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.

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.

Laparoscopic Management of an Invasive Mole Perforating the Uterus.

STUDY OBJECTIVE: To show the possibility of conservative laparoscopic management in a case of invasive mole perforating the uterus. DESIGN: Video with explanations. SETTING: An invasive mole is a potentially life-threatening complication of gestational trophoblastic disease [1]. This is a case of a 24-year-old female presenting with abdominal pain and vaginal bleeding. There have been several previous reports of cases of uterine perforation by an invasive mole, all of which were managed with abdominal hysterectomy [2-7]. To our knowledge, this is the first report of an invasive mole perforation with active bleeding managed by laparoscopy without hysterectomy. INTERVENTIONS: Sonography revealed a large amount of fluid and a 3 × 3-cm heterogeneous lesion next to the posterior uterine wall. Her hemoglobin level dropped from 10.6 mg/dL to 8.6 mg/dL, and her ß-human chorionic gonadotropin level was 19,004 mIU/mL. On laparoscopy, ∼2500 mL of hemoperitoneum was found, along with an actively bleeding bulging mass in the posterior uterine wall. This mass was dissected, and hemostasis was secured with sutures and electrocoagulation. Pathology confirmed the diagnosis of a complete mole. After surgery, the patient was treated with 5 courses of a methotrexate-folinic acid regimen. Her recovery was uneventful. CONCLUSION: Uterine perforation by an invasive mole can be managed conservatively with laparoscopic surgery and postoperative chemotherapy. The transmural lesion will increase the risk of future uterine rupture during pregnancy in this patient.

Septic Shock and Multiple Organ Failure After Office Endometrial Sampling.

BACKGROUND: Office endometrial biopsy with a Pipelle cannula is the main method for sampling the endometrial lining. The Pipelle biopsy is safe, efficient, and cost effective. This office endometrial sampling method is also an accurate and safe procedure for endometrial sampling of patients with endometrial carcinoma. It is associated with minimal pain and does not require anesthesia. CASE: Pipelle is the most common method used for sampling the endometrial lining. No data are available of infectious complications related to endometrial biopsy. The incidence is presumed to be negligible. We present an unusual case of a 52-year-old woman who experienced septic shock and multiple organ failure following Pipelle endometrial sampling. CONCLUSION: Lower abdominal pain is the cardinal presenting symptom in woman with pelvic infection. Our case emphasizes that an atypical symptom such as abdominal pain after endometrial biopsy could be a sign of infectious complications.

Laparoscopic Management of Uterine Rupture After Early Second-Trimester Medical Abortion in a Patient With a Prior Cesarean Section.

STUDY OBJECTIVE: To show the possibility of laparoscopic management of uterine rupture. DESIGN: Video with explanations. SETTING: In the medical management with misoprostol for termination of pregnancy at any time the risk of uterine rupture may be possible. The risk is likely higher in women with a previous uterus surgery. In a systematic review of available studies, the risk of rupture was .28% among women with a prior cesarean delivery who were undergoing second-trimester misoprostol-induced abortion, meaning if 414 women with a history of cesarean delivery were given misoprostol for second-trimester abortion, 1 would experience uterine rupture. Uterine rupture has only been reported 3 times in first-trimester abortion and only once managed via laparoscopy: a missed abortion reported in 2005, a case of a ruptured unscarred uterus in a women undergoing medical abortion, and a case of a delayed miscarriage at 8 weeks' gestation after misoprostol managed by laparotomy and sharp curettage. INTERVENTIONS: Total laparoscopic management in a patient with uterine tear after misoprostol treatment. CONCLUSION: Early second-trimester medical abortions with misoprostol can cause uterine rupture. In hemodynamically stable cases, total laparoscopic management is possible approach.

Pregnancy outcomes after cold knife conization related to excised cone dimensions. A retrospective cohort study.

OBJECTIVE: To analyze the perinatal outcome of pregnancies following cold knife conization and investigate its relationship, if any, with the amount of tissue removed, and to assess risk factors of perinatal complications. STUDY DESIGN: A retrospective cohort study was designed to compare perinatal outcomes between a group of patients who had prior conization operation (study group) and a group of patients who did not have a conization operation (control group). RESULTS: The preterm delivery rate and preterm premature rupture of membranes (PPROM) rate were significantly higher in the study group as compared with the control group. The mean cone volume was significantly higher in the group of patients who delivered at <37 weeks as compared with the group of patients who delivered at >37 weeks. For the patients who were diagnosed with PPROM, the mean excised volume and height were higher than those of the group of patients who were not diagnosed with PPROM. In cases with preterm delivery the cutoff value of excised cervix tissue volume was measured as 2.27 cm3, and in cases with PPROM the cutoff value of excised cervix tissue volume was measured as 3.99 cm3. CONCLUSION: The perinatal complication frequency was higher for the group of patients who had undergone conization procedure. We found that the volume of excised cervix tissue is more important than the height of the excised cervix tissue in regards to the assessment of perinatal complications. Colposcopy and conization procedure must be performed by the same, experienced specialist. During the procedure unnecessary tissue excision must be avoided.

Possible cause of failure after McCall culdoplasty.

OBJECTIVE: To evaluate prospectively the rate of postoperative failure of McCall culdoplasty and the presence of a history of vaginal delivery of macrosomic infants as risk factors in patients with stage III or symptomatic stage II apical prolapse without any other pelvic floor defects. MATERIALS AND METHODS: Patients with pelvic organ prolapse who underwent vaginal hysterectomy and McCall culdoplasty procedures were staged according to the POP-Q system before and after the operation (n = 70). POP-Q stages, age, gravidity, parity, body mass index (BMI), and the presence of diabetes mellitus in patients with or without history of vaginal delivery of macrosomic infants were analyzed. A birth weight of ≥4,000 g was accepted as macrosomia. Operative failure was defined as a postoperative POP-Q stage ≥ stage III of the apical segment. Follow-up period was 26.5 ± 6.37 months. RESULTS: Twenty-seven women had a history of macrosomic delivery and the remaining 43 did not. Postoperative failure was observed in 15 patients (44.4%) in the macrosomia group and in 3 patients (6.9%) in the control group. Postoperative failure was seen more frequently in the macrosomia group (Pearson's chi-square test, P = 0.000). No significant difference was found between the groups regarding age, gravidity, parity, BMI and the presence of diabetes mellitus. CONCLUSION: Failure of McCall culdoplasty occurs more frequently in patients with history of vaginal delivery of macrosomic infants, possibly due to direct pelvic floor damage. This technique should not be used in patients with a possible history of direct pelvic floor damage.

Is the extent of pelvic lymphadenectomy in the staging of endometrial cancer associated with the yield of metastatic nodes? An Israeli Gynecologic Oncology Group study.

OBJECTIVES: Primary, to explore correlation between the extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer and the number of nodes with metastasis. Secondary, evaluate survival measures in relation to the number of excised nodes. METHODS: A retrospective multi-center study of prospectively collected information of 2014 women with endometrial cancer, 1032 of whom underwent lymph node staging. Spearman's rank correlation was used to assess the correlation between the number of pelvic nodes excised and the number of metastatic nodes. Women's data were dichotomized by the median number of excised pelvic nodes. Kaplan-Meier and log rank tests were used to examine the effect of the number of pelvic nodes excised on survival. RESULTS: There was no significant correlation between the number of pelvic nodes harvested and the number of metastatic lymph nodes (r = 0.301; p = 0.28). The median number of excised pelvic nodes was 9 (range 1-77). There was no difference between women with up to 9 and women with more than 9 lymph nodes excised in the 5-year recurrence-free survival (82.4% vs. 83.9%; p = 0.90), disease-specific survival (83.6% vs. 86.7%; p = 0.37), or overall survival (75.8% vs. 82.8%; p = 0.11). CONCLUSIONS: The extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer is not associated with a higher yield of metastatic nodes or with longer survival. Current focus should be on sentinel node procedures that offer women the benefit of accurate staging without the complications associated with extensive lymphadenectomy.

An Israeli Gynecologic Oncology Group study of statin use and endometrial cancer prognosis.

OBJECTIVE: To assess whether statin use by endometrial cancer patients was associated with a survival advantage. METHODS: A retrospective chart review study, by the Israeli Gynecologic Oncology Group, of consecutive endometrial cancer patients who underwent surgery in one of 11 medical centers between 2002 and 2014. Clinical and pathological reports, and measures of survival were compared between statin users and nonusers. Kaplan-Meier and Cox proportional hazard models were used to assess the effect of using statins on survival measures. RESULTS: Over a mean follow-up period of 6.2 years (range, 1-12 years) for 2017 endometrial cancer patients with complete data, 663 (32.8%) used statins prior to diagnosis and 1354 (67.1%) did not. No statistically significant differences between the groups were observed for most demographic and clinical characteristics. There was no difference between statin users and nonusers in 5-year recurrence-free survival (82% vs 83%; P=0.508), disease-specific survival (86% vs 84%; P=0.549), or overall survival (77% vs 75%; P=0.901). CONCLUSIONS: In this large cohort of patients with endometrial cancer, no significant associations were found between use of statins and endometrial cancer survival.

Impact on pregnancy outcomes of exposure to military stress during the first or second trimester as compared with the third trimester.

OBJECTIVE: To compare pregnancy outcomes after exposure to military stress in different trimesters of pregnancy. METHODS: A retrospective study of medical records of deliveries in the Wolfson (WMC) and Barzilai (BMC) medical centers in Israel between July 2014 and April 2015. All parturients were exposed to military stress for 51 days during pregnancy. Pregnancy outcomes were compared between those exposed to military stress in the first or second trimester, and those exposed in the third trimester. Outcomes were also compared between WMC (a new-onset military stress exposure area) and BMC (a chronic military stress exposure area). RESULTS: At WMC, women exposed in the first or second trimester (n=2657) had a higher rate of preterm delivery (<37 weeks) as compared with those exposed in the third trimester (n=2037; 214 [8.1%] vs 121 [5.9%]; P=0.005). At BMC, women exposed in the first or second trimester (n=2208) had a tendency toward lower rates of diabetes mellitus (P=0.055) and macrosomia [103 (4.7%) vs 84 (6.3%); P=0.037], as compared with those exposed in the third trimester (n=1337). CONCLUSION: Exposure to military stress during pregnancy had different impacts on pregnancy outcomes, depending on the time of exposure and whether continuous exposure to stress occurred.

Do submucous myoma characteristics affect fertility and menstrual outcomes in patients underwent hysteroscopic myomectomy?

BACKGROUND: Submucous myomas may be associated with menorrhagia, infertility and dysmenorrhea. OBJECTIVE: The aim of this study was to determine the long term effects of submucousal myoma resection on menorrhagia and infertility; also to detect whether the type, size, and location of myoma affect the surgical success. MATERIALS AND METHODS: Totally 98 women referred to hysteroscopy for symptomatic submucousal fibroids (menorrhagia (n=51) and infertility (n=47)) between 2005- 2010 were enrolled in this historical cohort study Pregnancy rates and menstrual improvement rates were compared according to myoma characteristics (size, type and location). RESULTS: After a mean postoperative period of 23±10 months in 51 patients with excessive bleeding, 13 had recurrent menorrhagia (25%). In Other 38 patients excessive bleeding was improved (75%). The improvement rates by location and myoma type: lower segment 100%, fundus 92%, and corpus 63%; type 0) 70%, type 1) 78%, type 2) 80%. The mean sizes of myoma in recurred and improved patients were 23.33 mm and 29.88 mm respectively. 28 of 47 infertile women spontaneously experienced thirty pregnancies (60%). Pregnancy rates according to myoma location and type: lower segment 50%, fundus 57%, and corpus 80%; type 0) 75%, type 1) 62%, type 2) 50%. The mean myoma size in patients who became pregnant was 30.38 mm; in patients who did not conceive was 29.95 mm. CONCLUSION: The myoma characetesitics do not affect improvement rates after hysteroscopic myomectomy in patients with unexplained infertility or excessive uterine bleeding.

Fertility sparing surgery on placenta invasion anomalies and placenta previa.

BACKGROUND: Abnormal placental invasion has increased parallel with persistent rise in Caesarean delivery. Management relies on accurate diagnosis and delivery should be planned at an institution with appropriate expertise and resources for managing this condition. CASE: We present a case of a placenta invasion anomaly which is the major risk factors of peripartum deaths. In this case we try to explain our approach which reduces unnecessary hysterectomy rates. CONCLUSION: In order to avoid postpartum hemorrhage and hysterectomy protocols, our approach which consists bilateral hypogastric arterial ligation, Bakri balloon tamponade and if necessary methotrexate therapy can be applied succesfully.

Development of bladder stone after tension free vaginal tape procedure: a case report.

We present a case of a bladder stone which formed on the intravesical portion of tension free vaginal tape material secondary to bladder perforation. 8 years previously, a tension free vaginal tape (TVT) operation was performed. The patient was referred to hospital with persistent urinary infection and urinary incontinence. An intravesical stone that had formed on the TVT sling material was detected by cystoscopy and it was removed with the sling material by a supra pubic cystostomy approach. When evaulating patients presenting with urinary symptoms after a TVT procedure, bladder complications should be kept in mind.