Giambattista Massi

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.

Vaginal hysterectomy versus abdominal hysterectomy for the treatment of stage I endometrial adenocarcinoma

OBJECTIVE The aims of the current study were to (1) determine the effectiveness of vaginal hysterectomy for the treatment of stage I endometrial cancer and (2) analyze which clinical pathologic parameters were independent predictors of clinical outcome. STUDY DESIGN In a retrospective analysis, 5- and 10-year results of vaginal hysterectomy were compared with those of abdominal hysterectomy in 327 cases of stage I adenocarcinoma. No preoperative irradiation was given. Overall, 180 patients underwent vaginal hysterectomy, whereas 147 patients had abdominal hysterectomy (106 cases with lymphadenectomy). The log-rank test was used for evaluation of survival differences. RESULTS The 5- and 10-year survival rates (Kaplan-Meier method) were, respectively, 90% and 87% in the vaginal hysterectomy group and 91% and 90% in the abdominal hysterectomy group (difference not significant). The grade of differentiation, depth of myometrial invasion, and age were significantly correlated with survival, whereas histologic type, mode of surgery, lymphadenectomy, and adjuvant radiotherapy were not. In a multivariate analysis (Cox proportional hazards), grade of differentiation and age were independent predictors of clinical outcome, whereas depth of myometrial invasion lost significance. CONCLUSIONS Vaginal hysterectomy showed a high rate of cure in stage I endometrial cancer. Therefore it can be used as an alternative to the abdominal operation in obese and poor surgical risk patients and, possibly, in selected low-risk cases.

Prognostic value of flow cytometric deoxyribonucleic acid index in endometrial carcinoma: Comparison with other clinical-pathologic parameters

OBJECTIVE: The aims of the current study were to verify the impact of flow cytometric deoxyribonucleic acid index on clinical outcome in endometrial carcinoma and to assess whether its value is independent from the other clinical-pathologic features. STUDY DESIGN: In a prospective series 74 cases of endometrial carcinoma with surgery performed at our institution were studied. Flow cytometry was performed on fresh tumor samples. The median follow-up period was 31 months (range 8 to 52). Disease-free survival and actuarial survival were the end points of the study. RESULTS: Among the 74 patients (53 with diploid and 21 with aneuploid tumors) there were 14 recurrences and 10 deaths caused by the disease. The recurrence rate was 7.5% for the diploid and 47.6% for the aneuploid tumors (p < 0.001). Mortality was 3.8% for diploid and 38% for aneuploid cases (p < 0.001). Disease-free survival was 89.1% in the former group and 36.3% in the latter. Actuarial survival (Kaplan-Meier method) was 94.7% and 49.5%, respectively. Deoxyribonucleic acid index, stage (International Federation of Gynecology and Obstetrics), and grade of differentiation were significantly correlated with survival, whereas age, depth of myometrial invasion, and histologic type were not. In a multivariate analysis (Cox proportional hazards) deoxyribonucleic acid index was the strongest independent predictor of clinical outcome, followed by International Federation of Gynecology and Obstetrics stage, whereas grade of differentiation yielded no independent prognostic information. CONCLUSIONS: The flow cytometric deoxyribonucleic acid index is an important independent prognosticator, and its determination should be included in the standard management of endometrial cancer.

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.

GnRH Analogs in Gynecological Oncology: a Review

Chronic GnRH analogs (GnRH-A) administration has proven to be effective for the control of some hormone-dependent tumors. GnRH-A are now in the standard treatment of prostatic cancer. In the present paper experimental and clinical data on the use of GnRH-A in gynecologic oncology are reviewed in order to identify a possible role in the therapy of breast, endometrial and ovarian cancer. Besides the indirect hormonal effect of GnRH-A, mediated by the suppression of gonadal steroidogenesis, in vitro evidence suggests a direct anti-proliferative action involving autocrine-paracrine regulation of cellular function. In advanced or recurrent breast cancer objective responses were observed in 157 out of 378 premenopausal patients (41%) and in 18 out of 166 postmenopausal women (10%). In ovarian cancer complete and partial responses were observed in 14 out of 121 (11%). At present, data on advanced endometrial carcinoma are limited: only 18 treated patients are reported, of whom 7 responded (38.8%). However, in general, most of the responses observed were transient. Thus, so far, the use of GnRH-A in gynecologic oncology has to be considered for palliation, after the failure of other better understood treatment modalities. The possible use of GnRH-A as an adjuvant is still under investigation.

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.

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.

Estrogenic suppression by different administration schedules of goserelin depot for treatment of endometriosis.

Eighteen patients affected by laparoscopically confirmed endometriosis were randomly assigned to three different schedules of treatment with gonadotropin-releasing hormone agonist (GnRH-a) (goserelin depot formulation 3.6 mg) every 28 days for 6 months. Six women received the first implant in early follicular phase, 4 in late luteal phase and 8 in 3rd and 17th day from onset of menses. Pretreatment and posttreatment laparoscopic score, performed according to the American Fertility Society scoring system, were compared; a significant reduction in the extent of disease was observed in each group investigated (A and C: p<0.01; B: p<0.05). In each treatment group after the second GnRH-a implant the mean levels of estrone-3-glucuronide (E1-3G), daily measured in early morning urine specimens during the control cycle and the first three months of therapy, were suppressed to menopausal women range. In group B during the 2nd and 3rd month of therapy, the urinary mean levels of EI-3G were significantly lower than in group A and C. In conclusion the different goserelin depot administration schedules gave similar laparoscopic improvement, in spite of the first GnRH-a administration in luteal phase allowed a more marked estrogenic suppression.