In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival.

BACKGROUND: Carboplatin and cisplatin, alone or in combination with paclitaxel, have similar efficacies against ovarian cancer (OVCA) yet exhibit different toxicity profiles. We characterised the common and unique cellular pathways that underlie OVCA response to these drugs and analyse whether they have a role in OVCA survival. METHODS: Ovarian cancer cell lines (n=36) were treated with carboplatin, cisplatin, paclitaxel, or carboplatin-paclitaxel (CPTX). For each cell line, IC(50) levels were quantified and pre-treatment gene expression analyses were performed. Genes demonstrating expression/IC(50) correlations (measured by Pearson; P<0.01) were subjected to biological pathway analysis. An independent OVCA clinico-genomic data set (n=142) was evaluated for clinical features associated with represented pathways. RESULTS: Cell line sensitivity to carboplatin, cisplatin, paclitaxel, and CPTX was associated with the expression of 77, 68, 64, and 25 biological pathways (P<0.01), respectively. We found three common pathways when drug combinations were compared. Expression of one pathway ('Transcription/CREB pathway') was associated with OVCA overall survival. CONCLUSION: The identification of the Transcription/CREB pathway (associated with OVCA cell line platinum sensitivity and overall survival) could improve patient stratification for treatment with current therapies and the rational selection of future OVCA therapy agents targeted to these pathways.

Carcinoid tumor of the uterine corpus. A case report.

BACKGROUND: Carcinoid tumors are neoplasms of neuroendocrine origin that rarely affect the genital tract. CASE: A 75-year-old woman underwent hysterectomy and bilateral adnexectomy due to vaginal bleeding and uterine pathology (leiomyoma, cervical low grade squamous intraepithelial lesions and endometrial hyperplasia on ultrasound). Pathologic examination of the specimen disclosed a uterine corpus carcinoid tumor. The patient had been taking tamoxifen for adjuvant treatment of breast cancer diagnosed and treated seven years before. CONCLUSION: A review of the literature revealed one case of carcinoid tumor of the uterine wall. There does not appear to be any relationship between tamoxifen and the carcinoid tumors reported.

Malignant vulvo-vaginal melanoma: a report of 7 cases.

To evaluate the clinical outcome of patients suffering from primary vulvo-vaginal malignant melanoma retrospective review of clinical and pathological data of six patients with vulvar malignant melanoma and one patient with vaginal melanoma was done. Patients were staged using the 1988 FIGO histological classification for vulvar cancer, and the 1992 American Joint Committee on Cancer (AJCC) classification for malignant melanoma of the skin. Clinical features, type of surgery, adjuvant therapy, recurrences, distant metastasis, and survival were recorded. Of 174 primary cancers of the vulva, six were malignant melanomas (3.4%), the second most common cause of vulvar cancer. Within the same period, only one primary vaginal melanoma was detected among 57 primary vaginal cancers (1.7%). The median age of all patients was 71 (range 61-84). We performed different surgical procedures, including a radical local excision of the lesion in the vaginal melanoma, a radical hemivulvectomy in one case, a radical vulvectomy in an other case, and a radical vulvectomy with lymph node dissection en bloc in three cases. According to the 1988 FIGO classification for vulvar carcinomas, three patients were diagnosed as stage I and four as stage III melanomas; and using the 1992 AJCC classification for malignant melanoma of the skin, all patients were staged as stage III. Two out of five patients, with a follow-up longer than two years, continued to live and were disease free at the last check-up (40%): the rest of them (60%) died of disease 2.9 months after the diagnosis of the distant metastasis. Vulvo-vaginal malignant melanomas are neoplasias with a very poor prognosis and a short period of time between the detection of distant metastasis and death. Although treatment is not clear in vaginal melanoma, the most accepted treatment in vulvar melanomas is the radical local excision of the lesion with a homolateral inguinofemoral lymphadenectomy.

Uterine sarcoma: a clinicopathological study of 93 cases.

OBJECTIVE: To evaluate the clinical outcome of patients suffering from primary uterine sarcoma diagnosed and treated in our Hospital. SETTING: Department of Gynecologic Surgery/Gynecologic Oncology, Hospital Universitario Materno-Infantil Vall d'Hebron de Barcelona, Barcelona, Spain. SUBJECTS AND METHODS: A retrospective review from 1967 to 1995 of clinical and pathological characteristics of 93 patients with primary uterine sarcoma was done. Patients were staged using the 1988 FIGO histological classification for uterine cancer. Clinical features, type of surgery, adjuvant therapy, recurrences, distant metastasis, and survival were recorded. RESULTS: Our study included three main histologic types: 44 patients with leiomyosarcoma, 26 patients with endometrial stromal sarcoma, and 18 patients with mixed Müllerian sarcomas. The mean age for all patients was 54.8 years, and the most common symptom was vaginal bleeding. Other clinicopathological features were examined. Although surgery was the most frequent treatment, adjuvant therapies have been analyzed and discussed. The overall three-year survival rate was 67.9% and the overall five-year survival rate was 64.5%. We found statistical differences (p < 0.001) between the stage I survival rate and other stage survival rates. CONCLUSIONS: Uterine sarcoma is an uncommon neoplasia diagnosed in the 6th decade of life. Leiomyosarcoma is the most frequent histologic type (47.3%). Stage I uterine sarcoma has a better prognosis than other stages.

Treatment of cervical intraepithelial neoplasia in a prospective study comparing large-loop excision of the transformation zone, laser vaporization, and knife cone biopsy.

OBJECTIVE: Our aim was to compare cervical intraepithelial neoplasia (CIN) treatment results in the use of large-loop excision of the transformation zone (LLETZ), laser vaporization, and cold-knife cone biopsy. MATERIALS AND METHODS: We included in the study patients with CIN lesions diagnosed at the Hospital Universitario Materno-Infantil Vall d'Hebron and Hospital Clinic i Provincial de Barcelona, Barcelona, Spain, between March 1991 and March 1994. Patients with unsatisfactory colposcopy were excluded from the study. One hundred twenty-three patients were included in this study: 98 patients were compared for LLETZ treatment versus laser vaporization, and 69 CIN3 patients were compared for three treatments: LLETZ, laser vaporization, and knife cone biopsy. Patients were followed at 3-month intervals for at least 1 year. Follow-up included physical examination, cervical Papanicolaou (Pap) smear, cervical colposcopy, and a colposcopically guided biopsy when required. Treatment failure (persistence or recurrence) was defined by the presence of CIN confirmed histologically by a colposcopically guided biopsy. RESULTS: The mean age of patients was 34.1 years. The agreement between histology from the colposcopically guided biopsy and the surgical specimen was 60%, and the kappa coefficient was 40.7% (moderate agreement). Three cases of microinvasive carcinoma were diagnosed in patients whose initial diagnosis was CIN3 on colpobiopsy (4% of invasion in the initial CIN3 group of patients). In a comparison of LLETZ with laser treatment for all CIN grades, the unique independent prognostic factor for persistence-recurrence of the disease was the colposcopic size of the primary lesion (relative risk, 4.9; Cl, 1.33-18.45). CONCLUSIONS: We conclude that the LLETZ procedure for CIN treatment demonstrates an advantage over destructive methods for detection of occult microinvasive and invasive cancer. This process is a simple outpatient technique with the same failure as that of laser vaporization in all CIN grades. In the treatment of CIN3, cold-knife cone biopsy had better cure rates. Close follow-up is required in these patients, because of their risk of developing recurrent CIN or invasive carcinoma.

Squamous cell carcinoma of the vulva stage IA: long-term results.

OBJECTIVE: The aim of this study was to evaluate the risk of metastases to lymph nodes and long-term results of radical and modified radical surgery in patients with a T1 squamous cell carcinoma of the vulva and

Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery.

OBJECTIVE: To evaluate the results of surgical therapy and to specifically compare radical and modified radical vulvar surgery relative to survival, recurrence, metastasis, and complications. METHODS: A retrospective review of 225 patients with primary squamous cell cancer of the vulva was performed. Clinical, pathologic, surgical, and follow-up data were collected from the patient records. All pathology slides were reviewed with a pathologist. Radical surgery included 134 patients treated by the Basset operation. Modified radical surgery accounted for 91 patients with vulvar excision alone (65) or with lymphadenectomy (26) via separate groin incisions. RESULTS: The 5-year recurrence rate was 14%. The overall and disease-free survival rates at 5 years were 76. 1 and 83.4%, respectively. There were no statistically significant differences between the two procedures regarding overall survival, disease-free survival, or the development of recurrence, even after adjusting for stage (P > 0.05). Patients undergoing radical vulvar surgery were more likely to develop surgical complications and sequelae than patients having modified radical surgery, even after adjusting for stage. CONCLUSIONS: Modified radical vulvar surgery is associated with decreased complications and 5-year overall and disease-free survival and recurrence rates similar to those of radical vulvar surgery.

Merkel cell carcinoma of the vulva.

Merkel cell carcinoma is a very rare tumor. This is why it is not known whether this neoplasm behaves differently in the vulvar location than at other sites. We present a patient with a Merkel cell carcinoma assessed with a light optical microscope, immunohistochemistry, and electron microscope. Only eight previous cases have been reported in the literature. We discuss pathologic findings, such as histologic trabecular pattern under the optical microscope and neurosecretory granules (similar to Merkel cell carcinoma of the skin) under the electron microscope. Also discussed are the results of immunohistochemistry for low-molecular-weight cytokeratin, neuron-specific enolase, chromogranin, and Leu 7, and molecular study of N-ras, K-ras, N-myc, and p53 genes. Little is known about Merkel cell carcinoma of the vulva, but it seems to have a more aggressive behavior and poorer prognosis than Merkel cell carcinoma at other sites.