Liselotte Mettler

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery

BACKGROUND Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringers solution (LRS). METHODS Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Long-term treatment of atrophic vaginitis with low-dose oestradiol vaginal tablets

Fifty-one post-menopausal women suffering from symptoms of oestrogen deficiency-derived atrophic vaginitis were treated intravaginally with two therapeutic regimens based on doses of 25 micrograms 17 beta-oestradiol (E2) in an open, controlled study. All the patients received treatment daily for 2 weeks by way of induction therapy. They were then randomly allocated to either once-weekly (17 patients) or twice-weekly (34 patients) vaginal administration for a further 50 weeks as maintenance treatment. Endometrial histopathology was evaluated before and after 1 year of treatment. The effects on symptoms and oestrogen/gonadotrophin levels were determined before and after 2, 12, 24, 36 and 52 weeks of therapy. Nine women continued twice-weekly treatment for a further year, meaning that they underwent treatment for a total period of 2 years. Endometrial biopsies were obtained after 2 years of treatment. All the pretreatment endometrial biopsies indicated an atrophic endometrium. One patient out of the 14 who completed 1 year of therapy in the group treated once weekly showed weak proliferation of the endometrium, while the other 13 had an atrophic endometrium. In the group treated twice weekly, 2 out of the 31 patients who completed the study showed weak proliferation of the endometrium. The other 29 had an atrophic endometrium. All 9 women who received treatment for 2 years had an atrophic endometrium at the end of the treatment period. The twice-weekly dosage regimen gave complete relief of symptoms in almost all patients, whereas the majority of the patients in the group treated once weekly still had mild symptoms. No adverse effects were reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Macrophage‐ and lymphocyte‐subtypes in the endometrium during different phases of the ovarian cycle

The presence of immunocompetetive cells in the endometrium during the proliferative and secretory phase of the ovarian cycle is demonstrated on the light and electron microscopic level using monoclonal antibodies (MoAb). Subtypes of monocytes, macrophages and T‐lymphocytes appear during the different phases in variable extent and different localization. Some subpopulations of the monocyte/ macrophage system and T‐helper lymphocytes increase in number on day 21/22. Our observations indicate that cells with bone marrow origin take part in functional events of the endometrium during the ovarian cycle.

Laparoscopic myomectomy focusing on the myoma pseudocapsule: technical and outcome reports

BACKGROUND Our aim was to assess surgical complaints and reproductive outcomes of laparoscopic intracapsular myomectomies by a prospective observational study run in University affiliated hospitals. METHODS Between 2005 and 2010, 235 women underwent subserous and intramural laparoscopic myomectomy of fibroids (4-10 cm in diameter) for indications of pelvic pain, menstrual disorders, a large growing myoma or infertility. The main outcome measures were post-surgical parameters, including complications, the need for subsequent surgery or symptomatic relief, resumption of normal life and reproductive outcome. RESULTS Pelvic pain occurred in 27%, menorrhagia or metorrhagia in 21%, a large growing myoma in 10% and infertility in 42% of women. Single fibroids occurred in 51.9% of patients while 48.1% had multiple myomas. Of all patients, 58.2% had subserosal and 41.8% had intramural myomas. No laparoscopies were converted to laparotomy. In 3 years, 1.2% of patients had a second laparoscopic myomectomy for recurrent fibroids. The mean total operative laparoscopic time was 84 min (range 25-126 min), with mean blood loss of 118 ± 27.9 ml. By 48 h after surgery, 86.3% were discharged with no major post-operative complications. No late complications, such as bleeding, urinary tract infections or bowel lesions, occurred. Of the women who underwent myomectomy for infertility, 74% finally conceived. At term, 32.9% of patients underwent Caesarean section, 24.8% delivered by vacuum extractor and 42.2% had spontaneous deliveries. No case of uterine rupture occurred. CONCLUSIONS Intracapsular subserous and intramural myomectomy saving the fibroid pseudocapsule showed few early and no late surgical complications, enhanced healing by preserving myometrial integrity and allowed a good fertility rate and delivery outcome. In young patients suffering fibroids, laparoscopic intracapsular myomectomy is a potential recommended surgical treatment.

Treatment of female infertility due to tubal obstruction by operative laparoscopy.

The advent in recent years of safe endocoagulation (thermocoagulation within the abdomen) has permitted operative laparoscopic treatment of the tubal factor in infertility in selected cases. This paper reviews the results of operative laparoscopy in 223 cases treated for infertility between 1971 and 1976. Tubal occlusion was present in 133 patients before surgical intervention. Following operative laparoscopy, tubal patency was demonstrated in 67% on testing at the time of operation and in 12% at the first postoperative hydrotubation. In only 21% of cases was tubal patency not achieved by these methods. Those cases requiring isthmic salpingostomy, ampullary or isthmic-tubal implantation, or end-to-end anastomosis were further treated by laparotomy and microsurgery. Ninety cases of pelvic endometriosis were treated by a combination treatment of thermocoagulation, ovarian cyst resection, and the antigonadotropin agent, danazol. Ovariolysis, salpingolysis, fimbrioplasty, and salpingostomy can easily be performed using operative laparoscopy as the method of choice with a minimum of complications, shortened hospitalization time (2 days), and the potential for a repeat procedure or a follow-up laparotomy should this be necessary. The pregnancy rate following laparoscopic treatment for the correction of distal tubal occlusion was 30.5% and for endometriosis genitalis externa, 40%. These rates compare favorably with the rates following procedures involving laparotomy and microsurgery for correction of similar lesions.

Principles and safety measures of electrosurgery in laparoscopy.

This report stresses that a thorough knowledge of electrosurgical fundamentals by the entire operative team is essential for patient safety and recognizing potential complications.

Adhesion formation after intracapsular myomectomy with or without adhesion barrier.

OBJECTIVE To show the prevention of adhesion formation by placing an absorbable adhesion barrier after intracapsular myomectomy. DESIGN Prospective blinded observational study. SETTING University-affiliated Hospitals. PATIENT(S) Patients ≥ 18 years old with single or multiple uterine fibroids removed by laparoscopic or abdominal intracapsular myomectomy. INTERVENTION(S) A total of 694 women undergoing laparoscopic or abdominal myomectomy were randomized for placement of oxidized regenerated cellulose absorbable adhesion barrier to the uterine incision or for control subjects without barriers. The presence of adhesions was assessed in 546 patients who underwent subsequent surgery. MAIN OUTCOME MEASURE(S) The primary and secondary outcomes of the analysis were the presence and severity of adhesions for four groups: laparotomy with barrier, laparotomy without barrier, laparoscopy with barrier, and laparoscopy without barrier. RESULT(S) There was a higher rate of adhesions in laparotomy without barrier (28.1%) compared with laparoscopy with no barrier (22.6%), followed by laparotomy with barrier (22%) and laparoscopy with barrier (15.9%). Additionally, the type of adhesions were different, filmy and organized were predominant with an adhesion barrier, and cohesive adhesions were more common without an adhesion barrier. CONCLUSION(S) Oxidized regenerated cellulose reduces postsurgical adhesions. Cohesive adhesions reduction was noted in laparoscopy.

Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis)

Problem: As recent studies have suggested abnormalities in the regulation of specific genes in the development of endometriosis, we investigated differentially expressed genes in endometriosis compared to endometrium. Method of study: Gene expression profiles using the Atlas microarray were performed in endometriotic tissue and endometrium. Nine of the 13 genes of endometriotic tissue showed an up-regulation in relation to endometrium and four of the 13 genes a down-regulation. Results: Of the 1176 genes on the Atlas Human 1,2 array, only 13 differentially expressed identical genes were detected after repeating the gene analysis three times. Conclusion: According to our c-DNA analysis some differentially expressed genes may be involved in the pathogenesis of endometriosis. An imbalance in the genes responsible for the reproductive process may lead to a decrease in embryo implantation in patients with endometriosis.

Clinical diagnosis and treatment of ectopic pregnancy.

Background Implantation of the zygote outside the uterine cavity occurs in 2% of all pregnancies. The product of conception can be removed safely by laparoscopic surgery and be submitted for histological examination. The rate of ectopic pregnancies has increased from 0.5% in 1970 to 2% today. The prevalence of ectopic pregnancy in all women presenting to an emergency department with first-trimester bleeding, lower abdominal pain, or a combination of the 2 is between 6% and 16%. Designation Workup of all localizations of ectopic pregnancies at a university department of obstetrics and gynecology. Methods Comparison of diagnostic and therapeutic modalities from the surgical laparoscopic approach to nonsurgical, medical options. Findings Surgical treatment: Tubal pregnancies: (1) to preserve tubal function, salpingotomy, partial salpingectomy followed by laparoscopic anastomosis, or fimbrial milking is performed. (2) Tubectomy or salpingectomy is performed only in severely damaged or ruptured tubes or if the patient does not desire further pregnancies. Nontubal ectopic pregnancies (ovarian pregnancy, ectopic abdominal pregnancy, interstitial or cornual pregnancy/rudimentary horn, intraligamental and cervical pregnancies) all require their own specific treatment. Medical treatment The predominant drug is methotrexate, but other systemic drugs, such as actinomycin D, prostaglandins, and RU 486, can also be applied. Complications Tubal rupture is a complication of late diagnosed tubal pregnancy that is more difficult to treat conservatively and often indicates tubectomy or segmental resection. In 5% to 15% of treated ectopic pregnancy cases, remnant conception product parts may require a final methotrexate injection. Conclusions This article is a review to aid clinical diagnosis of ectopic pregnancies that now can be diagnosed earlier and treated effectively by laparoscopic surgery. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, obstetricians and gynecologists should be better able to diagnose ectopic pregnancy in its early stages to provide safe treatment, choose the appropriate treatment for patients with ectopic pregnancy, and identify the role that human chorionic gonadotropin plays in ectopic pregnancy.

Combined Surgical and Hormone Therapy for Endometriosis is the Most Effective Treatment: Prospective, Randomized, Controlled Trial

STUDY OBJECTIVE To evaluate 3 therapy strategies: hormone therapy, surgery, and combined treatment. DESIGN Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING University-based teaching hospital. PATIENTS Four hundred fifty patients with genital endometriosis, aged 18 to 44 years, before first laparoscopy. INTERVENTIONS Patients were randomly assigned to 1 of 3 treatment groups: hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focussed on the endometriosis stage, recurrence of symptoms, and pregnancy rate. MEASUREMENTS AND MAIN RESULTS All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of ≥50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. CONCLUSION In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group.