Ron Tepper

Induction of labor versus expectant management in macrosomia: A randomized study

Objective Macrosomia at term is associated with increased maternal and neonatal morbidity, including a higher rate of cesarean delivery and shoulder dystocia. Induction of labor has been suggested as a means to prevent further weight gain and improve outcome. The aim of this study was to determine whether or not induction of labor in these cases improves maternal and neonatal outcome. Methods Patients at term with an ultrasonic fetal weight estimation of 4000-4500 g were prospectively randomized into two groups: induction of labor (group I) and expectant management (group II). Patients with diabetes, a previous cesarean delivery, or nonvertex presentation were excluded. Outcome variables included mode of delivery, arterial cord pH, presence of shoulder dystocia, brachial plexus injury, clavicular fracture, cephalophematoma, and intraventricular hemorrhage. Results Of 273 patients who were eligible for the study, 134 were randomized to group I and 139 to group II. Parity, gestational age, and fetal weight estimation were similar in the two groups. The neonates of group II patients were significantly heavier (4132.8 ± 347.4 versus 4062.8 ± 306.9 g; P = .024). The rate of cesarean delivery was 19.4% in group I and 21.6% in group II patients (not significant [NS]). Cord pH was similar in both groups. shoulder dystocia was diagnosed in five grup I and six group Ii patients (NS). None developed brachial plexus injury in group Ii patients without documented shoulder dystocia. Mild intraventricular bemorrhage was diagnosed in three of 44 group I and two of 31 group II neonates evaluated (NS). Conclusion In this prospective, randomized study, induction of labor for suspected macrosomia at term did not decrease the rate of cesarean delivery or reduce neonatal morbidity. Ultrasonic estimation of fetal weight between 4000 and 4500 g should not be considered an indication for induciton of labor.

Endometrial pathology in postmenopausal tamoxifen treatment: comparison between gynaecologically symptomatic and asymptomatic breast cancer patients.

AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients.

High Frequency of Adenomyosis in Postmenopausal Breast Cancer Patients Treated with Tamoxifen

Pathologic evaluation for adenomyosis in uterine specimens as well as demographic characteristics, health habits and risk factors for endometrial cancer were compared in 28 postmenopausal breast cancer patients with tamoxifen (TAM) treatment and in 11 similar patients without TAM treatment in order to determine the association between postmenopausal TAM exposure and the frequency of adenomyosis. The same comparison was also made between TAM-treated patients with adenomyosis and TAM-treated patients without adenomyosis. Adenomyosis was histologically diagnosed in 53.6% TAM-treated patients and in 18.2% non-TAM patients. Overall, there were no significant statistical differences in all parameters tested between the 2 groups, as well as between the TAM-treated patients with adenomyosis and the TAM-treated patients without adenomyosis. It can be concluded that adenomyosis was significantly more common among postmenopausal breast cancer patients who were treated with TAM as compared to similar patients without TAM treatment (p = 0.0186). This significant high rate of adenomyosis may be attributed to the continuous and unopposed exposure to TAM. It is, however, impossible to predict which postmenopausal breast cancer patient will develop adenomyosis after treatment with TAM.

The distribution of the local entropy in ultrasound images

In this article, a model for the amplitude statistics of the backscattered ultrasonic signal is presented. We propose to view a tissue as being composed of a large number of small units, each having slightly different characteristics. This variability within the tissue is expressed by fluctuations in the parameters of the local probability distribution function (PDF). Based on analogous expressions derived for radio propagation and optical scintillations, the local PDF is modulated by a lognormal distribution of the local standard deviation. Integrating the local contributions yields the amplitude PDF for the entire tissue. We show that the local entropy is a normal variable, since for four different local PDFs it is linearly related to the logarithm of the local standard deviation. When the local entropy histogram exhibits distinct and multiple peaks, the local entropy distribution can be used for region segmentation. This fact is demonstrated for ultrasonic images of ovarian cysts.

Prenatal diagnosis of fetal cerebellar lesions: a case report and review of the literature.

The fetal cerebellar structure, size and consistency are looked at in every system survey. Among the acquired cerebellar events that might change the cerebellar consistency are haemorrhage, infections in utero and neoplasia. Additional fetal malformations, if present, assist in making the final diagnosis. We present a case of an isolated echogenic mass in one of the cerebellar hemispheres along with the differential diagnosis. Copyright

Successful co-treatment with LHRH-agonist for ovarian over-stimulation and cystic formation in premenopausal tamoxifen exposure

The present study evaluates the potential beneficial effect of co‐treatment with LHRH‐agonist in resolving premenopausal tamoxifens induced supraphysiological serum 17β estradiol levels and persistent ovarian cysts. Ultrasonographic and serum hormonal evaluations were performed before, during, and following three consecutive injections of long acting LHRH‐agonist administered to 14 premenopausal breast cancer patients treated with tamoxifen, who had supraphysiological serum 17β estradiol levels and simultaneous persistent ovarian cysts. Within 3 weeks of the first LHRH‐agonist injection, all patients had menopausal serum estradiol levels. Ovarian cysts completely disappeared within 2 months following the first injection. Following the discontinuation of LHRH‐agonist co‐treatment, serum estradiol levels remained in physiological levels and the ovaries remained a normal size in 64.3% of the patients for 13.3 ± 11.5 months. 28.6% of the patients had a gradual reappearance of high serum estradiol levels and of ovarian cysts, and were, therefore, treated with a second course of LHRH‐agonist. Following the second course, serum estradiol levels remained in physiological levels and the ovaries remained a normal size for 8–15 months. It is concluded that short duration of co‐treatment with long acting LHRH‐agonist administered to premenopausal breast cancer patients treated with tamoxifen, successfully resolved the tamoxifen‐induced supraphysiological serum 17β estradiol levels and the ovarian cysts.

Dose-dependent effect of tamoxifen therapy on endometrial pathologies in postmenopausal breast cancer patients.

To assess whether a higher cumulative tamoxifen dose is associated with increased incidence of various types of endometrial pathologies, we compared cumulative dose of tamoxifen treatment as well as demographic characteristics, risk factors for endometrial cancer, transvaginal ultrasonographic endometrial thickness, and various treatments for the primary breast cancer between 159 postmenopausal breast cancer tamoxifen-treated patients without endometrial pathologies (group I) and 67 similar patients with endometrial pathologies (group II). A similar comparison was made between group I patients and similar patients with proliferative endometrium (group IIa), with endometrial hyperplasia (group IIb), with endometrial polyps (group IIc), and with endometrial cancer (group IId). Overall cumulative tamoxifen dose was significantly higher in group II as compared to group I (27.4 ± 33.4 and 17.4±20.2, respectively;P < 0.0252). Transvaginal ultrasonographic endometrial thickness was significantly higher in group II than in group I patients (16.3 ± 11.3 mm and 12.1 ± 6.3 mm, respectively; P < 0.0147). The frequency of diabetes mellitus, of previous postmenopausal bleeding, and of previous exposure to hormone replacement therapy was significantly higher in group II than in group I patients (P < 0.001, P < 0.0001 and P < 0.001, respectively). There were no significant differences in all parameters tested between group I, group IIa, group IIb, group IIc, and group IId. However, there was an obvious trend for higher cumulative tamoxifen dose in patients with benign endometrial pathologies as compared to those without endometrial pathologies or to those with endometrial cancer (Group I = 17.4 ± 20.2g, group IIa = 22.5 ± 18.5g, group IIb = 28.1 ± 20.3g, group IIc = 31.4 ± 42.7g and group IId = 10.4 ± 12.6g).Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.

Different Coexisting Endometrial Histological Features in Asymptomatic Postmenopausal Breast Cancer Patients Treated with Tamoxifen

In an attempt to assess the hypothesis that different endometrial sites may respond differently to tamoxifen exposure in postmenopausal women, hysteroscopic selected endometrial histology was investigated in 175 postmenopausal breast cancer patients who received continuous treatment with tamoxifen, and in 27 similar patients not treated with tamoxifen who served as controls. In the tamoxifen-treated patients 14 (8.0%) developed endometrial polyps. Of 14 patients, 8 (57.2%) each displayed atrophic endometrium in the same histologic specimen, 5 (35.7%) each had coexisting simple hyperplasia, and 1 (7.1%) other had complex hyperplasia. Another 21 (12.0%) developed simple or complex hyperplasia. The endometrial hyperplasia coexisted with atrophic endometrium in all these patients. All these lesions were selectively identified by hysteroscopic examination prior to the endometrial biopsy. In the control group 3 (11.0%) had simple hyperplasia and 2 (7.4%) had endometrial polyps. The above results support the hypothesis that the endometrium of postmenopausal breast cancer patients on tamoxifen treatment may possess different responses to tamoxifen exposure.

Recurrent endometrial polyps in postmenopausal breast cancer patients on tamoxifen

OBJECTIVES Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure, with an incidence of up to 10.7% of malignancy. Some women tend to develop recurrent polyps. However, no one has yet described any risk factors for the development of recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients. METHODS We compared various clinical features of 64 postmenopausal breast cancer tamoxifen-treated patients with a primary endometrial polyp (Group I), with those of 27 similar patients with recurrent polyps (Group 2). RESULTS Previous exposure to hormone replacement therapy was significantly more common and duration of tamoxifen treatment, up to the diagnosis of primary endometrial polyp, was significantly shorter in Group II patients (P = 0.0217 and P = 0.0148, respectively). Logistic regression analysis revealed that the combination of shorter tamoxifen exposure before the diagnosis of primary polyp, lower parity, lower menopausal age at the diagnosis of primary polyp, and higher years of tamoxifen treatment was found to increase significantly the risk of developing recurrent endometrial polyps. Any additional year of tamoxifen treatment may increase by fivefold the risk of developing recurrent polyps. There was no significant difference in ultrasonographic endometrial thickness measured before resection of the primary polyps in both groups and before the resection of recurrent polyps in Group II. CONCLUSIONS Previous use of HRT, shorter duration of tamoxifen exposure, and additional years of tamoxifen treatment may significantly increase the risk of developing recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients.

Estrogen Replacement in Postmenopausal Women: Are We Currently Overdosing Our Patients?

As there are no proven optimal serum estradiol levels, we sought to evaluate the pharmacokinetic profiles of serum estradiol levels following a single oral dose of 2 mg estradiol and 1 mg of estriol (Trisequens) among 26 surgically induced, postmenopausal patients. Their serum estradiol levels were periodically measured over 24 h following oral administration of the drug. They were divided into two groups according to the computed hourly mean estradiol values: group A, < 250 pg/ml/h ( < 918 pmol/l/h) and group B, > 250 pg/ml/h ( > 918 pmol/l/h). The mean peak estradiol concentrations were noted 2 h after drug administration and amounted to 595 +/- 190 pg/ml (2,184 +/- 697 pmol/l) in the entire cohort; 435 +/- 117 pg/ml (1,597 +/- 430 pmol/l) in group A and 712 +/- 142 pg/ml (2,614 +/- 521 pmol/l) in group B (p < 0.001). The mean total area under the curve in group A was 4,887 pg/ml (17,940 pmol/l), which was significantly lower than that of 7,995 +/- 652 pg/ml/24 h (29,350 +/- 2,393 pmol/l/24 h) found for group B (p < 0.001). The mean body mass index showed a significant difference (p < 0.003) between group A and group B (29.4 +/- 0.56 vs. 24.3 +/- 0.24). We found that 57% of our patients were exposed to excessively high levels of estradiol during the 24-hour period following drug ingestion. We advise monitoring estradiol levels and individualizing estrogen replacement therapy, to avoid the long-term exposure of postmenopausal patients to superphysiological estradiol levels.