P16, Ki67, P53, and WT1 Expression in Uterine Smooth Muscle Tumors: An Adjunct in Confirming the Diagnosis of Malignancy in Ambiguous Cases.

The diagnosis of uterine smooth muscle tumors is sometimes difficult, as these tumors may show worrisome features, suspicious for but not diagnostic of malignancy. The recommended immunohistochemical panel in this setting is currently under debate. In this study, we aimed to find a panel of immunohistochemical stains that would be helpful in determining the correct diagnosis in ambiguous uterine smooth muscle tumors, with an emphasis on investigating the possible usefulness of the WT1 antibody. Uterine leiomyomas were found to be immunoreactive with WT1. Since a previous study reported on the lack of immunoreactivity of uterine leiomyosarcomas with WT1, we speculated that WT1 might be useful in this setting. We retrospectively reviewed the medical charts and slides of 91 patients: 22 with leiomyosarcoma, 15 with smooth muscle tumor of uncertain malignant potential, and 54 with leiomyoma. Immunohistochemical stains for WT1, p16, p53, and Ki67 were performed on each case. We found that immunoreactivity with p16 and Ki67 (>40% and >10% of the tumor cells, respectively) and loss of nuclear expression of WT1 (<10% of the tumor cells) were significantly more common in leiomyosarcomas (all P<0.001). Mutated p53 immunohistochemical staining pattern was significantly more prevalent in leiomyosarcomas than in leiomyomas (P<0.001). Thus, in diagnostically challenging uterine smooth muscle tumors, we recommend using an immunohistochemical panel composed of Ki67, p16, p53, and WT1. A positive result in either of the former 2 (p16 >40% and/or Ki67 >10%) has the strongest association with leiomyosarcoma (sensitivity: 95.5%, specificity=88.9%, positive predictive value=77.8%, negative predictive value=98.0%).

A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA Trial.

BACKGROUND: Platinum based chemotherapy is the treatment of choice for ovarian cancer patients with a platinum treatment free interval of >6 months. Niraparib is an oral poly (ADP-ribose) polymerase inhibitor approved as maintenance therapy after a response to platinum rechallenge, regardless of BRCA status. Atezolizumab is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). A combination of poly (ADP-ribose) polymerase inhibitor and anti-PD-L1/programmed cell death protein 1 (PD-1) has shown synergy in preclinical models and promising clinical activity. PRIMARY OBJECTIVE: To determine whether the addition of atezolizumab to carboplatin based chemotherapy and to subsequent maintenance with niraparib improves progression free survival compared with placebo in patients with recurrent disease and a platinum treatment free interval of >6 months. TRIAL DESIGN: The Atezolizumab and NIraparib Treatment Association (ANITA) trial is a GEICO (Grupo Español de Investigación en Cáncer de Ovario) led phase III, randomized, double-blinded, multicenter European Network for Gynecological Oncological Trials (ENGOT) study. Patients will be randomized to arm A (control arm) consisting of platinum based chemotherapy (investigator's choice) plus a placebo of atezolizumab followed by maintenance niraparib plus a placebo of atezolizumab, or to arm B (experimental arm) consisting of platinum based chemotherapy (investigator's choice) plus atezolizumab followed by maintenance niraparib plus atezolizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria are women aged over 18 years, diagnosed with relapsed high grade serous, endometrioid, or undifferentiated ovarian, fallopian tube, or primary peritoneal carcinoma. Patients are eligible if they received no more than two previous lines of chemotherapy, relapsed ≥6 months after the last platinum containing regimen, and have at least one measurable lesion according to the response evaluation criteria in solid tumors, version 1.1. PRIMARY ENDPOINT: The primary endpoint for this study is progression free survival. SAMPLE SIZE: Approximately 414 patients will be recruited and randomized in a 1:1 ratio, with the aim of demonstrating a benefit in progression free survival for the experimental arm with a hazard ratio of O.7, using a two sided alpha of 0.05 and a power of 80%. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The trial was launched in the fourth quarter of 2018 and is estimated to close in the second quarter of 2021. Mature results for progression free survival are expected to be presented by 2023. TRIAL REGISTRATION: Clinicaltrials.gov NCT03598270.

The association between a history of gestational diabetes mellitus and future risk for female malignancies.

OBJECTIVE: To investigate whether patients with a history of gestational diabetes mellitus (GDM) have an increased future risk for female malignancies. STUDY DESIGN: A population-based study compared the incidence of long-term female malignancies (ovary, uterine, breast, and uterine cervix) in a cohort of women with and without a diagnosis of GDM. Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Women with known malignancies prior to the index pregnancy were excluded. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) for female malignancy. RESULTS: During the study period, 1,04,715 deliveries met the inclusion criteria; 9.4% (n = 9893) occurred in patients with a history of GDM in at least one of their pregnancies. During the follow-up period, patients with GDM had a significantly increased risk of being diagnosed with female malignancies, including ovarian, uterine, and breast cancer. Using a Kaplan-Meier survival curve, patients with a previous diagnosis of GDM had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders, such as parity, maternal age, and fertility treatments, a history of GDM remained independently associated with female malignancies (adjusted HR, 1.3; 95% CI 1.2-1.6; P = 0.001). CONCLUSION: Patients with a history of GDM have an increased risk for future breast, ovarian, and uterine malignancies.

Preterm delivery and future maternal risk of female malignancies.

PURPOSE: To investigate whether an association exists between preterm delivery and a future risk for female malignancies. METHODS: A population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of PTD. Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. We excluded women with known genetic predisposition or malignancies prior to the index pregnancy. Malignancies investigated included ovarian, uterine, breast and cervix. Cumulative incidence was assessed using a Kaplan-Meier survival curve. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for female malignancy. RESULTS: During the study period, 105,033 women met the inclusion criteria; 16.8 % (n = 17,596) of the patients delivered preterm. Patients with a history of PTD did not have an increased risk of later being diagnosed with female malignancies. The results remained insignificant in a sub-analysis based on malignancy type, early PTD, induced vs. spontaneous, and number of episodes per patient. Kaplan-Meier cumulative incidence was similar between the groups, and the adjusted HR was not significant (1.04, 95 % CI 0.88-1.22; p = 0.665). CONCLUSION: A history of PTD does not appear to elevate the risk for subsequent long-term female malignancies.

Positive margin status in uterine cervix cone specimens is associated with persistent/recurrent high-grade dysplasia.

The frequency of positive cone margins and its significance in cervical intraepithelial neoplasia are under controversy. The purpose of the current study was to identify factors associated with positive cone margin status and to evaluate its clinical significance in high-grade cervical intraepithelial neoplasia. Medical records of women who underwent loop electrosurgical excision procedure at the Soroka Medical Center (January 2001-July 2011) were reviewed retrospectively. Patient age, extent of dysplasia, endocervical glands involvement, positive margin status, type of margin involved, degree of margin involvement, and postcone endocervical curettage results were evaluated as possible factors associated with persistent/recurrent disease. A total of 376 women were included in the study. Cone margin involvement was observed in 33% (endocervical-22%, ectocervical-8%, both margins-3%). Factors significantly associated with cone margin involvement were older age (older than 35 y), widespread dysplasia in the cone specimen (≥4 sections) (P<0.001 for each), and endocervical glands involvement (P=0.003). Fifty patients (13%) had persistent/recurrent disease. Involvement of the cone margins (focal: hazard ratio=17, P<0.001; extensive: hazard ratio=28, P<0.001) and older age (hazard ratio=1.18 for every 5 additional years, P=0.03) were associated with persistent/recurrent disease. We conclude that women older than 35 yr with widespread high-grade dysplasia in the cone specimen and involvement of endocervical glands are more likely to have positive cone margins. Positive cone margins, particularly when extensively involved, and increased patient age are associated with persistent/recurrent disease. These factors should be considered while planning for further management.

Uterine cervix conization based on Pap smear results: the "see and treat" approach.

BACKGROUND: The "see and treat" approach, proceeding without a biopsy directly to uterine cervix conization in women diagnosed with high grade squamous intraepithelial lesion (HGSIL) on Pap smear, shortens the treatment duration, lessens patient anxiety, and reduces health care costs. OBJECTIVES: To evaluate the level of diagnostic accuracy and the over-treatment rate in the "see and treat" versus conventional management of women diagnosed with HGSIL. METHODS: We retrospectively reviewed all women with HGSIL who had undergone the "see and treat" approach during 2001-2011 at Soroka University Medical Center. Similar cohorts, who were managed conventionally with a cervical biopsy prior to the conization, served as a comparison group. RESULTS: The study population consisted of 403 women: 72 (18%) had undergone the "see and treat" approach and 331 (82%) conventional management. The false positive rate was 11% for the "see and treat" group, compared to 6% for the conventional management group (P = 0.162). Similarly, no statistically significant difference was observed when comparing the positive predictive value (PPV) of high grade dysplasia diagnosed on Pap smear (PPV 88.9%) versus cervical biopsy (PPV 93.8%) (P = 0.204). Moreover, both the false positive rate and PPV remained similar in subgroups of patients, according to age, menopausal status, number of births, and colposcopy findings. CONCLUSIONS: The accuracy level of HGSIL diagnosis on Pap smear is similar to that of high grade dysplasia on a cervical biopsy. We therefore recommend referring patients with HGSIL directly to conization. Skipping the biopsy step was not associated with significant over-treatment or other adverse effects.

The significance of lower uterine segment involvement in endometrial cancer.

BACKGROUND: Limited data suggests lower uterine segment involvement (LUSI) in endometrial cancer may be associated with other poor prognostic factors. We assessed the unclear impact of LUSI on prognosis in endometrial cancer. METHOD: ology: A revision of pathological samples following surgical staging between the years 2002-2022 was performed and clinical data collected from patients' records. Characteristics and outcomes of women with and without LUSI were compared and analysed. Kaplan Meyer survival curves compared overall survival (OS) and progression-free survival (PFS). RESULTS: 429 women were included, of which 45 (10.5%) had LUSI. No differences were found between the groups regarding demographic or clinical characteristics. LUSI was significantly associated with lympho-vascular space invasion (40% vs. 22% p = 0.01), lymph node involvement (6.4% vs. 9.1%, p = 0.05), shorter PFS (4 vs. 5.5 years, p = 0.01) and OS (5.6 vs. 11.5 years, p = 0.03). Multivariate analysis showed higher hazard ratios for OS and PFS (1.55 95%CI 0.79-3.04 and 1.29 95%CI 0.66-2.53, respectively) but these were insignificant even in a sub-analysis of endometrioid histology (1.76 95%CI 0.89-3.46 and 1.35 95%CI 0.69-2.65, respectively). A trend towards decreased PFS and OS was demonstrated in the Kaplan Meyer survival curves for all cases (log rank test p = 0.5 and 0.29 respectively), endometrioid histology (log rank test p = 0.06 and 0.51 respectively) and early-stage disease (log rank test p = 0.63 and 0.3 respectively). CONCLUSION: LUSI may be related to poorer outcome of endometrial cancer and may represent an additional factor to consider when contemplating adjuvant treatment, especially in endometrioid-type and early-stage disease.

Weekly topotecan for recurrent ovarian, fallopian tube and primary peritoneal carcinoma: tolerability and efficacy study--the Israeli experience.

OBJECTIVES: The purpose of this study was to assess the clinical activity and toxicity of weekly topotecan in a large cohort of epithelial ovarian (EOC), primary peritoneal (PPC), and tubal cancer patients. METHODS: Records of patients with recurrent EOC, PPC, and tubal cancer who were treated with weekly topotecan (4.0 mg/m on days 1, 8, and 15 on a 28-day cycle) after failure of more than 1 prior regimen were retrospectively reviewed in 8 centers in Israel. RESULTS: Two hundred four patients were evaluated for efficacy and toxicity. Median age was 62 years (range, 27-89 years); 121 (59.3%) were platinum sensitive. Patients were exposed to a median of 2 previous lines (range, 1-9), and 48.5% received only 1 prior chemotherapy regimen. Median follow-up was 15.5 months (range, 2.5-112 months). Overall response rate was 26.5%, of which 11 patients (5.4%) had complete response, and 43 patients (21.1%) had partial response. Clinical benefit rate (complete response + partial response + stable disease) was 65.7%. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.5-4.5 months). There was no significant difference between platinum-sensitive and platinum-resistant patients regarding response rate or progression-free survival. Median overall survival from disease diagnosis was 45.0 months (95% CI, 40.04-49.6 months) and 16.0 months (95% CI, 12.3-19.7 months) from initiation of topotecan therapy. Overall survival was significantly different between patients with platinum-sensitive and platinum-resistant disease (19.9 vs. 10.8 months, respectively, P = 0.003; 95% CI, 8.1-16.3 months). Multivariate analysis showed that only platinum sensitivity and topotecan line were associated with overall survival. Weekly topotecan was well tolerated-with only 16.7% of patients experiencing grade 3 to 4 hematologic toxicities. There were no other grade 4 toxicities, and only 6.9% grade 3 toxicities. CONCLUSIONS: In this large cohort of recurrent EOC, PPC, and tubal cancer, weekly topotecan was well tolerated with good clinical benefit rate, comparable to previous studies.

Is radical hysterectomy necessary in early cervical cancer?

AIMS: To estimate the prevalence of tumor spread to the parametrium, vagina and uterine corpus in radical hysterectomy specimens and define a subgroup of patients with low-risk of extracervical involvement, who may benefit from less radical surgery. METHODS: We retrospectively reviewed 96 patients with stage IA1-IIA cervical cancer who had undergone radical hysterectomy and pelvic lymphadenectomy. RESULTS: Tumor spread beyond the uterine cervix was evident in 45 (47%) patients. Thirteen (13%) of the 96 patients had parametrial tumor spread, 12 (13%) had vaginal tumor extension, and 23 (24%) had uterine corpus involvement. Tumor size >2 cm, stromal invasion to a depth of ≥8 mm, and lymph vascular space invasion (LVSI) were significantly associated with extracervical invasion. Twenty-five patients had stromal invasion of <8 mm and no LVSI, of which only 1 (4%) had extracervical involvement. On the contrary, extracervical involvement was evident in 44 patients (63%) among those who had stromal invasion of ≥8 mm and/or LVSI (p < 0.001). Among women with LVSI, extracervical tumor spread was seen with any tumor size and any depth of stromal invasion. All patients with stromal invasion to a depth of >15 mm had extracervical invasion. CONCLUSION: Patients with tumor size <2 cm, depth of invasion of <8 mm and no LVSI could be considered for less radical surgery.

Positive pathological margins after loop electrosurgical excision procedure - Management and outcome.

OBJECTIVE: Pathological involvement of cervical conization margins is a risk factor for recurrence, although management of these patients is controversial. We aimed to define risk factors for positive margins and compare recurrence following additional surgical intervention compared to conservative management. METHODS: A retrospective study of all conizations at our center between 2010 and 2019. Univariate analysis identified characteristics associated with positive margins. Women were stratified by mode of management comparing three groups (surveillance, repeat conization or hysterectomy) then two groups (surveillance vs. additional surgery). Kaplan Meyer survival curves compared cumulative recurrence stratified by mode of management. Pathological results of subsequent surgical procedures were examined for residual disease. RESULTS: Of 448 conizations performed, 131 (29.2%) had positive margins which were associated with menopause, high-grade cytology and endocervical gland involvement. Women who underwent surveillance (n = 45) were more likely to be nulliparous, with low-grade histology and less endocervical gland involvement. Women who underwent hysterectomy (n = 61) were more likely to be postmenopausal and parous. Recurrence did not differ significantly in the three-group (p = 0.073) or two-group model (6.4% vs. 7.1% p = 0.869). Kaplan Meyer survival curves depicting cumulative recurrence did not differ significantly in either model (log rank test p = 0.642 for the three-group model, and p = 0.868 for the two-group model). Residual disease was found in 51.6% of hysterectomy specimens and 52.6% of repeat conizations. CONCLUSION: Surveillance is non-inferior to additional surgery in cases with positive conization margins and constitutes a valid option specifically for younger women at risk of future obstetric complications and those susceptible post-hysterectomy complications.

Obstetric outcome following cervical conization.

OBJECTIVE: The purpose of the present study was to examine obstetric outcome of patients following conization and specifically the risk for preterm delivery (PTD). METHODS: A population-based study was performed comparing pregnancies in women following conization with those who had not undergone the procedure. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. RESULTS: Out of 104,670 deliveries, 53 women (0.05%) had undergone conization. Most conizations were performed using loop electrosurgical excision procedure (LEEP). Using multivariable analysis, the following conditions were significantly associated with conization: advanced maternal age, PTD before the 34th week, low birth weight, and cervical incompetence with cerclage. Higher rates of perinatal mortality were noted in pregnancies of women with conization, but after controlling for PTD, the association lost its significance. The risk of PTD <34 weeks was significantly higher than the comparison group (OR 7.73 95% CI 3.77-15.85, p < 0.001). This association remained significant after controlling for confounders, such as cervical incompetence, smoking, maternal age, birth order and year of delivery (OR 2.8 95% CI 1.3-6.1, p = 0.008). When comparing pregnancy outcomes of women with and without cerclage due to cervical incompetence, no significant differences were documented. CONCLUSIONS: A clear association exists between conization and PTD before the 34th week. This association persists after controlling for variables considered to coexist with PTD. Careful surveillance is required in pregnancies of women following conization for early detection of preterm contractions and PTD.

The prevalence of human papillomavirus and cervical cytology abnormalities in women infected with human immunodeficiency virus in southern Israel.

BACKGROUND: Concomitant human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection increases both HPV persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer. OBJECTIVES: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center. METHODS: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed. RESULTS: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%). CONCLUSIONS: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Three-dimensional power Doppler ultrasound in ovarian cancer and its correlation with histology.

PURPOSE: The aim of this study was to evaluate and quantify intraovarian blood flow with 3D power Doppler histogram analysis before surgical intervention in women suspected of having ovarian carcinoma and to determine the correlation with histology findings. METHODS: A prospective study was designed and 17 consecutive patients undergoing oophorectomy were included. Two groups of women were evaluated: high-risk women for ovarian pathologies and low-risk women with no known ovarian disease scheduled for bilateral oophorectomy for nonmalignant related pathology. Transvaginal ultrasound was performed using 2D, 3D-power Doppler ultrasound and histogram techniques. Four main parameters were evaluated: vascularization index (VI), flow index (FI), vascularization-flow index (VFI) and mean grayness (MG). Histological confirmation of the findings was done in all patients. Data were analyzed by the Mann-Whitney U test with P<0.05 considered as significant. RESULTS: Ultrasound scanning was performed for a total of 24 ovaries: 9 ovaries with cancer and 15 controls. There were no significant differences between the groups in all four histogram measurements: FI, VI, VFI and MG. There were no differences between the groups regarding ultrasound findings of free fluid in pelvis (16.7% in women with malignancy, 18.2% in women without ovarian malignancy; P=0.938) and the presence of complex ovarian cyst (83.8% in women with malignancy, 36.4% in women without ovarian malignancy; P=0.131). CONCLUSIONS: No significant differences were noted between benign and malignant ovaries in our population in all four indices of vascularity and perfusion of 3D power Doppler. Further large prospective studies should evaluate the significance of 3D power Doppler using histogram analysis in the early detection of ovarian cancer.

Prepregnancy obesity: a risk factor for future development of ovarian and breast cancer.

The aim of this study was to investigate the association between a history of prepregnancy obesity and a woman's future long-term risk for the development of female malignancies. A population-based study compared the incidence of long-term female malignancies in a cohort of consecutive women with and without a diagnosis of prepregnancy obesity. Deliveries occurred between the years 1988 and 2013, with a mean follow-up duration of 11.6 years. Women with known malignancies before the index pregnancy and known genetic predisposition for malignancy were excluded from the study. Female malignancies were divided according to specific type (ovary, uterine, breast, and uterine cervix). A Kaplan-Meier survival curve was used to estimate the cumulative incidence of malignancies. A Cox proportional hazards model was used to estimate the adjusted hazard ratios for female malignancy. During the study period, 106 251 deliveries fulfilled the inclusion criteria; 2.2% (n=2360) occurred in patients with a history of prepregnancy obesity. During the follow-up period, patients with prepregnancy obesity had a significantly increased risk for hospitalization because of female malignancies as a group and specifically ovarian and breast cancer. Using a Kaplan-Meier survival curve, patients with a previous diagnosis of prepregnancy obesity had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders such as gestational diabetes mellitus and maternal age, prepregnancy obesity remained independently associated with long-term risk for female malignancies (adjusted hazard ratio: 1.4; 95% confidence interval: 1.1-1.9; P=0.045). Prepregnancy obesity is an independent risk factor for long-term female malignancies such as ovarian and breast cancer.

Escalating placenta invasiveness: repeated placenta accreta at the limit of viability.

Placenta percreta is an obstetric condition in which the placenta invades through the myometrium. This is the most severe form of placenta accreta and may result in spontaneous uterine rupture, a rare complication that threatens the life of both mother and fetus. In this case report, we describe a 32-year-old woman in her fourth pregnancy, diagnosed with repeated placenta accreta, which was eventually complicated by spontaneous uterine rupture at 24 weeks' gestation. This patient had a history of abnormal placentation in prior pregnancies and previous uterine injuries. This case demonstrates a pattern of escalating placental invasiveness, and raises questions regarding the process of abnormal placentation and the manifestation of uterine rupture in scarred uteri.

Primary rhabdoid tumor of the ovary: When large cells become small cells.

•The third case of pure primary malignant rhabdoid tumor of the ovary (MRTO) is described•SMARCA4 and SMARCB1 genetic analysis and immunohistochemistry are necessary for correct diagnosis of MRTO•MRTO and small cell carcinoma of the ovary, hypercalcemic type are essentially the same and should be treated as such.

Post-conization endocervical curettage for estimating the risk of persistent or recurrent high-grade dysplasia.

OBJECTIVE: To evaluate the association between post-cone endocervical curettage (ECC) results, either alone or with cone margin status, and persistent/recurrent high-grade dysplasia after conization. METHODS: The medical records of 250 women who underwent a loop electrosurgical excision procedure with post-cone ECC at Soroka Medical Center, Be'er Sheva, Israel, between January 2001 and July 2011 were reviewed retrospectively. RESULTS: Thirty-one women (12.4%) had evidence of high-grade dysplasia in the ECC sample. Factors associated with positive ECC were being older than 35 years (P=0.004) and positive margin status (P=0.001). Twenty-nine patients (11.6%) had persistent/recurrent high-grade dysplasia. Both high-grade dysplasia in the ECC sample (hazard ratio, 2.31; P=0.032) and positive cone margins (hazard ratio, 23.4; P<0.001) were associated with persistent/recurrent disease. CONCLUSION: High-grade dysplasia in the ECC sample was associated with positive cone margin status. These 2 factors were both associated with persistent/recurrent disease. Among patients with positive cone margins, a combination of margin status and ECC was superior to margin status alone for estimating the probability of persistent/recurrent disease. For women with negative cone margins, ECC was less useful. Because ECC is valuable for assessing the risk of persistent/recurrent high-grade dysplasia in many cases, post-cone ECC should be performed routinely with conization.

Sister Mary Joseph's nodule originating from endometrial carcinoma incidentally detected during surgery for an umbilical hernia: a case report.

INTRODUCTION: Umbilical metastasis (Sister Mary Joseph's nodule) is rare. It is encountered in 1-3% of patients with intra-abdominal and/or pelvic malignancy, with gastric carcinoma being the commonest origin in men and ovarian carcinoma-in women. Only 27 cases of Sister Mary Joseph's nodule originating from endometrial carcinoma have previously been documented in the literature. CASE REPORT: In a 51-year-old woman, a Sister Mary Joseph's nodule coexisting with a large fibroid uterus was incidentally detected during surgery for suspected strangulated umbilical hernia. Subsequent laparotomy confirmed endometrial carcinoma metastasizing to the umbilical region. CONCLUSION: This is the 28th case reported in the literature of Sister Mary Joseph's nodule originating from endometrial carcinoma and the first case of Sister Mary Joseph's nodule originating from endometrial carcinoma incidentally detected during surgery for umbilical hernia. Surgeons should be aware of the possibility of Sister Mary Joseph's nodule coexisting with an umbilical hernia.

Sister Mary Joseph's nodule as the first presenting sign of primary fallopian tube adenocarcinoma.

Umbilical metastasis (Sister Mary Joseph's nodule) is often the first sign of intraabdominal and/or pelvic carcinoma. We describe the fourth case reported in the literature of Sister Mary Joseph's nodule originating from fallopian tube carcinoma. In a 54-year-old woman, Sister Mary Joseph's nodule was unexpectedly detected during umbilical hernia repair. Subsequent laparoscopy revealed a 2-cm friable tumor located at the fimbriated end of right fallopian tube and 1-cm peritoneal implant in the pouch of Douglas. Laparoscopic bilateral adnexectomy and resection of the peritoneal implant were performed. Because frozen section examination revealed fallopian tube carcinoma, the procedure was continued with laparotomy including total abdominal hysterectomy, omentectomy, and pelvic lymph node sampling. Final diagnosis was stage IIIB fallopian tube carcinoma. The patient received postoperative adjuvant chemotherapy with single-agent carboplatin and has remained alive and with no evidence of disease. It is concluded that in cases of Sister Mary Joseph's nodule, laparoscopy can be a useful tool in the search of the primary tumor in the abdomen and/or pelvis. Laparoscopy can provide crucial information with respect to the location, size, and feasibility of optimal surgical resection of the intraabdominal and/or pelvic tumors.

Weekly carboplatin in a frail elderly woman with advanced peritoneal carcinoma.

INTRODUCTION: Standard chemotherapy for ovarian, peritoneal and fallopian tube carcinoma has been a combination of carboplatin (AUC = 6) and paclitaxel 175 mg/m2 every 3 weeks. For frail and elderly patients who may not tolerate the toxicity associated with combination chemotherapy there is the option of omitting paclitaxel and giving carboplatin (AUC = 6) as a single agent every 3 weeks. The toxicity may be reduced further, without decreasing effectiveness, by giving single-agent carboplatin at a reduced dose (AUC = 2) every week. CASE REPORT: A frail 79-year-old woman with advanced peritoneal carcinoma had first-line and second-line chemotherapy with single-agent carboplatin on day 1 every 7 days. This has resulted in disease stabilization, CA-125 partial response and improved quality of life. Toxicity has been negligible. CONCLUSION: Weekly carboplatin is an attractive option for the treatment of frail and elderly patients with ovarian, peritoneal and fallopian tube carcinoma.