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Biomedical subjects

J Shapira

Publications and source records attributed to J Shapira.

At least 37 records · Page 2Linked to original sources

Prognostic factors for local control of early glottic cancer: the Rabin Medical Center retrospective study on 207 patients.

PURPOSE: Different radiation therapy schedules and devices have been used over the last 20 years at Rabin Medical Center in patients with early glottic cancer. The aim of the present retrospective analysis was to identify the subgroup of patients at high risk of failure of radiation treatment. MATERIALS AND METHODS: Between 1974 and 1994, 207 patients with squamous cell carcinoma of the glottis, 182 Stage T1 and 25 Stage T2, underwent definitive radiation therapy. During this period, treatment was administered with different radiation devices (60Co or 6-MV X ray), using different dose/fraction protocols (1.8 or 2 Gy per day, 5 or 6 fractions per week), total doses (42-77.4 Gy), overall radiation times, and delays. These treatment variables, in addition to certain patient and tumor characteristics, were correlated with local control at a median follow-up of 57 months (range 18-265 months). RESULTS: The 5-year local control rates for T1 and T2 tumors were 88% and 73%, respectively. Univariate analysis showed that smoking, diabetes mellitus, anterior commissure involvement, T stage, and extension of tumor to one third or more of the vocal cord were highly significantly correlated with decreased local control. None of the treatment variables, including dosage at which complete tumor regression was noted, were found to be predictive. By multivariate analysis, only anterior commissure involvement was found to be highly significant (risk ratio 1.9, 95% CI 1.2-3.0, p = 0.027), and T stage was borderline significant (risk ratio 1.6, 95% CI 1.0-2.5, p = 0.054). CONCLUSION: This study suggests that only two tumor characteristics are predictive of local failure of early glottic cancer: anterior commissure involvement and T stage. Treatment variables apparently do not influence local control.

Adult↗

Ovarian overstimulation and cystic formation in premenopausal tamoxifen exposure: comparison between tamoxifen-treated and nontreated breast cancer patients.

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 17beta-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 17beta-estradiol, follicular-stimulating hormone, luteinizing 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 17beta-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 17beta-estradiol serum levels in premenopausal breast cancer patients.

Adult↗

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+/-20.2 g, group IIa = 22.5+/-18.5 g, group IIb = 28.1+/-20.3 g, group IIc = 31.4+/-42.7 g and group IId = 10.4+/-12.6 g). Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.

Aged↗

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 tamoxifen's induced supraphysiological serum 17beta 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 17beta 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 17beta estradiol levels and the ovarian cysts.

Adult↗

Endometrial cancers in postmenopausal breast cancer patients with tamoxifen treatment.

To evaluate possible predicting factors for endometrial cancer in postmenopausal 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 tamoxifen-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%.

Adenosarcoma↗

Morphometric variables of the primary second molar in children with Down syndrome.

Thirty-seven second primary molar teeth of children with DS were examined from casts of 6 girls and 8 boys aged 7-14 years, obtained from two centers for DS in Jerusalem and Haifa, Israel. One hundred and eighty-two primary second molars of normal children were examined from dental casts of 26 boys and 21 girls, which were taken for routine orthodontic evaluation. The following variables were examined on the teeth: all the inter-cuspal distances, the angle between the cusps, the area within the line connecting cusp tips, maximal buccolingual and mesiodistal dimensions, maximal perimeter of the occlusal table, maximal area of the occlusal table, maximal perimeter of the tooth crown from occlusal view, and maximal area from occlusal view. The results indicate that the second primary molars in individuals with DS are generally larger in the external dimensions (bl, md) than teeth of normal children, with larger inter-cuspal distances ('internal dimensions'). No significant change in the angles between the cusps were recorded. Thus, it seems that DS second primary molars retain the same cuspal shape of normal teeth, but with larger proportions. Sexual dimorphism was found to be more pronounced in the DS children. It is suggested that in DS, there may be a transitory acceleration in mitotic activity of developing enamel organs at about the early stage of gestation, which persists during the initial stages of mineralization of the primary teeth. The initial acceleration would then be followed by the widely recognized retardation in growth, reflected in smaller permanent teeth.

Adolescent↗

Modified cuspal relationships of mandibular molar teeth in children with Down's syndrome.

A total of 50 permanent mandibular 1st molars of 26 children with Down's syndrome (DS) were examined from dental casts and 59 permanent mandibular 1st molars of normal children were examined from 33 individuals. The following measurements were performed on both right and left molars (teeth 46 and 36 respectively): (a) the intercusp distances (mb-db, mb-d, mb-dl, db-ml, db-d, db-dl, db-ml, d-dl, d-ml, dl-ml); (b) the db-mb-ml, mb-db-ml, mb-ml-db, d-mb-dl, mb-d-dl, mb-dl-d angles; (c) the area of the pentagon formed by connecting the cusp tips. All intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to design a multivariate probability model for DS and normals. A model based on 2 distances only, mb-dl and mb-db, proved sufficient to discriminate between the teeth of DS and the normal population. The model for tooth 36 for example was as follows: p(DS) = (e(30.6-5.6(mb-dl)+25(mb-db)))/(1 + e(30.6 5.6(mb-dl)+25(mb db))). A similar model for tooth 46 was also created, as well as a model which incorporated both teeth. With respect to the angles, significant differences between DS and normals were found in 3 out of the 6 angles which were measured: the d-mb-dl angle was smaller than in normals, the mb-d-dl angle was higher, and the mb-dl-d angle was smaller. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in the DS population.

Adolescent↗

Estrogen and progesterone receptors of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen.

Adenomyosis is an ectopic endometrial tissue located in the myometrium. It has been reported to develop at a higher rate among postmenopausal breast cancer patients on tamoxifen (TAM) treatment than in untreated patients. It has also been reported to be stimulated by estrogen. Assessing receptor levels in adenomyotic tissue may indicate the adenomyotic cell's potential to interact with TAM. In the present study the estrogen receptor (ER) and progesterone receptor (PR) were analyzed by an immunohistochemical technique in adenomyotic and the corresponding endometrial tissues of 14 postmenopausal breast cancer patients treated with TAM and in 15 healthy postmenopausal patients who served as controls. All TAM-treated patients had normal postmenopausal serum estradiol levels. Overall the ER and PR contents in adenomyotic tissue (42.9 and 71.4%) and in the endometriotic tissue (64.3 and 78.6%) obtained from the study patients were similar to those obtained from the control group (adenomyosis, ER and PR = 46.7 and 86.7%; endometrium, ER and PR = 40 and 73.3%; p = NS). In the study group, the ER content was lower in the adenomyotic (42.9%) than in the endometriotic tissue (64.3%). No correlation was found between the duration of TAM therapy, the TAM dosage level or the ER or PR content in the adenomyotic or endometrial tissues. The finding of a relatively low ER content in the adenomyotic tissue than in the endometriotic tissue in postmenopausal TAM-treated patients without endogenous estrogens, similar to that observed in healthy premenopausal women, may be attributed to the estrogen-like effect of TAM.

Aged↗

Estrogen and progesterone receptors in benign ovarian tumors of menopausal breast cancer patients treated with tamoxifen.

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.

Aged↗

Different coexisting gynecological and endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen.

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.

Aged↗

Ovarian volume in postmenopausal breast cancer patients treated with tamoxifen.

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.

Aged↗

Value of sonohysterography in asymptomatic postmenopausal tamoxifen-treated patients.

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 > or = 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.

Antineoplastic Agents, Hormonal↗

Estrogen and progesterone receptors in the endometrium of postmenopausal breast cancer patients treated with tamoxifen and progestogens.

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 assess in vivo such 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.

Adult↗

Estrogen and progesterone receptor expression in postmenopausal tamoxifen-exposed endometrial pathologies.

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, and P = 0.00003 and 0.00001, respectively; benign endometrial polyps: P = 0.02889 and 0.00596, respectively; and P = 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.

Antineoplastic Agents, Hormonal↗

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.

Aged↗

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.

Aged↗