Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in cervical cancer.

OBJECTIVE: The aim of this work was to examine three types of radical vaginal hysterectomy with different degrees of radicality, performed in order to reduce surgical complications and sequelae in different indications, and to test the feasibility of a new simple and quick technique for extraperitoneal pelvic lymphadenectomy to be used in combination with radical vaginal hysterectomy for treatment of cervical cancer. In this way the advantages of vaginal surgery (e.g.: unnecessary general anaesthesia, reduced surgical trauma, applicability to obese and poor surgical risk patients, fast time-saving procedure) can be preserved. METHODS: We compared retrospectively the long-term results of radical vaginal and radical abdominal operations in a large series of stage IB-IIA cervical cancer patients treated at our institution in Florence from 1968 to 1983. Furthermore, we analysed the results of our experience from 1995 to 1998, when we performed extraperitoneal pelvic lymphadenectomy, followed by radical vaginal hysterectomy, on 48 patients affected by cervical cancer. Extraperitoneal pelvic lymphadenectomy was performed through two small abdominal incisions (6-7 cm). Twenty-two patients (45%) were obese (BMI>30 kg/m2) and 20 were poor surgical risks. FIGO stage was: IB1 in 18 cases, IB2 in eight, IIA in six, IIB in 12, IIIB in four. Neoadjuvant chemotherapy was given in 12 cases and preoperative irradiation was given in ten. General and regional anaesthesia were used in 30 (62.5%) and in 18 (37.5%) cases, respectively. RESULTS: As for past experience, in stage IB the five-year survival of 356 patients who underwent radical vaginal hysterectomy and that of 288 who had radical abdominal hysterectomy with pelvic lymphadenectomy were 81% and 75%, respectively (p<0.05). Surgical complications were fewer with no mortality in the first group. In stage IIA, survival rates were 68% for radical vaginal hysterectomy and 64% for radical abdominal hysterectomy, in 76 and 64 cases, respectively (p=n.s.). As for the more recent experience, median operative time for extraperitoneal pelvic lymphadenectomy was 20 minutes for each side (range 15-36). In each patient a median of 26 lymph nodes were removed (range 16-48). Positive nodes were found in 12 cases (25%). Median operative time for radical vaginal hysterectomy was 40 minutes (range 30-65). Extraperitoneal pelvic lymphadenectomy complications included: lymphocyst, five cases (10%) and retroperitoneal hematoma, one (2%); all occurred at the beginning of the experience. Radical vaginal hysterectomy complications included: ureteral stenosis, one (2%) and uretero-vaginal fistula, one (2%). All complications occurred in patients who received radiotherapy or chemotherapy preoperatively. Median hospital stay was ten days (range 6-20). CONCLUSIONS: The results of our work demonstrate that our technique for extraperitoneal pelvic lymphadenectomy shows a good applicability to cervical cancer patients submitted to radical vaginal hysterectomy, which has a high rate of cure for stage IB and IIA as shown by our past experience. The procedure of extraperitoneal pelvic lymphadenectomy was quick, easy, and safe, and its realization was not detrimental to the advantages of radical vaginal hysterectomy. Our experience supports the continued use of this combined extraperitoneal and vaginal approach in the treatment of cervical cancer. Moreover, the three classes of radical vaginal hysterectomy allow tailoring the type of the operation to the clinical and physical characteristics of the patients.

[The "age factor" in ovarian cancer. Clinical, therapeutic and prognostic aspects]. / Il "fattore età" nei carcinomi dell'ovaio. Considerazioni cliniche, terapeutiche, prognostiche.

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.

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.

Ureteral obstruction due to retroperitoneal endometriosis: a conservative approach including surgery and GnRH analogs.

Ureteral obstruction due to endometriosis is an infrequent condition which can be asymptomatic for a long time. Irreversible loss of renal function may result in cases with delayed diagnosis. Our report concerns a case of unilateral hydronephrosis and hypertension due to retroperitoneal endometriosis occurring in a 24-year-old woman. The management of patients bearing obstructive uropathy caused by endometriosis is discussed. In the present case, a conservative operation followed by medical treatment, including GnRH analogs, was used to preserve reproductive capacity.

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 E1-3G 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.

Nimesulide in the treatment of mastalgia.

Sixty patients with mastalgia, either idiopathic or secondary to dysplastic lesions, were treated with oral nimesulide (100mg tablets twice daily) for 15 days. Breast tension and pain, assessed at baseline and on completion of the treatment period, improved or resolved with therapy. Indeed, breast pain (which most likely manifests as a consequence of periductal inflammation) was most noticeably reduced. The drug was well tolerated in nearly all patients. These results support the usefulness of nimesulide and other nonsteroidal anti-inflammatory drugs in the treatment of mastalgia.

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.

Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium.

Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.

[Defibrotide vs. calcium heparin in the prevention of deep vein thrombosis in gynecologic oncologic surgery]. / Defibrotide versus eparina calcica nella profilassi delle TVP in chirurgia ginecologica oncologica.

Eighty-one patients were submitted to gynaecological malignancy surgery in a randomized study aimed at the evaluation of the efficacy of defibrotide (40 patients) and calcium heparin (41 patients) in perioperative prophylaxis. They were randomly allocated to defibrotide group (400 mg bid im starting one day before surgery and continuing until the 7th postoperative day) or calcium heparin group (5000 IU bid sc starting two hours before surgery and continuing likewise for 7 days). No cases of DVT diagnosed by means of a Doppler CW were observed in either treatment group. Laboratory parameters have shown similar modifications in the two treatment groups. Three cases of bleeding were observed in the calcium heparin group while no cases of bleeding were detected in the defibrotide group. The results obtained suggest that defibrotide is at least as effective as calcium heparin in perioperative DVT prevention and that the former drug has a possibly better tolerability profile, due to a decisively lower tendency to bleeding.

Role of vaginal surgery in the 1st stage endometrial cancer. Experience of the Florence School.

The role of vaginal surgery in first stage endometrial carcinoma is reviewed. Out of total of 231 patients with endometrial cancer, observed at the Gynecologic Clinic of Florence from 1977 to 1981, 187 were at Stage I and 180 of them were submitted to surgery. During the period 1977-1979, the treatment protocol recommended vaginal hysterectomy; since 1980 abdominal surgery has prevailed. Depending on risk factors, adjunctive radiotherapy was employed. No statistically significant difference was observed in the actuarial survival curves between different surgery routes. However, severe complications and operative mortality was significantly lower in patients operated by vaginal hysterectomy. The vaginal route may be considered an adequate alternative therapy for endometrial carcinoma Stage I.

Systemic absorption of 3H-fenticonazole after vaginal administration of 1 gram in patients.

Fourteen women, five with normal cervicovaginal mucosa (Group 1), five with cervical carcinoma (Group 2) and four with relapsing vulvovaginal candidiasis (Group 3) were enrolled and completed this open clinical trial. Each subject received a single dose of 1.82 +/- 0.3 g on average of vaginal paste (for ovules) containing about 1000 mg of 3H-fenticonazole nitrate (266 microCi). Twelve hours after vaginal administration, the paste was removed by vaginal washing. Blood, urine and stool samples were collected at specified time intervals for five days. Plasma, urine, stools and all used material in contact with the paste were assayed for radioactivity. No measurable levels of radioactivity were detected in plasma of subjects of Groups 1 and 3 while in 4 of the 5 subjects with cervical carcinoma (Group 2) fenticonazole was detected during the 24 h after administration with a peak level at about 8 hours. For a period of 5 days, 0.4-1.5% of the dose on average was recovered from urine, and 0.18-0.32% from feces. Based on the excretion data, the extent of vaginal absorption of fenticonazole nitrate in women with vulvovaginal candidiasis was 1.81 +/- 0.57% of the dose, while in women with normal cervicovaginal mucosa it accounted for 0.58 +/- 0.28% of the administered dose. In patients with cervical carcinoma, absorption was 1.12 +/- 0.53%. The maximum amount absorbed corresponds to an exposure of about 0.4 mg/kg of fenticonazole nitrate (for a subject weighing 50 kg). Consequently, the vaginal administration of one ovule containing 1000 mg of fenticonazole nitrate seems to be devoid of risk for patients.

Monoclonal antibodies in serological, immunoscintigraphic and immunocytochemical diagnosis of epithelial ovarian cancer.

In present work the Authors examine the utility of CA 125 assay in patients affected by epithelial ovarian cancer. It is stressed that marker negativity does not necessarily imply the absence of disease. On the other hand the Authors underly the almost total absence of false positives, the only problem being with cases of benign gynaecological pathologies. The CA 125 assay appears to provide informations in the evaluation of response to therapy. Finally they note two more recent applications of monoclonal antibodies: first, marking these substances with radioisotopes; second, immunohistochemistry that shows the presence and location of the antigen at the histological level. (By editorial staff).

Interference of exogenous HCG on pregnancy tests.

New urinary tests of pregnancy have recently been developed that are exceptionally sensitive to HCG. Our study was undertaken to explore the possibility that exogenous HCG, administered to induce ovulation, may interfere with these low-threshold tests of pregnancy. Six healthy volunteers participated in our study. Each woman received three sequential 5,000-U doses of HCG by im route on days 3, 5, and 7 after ovulation. Blood and urine for HCG assay were taken daily from each subject. Urine specimens were subjected to a traditional high-threshold pregnancy test (sensitivity limit = 2000 U/L) and to a low-threshold pregnancy test (sensitivity limit = 50 U/L); HCG in plasma and urine was determined by ELISA assay. Plasma HCG levels increased gradually under HCG dosing and attained a peak on day 8 (average = 73.7 U/L; range 24-124 U/L). As regards urinary HCG levels, the average value on days 8, 9, and 10 was above the 50-U/L detection limit of the low-threshold test, which was in fact positive in the majority of patients. Also on days 11 and 12, however, urinary HCG levels were above this limit in a certain proportion of subjects (day 11, 2/6; day 12, 1/6); accordingly the low-threshold pregnancy test was positive with a frequency of 2/6 on day 11 and of 1/6 on day 12. By contrast, the traditional high-threshold pregnancy test was negative in urine samples of all subjects. Our study indicates that the increased sensitivity of modern low-threshold pregnancy tests may cause false positive results in those cases where exogenous HCG has been administered during the luteinic phase.

Polychemotherapy in ovarian cancer: treatment with Adriamycin, BCNU and cyclophosphamide vs. Adriamycin and cyclophosphamide.

The authors compared both therapeutic efficacy and toxicity of two different treatment regimens: ABC = adriamycin, nitrogen mustard (BCNU) and cyclophosphamide (CTX) vs. AC = adriamycin and cyclophosphamide in ovarian cancer. Thirty-one patients were entered under treatment plan ABC and 26 under treatment plan AC simultaneously. Therapeutic evaluation was subdivided into different risk groups (adjuvant therapy, residual disease less than or greater than 2 cm). A similar result could be noted in the two different treatment regimens. Toxicity was more severe and frequent in the group treated with BCNU. The AC regimen was preferred because of its lower incidence of side-effects and for its easier mode of administration.

The significance of measurement of several oncofetal antigens in diagnosis and management of epithelial ovarian tumors.

Association of serum alphafetoprotein (alpha FP), human chorionic gonadotropin beta-subunit (beta-HCG), carcinoembryonic antigen (CEA) and ferritin (FER) was studied in a group of 72 patients with epithelial ovarian cancer 15 days after surgery and at various times during 2 years. Only CEA and ferritin are able to reflect tumor burden in detecting evolutive disease; alpha FP and beta-HCG have a diagnostic significance in few cases, probably related to a particular, not evident, histological component of the tumor. Nevertheless the data indicate that the use of marker association can improve our capacity to detect, overall in the residual and evolutive disease, the real clinical burden of the patients.

Ferritinemia in ovarian malignant tumours.

Seriated ferritin assays were carried out on 95 patients affected by primitive ovarian epithelial tumour over a period of three years (1979/82), by radioimmunometric assay for human spleen ferritin. Ferritin was elevated in endometrioid tumours and in the presence of active progressing disease and chemotherapy did not influence these values. The ferritin/sideremia ratio was high in the case with pathological levels. Studying the glicosilation of this protein a significant amount of ferritin was not bound to concavallin A, suggesting direct release of this protein by tumour cells.

[Pelvic inflammatory disease and the intrauterine device]. / Malattia infiammatoria pelvica e dispositivi intrauterini.

PIP: The authors examined the incidence of pelvic inflammatory disease (PID) in women using an IUD among the population of an area served by a public health service for family planning. Among 300 women who used the IUD for at least 12 months, 7 cases (2.3%) showed a pelvic infection and 10 patients (3.3%) only a slight salpingitis without other symptoms. The incidence of PID in women using an IUD is about 3-4% and it increases in nulligravidae, in those subjects who engage in frequent intercourse, and in those women who have previously suffered from gonococcal infection. The IUDs are associated with a low incidence of pelvic infection, in most cases slight, so that the use of an IUD does not involve a significant risk of infection. (author's)^ieng