The rationale of opportunistic bilateral salpingectomies (OBS) during benign gynaecological and obstetric surgery: a consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG).

Ovarian cancer (OC), is a disease difficult to diagnose in an early stage implicating a poor prognosis. The 5-year overall survival in Belgium has not changed in the last 18 years and remains 44 %. There is no effective screening method (secondary prevention) to detect ovarian cancer at an early stage. Primary prevention of ovarian cancer came in the picture through the paradigm shift that the fallopian tube is often the origin of ovarian cancer and not the ovary itself. Opportunistic bilateral salpingectomy (OBS) during benign gynaecological and obstetric surgery might have the potential to reduce the risk of ovarian cancer by as much as 65 %. Bilateral risk-reducing salpingectomy during a benign procedure is feasible, safe, appears to have no impact on the ovarian function and seems to be cost effective. The key question is whether we should wait for a RCT or implement OBS directly in our daily practice. Guidelines regarding OBS within our societies are therefore urgently needed. Our recommendation is to inform all women without a child wish, undergoing a benign gynaecological or obstetrical surgical procedure about the pro's and the con's of OBS and advise a bilateral salpingectomy. Furthermore, there is an urgent need for a prospective registry of OBS. The present article is the consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG) regarding OBS.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.

The clinical value and the cost-effectiveness of follow-up in endometrial cancer patients.

The aim of the present article was to evaluate the cost-effectiveness of follow-up in endometrial cancer patients. A literature review was performed regarding the studies that addressed routine follow-up of endometrial cancer. For each published study, the costs of the follow-up program were calculated according to Belgium standards. A mean total of 13% relapsed. Symptomatology and clinical examination detected over 83% of the recurrences. The follow-up cost in euro after 5 and 10 years ranged between 127.68 and 2,028.78 and between 207.48 and 2,353.48, respectively. Based on the available data, there is little evidence of routine follow-up improving survival rates. Multiple protocols are used in practice without an evidence base. There is an urgent need for prospective randomized studies to evaluate the value of the current so-called 'standard medical practice of follow-up.' It is to be expected that the cost of follow-up could be reduced considerably, for instance, by tailoring to low- and high-risk groups, or by abandoning routine follow-up. Symptomatic patients, however, should be evaluated immediately. A reduction in the number of visits and examinations would mean an enormous reduction in costs. This economic benefit would be warmly welcomed in the times of increased health costs and decreased budgets.

Fertility preservation in gynecologic cancer.

SUBJECT: Management of patients with gynecologic cancer can now often be tailored to the extent of the disease and preservation of child-bearing ability and/or sexual function may be possible for certain women with early invasive disease. METHOD: A better understanding of the tumor-biology, and the consideration of different clinicopathologic factors, that bear prognostic significance in therapeutic modalities, will allow more and more individualization of treatment. DISCUSSION: Management of young women with early gynecologic cancer should therefore be individualized with the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. Experts in gynecologic oncology and infertility together with an informed patient and her family should make treatment decisions. OUTCOME: This article will review the conservative surgical management of early invasive cancers of the ovary, cervix and endometrium, in order to help preserve child-bearing capacity. In addition, management of gynecologic cancers diagnosed during pregnancy will also be discussed.

Surgical management of stage I and II vulvar cancer: the role of the sentinel node biopsy. Review of literature.

Recognition of the psychosexual consequences of radical vulvectomy and better understanding of the lymphatic drainage and histopathologic features of vulvar cancer have led to a more conservative surgical approach, especially in patients with early-stage disease. Every patient with early vulvar cancer should be managed individually and the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. The results of the sentinel node (SN) procedure in early cancer of the vulva are encouraging, and it might be possible in the near future to avoid the morbidity of inguino-femoral lymphadenectomy. This article reviews surgical management of early vulvar cancer and the place of SN biopsy.

[Fertility preservation in gynecologic cancer]. / Fertilitetsbevarende behandling ved gynekologisk kreft.

Recent advances in both the staging and the understanding of the natural history of gynecologic cancers have led to new approaches to treatment. The treatment can now often be tailored to the extent of the disease, and preservation of child-bearing ability and/or sexual function may be possible for certain women with early invasive cancers of the ovary, cervix, endometrium, vagina and vulva. Better understanding of the tumour biology and clinicopathologic factors of prognostic significance will allow for individualization of treatment. Management of patients with early gynecologic cancer should be individualized with the risks of conservative therapy balanced against the dangers and advantages of more radical therapy. Specialists in gynecologic oncology and infertility together with an informed patient and her family should make treatment decisions. In this article we present an overview of the therapeutic management of early invasive cancers of the ovary, cervix and endometrium, and present guidelines that may help preserve childbearing capacity.

Hormone therapy in epithelial ovarian cancer.

Although epidemiologic studies, animal experiments and receptor studies have shown that not only normal ovaries but also many malignant ovarian tumors can be considered as endocrine related and hormone dependent, the place of hormonal therapy in the management of patients with ovarian cancer remains unsettled. Most trials of hormonal treatment in ovarian cancer have been retrospective, involved only limited numbers of patients, and lacked important patient-related data and information pertaining to tumor characteristics. In addition, a variety of hormonal preparations with different degrees of potency and in different dosages were included in these studies. A literature review shows that response to hormonal therapy even in a preterminal setting, is modest, with about 8% objective response but almost no side effects. In a similar patient setting, more toxic therapeutic agents do not yield a better response. The place of hormonal therapy in the management of patients with epithelial ovarian cancer needs more thorough evaluation in well-designed randomized trials.

The prognostic significance of residual disease, FIGO substage, tumor histology, and grade in patients with FIGO stage III ovarian cancer.

Survival was evaluated in 455 patients with FIGO stage III invasive ovarian cancer managed between 1983 and 1991. Median follow-up was 73 months. The prognostic significance of clinical and histopathological variables was evaluated. In Cox multivariate analysis, FIGO substage was an independent prognostic factor with a relative hazard (RH) of 1.2 and 1.7 for substage IIIB and IIIC, respectively (P = 0.013). Size of residual disease after surgery was a stronger factor with an RH of 1.2 and 2.4 for residual disease of 0 to 2 cm and more than 2 cm, respectively (P < 0.001). Histologic type had prognostic significance because patients with endometrioid tumors did best, those with mixed, serous, and unclassified tumors had an RH of 1.5 to 1.9, and those with mucinous and clear cell tumors had an RH of 5.4 to 7 (P < 0.001). Grade, ascites, and age had also independent significance. Grade had an RH of 2.5 for grade 2 plus 3 (P < 0.001), ascites had an RH of 1.4 (P 0.018), and age had an RH of 1.7 and 2.4 for age 40 to 70 years and above 70 years, respectively (P < 0.001).

Is serum CA 125 at the time of relapse a prognostic indicator for further survival prognosis in patients with ovarian cancer?

The prognostic significance of serum CA 125 level before treatment of relapse for invasive epithelial ovarian cancer has been evaluated in 135 patients. At time of relapse, serum CA 125 level was higher than 35 U/ml in 110 (82%) patients. Those with serum CA 125 level of 35 U/ml or less at relapse had a better prognosis than those with higher values. Among patients with serum CA 125 level higher than 35 U/ml no difference in survival was observed. By multivariate analysis the independent prognostic factors for survival were histologic type (P < 0.0001) and serum CA 125 level (P < 0.01). Randomized trials are needed to further evaluate whether early detection of disease relapse because of serial serum CA 125 measurements does have prognostic significance.

Serum CA 125 level allows early identification of nonresponders during induction chemotherapy.

CA 125 was measured during induction chemotherapy in 119 patients with advanced epithelial ovarian cancer who had residual disease after primary surgery in order to determine whether patients with poor response to further treatment could be identified during early chemotherapy. All patients had a prechemotherapy serum CA 125 level higher than 35 U/ml. Blood samples were further obtained 4 weeks after the first, second, and third course. Four weeks after the second course of chemotherapy, all 20 patients with PCR, or microscopic disease at second-look, all 17 who achieved complete clinical remission, and 36 of 40 who achieved partial remission had serum CA 125 of 65 U/ml or less or had a decrease of 50% or more of the prechemotherapy level. Survival analysis showed that patients with a serum CA 125 level of 65 U/ml or less 4 weeks after the second course of chemotherapy had the best prognosis. In patients with a serum CA 125 level higher 65 U/ml at that time, a decrease of 50% or more of the prechemotherapy level indicated a prognosis better than that with a lesser decrease. The combined criteria for serum CA 125 (level > 65 U/ml 4 weeks after the second course and a decrease < 50% of the prechemotherapy level) allowed for identification of a real high-risk group with a median survival of 8.9 months and was identified by Cox regression multivariate analysis as the most powerful indicator for survival (P < 0.0001).

Prognostic value of pre- and postoperative serum CA 125 levels in ovarian cancer: new aspects and multivariate analysis.

The prognostic significance of the serum CA 125 level was studied in 687 patients with invasive epithelial ovarian malignancies. The samples were collected preoperatively in 200 and postoperatively in 487 patients. Median follow-up was 27 months (range 3-84). The serum CA 125 level was elevated preoperatively in 90% of cases, with a median value of 429 U/mL. In patients with evidence of disease at the time of sampling, the CA 125 serum level correlated directly to tumor stage, tumor load, and histologic grade. Using Cox multivariate analysis, the preoperative serum CA 125 level had no independent prognostic significance, whereas the postoperative level did. In patients without residual disease after primary surgery, histologic type (P less than .0001), postoperative CA 125 level with 35 U/mL as the cutoff value (P = .0009), and tumor grade (P = .034) were independent prognostic factors for survival. For those with residual tumor after primary surgery, histologic type (P less than .0001), postoperative treatment (P = .0002), size of residual disease (P = .0005), and postoperative serum CA 125 level with 65 U/mL as a cutoff (P = .003) were independent prognostic factors.

Gynecologic malignancy and surgery: from quantity to quality of life.

With modern anesthesia and better postoperative care, the mortality and morbidity of radical surgery have been markedly reduced during the last decades. With the maximum quantity of life achieved from radical surgery, increasing emphasis is now being placed on the quality of life. A better understanding of tumor biology and the consideration of different clinicopathologic factors that bear prognostic significance in therapeutic modalities will allow individualization of treatment. This will lead to less surgical morbidity and less functional and psychosexual impairments without sacrificing benefits of survival.

CA 125 measured before second-look laparotomy is an independent prognostic factor for survival in patients with epithelial ovarian cancer.

The prognostic significance of serum CA 125 level measured in the week before second-look operation was evaluated in 208 patients with invasive epithelial ovarian cancer. Serum CA 125 level was greater than 35 U/ml in 44.7% of patients. All patients with pathological complete response (PCR) had a serum CA 125 level less than or equal to 35 U/ml except one who developed lung metastases 2 months later. The sensitivity of serum CA 125 for identifying residual tumor at second-look operations was 58%, the specificity was 98%, the predictive value of a positive test was 99%, and the predictive value of a negative test was 43%. By Cox regression analysis, tumor state of second look, serum CA 125 level, histologic type, FIGO stage, and tumor grade were identified as independent prognostic factors for survival. We conclude that measurement of serum CA 125 level after induction chemotherapy represents a noninvasive method to identify patients at high risk for subsequent death from ovarian cancer. As far as we know, this is the first report to identify serum CA 125 level as an independent prognostic factor at the time of second-look laparotomy.

Laser excision of the transformation zone as treatment of cervical intraepithelial neoplasia with satisfactory colposcopy.

A series of 123 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) with satisfactory colposcopy were treated with outpatient laser excision of the transformation zone. Punch biopsy and/or endocervical curettage proved CIN III in 111 patients (90%). Histology of the laser excision specimen showed microinvasive disease in 3 patients. Operative hemorrhage occurred in 2 patients. The follow-up ranged from 12 to 59 months (median, 30 months). Four patients were found to have residual/recurrent CIN during the observation period, resulting in a cure rate of 97%. All patients with recurrence are free of disease after a second laser treatment. Only 1 patient out of 26 with involved resection margins relapsed. Laser excision of the transformation zone is proposed as a suitable replacement for laser vaporization in patients with CIN with satisfactory colposcopy, offering the major advantage of providing a histological specimen without an increase in morbidity.

Epidemiology, etiology, screening, prevention, and diagnosis in female genital cancer.

Cancers of the endometrium, ovary, and cervix share certain characteristics. Etiologic factors are generally environmental. Prevention of the three cancers requires further improvement in the efficiency of the available screening methods. Trials to improve survival require more accurate staging and diagnosis, in addition to the identification of more significant prognostic factors that could allow recognition of low- and high-risk groups of patients.

Female sterilization failure after bipolar electrocoagulation: a 6 year retrospective study.

A 6 year retrospective study was conducted from January 1983 till December 1988. During this period there were 13,014 births, 1,776 registered spontaneous abortions and 200 tubal pregnancies. 1,437 sterilizations were performed in the same period via bipolar electrocoagulation. 11.5% of the ectopic pregnancies were in patients who had previously undergone a tubal sterilization. The failure ratio following bipolar coagulation was 1.18%, and all failures were extra-uterine pregnancies, with an average interval between sterilization and ectopic pregnancy of 28.8 months. This reflects the importance of previous sterilizations as an etiologic agent in ectopic gestations. We will discuss the possible etiological factors for our sterilization failures and how these failures can be avoided or minimized. Also diagnostic difficulties and management of an extra-uterine pregnancy (EUP) following sterilization will be presented.

PIP: A 6-year retrospective study was conducted from January 1983-december 1988. During this time, there were 13,014 births, 1776 registered spontaneous abortions, and 200 tubal pregnancies. 1437 sterilizations were performed in the same period via bipolar electrocoagulation. 11.5% of the ectopic pregnancies were inpatients who had previously undergone a tubal sterilization. The failure ratio following bipolar coagulation was 1.18% and all failures were extrauterine pregnancies, with an average interval between sterilization and ectopic pregnancy of 28.8 months. This reflects the importance of previous sterilizations as a contributing factor in ectopic gestations. The authors discuss the possible etiological factors involved in these sterilization failures and how these could by avoided or minimized. Also, diagnostic difficulties and management of an extrauterine pregnancy (EUP) following sterilizations presented.