Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Successful response to docetaxel treatment in recurrent ovarian granulosa cell tumor: a case report.

BACKGROUND: Ovarian granulosa cell tumor (GCT) is primarily treated surgically. Treatment for advanced or recurrent disease includes primary or adjuvant chemotherapy. Data about the efficacy of treatment with paclitaxel are limited, without data about the role of docetaxel in treating recurrent GCT. CASE: A 68-year-old patient with Stage IA ovarian GCT diagnosed ten years earlier, presented with a third episode of recurrent disease. Following the first event of recurrent disease, she underwent a second laparotomy followed by BEP chemotherapy. Because of new liver masses, she was treated with paclitaxel, with complete response. Following diagnosis of new liver lesions, third-line chemotherapy with docetaxel was initiated, resulting in stable disease and a PFI of 24 months. CONCLUSION: Docetaxel might be a good alternative for treating recurrent GCT.

HPV-related vulvar intraepithelial neoplasia: outcome of different management modalities.

OBJECTIVE: To evaluate the outcome of various management schemes for HPV-related vulvar intraepithelial neoplasia (VIN, usual type). METHODS: Retrospective chart review of patients with histologically diagnosed grade 2/3-VIN who had at least one year of follow-up. The variables that were collected included patient characteristics, management modalities, and clinical outcome. RESULTS: Fifty patients with a median age of 45 years old were evaluated. The median duration of follow-up was 43.5 months (12-186). Complete response (CR) and partial response occurred in 28 (56%) and 4 (8%), respectively. Nineteen of 28 patients with CR recurred with VIN. Surgical excision yielded higher CR (77%) than did either ablational techniques (21-33%) or topical immunotherapy (33%). CONCLUSION: In this experience, surgical excision for VIN, usual type, resulted in better therapeutic success rates than other treatment modalities. Management schemes should be individualized based on extent of disease and patient compliance.

Doxorubicin levels in the serum and ascites of patients with ovarian cancer.

AIMS: To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs. METHODS: The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin. RESULTS: Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum. CONCLUSIONS: Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.

Expression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta.

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM.

Adjuvant therapy for patients with stage I papillary serous endometrial cancer.

Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer characterized by a high recurrence rate and poor prognosis. Several studies have demonstrated that UPSC has a tendency to manifest with extra-uterine disease, even for tumors which appear to be limited to the endometrium. The data on adjuvant chemotherapy for stage I UPSC are limited, and the available studies are generally under-powered to assess if chemotherapy improves survival. However, we believe that, patients with UPSC should receive complete surgical staging, including omentectomy and peritoneal biopsies, and then until the results of larger series or randomized controlled trials will be available, we feel that combined radiotherapy and chemotherapy is justified for all stage I UPSC.

Cervical cancer in pregnant women: laparoscopic evaluation before delaying treatment.

BACKGROUND: Cervical carcinoma diagnosed during pregnancy generates conflicting concerns between control of malignancy and continuation of pregnancy. CASE: An invasive cervical carcinoma FIGO Stage IB2 was diagnosed in a 33-year-old primigravida during the first trimester of pregnancy. Because the patient strongly desired to preserve her pregnancy, laparoscopic lymphadenectomy was performed at 16 weeks of gestation to determine the extension of disease. Negative lymph node status was found and the patient was counseled about the possibility of proceeding until adequate fetal maturity had been achieved. An elective cesarean section and radical hysterectomy were performed at 36 weeks, followed by postoperative chemoradiation therapy. The clinical and Pap smear follow-up remain normal after four years. CONCLUSION: Pregnant women diagnosed with early stage cervical carcinoma should receive a complete evaluation including lymphadenectomy before considering delayed therapy. This strategy seems to be an acceptable option in well-defined conditions, and offers these patients the possibility of maternity.

Analyses of p53 expression pattern and BRCA mutations in patients with double primary breast and ovarian cancer.

OBJECTIVE: To analyze the somatic pattern of p53 expression and BRCA germline mutation status in Israeli patients with both ovarian (OvCa) and breast cancer (BrCa). METHODS: The study group comprised 43 Israeli patients with OvCa, all of whom had previous primary BrCa. p53 immunohistochemistry (IHC) on all available archival tissues and genotyping for the three predominant Jewish germline BRCA1-2 mutations were carried out. Samples from 64 patients with solitary OvCa and 61 with solitary BrCa were similarly analyzed as controls. RESULTS: p53 expression pattern and the immunopositivity rate were similar in the ovarian and breast tumors within the study group and in the two control groups: positive p53 staining was detected in 68% of ovarian tumors in the study group compared with 71.9% in the controls, and in 19.4% of the BrCa tissues versus 21.3% in the controls. Within the study group, advanced stage OvCa had a higher rate of p53 expression (84%) compared to early stage disease (38.5%) (P = 0.006). This difference was not apparent in the solitary OvCa control group. OvCa in BRCA1-2 mutation carriers from the study group were more likely to display positive p53 staining (79%), especially in tumors diagnosed before the age of 60 (90%) compared with the OvCa of noncarriers (60%), but this difference was statistically insignificant. The p53 expression rate in BrCa samples from the study group was not associated with BRCA1-2 mutation status. CONCLUSIONS: Positive p53 expression, detected by IHC, in OvCa patients with previous primary BrCa is significantly higher in advanced stage disease in BRCA1-2 mutation carriers. There is a higher positive p53 expression somatically in OvCa in BRCA1-2 carriers in whom OvCa was diagnosed before the age of 60 years, although this trend is not statistically significant. These observations suggest that somatic p53 inactivation may be an important event in ovarian tumorigenesis in this subset of patients.

Postpartum chills phenomenon: is it a feto-maternal transfusion reaction?

OBJECTIVE: To examine the theory that the postpartum shivering phenomenon is related to feto-maternal bleed during the third stage of labor. METHODS: One hundred laboring low-risk women who had a normal vaginal delivery were observed for the presence of postpartum chills. The duration of the first and second stages of labor changes in body temperature, maternal and fetal blood types and the use of epidural anesthesia were recorded. Following the delivery maternal blood was examined for the presence of fetal red blood cells using the Kleihauer-Betke stain. RESULTS: Complete data was available in 97 patients. Post-partum chills occurred in 31 of them (32%). Women with and without chills were similar in their maternal and gestational age, the use of epidural anesthesia, and length of second stage of labor. Women with chills delivered smaller babies but the difference did not reach significance. Maternal-fetal blood group incompatibility was significantly more common among shivering than non-shivering women (48% vs. 20% respectively, p=0.006). Kleihauer-Betke test was positive in 11 women. The only two women in this group who experienced chills had maternal-fetal blood group incompatibility. CONCLUSION: Post-partum chills are a common phenomenon. It may be the clinical presentation of feto-maternal transfusion reaction. The small number of positive Kleihauer-Betke tests may reflect its low sensitivity in the detection of small feto-maternal bleeds.

Complete hydatidiform mole and a coexistent viable fetus: report of two cases and review of the literature.

OBJECTIVE: The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. PATIENTS: In this article, we report on the well-documented follow-up of 2 cases of twin pregnancies with complete hydatidiform mole and a viable fetus, both of which ended with the delivery of a normal infant at 41 and 26 weeks of gestation. It is of interest that both pregnancies were achieved following induction of ovulation with hMG/hCG. Since 1977, the year in which complete and partial moles were characterized as distinct pathologic entities, 15 cases (including our 2) have been reported. RESULTS: Persistent GTT developed in eight patients (53.3%) and four patients (27.7%) developed metastatic disease. Seventy-five percent patients with persistent GTT were treated with single-agent chemotherapy. The median gestational age of the patients with subsequent persistent GTT was 34.5 weeks compared to 38 weeks in the patients without persistent GTT. CONCLUSION: Complete hydatidiform mole and coexistent fetus is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic tumor. Based on currently available information, it seems that in the presence of a stable pregnancy, normal karyotype, and a normal sonogram it is reasonable to allow the pregnancy to continue.

Effect of adjuvant therapy on development of diabetes in mouse and man.

Freund's complete adjuvant (CFA) and BCG vaccine modulate the development of type 1 diabetes in animal models. In non-obese diabetic mice, CFA and BCG significantly reduced the proportion developing diabetes compared with controls. Histological examination showed that autoimmune disease still developed but had been diverted to become nondestructive. In a preliminary trial in 17 newly diagnosed, type 1 diabetic patients, intracutaneous administration of 0.1 mL of BCG 1 mg/mL led to clinical remission in 11 (65%)--by week 4 in 6. Remission has been sustained in 3 for 6-10 months. No side-effects were reported. A double-blind trial of BCG is warranted.