Ulipristal acetate vs gonadotropin-releasing hormone agonists prior to laparoscopic myomectomy (MYOMEX trial): Short-term results of a double-blind randomized controlled trial.

INTRODUCTION: Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes. MATERIAL AND METHODS: We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease. RESULTS: Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa. CONCLUSIONS: Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters.

Open versus laparoscopic pelvic lymph node dissection in early stage cervical cancer: no difference in surgical or disease outcome.

OBJECTIVE: This study aimed to investigate in a retrospective study the effect of laparoscopic surgery, introduced in our center in 1994 as part of the standard treatment of early stage cervical cancer, on surgical and disease outcomes. PATIENTS AND METHODS: A total of 169 women with cervical carcinoma stage IB1 (n = 150) or IB2 (n = 19) were included in the study. Seventy-six patients who underwent laparoscopic pelvic lymph node dissection (LPLND), followed either by open radical hysterectomy (n = 63) or, in case of positive lymph nodes, by primary chemoradiation (n = 13), were compared with an historic cohort of 93 patients who underwent a fully open, traditional Wertheim-Meigs procedure (WM). Recorded clinical characteristics of patients included age, International Federation of Gynecology and Obstetrics stage, histologic diagnosis, differentiation grade, tumor diameter, lymph node status, and adjuvant therapy. Operation time; lymph node yield; intraoperative, early, and late complications; site of recurrences; and disease-free and overall survival rates were analyzed and compared between groups. RESULTS: Clinical characteristics did not differ between groups. Duration of total surgery time was longer in patients with LPLND followed by open radical hysterectomy compared with that in the WM group (P < 0.001). In patients with negative lymph nodes (n = 129), the number of resected nodes was higher (P = 0.002) in the LPLND (median, 26 nodes; range, 8-55 nodes) than in the WM group (median, 21 nodes; range, 7-50 nodes). In patients with positive lymph nodes (n = 40), no significant difference in the number of resected lymph nodes between the 2 groups (P = 0.904) was found. Intraoperative, early, and late complications did not differ between the 2 surgical procedures. The number of locoregional recurrences, but not of distant metastases, was significantly higher (P = 0.018) in the WM group compared with the LPLND group. No difference in disease-free or disease-specific survival was found between the LPLND and WM group, neither with nor without adjuvant or primary (chemo)radiation. A benefit in disease-free survival (P = 0.044), but not in disease-specific survival (P = 0.070), was found in the LPLND compared with the WM group in those patients who received adjuvant therapy or primary chemoradiation. CONCLUSIONS: Introduction of a laparoscopic procedure in the surgical staging and treatment of cervical cancer patients did not have a detrimental effect on surgical or disease outcome, and this can be safely applied to the treatment of early stage cervical cancer.

SCC-Ag, lymph node metastases and sentinel node procedure in early stage squamous cell cervical cancer.

OBJECTIVES: We analyzed pretreatment SCC-Ag levels, lymph node (LN) status and disease outcome in early stage squamous cell (SCC) cervical cancer. METHODS: Serum SCC-Ag was measured before primary treatment in 91 patients (FIGO stage IB1 72, IB2 10, and IIA 9). Of these, 58 underwent laparoscopic sentinel lymph node (SLN) procedure followed by pelvic lymphadenectomy. RESULTS: No false negative SLN were observed. SCC-Ag levels were higher in patients with positive LN compared to patients with negative LN (p=0.010), but no difference was found in the SLN patients (p=0.344). The accuracy to predict LN metastases of SCC-Ag at ROC established cutoff of 1.65 ng/mL and 5.5 ng/mL was 76% and 78%, respectively, in stage IB1, and 53% and 79%, respectively, in stages IB2+ IIA. Whereas no deaths were observed in patients with negative LN and negative SCC-Ag levels (at previously established cutoff of 1.1 ng/mL), overall survival (OS) for patients with negative LN but elevated SCC-Ag was similar to that of patients with positive LN, irrespective of their marker levels (Kaplan-Meier analysis of all patients and in stage IB1, p=0.002 and p=0.026, respectively). CONCLUSIONS: SCC-Ag (>1.65 ng/mL) can predict LN metastases more accurately in stage IB1 than in stage IB2+ IIA. Since SCC-Ag levels above 1.1 ng/mL are already associated with a poor prognosis, the marker seems to identify a subgroup of LN negative patients with occult disease that may benefit from full lymphadenectomy following a SLN procedure.

A combination of serum tumor markers identifies high-risk patients with early-stage squamous cervical cancer.

We aimed to investigate whether pretreatment serum levels of squamous cell carcinoma (SCC) antigen (SCC-Ag), cytokeratin 19 (CYFRA 21-1) and two mucins (CA 15-3 and CA 125) identify patients with occult disease in early-stage SCC of the cervix. Therefore, pretreatment serum samples were obtained from 78 patients with SCC of the cervix (52 IB, 9 IIA and 18 IIB), and tumor markers were measured with commercial immunoassays. SCC-Ag, CYFRA 21-1 and CA 15-3 (analyzed as continuous variables) were significantly associated with overall (OS) and disease-free survival (DFS) in univariate analysis (p < 0.001 in all cases). Multivariate analysis identified lymph node status as the strongest predictor for OS and DFS (p < 0.001 and p = 0.001, respectively), followed by CYFRA 21-1 (p = 0.060 and p = 0.027, respectively) and CA 15-3 (p = 0.082 and p = 0.017, respectively). Clinical cutoff values for each marker were defined by maximizing the log-rank statistics for OS in the total population: 1.1 microg/l for SCC-Ag (n = 47, 60.3%), 1.4 microg/l for CYFRA 21-1 (n = 47, 60.3%), 40 U/ml for CA 15-3 (n = 11, 14.1%) and 30 U/ml for CA 125 (n = 10, 12.8%). Stage IB patients with positive SCC-Ag and CYFRA 21-1 had significantly lower OS (mean 8.3 years, 95% confidence interval, CI, 5.8-10.7 years) and DFS (mean 7.3 years, 95% CI 4.6-10 years) than all other stage IB patients (OS, mean 14.5 years, 95% CI 13.5-15.5 years; DFS, mean 13.9 years, 95% CI 12.5-15.4 years). Stage IB patients with tumors <4 cm or with negative lymph nodes and positive SCC-Ag and CYFRA 21-1 had significantly poorer OS and DFS compared to all other patients in the same group. Elevated levels of both CA 125 and CA 15-3 (3 patients) were associated with an extremely poor prognosis. In conclusion, a combination of SCC-Ag and CYFRA 21-1 may help to identify early-stage cervical cancer patients with occult disease requiring adjuvant therapy.

Residents' perceptions of the ideal clinical teacher--a qualitative study.

OBJECTIVE: The object of this study was to establish what residents in 1994 and 2003 characterised as an ideal clinical teacher and whether differences existed between residents' views in 1994 and 2003. SETTING: postgraduate medical education in the Netherlands. SUBJECTS: 207 obstetric-gynaecologic residents. INTERVENTION: open-ended questionnaire. ANALYSIS: qualitative data analysis with two coding dictionaries based on current literature. Differences between 1994 and 2003 were estimated using the Chi-square test. RESULTS: Residents preferred the 'person' role both in 1994 (42%) and in 2003 (48%). The 'physician' role was significantly more important in 1994 than in 2003; the 'supervisor' role was significantly more important in 2003 than in 1994 (p<0.05). Seventy percent of the comments related to 'direct interaction' (i.e., between residents and clinical teachers), 30% to 'indirect interaction' (i.e., clinical teachers' behaviour affecting residents indirectly). CONCLUSION: The data showed that almost half of residents' comments described 'person' role characteristics. There was a significant shift in the role ranked second, from the physician role in 1994 to the supervisor role in 2003. The findings highlighted that teachers, in order to be perceived as ideal, should adapt their behaviour to residents' learning needs.

Sentinel lymph node detection in early stage uterine cervix carcinoma: a systematic review.

OBJECTIVE: The aim of this study was to systematically review the diagnostic performance of Sentinel Node (SN) detection for assessing the nodal status in early stage cervical carcinoma, and to determine which technique (using blue dye, Technetium-99m colloid (99mTc), or the combined method) had the highest success rate in terms of detection rate and sensitivity. METHODS: A comprehensive computer literature search of English language studies in human subjects on Sentinel Node procedures was performed in MEDLINE and EMBASE databases up to July 2006. For each article two reviewers independently performed a methodological qualitative analysis and data extraction using a standard form. Pooled values of the SN detection rate and pooled sensitivity values of the SN procedure are presented with a 95% confidence interval (95% CI) for the three different SN detection techniques. RESULTS: We identified 98 articles, and 23 met the inclusion criteria, comprising a total of 842 patients. Ultimately, 12 studies used the combined technique with a sensitivity of 92% (95% CI: 84-98%). Five studies used 99mTc-colloid, with a pooled sensitivity of 92% (95% CI: 79-98%; p=0.71 vs. combined technique), and four used blue dye with a pooled sensitivity of 81% (67-92%, p=0.17 vs. combined technique). The SN detection rate was highest for the combined technique: 97% (95% CI: 95-98%), vs. 84% for blue dye (95% CI: 79-89%; p<0.0001), and 88% (95% CI: 82-92%, p=0.0018) for 99mTc colloid. CONCLUSION: SN biopsy has the highest SN detection rate when 99mTc is used in combination with blue dye (97%), and a sensitivity of 92%. Hence, according to the present evidence in literature the combination of 99mTc and a blue dye for SN biopsy in patients with early stage cervical cancer is a reliable method to detect lymph node metastases in early stage cervical cancer.