Perspectives in adhesion prevention in gynaecological surgery.

Adhesions are a frequent, clinically relevant, and often costly complication of surgery that can develop in any body location regardless of the type of surgical procedure. Adhesions result from surgical trauma inducing inflammatory and coagulation processes and to date cannot be entirely prevented. However, the extent of adhesion formation can be reduced by using good surgical technique and the use of anti-inflammatory drugs, haemostats, and barrier agents. Strategies are needed in the short-, medium- and longer-term to improve the prevention of adhesions. In the short-term, efforts are needed to increase the awareness amongst surgeons and patients about the potential risks and burden of surgically induced adhesions. To aid this in the medium- term, a risk score to identify patients at high risk of adhesion formation is being developed and validated. Furthermore, available potentially preventive measures need to be highlighted. Both clinical and health economic evaluations need to be undertaken to support the broad adoption of such measures. In the longer- term, a greater understanding of the pathogenic processes leading to the formation of adhesions is needed to help identify effective, future treatments to reliably prevent adhesions from forming and lyse existing ones.

Melatonin activity and receptor expression in endometrial tissue and endometriosis.

STUDY QUESTION: Are melatonin receptors (melatonin receptor 1A (MR1A) and melatonin receptor 1B (MR1B)) expressed in human endometrium and endometriotic tissue, and does melatonin affect endometrial cell proliferation? SUMMARY ANSWER: Melatonin receptors are expressed in human eutopic endometrium, endometriomas and peritoneal lesions, although to different extents, and melatonin treatment attenuated estradiol-induced endometrial epithelial cell proliferation in culture. WHAT IS KNOWN ALREADY: Melatonin decreased endometriotic lesion volume in a rat model of endometriosis. Melatonin treatment reduced pain scores in and analgesic use by women with endometriosis. STUDY DESIGN, SIZE, DURATION: Basic science study using human endometrial tissue and an endometrial epithelial cell line. PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurement of melatonin receptor expression (mRNA and protein) in women with surgically confirmed endometriosis (endometrioma (n = 20) or peritoneal lesion (n = 11) alone) and women without surgical evidence of endometriosis (control, n = 15). Collection of endometrial and endometriotic tissue samples, gynecologic history and demographic information. Quantification of estradiol (1.0 nM) and melatonin (0.1 nM-1.0 µM) ± estradiol-induced endometrial epithelial cell proliferation in cultures of endometrial epithelial cells (CRL-1671) following 24 and 48 hours of culture. MAIN RESULTS AND THE ROLE OF CHANCE: MR1A and MR1B were localized by immunohistochemistry in glandular epithelial cells of endometrial biopsies from women with and without endometriosis. Both receptors were expressed in eutopic and ectopic endometrial tissue. mRNA expression of MR1A and MR1B was significantly greater in peritoneal lesions than in either endometriomas or eutopic endometrium. However, protein expression of MR1A was decreased in peritoneal lesions compared to control eutopic endometrium, whereas MR1B expression did not differ between the groups. Melatonin (0.1 nM-1.0 µM) treatment inhibited estradiol (1.0 nM)-induced endometrial epithelial cell proliferation at 48 hours but not 24 hours of culture. LIMITATIONS, REASONS FOR CAUTION: Beneficial effects of melatonin seen in culture have yet to be comprehensively evaluated in women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that melatonin may be useful as an adjunct to current endometriosis treatments. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Canadian Institutes of Health Research (grant MOP142230 to W.G.F.). A.A.M. is supported by a resident research grant through the Physicians Services Incorporated Foundation. The authors have no conflicts of interest.

Clinical markers of endometriosis: have we been too quick to judge?

Numerous biochemical differences have been documented in women with endometriosis compared to controls; however, identification of a clinically useful marker of endometriosis remains elusive. We postulate that the diversity of clinical presentations, patient objectives, and complexity of the pathophysiology of endometriosis mandates rigorous attention to study design and standardization of procedures and questionnaires that has heretofore been overlooked in the pursuit of clinical markers of this enigmatic disease. We further propose that it is premature to conclude that clinical markers of endometriosis brought forward in the literature lack clinical value in the diagnosis of endometriosis. To address this hypothesis we reviewed the literature and assessed papers according to a modified version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria from which 55 high quality papers were reviewed. While pelvic inflammation and pain is a known significant component of endometriosis, control group definitions were widely divergent and included healthy women through to women with other inflammatory conditions. Although pain is a common presenting complaint in women with endometriosis, it was assessed in only 4 of 55 studies (7.3%) whereas infertility was documented in 34/55 studies (61.8%). Disease severity was assessed in 44 of 55 studies (80%) whilst the association between active vs. inactive disease was attempted in only 2 of the studies reviewed (3.6%). We conclude that experimental design criteria are inconsistently applied making comparisons across studies difficult. Thus, the clinical utility of previously described diagnostic markers of endometriosis remains uncertain.

A safety and efficacy study of a resorbable hydrogel for reduction of post-operative adhesions following myomectomy.

BACKGROUND: This multicenter, randomized, single-blind study assessed the safety and efficacy of a resorbable hydrogel ('Hydrogel') for the reduction of post-operative adhesion formation following myomectomy. METHODS: Women (n = 71) who were undergoing laparoscopic (67.6%) or laparotomic myomectomy were randomized (2:1) to Hydrogel (sprayed over surgically treated areas prior to wound closure, n = 48) or to control (standard care, n = 23). Patients (38 Hydrogel, 20 control) returned 8-10 weeks later for a second look. Adhesions were graded using a modified American Fertility Society (mAFS) scoring method. The primary efficacy measure was the posterior uterus mAFS score. RESULTS: For Hydrogel and control patients, respectively, mean +/- SD mAFS scores were 0.5 +/- 1.4 and 0.0 +/- 0.0 at baseline, and 1.1 +/- 1.9 and 2.6 +/- 2.2 at the second look. Similarly, mean changes from baseline were 0.8 +/- 2.0 and 2.6 +/- 2.2 (P = 0.01); 95% confidence intervals for these mean changes were (0.16-1.44) and (1.64-3.56). Adverse events were reported by 9.6 and 17.4% of Hydrogel and control patients, respectively. No intra-abdominal infections or post-operative site infections were reported. CONCLUSIONS: This 71-patient study provides the first clinical evidence of the safety and efficacy of Hydrogel for the reduction of adhesions following myomectomy. The ClinicalTrials.gov Identifier is NCT00562471.

Endoscopy teaching in Canada: a survey of obstetrics and gynecology program directors and graduating residents.

OBJECTIVE: To examine the current state of basic and advanced gynecologic endoscopy teaching in Canadian Obstetrics and Gynecology (Ob/Gyn) residency programs. METHODS: On Institutional Research Board approval, 2 pretested anonymous questionnaires were developed: one distributed to all Canadian Ob/Gyn program directors and a second to graduating residents (Canadian Task Force classification III). Two mailings were sent to maximize response, and some department chairs received personal telephone calls by the senior author to encourage participation. Residents on maternity leave were excluded from the study. RESULTS: Fifteen of 16 (94%) program directors, and 47 of 62 (76%) residents participated. Directors expect all residents to be knowledgeable and competent performing basic endoscopic procedures on graduation. However, considerable variation exists among programs that teach advanced endoscopy. Some of the more important factors limiting integration of advanced endoscopic teaching include paucity of trained faculty, lack of attending interest, scarcity of operating time, and financial constraints. Most graduating residents consider undertaking additional gynecologic endoscopy fellowships. CONCLUSION: Most Ob/Gyn program directors and graduating residents consider endoscopic surgery essential to contemporary practice. There is consensus to improve resident teaching in gynecologic endoscopy and commitment to better prepare future practitioners to ensure patient safety. Paucity of trained faculty and fiscal constraints appear to be important limiting factors.

pGreen: a versatile and flexible binary Ti vector for Agrobacterium-mediated plant transformation.

Binary Ti vectors are the plasmid vectors of choice in Agrobacterium-mediated plant transformation protocols. The pGreen series of binary Ti vectors are configured for ease-of-use and to meet the demands of a wide range of transformation procedures for many plant species. This plasmid system allows any arrangement of selectable marker and reporter gene at the right and left T-DNA borders without compromising the choice of restriction sites for cloning, since the pGreen cloning sites are based on the well-known pBluescript general vector plasmids. Its size and copy number in Escherichia coli offers increased efficiencies in routine in vitro recombination procedures. pGreen can replicate in Agrobacterium only if another plasmid, pSoup, is co-resident in the same strain. pSoup provides replication functions in trans for pGreen. The removal of RepA and Mob functions has enabled the size of pGreen to be kept to a minimum. Versions of pGreen have been used to transform several plant species with the same efficiencies as other binary Ti vectors. Information on the pGreen plasmid system is supplemented by an Internet site (http://www.pgreen.ac.uk) through which comprehensive information, protocols, order forms and lists of different pGreen marker gene permutations can be found.

Post-hysteroscopic ablation reaction: a histopathologic study of the effects of electrosurgical ablation.

Ablation of the endometrium is now an established treatment modality for dysfunctional uterine bleeding (DUB). There have been few reports of the inflammatory and healing reaction within the endomyometrium subsequent to this therapy, and its identifying characteristics. The morphologic reaction after electrosurgical ablation in particular has received scant attention. In this retrospective study, 19 women were identified who had undergone both an endometrial ablation using electrosurgical rollerball ablation and a subsequent endometrial sampling or hysterectomy. The average age of the patients was 47 years (range, 28 to 60). Fifteen patients had been ablated for DUB, while four had been ablated immediately after a resection that later revealed atypical hyperplasia. Histopathologic specimens were examined from 1 to 48 months postablation. The six specimens examined at 3 months or less after ablation all exhibited necrotic myometrium, and in five of these six cases, a florid foreign body and granulomatous reaction to necrotic myometrium and spicules of thermally damaged myometrium. A variable degree of acute inflammation was evident in all six cases and was exclusively present in one case. The remaining 13 cases were examined at > 3 months posttreatment. Necrotic myometrium was no longer evident, but a persistent granulomatous, a foreign-body reaction, or both was detected in 5 of 12 cases up to 16 months postablation. In most cases (9 of 12), there was striking endometrial scarring. The morphologic response of the endometrium after electrosurgical endometrial ablation is similar to that reported previously for both resection and laser ablation. Post-hysteroscopic ablative reaction should be recognized and distinguished from other causes of granulomatous endometritis.

Hysteroscopic endometrial resection and high-dose-rate brachytherapy: treatment of endometrial cancer in a medically compromised patient.

OBJECTIVE: The use of a combined treatment option for endometrial cancer in a medically compromised patient is outlined. METHODS/RESULTS: A case of a 49-year-old severely medically compromised patient with endometrial cancer is described. A complete hysteroscopic endometrial resection with insertion and suturing in place of an endocervical cannula allowed weekly outpatient delivery of high-dose-rate intracavitary radiation without anesthetic or repeat dilatation of the endocervical canal. CONCLUSION: The use of hysteroscopic endometrial resection with adjuvant high-dose-rate radiation therapy is a feasible treatment option for patients with endometrial cancer in whom surgery is contraindicated.

Elevated glutathione biosynthetic capacity in the chloroplasts of transgenic tobacco plants paradoxically causes increased oxidative stress

Glutathione (GSH), a major antioxidant in most aerobic organisms, is perceived to be particularly important in plant chloroplasts because it helps to protect the photosynthetic apparatus from oxidative damage. In transgenic tobacco plants overexpressing a chloroplast-targeted gamma-glutamylcysteine synthetase (gamma-ECS), foliar levels of GSH were raised threefold. Paradoxically, increased GSH biosynthetic capacity in the chloroplast resulted in greatly enhanced oxidative stress, which was manifested as light intensity-dependent chlorosis or necrosis. This phenotype was associated with foliar pools of both GSH and gamma-glutamylcysteine (the immediate precursor to GSH) being in a more oxidized state. Further manipulations of both the content and redox state of the foliar thiol pools were achieved using hybrid transgenic plants with enhanced glutathione synthetase or glutathione reductase activity in addition to elevated levels of gamma-ECS. Given the results of these experiments, we suggest that gamma-ECS-transformed plants suffered continuous oxidative damage caused by a failure of the redox-sensing process in the chloroplast.

Cervical ripening and labor induction with prostaglandin E2 gel: a placebo-controlled study.

A randomized double-blind, placebo-controlled study was undertaken to evaluate the effect of a single intracervical application of prostaglandin E2 gel on the ripening of the cervix and on the subsequent induction of labor with oxytocin in patients with low Bishop scores (less than or equal to 4). Compared to controls receiving gel only, the group receiving prostaglandin E2 gel had significant increases in their cervical Bishop scores, shorter induction-to-delivery intervals, shorter time requiring use of oxytocin, and more successful labor induction without oxytocin. Systemic side effects were minimal and fetal outcomes were comparable, as were the routes of delivery.

PIP: A randomized double-blind, placebo-controlled study was undertaken to evaluate the effect of a single intracervical application of prostaglandin E2 gel on the ripening of the cervix and on the subsequent induction of labor with oxytocin in patients with low Bishop scores (or =4). Women who presented with medical and/or obstetric indications for the induction of labor were enrolled in the study from the Mount Sinai and Toronto General Hospitals in Canada. 107 women were included in the analysis. Participants had a gestational age of 36 or more weeks and a parity of 3 or under. Compared to controls receiving gel only, the group receiving prostaglandin E2 gel had significant increases in their cervical Bishop scores, shorter induction-to-delivery intervals, shorter time requiring use of oxytocin, and more successful labor induction without oxytocin. Systemic side effects were minimal and fetal outcomes were comparable, as were the routes of delivery. A single low-dose intracervical application of prostaglandin E2 gel proved to be a safe and reliable aid in dealing with indicated but potentially difficult inductions. The product has the advantages of being uniformly prepared, accurate in dosage, stable, easy to apply, and associated with minimal side effects for mother or fetus.