Lene Lundvall

Botulinum Toxin Type A—A Novel Treatment for Provoked Vestibulodynia? Results from a Randomized, Placebo Controlled, Double Blinded Study

INTRODUCTIONnVestibulodynia is an increasingly recognized problem among women and is often difficult to treat.nnnAIMnThis randomized, double blinded, placebo-controlled study aimed to evaluate the efficacy of Botox in the treatment of vestibulodynia.nnnMETHODSnSixty-four women were randomized to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline.nnnMAIN OUTCOME MEASURESnPain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale at baseline and at 3 and 6 months follow up. Quality of life was measured using the 36-item short-form (SF-36).nnnRESULTSnSixty women (94%) completed the 6 months follow up. Both Botox and placebo produced significantly pain reduction (P < 0.001). There was no significant difference in the median VAS score between the groups at 6 months follow up (P = 0.984). An improvement on the FSFI full score from baseline until 6 months was not significantly different between the groups (P = 0.635). In the placebo group a statistical significant larger reduction in sexual distress was observed from baseline until 6 months follow up compared to the Botox group (P = 0.044). No statistical significant differences were observed between the B- and P-groups in regard to the SF-36 scores.nnnCONCLUSIONnInjection of 20 I.E. Botox in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months follow up. Women with vestibulodynia have difficulty with sexual function and present with sexual distress, which has to be addressed in conjunction with pain to eliminate the disorder.

The effect of accelerated rehabilitation on recovery after surgery for ovarian malignancy

Background. In patients undergoing colonic surgery the postoperative hospital stay has been reduced from 8–12 days to 2–4 days with multimodal rehabilitation programs. The aim of this study was to evaluate the postoperative outcome after surgery for ovarian malignancy with conventional care compared to fast‐track multimodal rehabilitation. Methods. Seventy‐two consecutive patients receiving conventional care (group 1) were compared with 69 consecutive patients receiving multimodal, fast‐track rehabilitation with a planned care program including continuous epidural analgesia, early oral feeding and mobilization (group 2) in the same department. Outcome was postoperative hospital stay and morbidity during the first postoperative month. Results. Median age was 63 years (group 1) and 62 years (group 2). Median postoperative hospital stay was reduced from 6 days in group 1 (mean 7.3) to 5 days in group 2 (mean 5.4) (p<0.05). There was no difference in the overall complication rate, although severe medical complications were reduced in group 2 (14% versus 2%; p<0.01). Readmission rate was 10% in group 1 and 3% in group 2 (p>0.05). Conclusions. The concept of fast‐track multimodal rehabilitation appears to be beneficial in patients operated for ovarian malignancy, as hospital stay and medical morbidity are reduced.

Does the use of diagnostic PET/CT cause stage migration in patients with primary advanced ovarian cancer?

OBJECTIVEnTo investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT.nnnMETHODSnFrom September 2004 to August 2007, 201 patients with a Risk of Malignancy Index (RMI) >150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic tumor. On 15 August, 2009 overall survival and prognostic variables were analysed in 66 ovarian cancer patients (64 stage III and 2 stage IV).nnnRESULTSnMedian follow-up was 30.2 months; median age was 62.5 years (range 35-85 years); 97% (64/66) had a performance status <or=2; 38% (25/66) underwent complete debulking (no macroscopic residual tumor); 51% (39/66) was diagnosed with PET/CT stage III and 41% (27/66) was diagnosed with PET/CT stage IV. Survival was significantly longer for patients with PET/CT stage III than for patients with PET/CT stage IV (P=0.03). Using univariate analysis, PET/CT stage III (P=0.03), complete debulking (no macroscopic residual tumor) (P=0.002), and GOG performance status <or=2 (P=0.04) were statistically significant prognostic variables. Using multivariate Cox regression analysis, complete debulking was the only statistically significant independent prognostic variable (P=0.02).nnnCONCLUSIONnIn primary advanced ovarian cancer the use of diagnostic FDG-PET/CT leads to stage migration. Adequate staging is the foundation for ovarian cancer treatment and advanced imaging for optimal evaluation of metastases should be promoted in clinical trials. The strongest determinant of patient outcome is residual abdominal tumor after primary surgery.

Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology.

Objective. To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. Methods. A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at −80° until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry. Results. Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann–Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z = 2570.21), collagen alpha 1 (III) fragment (m/z = 2707.32) and fibrinogen beta NT fragment (m/z = 4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96. Conclusion. This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.

Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

Abstract Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From September 2004 to August 2007, 201 consecutive patients with a pelvic tumor and a Risk of Malignancy Index (RMI) > 150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within two weeks prior to standard surgery/debulking of a pelvic tumor. At two-year follow-up (August 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35–85 years); 97% (58/60) had a performance status ≤2; 42% (25/60) underwent complete debulking (no macroscopic residual tumor); median SUVmax was 13.5 (range 2.5–39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUVmax in patients alive was not statistically different from SUVmax in dead patients (p=0.69), and SUVmax was not correlated with the amount of residual tumor after surgery (p=0.19). Using univariate Cox regression analysis, residual tumor was a significant prognostic variable (p=0.001); SUVmax was not a statistically significant prognostic variable (p=0.86). Discussion. FDG uptake (SUVmax) in the primary tumor of patients with advanced ovarian cancer was not a prognostic variable and the FDG uptake did not predict complete cytoreduction after primary surgery. Future prospective clinical trials will need to clarify if other PET tracers can serve as prognostic variables in ovarian cancer.

Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: A randomized trial

Objective. To determine which treatment should be offered to women with a non‐ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. Design. Prospective, randomized, open multicenter study. Setting. Seven Danish departments of obstetrics and gynecology. Sample. A total of 106 women diagnosed with ectopic pregnancy (EP). Methods. Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were randomized to either medical (MTX; 53) or surgical (laparoscopic salpingotomy; 53) treatment. Follow‐up by questionnaire and through national patient databases for a maximum of 10 years. Main outcome measures. Uneventful decline of plasma‐human chorionic gonadotropin to less than 5 IU/L, rates of spontaneous, subsequent intrauterine, and recurrent ectopic pregnancies. Results. The success rates were 74% following MTX treatment and 87% after surgery (n.s.); the subsequent spontaneous intrauterine pregnancy rate was 73% after MTX and 62% after surgery; and the EP rate was 9.6% after MTX and 17.3% following surgery (n.s.). Conclusions. In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment modalities seemed to be similar in outcome, it is crucial that the diagnosis is based on a high‐quality ultrasonographic evaluation, as two patients had intrauterine pregnancies despite fulfilling the diagnostic algorithm for EP.

Vulvodynia. Definition, diagnosis and treatment

Vulvodynia is a chronic painful disorder with an estimated prevalence of 9–12%. A rising incidence of the condition constitutes a growing problem. This has lead to an increased focus on etiology and treatment, while the definition also requires attention. Previous assumptions stating that the problem is solely a psychological disorder have been abandoned, because inflammatory mechanisms and genetic factors have been found to be involved in the pathogenesis as well as psychosexual contributors.

Comparison between abnormal cytology, colposcopy and histopathology during pregnancy

During a 3 year period, 35 pregnant woman with grade III or IV cytological changes found at pregnancy control were followed during pregnancy and up to 4 years after delivery. These 35 patients constitute 0.35% of all the pregnant women admitted for antepartum consultation. Complete regression of dysplasia was seen in one third of the patients. The patients were followed with colposcopy and sometimes punch biopsy and the decision regarding final treatment was postponed until 8 weeks after delivery. No invasive lesion was found, and no recurrences or invasive lesions were found at follow up. It is concluded that cytology and colposcopy with punch biopsy on suspicion of early invasion is an adequate control procedure during the pregnancy at intervals of 2–3 months.

Surgical‐site infections and postoperative complications: agreement between the Danish Gynecological Cancer Database and a randomized clinical trial

Objective. Surgical‐site infections are serious complications and thorough follow‐up is important for accurate surveillance. We aimed to compare the frequency of complications recorded in a clinical quality database with those noted in a randomized clinical trial with follow‐up visits. Design. Evaluation study. Setting. Danish Gynecological Cancer Database (DGCD) and the Danish multicenter trial on perioperative oxygen and surgical‐site infections (PROXI). Sample. Paired data from 222 patients who participated in the PROXI trial taking place at Copenhagen University Hospital, Rigshospitalet between November 2006 and October 2008 and data from the DGCD. Methods. Outcomes within 30 days from the trial and the database were compared and levels of agreements were calculated with kappa‐statistics. Main Outcome Measures. Primary outcome was surgical‐site infection. Other outcomes included re‐operation, urinary tract infection, pneumonia and sepsis. Results. Surgical‐site infection was found in 21 of 222 patients (9.5%) in the PROXI trial versus 6 of 222 patients (2.7%) in the DGCD (p < 0.01, kappa 0.42). Twelve of 15 superficial and three of six deep or organ‐space surgical‐site infections were registered in the PROXI trial, but not in the DGCD. Agreements between secondary outcomes were very varying (kappa‐value 0.77 for re‐operation, 0.37 for urinary tract infections, 0.19 for sepsis and 0.18 for pneumonia). Conclusions. The randomized trial reported significantly more surgical‐site infections than the clinical database. The DGCD reported only 50% of the deep and organ‐space infections, and hence, the low‐overall agreement indicates a need for more careful database registration.

Diagnostic accuracy of risk of malignancy index in predicting complete tumor removal at primary debulking surgery for ovarian cancer patients

Ovarian cancer patients in whom complete tumor removal is impossible with primary debulking surgery (PDS) may benefit from neoadjuvant chemotherapy and interval debulking surgery. However, the task of performing a pre‐operative evaluation of the feasibility of PDS is difficult. We aimed to investigate whether the risk of malignancy index (RMI) was a useful marker for this evaluation. RMI and surgical outcome were investigated in 164 patients, 49 of whom had no residual tumor after PDS. The receiver operating characteristic curve showed an area under the curve of 0.72 (confidence interval: 0.64–0.80). The possibility of complete tumor removal decreased with increasing RMI and there was a tendency towards higher RMI in patients with residual tumor after PDS, but no single cut‐off value of RMI produced useful clinical predictive values. In conclusion, RMI alone is not an optimal method to determine whether complete tumor removal is possible with PDS.