Conservative management of endometrial cancer: a survey amongst European clinicians.

OBJECTIVE: To investigate differences and similarities in the clinical approach of young clinicians managing women with endometrial cancer (EC) conservatively. METHODS: A web-based survey was carried out. A platform of the European Network of Young Gynaecological Oncologists (ENYGO) database was used. A 38-item multiple-choice questionnaire was used to evaluate current practice in fertility-sparing management of EC. The survey covered investigations, treatment options, follow-up and management of recurrence and future family planning. Descriptive statistics were used. RESULTS: Overall, 116 out of 650 (17.84%) ENYGO members responded to the survey. In 92 (79.3%) centres, the caseload of early stage EC treated conservatively was less than 10 per year. One hundred and seven responders (93.8%) believe that treatment with progestins could be offered in grade 1 EC without myometrial invasion, but a minority would recommend it even for grade 2 tumours with no myometrial invasion or grade 1 with superficial invasion. The diagnostic tool for establishing grade of tumour was hysteroscopy with dilatation and curettage in 64 (55%) centres. Medroxyprogesterone acetate represents the most commonly prescribed progestogen (55, 47.4%). In 78 (67.2%) centres, a repeat endometrial biopsy was offered after 3 months of treatment commencement. Recurrences are treated mostly with hysterectomy (81, 69.9%) with only a small number of responders recommending to repeat progestin treatment. Lynch syndrome is a contraindication for conservative management in half of the responders (57, 49.1%). Most clinicians agree that patients should be referred promptly for assisted reproductive techniques once complete response has been achieved (68, 58.6%). CONCLUSIONS: Our study shows that conservative management is increasingly offered to women affected by early stage EC wishing to preserve their fertility. Further studies and joint registries are required to evaluate safety and effectiveness of this approach in this probably growing number of patients.

The spread pattern of right and left epithelial ovarian cancers.

OBJECTIVE: No attention has been paid in the past to the spread pattern of right and left epithelial carcinomas of the ovaries. We aimed to investigate the incidence, spread pattern and distribution of lymph node metastasis in epithelial ovarian cancer (EOC), comparing right versus left EOC of any stage, where the contralateral ovary is apparently and histologically tumor-free. METHODS: Out of a total of 442 patients with EOC, 318 (72%) patients in the study had bilateral and 124 (28%) patients had unilateral ovarian cancer. The study enrolled 60 (48%) patients with right and 64 patients with left ovarian involvement (52%) where the contralateral ovary was tumor-free. Groups Right and Left were compared in terms of age, the tumor status of the lymph nodes, surgical stage, histology, grade, tumor extension out of the ovaries, omental tumor involvement and also omental and nodal involvement together. RESULTS: The comparisons of the variables between Groups Right and Left did not show significant differences except for metastasis patterns in the left iliac lymph nodes and omentum (p < 0.05). Independent of age and histological type of the tumor, women with left-side EOC showed a significantly higher incidence of metastasis in the left iliac lymph nodes (OR: 7.04, 95% CI, 1.36-36.44) and omentum (OR: 2.87, 95% CI, 1.03-8.01), when compared to right-side EOC (p < 0.05). CONCLUSION: In this cohort of patients, we found that left-side unilateral EOC was more likely to metastasize to the left iliac lymph nodes and omentum than the right side where the contralateral ovary was tumor-free. This might be due to the difference in lymphatic drainage on the right and left side and/or the influence of peritoneal fluid movements. This suggestion needs to be supported by further studies.

Ovarian transposition for the preservation of ovarian function in young patients with cervical carcinoma.

Radiotherapy with or without surgery for the treatment of pelvic malignancies irreversibly destroys the hormonal activity and reproductive capacity of ovaries in young women. On the other hand, menopausal symptoms associated with estrogen deficiency is an important contributor to the poor quality of life scores in gynecologic cancer survivors. Transposing of the ovaries into the paracolic gutters (ovarian transposition) was described in 1958 with the aim of protecting gonadal functions in reproductive-aged women treated by pelvic radiotherapy and/or surgery. Although the laparatomic approach has been used as a parallel to development in endoscopic surgery, today it is generally performed laparoscopically. However, there is ongoing debate about the effectiveness of ovarian tranposition with respect to protecting gonadal functions. Moreover, metastasis to the transposed ovaries and port sites is another concern about this procedure. In this short review, indications, techniques and functional outcomes of ovarian transposition have been summarized.

Current management of endometrial hyperplasia and endometrial intraepithelial neoplasia (EIN).

Endometrial hyperplasia is a commonly seen disorder in daily gynecology practice. The clinical importance of this pathological entity is the underlying risk of carrying a concomittant genital cancer or risk of progression to endometrial carcinoma during the follow-up. Despite recent advances in non-invasive techniques to define underlying endometrial cancer during the initial diagnosis of endometrial hyperplasia, none of these studies are conclusive yet. Today, in spite of intense discussions and related studies which aimed to define certain prognostic factors (WHO94 vs EIN) to predict cases that would progress to cancer, we still do not have a practical and accurate system available to use during daily practice. Treatment of endometrial hyperplasias depends on the patient's age, fertility desire and the type of hyperplasia. Progestagens are still the most commonly used medical treatment modality in these patients. Response rates are higher for cases without atypia. In selected cases, hysterectomy may be performed as a definitive treatment modality. In this review article, the current management of endometrial hyperplasias is summarized in light of the associated literature. We also give a brief overview of the EIN classification and its clinical importance.

Bilateral breast metastasis of ovarian carcinoma.

Primary breast carcinoma is the most common malignancy in women, however, metastatic breast carcinoma is rarely seen in clinical practice. It has been reported that lymphoma-leukemia, melanoma and sarcomas, the most common primary malignancies, can metastasize to the breast. On the other hand, ovarian carcinoma and other gynecologic cancers rarely develop into breast metastasis. However, the incidence of breast metastasis arising from ovarian carcinoma might be increasing as a result of prolongation in survival and improvement in treatment modalities. Bilateral breast metastasis originating from an ovarian carcinoma is an extremely rare clinico-pathological situation. In our literature review we found just nine cases of bilateral breast metastasis from primary ovarian carcinoma. In this study, the mean age was 46 years (range 16-68). Mean interval from initial diagnosis of ovarian carcinoma to bilateral breast metastases was 22 months (range 11-24) and mean survival was 12 (range 5-27) months after the diagnosis of breast metastasis. Serous papillary adenocarcinoma was the predominant histological subtype. Interestingly, five of the nine (56%) cases reported were from Turkey. This interesting observation can be explained by a genetic predisposition, but it requires further research. In conclusion, although it is a rare entity, breast metastasis should not be ruled out in patients with a history of ovarian carcinoma, if patients present with any symptoms of breast diseases.

Interval debulking in epithelial ovarian carcinomas: the past, present and the future.

Primary cytoreductive surgery followed by combination chemotherapy of paclitaxel and cisplatinum is the standard treatment for advanced staged epithelial ovarian cancers. Despite the maximal efforts to increase optimal cytoreductive success rates and related ultra-radical surgeries, five-year survival rates are still poor. Primary cytoreductive surgeries and their radicalities have been criticized since the early nineties. Interval debulking surgery (IDS) and neo-adjuvant chemotherapy (NAC) are the two suggested alternatives to the primary debulking approaches. In this article, the authors summarize and discuss the IDS approach with an associated literature review.

Radical vaginal trachelectomy (Dargent's operation): a critical review of the literature.

AIMS: To present a review of the most recent articles about radical vaginal trachelectomy (RVT). METHODS: Recent literature has been reviewed, concentrating on surgical, oncological and obstetrical outcome of RVT. Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms "trachelectomy" and "radical vaginal trachelectomy", "cervical carcinoma", and "fertility saving". FINDINGS: Although a considerable number of women in their reproductive years have been diagnosed with cervical carcinoma, conservative management of early-stage cervical carcinoma did not come into practice until the beginning of the new millennium. To date, 7 gynecologic oncologic centers worldwide have reported oncological and pregnancy outcomes since Dargent made his first announcement of radical vaginal trachelectomy (RVT) in 1994. Recurrence and death rates (4.2% and 2.8%, respectively) of RVT seem to be comparable to classical radical abdominal hysterectomy. It appears that RVT's overall recurrence and death rates were similar to early-stage cervical cancer treated by radical hysterectomy (RH) or radiotherapy. Furthermore fertility results of RVT seem to be promising. A 70% pregnancy rate was reported in the women who wanted to conceive following RVT, though such patients should be informed about the risk of second trimester loss and preterm delivery. On the other hand, there is a lack of satisfactory information about the follow-up of post-RVT patients, both after the operation and during subsequent pregnancy. CONCLUSION: RVT looks as if it is a valid uterus-conserving surgery for women of reproductive age who have early-stage cervical carcinoma. However, in order to reach a final conclusion about the oncological and obstetrical results, further studies are needed with larger sample sizes and longer follow-up periods.

Neoadjuvant chemotherapy in gynecological cancers.

Neoadjuvant chemotherapy in gynecological cancers is an approach that is shown to have positive effects on survival. It increases the rate of resectability in ovarian and cervical cancers and thus contributes to survival. However, there are studies reporting that despite increasing operability, the approach does not make any changes in terms of survival. Nevertheless, no negative effects have been reported in studies conducted till today. Prospective and randomized well-designed studies that encompass a high number of cases and parameters, including cost-effectiveness, are needed in both types of cancers. Until the results of such studies are obtained, neoadjuvant chemotherapy may be taken into consideration as an alternative when conventional methods do not suffice. The number of studies concerning endometrial, vulvar and vaginal cancers are few in the area of neoadjuvant chemotherapy.

Prognostic and therapeutic importance of lymphadenectomy in gynecological cancers.

Lymphadenectomy has been a matter of interest for years because of the increased morbidity rates in gynecological cancers due to the procedure itself and because the procedure requires experience. Although a number of alternative methods have been developed to find out the prevalence of gynecological cancers, dissection and histopathological evaluation of lymph nodes is still the gold standard in detecting disease. Even though there are opposing views regarding this approach, since the morbidity rate has decreased over the years many studies in the literature report that lymphadenectomy has prognostic and therapeutic value. Its contribution to survival can be attributed both to its being determinant in postoperative treatment modifications and to debulking and lymphadenectomy itself. In order to reap the prognostic and therapeutic benefit expected from lymphadenectomy, a sufficient number of lymph nodes must be dissected. Surgical experience is important both for the procedure itself and to reduce the morbidity due to the procedure. This study discusses the prognostic and therapeutic importance of lymphadenectomy in ovarian, endometrial, cervical and vulvar cancers.

Nuchal cord type B associated with an excessively long umbilical cord as a cause of stillbirth: a case report.

Nuchal cord (NC) is defined as the umbilical cord being wrapped 360 degrees around the fetal neck. It is one of the most common complications of the umbilical cord and any pregnancy might be complicated with a nuchal cord. If a nuchal cord occurs in a pregnant woman with decreased fetal movements, it should be considered to be at high risk, particularly for fetuses with multiple nuchal cords. We report a case in breech presentation with an excessively long umbilical cord (190 cm) which was complicated with five nuchal loops around the fetal neck and resulted in intrauterine death at the 37th week of pregnancy.

New surgical approaches for the management of cervical carcinoma.

Cervical carcinoma remains an important health problem in both developed and developing countries even though population-based screening programs are widely available. The classical surgical management of early-stage cervical carcinoma, known as radical hysterectomy (RH), was first described by Wertheim more than one hundred years ago and was then modified and re-popularized by Meigs in 1950s. The surgical principles of this operation have undergone only minor modifications and remain the basis for the surgical approach utilized by gynecologic oncologists today. However, some recent studies have questioned the role of RH due to a high rate of postoperative complications involving the pelvic autonomic nerve system and poor oncological outcomes despite postoperative adjuvant chemoradiation. During the last 2 decades, new surgical operations (radical vaginal trachelectomy, nerve-sparing hysterectomy, total mesometrial resection, laterally extended endopelvic resection, laparoscopic assisted radical vaginal hysterectomy, laparoscopic lumbo-aortic lymph node dissection, and laparoscopic pelvic exenteration) have been proposed for the management of both early- and late-stage cervical carcinoma. In this manuscript, some technical details and oncological outcomes of these new surgical approaches are summarized.

Cyclooxygenase-2 expression in cervical intraepithelial neoplasia III and squamous cell cervical carcinoma, and its correlation with clinicopathologic variables.

The objective of the study was to compare cyclooxygenase-2 (COX-2) expression in cervical intraepithelial neoplasia III (CIN III) and squamous cell carcinoma (SCC) of the cervix, and its correlation with clinicopathologic factors of SCC with a review of the available literature. This study included 25 patients with CIN III and 67 patients with stage I-IIa SCC. All patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy and postoperative chemoradiotherapy based on their histopathologic risk factors. Immunohistochemical analysis was performed on paraffin-embedded sections with COX-2 antibody. COX-2 expression in the SCC group was significantly higher than in the CIN III group (55.2% [37/67] vs 24% [6/25]; P= 0.008). Significantly higher expression of COX-2 was observed in patients with lymphovascular space invasion (LVSI) compared to patients without LVSI (61.9% [34/55] vs 33.3% [3/9]; P= 0.02). Additionally, patients with tumor sizes >4 cm had significantly higher COX-2 expression than patients with tumor sizes <4 cm (65.9% [27/41] vs 39% [10/26] P= 0.028). There was no significant relationship with respect to COX-2 expression and parametrial involvement, lymph node metastasis, recurrences, and survival. In multivariate analysis, LVSI was the only statistically significant determinant for COX-2 expression (P= 0.024; OR = 2.35; 95% CI = 1.1-4.9). Our results and a review of the literature both suggest that COX-2 expression may have a role in the development and progression of CIN III and it is related to some clinicopathologic variables of cervical carcinoma. Further studies are needed to clarify the role of COX-2 inhibitors in the management of CIN and SCC.

Loss of epithelium cadherin expression is associated with reduced overall survival and disease-free survival in early-stage squamous cell cervical carcinoma.

Epithelium cadherin (E-cad) is important for cell-to-cell adhesion of epithelial cells. Impairment of E-cad may have a role in the development and spreading of different malignancies and associated with poor differentiation, increased invasiveness, and poor prognostic factors in nongynecological carcinomas. However, prognostic significance of E-cad expression has not been investigated properly in cervical squamous cell carcinoma (SCC). The objective of this study was to investigate the association between reduced E-cad expression and clinicopathologic variables of cervical carcinoma. Specimens from 53 consecutive patients with stage IB-IIA SCC were evaluated immunohistochemically for E-cad expression, and the results were compared to grade, lymphvascular space invasion (LVSI), deep stromal involvement (DSI), parametrial involvement, lymph node metastasis, recurrences, and survival. Patients were divided into two groups arbitrarily: E-cad expression less than 10% (group 1) and E-cad expression more than 10% (group 2). There was no significant relationship between E-cad expression and DSI, LVSI, lymphatic metastasis. However, there was significant relationship between reduced E-cad expression and parametrial involvement (P= 0.024). Kaplan-Meier survival analysis revealed that reduced E-cad expression is significantly associated with reduced overall survival (OS) and disease-free survival (DFS). Furthermore, Cox regression analysis revealed that reduced E-cad expression is significantly associated with OS (P= 0.004, RR = 6.08, 95% CI: 1.75-21.1) and recurrences (P= 0.027, RR = 1.75, 95% CI: 1.06-2.88). We conclude that loss of E-cad expression is significantly associated with reduced OS and DFS in patients with SCC. Therefore, it might be used as an indicator of aggressive clinical behavior and tailoring aggressive adjuvant therapy in early-stage SCC. Further studies with larger number of patients are needed to evaluate the clinical significance of reduced E-cad expression in SCC.

Ascites and epithelial ovarian cancers: a reappraisal with respect to different aspects.

Ascites is a common finding in patients with epithelial ovarian cancer (EOC). Clinico-pathologic correlations with respect to the presence of ascites, positive cytology and prognostic role of ascites, and the impact of ascitic volumes were not previously studied extensively. A total of 372 patients with EOC were retrospectively evaluated with respect to presence and amount of ascites, cytologic findings, and survival. Two groups were compared by using Chi-square, Student's t and Mann-Whitney U, binary logistic regression, Kaplan Meier and Cox-regression analysis tests, where appropriate. Omental metastasis (P < 0.001; OR: 3.21, 95% CI = 1.945-5.297) and mean number of metastatic lymph nodes (P= 0.008; OR: 1.063, 95% CI = 1.016-1.112) were significantly related with presence of ascites. Evaluation of ascitic volume at different thresholds revealed lymphatic-omental metastasis, and also the disease stage to be significantly different among patient groups at lower threshold values and the positive cytology and high-grade diseases at higher threshold values. In conclusion, presence of ascites correlates with both the intraperitoneal and also the retroperitoneal tumor spread. Amount of ascites has different correlations with the clinico-pathologic factors depending on the thresholds chosen. At lower volumes, lymphatic and omental metastasis seems to correlate with the development of ascites. Once ascites develops, tumor grade seems to be important for larger ascites volumes. Neither the presence of ascites or its volume nor the cytologic positivity was an independent predictor of survival.

Skeletal carcinomatosis in endometrial clear cell carcinoma at initial presentation: a case report.

Bone metastasis is frequently seen in different solid tissue malignancies. However, it is a very rare entity in endometrial cancers and most of the previous reports were localized to a single bone. To the best of our knowledge, this is the first report of a case with disseminated bone metastasis from endometrial clear cell carcinoma. A 69-year-old, multiparous woman presented with the complaint of postmenopausal bleeding. Diagnostic workup revealed endometrial clear cell carcinoma. After comprehensive surgical staging, the patient was found to be at FIGO stage IIIC. Three weeks after the operation, an intractable back pain developed. Direct graphics of the lumbosacral region were suspicious of metastasis, and further evaluation of the patient revealed metastasis in multiple bones including calvarium, thoracolumbal vertebrae, pelvic bones, costae, collum of the right femur, and trochanter major of the left femur. Bone metastasis in endometrial clear cell carcinoma may be seen at initial presentation and may involve multiple bones. Whole-body scanning with scintigraphic evaluation is a reasonable approach to evaluate the extension of the bone involvement. Further studies are needed to elucidate the true incidence and management of bone metastasis in endometrial clear cell carcinoma.

Disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor: a case report.

It is well known that peritoneal tuberculosis may mimic advanced-stage epithelial ovarian carcinoma because of similar clinical, radiologic, and laboratory findings. However, disseminated peritoneal tuberculosis mimicking advanced-stage endodermal sinus tumor (ESS) has not been reported previously. An 18-year-old nulliparous woman came with the complaint of pelvic pain and weight loss. Imaging studies demonstrated that she had multiple peritoneal implants and left adnexial mass. Also, laboratory studies showed elevated CA125 and alpha fetoprotein levels suggesting an initial diagnosis of ESS. However, intraoperative frozen section examination showed caseous necrosis, and she was diagnosed as having disseminated peritoneal tuberculosis. Two months after the initial exploration, the patient required liver transplantation because of hepatic failure due to widespread hepatic involvement of the tuberculosis. Concomitant peritoneal and hepatic involvement of tuberculosis may cause false elevation of multiple tumor markers of gynecological cancers and may lead to misdiagnosis and mismanagement of patients. Elevation of these markers should be carefully investigated especially in premenopausal women. To our knowledge, this is the first reported case of peritoneal tuberculosis misdiagnosed as endodermal sinus tumor.

Primary ovarian fibrosarcoma: a case report and review of the literature.

Primary ovarian fibrosarcomas are very rare tumors with great heterogeneity among reported cases. There are only a few reports of the subject in the literature, and along with the nature of the disease, diagnosis and treatment still remain to be established. In this report, we reviewed the cases published in the English literature within the past 30 years and tried to highlight certain aspects of the disease. A 52-year-old parous woman was admitted to our hospital with the complaints of abdominopelvic pain. Initial diagnostic work-up revealed a solid mass on the right ovary. After explorative laparotomy, the pathologic examination reported a primary ovarian fibrosarcoma. The patient has been free of disease for 1 year without any adjuvant therapy. Although ovarian fibrosarcomas are unusual causes of solid masses in postmenopausal women, it should be kept in mind when evaluating adnexal masses in this age group.