The added benefit of transvaginal sonography in the clinical staging of cervical carcinoma.

INTRODUCTION: Patients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high-detail TVS, and positron emission tomography with 18 F-labeled fluoro-2-deoxyglucose and computed tomography (18 F-FDG PET/CT) may contribute to triage efficiency of cervical cancer patients. MATERIAL AND METHODS: This is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010-2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities-a thorough physical examination, a high-detail TVS, and positron emission tomography (PET) with 18 F-FDG and computed tomography (18 F-FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation. RESULTS: Seventy-three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone. CONCLUSIONS: The combination of high-detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18 F-FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.

Clinical Use and Optimal Cutoff Value of Ca15-3 in Evaluation of Adnexal Mass: Retrospective Cohort Study and Review of the Literature.

OBJECTIVE: To estimate the diagnostic performance and reference values of serum cancer antigen (Ca)15-3 levels in the triage of adnexal masses. MATERIALS AND METHODS: This retrospective cohort study was carried out in 481 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass between years 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and routine preoperative measurements of serum Ca125 and Ca15-3. RESULTS: Combination of Ca125 with Ca15-3 elevated the sensitivity of Ca125 alone (from 86.9% to 93.2%; P=0.029), along with reduction of its specificity (from 80.5% to 69.5%; P=0.005) in differentiation between malignant and benign cases. According to receiver operating characteristic curve, Ca15-3 level of 21 U/mL was shown to be the optimal reference value for malignancy detection. All cases with Ca15-3 levels above 44.5 U/mL were malignant, mostly of primary ovarian source. CONCLUSIONS: As Ca15-3 assessment allowed detection of significantly more malignancy cases, we believe that measurement of this marker in combination with Ca125 is worthwhile in patients presenting with adnexal masses. The cutoff of 21 U/mL seems to be the optimal value in this specific population. High Ca15-3 levels (above 44.5 U/mL) strongly direct to a diagnosis of malignancy, mostly of primary ovarian tumors rather than breast malignancy.

Should the Risk of Invasive Cancer in Pregnancy and the Safety of Loop Electrosurgical Excision Procedure During the First 15 Weeks Change Our Practice?

OBJECTIVE: The aim of this article was to describe the outcome of women diagnosed with cervical intraepithelial neoplasia (CIN) grades 2 or 3 in pregnancy either observed or treated by loop electrosurgical excision procedure (LEEP) in the first 15 weeks of gestation. METHODS: Loop electrosurgical excision procedure during the first 15 gestational weeks compared with observation of CIN2/3. This is a retrospective analysis of a nonrandomized study at tertiary, academic, and referring centers in Israel. Ninety-three pregnant women diagnosed with CIN2/3 between 2006 and 2016 were included in this study. Fifty patients with CIN2/3 on cervical biopsy were conservatively followed-up, and 43 patients have undergone LEEP during the first 15 gestational weeks. Main outcome measures were ultimate diagnosis of invasive cancer or CIN, pregnancy outcome, and complications. RESULTS: In 5.4% of CIN2/3 during pregnancy, the final diagnosis was invasive cancer. The postpartum results of 50 women who were conservatively observed were as follows: 3 (6.0%) had cervical cancer and undergone radical hysterectomy, 33 (66.6%) had CIN2/3, and 14 (28%) had CIN1 or normal histology. The diagnoses of the 43 patients who have undergone LEEP were invasive cancer in 2 patients (4.6%) but did not undergo hysterectomy, CIN2/3 or adenocarcinoma in situ (AIS) in 38 patients (88.4%), and 3 women (7%) had CIN1 or normal histology. None of them suffered severe bleeding. Thirty-seven women continued their pregnancy, 34 (91.9%) had term deliveries, 2 (5.4%) gave birth at 34 and 36 weeks, and 1 patient had missed abortion (2.7%). CONCLUSIONS: The LEEP procedure during the first 15 weeks of pregnancy is safe. A total of 5.4% of the women with CIN2/3 during pregnancy were diagnosed with invasive cancer. It is time to reconsider the recommendations about CIN2/3 in early gestation.

CEA in evaluation of adnexal mass: retrospective cohort analysis and review of the literature.

BACKGROUND: The aim of this study was to estimate the diagnostic accuracy of serum carcinoembryonic antigen (CEA) levels in conjunction with Ca125 in the triage of adnexal masses. METHODS: This retrospective cohort study was carried out in 495 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass, between 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and preoperative measurements of serum Ca125 and CEA. For each marker, sensitivity, specificity, positive predictive value, negative predictive value and risk ratio were calculated. RESULTS: Combination of CEA with Ca125, compared with Ca125 levels alone, yielded a nonsignificant effect on sensitivity (87.4% vs. 88.9%, respectively, p = 0.64) and specificity (79.3% vs. 74.3%, p = 0.18) in differentiating malignant from benign adnexal masses. CEA levels were higher in mucinous histological types, but were not helpful in detection of borderline tumors. Significantly higher CEA (21.4 ± 53.6 vs. 3.2 ± 11.9 ng/mL, p = 0.0002) and lower Ca125 values (103.9 ± 84.9 vs. 796 ± 1,331.5 U/mL, p = 0.0338) were demonstrated in the 17 metastatic cases compared with 181 primary ovarian malignancies. CONCLUSIONS: The combination of the tumor markers CEA and Ca125 did not contribute significantly to the detection of malignant adnexal masses compared with Ca125 alone. As our results suggest that higher CEA levels could be useful in differentiating metastatic tumors from primary ovarian malignancy and in diagnosis of mucinous histology, this issue should be investigated in large, well-designed, prospective cohort trials.

CA 19-9 in evaluation of adnexal mass: retrospective cohort analysis and review of the literature.

OBJECTIVE: The aim of this study was to estimate the diagnostic accuracy of serum marker CA 19-9 levels in the triage of adnexal masses. METHODS: This retrospective cohort study was carried out in patients referred to the Gynecology Department at Carmel Medical Center due to adnexal masses. All patients underwent preoperative measurements of serum CA 125 and CA 19-9 and surgery with histopathologically confirmed diagnosis. RESULTS: Between January 2005 and December 2012, 503 patients with adnexal masses were evaluated with serum tumor markers. Combination of CA 19-9 with CA 125, compared with CA 125 levels alone, suggested a nonsignificant effect on sensitivity (86.9% vs. 88.9%, respectively, p = 0.54) or specificity (79.5% vs. 73.5%, p = 0.1) in differentiating malignant from benign adnexal masses. CA 19-9 was not helpful in detecting mucinous histological types or borderline tumors. Mean CA 19-9 levels were higher in metastatic cases compared with primary ovarian malignancy (488.7 ± 1,457 vs. 46.3 ± 149.8 U/mL, respectively, p = 0.001). In mature cystic teratomas, mean CA 19-9 levels were higher and CA 125 levels were lower than in ovarian carcinoma (p = 0.049 and p = 0.0012, respectively). CONCLUSIONS: The combination of the tumor markers CA 19-9 and CA 125 did not contribute significantly to the detection of malignant adnexal masses compared with CA 125 alone. As our results suggest that higher CA 19-9 levels could be helpful in differentiating metastatic tumors from primary ovarian malignancy; this issue should be investigated in large well-designed prospective cohort trials.

[Human papillomavirus types in women with cervical cancer in Haifa District].

BACKGROUND: Human papillomavirus (HPV) is recognized as the absolute cause of cervical cancer and is found in 99% of the Lesions. HPV 16 and 18 are detected in 70% of the cases. Two vaccines against HPV 16 and 18 were approved for use in Israel in recent years. PURPOSE: To determine the prevalence of human papillomavirus (HPV) in women with invasive cervical cancer in the Haifa district, and to see if the vaccine is suitable for our population. METHODS: The study population included 65 women from the Haifa District who were diagnosed with invasive cervical cancer in the Cervix Clinic of Carmel Medical Center. Samples for HPV typing were obtained during the evaluation of those patients. DNA was extracted from brush samples and HPV genotype was determined by nested-PCR followed by sequencing. RESULTS: Out of 65 patients with cervical carcinoma, 64 were found positive for HPV. The main HPV types in our patients were HPV 16 in 53.8% of the patients, HPV 18 in 12.3% of the patients and HPV type 45 in 13.8% of the patients. HPV type 33 was found in 4.6% of the patients, and HPV types 31 and 66 in 3.1% of the patients. Each of HPV types 54, 56, 58 and 59 were found in one patient. The main complaint was postmenopausal bleeding or menometrorrhagia in 24 patients (36.9%), post coital bleeding in 18 patients (27.7%) and 14 patients (21.5%) were evaluated due to an abnormal cytological smear Squamous cell carcinoma was diagnosed in 83% of the patients and cervical adenocarcinoma in 15.1% of them. CONCLUSIONS: The prevalence of HPV types in Haifa district is similar to world prevalence of HPV's, where HPV 16 and 18 cause 66.1% of cervical cancer, while in our study HPV45 and HPV 66 were found in higher proportions of cases than reported worldwide. In our population the vaccine against HPV 16/18 can prevent almost 70% of cases of cervical cancer, but a multicenter study should be performed in order to obtain larger numbers.

Displacement of ureteral orifices following anterior colporrhaphy.

INTRODUCTION AND HYPOTHESIS: It is currently unknown whether ureteral orifices maintain their anatomic location after reconstructive pelvic surgeries. We therefore aimed to assess ureteral orifices' location after anterior colporrhaphy. METHODS: Between August and December 2007, patients undergoing anterior colporrhaphy for advanced cystocele in our institution underwent cystoscopy with intravenous dye injection and placement of ureteral catheters before and after the surgery. Each ureteral orifice location was marked on an X-Y coordinate on the posterior bladder wall before and after surgery. RESULTS: Thirteen women aged 44-80 years were included in the study. Postoperatively, ureteral orifices were noted to migrate 0.65 +/- 0.3 cm caudally (closer to the urethrovesical junction) (p = 0.002) and 0.32 +/- 0.5 cm laterally (p < 0.05). CONCLUSIONS: Anterior colporrhaphy is associated with significant caudal and lateral displacement of both ureteral orifices. These findings are of potential importance for pelvic reconstructive surgeons and may facilitate faster cystoscopic evaluation of ureteral patency postoperatively. They may also have implications on the angle of the preferred optical equipment to be used.

Primary repair of advanced obstetric anal sphincter tears: should it be performed by the overlapping sphincteroplasty technique?

Advanced obstetric anal sphincter tears are often associated with a high incidence of fecal and flatus incontinence. We aimed to assess the clinical outcome of these repairs when done by the overlapping sphincteroplasty technique with reconstruction of the internal anal sphincter and perineum. Between August 2005 and December 2006, all grades 3 and 4 obstetric anal sphincter tears in our department were repaired by a reconstructive pelvic surgeon, primarily using the overlapping sphincteroplasty technique with reconstruction of the internal anal sphincter and perineum. All women were followed every 6 months using the Colorectal Anal Distress Inventory and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, a physical examination of the anal sphincter, anal manometry, and transperineal anal sonography. There were 3,478 deliveries of which 22 (0.63%) anal sphincter tears were repaired in women aged 22-41 years. Two women were diagnosed with Royal College of Obstetricians and Gynecologists grade 3a, eight with grade 3b, nine with grade 3c, and three with grade 4 anal sphincter tears. Postoperatively, 21 patients attended the outpatient clinic, with an average follow-up time of 9.2+/-1.4 months. Only two women (9.5%) complained of flatus incontinence and fecal urgency and had mildly decreased anal sphincter squeeze pressure and a small sonographic anal sphincter defect. None of the women complained of fecal incontinence. Two women (9.5%) reported on transient perineal pain and one (4.8%) on transient dyspareunia. All other women were asymptomatic and had normal anal manometry and sonographic evaluation. Repair of obstetric anal sphincter tears using the overlapping sphincteroplasty technique with reconstruction of the internal anal sphincter and perineum seems to carry favorable clinical outcome and reduced risk for anal incontinence, perineal pain, and sexual dysfunction.

[Prenatal diagnosis of chorioangioma].

Chorioangioma is a benign tumor ot aberrant vessels originated from the chorion. This is a case study of a 22 year-old woman presented at 22 weeks of her first gestation with polyhydramnios and a sonographic finding consistent with placental chorioangioma. The fetus developed hydrops two weeks later. After three more days the patient was admitted due to abdominal pain and vaginal bleeding. The membranes ruptured spontaneously. Five hours from admission she delivered spontaneously a dead 1450 grams male abortus. Uterine revision was performed due to incomplete placental expulsion. A solid mass was removed during the procedure. The mass was sent to pathology and was diagnosed as placental chorioangioma. Large chorioangioma require careful follow-up due to the possibility of rapid deterioration in fetal condition.

BRCA germline mutations in Jewish women with uterine serous papillary carcinoma.

OBJECTIVE: Our recent study determined the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma (USPC). The purpose of this study was to determine the incidence of these mutations in an enlarged series of USPC. METHODS: We screened DNA from 27 women with USPC for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382 insC,BRCA2-6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity (LOH) at the appropriate loci. RESULTS: Women (20) were of Jewish Ashkenazi origin and seven were non-Ashkenazi. Four of 20 (20%) Ashkenazi women were carriers of germline mutations: three 185delAG mutation and one 5382insC mutation. All carriers had strong family histories of breast-ovarian carcinoma. Seven out of 20 (35%) women had been diagnosed for breast carcinoma before diagnosis of USPC. Family histories of 12 women (60%) showed at least one first-degree relative with breast, ovarian, or colon carcinoma. Loss of heterozygosity analysis found a loss of the wild-type BRCA1 allele in three of the four primary uterine tumors that were examined. CONCLUSIONS: Our findings further support our previous published data suggesting a high incidence of BRCA carriers among USPC Ashkenazi Jewish patients. The loss of heterozygosity in the tumor tissue of carriers coupled with the high frequency of patient and family history of breast and ovarian malignancies suggest that USPC might be part of the manifestation of familial breast-ovarian cancer in Ashkenazi Jewish patients.

Evaluating the risk of tuberous sclerosis in cases with prenatal diagnosis of cardiac rhabdomyoma.

OBJECTIVE: To evaluate the prenatal parameters that increase the risk of tuberous sclerosis in prenatal management of fetal cardiac tumors suspected as rhabdomyoma. METHODS: The study was a retrospective survey of 18 documented cases in which cardiac rhabdomyoma was suspected during pregnancy. The following parameters were evaluated as possible risk factors associated with tuberous sclerosis: tumor size, isolated or multiple, and family history of tuberous sclerosis. RESULTS: Eighteen documented cases in which cardiac rhabdomyoma was found during pregnancy were evaluated. Of these cases, seven (39%) had proven tuberous sclerosis and 11 were found to be non-associated tuberous sclerosis tumors. When combining the present data with previous series, cases with diagnosis of tuberous sclerosis had equal mean tumor size to those with normal outcome. Family history of tuberous sclerosis in the presence of cardiac rhabdomyoma almost invariably ended with tuberous sclerosis (86%). All other cases with diagnosis of tuberous sclerosis and no family history had all multiple cardiac tumors. CONCLUSION: The present data suggest that 39% of in utero suspected cardiac rhabdomyoma would have tuberous sclerosis. Family history and multifocality remain the strongest predictors of tuberous sclerosis, whereas size of the cardiac tumor can not reliably be used to predict tuberous sclerosis in prenatal counseling.