Efficacy and safety of niraparib in patients aged 65 years and older with advanced ovarian cancer: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To evaluate the impact of age on the efficacy and safety of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Patients in the intent-to-treat population were categorized according to age at baseline (<65 years vs ≥65 years), and progression-free survival (PFS), safety, and health-related quality of life (HRQOL) were evaluated for each age subgroup (clinical cutoff date, May 17, 2019). Safety findings were also evaluated according to a fixed starting dose (FSD) or an individualized starting dose (ISD). RESULTS: Of 733 randomized patients, 289 (39.4%) were ≥65 years (190 niraparib, 99 placebo) at baseline. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) were similar in patients aged <65 years (13.9 vs 8.2 months; HR, 0.61 [0.47-0.81]) and ≥65 years (13.7 vs 8.1 months; HR, 0.53 [0.39-0.74]). The incidences of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) were similar across age subgroups; in the niraparib arm, TEAEs leading to dose discontinuation occurred in 7.8% of patients <65 years and 18.4% of patients ≥65 years. ISD use lowered the incidence of grade ≥3 thrombocytopenia events in niraparib-treated patients compared with the FSD (<65 years: 42.8% vs 18.0%; ≥65 years 57.0% vs 26.1%). HRQOL was comparable across age subgroups. CONCLUSION: Niraparib efficacy, safety, and HRQOL were generally comparable across age subgroups, although patients ≥65 years had a higher rate of discontinuations due to TEAEs. ISD use reduced grade ≥3 thrombocytopenia events regardless of age.

D&C has the best concordance between preoperative and postoperative grades among morbidly obese endometrial cancer patients.

AIM: Endometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%-25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect. METHODS: We conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method. RESULTS: A total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C. CONCLUSIONS: Increasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

INTRODUCTION: High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false-positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high-grade cervical intraepithelial lesion detection rate in the young age group of 25-30 years. MATERIAL AND METHODS: Retrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25- to 30-year-old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid-based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+). RESULTS: During the study period, 42 244 women 25-30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2-1.37; p < 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2-1.6; p < 0.001) compared with LBC. HPV infections with non-16/18 hrHPV (other hrHPV) were the most prevalent (84.8%). CONCLUSIONS: In women 25-30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.

Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population. RESULTS: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37). CONCLUSIONS: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.

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.

Anatomic Asymmetry in Sentinel Lymph Node Detection in Endometrial Cancer.

STUDY OBJECTIVE: To determine whether the concomitant use of indocyanine green (ICG) with technetium-99m-filtered sulfur colloid (Tc99m-FSC) improves bilateral sentinel lymph node (SLN) detection rate in endometrial cancer and whether anatomic concordance of pelvic lymph nodes exists and can be used to predict SLN location in cases of unilateral mapping failure. DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center in Holon, Israel. PATIENTS: Patients diagnosed with endometrial cancer, who underwent SLN mapping with Tc99m-FSC, ICG, or both, at our center between 2014 and 2019. INTERVENTIONS: A total of 111 patients were included in the study. SLN mapping using Tc99m-FSC was performed in 101 (91.9%) patients, and ICG injection was given to 64 (57.6%) patients of whom 55 (49.5%) received both. We compared SLN detection rates (unilateral and bilateral) and anatomic symmetry for each method alone and for a combination of the 2. MEASUREMENTS AND MAIN RESULTS: The overall detection rate for unilateral SLNs was 96.4%; 96.9% with ICG, 93.1% with gamma-probe, and 98.2% by combining both methods. The total bilateral detection rate was 72.1%, with ICG performing better as a single tracer than Tc99m-FSC (75% vs 63.4%, respectively). In 55 women in whom both tracers were used, the bilateral detection rate was significantly higher compared with Tc99m-FSC alone. Symmetric pelvic anatomic concordance of SLN was found in only 35 of 80 patients with bilateral SLN detection (43.8%). CONCLUSION: The combination of preoperative radioisotope injection and intraoperative ICG administration may yield the best bilateral SLN detection rate. In cases of unilateral mapping failure, one cannot rely on the anatomic location of the ipsilateral SLN detected to harvest the complementary node because the symmetric concordance is poor.

Posterior reversible encephalopathy syndrome case report in an untreated, normotensive, ovarian cancer patient in the presence of paraneoplastic antibodies.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological condition with many associated risk factors. The presentation varies and consists of seizures, impaired visual acuity or visual field deficits, disorders of consciousness, headaches, confusion and focal neurological deficits. The diagnosis relies on clinical presentation and MRI findings. Treatment and prognosis are related to the underlying etiology. CASE PRESENTATION: We present a 58-year-old woman with ovarian cancer who developed symptoms and radiologic signs of PRES with no apparent trigger other than a sudden increase in blood pressure for the first time in her life and before any treatment has begun. Antibodies to collapsin response-mediator protein-5 (CRMP-5), a malignancy related paraneoplastic protein, were identified in her CSF. CONCLUSIONS: We present a novel and intriguing association between PRES and antibodies against CRMP-5 which may highlight a new etiology for this condition.

Characteristics and prognosis of borderline ovarian tumors in pre and postmenopausal patients.

OBJECTIVE: To compare patient characteristics, imaging results, surgical management and prognosis of borderline ovarian tumors (BOT) between pre and postmenopausal patients. MATERIALS AND METHODS: A retrospective cohort of all cases of histologically verified BOT between 1990-2018, comparing presentation, imaging, surgical procedures and recurrence. Patients were included in the postmenopausal group if they reported 12 months of amenorrhea with or without menopausal symptoms. RESULTS: During this 28 year study period, 66 operations were performed in which BOT was confirmed. Postmenopausal patients were 37-89 years old and premenopausal patients 18-50 years old, with an average age of 63.9 ± 13.4 and 36.2 ± 8.4 years, respectively (p < 0.001). The majority of patients in both groups were diagnosed due to abdominal pain, followed by incidental diagnosis on routine ultrasound. Imaging and CA-125 levels upon presentation were similar. Almost sixty percent of postmenopausal and 26.3% of premenopausal patients underwent laparotomy (p = 0.01), while those who underwent laparoscopy were 35.7% and 60.5%, respectively (p = 0.03). Most postmenopausal patients underwent bilateral salpingo-oophorectomy (BSO), whereas premenopausal surgeries involved cystectomy. Nearly all study patients were diagnosed in stage one. Malignant transformation occurred in 7.1% of postmenopausal patients. No malignant transformation was found in premenopausal patients. CONCLUSION: BOT's present similarly in pre and postmenopausal patients. Postmenopausal patients undergo more extensive surgery, and are diagnosed in early stage disease. Despite a tendency for a more conservative approach in premenopausal patients, prognosis is similar in both groups.

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.

The Association of an Elevated Thrombocyte Count with Clinicopathological Prognostic Factors and Survival in Patients with Uterine Carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce. OBJECTIVES: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival. METHODS: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. RESULTS: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival. CONCLUSIONS: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.

Hysterscopic Resection of Premalignant and Malignant Endometrial Polyps: Is it a Safe Alternative to Hysterectomy?

STUDY OBJECTIVE: The standard treatment of endometrial cancer (EC) and complex atypical hyperplasia (CAH) is hysterectomy with or without adnexectomy. In the last decade several centers have attempted to perform hysteroscopic resection of malignant and premalignant polyps as an alternative to hysterectomy. In the present study we evaluated the safety of this procedure in regard to residual uterine pathology. DESIGN: Retrospective chart review (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Women (n = 1766) who underwent hysteroscopic polypectomy during the years 1998 to 2016. INTERVENTIONS: Patients with CAH and endometrioid type EC in the removed polyps who underwent hysterectomy were included in the study. Patients with nonendometrioid pathology were excluded. The operative and pathologic reports of the hysteroscopy and hysterectomy procedures were revised. MEASUREMENTS AND MAIN RESULTS: Forty-three women (2.4%) were diagnosed with premalignant and malignant polyps: 21 with EC and 22 with CAH. Thirty-four women (79.0%) underwent hysterectomy and were included in the study group. The median age was 62 years (range, 35-83). Most women (79.4%) presented with postmenopausal bleeding or menorrhagia. In 13 patients (38.2%) more than 1 polyp was removed. The median size of the polyps was 2 cm (range, 1-4). In 27 women there were no other visible endometrial findings during the hysteroscopy except for the removed polyp. However, in 24 women (88.9%) residual CAH or EC was present in the hysterectomy specimen, mostly (55.6%) as multifocal lesions. CONCLUSION: Our results indicate that hysteroscopic evaluation of the uterine cavity and polyp resection are not enough for the eradication of premalignant and malignant endometrial lesions. This alternative should be reserved for well-selected cases such as for fertility preservation and for patient with surgical risk factors that after the hysteroscopic polypectomy will receive further medical treatment.

A phase 1/2a, dose-escalation, safety, pharmacokinetic, and preliminary efficacy study of intraperitoneal administration of BC-819 (H19-DTA) in subjects with recurrent ovarian/peritoneal cancer.

BACKGROUND: H19 is a paternally imprinted, oncofetal gene expressed in various embryonic tissues and in 85% of the ovarian tumors. H19-DTA (BC-819) is a DNA plasmid that drives the expression of the diphtheria toxin gene under the regulation of the H19 promoter sequence and therefore is a potential treatment for various tumors that overexpress the H19 gene, among them-ovarian cancer. OBJECTIVE: To assess the safety and efficacy of intra-peritoneal (IP) instillations of H19-DTA (BC-819) plasmid in treating ovarian/peritoneal cancer patients with advanced recurrent disease. METHODS: A phase 1-2A multi-centric trial included 14 eligible patients who were either platinum-refractory or platinum-resistant with positive H19 expression. Patients were treated IP with escalating weekly doses of BC-819 for a maximum of 6-9 weeks. Dose-limiting toxicities (DLT) were assessed after the first course of treatment for each patient and each subsequent cohort was enrolled once each subject had completed the first course of treatment and its 4-week follow-up period. The occurrence of adverse events (AEs) and response to treatment were assessed after the induction course and then periodically. RESULTS: During the study, no DLTs were observed. Only 5 grade 1 and 2 AEs, which occurred in 4 patients were considered as possibly related to BC-819. The best tumor response seen was stable disease. Median survivals of 3.2, 5.3 and 6.5 months were observed for the 60, 120 and 240 mg cohorts, respectively. CONCLUSIONS: BC-819 can be considered safe and well tolerated in intraperitoneal doses up to 240 mg. Hybridization of intraperitoneal chemotherapy with the biological treatment of BC-819 should be further evaluated in phase 2 and 3 studies.

Unexpected Significant Uterine Pathological Findings at Vaginal Hysterectomy Despite Unremarkable Preoperative Workup.

BACKGROUND: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation. OBJECTIVES: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel. METHODS: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study. RESULTS: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%. CONCLUSIONS: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

Gemcitabine-Induced Subacute Cutaneous Lupus Erythematosus: A Case Report.

Subacute cutaneous lupus erythematosus (SCLE) is a rare eruption related to several pharmacological and chemotherapy agents. We present a 63-year-old female with recurrent epithelial ovarian cancer who developed SCLE after administration of gemcitabine. Following discontinuation of gemcitabine and after oral steroid treatment, all skin lesions disappeared. In view of the extensive use of gemcitabine in recurrent ovarian cancer, it is important to be aware of the possibility of SCLE occurrence in these patients.

The Effect of Cyclooxygenase-2 Expression in Uterine Carcinosarcoma on Survival: A Reassessment Based on Mature Data.

OBJECTIVE: To reassess the effect cyclooxygenase-2 (COX-2) expression in carcinosarcoma on survival based on mature 5-year survival data. METHOD: A comparison of 5-year survival of 27 patients with carcinosarcoma according to the presence of COX-2 immunohistochemical staining and staining score was performed. RESULTS: The 5-year survival of those with positive and negative COX-2 staining was statistically not different. However, there was a clear trend for more favorable 5-year survival in patients with a high staining score than in those with a low score, and the difference was of borderline significance (38.5% vs 7.1%; P = 0.06). CONCLUSION: In view of the role of COX-2 in carcinogenesis, our finding that COX-2 expression may confer a better survival in patients with carcinosarcoma is intriguing. Larger studies are indicated to elucidate the effect of COX-2 expression on survival in patients with carcinosarcoma because this may have therapeutic implications.

Very late recurrence (after more than 20 years) of epithelial ovarian carcinoma: case report and literature review.

PURPOSE: To present a case of very late (more than 20 years) recurrence of epithelial ovarian carcinoma and to review the pertinent literature. We encountered a 50-year-old patient who, at the age of 22, underwent cytoreductive surgery and adjuvant chemotherapy for stage III serous ovarian carcinoma. She recurred after 28 years and underwent secondary surgery and chemotherapy. METHOD: A PubMed search of the English literature containing the following key words: ovarian cancer, late recurrence, late relapse, late metastasis was performed. RESULTS: Only five cases (including the present one) with recurrence after more than 20 years are so far on record. Of these, four patients were 33 years old or younger and had advanced stage at diagnosis. Time to recurrence ranged from 21 to 28 years. All patients had serous carcinoma and three had recurrence in lymph nodes. CONCLUSIONS: Very late recurrence is an extremely rare event and may result from either regrowth of dormant tumor cells or from development of a new cancer. Lifelong follow-up is critically important for ovarian cancer patients.

Weekly carboplatin with paclitaxel compared to standard three-weekly treatment in advanced epithelial ovarian carcinoma--a retrospective study.

OBJECTIVE: To retrospectively compare primary treatment with weekly carboplatin/paclitaxel (PC-W) to the standard 3-weekly carboplatin/paclitaxel (PC-3 W) in women with advanced epithelial ovarian cancer, tubal carcinoma and primary peritoneal carcinoma. METHODS: Medical records were assessed for age, stage of disease, tumor histology and grade, BRCA mutation status, and platinum sensitivity. Patients were treated with either paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every three weeks (PC-3 W; 133 patients), or with weekly paclitaxel (80 mg/m(2)) and weekly carboplatin (AUC 2) on days 1, 8, and 15 every 28 days (PC-W; 267 patients). RESULTS: Patient baseline characteristics were similar in both groups. Median overall survival (OS) was similar for PC-W and PC-3 W (64.5 months vs. 61.5 months), but PC-W had longer median progression-free survival [PFS: 27.4 months (95% CI, 22.7-31.4) vs. 19.5 months (95% CI, 15.6-22.2) for PC-3 W, p = 0.0024] and a longer median platinum-free interval [PFI: 22.1 months (95% CI, 16.0-24.5) vs. 14.2 months (95% CI, 10.7-17.2) for PC-3 W, p = 0.0075]. PC-W showed a significantly higher response rate (86.4% vs. 77.9% for PC-3 W, p = 0.0435). Multivariate analysis including for age at diagnosis, stage of disease, optimal debulking, histology, BRCA status, pretreatment CA-125 and PFI revealed that the PC-W women had lower risk of death (HR = 0.587, 95% CI, 0.402-0.857, p = 0.0058), lower risk of disease progression (HR = 0.494, 95% CI, 0.359-0.680, p < 0.0001), higher 2- and 3-year survival rates, and decreased grade II hair loss, neuropathy and thrombocytopenia compared with the PC-3 W women. CONCLUSION: The PC-W protocol improved PFS and had a similar OS as PC-3W.