METHODS: A retrospective review of stage III/IV high-grade serous ovarian cancer patients who underwent primary surgery at two centers between March 2003 to June 2016. Patients were categorized as low-volume ascites (≤ 200 mL) vs high-volume (≥ 1 L). Patients with an unknown volume of ascites or neoadjuvant chemotherapy were excluded. Patients' characteristics were compared for the two groups. Probability of recurrence over time and the HR from a proportional hazards model for sub-distribution were calculated. RESULTS: A total of 210 patients were included, 90 (42.9%) patients in the low-volume and 120 (57.1%) patients in the high-volume group. Patients in the low-volume group were older with a median age of 60.2 years vs 56.8 years in the high-volume group and had lower serum CA-125 levels (mean 223 vs 971.5 U/mL). The low-volume group had better surgical outcome with suboptimal debulking (> 1 cm residual disease) in only 17.8 % vs 39.2 % in the high-volume group and had longer median time to recurrence (2.8 years in low-volume vs 1.6 years high-volume group). At the time of recurrence, the low-volume group had a less disseminated pattern of recurrence, lower rates of ascites (20 % in the low-volume group vs 37.2 % in the high-volume group), and a trend toward lower serum CA125 levels (mean 352.8 vs 596.9 U/mL). CONCLUSIONS: Advanced stage serous ovarian cancer patients who present with low-volume ascites have lower serum CA125 levels, more optimal cytoreduction rates, and longer disease-free interval. The low-volume group had less ascites, less disseminated disease, and a trend toward lower serum CA125 levels at the time of recurrence.

Impact and cost of preoperative computed tomography imaging on the management of patients diagnosed with high-grade endometrial cancer.

OBJECTIVE: To investigate the cost and impact of routine preoperative computed tomography (CT) in patients with high-grade endometrial cancer, and its role in identifying extrauterine disease. METHODS: We retrospectively identified patients with high-grade endometrial cancer who underwent routine CT scan prior to surgical procedure between September 1, 2005, and January 31, 2015. Cases in which CT findings led to alterations in the treatment plan were documented. Incidental findings unrelated to endometrial cancer diagnosis were captured. Cost of imaging and diagnostic procedures was based on Ontario's Physician Services-Schedule of Benefits. RESULTS: Of 179 patients included, 57 (31.9%) were diagnosed with stage 3-4 disease. CT showed evidence of metastatic disease in 30 (16.8%) patients; however, planned surgical procedure was altered in only nine (5.0%) cases. CT results showed incidental findings requiring follow-up in 78 (43.6%) cases, three of which were second malignancies. We estimate an expenditure of CAD$14 185.85 on routine imaging for every case in which surgical management was changed. CONCLUSIONS: Preoperative CT imaging is efficacious in identifying extrauterine disease in patients with high-grade endometrial cancer, although it seldom alters surgical management. Many of these CT scans will identify incidental findings requiring further interventions, resulting in substantial costs.

BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.

Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Gene set enrichment analysis revealed increased NFκB and EGFR signaling at baseline in mtBRCA1 samples, with increased interferon target gene expression, including members of the ISGylation pathway, observed after recovery from FF exposure. Gene set enrichment analysis did not identify altered pathway signaling in mtBRCA2 samples. An inverse relationship between EGFR signaling and ISGylation with BRCA1 protein levels was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1 cDNA. Suppression of ISG15 and ISGylated protein levels by increased BRCA1 expression was found to be mediated by decreased NFκB signaling. These studies indicate that increased NFκB signaling associated with decreased BRCA1 expression results in increased ISG15 and protein ISGylation following FF exposure, which may be involved in predisposition to HGSOC.

The Feasibility of Laparoscopic Surgery in Gynecologic Oncology for Obese and Morbidly Obese Patients.

BACKGROUND: Surgical interventions are the mainstay of treatment for many gynecological cancers. Although minimally invasive surgery offers many potential advantages, performing laparoscopic pelvic surgery in obese patients remains challenging. To overcome this, many centers have shifted their practice to robotic surgery; however, the high costs associated with robotic surgery are concerning and limit its use. OBJECTIVE: This study aimed to examine the feasibility of performing laparoscopic gynecologic oncology procedures in obese and morbidly obese patients. MATERIALS AND METHODS: This retrospective study evaluated patients who underwent laparoscopic surgeries by a gynecologic oncologist from January 2012 to June 2016 at a designated gynecologic oncology center. Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m), obese (BMI 30-39.9 kg/m), and morbidly obese (BMI ≥ 40 kg/m). Intra and postoperative complications and outcomes were recorded. Group differences were computed with Kruskal-Wallis nonparametric test (continuous) or Fisher exact test (categorical). RESULTS: Of 497 patients, 288 were nonobese (58%), 162 obese (33%), and 47 morbidly obese (9%). Complex surgical procedures were performed in 57.4% of obese patients and 55.3% of morbidly obese patients. Although morbidly obese and obese patients had longer operative times (mean of 181 and 166 minutes vs 144 minutes, P = 0.014), conversion from laparoscopy to laparotomy occurred in 9.05% of all patients, with no group differences. Low intraoperative (9%-11%) and severe postoperative (2.41%) complication rates were observed overall, with no group differences. There was no statistically significant difference in the rate of emergency room visits 30 days postoperation between the 3 BMI groups (P = 0.6108). Average length of postoperative stay was statistically significant (P = 0.0003) but was low overall (1-2 days). Hospital readmission rates were low, with the lowest rate among morbidly obese patients (2.13%). CONCLUSIONS: Our data suggest that laparoscopic gynecologic-oncology procedures for obese patients are feasible and safe.

Feasibility and safety of same-day discharge after minimally invasive hysterectomy in gynecologic oncology: A systematic review of the literature.

OBJECTIVE: To compare same-day discharge (SDD) versus traditional admission to the hospital following minimally invasive hysterectomy (conventional laparoscopy and robotic assisted laparoscopy) for the treatment of gynecologic malignancies. METHODS: A systematic review was conducted in which MEDLINE and Cochrane Center Register of Controlled Trials were searched using terms related to same-day discharge, outpatient, and hysterectomy. We reviewed published English language trials and studies that compared safety, feasibility, readmission rate, emergency department (ED) visits, complication rate, and associated risk factors for admission. Studies of any design that included at least 20 patients who underwent minimally invasive hysterectomy (conventional laparoscopy and robotic laparoscopy) for gynecologic oncology indications were included. RESULTS: The literature review yielded 421 citations, of which 27 full-text articles were reviewed. Six comparative studies met eligibility criteria. Study data were abstracted and inputted into structural electronic forms. CONCLUSION: Our results suggest that in comparison to admission post minimally invasive hysterectomy with or without full staging, SDD in gynecologic oncology procedures is safe, and feasible. It is associated with low complication and readmissions rates, few visits, and low rates of unscheduled visits within the follow up period of two to six weeks after surgery.

Using adhesive glue to repair first degree perineal tears: a prospective randomized controlled trial.

Our objective was to evaluate the effectiveness of adhesive glue in repairing first degree perineal tears. We conducted a noninferiority prospective, randomized, controlled trial comparing adhesive glue with traditional suturing. Each case was evaluated immediately after birth and after the puerperium. The two-sample t-test and the Mann-Whitney nonparametric test were applied to compare quantitative variables between the treatment groups. The chi-squared test and Fisher's exact test were used to assess the association between qualitative variables. A total of 102 women participated, 28 in the suture arm and 74 in the adhesive glue arm. While cosmetic and functional results of adhesive glue use were not inferior to suturing, the use of adhesive glue was associated with a shorter procedure, less need for local anesthetic, less pain, and greater satisfaction. Our results suggest a novel approach for the repair of common postpartum first degree lacerations. The use of adhesive glue achieves cosmetic and functional results equal to traditional suturing and offers some immediate advantages for the patient. While further clinical trials are needed to validate our results, it is important to inform obstetrician of the possible use of adhesive glue in these very common clinical scenarios. This trial is registered with NCT00746707.

Molecular profiling and clinical outcome of high-grade serous ovarian cancer presenting with low- versus high-volume ascites.

Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes.

Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin.

OBJECTIVE: Oral progestin is an alternative to hysterectomy for women with complex atypical hyperplasia (CAH) or grade one endometrial cancer (G1EC) who wish fertility preservation. We evaluated treatment efficacy and fertility outcomes in this population. METHODS: Women <45 y treated with oral progestin for CAH or G1EC were identified from two cancer centers. Data were obtained from medical records and telephone questionnaires. Time until complete response (CR), and from CR until recurrence was censored for patients without events and analyzed for associations with patient and treatment characteristics; cumulative incidence functions were used to estimate event probability over time. RESULTS: 44 patients were identified, 19 (43%) with CAH and 25 (57%) with G1EC. Median age was 36.5 y (26-44). 24 (55%) achieved CR (median time: 5.7 months). Older age was associated with a lower likelihood of CR (HR 0.84, p=0.0003, 95% CI, 0.8-0.9). CR probability appeared to plateau after 12 months of therapy. Among those with CR, 13 (54%) recurred (median time 3.5 y). 24 patients (55%) underwent hysterectomy; 3 (13%) were upstaged. 11 (25%) underwent fertility treatment with the following outcomes: 6 (55%) no pregnancy, 2 (18%) at least one live infant, and 3 (27%) spontaneous abortion. One achieved a live birth without intervention. CONCLUSION: Oral progestin is an effective temporizing fertility-sparing treatment for women with CAH/G1EC. Fertility specialist involvement is recommended due to the low live birth rate without intervention. Progestin therapy should be re-evaluated at 1 year in non-responders due to a low probability of success. Hysterectomy is recommended after childbearing due to a high recurrence rate.

Expression of the h19 oncofetal gene in premalignant lesions of cervical cancer: a potential targeting approach for development of nonsurgical treatment of high-risk lesions.

Background. Recent data suggest a role for H19 gene in promoting cancer transformation and progression. Cervical cancer, progresses from high-grade lesions (CIN3). At present, it is unclear if CIN lesions express H19. Objectives. To determine H19 expression in patient samples of CIN3 as well as the ability of a construct in which the promoter from the H19 gene drives expression of the diphtheria toxin A chain (DTA) to inhibit cervical cancer cell growth in vitro. Methods. H19 transcript levels were evaluated on 10 biopsies of CIN3 using in situ hybridization. PCR was used to examine H19 expression in cervical cancer cell lines and in two samples from a patient with cervical carcinoma. Cell lines were transfected with H19-DTA to determine its impact on cell number. Results. H19 gene was expressed in the area of CIN3 in 9 out of 10 samples. RT-PCR indicated expression of H19 in cervical cancer samples and in one of the three cell lines examined. Transfection of all cell lines with H19-DTA vector resulted in inhibited cell growth. Conclusions. H19 is expressed in the majority of CIN3 samples. These results suggest that most CIN3 lesions could be targeted by H19-DTA. Further in vivo preclinical studies are thus warranted.

Is routine appendectomy at the time of primary surgery for mucinous ovarian neoplasms beneficial?

UNLABELLED: The question whether the appendix should be removed at the time of surgery for apparent early-stage ovarian cancer is controversial. Removal of the appendix in the setting of mucinous histologic type is primarily driven by the existing challenge to distinguish between primary ovarian mucinous neoplasm and metastatic appendiceal carcinoma to the ovary. OBJECTIVES: To evaluate the value of an appendectomy at the time of surgery for ovarian mucinous borderline tumors or carcinoma. METHODS: A retrospective single institute-based study was conducted. We identified patients who were operated on by a gynecologic oncologist for an abnormal pelvic mass, which was diagnosed as mucinous adenocarcinoma or mucinous borderline tumor between January 2000 and December 2010. Cases were included in the study if an appendectomy was performed at the time of initial surgery. RESULTS: Seventy-seven cases meeting the inclusion criteria were identified. The ovarian mass of 11 patients (14%) was diagnosed as metastatic appendiceal carcinoma involving the ovary. Evidence of metastatic disease, abnormal-looking appendix, or pseudomyxoma peritonei, were identified at the time of surgery for all of these cases. The condition of 30 patients (39%) and 36 patients (47%) were diagnosed as mucinous borderline ovarian tumor and invasive or microinvasive mucinous ovarian carcinoma, respectively. Evidence of metastasis from the ovary to the appendix was not identified in any of the cases. CONCLUSIONS: Our data suggest that in cases of apparent early-stage mucinous ovarian borderline tumors and cancer, adding an appendectomy at the time of surgery is not warranted in the absence of a grossly abnormal appendix or evidence of metastatic disease.

Radical trachelectomy: a fertility-sparing option for early invasive cervical cancer.

For the past 15 years gynecological oncologists have been seeking ways to preserve woman's fertility when treating invasive cervical cancer. For some women with small localized invasive cervical cancers, there is now hope for pregnancy after treatment. Many cases of cervical cancer are diagnosed in young woman who wish to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. The standard surgical treatment for stage IA2-IB1 cervical cancer is a radical hysterectomy and bilateral pelvic lymphadenectomy. This surgery includes removal of the uterus and cervix, radical resection of the parametrial tissue and upper vagina, and complete pelvic lymphadenectomy. Obviously, the standard treatment does not allow future childbearing. Radical trachelectomy is a fertility-sparing surgical approach developed in France in 1994 by Dr. Daniel Dargent for the treatment of early invasive cervical cancer. Young women wishing to bear children in the future may be candidates for fertility-preservation options. The radical trachelectomy operation has been described and performed abdominally, assisted vaginally by laparoscopy and robotically. In this review we discuss the selection criteria for radical trachelectomy, the various possible techniques for the operation, the oncological and obstetric outcomes, and common complications.