Survival Outcomes of Epithelial Ovarian Cancer Patients Following Dose-dense Versus 3-Weekly Platinum-Paclitaxel Chemotherapy: A Meta-Analysis.

AIMS: Dose-dense chemotherapy has proven its value in several cancer fields. The purpose of the present systematic review is to evaluate the impact of dose-dense chemotherapy on survival outcomes of epithelial ovarian cancer patients. MATERIALS AND METHODS: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta and metafor functions. A sensitivity analysis was carried out to evaluate the possibility of small study effects and P-hacking. The methodological quality of the included studies was assessed using Risk of Bias 2 (RoB2) and Risk of Bias in non-Randomized Trials (RoBINS) tools. RESULTS: Overall, 12 studies were included in the present systematic review, involving 4979 epithelial ovarian cancer patients. The risk of recurrence was substantially improved in patients receiving dose-dense chemotherapy (hazard ratio 0.82, 95% confidence interval 0.70, 0.96); however, the result of the meta-analysis may be attributed to the effect size of smaller studies as following adjustment for small study effects the outcome becomes non-significant (hazard ratio 0.91, 95% confidence interval 0.81, 1.02, P = 0.123). Overall survival rates were not improved by dose-dense chemotherapy (hazard ratio 0.79, 95% confidence interval 0.60, 1.04). Thirty-five types of adverse effect were identified following retrieval of data from the original studies. Dose-dense chemotherapy did not increase significantly the rates of severe adverse effects, although thrombosis, severe diarrhoea and severe nausea were more prevalent in this group of patients. CONCLUSION: Dose-dense chemotherapy is associated with comparable side-effects to those of standard chemotherapy; however, data related to survival outcomes are not positive; hence, its use outside the setting of clinical trials should be discouraged.

Ocular metastasis of primary gynecological malignancies, a rare but not insignificant entity: A systematic review.

The genital system remains one of the most common sites of carcinogenesis in women. Advances in surgery, radiation treatment, and chemotherapy have increased their efficacy and many patients survive for many years after their initial diagnosis. The eye is a rare site of metastasis from gynecological cancer due to its distant location from the genitalia. In this systematic review, we retrieved all case reports of patients with ocular metastasis from gynecological neoplasms. The demographic, clinical, and treatment characteristics were retrieved and analyzed. A total of 70 case reports were included. Forty-eight of these reports concerned patients with a known malignancy that recurred in the eye and in 22 patients' ocular symptomatology accompanied the initial diagnosis of the gynecologic malignancy. 73.9% of these patients exhibited concomitant metastasis to other organs. The mean disease-free interval was found at 25.7 months and mean survival time after the eye metastasis was 13.5 months. Refractory disease was identified as the most important risk factor associated with mortality. Because eye metastasis has such a dismal prognosis, all gynecologists who treat oncological patients should be highly suspicious for reported eye complaints.

Neutrophil-to-lymphocyte ratio and chemotherapy response score as prognostic markers in ovarian cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is the recommended approach in patients with advanced epithelial ovarian cancer (EOC). However, most patients eventually relapse despite the initial high response rate to chemotherapy. Neutrophil-to-lymphocyte ratio is a well-known biomarker that reflects severe inflammation, critical illness, and mortality in various diseases. Chemotherapy response score (CRS) and neutrophil-to-lymphocyte ratio (NLR) have been identified as potential biomarkers of platinum resistance and disease prognosis. We retrospectively evaluated 132 patients with stage IIIc or IV ovarian/fallopian tube/primary peritoneal cancer who had received NACT followed by IDS from 01/01/2003 to 31/12/2018. CRS was assessed on omental specimens collected from IDS according to ICCR guidelines. RESULTS: Median age was 64.57 years (SD: 9.72; range 39.2-87.1). Most ovarian tumors were serous epithelial (90.9%; 120/132). An elevated NLR (defined as > 3) was observed in 72% (95/132) of patients in contrast with 28% (37/132) of patients characterized by low NLR status. Median PFS (mPFS) and median overall survival (mOS) were 13.05 months (95% CI: 11.42-14.67)) and 34.69 months (95% CI: 23.26-46.12) respectively. In univariate analysis, CRS3 score was significantly associated with prolonged mPFS (CRS1/2: 12.79 months vs CRS3: 17.7 months; P = 0.008). CRS score was not associated with mOS (P = 0.876). High NLR was not significantly associated with mPFS (P = 0.128), however it was significantly associated with poor mOS (P = 0.012). In multivariate analysis, only performance of surgery maintained its statistical significance with both PFS (P = 0.001) and OS (P = 0.008). CONCLUSION: NLR could serve as a useful predictor of OS but not PFS in ovarian cancer patients receiving NACT. In accordance with our previous study, CRS score at omentum was found to be associated with PFS but not OS in ovarian cancer patients treated with NACT and IDS.

Biomarkers that would predict response to neoadjuvant chemotherapy in advanced ovarian cancer patients are eagerly needed:• Neutrophil to Lymphocyte Ratio (NLR) is an indicator of systemic inflammatory response to the malignancy.• NLR was evaluated in 132 patients undergoing Neoadjuvant Chemotherapy for advanced ovarian cancer.• Elevated NLR was associated with worse prognosis.• No association between NLR and response to chemotherapy was noted.

Changing the way we train surgeons in the 21th century: A narrative comparative review focused on box trainers and virtual reality simulators.

The traditional method of acquiring surgical skills by observing and assisting in surgical procedures involving human beings has been challenged during the past several years. Lessons obtained from aviation suggested that the use of simulators is related to reduced costs, increased efficiency in performing certain tasks and above all safety. A shift in paradigm is also required in modern surgical training. The development of endoscopic surgery allowed for the incorporation of medical simulators into training programmes. A review of the literature was conducted using specific inclusion and exclusion criteria, for articles published up to July 31th, 2018. Relevant studies were identified using computerized bibliographic searches of MEDLINE database. The keywords that were used in various combinations were: "Medical Simulators", "Surgical Training", "Laparoscopy", "Surgical Skills", "Box trainers", "Virtual reality simulators", "Surgical Education". Surgical training with box trainers and/or virtual reality simulators confers a significant benefit in terms of surgical skills development, increases patient safety and reduces costs. Nevertheless, the use of virtual reality simulators was significantly more expensive. Simulation training allows trainees to learn from their mistakes, to repeat surgical tasks multiple times so as to establish muscle memory, and enhance skill competency with the aid of informative feedback. Simulators are necessary for the development of the skills required to meet the specific needs of endoscopic surgery in the 21st century. Teaching hospitals should introduce simulation training programmes in order to increase efficiency, reduce costs and improve patient safety. As medical advancements continue to transform the way we perform surgery day by day, simulation training will play a pivotal role in every surgical specialty.

The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO).

BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.

VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2.

BACKGROUND: Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites. METHODS: T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed. RESULTS: The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells. CONCLUSION: Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.

Prognostic evaluation of tumour type and other histopathological characteristics in advanced epithelial ovarian cancer, treated with surgery and paclitaxel/carboplatin chemotherapy: cell type is the most useful prognostic factor.

AIM: Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. PATIENTS AND METHODS: Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. RESULTS: Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. CONCLUSION: The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.

Prognostic factors for early-stage epithelial ovarian cancer, treated with adjuvant carboplatin/paclitaxel chemotherapy: a single institution experience.

OBJECTIVE: Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy. METHODS: Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy. RESULTS: Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p<0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%). CONCLUSIONS: Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.

Peritoneal implantations of papillary serous ovarian cystadenocarcinoma 13 days after initial laparoscopic treatment for a presumed benign ovarian cyst.

We report a case of a 24-year-old female who underwent laparoscopy for a presumed benign ovarian mass. Frozen sections at laparoscopy initially revealed a borderline papillary serous ovarian tumour. Final histology showed an invasive papillary serous ovarian tumor (grade 1). Subsequent staging laparotomy conducted 13 days later revealed peritoneal implantations thus upgrading the initially thought Stage Ia papillary serous ovarian tumour at laparoscopy to Stage IIc. The patient after laparotomy had an uneventful postoperative course and received six cycles of chemotherapy based on taxol and carboplatin. A short review of the literature is also presented, concerning the factors which affect the patient's prognosis in cases of unexpected ovarian malignancy found during laparoscopy that are treated with subsequent staging laparotomy.

Management of a pregnancy complicated by yolk sac tumor.

BACKGROUND: The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach. CASE: A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle. CONCLUSION: In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Cervical intraepithelial neoplasia in young women.

The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 - 20 years with a histological diagnosis of CIN during the years 1999-2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67.5%) had CIN1 and 26 (32.5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 - 20 years. Nevertheless, close monitoring is mandatory, as 10 - 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety.

Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina?

The aim of the present study was to assess the local application of imiquimod cream 5% as an alternative mode of therapy for high-grade vaginal intraepithelial neoplasia (VAIN 2/3). Positive human papillomavirus (HPV) patients with multifocal high-grade VAIN (2/3) not involving the vaginal vault in hysterectomized patients took part in this study. The treatment consisted of vaginal application of the cream under colposcopic guidance. Following management, biopsies were obtained from the previously recorded lesions. p53 expression was recorded prior and after therapy. Seven patients with VAIN 2/3 took part in this study. Six patients (86%) were positive for high-risk HPV type while three (43%) women who were positive for p53 nuclei prior to therapy were found to be negative following treatment. After treatment, 86% of the patients were found to have either HPV infection or low-grade VAIN. During follow-up, two patients (28.5%) were managed by vaginectomy, one for persistent and one for recurrent high-grade VAIN. Currently, from the five patients that are followed, three have simple HPV infection and two, VAIN 1. Imiquimod cream 5% might represent an alternative although not permanent method of management in young, HPV-positive women with multifocal high-grade lesions of the vagina (VAIN 2/3).

Pregnancy outcome in women with pre-existing lupus nephritis.

The aim of the present study was to assess the fetal and maternal outcome in a cohort of patients with lupus nephritis. Twenty-four pregnancies in 22 women with lupus nephritis occurring between 1991 and 2000 were analysed retrospectively. Lupus nephritis was biopsy proven before pregnancy in all cases. Women were followed from the beginning of pregnancy up to 6 months postpartum. Close fetal-maternal monitoring and frequent laboratory investigations were applied routinely to all patients. All women were prescribed steroid therapy from the beginning of the pregnancy. There were 18 live births, four spontaneous abortions and two stillbirths. Of the 18 live births, 14 were premature and four were term deliveries, representing a 25% fetal loss rate and 58% prematurity rate. There were two fetuses with congenital heart block. We recorded hypertension in 42%, proteinuria in 50% and pre-eclampsia in 25% of our patients. Proteinuria was irreversible in four cases. No maternal deaths or postpartum exacerbation of the disease were recorded in the study period. All renal flares were reversed postpartum. Patients positive for antiphospholipid antibodies had a worse perinatal outcome. Hypertension, proteinuria and antiphospholipid antibodies appear to be associated with adverse perinatal outcome and pregnancy complications. Pregnancy is not contraindicated in women with lupus nephritis, but is associated with significant fetal and maternal risks.

Malignant rhabdoid tumor of the clitoris in an elderly patient: report of a case.

Malignant rhabdoid tumors of the vulva are rare neoplasms which most of the time show aggressive behavior and a dismal prognosis. We report a case of malignant rhabdoid tumor of the clitoris occurring in an elderly patient. Due to the similarities that these neoplasms show with other low-differentiated tumors, immunohistochemical and ultrastructural assessment should always be conducted so that accurate diagnosis is achieved. Individualized extensive surgical treatment might decrease relapsing disease.

Vaginal intraepithelial neoplasia: report of 102 cases.

BACKGROUND: Vaginal intraepithelian neoplasia (VAIN) is a rare asymptomatic disorder. The aims of the current study were to profile patients with VAIN and to evaluate the response to treatment. MATERIAL AND METHODS: We reviewed the records of 102 patients with VAIN diagnosed from 1990 to 2000. RESULTS: Patients with VAIN, VAIN2 and VAIN3 had the following mean ages 44.5, 47.8 and 61.8 years, respectively (p < 0.001). All patients with VAIN were found to have abnormal Papanicolaou smears. Localization of the lesions to the upper third of the vagina was observed in 80% of the cases. Recurrences following laser ablation and partial vaginectomy reached 21%. Patients with minimal VAIN lesions from whom punch biopsies were obtained had the lowest recurrence rate. Multifocality significantly affected the risk of recurrence (p = 0.03). CONCLUSION: VAIN most often involves the upper third of the vagina and is often multifocal. Patient selection and operator skill have a significant influence on the treatment outcome.

Treating intraepithelial lesions of the uterine cervix by laser CO2. Evaluation of the past, appraisal for the future.

BACKGROUND AND OBJECTIVE: Carbon dioxide laser (CO2) has been widely used in the past for the treatment of squamous intraepithelial lesions (SIL) of the uterine cervix. We present our 10-year experience of using this modality while evaluating its current and future use. MATERIALS AND METHODS: From 1988 to 1998, 3,078 women were treated for an intraepithelial lesion of the uterine cervix (SIL) by laser CO2 either by vaporization or conization. The procedure was performed on an outpatient basis and was well tolerated by the great majority of patients. The mean age of the women treated by vaporization was 27.5 years whereas of those managed by conization, 34.8 years. RESULTS: From the 3,078 women, 750 (24.4%) underwent laser vaporization and the remaining 2,328 (75.6%), conization of the cervix. Complications were minimal and consisted of intraoperative and postoperative bleeding (0.56%), pelvic infections (0.04%) and cervical stenosis (1.1%). Mean follow-up time was 83 months (range 24-142). Relapsing disease (either persistent or recurrent) was detected in 5.6% of the vaporization and 3.9% of the conization group. CONCLUSIONS: The management of SIL of the uterine cervix by laser CO2 offers excellent success rates with minor complications. The preservation of the anatomical integrity of the cervical tissue offers a better follow-up of these patients and the potential for repeat treatment. Although other treatment modalities are available, we believe that laser CO2 represents an excellent surgical tool for the management of intraepithelial lesions of the uterine cervix.

Conservative management of cervical intraepithelial neoplasia (CIN(2-3)) in pregnant women.

The management of cervical intraepithelial neoplasia (CIN(2-3)) diagnosed during pregnancy was the subject of this study. Two hundred and eight pregnant women with an abnormal cytology were assessed in our unit over a 10-year period. The age of the patients ranged from 20 to 45 (mean 28) years. Seventy-eight of these women were histologically proven to have CIN(2-3). All patients were followed up every 8-10 weeks by cytology and colposcopy during pregnancy and reassessed 8-12 weeks postpartum. The disease persisted in 30 cases (38.4%), whereas in the remaining 48 cases it regressed to CIN(1). No case of invasive disease developed during the follow-up period in these pregnant patients. Conservative management of CIN(2-3) during pregnancy is acceptable, but close follow-up and colposcopic expertise are necessary.

Vulvar lichen sclerosus in postmenopausal women: a comparative study for treating advanced disease with clobetasol propionate 0.05%.

BACKGROUND AND OBJECTIVE: Clobetasol propionate 0.05% has been the mainstay in treating vulvar lichen sclerosus (VLS) for the past ten years. The usual length of therapy is two to 12 weeks. We conducted this study to evaluate the efficacy and safety of treating severe lesions of VLS in postmenopausal women for a longer time on a regular basis using clobetasol propionate. MATERIALS AND METHODS: From 1997-2000, 137 women with VLS were examined in the Colposcopy and Laser Surgery Unit of "Alexandra" Hospital. Patients who were premenopausal, had previous therapy, exhibited mild or moderate disease or showed VIN or invasive cancer on vulvar biopsies were excluded from the study. The remaining women were divided into two groups. The first group applied clobetasol propionate 0.05% for three months and afterwards on an "as required" basis, whereas the second group used the ointment for six months on a regular basis. All patients were examined at two, three, six and 12 months following treatment. Signs and symptoms before and after therapy as well as side-effects caused by the ointment were recorded. RESULTS: The mean age of the women was 60.2 years. Fifty-four patients were divided into two categories. In the 6-month follow-up, 59% of the 1st group and 85% of the second had complete response regarding their symptoms whereas on the 12-month follow-up, the respective numbers were 48% and 74%. Concerning the signs, 30% of the first group and 55.5% of the second showed to have complete response after six months and 26% and 41% respectively after 12 months. All differences between the two groups, except the signs after 12 months, were statistically significant. There were no side-effects from the long-term use of clobetasol propionate 0.05%. CONCLUSIONS: Conservative management of severe lesions of VLS in postmenopausal women using clobetasol propionate 0.05% for a long time (6 months) on a regular basis, seems to be a safe and effective therapy. Improvement is observed primarily on the symptoms and less on the signs.

Primary invasive vaginal cancer. Report of 12 cases.

The aim of this study was to describe the clinical features, methods of treatment and results of treatment among patients with primary invasive cancer. Twelve women in whom primary invasive cancer of the vagina was diagnosed between 1996 and 2001 were studied. The mean age of women with primary invasive vaginal cancer was 70.1 years. Half of the patients had advanced stage carcinoma at the time of the diagnosis and 85% of patients had not had a Pap-smear in the last 15 years. Treatment consisted of radiotherapy or a combination of surgery and radiotherapy. Four patients out of six with advanced stage disease died in 30 months. In conclusion, the present study confirms that early detection of the disease could lead to more successful management and therefore better prognosis.

Behçet's disease: part of the differential diagnosis of the ulcerative vulva.

BACKGROUND: Behçet's disease is a heterogeneous pathological entity of unknown etiology, most of the time affecting many organs concurrently. CASES: We report two cases of women who presented with ulcerations of the vulvar area as the first symptom, highlighting the diagnostic difficulties that were encountered until the diagnosis of Behçet's disease was confirmed. CONCLUSION: Behçet's disease should be kept in mind as a part of the differential diagnosis of vulvar ulcers.