Pathobiology of myomatosis uteri: the underlying knowledge to support our clinical practice.

INTRODUCTION: Uterine myomatosis, a benign condition, is the most common indication for hysterectomies worldwide, affecting the reproductive goals and quality of health of women. However, gynecologists have been provided with interesting insights on its pathobiology, which are the basis for uterine-preserving therapies. The aim of this paper is to discuss the latest evidence on these mechanisms and its importance in the clinical practice. METHOD: A comprehensive literature search was made in Pubmed, Medline, the Cochrane Library, Orbis plus and Google Scholar for articles related to the epidemiological, biological, and genetic bases. RESULTS: There is extensive evidence that genetic, epigenetic, hormonal, environmental, proinflamatory, angiogenetic, and growing factors are involved in the biology of myomatosis. Such factors are capable of activating and promoting inhibitory signaling pathways leading to initiation, development, and regression of myomata through changes in myometrial cells and myomata fibers, such as cellular proliferation, differentiation, apoptosis, angiogenesis, and changes in the surrounding environment. CONCLUSION: A good understanding of the pathobiologic mechanisms of myomatosis gives reasons to physicians to elect conservative or combined therapies, and allow affected women to receive an individualized management, according to age, reproduction desire, and clinical condition.

Laparoscopy or laparotomy as the way of entrance in myoma enucleation.

PURPOSE: Uterine myomas are the main cause of benign uterine diseases in premenopausal women. Objective of the present paper is to investigate the current best treatment modalities of myomas, depending on age of the patient and her desire to preserve fertility, as well as on clinical presentation of this pathology, such as size, number, and location of fibroids and, furthermore, on surgical experience of the gynecologist. METHODS: The design of our work is a systematic literature review of existing studies, reviews, and meta-analysis conducted in PubMed and Cochrane Library to identify relevant literature. Commonly, the myomectomy is to be recommended in women desiring to preserve fertility when myomas are associated with symptoms such as excessive bleeding, pelvic discomfort, or palpable abdominally fibroids. The decision of surgical approach for myomectomy should be individualized, depending on size and location, as well as on surgeon's experience. The different modalities of myomectomy, laparoscopic, hysteroscopic, robotic-assisted, or laparotomic are in detail presented in the paper, according to Society of Obstetricians and Gynecologists of Canada (SOGC) clinical practice guidelines and taking into consideration possible concerns of myomectomy such as uterine rupture, development of adhesions, and myomas' recurrence.

The Laparoscopic-Assisted Combined Hysterectomy: A New Surgical Concept Compared to the Classical Laparoscopic-Assisted Vaginal Hysterectomy by a Prospective Study.

BACKGROUND AND AIMS: This controlled trial with II-1 evidence compared the safety and efficacy of the new laparoscopic-assisted combined hysterectomy (LACH) with the standard surgical technique laparoscopic-assisted vaginal hysterectomy (LAVH) in general and in patients displaying risk factors (large uterus, vaginal nulliparity, prior caesarean section). METHODS: From June 2007 to September 2008, 101 patients underwent a hysterectomy at the Clinic of Gynaecology, Obstetrics and Gynaecological Oncology at the Pius Hospital, University Hospital for Gynaecology in Oldenburg. The main outcome measures were feasibility, postoperative analgesia, postoperative inflammatory reaction, and duration of surgery. Statistical analyses were performed using SPSS for Windows (p < 0.05). RESULTS: We observed no significant differences between LACH and LAVH regarding outcome parameters or when risk factors were considered. Within the LACH group, the duration of surgery was significantly shorter for patients with UW <400 g. Still within the normal range, caesarean sections from both groups revealed significant differences in the number of leucocytes on the 2nd post-operative day. No urinary tract injuries, no unplanned conversion to laparotomy, no severe perioperative complications occurred in either group. CONCLUSION: In terms of technical feasibility, LACH represents a safe alternative for abdominal HE when LAVH is contraindicated.

Uterine perforation following a fractional curettage successfully treated with the modified polysaccharide 4DryField® PH: a case report.

BACKGROUND: Uterine perforation is the most common complication of curettage and may result in bleeding. Therefore, urgent control of bleeding from the uterine wall perforation is necessary to avoid an emergency hysterectomy or blood transfusion, to prevent peritoneal adhesion formation, possible chronic pelvic pain, and infertility. In the present case, an active bleeding secondary to a perforation of the uterus during curettage, for diagnosis of endometrial carcinoma, was instantaneously and successfully treated with only the application of a novel modified polysaccharide powder. This is, to the best of our knowledge, the first time that the agent 4DryField® has been used for this purpose. CASE PRESENTATION: A 71-year-old German woman with serometra and endometrial hyperplasia suffered a perforation of the anterior wall of the uterus during the hysteroscopic resection of submucosal polyps and a fractional curettage. Subsequently, an immediate laparoscopy showed an active bleeding from the wound, which was promptly stopped with only the application of the hemostatic and anti-adhesion polysaccharide powder, 4DryField®. There were no postoperative complications. Nine weeks later, a laparoscopic hysterectomy with bilateral salpingoophorectomy for endometrial carcinoma (histology: stage IA, pT1a, cN0, L0 V0 M0/G2) was performed. The former injured area looked slightly prominent, was completely healed, and showed a shiny serosa. All her pelvic organs were free of adhesions, and there was one 0.5-mm calcified granuloma in the Douglas pouch. CONCLUSIONS: The efficient hemostasis combined with the adhesion prevention effect of 4DryField®, allowed a fast control of the uterine wall bleeding, saved operation time, avoided the risks of other procedures for bleeding control and contributed to the normal healing of the uterine wall without any adhesion formation.

Long term follow-up concerning safety and efficacy of novel adhesion prophylactic agent for laparoscopic myomectomy in the prospective randomized ADBEE study.

We conducted a prospective randomized single blind - subject study in the University Clinic of Gynecology of Pius-Hospital Oldenburg. The primary objective of the ADBEE study was to assess the safety and manageability of ADBLOCK when used as an adjunct to laparoscopic surgery for the primary of myomas in women wishing to improve pregnancy outcomes. The study population included 32 women aged between 18-45 years, in good general health condition, who have not completed their family planning and who are undergoing primary ('virgin') laparoscopic myomectomy with an aim to improve pregnancy outcomes. The patients were randomized in 2 groups, ADBLOCK arm with 21 patients and surgery only arm with 11 patients. The study was single blind - subject and the investigators were blinded to treatment group assignment until completion of uterine suturing and prior to removal of the endoscope. A vigorous follow-up of subjects was organized, focusing on its two critical characteristics: completeness and duration. Completeness represented the percentage of subjects who returned to every planed follow - up appointments. The patients were evaluated in a specific period of time, which defined the duration of follow-up. Safety of the ADBLOCK was estimated after analyzing and documentation of any adverse events occurred, clinical and physical examination of patients as well as evaluation of laboratory measures. There were 25 adverse events reported in ADBLOCK treatment group and 12 events in NO-ADBLOCK group over the 24-months treatment. All adverse events in both treatment arms were not anticipated, with all events in the ADBLOCK group being resolved. At 28 days, there was no significant difference in proportion of events between the two treatments (p = 0.440). Overall, the number of events reported was low and the severity of events was generally mild with an unlikely or no relationship to treatment. There were no unanticipated device related adverse events seen in both treatment groups over the immediate post-operative period or during the 24 months follow up period. By 12 weeks all patients reported their wound as healing well or healed and at 6 months all wounds were reported as healed. There were no differences between both treatment groups regarding the use of painkillers over 24 months follow up period. This clinical first - in - human study, sustained by a rigorous follow-up of the subjects has demonstrated that ADBLOCK is a safe product, presenting no additional safety risk or burden to the patients over surgery alone. The device was relatively easy to use, with a low device failure rate that had no impact on the surgical procedures.

Evaluation of the HystSim™-virtual reality trainer: an essential additional tool to train hysteroscopic skills outside the operation theater.

BACKGROUND: Minimally invasive surgery is a major pillar of gynecological surgery. However, there are very few training opportunities outside the operation theater (OR) due to the cost and equipment requirements of organ simulators, virtual reality trainers (VRT) are promising tools to fill this gap. METHODS: Experienced and inexperienced participants of a minimally invasive surgery course followed the standardized HystSim™-VRT training program. RESULTS: Performance of 39 Participants (15 inexperienced and 24 experienced) was evaluated in the standardized hysteroscopic program HystSim™. Tasks included three rounds of both a polyp and a myoma resection. Primary measurements were improvement in resection time, cumulative resection path length, and distention media use. CONCLUSION: The HystSim™-VRT is an effective tool to improve the psychomotor skills needed in hysteroscopic surgery for experienced and inexperienced surgeons prior to OR exposure. Additional organ models training is advisable for hysteroscopic haptic skills.

Plastic neo-vaginal construction in Mayer-Rokitansky-Küster-Hauser syndrome: an expert opinion paper on the decision-making treatment process.

Vaginal agenesis is a congenital anomaly that affects the life of one of each four thousand women around the world. There is a trend that patients request immediate surgical correction, instead of passive vaginal dilatation. Therefore a differentiated counselling should be provided. We present a comparative chart, based on published evidence, with aspect to the available techniques, which will facilitate the decision-making process in the clinical practice. From our point of view, the best results are achieved with techniques that combine the advantages of the minimal-invasive surgery with those derived of the use of peritoneum as covering tissue of the neovagina. Nevertheless there is a lack on interdisciplinary consensus about the best option to restore the physical and sexual quality of life.

How to avoid risks for patients in minimal-access trials: Avoiding complications in clinical first-in-human studies by example of the ADBEE study.

A clinical trial is a prospective study designed to establish the safety and efficacy of investigational devices in humans, in accordance with the strict guidelines of the Food and Drug Administration (FDA; USA) or European Medicines Agency (EMA; Europe). Before a clinical first-in-human study is initiated, preclinical studies of the investigational product are mandatory, and the results should be sufficient to indicate that the investigational device is acceptably safe for the proposed evaluation in human subjects. The present paper describes an experience of clinical trials, highlighting ways of avoiding possible complications in clinical first-in-human studies. For a better approach to our aim, we exemplified a prospective, randomized, single-blind study, ADBEE. The primary objective was to assess the safety of the ADBLOCK system when used as an adjunct to laparoscopic primary removal of myomas in women wishing to improve pregnancy outcomes.

Validation of a score to guide endometriosis therapy for the non-specialized gynecologist.

OBJECTIVE: To validate a tool-the ECO system-developed to guide non-specialized gynecologists in the treatment of patients with suspected endometriosis in outpatient clinics. METHODS: In a retrospective study, data were assessed from patients presenting to a center in Brazil or a center in Germany with suspected endometriosis and pelvic pain between July 2012 and June 2013. Data reviewed included patient complaints, clinical extent of disease, patient goals, recent use of medication, previous pelvic surgeries, visual analog pain scale, treatment provided, and histopathology after surgery. Data were transformed into a score according to the ECO system (0-6) indicating the suggested management, which was compared with the approach used in the study hospitals. RESULTS: Among 166 patients, 78 (47.0%) were medically treated and 88 (53.0%) underwent therapeutic laparoscopy. All 3 patients scoring 2 had undergone hormonal treatment. Among 51 patients scoring 3, 49 (96.1%) were clinically managed and 2 (3.9%) underwent surgery. Among 52 patients scoring 4, 26 (50.0%) had undergone medical treatment and 26 (50.0%) surgical treatment. All 56 patients who scored 5 and the four patients who scored 6 underwent surgery. CONCLUSION: The ECO system seems to effectively represent the management of patients with endometriosis in specialized services.

Can we still have a clear conscience, routinely offering vaginal mesh operations in plastic and reconstructive surgery of the pelvic organ prolapse?

INTRODUCTION: Since many years, plastic and reconstructive surgery in pelvic organ prolapse (POP) has been performed by vaginal mesh surgery. Although warnings from the scientific societies and the FDA have been published, vaginal mesh surgery still remains a routine treatment of genital prolapse in the female. BACKGROUND: Many third-degree referral centres in operative gynaecology found a high number of severe complications after mesh repair. Compared to the minor complications known from the classical non-mesh plastic and reconstructive surgery, there is a clear difference concerning the severity of complications. Additionally, mesh vaginal surgery was implemented in gynaecological prolapse operations because of the relatively high recurrence rate in classical vaginal surgery without implants; no major studies however have revealed a lower long-term recurrence rate with mesh vaginal techniques. DISCUSSION: As the recurrence rate could not be lowered evaluating the meta-analysis of the published scientific studies, the higher rate of severe complications should emphasise the fact that the risk of vaginal mesh surgery is too high for these techniques to be implemented in the surgical work of a routine gynaecological operative department. CONCLUSION: Vaginal mesh surgery can no longer be a primary plastic and reconstructive therapy of pelvic organ prolapse in a routine gynaecological operative setting and department, due to the high rate of severe complications.

Efficacy risks of the minimal-invasive plastic and reconstructive neovagina Vecchietti technique in Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder clinically defined by primary amenorrhea and infertility, congenital aplasia of the uterus and upper vagina. The patients with MRKH-syndrome have a female karyotype (46, XX), normally functioning ovaries and regular development of secondary sexual characters. Generally, the initial clinical sign of the syndrome is the failure to begin the menstrual cycle. Even though the psychological impact of the disease may be overwhelming, its physiological disorder can be successfully treated, after the surgical intervention the patients being able to have a normal sexual function. Reproduction may also be possible with assisted techniques. OBJECTIVE: The aim of the study was to evaluate the efficacy risks of the traditional laparoscopic Vecchietti method in the plastic and reconstructive treatment of vaginal agenesis, documenting complications, as well as anatomical and functional results by means of a prospective, single center, single arm study. MATERIAL AND METHODS: Between 2003 and 2011, 53 patients with MRKH-syndrome were treated in the gynecological clinic of the Kochi's Lakshmi Hospital, Kerala, India. All the patients suffered from primary amenorrhea and the karyotype was (46, XX). The clinical suspicion was confirmed sonographically and intraoperatively, showing an absent uterus or the presence of rudimentary uterine horns, with normal ovaries. All the patients received a plastic laparoscopic neovagina construction, in order to achieve a satisfactory sexual function. We adopted a combined strategy: the patients were prepared by a psychological counselling, followed by the surgical intervention and a postoperative follow-up. The surgical procedure used in this series was a laparoscopic modified Vecchietti's technique. All the patients were dismissed with the obligation to have intercourse and/or vaginal dilation 3 times a week for 6 months. RESULTS: The patients' ages varied between 13 and 40 years, with a mean age of 25 years. The mean operation time was 42.3 minutes, with a range between 36 and 63 minutes. In 2 cases, an intraoperative bladder injury occurred. A good qualitative vaginal tissue was clinically achieved in all the patients. The mean follow up period of the patients was 4 years ranging from 1 to 5 years. The anatomic success was observed in 94% of the cases and functional success in 79%. CONCLUSION: The anatomical failures in 6% were in women not having regular intercourse or not performing vaginal dilatation postoperatively. The psychological impact of the disease in combination with the performed surgery seems responsible for the difference of 15% of the cases where the anatomical result was good, but no regular intercourse could be achieved. The minimal-invasive plastic and reconstructive neovagina Vecchietti technique in MRKH-syndrome has a high success rate. In case of an intraoperative urinary bladder injury, the repair can be performed laparoscopically during the same session. Qualitatively good vaginal tissue and anatomical reconstruction can easily be achieved. In one patient desiring assisted reproductive medicine, a transvaginal oocyte retrieval was achieved.