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Increased risk of malignancy and uterine disease following perimenarchal hospitalization: an estrogen window effect.

The estrogen window hypothesis postulates that tumor induction by environmental carcinogens is facilitated by the endocrine effects of incomplete ovarian maturation at menarche. To determine if illness and operation at or near menarche might modify ovarian maturation and thus increase cancer risk, we studied the subsequent reproductive, surgical, and malignancy history of 125 women who were aged 10 to 15 years when admitted for possible appendicitis during 1945 to 1951. Total operative experience and cholecystectomy rates were within expectation, but excess rates for dilatation and curettage (98 versus 57 expected, P less than 0.001) and hysterectomy (41 versus 23 expected, P less than 0.0006) suggest disturbed endocrine maturation. In addition, one patient developed Cushing's syndrome and five patients developed rheumatoid arthritis. Eight malignancies were observed (twice the expected rate of 3.4, P = 0.047); six occurred before age 40 years (versus 1.54 expected, P = 0.001). Tumors and age at diagnosis were: lymphoma (20), ovarian (28), breast (32), thyroid (34), lung (36), cervix (39), endometrium (48), and colon (50). Compared with standard rates, the peak incidence in those who were menarchal at hospitalization was 20 times the expected incidence; in those who were premenarchal the rate was five times the expected incidence, and in those who were postmenarchal the rate was as expected. The results of this study support the validity of the estrogen window hypothesis and indicate the serious consequences of perimenarchal illness. Enteric disease requiring hospitalization at or near menarche appears to define a group of women at risk for gynecologic disease and malignancy; further study is needed to determine if there is an appropriate prophylactic therapy to reduce that risk.

Adolescent↗

[Pyometra without accompanying malignant uterine disease].

Twenty-two cases of non-malignant pyometra which were observed during a period of 15 years are described. 22% were recurrences. All of the women were postmenopausal with discharge and haemorrhage as the commonest symptoms. Pyrexia was rare. Pyometra cannot be excluded or diagnosed by means of gynaecological examination. In cases of suspected pyometra, thorough cervical dilatation and curettage are recommended. Antibiotics should only be administered if there is evidence of invasive infection, in the form of pyrexia, generalised malaise or altered laboratory parameters. In cases such as these, preparations which are effective for aerobic and also anaerobic bacteria should be employed. Follow-up control every six months is recommended on account of the great tendency to recur.

Aged↗

Evaluation of a device for objective determination of cervical consistency: a pilot study of device's validity on uterine specimens obtained by total abdominal hysterectomy for benign uterine disease.

A new device in assessment of cervical consistency by means of resistance to electrical current was compared to observations made by traditional clinical assessment of the cervix. The cervix of 50 specimens obtained consecutively at a series of total abdominal hysterectomies done for benign disease was evaluated for cervical consistency first by palpation preoperatively and then by the new device, using 5 prototypes, after the specimen was removed. Obtained results showed that intra-observer error for all five prototypes averaged 1.28 +/- 2.5% (mean +/- standard deviation), whereas inter-observer error was 8.44 +/- 7.9%. Stratified by clinical cervical consistency as soft, moderate and firm, there was a statistically significant difference in the resistance to electrical current (f = 29.0, r2 = 0.19, p < 0.0001). Resistance to electrical current was highest for firm cervices, less for those of moderate consistency, and least for soft ones (21.8 +/- 2.73, 19.6 +/- 2.91 and 15.6 +/- 4.09 ohms, respectively). In conclusion, measurements of cervical resistance obtained objectively by a new device reliably correlated with traditional clinical assessment of cervical consistency.

Cervix Uteri↗

Bacteriological findings, blood chemistry profile and plasma endotoxin levels in bitches with pyometra or other uterine diseases.

Uteri from 60 bitches with a clinical diagnosis of pyometra, or with an enlarged uterus as revealed radiographically or ultrasonographically, underwent histopathological examination, at which a diagnosis of pyometra was established in 48 of the 60 (80%) cases. Escherichia coli was isolated from 43 (90%) of the 48 uteri with pyometra. In 8 of the 60 cases, other pathological uterine conditions, such as endometrial hyperplasia, adenomyosis, mucometra or hydrometra, were diagnosed histopathologically. No bacterial growth was observed in the uteri of these 8 cases. Four of the 60 bitches (6%) showed no pathological changes in the uterus, and in 3 of these no bacteriological growth was seen in the uterus, while in one case a sparse growth of mixed culture was found. Blood samples from bitches with uterine infection caused by gram-negative bacteria showed marked hematological changes. These included higher total WBC counts and a more marked left shift in the differential WBC count than among the other bitches. Toxic degeneration of neutrophils was present among the bitches with gram-negative uterine infection and the serum ALP level was slightly higher than in the other groups of bitches. The plasma endotoxin concentration was determined in 53 bitches before surgery, in 28 bitches after surgery and in 11 control dogs. Only in 7 of the samples was endotoxin detected. The general condition of the bitches included in the present study was only mildly to moderately affected, and in no case indicated severe endotoxemia.

Animals↗

Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment.

A single gene encodes the key enzyme for estrogen biosynthesis termed aromatase, inhibition of which effectively eliminates estrogen production. Aromatase inhibitors successfully treat breast cancer and endometriosis, whereas their roles in endometrial cancer, uterine fibroids, and aromatase excess syndrome are less clear. Ovary, testis, adipose tissue, skin, hypothalamus, and placenta express aromatase normally, whereas breast and endometrial cancers, endometriosis, and uterine fibroids overexpress aromatase and produce local estrogen that exerts paracrine and intracrine effects. Tissue-specific promoters distributed over a 93-kilobase regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway- and tissue-specific manner. Three mechanisms are responsible for aromatase overexpression in a pathologic tissue versus its normal counterpart. First, cellular composition is altered to increase aromatase-expressing cell types that use distinct promoters (breast cancer). Second, molecular alterations in stromal cells favor binding of transcriptional enhancers versus inhibitors to a normally quiescent aromatase promoter and initiate transcription (breast/endometrial cancer, endometriosis, and uterine fibroids). Third, heterozygous mutations, which cause the aromatase coding region to lie adjacent to constitutively active cryptic promoters that normally transcribe other genes, result in excessive estrogen formation owing to the overexpression of aromatase in many tissues.

Animals↗

The postpartum uterus.

The cow is notable among the domestic species for the almost ubiquitous bacterial contamination of the uterine lumen after parturition and the high incidence of clinical uterine disease. Such uterine disease not only disrupts uterine tissues, but also ovarian follicle growth and function by perturbation of the hypothalamus, pituitary, and ovary. Other events such as the postpartum negative energy balance also have similar multilevel effects on postpartum endocrinology. Return of ovarian cyclical activity is dependent on the innate immune system resolving uterine bacterial contamination,prompt uterine involution, and a short interval to the negative energy balance nadir. Although the risk factors for uterine disease have been described, preventive strategies are not widely adopted. Thus, veterinarians must identify and treat uterine disease efficiently to limit their negative effect on fertility.

Animals↗

Evaluation of perioperative stress after laparoscopic and abdominal hysterectomy in premalignant and malignant disease of the uterine cervix and corpus.

OBJECTIVE: To compare the differences in laparoscopic and abdominal hysterectomy in surgery of premalignant and malignant uterine disease. DESIGN: Prospective study. SETTING: Baby Friendly Hospital, Kladno, Czech Republic. SUBJECT: A total 32 patients underwent hysterectomies for premalignant and malignant uterine conditions. INTERVENTIONS: Patients were assigned to either laparoscopic-assisted vaginal hysterectomy or total abdominal hysterectomy (LAVH), with bilateral salpingo-oophorectomy and lymph node dissection. MEASURES: Clinical data and value of total creatine kinase and C-reactive protein were measured. RESULTS: All 32 procedures were successfully completed. There were no major complications. Mean order of CRP concentrations was significantly lower (p = 0.001) in patients with LAHV. Mean order of total CK activities was also significantly lower in these patients (p = 0.003) and the median hospital stay was 4.1 days (p = 0.05). CONCLUSIONS: Laparoscopic procedures were followed by shorter hospital stays and the proposed evaluation of tissue damage using serum enzymes and proteins demonstrates that the laparoscopic approach to hysterectomy and accessory procedures has considerable importance in decreasing perioperative patient stress. The presented results are supported by clinical experience and should have a decisive impact on the chosen approach to the course and duration of convalescence in patients undergoing a hysterectomy in premalignant and malignant disease of the uterine cervix and corpus.

C-Reactive Protein↗

Early uterine serous carcinoma: clonal origin of extrauterine disease.

Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial carcinoma that is frequently associated with extrauterine disease despite minimal or no myometrial invasion. The origin of the extrauterine tumors in this setting remains controversial. The majority of USCs (90%) and endometrial intraepithelial carcinomas (78%), the putative precursor of USC, have p53 mutations, suggesting that p53 alterations occur early in the pathogenesis of USC. To determine if the extrauterine tumors associated with minimally invasive USC and endometrial intraepithelial carcinoma (EIC) represent metastases or multifocal primary tumors, we examined the mutational pattern of the p53 gene in 3 cases of minimally invasive USC and 1 case of EIC and in the corresponding extrauterine tumors associated with each of the cases. In all 4 cases, the primary tumors and the associated extrauterine tumor foci had identical p53 mutations. Our results support the premise that extrauterine serous tumors found in association with EIC or minimally invasive USC represent a unifocal process and thus are early metastases.

Abdominal Neoplasms↗

Digital subtraction angiography for the evaluation of persistent uterine trophoblastic disease.

In three patients with persistent uterine trophoblastic disease, follow-up after primary chemotherapy was undertaken by digital subtraction angiography. It was found that the angiographic appearance of the intramural uterine lesions was comparable with that obtained by conventional pelvic angiography. Digital subtraction angiography may be applicable as an easy, safe, and valuable diagnostic method for gestational trophoblastic disease in place of conventional pelvic angiography because it is a relatively noninvasive procedure that can be performed on outpatients.

Adult↗

Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and a poor prognosis. Prior studies evaluating treatment of UPSC have been limited by small numbers of patients and inclusion of partially staged patients. The purpose of this study was to evaluate the efficacy of adjuvant platinum-based chemotherapy and vaginal cuff radiation in a large cohort of surgical stage I UPSC patients. METHODS: We retrospectively reviewed 74 stage I patients with UPSC who underwent complete surgical staging at our institution between 1987 and 2004. RESULTS: Stage IA patients were divided into two groups: patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) and patients with cancer in the hysterectomy specimen (defined as residual uterine disease). Stage IA patients with no residual uterine disease had no recurrences, regardless of adjuvant therapy (n = 12). Stage IA patients with residual uterine disease who were treated with platinum-based chemotherapy had no recurrences (n = 7). However, 6 of 14 (43%) stage IA patients with residual uterine disease who did not receive chemotherapy recurred. The 15 patients with stage IB UPSC who received platinum-based chemotherapy had no recurrences but 10 of the 13 (77%) stage IB patients who did not receive chemotherapy recurred. One of the 7 patients with stage IC UPSC who received platinum-based chemotherapy recurred and 4 of the 5 (80%) stage IC patients who did not receive chemotherapy recurred. Overall platinum-based chemotherapy was associated with improved disease-free survival (P < 0.01) and improved overall survival (P < 0.05) in patients with stage I UPSC. None of the 43 patients who received radiation to the vaginal cuff recurred locally, but 6 of the 31 (19%) patients who were not treated with vaginal radiation recurred at the cuff. CONCLUSIONS: Platinum-based chemotherapy improves the disease-free and overall survival of patients with stage I UPSC and vaginal cuff radiation provides local control. Stage IA UPSC patients with no residual uterine disease can be observed but concomitant platinum-based chemotherapy and vaginal cuff radiation (referred to as chemoradiation) should be offered to all other stage I UPSC patients.

Aged↗