The Added Value of SPECT/CT in Sentinel Lymph Nodes Mapping for Endometrial Carcinoma.

OBJECTIVES: This study was designed to evaluate the detection rate (DR) and sensitivity of sentinel lymph node (SLN) mapping in patients with endometrial cancer using TC99m colloid and blue dye and to evaluate the contribution of preoperative planar lymphoscintigraphy (PLSG) and SPECT/CT. METHODS: A retrospective analysis of patients who underwent SLN mapping as part of their primary surgery for endometrial cancer. Patients underwent preoperative PLSG and later with additional SPECT/CT. Intraoperative detection was performed using TC99m colloid and blue dye by cervical injections. SLNs were sent separately for pathologic evaluation with ultrastaging. RESULTS: Fifty-three patients were included in this study. Successful preoperative mapping was achieved in 31 of 37 patients (84 %) who underwent SPECT/CT compared with only 30 of 45 patients (67 %) who underwent PLSG. SPECT/CT localizations of SLNs were anatomically accurate in 91 % of cases. Intraoperative DR of at least one SLN was 77 %, whilst the bilateral DR was 49 %. DR was significantly better using combined blue dye and TC99m colloid injections compared with blue dye alone: 81 versus 57 % for unilateral and 54 versus 28 % for bilateral mapping (P = 0.01, 0.009, respectively). Six cases of nodal metastasis were diagnosed: four by positive SLNs, and two cases were diagnosed using side-specific full dissection according to the SLN algorithm when SLN detection failed. There were no cases of false-negative results. CONCLUSIONS: SLN detection using cervical injections of TC99m colloid and blue dye is feasible and sensitive for patients with endometrial cancer. SPECT/CT aids to accurate locating of the SLN.

Can angle of progression in pregnant women before onset of labor predict mode of delivery?

OBJECTIVES: The angle of progression (AOP), measured by transperineal ultrasound, has been used to assess fetal head descent during labor. Our aim was to assess whether, before onset of labor, parous women have a narrower AOP than do nulliparous women and if a narrow AOP is associated with a higher rate of Cesarean delivery. METHODS: In this prospective, observational study, we performed transperineal ultrasound in pregnant women not yet in labor at ≥ 39 weeks' gestation who delivered within 1 week of sonography. The AOP was compared as follows: in nulliparous women, between those who had a Cesarean section and those who delivered vaginally; and among women who delivered vaginally, between those who were nulliparous and those who were parous. RESULTS: Included in the study were 100 nulliparous and 71 parous women. Among those who delivered vaginally (n = 161), the median AOP before onset of labor was narrower in parous than in nulliparous women (98° (interquartile range (IQR)), 90-107° vs 104° (IQR, 97-113°), P < 0.001). Among the 100 nulliparous women, (1) the median AOP before onset of labor was narrower in those who went on to deliver by Cesarean section (n = 9) than in those delivered vaginally (n = 91) (90° (IQR, 85.5-93.5°) vs 104° (IQR, 97-113°), P < 0.001); (2) an AOP ≥ 95° (derived from the receiver-operating characteristics curve) was associated with vaginal delivery in 99% of women; and (3) 89% (8/9) of women who delivered by Cesarean section had an AOP < 95°. Among the 71 parous women, only one delivered by Cesarean section and all of those with an AOP < 95° delivered vaginally. CONCLUSION: A narrow AOP (< 95°) in non-laboring nulliparous women at term is associated with a high rate of Cesarean delivery. Parous women have a narrower AOP than do nulliparous women before the onset of labor; however, unlike in nulliparous women, a narrow AOP in parous women does not appear to be associated with Cesarean delivery and most parous women with such an angle go on to deliver vaginally.

Does hysteroscopy affect prognosis in apparent early-stage endometrial cancer?

The objective of the study was to compare the outcome measures of patients with endometrial adenocarcinoma diagnosed by endometrial biopsy, uterine curettage, or hysteroscopy. Medical records of 392 women diagnosed with apparent early-stage endometrial adenocarcinoma were reviewed. Data concerning the mode of diagnosis, histologic type and grade, surgical stage, peritoneal washings and lymph nodes status, and patient's outcome were retrieved. During the study period, 99 (25.3%) cases were diagnosed by endometrial biopsy, 193 (49.2%) by uterine curettage, and 100 (25.5%) by hysteroscopy. There were 347 (88.5%) cases of endometrioid adenocarcinoma and 45 (11.5%) of poor histologic types, including serous papillary, clear cell, and small cell cancer. Three hundred and sixteen (80.6%) patients had stage I disease, 8 (2.0%) stage II, and 68 (17.4%) stage III. Peritoneal cytology was positive in only one case. Recurrent disease occurred in 6.9% patients, of which 50% had local recurrence and 50% had distant. Recurrent disease was found in 15.2% patients diagnosed by endometrial biopsy, in 4.7% where uterine curettage was used, and in 5% when hysteroscopy was applied. No statistically significant difference in the survival rate between the different diagnostic methods applied was found, although a higher recurrence rate was noted following endometrial biopsy. After a median follow-up time of 25 months for patients undergoing hysteroscopy, there was no difference in recurrence rates and/or overall survival compared to other diagnostic procedures implying that hysteroscopy can be safely used in the diagnosis of endometrial cancer.

Does the addition of salpingectomy or fimbriectomy to hysterectomy in premenopausal patients compromise ovarian reserve? A prospective study.

OBJECTIVE: To evaluate changes in ovarian reserve in patients following hysterectomy, with or without bilateral salpingectomy or fimbriectomy. STUDY DESIGN: Open-label, prospective cohort trial of patients undergoing hysterectomy for benign uterine indications. Levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and ultrasonic measures of peak systolic flow velocity/diastolic velocity (S/D) ratio and resistance index (RI) in the ovarian artery were taken from patients before and 6 weeks after hysterectomy, hysterectomy+salpingectomy or hysterectomy+fimbriectomy. RESULTS: The study period was from November 2011 to May 2014. Sixty patients were included in the final analysis, after two patients were lost to follow-up and one patient underwent bilateral oophorectomy. Of these 60 patients, 16 underwent hysterectomy alone (control group), and 44 were included in the study group (22 patients underwent hysterectomy+fimbriectomy and 22 patients underwent hysterectomy+salpingectomy). The mean age of patients was 46 years (standard deviation 4.07 years). Between-group dfferences in FSH, AMH, ovarian volume, ovarian artery S/D ratio and ovarian artery RI were not significant. CONCLUSION: The addition of salpingectomy or fimbriectomy to routine hysterectomy in premenopausal patients does not diminish ovarian reserve.

Safety of extraovular catheter insertion for second-trimester abortion.

OBJECTIVE: To evaluate the efficacy and safety of second-trimester abortions using transcervical catheter insertion and extraovular prostaglandin (PG) administration. METHODS: Ninety women admitted for terminations of pregnancy at 17-24 weeks' gestation had transcervical catheters inserted and extraovular PGE(2) administered. Success rates were recorded, measured by induction of abortion within 24 hours, need for a complement uterine curettage, and complications. RESULTS: The technique induced abortion in 67 women (74.4%). The induction-to-abortion median interval was 12 hours (7 and 22 hours, fifth and 95th percentiles, respectively). Thirty-seven women needed uterine curettages because of incomplete abortions or excessive uterine bleeding after fetal and placenta expulsion. One woman had shivering, weakness, and nausea attributed to systemic absorption of PG, and nine women developed systemic inflammatory response syndrome associated with transcervical catheter insertion. Two of those women had septic shock, one of whom deteriorated to a life-threatening situation. CONCLUSION: Transcervical catheter insertion for extraovular PG administration is effective for inducing second-trimester abortions. Although the method is considered safe, with generally few mild, treatable complications, we observed a high rate of systemic inflammatory response syndrome, bacteremia, and sepsis caused by transcervical catheter insertion before PG administration. A reconsideration of this method's safety is warranted.

BRCA1 germline mutations in women with uterine serous papillary carcinoma.

OBJECTIVE: To determine the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma. METHODS: We screened DNA from 12 women with uterine serous papillary carcinoma for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382insC, BRCA2-6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity at the appropriate loci. RESULTS: Nine women were of Jewish Ashkenazi origin and three were non-Ashkenazi. Two of nine Ashkenazi women were carriers of germline mutations: one 185delAG mutation and one 5382insC mutation. Five women had histories of breast carcinoma before diagnosis of uterine serous papillary carcinoma. Family histories of seven women had at least one first-degree relative with malignant disease. Of those, four had at least one first-degree relative with breast, ovarian, or colon carcinoma. Both carriers had strong family histories of breast-ovarian carcinoma. Loss of heterozygosity analysis found loss of the wild-type BRCA1 allele in the primary uterine tumors. CONCLUSION: BRCA1 germline mutations were observed in two of nine of the women in this series. The loss of heterozygosity in the tumor tissue of the carriers, coupled with the high frequency of family and patient histories of breast or ovarian malignancies, suggest that uterine serous papillary carcinoma might be a manifestation of familial breast-ovarian cancer.

Prospective evaluation of endometrial thickness as a predictor of pituitary down-regulation after gonadotropin-releasing hormone analogue administration in an in vitro fertilization program.

OBJECTIVE: To determine whether pituitary down-regulation after gonadotropin-releasing hormone analogue (GnRH-a) administration can be accurately predicted by transvaginal ultrasonographic measurement of endometrial thickness. DESIGN: Prospective study. SETTING: An IVF unit of an academic medical center. PATIENT(S): One hundred eighty-one patients undergoing 265 IVF-ET treatment cycles using GnRH-a in the long protocol. MAIN OUTCOME MEASURE(S): Serum concentrations of E2 were determined, and endometrial thickness was measured by transvaginal sonography. The accuracy of endometrial thickness for predicting pituitary down-regulation was calculated. RESULT(S): Pituitary down-regulation, defined as a serum E2 concentration of < or = 55 pg/mL, was achieved in 77% (204 of 265) of the cycles. An endometrial thickness of < or = 6 mm was found in 92.2% (188 of 204) of cycles in which down-regulation was achieved. An estradiol level of < or = 55 pg/mL was present in 95.9% (188 of 196) of cycles with endometrial thickness of < or = 6 mm. CONCLUSION(S): A state of relative hypoestrogenism after GnRH-a administration, indicative of pituitary down-regulation, can be predicted with a high degree of accuracy by ultrasonographic measurement of endometrial thickness. Thus, routine testing for serum E2 concentration may be safely omitted. This may allow further simplification of IVF protocols and increase both cost-effectiveness and patients' convenience.

Acute changes in endometrial thickness after aspiration of functional ovarian cysts.

OBJECTIVE: To evaluate the influence of aspiration of functional ovarian cysts on endometrial thickness. DESIGN: Prospective study. SETTING: An IVF Unit of an academic medical center. PATIENT(S): Twenty-two patients from our IVF program, in whom administration of a gonadotropin-releasing hormone agonist preparation in the "long protocol" failed to induce pituitary desensitization, as evidenced by a serum E2 concentration of >55 pg/mL and the presence of an ovarian cyst of >20 mm in diameter. INTERVENTION(S): Transvaginal ultrasonographic-guided cyst aspiration was performed, and 2 days later, serum E2 concentration and endometrial thickness were reassessed. MAIN OUTCOME MEASURE(S): The values of serum E2 concentration and endometrial thickness before and after cyst aspiration were compared. RESULT(S): Two days after ovarian cyst aspiration, the serum E2 concentration dropped from a mean (+/-SD) of 203 +/- 93 to 37 +/- 34 pg/mL. The mean (+/-SD) endometrial thickness was 9.6 +/- 2.0 mm before cyst aspiration and decreased to 5.9 +/- 2.4 mm after the procedure. CONCLUSION(S): Within 48 hours after ovarian cyst aspiration, a significant reduction in endometrial thickness occurs concomitant with a sharp decline in serum E2 levels. The phenomenon of acute reduction in endometrial thickness in response to acute estrogen withdrawal has not been described previously. The exact mechanism and endometrial component involved in the "shrinking" process should be further investigated.

Effects of dietary fiber on the rat intestinal mucosa exposed to low doses of a carcinogen.

BACKGROUND: Changes in morphological and immunohistochemical parameters were studied in the rat intestinal mucosa exposed to low doses of a carcinogen and administered with dietary fibers. METHODS: Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine, 10 mg/kg rat, once a week. Rats were fed a semi-synthetic fiber-free diet (control) or a high-fiber diets (15%) derived from cellulose, tomato peels or white grape. The rats were sacrificed 24 weeks after the first carcinogen's injection. The ileum, colon and tumors were removed for the study. Areas of the mucosal stroma and of lymph infiltrations, and mitotic index were studied along with morphological parameters. Immunohistochemical parameters included determination of Ki-67 proliferating protein and apoptotic index. RESULTS: Areas of the stroma in colon tumors increased in rats fed tomato peels. Changes in areas of lymphoid infiltrates were related to the type of diet and tumor presence. Lymphoid infiltrations were found to be highly developed in the colon area close to tumors, especially in rats fed the white-grape diet. Mitotic index and Ki-67 protein increased significantly in the colon area close to a tumor and in tumors themselves without any relation to the fiber varieties consumed. Changes in the rate of apoptosis were not related to the preventive effect of diets: apoptotic index was high in tumors obtained from rats fed the high-cellulose diet with high tumor-preventive effects and also from rats fed the high-tomato-peel diet with low tumor-preventive effects. CONCLUSIONS: No morphological changes were found in the ileum of rats exposed to a carcinogen and fed different dietary fibers. In the colon, a carcinogen even in low concentrations inhibited the lymphoid system in the mucosa located far from the tumor or close to the tumor. An increase in the proliferation rate in the colon close to the tumor may reflect the development of precanceromatous processes or may be related to the effect of growth factors expressed by tumor cells. Finding adenoma-like dysplasia near tumors may be possible in early stages of the development of new tumors. In addition, activation of the lymphoid system of the colon following consumption to specific dietary fiber may be a mechanism by which fiber protect against cancer.

Adnexal torsion in adolescents: prompt diagnosis and treatment may save the adnexa.

Adnexal torsion, although infrequent, may have a devastating effect on the future reproductive performance of adolescents and young women. However, clear variables predicting a favorable operative outcome have not yet been identified. In this retrospective study the authors analyzed the charts of 72 adolescent girls hospitalized for acute lower abdominal pain. In 13 cases (18%) torsion of the adnexa was found and six of them ended with reproductive compromise expressed by either adnexectomy or salpingectomy. We have found that in the cases of adnexal torsion, the time factor, from admission until final diagnosis and treatment, was the only significant variable affecting the operative results. A shorter time until the operation, resulted in less harm to the reproductive organs involved. Therefore, we conclude that whenever an adnexal torsion is suspected, a quick diagnostic laparoscopy followed by an operative procedure when needed, may contribute to better reproductive performance in the future.

Elevated serum alkaline phosphatase may enable early diagnosis of ovarian cancer.

A case of endometrioid ovarian carcinoma associated with elevated levels of serum placental-like alkaline phosphatase (PLAP) is presented. Two and a half years before a final diagnosis was made following explorative laparotomy, an incidental blood test revealed elevated alkaline phosphatase in the patient's serum. A thorough investigation for the source of this elevation was negative. Postoperative immunohistochemical staining of the tumor, showed diffuse stain with PLAP, along with gradual decline to normal values of serum total alkaline phosphatase. It is suggested, that whenever serum alkaline phosphatase is elevated due to unknown reason, an investigation including alkaline phosphatase isoenzymes, serum Ca-125, trans-vaginal pelvic sonogram and even diagnostic laparoscopy, should be considered in a search for early preclinical ovarian cancer.

Trophoblastic peritoneal implants after laparoscopic treatment of ectopic pregnancy.

Persistent trophoblastic activity after salpingostomy for ectopic pregnancy implies the presence of intra-abdominal trophoblastic tissue, usually within the fallopian tube. We report a case of disseminated trophoblastic peritoneal implants, presenting as hemoperitoneum three weeks after laparoscopic salpingectomy. Only 23 such cases have been reported. Surgical treatment of ectopic pregnancy, especially by the laparoscopic technique, may cause intraperitoneal spread and reimplantation of trophoblastic tissue. Precautions for minimizing this complication are discussed.

The impact of external cephalic version on the rate of vaginal and cesarean breech deliveries: a 3-year cumulative experience.

The authors have reviewed the impact of their practice of external cephalic version (ECV) at term, with respect to success rate, factors associated with successful version and the effect of this protocol on the overall breech and cesarean breech rate. Two hundred and forty-nine parturients identified as having a breech presenting fetus after the 36th gestational week over a 3-year period, after excluding contraindicated cases, were offered a trial of ECV, with the use of ritodrine tocolysis. ECV was effected by one operator, using the minimally effective force necessary. Successful ECV was achieved in 196 attempts (78.7%). No deleterious effects in fetuses or mothers were noted. Of successfully turned fetuses, 78% eventually had a vaginal vertex delivery. Parity, birthweight and amount of amniotic fluid were found to have a significant effect on the success rate of ECV, whereas gestational age at version or placental location were not found to have a significant effect on success rate. Introduction of the ECV protocol effected a significant decrease in breech presentation at term, from 3.9 to 2.4% (P < 0.01), which can be translated into a decrease of 5.5% in the overall cesarean section rate. The authors conclude that ECV is a safe and effective procedure, in properly selected cases. Institution of a screening protocol to identify breech presentation after 36 weeks, and utilizing ECV where possible, may lead to a significant reduction in the breech delivery rate, and may prevent serious infant morbidity.

Reseal of ruptured membranes after genetic amniocentesis. A case report.

BACKGROUND: One of the most significant complications following genetic amniocentesis is rupture of membranes, reported to occur in 1.15-1.7% of cases. Management of such cases is controversial. CASE: Genetic amniocentesis complicated by ruptured membranes was diagnosed in a 36-year-old woman. The membranes resealed after 48 hours, and the patient had a favorable outcome. CONCLUSION: In the case of genetic amniocentesis complicated by ruptured membranes, if chorioamnionitis does not develop, reseal can be expected to occur within seven days in the majority of cases. Thus, conservative management should be the first option.

Diagnostic dilemmas and current therapy of Fallopian tube cancer.

Primary tubal cancer, unlike ovarian cancer, is not routinely suspected preoperatively, and thus diagnosis and therapy are delayed. We have recently encountered two cases in which primary Fallopian tube cancer masqueraded as other lesions. One presented as a pelvic inflammatory process, the second as cervical cancer. Primary Fallopian cancer should be suspected by the clinician, even if the presenting symptoms are atypical. Chemotherapy with taxol and cisplatin was instituted following debulking surgery.

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, bcl-2, p53) in macrophages of human ovarian epithelial tumors.

Apoptosis and the apoptosis-related proteins (ARP) (Fas, Fas ligand (FasL), bcl-2 and p53) were analyzed in macrophages of different human ovarian epithelial tumors. Few macrophages were found in ovaries of women without oncologic disorders. In ovarian benign cysts, macrophagic density reached 4.9+/-1.2 per 50,000 microm2, most were present in lymphoid-macrophagic infiltrates of the sub-epithelial stroma (3.7+/-0.5% of the area of a slide), and 23.4% were Fas and FasL positive. In borderline tumors, the expanse of lymphoid infiltrates increased to 15.6% of the area of a slide, and the number of macrophages increased 2.4-fold compared to benign cysts. Of the macrophages, 83-88% expressed Fas and FasL, few had bcl-2 and CD25 receptors, and isolated ones were apoptotic. In carcinomas with high lymphoid-macrophagic infiltration, the infiltrate occupied 17.5% of the slide and macrophages amounted to 12.1+/-1.5/50,000 microm2. Many macrophages were in regions of grouping apoptosis of tumor epithelial cells and significantly fewer expressed Fas, FasL and bcl-2. Macrophages destroyed by apoptosis accounted for 4.6%. In carcinomas with low lymphoid-macrophageal infiltration, the area of the last was 5.1% of the slide. There were 8.6+/-0.8 macrophages/50,000 microm2, mainly at the margins of zones of necrosis and of tumor cells' grouping apoptosis. Extensive macrophagic infiltration into tumor parenchyma is one way by which the host immune system destroys tumors. Fas and FasL appear in macrophages of benign cysts, but in borderline tumors and in carcinomas with low infiltration their concentration increases sharply, to 79.8% and 96.6%, respectively. In 4.5% of these cells, apoptosis of macrophages was seen. The findings suggest that macrophages participate in the transfer of ARP to tumor epithelial cells, thereby inducing their apoptosis, but undergoing the simultaneous apoptosis.

Apoptosis and apoptosis-related proteins in the epithelium of human ovarian tumors: immunohistochemical and morphometric studies.

BACKGROUND: The origin of malignant ovarian tumors is the subject of considerable controversy, which may be resolved by elucidation of molecular mechanisms of tumorigenesis. Therefore we have undertaken the study of apoptosis in these tumors. METHODS: Apoptosis and the expression of its related proteins, Fas, Fas ligand (FasL), bcl-2 and p53, in epithelial cells of human ovarian tumors of different histological grades, were determined immunohistochemically and morphometrically. RESULTS: Apoptosis-related proteins were absent from ovarian epithelia of patients afflicted with non-cancerous diseases. In ovarian tumors, the distribution of individual proteins varied, and depended on the grade and type of tumor. Fas and FasL were highly expressed in all tumors, while epithelial cells expressing bcl-2 were abundant in benign tumors, but their numbers significantly dwindled with the progression of malignancy. Cells expressing p53 were found in borderline tumors, and their numbers increased with malignancy, inverse of bcl-2 expression. Apoptotic tumor cells were scarce in borderline tumors and abundant in carcinomas. Grouping apoptosis was found in approximately 60% of the carcinomas. CONCLUSIONS: The initial development of ovarian tumors is accompanied by high epithelial expression of Fas, FasL and bcl-2 proteins, while apoptosis and p53 proteins are detected only at later stages of tumorigenesis.

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors.

Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.