First trimester diclofenac exposure and pregnancy outcome.

OBJECTIVE: To assess the safety of diclofenac during pregnancy. METHODS: A prospective observational cohort study, evaluating follow-up data of women who contacted Teratology Information Services to get counseling. The exposed group included 145 pregnant women who were exposed to diclofenac between the 5th and the 14th gestational week. A contemporary control group (501 women) was randomly selected from among patients who contacted Teratology Information Services with regard to exposures to agents known not to be teratogenic during a similar period of pregnancy. RESULTS: Major birth malformations were not more common in the study group than in the control group (p=0.07). CONCLUSION: Our study suggests that the use of diclofenac is relatively safe during the first trimester of pregnancy and the studied sample size makes it possible to exclude a risk of congenital malformation higher than 3.3, with a power of 80%.

Compliance to surgical and radiation treatment guidelines in relation to patient outcome in early stage endometrial cancer.

RATIONALE, AIMS AND OBJECTIVES: We evaluated the adherence to treatment guidelines in early stage endometrial cancer and the influence of adherence to guidelines on overall survival. METHOD: Patients were identified in the central region in the Netherlands from 1990 till 1995. Patient and tumour characteristics, surgical findings, radiation and follow-up data were abstracted from medical records. Endpoint was overall survival. Kaplan-Meier method was used to perform time-to-event analysis. Hazard ratios for overall survival were estimated with a Cox Proportional Hazards model. RESULTS: 359 patients were eligible for analysis. 335 patients presented with a clinical stage I cancer. 333 patients underwent a Total Abdominal Hysterectomy with Bilateral Salpingo Oophorectomy (TAH/BSO), of which 301 were staged as International Federation of Gynaecology and Obstetrics (FIGO) stage I, whereas 34 (10.2%) as FIGO stage II. Of the 24 patients with a clinical stage II cancer, 12 underwent a Radical Hysterectomy with Pelvic Lymph Node Dissection (RH/PLND), of which seven were diagnosed with FIGO stage II. In 72.1% of the patients adjuvant radiation was given or not in adherence to the guidelines. Whether treatment was given according to the guidelines or not did not affect 5 years overall survival. CONCLUSION: This suggests that extensive surgical procedures are redundant in the treatment of occult stage II endometrial cancer.

Recurrent cervical cancer: detection and prognosis.

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.

Recurrent cervical cancer: detection and prognosis.

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.

The prognostic value of immunohistochemically detected CD44v3 and CD44v6 expression in patients with surgically staged vulvar carcinoma: a multicenter study.

BACKGROUND: Isoforms of the adhesion molecule CD44 are involved in carcinogenesis and the metastatic cascade of tumor cells by increasing the affinity of malignant cells to their extracellular matrix. Preliminary data with respect to the prognostic value of the CD44 isoforms CD44v3 and CD44v6 in patients with vulvar carcinoma showed promising results. The current multicenter study aimed to determine the prognostic value of CD44v3 and CD44v6 in patients with surgically staged vulvar carcinoma. METHODS: Expression of CD44v3 and CD44v6 in vulvar carcinoma tissue was assessed by immunohistochemistry. Immunohistochemical staining was performed according to established protocols. Results were correlated to clinical data. RESULTS: A positive CD44v3 and CD44v6 staining was detected in 33.3% (33 out of 99) and 39.4% (39 out of 99) of the tumor samples, respectively. Overexpression of CD44v6 was associated with an impaired prognosis with respect to disease-free survival (P = 0.01) and overall survival (P = 0.04). Multivariate analysis showed that CD44v6 provided prognostic information with respect to disease-free survival (P = 0.001) and overall survival (P = 0.005) independently of the two established prognosticators, tumor stage and groin lymph node involvement. Overexpression of CD44v3 had no impact on patient survival. CONCLUSIONS: The current multicenter study, involving a large series of patients with surgically staged vulvar carcinoma, allowed for multivariate survival analysis and showed that CD44v6 confers prognostic information in addition to that provided by the established clinicopathologic parameters of tumor stage and lymph node status.