Dynamic spectral imaging: improving colposcopy.

PURPOSE: Colposcopy occupies a key role in the prevention of cervical cancer by identifying preinvasive or invasive lesions. However, colposcopy is subjective and is responsible for 52% of screening failures. Dynamic spectral imaging (DSI) is based on the objective, quantitative assessment of the acetowhitening effect. This study compared DSI with colposcopy. EXPERIMENTAL DESIGN: Women referred for colposcopy were examined simultaneously with colposcopy and DSI using a precommercial DySIS model (FPC-03) in an international, multicenter trial. The colposcopy impression and DySIS values were compared with consensus histology reports of biopsies. Subjects were recruited to a training group and subsequently to a test group. Measures were taken to avoid verification bias. RESULTS: The training and test groups comprised 82 and 308 eligible women, respectively. A cutoff value to identify high-grade disease was selected from the results of the training group and data from previous work. Receiver operator curve analysis of the test data showed an area under the curve of 0.844. DySIS detected 62.9% more high-grade cases than colposcopy (57 versus 35, P=0.0001). DySIS exceeded end points approved by the Food and Drug Administration for similar studies, with increments in the true positive rate of 22/308 (7.1%; lower 95% CL, 4.5% versus 2%) and in the false positive rate of 32/308 (10.4%; upper 95% CL, 14.7% versus 15%). CONCLUSIONS: DySIS is more sensitive than colposcopy in detecting high-grade lesions and can provide improved guidance for biopsy. The results are obtained in a user-independent fashion, making it suitable for use by nursing personnel.

Histologic implications of Pap smears classified as atypical glandular cells.

OBJECTIVE: To evaluate the histologic outcome of Pap smears reported as atypical glandular cells (AGC). STUDY DESIGN: Cervical cytology smears reported as AGC were reviewed and correlated with histologic follow-up. RESULTS: Of a total of 41,500 Pap smears performed at Alexandra Hospital during 2000-2002, 113 (0.2%) were reported as AGC. Of these, 64 were classified as AGC not otherwise specified (NOS) (56.6%), 48 AGC favor neoplasia (42.5%) and 1 (0.9%) adenocarcinoma in situ. All these women underwent histological evaluation. The mean age of the patients was 52 years. Significant abnormality was found in 30 women (26.5%). Eleven percent of women with smears reported as AGC NOS and 45.8% of those with AGC favor neoplasia had significant abnormality. Of these patients, 14 (12.4%) had endometrial involvement, whereas cervical abnormalities were identified in the remaining 16 (14.1%). Older women were more likely to have involvement of the endometrium and younger women, involvement of the cervix. CONCLUSION: Cytologic criteria and patient age might effectively direct the clinician toward the likely origin of AGC.

The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature.

BACKGROUND: There is an emerging interest concerning the role HPV DNA testing in the follow-up period after conservative treatment for cervical intraepithelial neoplasia. METHODS: A MEDLINE and EMBASE search was done (1985 to March 2002), using the keywords HPV/HPV DNA, together with CIN, follow-up, recurrence and LLETZ. References of retrieved articles were also screened. Selection criteria were original published English-language reports of prospective or retrospective studies, including women with an initial diagnosis of cervical intraepithelial neoplasia, who received conservative surgical treatment and were followed with HPV DNA testing in addition to cytology, colposcopy and/or biopsy); the latter methods were used for verification of residual or recurrent disease. RESULTS: There is a marked heterogeneity in the design, population, intervention and follow-up policy across different studies. The sensitivity of HPV DNA testing in detecting treatment failures was quite good in most studies, reaching 100% in four of them, whereas the specificity of the test differed across the studies, ranging from 44% to 95%. Among women in whom the treatment was considered to be successful, 84.2% had a negative postoperative HPV DNA test and 15.8% a positive one. The corresponding rates for cases with treatment failures were 17.2% and 82.8%, respectively. CONCLUSIONS: It seems that a positive HPV test, even in the presence of normal cytology, may pick up early and accurately a treatment failure. Cytology and colposcopy may still be needed in order to rule out false positive and false negative results. MINI-ABSTRACT: A systematic review of studies concerning HPV DNA testing in the follow-up period after conservative treatment for cervical intraepithelial neoplasia indicates that a positive HPV test, even in the presence of normal cytology, may pick up early and accurately a treatment failure. Cytology and colposcopy may still be needed in order to rule out false positive and false negative results.

Laser CO(2) conization: a safe mode of treating conservatively microinvasive carcinoma of the uterine cervix.

OBJECTIVE: To evaluate the outcome of conservative treatment by laser CO(2) conization, for the management of microinvasive carcinoma of the uterine cervix (MIC). STUDY DESIGN: From 1990 to 1999, 90 women with the diagnosis of MIC were treated in the Gynecological Oncology Unit of "Alexandra" Hospital. Final diagnosis of MIC was based on cervical conization as well as simple and radical hysterectomy specimens. The cytological and colposcopical diagnoses prior to conization were reviewed. The cone specimen parameters examined by the pathologists were depth and width of invasion, lymph-vascular space invasion (LVSI) and surgical margins status. The modality used for all conizations, either primary or secondary, was the laser CO(2) under local anaesthesia. RESULTS: Diagnosis of MIC was made on cone biopsy in 73 women (81%), in simple hysterectomy in 10 (11%) and in radical hysterectomy specimens in 7 (8%). From the patients that underwent conization, two (2.5%) were detected with LVSI. Five patients (7%) were found to have involved margins and from those, the majority was managed by a second conization. Mean follow-up time was 54 months (range: 30-110 months). Four patients (6.6%) with recurrence were observed during follow-up, all of them with LSIL. No cases of invasive disease or HSIL were encountered. CONCLUSIONS: Laser CO(2) conization is a safe and effective mode of treatment for women suffering from MIC and wish to retain their fertility. However, this type of management should be advocated only in cases fulfilling the strict criteria for MIC as these have been defined by FIGO.

Tubo-ovarian abscesses in postmenopausal women: gynecological malignancy until proven otherwise?

OBJECTIVE: To investigate the incidence of gynecological malignancy in menopausal women who develop tubo-ovarian abscesses (TOAs), and to address the differences in presentation and underlying pathology between premenopausal and postmenopausal women with TOAs. STUDY DESIGN: In a retrospective study we included 93 patients with a diagnosis of a TOA and compared a premenopausal group (group 1) with a postmenopausal group (group 2). RESULTS: Group 1 included 76 (82%), and group 2 17 (18%) patients. Abdominal pain and pyrexia >38 degrees C were present in 93 and 74% cases of group 1, and in 71 and 41% cases of group 2 (P=0.016 and 0.019, respectively). Irregular vaginal bleeding and gross ascites were significantly more frequent in group 2. With respect to benign additional pathology we found no differences between the two groups. On the contrary a significant association between TOAs in menopause and malignancy was established. In 8 (47%) postmenopausal cases a concomitant gynecological malignancy was found including a variety of cancers. CONCLUSION: Postmenopausal women presenting with TOAs, should be thoroughly investigated to exclude a concomitant pelvic malignancy. Conservative treatment of TOAs has no place during the menopause.

Management of ureteric injuries during gynecological operations: 10 years experience.

OBJECTIVE(S): To present our 10 years experience in the management of ureteric injuries occurring during gynecological surgery. STUDY DESIGN: Seventy-six patients had a variety of injuries. In 29 cases, the ureteric damage was diagnosed intraoperatively. Management of early-diagnosed injuries included suturing, ligature removal, end-to-end anastomosis, and reimplantation of the ureter. In 47 cases, the injury was diagnosed postoperatively. Ureteric catheterization was attempted in all cases presenting with obstruction. Catheterization failures were managed with ureterolysis, and reimplantation. Small ureteric fistula were managed with catheterization, and large communications with reimplantation. Two cases with urinomas were treated with surgical evacuation and anastomoses. RESULTS: Management of early-diagnosed injuries was relatively easy in most cases. Postoperatively-diagnosed injuries were more difficult to treat. Catheterization failed in 28/44 (65.9%) ureters and surgical re-exploration was necessary. Long-term morbidity was minimal and no relapses occurred. CONCLUSION(S): Early recognition of a ureteric injury is the key to a complications-free repair. Unrecognized injuries cause prolonged morbidity, and their management can be difficult. Treatment of these injuries by experienced teams may minimize long-term consequences.

Negative cone biopsies. A reappraisal.

OBJECTIVE: To analyze the incidence of negative cone biopsies and evaluate the significance of the findings. STUDY DESIGN: The study population consisted of women who underwent cervical conization at a university teaching hospital from February 1996 to December 2001. Three modalities were used for conization: CO2 laser, large loop excision of the transformation zone and needle excision of the transformation zone. Negative cones were defined as those not showing evidence of human papillomavirus infection, intraepithelial neoplasia of squamous or glandular origin, or invasive disease. RESULTS: During the study period, 817 conizations were performed. Of these, 206 (25%) were negative. Less than half the patients (41.7%) had a punch biopsy that matched the subsequent cone biopsy specimen. The negative cone rate in women with a punch biopsy showing cervical intraepithelial neoplasia (CIN) 1 was 60% in contrast with those who had a biopsy indicating CIN 2-3; the latter percentage was 16.5%, and the difference was statistically significant. CONCLUSION: Close adherence to international guidelines during workup of an abnormal smear, meticulous colposcopy performed by a certified colposcopist and careful evaluation of punch biopsies by pathologists might help to decrease the negative cone rate.

Empty follicle syndrome associated with ovarian torsion in an in vitro fertilization program.

We report a very rare case of ovarian torsion following controlled ovarian stimulation for in vitro fertilization in which no oocytes were obtained at the time of ovum retrieval from the left torsed ovary. The patient was a 33-year-old nulligravida female undergoing controlled ovarian stimulation. On day 14, the patient complained of lower left abdominal pain with nausea. Transvaginal oocyte retrieval from the right ovary was performed. The patient subsequently underwent laparoscopy 6 hours following oocyte retrieval. A portion of the left ovary was observed. The ovary was detorsed at the time of laparoscopy followed by peritoneal lavage.

p16 INK4A is a strong biomarker for cervical intraepithelial neoplasia and invasive cervical carcinoma: a reappraisal.

To assess the role of p16( INK4A), bcl-2, and p53 in cervical cancer screening, we conducted a retrospective trial of prospectively collected data. Sixty two women with abnormal Pap smears were subjected to colposcopy and biopsies from any abnormal lesion. Human papillomavirus (HPV)-DNA typing, histology, and immunochemistry for p16(INK4A), bcl-2, and p53 were performed for these women. Histologic diagnosis was that of low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), or cancer in all cases. Human papillomavirus strains were identified in 56 patients (90.3%). All HSIL and invasive cancer cases were HPV positive. p16(INK4A) immunostaining yielded 100% sensitivity, 76% specificity, 61% positive predictive value, and 100% negative predictive value in cancer patients. The corresponding performance indicators for HSIL patients were 75%, 62%, 32%, and 91%. bcl-2 and p53 expression did not correlate with worsening grades of cervical disease. We conclude that p16(INK4A) seems to be a sensitive biomarker of high grade cervical intraepithelial neoplasia and cancer.

Primary malignant mixed mullerian tumor of the vagina immunohistochemically confirmed.

CASE REPORT: We report the case of a 74-year old woman who presented with an ulcerated mass of the vagina. Histology of the tumor showed malignant mixed mullerian tumor (MMMT) with squamous and spindle cell stromal components, associated with high-grade vaginal intraepithelial neoplasia (VaIN 3). Immunohistochemical study of the neoplasm revealed that the malignant stromal tumor was a high-grade leiomyosarcoma. Despite the multimodal therapeutic approach, the patient died within 11 months. CONCLUSION: The vagina is a rare site of presentation of primary MMMTs and the present case is the second one immunohistochemically confirmed.

Coexistence of verrucous and squamous carcinoma of the vulva.

AIM: To evaluate the coexistence of verrucous and squamous carcinoma of the vulva and to assess the clinical course, survival and rate of recurrent disease of these patients. METHODS: The records of 17 patients who were diagnosed with verrucous carcinoma of the vulva over a 12-year period were studied retrospectively. Presence of genuine verrucous carcinoma or coexistence of verrucous and squamous carcinoma of the vulva on vulvar biopsies, results of histopathological assessment of final vulva and inguino-femoral node specimens and histological evaluation of recurrent disease specimens were the main outcome measures. RESULTS: Five of the 17 patients (29.5%) initially underwent radical vulvectomy and inguino-femoral lymphadenectomy. Histology of the specimens verified the coexistence of verrucous and squamous carcinomas in four of the five cases. Twelve women (70.5%) underwent simple vulvectomy for genuine verrucous carcinoma; in the final histology, 10 of these women (58.8%) were confirmed as having genuine verrucous carcinomas while two (11.7%) were found to have both verrucous and squamous carcinomas and were further managed by lymphadenectomy. None of our patients died of the disease. Three women (17.5%) presented with local relapse of the tumour, and were managed by wide local excision of the tumour. CONCLUSIONS: In the present study, 35% of patients with verrucous carcinomas of the vulva had coexistent squamous carcinoma. Separation of the cases of genuine verrucous carcinoma from coexistent verrucous and squamous tumours is based on the establishment of correct diagnosis by a large and deep vulvar biopsy as well as the meticulous assessment of the specimen by the pathologist. This will result in the decrease of the rate of over- and under-treatment of these patients.

Miliary tuberculous peritonitis mimicking advanced ovarian cancer.

Primary peritoneal tuberculosis is a rare presentation of this disease. It is usually associated with ascites and raised CA-125 levels. Occasionally a pelvic mass may be present making the preoperative differential diagnosis from advanced ovarian cancer extremely difficult. Acid-fast stains and special cultures of the ascitic fluid for Mycobacterium tuberculosis are frequently negative, and confirmation of the diagnosis commonly requires histologic examination of biopsy specimens, in which epithelioid granulomas with central caseous necrosis can be identified. We present a case of unexplained pyrexial ascites in a postmenopausal woman in whom the diagnosis of miliary peritoneal tuberculosis was confirmed laparoscopically. The role of noninvasive tools such as measurement of ascitic fluid adenosine deaminase levels is also discussed.

Management of early-stage cervical carcinoma by modified (Type II) radical hysterectomy.

OBJECTIVE: . Surgical management of cervical carcinoma by radical hysterectomy has been proven a highly effective method in treating early-stage disease. The purpose of this study was to evaluate the efficacy and safety of modified (Type II) radical hysterectomy for the treatment of early-stage (I-IIA) cervical carcinoma. METHODS: A retrospective analysis of data on 435 patients with cervical carcinoma who were managed by modified radical hysterectomy was performed. In 145 cases a multimodal approach was used due to the presence of one or more risk factors such as lymph node metastasis, CLS involvement, bulky tumor, and exocervical extension of disease. Preoperative irradiation was offered to 62 patients, whereas adjuvant irradiation was offered to 101 patients. RESULTS: The mean age of the patients was 42.5 years. The majority of the patients had squamous cell cancer (81.6%). The patients were clinically staged as IA (3.2%), IB (86.7%), and IIA (10.1%). Positive pelvic lymph nodes were noted in 65 patients (14.9%). Operative morbidity was minimal, whereas adjuvant radiation treatment had no impact on the disease but caused genitourinary morbidity in terms of ureteral stricture and postoperative bladder dysfunction (P < 0.001). The overall 5-year survival was 88.7%. The most significant predictors related to 5-year survival were nodal metastasis (P < 0.001), adenomatous histology (P < 0.001), lesion size (P < 0.001), and CLS involvement (P = 0.004). Adjuvant radiation resulted in better local pelvic control of the disease. CONCLUSION: The results of our study support the concept that less radical procedures could be effectively applied to early-stage cervical carcinoma 4 cm or smaller with optimal surgical margins.

Leptin and body mass index in relation to endometrial cancer risk.

BACKGROUND/AIM: Because leptin is a hormone associated with obesity and reproduction, we attempted to examine whether there is a relationship between leptin and endometrial cancer. METHODS: Cases were 84 women with histologically confirmed incident endometrial cancer, whereas controls were 84 women admitted to the same hospital for small surgical operations. The serum leptin levels were determined in fasting morning blood samples by using radioimmunoassay. The mean values of leptin levels among cases and controls were compared with simple t test, and the data were further analyzed using multiple logistic regression procedures. RESULTS: The serum leptin levels were 36.7 +/- (SD) 25.7 ng/ml among cases and 26.9 +/- 19.8 ng/ml among controls (p = 0.006). After adjustment for known risk factors of endometrial cancer, components of the insulin-like growth factor system did not confound the association of leptin with endometrial cancer, but this association was eliminated, when the body mass index was adjusted for. Thus, the odds ratio for an increment of 1 SD of blood leptin was 1.52 (p = 0.03) before adjustment for body mass index, but only 1.13 (p = 0.62) after adjustment for it. CONCLUSIONS: In a case-control study of incident endometrial cancer in Greece, we found evidence that leptin is strongly positively associated with endometrial cancer. It cannot be conclusively inferred, however, whether leptin elevation, as a consequence of obesity, plays a role in endometrial carcinogenesis or whether it is a simple correlate of obesity.

Treatment of vaginal intraepithelial neoplasia with laser ablation and upper vaginectomy.

To assess the effectiveness of laser ablation and upper vaginectomy in the treatment of vaginal intraepithelial neoplasia (VAIN), we have reviewed the charts of 52 patients managed with laser ablation (28 patients) and upper colpectomy (24 patients). On the basis of our results, patient selection and operator skill have a significant influence on the outcome. In posthysterectomy patients with VAIN(3) at the vaginal apex, in the region of vaginal cuff scar, upper vaginectomy is the treatment of choice, while multifocal VAIN(2-3) or colposcopically well defined lesions, involving large areas of vaginal mucosa, could be successfully managed by CO(2) laser ablation.

Safety and efficacy of locally applied imiquimod cream 5% for the treatment of condylomata acuminata of the vulva.

AIM: The aim of the present study was to assess the efficacy and safety of local application of imiquimod cream 5% for managing condylomata acuminata of the vulva in women referred to a tertiary University Hospital centre. METHOD: From a total of 283 patients referred over a 3-year period, 73(26%) were treated with imiquimod. RESULTS: Approximately 6% failed to continue therapy due to lack of therapeutic effect whereas 71% experienced total clearance of the lesions and 85% reduction of more than 50% in the size of the condylomata. Forty-three percent of the patients observed complete response in the first 6 weeks of therapy. There were no serious adverse events encountered with mild erythema being the commonest. From the patients who were followed-up for the next 12 weeks from the completion of treatment, 13% presented recurrent warts and were managed by a different mode of therapy. CONCLUSION: Imiquimod cream 5% seems to be an effective and safe method for treating condylomata acuminata of the vulva resulting possibly in lower recurrence rates than other current therapies.