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Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure. Up to 3% of these polyps may show malignant changes. However, to the authors' knowledge no one has described any risk factor for the development of this pathology in postmenopausal patients with breast carcinoma treated with tamoxifen. OBJECTIVE. The objective of this study was to evaluate whether risk factors can be identified for the development of endometrial polyps in postmenopausal patients with breast carcinoma treated with tamoxifen. The authors reviewed the medical records of 54 postmenopausal patients with breast carcinoma in whom endometrial polyps were resected by hysteroscopy after at least 6 months of tamoxifen treatment (Group I). Demographic characteristics, health habits, risk factors for endometrial carcinoma, and clinical factors related to the primary breast disease were examined. The results were compared with those obtained from 210 similar patients in whom hysteroscopy did not reveal any endometrial pathology (Group II). Age at menopause was significantly older, duration of breast disease was significantly longer, and body weight was significantly heavier among Group I patients compared with Group II patients (P = 0.0162, P = 0.0026, and P = 0.0364, respectively). Endometrial thickness, measured by transvaginal ultrasonography, was significantly thicker in Group I patients (16.3 ± 7.2 mm) compared with that detected in Group II patients (11.8 ± 6.3; P = 0.0001). Various factors, such as older age at menopause, longer duration of breast disease, heavier weight, and thicker endometrium may contribute to the prediction of increased risk of development of endometrial polyps in postmenopausal patients with breast carcinoma treated with tamoxifen. Cancer 2001;92:1151–5. © 2001 American Cancer Society.

Objective To assess whether there is a decrease in endometrial thickness following discontinuation of tamoxifen treatment as measured by ultrasound.

A new mutation, I1307K, recently was reported in the adenomatous polyposis coli (APC) gene. This mutation was found to be predominant in Ashkenazi Jews, creating a hypermutable area and predisposing the development of carcinoma. The objective of the current study was to estimate the prevalence of this mutation in several of the ethnic groups that comprise the Israeli population and to elucidate the clinical features of the mutation carriers with colorectal carcinoma (CRC). A total of 111 consecutive CRC patients were evaluated and their medical history and clinical data recorded. The general population (298 Ashkenazim and 189 Yemenites) also was tested for the presence of this mutation. Mutation screening was performed using both the polymerase chain reaction-based amplification refractory mutation system and a commercial APC kit. Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mutation and 26 of 487 subjects from the general population (5.3%) carried the I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there were 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general population (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yemenite origin, 3 carried the mutation and 9 carriers were found among 189 subjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late age at diagnosis (64.6 years ± 10.0, which is similar to that of the noncarriers), mostly right-sided tumors, and moderate to good differentiation constituted the phenotype of the mutation carriers. The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is prevalent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance. Cancer 2000;88:755–60. © 2000 American Cancer Society.

To evaluate possible predicting factors for endometrial cancer in posimenopausal breast cancer patients with tamoxifen treatment, we compared various clinical features between 12 postmenopausal breast cancer tamoxifen-treated patients with endometrial cancer and a control group of 261 otherwise similar patients without this endometrial pathology. These comparisons were based on a long-term prospective follow-up. Several clinical factors such as longer duration of breast disease, older patient age, lower frequency of chemotherapy administration, and higher frequency of postmenopausal bleeding were found among the lampxifen-treated patients with endometrial cancers, and were significantly different when compared to the control group. Only eight (66.7) had postmenopausal bleeding, and a preoperative diagnosis of endometrial cancer was made in only six (50.0). When considering postmenopausal bleeding as a marker for endometrial cancer in the study patients, sensitivity was 67 and specificity was 98.

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 uteroand 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 © 1999 John Wiley & Sons, Ltd.

Background.Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure. It is generally accepted that the occurrence of malignancy in endometrial polyps among healthy women is up to 0.5%. However, no one has yet described the incidence of this malignant transformation among postmenopausal breast cancer tamoxifen-treated patients.

Histological findings of endometrial specimens collected by hysteroscopy from 261 postmenopausal breast cancer patients with tamoxifen treatment (group I) and from endometrial specimens obtained following hysterectomy from 40 similar patients (group II) were compared. This comparison was performed in order to assess whether endometrial pathologies are more frequently diagnosed in specimens collected by hysterectomy than by those collected during hysteroscopy in such patients. Overall positive endometrial histological findings were significantly more common in group II patients than in group I patients (82.5 and 24.5%, respectively; p < 0.0001). Atrophic endometrium was significantly more common in group I patients than in group II patients (75.5 and 15.0%, respectively; p < 0.0001). All other different endometrial pathologies, except for proliferative endometrium, were significantly more common in group II patients than in group I patients (endometrial hyperplasia = 17.5 and 4.2%, respectively; p < 0.0003; endometrial polyps = 30.0 and 11.5%, respectively; p < 0.006; endometrial polyps with hyperplasia = 17.5 and 4.2%, respectively; p < 0.0003; endometrial carcinoma = 15.0 and 0.4%, respectively; p < 0.0001). These findings suggest that in postmenopausal breast cancer patients treated with tamoxifen, the frequency of various endometrial histological findings and of overall positive endometrial histological findings were significantly higher in specimens collected by hysterectomy than in specimens obtained by hysteroscopy.

Objective.The aim of this study was to evaluate changes in transvaginal ultrasonographic endometrial thickness with increased duration of tamoxifen treatment in postmenopausal breast cancer patients.

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 © 1999 John Wiley & Sons, Ltd.

The present study evaluates the potential beneficial effect of co‐treatment with LHRH‐agonist in resolving premenopausal tamoxifen's 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.

Tamoxifen is widely used as adjuvant therapy for postmenopausal breast cancer patients with positive estrogen receptors. Data on a possible association of endometrial pathologies with tamoxifen treatment have been accumulating. In this review, we examine the current literature and include our own experience with this occurence. We recommend close supervision of these patients.

Microsurgical fimbriectomy with removal of the fimbria ovarica was performed on one side in 19 rabbits. The other tube was left intact as a control. In 10 animals the new ostium was left free, some distance from the ovary. In the remainder, the ostium was fixed to the ovarian capsule. Three animals with a fixed ostium developed mild hydrosalpinx even though the neostomy was patent. Of the remaining 16 rabbits, 15 conceived and became pregnant in both uterine horns. There was no significant difference between nidation index on the two sides. It is concluded that intact fimbriae with a fimbria ovarica are not essential for normal ovum capture. It is therefore suggested that methods for clinical salpingostomy may require re-evaluation.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for >48 consecutive months (30.8) when compared with similar patients who were treated for 6–24 months or for 25–48 months (20.8 and 12.5, respectively), However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for >48 months. Overall, 20.7 of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for >48 consecutive months to have a higher frequency of endometrial lesions.

Summary: In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66) showed evidence of strong endometrial stromal decidualization, while three (25) had decidual reactions in endometrial polyps. Overall, 11 (91.66) of the patients had decidual reactions, and all were treated with progestogens for ≥3 consecutive months. One patient, treated with progestogens for 1 month, had an inactive endometrium. All but three had thickened endometria (>10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for ≥3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Ovarian implantation into the uterus was performed in 27 women, none of whom conceived during the 4- to 6-year follow-up period. Bypassing the fallopian tube may, in itself, explain the disappointing results of this procedure in our series as well as in those reported in the literature. Experimental ovarian implantation into the uterus of rats supplied information regarding additional factors underlying the low success rate of this operation. It is concluded that this surgical intervention has been made superfluous in view of the poor results and the modem methods for extracorporal fertilization at present being developed.

Five women with ovarian failure who repeatedly failed to conceive following embryo transfer from donated eggs underwent endometrial development investigation. One endometrial biopsy was obtained on cycle days 19, 21, and 23 during three consecutive artificially induced cycles. All five patients had only early secretory changes on days 19 and 21. Histological evaluation on cycle day 23 revealed various developmental stages: two women had “in-phase” endometrium, two patients had adequately developed stroma but significantly retarded glandular maturation, and one women showed no progress. The histological findings were conclusive for a significant maturation delay and an impaired endometrial receptivity. There was a lack of correlation between the peripheral hormonal blood levels and the endometrial maturation.

Abstract

A 28-year-old woman was evaluated for late onset secondary amenorrhea, progressive hirsutism and an elevated serum testosterone concentration. Her serum cortisol, androstenedione, dehydroepiandrosterone sulfate and 17-hydroxyprogesterone levels were normal. Bilateral ovarian and adrenal vein catheterization demonstrated mild elevated testosterone and androstenedione levels in the right ovarian vein. Fifteen minutes after administering the intravenous injection of 5,000 IU human chorionic gonadotropin, there was a six and a half to sevenfold increase in the level of these two hormones in the right ovarian vein with no significant change in hormone levels from other sources. Based on the ovarian peripheral vein gradients obtained during venography following ovarian stimulation, the diagnosis of right ovarian hyperthecosis was made. This diagnosis could not have been reached without the combination of selective ovarian vein catheterization and ovarian stimulation. We recommend that this combined test, which may provide additional information on the source of the androgens in women with hyperandrogens, be performed in selected cases, when a virilizing tumor is suspected.

Postmenopausal breast cancer patients who were treated with tamoxifen and progestogens showed a uniform decidual reaction of the endometrium. It is well established that progestogens antagonize the estrogen effect on the endometrium by reducing its receptors in the endometrium. To assessin vivosuch a possible effect of progestogens on endometrium primarily exposed to tamoxifen, we analyzed estrogen and progesterone receptors (ER, PR) on endometrial specimens showing decidualization from nine postmenopausal breast cancer patients on tamoxifen and progestogen treatment and on endometrial polyps with areas of decidualization from two other similar patients. ER was weakly detected in the endometrial glands of four (36.4%) patients and in the endometrial stroma of one (9.1%) patient. PR was detected in the endometrial gland of only one (9.1%) patient. No PR was detected in the endometrial stroma. There was no correlation between the length of tamoxifen treatment, the tamoxifen dosage, or the length of progestogen treatment and the ER or PR content, although progestogens were administered for more than 3 consecutive months in all patients. This relatively very low ER and PR content may be attributed to the antagonistic effect of progestogens on the “priming” estrogen-like effect of tamoxifen on the endometrium.

Background: Postmenopausal breast cancer patients treated with tamoxifen have been found to have a high incidence of ovarian tumors. Transvaginal ultrasonography is an accurate and reliable method for measuring ovarian size. The purpose of this study was to establish normal values for basal ovarian volume in postmenopausal tamoxifen-treated patients and compare them with those established for healthy, postmenopausal women in the same population with no exposure to hormone treatment. Methods: In a prospective open pilot study, the ovaries of 65 postmenopausal breast cancer patients treated for at least 6 months with tamoxifen were measured by transvaginal ultrasonography. From the same population, 311 healthy postmenopausal women with no exposure to hormone therapy were examined and served as controls. After matching for menopausal age, ovarian volume was compared between groups. Results: Mean ovarian volume of postmenopausal tamoxifen-treated patients was persistently low through the menopause, whereas the mean ovarian volume of the controls was large, gradually decreasing up to the 10th menopausal year (8.6 ± 2.3 and 2.8 ± 2.1 cm3, respectively). Mean ovarian volume of the tamoxifen-treated patients was significantly lower than that of the controls during the initial menopausal years. Conclusions: An ovarian volume that is considered within normal range for a specific menopausal age in a healthy postmenopausal woman is abnormal for a postmenopausal tamoxifen-treated patient.

Background. The purpose of our study was to determine whether ovarian volume, as measured by transvaginal ultrasound and plotted on the nomogram of normal postmenopausal ovarian volume, could assist in the diagnosis of ovarian neoplasia.Methods. A retrospective study was undertaken, in which the ovaries of 85 postmenopausal women were examined by transvaginal ultrasonography prior to laparotomy. Three dimensions of each ovary were measured and ovarian volume was calculated. The results were plotted on the nomogram of normal postmenopausal ovarian volume.Results. Eighty-five ovarian tumors were diagnosed. The range of the mean ovarian volume varied between 98.15 cm3 to 161.81 cm3 from perimenopausal age to >15 postmenopausal years, as compared to 2.21.4 - 8.6±2.8 cm in the normal postmenopausal women. The deviation from the normal volume was more striking in the malignant tumors group (100%) than in the benign group (86%). When plotted on the nomogram, these values showed significant deviation (above 2 s.d.) from the norm for each group of neoplasms in every menopausal age.Conclusions. Sonographic detection of abnormal postmenopausal ovarian volume and the demonstration of the deviation from the ovarian volume nomogram, could assist the physician in early diagnosis of ovarian neoplasia. Ovarian volume measurements can serve as the primary method leading to diagnosis of ovarian cancer.

Adjuvant tamoxifen therapy for breast cancer patients has been found to be associated with various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopause may aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed 18 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%) were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and 1 had an endometrial polyp. In the second endometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the first visit had endometrial hyperplasia in the second visit. None of the patients developed endometrial cancer, and generally there was no increase in ultrasonographically-measured endometrial widths. The results of this preliminary study may suggest that there is no increased risk of development of endometrial pathologies during an additional 18 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies. Copyright 1994, 1999 Academic Press

We present the first case of heterologous mixed mesodermal tumor that developed 9 years following tamoxifen therapy in a climacteric woman with no previous pelvic irradiation and was initially treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. She continued tamoxifen therapy for 2 years, following the initial treatment, until the diagnosis of a recurrent tumor by laparotomy. The patient died of the disease 5 months subsequent to the second surgery. The association of prolonged unopposed estrogenic stimulation, with tamoxifen as a possible etiologic factor in the development of endometrial sarcomas, is discussed.

From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors’ institutions. During this period, 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 ± 24.9 (range 9–86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screenings with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them.

We present the first case of ovarian endometrioid carcinoma and endometriosis in a postmenopausal patient who was treated with tamoxifen for breast cancer. The association with prolonged unopposed estrogen-like stimulation with tamoxifen as a possible factor in the development of ovarian endometrioid carcinoma is discussed. Copyright 1994, 1999 Academic Press

Endometrial thickness, as evaluated by vaginal ultrasonography, and endometrial histologic findings, as well as demographic characteristics, health habits, and risk factors for endometrial cancer, were compared between 93 asymptomatic postmenopausal breast cancer patients who had been on tamoxifen treatment and 20 patients who had not. The mean ultrasonographic endometrial thickness in the women on tamoxifen treatment was 13.1 ± 10.4 mm, which was significantly thicker than the 4.0 ± 3.2 mm found in the nontreated women (P= 0.001). The frequency of endometrial pathological findings was remarkably high (35.5%) among the tamoxifen-treated patients, compared with nontreated patients (20.0%), with a Pvalue of 0.058 and an odd ratio of 4.6. Thus, it is suggested that the remarkably high prevalence of pathological endometrial changes was due to the continuous and unopposed exposure of the endometrium to tamoxifen.

The vulvar biopsy specimens from 128 patients were grouped according to a predetermined classification. When the charts on these 128 patients were reviewed, several facts relative to the vulvar dystrophies were noted. The presence of a vulvar dystrophy, when adequately treated, does not significantly predispose the patient to the developent of vulvar carcinoma. When first seen, the one patient who did develop carcinoma of the vulva had an initial vulvar carcinoma 3 years prior to the diagnosis of a second vulvar carcinoma and associated lichen sclerosus et atrophicus. The symptoms related to the vulvar dystrophies can be adequately controlled with medical treatment. Since the treatment will vary according to the type of dystrophy present, it is important that the diagnosis be accurately made. Vulvectomy is contraindicated as a means of treatment in the vast majority of patients with a vulvar dystrophy.

The application of autologous and frozen red blood cell (RBC) programs is described for 3 pregnant women with antibodies to high-incidence blood group antigens (anti- Lutheranb, anli-Cellano, anti-Vel). The cases illustrate how readily available supplies or rare blood types can be maintained throughout pregnancy using autologous and frozen RBC techniques, including selective predeposit, “family-sharing,” and intensive phlebotomy with fluid replacement. The RBC phenotypes described in this paper are exceedingly rare since they occur in only 0.1— 0.001 of random donors. However, the principles of autologous blood transfusions are universal and they can be applied to the general problems of blood group incompatibility in pregnancy.

Tamoxifen administration to postmenopausal women has been described as being associated with various endometrial and other gynecological pathologies. However, different coexisting gynecological pathologies in such patients have not yet been described. In the present study, we assessed the histopathological conditions diagnosed in endometrium, myometrium, and ovaries of 28 postmenopausal breast cancer patients who were treated with tamoxifen (study group) and compared the findings to those obtained from 14 similar patients without tamoxifen treatment (control group I) and from 28 age-matched healthy postmenopausal controls (control group II). All specimens were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. The overall incidence of two or more different coexisting gynecological pathologies was significantly higher among the study group (92.9%) than in control group I or in control group II (42.9 and 50%, respectively; p = 0.0001). There was no significant statistical difference between the control groups. Overall endometrial (and endometrial-like) origin of pathological conditions was significantly more common in the study group (92.6%) than in control group I (50%; p = 0.00072) and control group II (32.1%; p = 0.0000), while there was no significant difference between the latter two groups. These findings suggest that there might be an association between postmenopausal tamoxifen exposure and the development of such different coexisting or specific single gynecological pathologies originating from the endometrium.

In order to assess possible ovarian cell potential for interaction with tamoxifen, thus demonstrating possible effects of this agent on the development of ovarian pathologies through growth stimulation and cell proliferation, we measured estrogen receptors (ER) and progesterone receptors (PR) by immunohistochemical method in 16 benign ovarian tumors removed from 11 postmenopausal breast cancer patients treated with tamoxifen (study group). The results were compared with those measured in 7 similar ovarian tumors obtained from 5 similar patients without tamoxifen treatment (control group I), and in 9 similar tumors removed from 9 age-matched postmenopausal women (control group II). There were no significant differences with regard to ER or PR expression between the study group and control group I and II (ER = 18.75, 0.0 and 11%, respectively; PR = 43.75, 28.5 and 44%, respectively; p = NS). There were also no significant statistical differences between the three groups when subdividing the ovarian pathologies according to different histological types. From the results obtained in this study, it seems that tamoxifen probably does not have any direct influence on the ovaries of menopausal breast cancer patients.

Uterine leiomyomata develop during the reproductive years and may interfere with fertility through mechanisms as yet not fully understood. A developing intramural or large submucosal leiomyoma causes hypertrophy of the myometrium. Conservative myomectomy, as opposed to hysterectomy, is the preferred surgical procedure for patients who wish to preserve their fertility. Ten patients were ultrasonographically evaluated at monthly intervals foltowing myomectomy and the changes in uterine (myo-metrial) volume were assessed. There was a gradual decrease in uterine volume in all patients during the six months following removal of intramural and submucosal leiomyomata. The most remarkable decrease in size occurred during the initial two to three months for the majority of the patients. The impact of this process on fertility should be further evaluated. One of the intriguing questions is whether the period of uterine shrinkage represents the time of the healing process during which conception should be prevented.

To outline the sonographic and color Doppler flow imaging characteristics of ovarian tumors of low-malignant potential (OCLMP). Fourteen women with ovarian tumors of low-malignant potential were compared with 26 women with ovarian cystadenomas and 23 with ovarian carcinomas. Sonographically, more complex structures and echogenic lesions were found in the OCLMP and malignant tumors than in the cystadenomas, and the difference was statistically significant. Color blood flow imaging revealed a similar resistant index (RI) in the OCLMP (0.487 ± 0.07) and cystadenomas (0.489 ± 0.09) when compared with statistically significant lower RI in the ovarian carcinomas (0.391 ± 0.05) (P &lt; 0.001). Among young women, the combination of a complex ovarian mass with turbid fluid and echogenic lesions whose color Doppler flow imaging registers in the low range (RI &lt; 0.5) should raise the suspicion of an ovarian tumor of low-malignant potential. © 1997 John Wiley & Sons, Inc.

A prospective study was performed to assess the efficacy of sonohysterography (SHG) in identifying endometrial pathologies among asymptomatic, postmenopausal breast cancer patients treated with tamoxifen. In this study the uterine cavity of 68 such patients with endometrial thickness of ≥8 mm was prospectively evaluated by SHG. Forty-six (67.6%) patients in whom SHG did not identify any findings in the uterine cavity (negative group) were followed by diagnostic hysteroscopy. Another 22 (32.4%) who were identified by SHG to have abnormal endometrial findings, such as an echogenic or polypoid mass (positive group), were followed by operative hysteroscopy and by postoperative SHG. In the positive group the basal transvaginal sonogram revealed an endometrial echogenic mass in only 10 (45.5%). In the remaining 12 (54.5%) patients, the transvaginal sonogram identified only thick endometrium. In these latter 12 patients, histological assessment confirmed endometrial polyps in 8 (66.7%) and fibroid in 1 (8.3%). Four (18.2%) patients in the positive group had no histological endometrial pathology. Two (50%) of them had a uterine septum as diagnosed during hysteroscopy, in one (25%) operative hysteroscopy failed to resect the endometrial polyp, and in another (25%) there was a false-positive SHG diagnosis. Overall, SHG accurately diagnosed endometrial and/or other intrauterine pathology in 95.5% of these patients. In the 46 patients with “negative” basal SHG features, diagnostic hysteroscopy confirmed this diagnosis. Thus, there was no SHG false-negative diagnosis. Comparing the results of the basal SHG with those of operative hysteroscopy and/or the histopathological findings in the positive group, the sensitivity of SHG was 1.0, the specificity 0.0, positive predictive value 95.5%, and negative predictive value 0.0. It is suggested that SHG is a useful diagnostic tool for the assessment of specific endometrial pathologies in asymptomatic postmenopausal breast cancer patients treated with tamoxifen who were diagnosed by transvaginal sonography to have thick endometrium.

To provide an up-to-date review of studies that have examined the relative role of endometrial development in in vitro fertilization (IVF) and embryo transfer (ET) treatment in relation to the treatment outcome.

Between September 1, 1989 and October 31, 1994, 173 post-menopausal breast cancer women on tamoxifen treatment were followed up in the authors' institutions. During this period, 14 (8.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. Eight (57.1%) were found to have adenomyosis, of whom one had a large fundal adenomyotic lump and the other seven patients had two to four small microscopic fact of adenomyosis. In this study, the rate of adenomyosis described among those postmenopausal breast cancer patients treated with tamoxifen is nearly three to four times higher than the rate reported in the literature for pre- and postmenopausal women. There is no previous reported increased incidence of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Thus, it is suggested that the prolonged and unopposed estrogen-like stimulation by tamoxifen may play a causal role rather than be a casual factor in the development of this pathologic entity. Copyright 1995, 1999 Academic Press

To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility.

To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies.

Objective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome

Abstract: Objective: Corpus luteum steroidogenesis is lower for in vivo ectopic pregnancy than for intrauterine pregnancy. There is a progesterone hallmark level distinguishing between viable intrauterine pregnancy and nonviable or ectopic pregnancy. This study attempts to answer whether this is also true for in vitro fertilization-treated patients. Study Design: Using information retrieved from a computerized database, we compared the plasma 17Β-estradiol (E 2) and progesterone during the luteal phase and for every 2 to 3 days for several weeks during early pregnancy between those patients with proven ectopic pregnancies and those with singleton and multiple intrauterine pregnancies. Vaginal ultrasonography to detect an intrauterine gestational sac was performed from day 19. A total of 73 pregnancies resulted from the replacement of fresh embryos in our in vitro fertilization-embryo transfer program. Results: Only at day 10 post embryo transfer did those patients with ectopic pregnancy show statistically lower mean (SD) serum levels of E 2 [2257 (SD, 2351) pmol/L] and plasma progesterone [PP; 221 (SD, 283) nmol/L] compared with patients with intrauterine pregnancy, whose mean E2 was 8846 (SD, 5871) pmol/Land mean PP was 805 (SD, 582) nmol/L (P=0.008). For the rest of the follow-up until surgery was performed in ectopic pregnancy, there were no differences of statistical significance between extrauterine pregnancy and the intrauterine pregnancy groups. Furthermore, only on day 10 post embryo transfer, did we find a discriminatory zone (confidence interval, 95%) for E 2 levels (903 to 3502 pmol/L for EP vs 6116 to 9493 pmol/L for a singleton and 4875 to 9493 pmol/L for multiple pregnancies). PP levels were 26 to 283 nmol/L for ectopic pregnancy versus 496 to 1096 nmol/L for both singleton and multiple pregnancies. An intrauterine gestational sac was visualized at a mean of 23.2 (SD, 4) days after embryo transfer. On this day, the mean P levels were 982.6 (SD, 286.2) nmol/L for intrauterine and 804.5 (SD, 502.4) nmol/L for ectopic pregnancies (P=NS. Conclusions: Except for day 10 post embryo transfer, the steroidogenesis in ectopic pregnancy after in vitro fertilization treatment does not differ from successful intrauterine pregnancy. This observation negates an impaired steroidogenesis for ectopic pregnancy after in vitro fertilization and makes the PP level irrelevant in the diagnosis of pregnancy implantation.

In vitro fertilization cycles yield a low percentage of pregnancies. Eighty-five to ninety percent of the transferred embryos do not implant, and the abortion rate approaches 30%. Aneuploidy is assumed to be responsible for a major portion of this pregnancy wastage. The purpose of this study was to determine if there was any correlation between morphology and chromosomal content of unfertilized oocytes and rejected embryos. To assess the chromosomal content of oocytes and embryos, we used the method described by Tarkowski in 1966. Sixty oocytes from 28 women, aged between 27 and 41 years, were analyzed. Sixty-seven percent were aneuploid; of these, 23.35% were hyperhaploid, 23.35% were hypohaploid, 8.35% were hyperdiploid, 3.35% were diploid, and 8.35% showed premature chromosome condensation. Of 20 preimplantation embryos analyzed, 80% were aneuploid, 10% were diploid, 5% were haploid, and 5% showed structural anomaly. Correlation was found between maternal age and aneuploidy in oocytes and between morphology and genetic balance in preimplantation embryos.

Loss of replication synchrony during the S-phase of the cell cycle has been shown to be associated with aneuploidy in malignant cells. The replication pattern of cervical cells obtained from normal patients and from patients with preinvasive and invasive carcinoma of the cervix was evaluated. The fluorescence in situ hybridization technique was applied to Papanicolaou smear slides using p53 and 21q22 loci. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchrony in low grade squamous intraepithelial lesions was not significantly different from that of normal controls. However, the rate of asynchrony was significantly higher in the high grade squamous intraepithelial lesions and even higher in the invasive carcinoma. The authors believe these results reflect impairment of the replication control of homologous loci and that this phenomenon may be correlated to the phenotype of the tumor. Cancer 1998;83:1966-1971. © 1998 American Cancer Society.

Aim.Tamoxifen is the antihormonal treatment of choice for premenopausal breast cancer patients with advanced breast disease. Its premenopausal administration has been shown to induce supraphysiological 17β-estradiol serum levels and to be associated with the presence of persistent, bilateral functional ovarian cysts. However, these abnormalities have not yet been compared to controls. In this study we evaluated the possibility that the above hormonal and/or ovarian abnormalities are more frequent among premenopausal breast cancer patients treated with tamoxifen than among similar nontreated patients, and thus they may be attributed to tamoxifen effect.Methods.We evaluated serum hormone levels of 17β-estradiol, follicular-stimulating hormone, lutenizing hormone, and progesterone, the presence of ovarian cysts, and various demographic and clinical characteristics in 20 premenopausal breast cancer patients treated with tamoxifen (study group) and compared them to those observed in 12 similar nontreated patients (control group).Results.Ovarian cysts were found in 80% of the study patients and only in 8.3% of the control patients (P= 0.001). The incidence of oligomenorrhea was nearly significantly higher in the study than in the control group (50 and 16.7%, respectively;P= 0.0651). Various serum hormone levels tested were not found to be significantly different between the two groups, except for 17β-estradiol serum levels as detected on days 14 and 21 of the menstrual cycle, which were significantly higher among the study than in the control patients. (Day 14 serum estradiol: 757.7 ± 372.0 pg/mL versus 206.5 ± 275.0 pg/mL,P= 0.0012. Day 21 serum estradiol: 300.0 ± 134.5 pg/mL versus 96.5 ± 71.5 pg/mL,P= 0.0008.)Conclusions.Tamoxifen treatment increases the incidence of ovarian cysts and the significantly higher 17β-estradiol serum levels in premenopausal breast cancer patients.

Transvaginal ultrasonography is an effective diagnostic procedure, and thus, it can reasonably be used to determine which asymptomatic, postmenopausal breast cancer patient with tamoxifen treatment will require endometrial sampling.Overall, it seems that the contribution of pulsed Doppler flow in the diagnosis of endometrial pathologies in such patients is nonconclusive. It is suggested that sonohysterography is a useful diagnostic tool for the assessment of specific endometrial pathologies, especially of space-occupying lesions in the endometrial cavity, in such 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.

Assessment of receptor levels in tamoxifen-exposed endometrial pathologies may indicate endometrial cells potential for interaction with tamoxifen. To assess this assumption, we analyzed estrogen receptor (ER) and progesterone receptor (PR) expression by an immunohistochemical technique in endometrial specimens with benign hyperplasia, benign polyps, and carcinoma obtained from postmenopausal breast cancer patients treated with tamoxifen (study group) and from age-matched healthy postmenopausal women treated with estrogen replacement therapy (control group I) and not treated with estrogen replacement therapy (control group II). Overall gland and stromal ER expression of benign endometrial hyperplasia and of benign endometrial polyps was significantly higher in control groups I and II than that obtained from the study group (endometrial hyperplasia:P= 0.0274 and 0.00093, respectively, andP= 0.00003 and 0.00001, respectively; benign endometrial polyps:P= 0.02889 and 0.00596, respectively; andP= 0.00228 and 0.00005, respectively), while there were no differences between the two control groups. Overall gland and stromal PR expression was nearly similar in all the three groups (P= NS). There was no correlation between the length of tamoxifen treatment and the presence of ER and PR in various endometrial pathologies in the tamoxifen-treated patients. The significantly lower ER expression in most benign endometrial pathologies obtained from postmenopausal tamoxifen treated patients may further support the weak estrogen-like effect of tamoxifen on the endometrium in the menopause.

Uterine leiomyoma is the most common benign uterine tumour. Two thirds of leiomyomata undergo degeneration, 4% of which are cystic. We present a case with an unusual parametrial ultrasonographic cystic finding, thought to be of ovarian pathology, which was in fact a leiomyoma with cystic degeneration.

We present a case of a lipomeningocele in a newborn. Prenatal sonography revealed dysraphia and a 3.8 × 4.3 cm, semisolid, echogenic mass that was continuous with the sacral area and bulged posteriorly under the skin. The mass was diagnosed after birth as a lipomeningocele based on the results of MRI. This diagnosis was confirmed histologically. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:150–152, 2000.