Expression of metalloproteinases 2 and 9 and cyclooxygenase 2 in endometrial carcinoma.
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Aged↗
Biomedical subjects
T Susini
Publications and source records attributed to T Susini.
Systematic pelvic and aortic lymphadenectomy in elderly gynecologic oncologic patients.
BACKGROUND: Retroperitoneal lymph node dissection is a fundamental step in the surgical management of patients with pelvic gynecologic malignancies, but its applicability to geriatric patients is controversial. The objective of this study was to evaluate whether pelvic and aortic lymphadenectomy in elderly patients with gynecologic malignancies can be a safe procedure in terms of morbidity and mortality. METHODS: In a retrospective case-control study, the authors compared morbidity, mortality, and surgical data in a series of elderly patients (age > 70 years) with endometrial and ovarian carcinoma who underwent surgery. Patients were divided into two groups: Cases were 36 elderly patients who underwent surgery and pelvic and/or aortic lymphadenectomy and were matched with 72 controls, who were patients who underwent surgery without lymphadenectomy. RESULTS: Cases showed a significantly longer median operative time than controls (median, 162 minutes [range, 85-330 minutes] vs. median, 100 minutes [range 20-310 minutes], respectively; P = 0.003). No significant difference between the two groups in terms of blood loss, blood transfusions, intraoperative complications, duration of ileus, reintervention required, or postoperative hospital stay were observed. One patient in the control group died. The type and frequency of severe postoperative complications in the two groups were not substantially different. CONCLUSIONS: Pelvic and aortic lymphadenectomy was performed safely in elderly patients age > or = 70 years with endometrial and ovarian carcinoma without an increase in morbidity and mortality. Advanced chronologic age alone should not be considered a contraindication to full surgical treatment in these patients.
Age Factors↗
Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma.
The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.
Adenocarcinoma↗
[Recurrence of malignant epithelial tumors of the ovary].
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Carcinoma↗
Eating attitudes and behavior throughout the menstrual cycle in obese women: a case-control study.
Premenstrual variations of eating behavior are reported in several studies, but their relationship with mood is unclear. Eating behavior and physical and psychological complaints during the menstrual cycle were studied in 107 obese patients and 93 matched controls using retrospective (Weekly Bulimic Test Edinburgh, W-BITE and Premenstrual Assessment Form, PAF) and prospective (Daily Rating Form, DR) questionnaires. Eating disorder symptoms increased in the premenstrual phase, as shown by the W-BITE scores both in patients (6.2 +/- 5.3 premenstrual week vs 4.9 +/- 4.4 postmenstrual week, p < 0.05) and in control subjects (4.9 +/- 4.1 premenstrual week vs 4.2 +/- 3.0 postmenstrual week, p < 0.05) and were correlated to premenstrual complaints in control subjects (r = 0.5; p < 0.05) but not in obese women (r = 0.2; p = NS). A close relationship between physical and psychological premenstrual disturbances was observed in obese patients only. Premenstrual variation of eating behavior could be the target of specific treatment.
Adult↗
Extraperitoneal pelvic lymphadenectomy to complement vaginal operations for cervical and endometrial cancer.
OBJECTIVE: The aim of the current study was to test the applicability of a personal modification of Mitra extraperitoneal pelvic lymphadenectomy in combination with radical vaginal operations for treatment of endometrial and cervical cancer. METHOD: In a prospective series, 82 patients were submitted to extraperitoneal pelvic lymphadenectomy. In 34 cases of stage I endometrial cancer the procedure was combined with a class I vaginal hysterectomy and in 48 cases of cervical cancer stage Ib-IIIb lymphadenectomy was associated with a class II or III radical vaginal hysterectomy. Type of anesthesia, number of lymph nodes removed, operating time, blood loss and postoperative complications were recorded. RESULT: The operation was performed with spinal anesthesia in 43% of the cases. Thirty-seven patients (45%) were high surgical risk because of associated diseases. The median operative time for lymphadenectomy was 20 min for each side; the vaginal procedures took a median of 25 min (class I) and 40 min (class II-III). Blood transfusions were necessary in seven cases (8. 5%). A median of 26 lymph nodes were removed from each patient. Lymphocyst occurred in seven patients (8.5%), retroperitoneal hematoma in two and retroperitoneal abscess in one. CONCLUSION: Extraperitoneal pelvic lymphadenectomy has proven to be a safe and quick technique to complement vaginal operations for endometrial and cervical cancer. Specific features of this approach are: (1) fast, timesaving procedure; (2) possible use of spinal anesthesia; and (3) applicability in high surgical risk patients.
Adult↗
Giant pelvic retroperitoneal liposarcoma.
BACKGROUND: Pelvic retroperitoneal liposarcomas are rare in young women (under 30 years old). We present a case of a giant well-differentiated liposarcoma of the retroperitoneum in a young woman. CASE: A 27-year-old nulligravida presented with rapid abdominal enlargement. Pelvic examination found a huge mass extending from the left adnexa to the epigastric region. At surgery, the pelvic organs were displaced to the right side by a retroperitoneal mass that marginally involved the left fallopian tube. The left ovary, uterus, and right adnexa were not involved and were not removed. No adjuvant irradiation was given. The patient was alive and well 2 years after the operation and was 23 weeks pregnant. CONCLUSION: Gynecologists should be familiar with pelvic retroperitoneal liposarcomas and their treatment.
Adult↗
Preoperative evaluation of tumor ploidy in endometrial carcinoma: An accurate tool to identify patients at risk for extrauterine disease and recurrence.
BACKGROUND: Tumor ploidy is a strong prognostic factor in patients with endometrial carcinoma, but generally is evaluated only after surgery. The availability of a simple and reliable method to determine tumor ploidy before any treatment is initiated could be helpful in the selection of patients at high risk for advanced primary disease and subsequent recurrence, with several possible benefits. The objectives of the current study were: 1) to test the accuracy of flow cytometric determination of tumor ploidy from preoperative outpatient endometrial biopsies compared with standard postoperative evaluation from the surgical specimen and 2) to correlate this preoperative parameter with the local recurrence and extrauterine tumor spread. METHODS: Tumor ploidy from both preoperative biopsy material and the macroscopic surgical specimens was evaluated prospectively in 50 consecutive patients with endometrial carcinoma. DNA analyses were performed in a blind fashion. Patients were followed for a median of 26 months (range, 16-46 months). RESULTS: In 9 of 50 cases (18%) an aneuploid tumor was found by the standard postoperative analysis. All 9 aneuploid tumors (100%) also were identified correctly by the preoperative test on biopsy material. Occult extrauterine tumor spread was found in 10 patients (20%). The incidence rate of aneuploidy among these tumors was 50% compared with 10% in surgical International Federation of Gynecology and Obstetrics Stage I tumors (P = 0.01). The recurrence rate was 55.5% (5 of 9 tumors) in the aneuploid group and 2.4% (1 of 41 tumors) in the diploid group (P < 0.001). The disease free survival rates of patients with diploid and aneuploid tumors were 97.5% and 44.4%, respectively (P < 0.0001). CONCLUSIONS: Preoperative tumor ploidy determination based on outpatient endometrial biopsy is as accurate as the standard postoperative evaluation in patients with endometrial carcinoma. Tumor aneuploidy confirms the usefulness of this method in selecting patients at risk for occult extrauterine tumor diffusion and recurrence.
Adult↗
Gynecologic oncologic surgery in the elderly: A retrospective analysis of 213 patients.
OBJECTIVES: The aims of the study were (1) to analyze morbidity and mortality for elderly women (>/=70 years) operated on for gynecological malignancies at our department between 1985 and 1996; and (2) to compare two periods of time (years 1985-1990 versus years 1991-1996) to investigate whether new expedience in the surgical technique as well as in the perioperative management introduced by 1991 influenced the feasibility and tolerability of surgery in elderly patients. METHODS: In a retrospective analysis, we evaluated tumor site, comorbidities, surgical features, morbidity, and mortality. By 1991, several modifications in management were introduced, including: (1) early postoperative mobilization; (2) self-donation with autologous blood transfusion; (3) intraoperative antibiotic prophylaxis; (4) the retroperitoneum was left open and drains were not used after pelvic and aortic lymphadenectomy; (5) use of coagulator forceps and hemoclips for meticolous hemostasis. RESULTS: In 213 patients, tumor site distribution was uterine corpus n = 93, ovary n = 51, vulva n = 29, cervix n = 23, breast n = 15, and vagina n = 2. There were advanced stage diseases in 47%, comorbid illnesses in 76%, and high surgical risk in 48%. Sixty-nine patients (group A) and 144 patients (group B) were treated in the first and second study periods, respectively. Overall, severe postoperative morbidity and mortality were 17 and 2.8%, respectively. Group B compared to group A showed more frequent use of major surgical procedures (P < 0.01) and lymphadenectomy (P < 0.04), lower transfusion rate (P < 0.001), reduced severe morbidity (P < 0.002), lower mortality (P = 0.3), and shorter hospital stay (P < 0.001). CONCLUSIONS: Our study suggests that surgery, including very radical procedures, is reasonably feasible and well tolerated by elderly patients. The introduction of technical and medical advances in the later years of the study resulted in a significant improvement of surgical rates.
Aged↗
Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.
PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.
Aged↗
[The "age factor" in ovarian cancer. Clinical, therapeutic and prognostic aspects].
115 patients affected by ovarian tumors, were studied retrospectively, each with a follow-up of a minimum of 5 years. These cases were subdivided into two subgroups according to the age (younger or older than 65 years) to value the differences, from a prognostic and therapeutic point of view about the age of neoplasm onset. In patients older than 65 years, there were prevalent cases with worse prognosis, linked both to the neoplasm (greater incidence of advanced stages at the moment of the diagnosis; prevalence of tumours of low degree of differentiation), and to the treatment given (less destroying intervention, with a higher frequency of non optimal residual disease; fewer chemotherapeutic cycles for every patient, with lower doses and fewer times of administration of drugs; higher incidence of phenomena of resistance and rejection of the I line therapy). The survival curves were significantly different in the two groups of patients, proving a worse prognosis for older women. At last, a multivaried statistical analysis, revealed that age, like stage, residual disease and the number of chemotherapeutic cycles performed, represent an independent prognostic factor.
Adolescent↗
Identification, characterization, and biological activity of endothelin receptors in human ovary.
We previously reported the expression of endothelin-1 (ET-1) in granulosa cells (GCs) of the human ovary and the presence of ET-1-like immunoreactivity in human follicular fluid obtained from women in an in vitro fertilization program. In follicular fluid, but not in plasma, the levels of ET-1-like immunoreactivity were higher in gonadotropin-stimulated vs. spontaneous cycles, suggesting hormonal regulation of follicular ET-1. To identify and characterize ET receptors in human ovary, we performed autoradiography, radioligand binding, and functional studies. Mathematical analysis of families of self- and cross-competition curves among [125I]ET-1, [125I]ET-3, and selective analogs indicates that human ovary expresses both subtypes of ET receptors, i.e. ETA and ETB receptors. However, the concentration of the ETB site was 100-fold lower than that of the ETA one. By using [125I]ET-1, we demonstrated that the density of binding sites in human ovary is not affected by the hormonal milieu (similar concentrations in normal cycling, postmenopausal, and combined oral contraceptive-treated women). In situ binding studies indicate that the majority of ETA and ETB receptors are expressed in the blood vessels of the ovary. In particular, ETA receptors are abundant in the ovulatory follicles and localized in the theca interna, in close proximity to the granulosa layer. Few GCs of the ovulatory follicle were specifically labeled. Conversely, in the rat ovary, used as a control, ETB receptors were predominantly expressed and localized in GCs. Accordingly, ETB receptors negatively regulated estrogen accumulation in rat GCs. In human granulosa-luteal cells, neither ET-1 (unselective ligand) nor ET-3 or sarafotoxin 6c (ETB ligands) affected estrogen or progesterone secretion. ET-1 was 2.5-fold more potent than noradrenaline in eliciting contraction of ovarian artery, acting through the ETA receptor. Our results indicate that in human ovary, at variance with rat ovary, the endothelin system is primarily involved in the regulation of ovarian blood flow and not steroidogenesis.
Adult↗
Hypothesis of clinical use of preoperative evaluation of DNA-index in endometrial carcinoma management.
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Disease Management↗
Management of benign adnexal masses by vaginal route.
Until recently, surgical treatment of a benign adnexal mass implied a laparotomy. In recent years, the development of laparoscopic surgery, as well as ultrasound-guided aspiration techniques, have significantly modified the treatment options for these patients. These procedures have shown considerable advantages. They have reduced surgical trauma and have shortened the hospital stay. We present the results of our experience on the feasibility of a trans-vaginal surgical approach for the removal of benign adnexal masses. This technique, using traditional and cheap surgical instruments, allows the surgeon to excise benign adnexal masses, by entering the peritoneum through the posterior vaginal fornix and thus avoids the trauma of laparotomy. Fifty-four patients were operated on by this technique at our Department. The mean age was 39 years (range 21-66). In all cases, the operation was completed by the trans-vaginal approach. The median operative time was 30 minutes (range 20-45), and no blood transfusion was needed. The pathological diagnoses were as follows: functional ovarian cyst; 19, endometriotic cyst; 18, dermoid cyst; 11, parovarian cyst; 4 and peduncolated fibroid of the uterine fundus; 2 cases. The diameter of the adnexal masses ranged from 3 to 10 cm (median of 6 cm). In 30 cases, a conservative surgery was done (including 2 myomectomies), whereas in 24 cases, the adnexectomy was needed. Median post-operative stay in hospital was 4 days (range 1-14). This study shows the feasibility of trans-vaginal surgical approach for benign adnexal masses. The advantages and limitations of this technique, as well as of the traditional and laparoscopic surgery are considered and discussed. We believe that the transvaginal approach could be useful and cost-effective for the treatment of selected cases of adnexal masses.
Adnexal Diseases↗
Flow cytometric measurement of DNA content in human solid tumors: a comparison with cytogenetics.
The aims of this study were: (1) to test the accuracy of flow cytometery (FC) in the measurement of DNA content in human solid tumors, (2) to correlate the FC DNA-index (DI) with the chromosome modal number (CMN) provided by cytogenetic analysis (CG), and (3) to investigate the most frequent pitfalls in FC histograms classification. FC and CG analyses were performed in parallel on 113 samples of human solid tumors of different origin. FC provided an evaluable histogram in 110 out of 113 cases (97%), whereas a successful CG culture was obtained in 79 out of 113 samples (72%). In the 79 cases evaluable by both FC and CG, a concordant ploidy status was found in 66 cases (84%) (47 diploid and 19 aneuploid) (P < 0.001, chi-square test). In the 19 concordant aneuploid tumors a close correlation between the CMN and the DI was found (y = 0.019 x + 0.151; r = 0.860). Concerning the 13 discordant cases, 11 (85%) were classified as aneuploid by FC and as diploid by CG, while 2 cases (15%) were CG aneuploid (1 near-diploid and 1 tetraploid) and FC diploid. The current study suggests that FC is a reliable method for the measurement of tumor DNA content of the studied solid tumors. Special attention should be paid to the improvement of DNA histograms quality, in order to reduce the difficulties in the detection of near-diploid and near-tetraploid cell populations. Multiple sampling should be warranted whenever possible.
Aneuploidy↗
Epithelial ovarian tumors in the reproductive age group: age is not an independent prognostic factor.
BACKGROUND: While ovarian carcinoma is rare in the reproductive age group, these younger patients are known to fare better than the older patients. To determine whether age is an independent prognostic factor, as well as to investigate the clinicopathologic profile and survival rate of young women with ovarian carcinoma, a retrospective analysis in a series of patients aged 40 years or younger was performed. METHODS: We collected data on 74 patients with borderline or invasive ovarian carcinoma treated at the Department of Obstetrics and Gynecology at the University of Florence between 1969 and 1994. The median follow-up was 72 months (range, 11-288 months). To assess the clinicopathologic profile and survival differences according to age, the series was subdivided into "very young" (30 years or younger) and "young" (31-40 years) groups of 34 and 40 patients, respectively. Survival rates (Kaplan-Meier method) were compared by the log rank test. A multivariate analysis (Cox proportional hazards) was used to determine the independent effect of each variable on survival. RESULTS: The overall 5-year and 10-year survival rates were 58.2% and 46.1%, respectively. Several prognostic factors were found significant by univariate analysis, including stage (P < 0.001), grade (P < 0.001), residual disease (P < 0.001), histologic type (P < 0.05), and age (< or = 30 years vs. 31-40 years; P = 0.009). Five year survival rates for the patients age 30 years and younger and patients age 31-40 years were 71.3% and 47.1%, respectively. In the former group, low malignant potential tumors and well differentiated carcinomas were significantly more frequent (68.8% vs. 37.5%; P = 0.01). In the multivariate analysis, only stage (I vs. >I; P = 0.004), grade (0-1 vs. 2-3; P = 0.03) and residual disease (P = 0.02) were found to be significant independent prognostic factors, whereas age (< or = 30 years vs. 31-40 years) yielded no independent information (P = 0.36). CONCLUSIONS: Epithelial ovarian cancer patients age 30 years or younger have a more favorable prognosis because of a higher rate of early stage, low grade tumors. Patients aged 31-40 years also show a more favorable disease profile and clinical outcome, although to a lesser extent, than the average ovarian cancer population. Age does not emerge as an independent prognostic factor for ovarian carcinoma in women younger than 40 years.
Adult↗
Three classes of radical vaginal hysterectomy for treatment of endometrial and cervical cancer.
OBJECTIVES: The aims of this study were to (1) describe three types of extended vaginal hysterectomy with different degree of radicality, (2) to identify possible indications for each one of them, and (3) to encourage individualization of the treatment, with special reference to the reevaluation of the role of vaginal surgery in gynecologic oncology. STUDY DESIGN: The surgical-anatomic principles of radical vaginal surgery and the techniques of three increasingly extended vaginal hysterectomies are illustrated. Possible indications are pointed out on the basis of our personal experience from previously published retrospective studies. RESULTS: Class I extended vaginal hysterectomy allows the "en bloc" dissection of the uterus along with the upper third of vagina and both the adnexa. The parametria are not removed. This procedure has proved to be of value for treatment of stage I endometrial cancer. In the class II extended vaginal hysterectomy the distal tract of the anterior and posterior parametria are preserved, whereas the cardinal ligament is entirely removed. This operation has shown promising results for treatment of stage IB-IIA cervical cancer of small volume while reducing the incidence of bladder and rectal dysfunctions. The class III procedure includes the complete removal of the parametria (anterior, lateral, and posterior). This operation has been shown to provide a high rate of cure for stage IB-IIA cervical cancer. CONCLUSIONS: In view of the several advantages of vaginal surgery, this approach should be considered in the individualized treatment of selected cases of endometrial and cervical cancers. The three classes of radical vaginal hysterectomy allow tailoring the type of vaginal operation to the clinical and physical characteristics of the patients. The combined use of extraperitoneal or laparoscopic lymphadenectomy would considerably extend the indications for radical vaginal operations.
Endometrial Neoplasms↗