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).

The role of liquid-based cytology associated with curettage in the investigation of endometrial lesions from postmenopausal women.

OBJECTIVE: This study investigates the role of liquid-based cytology with ThinPrep technique, in the detection of endometrial lesions, using direct endometrial sampling from postmenopausal women with the Endogyn endometrial device. METHODS: It was performed on 491 postmenopausal women referred to our clinic for abnormal bleeding or other symptoms and/or a thickness of endometrium >5 mm on ultrasound. Endometrial sampling, dilatation and curettage (D&C) and hysterectomy were performed on all patients. For the diagnosis, the WHO classification scheme was used. RESULTS: According to our findings a sensitivity of 98.08%, specificity of 100%, positive predictive value of 100%, negative predictive value of 100% and overall accuracy of 98.98% were observed in both endometrial sampling and in D&C. CONCLUSIONS: Endometrial sampling is complementary to D&C for the diagnosis of endometrial lesions and it is necessary for it to be performed before D&C and/or hysterectomy.

Angiogenic properties of carcinoma in situ and microinvasive carcinoma of the uterine cervix.

Neovascularization is a critical step in the growth, progression and metastasis of tumors. The degree of angiogenesis may correlate with disease stage and provide prognostic information in various neoplasms. Microvessel density was studied in 24 patients with severe cervical intraepithelial neoplasias, 15 patients with microinvasive carcinomas (International Federation of Gynecology and Obstetrics IA1) and 15 healthy controls who had undergone hysterectomy for benign conditions. The microvessel density (MVD) in microinvasive squamous cell carcinomas was 40 +/- 2.42 (mean +/- SD) and in squamous carcinomas in situ (CIS) 20.41 +/- 2.29 (p < 0.05). Among patients with CIS and controls (13.33 +/- 1.59) there was also a significant difference in the number of vessels (p < 0.05). No significant correlation was found in relation to depth of invasion and histological grade of the microinvasive carcinomas. It is concluded that microinvasive squamous cell cervical carcinoma is an angiogenetic disorder and it seems that the onset of angiogenesis is an early event, usually in a preinvasive stage.

The prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erb B-2 and cathepsin-D in ovarian cancer patients receiving platinum with cyclophosphamide or paclitaxel chemotherapy.

PURPOSE: To evaluate the prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erbB-2 and cathepsin-D in epithelial ovarian cancer (EOC). METHODS: We analyzed 100 patients with ovarian carcinoma, FIGO Stage IC-IV who underwent primary cytoreductive surgery and received adjuvant chemotherapy with cyclophosphamide and a platinum analogue (CP) (n = 46) or paclitaxel and a platinum analogue (TP) (n = 54). Immunohistochemical expression was studied on paraffin-embedded tissue from the primary tumor. RESULTS: After a median follow-up of 55 months median progression-free survival (PFS) and overall survival (OS) were 16 and 41 months, respectively. Positive bcl-2 staining and absence of cathepsin-D expression were associated with an increased complete response rate in the CP group (p = 0.011 and p = 0.003) but not in the TP group. PFS and OS were not associated with the expression of any of the markers studied. FIGO stage (p = 0.006) and histology (p = 0.047) were the only independent prognostic factors for survival. CONCLUSION: Bcl-2 and cathepsin D expression are associated with response to CP but not TP chemotherapy. P53, bcl-2, c-erb B-2 and cathepsin D expression was not correlated with PFS and OS in our study.

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.

Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia.

PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. However, women with incomplete excision have a variable risk of CIN recurrence. The aim of this study was to identify possible risk factors for recurrence of CIN after large loop excision of the transformation zone (LLETZ) with involved margins of excision. METHODS: All cases of women treated with LLETZ for CIN between 1989-2000, in whom histological evaluation of the excised specimen revealed extension of CIN to the excision margins, were retrospectively studied. A woman was considered to have recurrence when she had histologically confirmed CIN following a second LLETZ or hysterectomy during the follow-up period. The characteristics that were examined as possible risk factors were age, parity, smoking habit, grade of initial lesion and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was diagnosed in 18 out of 65 (27.7%) women with involved margins. The only characteristic that reached statistical significance was age. The mean age of women with recurrence was 35.8 years, whereas the mean age of women without recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the endocervical margins (p = 0.149). No differences were observed between the two groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk factor for recurrence in women with incomplete excision of CIN after LLETZ. Larger studies are required for definite conclusions.

Vulvar intraepithelial neoplasia (VIN)--diagnostic and therapeutic challenges.

PURPOSE: Vulvar intraepithelial neoplasia (VIN) represents a current diagnostic and therapeutic challenge. The present retrospective study is an institutional experience on the diagnosis and management of VIN. METHODS: One hundred and thirteen women with VIN were reviewed and analyzed. Diagnosis was established by colposcopically directed biopsies whereas treatment was performed by either a surgical or a laser CO2 approach. RESULTS: The mean age of all VIN patients was 47.4 years. The most common symptom was pruritus (60.1%). The majority of the lesions were multifocal (N = 64, 56.6%) and located in the non-hairy part of the vulva (87.6%). VIN management consisted of laser CO2 treatment in 51 patients (45.1%), surgical treatment in 37 (32.7%) whereas 25 VIN, cases were managed by conventional medical treatment. The risk of disease relapse was not associated with VIN grade (p = 0.35) nor with the treatment modality used (p = 0.42). The risk of disease relapse was significantly higher for multifocal lesions (p < 0.001). Long-term follow-up of our patients showed that four patients (3.5%) developed an invasive vulvar carcinoma. CONCLUSION: Our study confirms other reports concerning the diagnostic and treatment difficulties of the management of VIN. Although the benefits of treatment are obvious there seems to be no guarantee that invasion will not occur.

Intravenous leiomyomatosis.

INTRODUCTION: Intravenous leiomyomatosis (IVL) is rare and it is characterized by intravascular nodular masses of histologically benign smooth muscle that may extend variable distances. Although histologically benign, IVL might be malignant in its mode of behavior. CASE REPORT AND DISCUSSION: A case of IVL is reported with emphasis on immunohistochemical analysis and recent literature.

Septic lithiasis of the pelvis.

Laparoscopic cholecystectomy has become a standard technique for the treatment of symptomatic cholelithiasis. Despite a significant reduction in the complication rate with increasing experience, bile duct injury and gallstone spillage still occur more frequently with this approach than with the open procedure. Unretrieved gallstones, in particular, have been associated with late infection and the formation of abscesses in virtually every area of the abdominal cavity. We present a rare case of an isolated pelvic abscess that developed in a postmenopausal woman 5 months after laparoscopic cholecystectomy for recurrent cholecystitis. The preoperative differential diagnosis of this case is also discussed.

Fecundity of infertile women with minimal or mild endometriosis. A clinical study.

Despite significant developments in medical and surgical approaches for treating endometriosis, the optimal therapy has yet to be established. The relationship between prevalence of fecundity and stage of endometriosis according to their management was studied. Of 151 consecutive women with laparoscopy-proved endometriosis stage-1 and 2, operative laparoscopy was performed in 49, medical treatment in 59 and expectant management in 43 cases. During a 24-month period the cumulative pregnancy rates were found to be 36.7%, 30.5% and 20.9% respectively. Survival analysis showed that the probability of carrying the pregnancy beyond 20 weeks were 30.6%, 25.4% and 16.2% respectively. Diagnosis and treatment of early endometriosis is beneficial for the infertile women. Laparoscopic surgery seems to be the milestone of treatment in these cases, increasing the fecundity and involving minimal risk.

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.

Ifosfamide, paclitaxel and cisplatin first-line chemotherapy in advanced, suboptimally debulked epithelial ovarian cancer.

BACKGROUND: The combination of paclitaxel with a platinum analogue is the preferred chemotherapy regimen in the treatment of advanced epithelial ovarian carcinoma. The alkylating agent ifosfamide has shown activity in refractory or recurrent ovarian cancer. We conducted a Phase II study with the combination of ifosfamide, paclitaxel, and cisplatin for the treatment of newly diagnosed patients with advanced, suboptimally debulked ovarian carcinoma. METHODS: Thirty-five consecutive patients with advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage III or IV) and residual disease larger than 2 cm after staging laparotomy and cytoreductive surgery were treated with paclitaxel, 175 mg/m(2), as a 3-hour intravenous infusion on Day 1, cisplatin 75 mg/m(2) intravenously over 2 hours on Day 2, and ifosfamide 1500 mg/m(2) intravenously over 1 hour on Days 1-3 (with sodium 2-mercaptoethane sulfonate [MESNA] uroprotection). Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was given at a dose of 5 microg/kg/day on Days 7-11. RESULTS: Among 26 patients with measurable disease, 22 (85%) achieved an objective response including 15 complete and 7 partial responses. With a minimum follow-up of 46 months, the median overall survival was 52.8 months (range, 5.3-56.6+ mos), whereas the median time to progression for all patients was 22.2 months. The median remission duration for women with measurable disease who responded to treatment was 12.6 months. The treatment was tolerated relatively well without toxic deaths; the most common toxicity was Grade 3 or 4 neutropenia that occurred in 42% of patients. Significant peripheral neuropathy (Grade 2 or higher) developed in 35% of patients. CONCLUSION: The combination of ifosfamide, paclitaxel, and cisplatin is a well-tolerated outpatient regimen with significant activity in the treatment of newly diagnosed FIGO Stage III or IV epithelial ovarian carcinoma. Further evaluation is justified to clearly define the role of ifosfamide as an additional agent to the current platinum and paclitaxel regimens.

Cervical intraepithelial neoplasia in the young female. Diagnosis and management.

The prevalence of HPV and CIN in young women has increased in recent years. During a 5-year period (1996-2000), 78 sexually active young females, aged 15-20 years, were referred to the Colposcopic Unit of the 1st Department of Obstetrics and Gynecology of the University of Athens in the major University-appointed hospital in Greece, because of an abnormal cytology or a suspicious cervical abnormality in the presence of negative cytology. Colposcopic examinations were found to be within normal limits in 12/78 (15.4%) of cases. Cervical pathology was related in 22 cases (28.2%) to HPV infection, 23 (29.5%) cases to CIN 1, 18 (23.1%) cases to CIN II and 3 (3.8%) to CIN III. No relation between oral contraceptive use and cigarette smoking with HPV infection was found. Our findings strongly confirm the necessity of obtaining cervicovaginal smears on all sexually active gynecologic and obstetric teenage patients.