Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

<p>Abstract</p> <p>Background</p> <p>Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.</p> <p>Methods</p> <p>A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO₂insufflation at the 10 cm of water. TIR was evaluated at the 24^th, 72^nd, 120^thand 168^thhour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.</p> <p>Results</p> <p>More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24^thand 72^nd; p < 0.01 - 120^thand p < 0.001 - 168^thhrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.</p> <p>Conclusions</p> <p>MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO₂insufflation however, led to moderate inflammation and less adhesion formation.</p

Transcriptome Analysis during Human Trophectoderm Specification Suggests New Roles of Metabolic and Epigenetic Genes

In humans, successful pregnancy depends on a cascade of dynamic events during early embryonic development. Unfortunately, molecular data on these critical events is scarce. To improve our understanding of the molecular mechanisms that govern the specification/development of the trophoblast cell lineage, the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos from our in vitro fertilization program by using Human Genome U133 Plus 2.0 microarrays. Some of the microarray data were validated by quantitative RT-PCR. The TE molecular signature included 2,196 transcripts, among which were genes already known to be TE-specific (GATA2, GATA3 and GCM1) but also genes involved in trophoblast invasion (MUC15), chromatin remodeling (specifically the DNA methyltransferase DNMT3L) and steroid metabolism (HSD3B1, HSD17B1 and FDX1). In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as NANOG and DPPA2, this signature included genes belonging to the NLR family (NALP4, 5, 9, 11 and 13), Ret finger protein-like family (RFPL1, 2 and 3), Melanoma Antigen family (MAGEA1, 2, 3, 5, 6 and 12) and previously unreported transcripts, such as MBD3L2 and ZSCAN4. This study provides a comprehensive outlook of the genes that are expressed during the initial embryo-trophectoderm transition in humans. Further understanding of the biological functions of the key genes involved in steroidogenesis and epigenetic regulation of transcription that are up-regulated in TE cells may clarify their contribution to TE specification and might also provide new biomarkers for the selection of viable and competent blastocysts

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

<p>Abstract</p> <p>Background</p> <p>Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.</p> <p>Methods/Design</p> <p>This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part^®Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.</p> <p>Discussion</p> <p>This trial aims to assess, whether the intra-peritoneal application of A-Part^®Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.</p> <p>Trial registration</p> <p>NCT00646412</p

Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

The effect of endometrial thickness on pregnancy outcome in patients with Asherman&rsquo;s syndrome post-hysteroscopic adhesiolysis

Saeed Baradwan,1 Dina Shafi,1 Amira Baradwan,2 Muhammad Salman Bashir,3 Dania Al-Jaroudi1,4 1Department of Obstetrics and Gynecology, Women&rsquo;s Specialized Hospital, King Fahad Medical City, Riyadh, 2Faculty of Medicine, King Abdulaziz University, Jeddah, 3Research Center, King Fahad Medical City, Riyadh, 4Department of Obstetrics and Gynecology, Reproductive Infertility and Medicine Department, King Fahad Medical City, Riyadh, Saudi Arabia Background: Hysteroscopic adhesiolysis anatomically restores the uterine cavity in cases of Asherman&rsquo;s syndrome (AS); however, the extent of endometrial fibrosis could determine the pregnancy outcome.Objectives: To determine whether endometrial thickness could influence pregnancy outcome of hysteroscopic adhesiolysis in women with a history of AS.Subjects and methods: This was a retrospective cohort study that included 41 women who attended Women&rsquo;s Specialized Hospital, King Fahad Medical City from December 2008 to December 2015, presented with a history of infertility or recurrent pregnancy loss, and were diagnosed with intrauterine adhesions and treated by hysteroscopic adhesiolysis. To analyze the causative factors of AS, history of curettage, miscarriage, postpartum hemorrhage, hysteroscopy, endometritis, and any uterine surgery were recorded. Patients were followed up for 2 years to account for pregnancy. Patients were divided into two groups based on measurement of endometrial thickness in the midsagittal plane at mid-cycle of a menstrual period. Group A consisted of 26 patients with endometrial thickness &le;5 mm, and group B included 15 patients with endometrial thickness &gt;5 mm. The main outcome measures included endometrial thickness and pregnancy outcome.Results: Group A had significantly (P&lt;0.001) lower pregnancy rates compared with group B (38.4% versus 80%, respectively). Five of 10 pregnancies (50%) from group A miscarried, compared with 1 of 12 (8.3%) pregnancies in group B. This was statistically significant (P&lt;0.001).Conclusion: Pregnancy rates were observed to be higher when the endometrium was &gt;5 mm in thickness among patients with AS and miscarriage rates may be reduced in this group. Keywords: intrauterine adhesion, operative hysteroscopy, Asherman&rsquo;s syndrome, endometrial thicknes

Virtual reality-based assessment of basic laparoscopic skills using the Leap Motion controller

Background: The majority of the current surgical simulators employ specialized sensory equipment for instrument tracking. The Leap Motion controller is a new device able to track linear objects with sub-millimeter accuracy. The aim of this study was to investigate the potential of a virtual reality (VR) simulator for assessment of basic laparoscopic skills, based on the low-cost Leap Motion controller. Methods: A simple interface was constructed to simulate the insertion point of the instruments into the abdominal cavity. The controller provided information about the position and orientation of the instruments. Custom tools were constructed to simulate the laparoscopic setup. Three basic VR tasks were developed: camera navigation (CN), instrument navigation (IN), and bimanual operation (BO). The experiments were carried out in two simulation centers: MPLSC (Athens, Greece) and CRESENT (Riyadh, Kingdom of Saudi Arabia). Two groups of surgeons (28 experts and 21 novices) participated in the study by performing the VR tasks. Skills assessment metrics included time, pathlength, and two task-specific errors. The face validity of the training scenarios was also investigated via a questionnaire completed by the participants. Results: Expert surgeons significantly outperformed novices in all assessment metrics for IN and BO (p &lt; 0.05). For CN, a significant difference was found in one error metric (p &lt; 0.05). The greatest difference between the performances of the two groups occurred for BO. Qualitative analysis of the instrument trajectory revealed that experts performed more delicate movements compared to novices. Subjects’ ratings on the feedback questionnaire highlighted the training value of the system. Conclusions: This study provides evidence regarding the potential use of the Leap Motion controller for assessment of basic laparoscopic skills. The proposed system allowed the evaluation of dexterity of the hand movements. Future work will involve comparison studies with validated simulators and development of advanced training scenarios on current Leap Motion controller. © 2017, Springer Science+Business Media New York

Hysterosalpingogram findings among subfertile women undergoing assisted reproductive technology

Dania Al-Jaroudi,1 Abeer Abdullah Aldughayyim,2 Wadha Suliman Alshamry,3 Ahlam Saud Alrashidi,3 Ahmed A Bahnassy4 1Reproductive Endocrine and Infertility Medicine Department, King Fahad Medical City, Riyadh, Saudi Arabia; 2AL Maarefa College King Khaled Branch, Ad Diriyah for Science and Technology MCST, Riyadh, Saudi Arabia; 3Faculty of Medicine, King Khalid Hospital, Hail, Saudi Arabia; 4Faculty of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia Purpose: The objectives of our study included comparing reproductive histories and causes of infertility between patients with and without a hysterosalpingogram (HSG) investigation, and summarizing the prevalence and extent of tubal abnormalities among patients who underwent HSG. Outcomes following assisted reproductive technology (ART) were compared between HSG and non-HSG groups. Materials and methods: A cross-sectional study was conducted to review the medical records of 200 Saudi women with subfertility. In addition to information on HSG, patient data extracted included age, body mass index (BMI), infertility duration, miscarriage experience, parity, cause of infertility, and history of previous surgery, ectopic pregnancy, endometriosis, tubal surgery, pelvic inflammatory disease (PID), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), pregnancy, and live birth. Results: One hundred and ninety six (98.0%) patients had either IVF (n=18; 9.0%) or ICSI (n=178; 89.0%) performed; ICSI was performed in 157 (90%) and 21 (81%) patients. Of the 12 women with tubal factor who did not undergo HSG, 3 (25.0%) became pregnant after ART, 8 (66.7%) did not, and the status of 1 (8.3%) is yet unknown. Conclusions: Our study aimed to contribute to resolving the debate regarding the continuing role of HSG in an environment where ART has become established as a successful approach to treat infertility. Most of the HSGs were done as per the attending physician&rsquo;s discretion, and not according to any specific policy. Keywords: assisted reproductive technology, hysterosalpingogram, intracytoplasmic sperm injection, infertility, in vitro fertilizatio