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Protein stability against aggregation is a major quality concern for the production of safe and effective biopharmaceuticals. Amongst the different drivers of protein aggregation, increasing evidence indicates that interactions between proteins and interfaces represent a major risk factor for the formation of protein aggregates in aqueous solutions. Potentially harmful surfaces relevant to biologics manufacturing and storage include air-water and silicone oil-water interfaces as well as materials from different processing units, storage containers, and delivery devices. The impact of some of these surfaces, for instance originating from impurities, can be difficult to predict and control. Moreover, aggregate formation may additionally be complicated by the simultaneous presence of interfacial, hydrodynamic and mechanical stresses, whose contributions may be difficult to deconvolute. As a consequence, it remains difficult to identify the key chemical and physical determinants and define appropriate analytical methods to monitor and predict protein instability at these interfaces. In this review, we first discuss the main mechanisms of surface-induced protein aggregation. We then review the types of contact materials identified as potentially harmful or detected as potential triggers of proteinaceous particles in formulations and discuss proposed mitigation strategies. Finally, we present current methods to probe surface-induced instabilities, which represent a starting point towards assays that can be implemented in early-stage screening and formulation development of biologics.

Study Objective To assess the efficacy of a superior hypogastric plexus nerve block in reducing opioid requirements in the first 24 hours after minimally invasive gynecologic surgery. Design Patient-blinded randomized controlled trial. Setting Single-center academic institution (Sydney Women's Endosurgery Centre). Two surgeons administering the blocks in their own surgeries. Patients Patients undergoing either laparoscopic or robot-assisted laparoscopic hysterectomy or myomectomy for benign indications. Interventions Ropivacaine 10 mL (0.75%) infiltrated into the retroperitoneal space overlying the superior hypogastric plexus vs control of no block given at the completion of surgery. Measurements and Main Results The primary outcome was the total opioid use in the first 24 hours after surgery, measured in morphine milligram equivalents (MME). Standardized fentanyl patient-controlled analgesia was given to all patients in the trial. The secondary outcome was pain measured on a visual analog scale (1 to 10) at 1, 2, 6, 12, and 24 hours after surgery. Fifty patients out of 56 approached for the study participated in, and completed, the study (89.2%). The patients were randomized over a 5-month period, March 2020 to July 2020. A total of 27 patients were randomized to receive a nerve block, and 23 were randomized to the control. There was a difference of –21.8 MME in the block group compared with the no-block group (95% confidence interval [CI], –38.2 to –5.5; p = .008). This correlated to a 38% reduction in opioid use in the block group. The mean opioid use in the patients in the block group was 33.1 MME (95% CI, 24.2–41.9) and in those in the no-block group 54.9 MME (95% CI, 40.7–69.1). For the block group, opioid use ranged from 1.0 to 76.5 MME, with an interquartile range of 37 (14–51). For the control group, the range was 7.5 to 113.5 MME, with a higher interquartile range of 60 (28–88). Pairwise comparisons of the mean pain scores over the 24 hours showed a lower pain score with a nerve block of 1.8 (95% CI, 1.5–2.1) compared with a no-block score of 2.6 (95% CI, 2.3–2.9) No adverse effects of local anesthetic toxicity, nerve injury, or bowel/vascular injury were noted in any patient. Conclusion A superior hypogastric plexus nerve block is a simple technique for reducing postoperative opioid requirements and pain in the first 24 hours after minimally invasive gynecologic surgery.

BACKGROUND Hysterectomy is the most commonly performed benign gynaecological surgery. Recently, the rates of minimally invasive hysterectomy have fallen due to the banning of mechanical morcellation techniques that rendered minimal invasive gynaecology surgeons unable to extract large uteri from the relatively small colpotomy incisions. AIMS This study aims to share our experience in utilising Colpo-V incision to remove large uterine specimens transvaginally and report its success and complication rates to promote a minimal invasive approach in patients with large uteri without the need to perform large abdominal incisions or transabdominal morcellation. METHODS This is a prospective case series study in which women with large uteri and|or narrow vaginal canal underwent total laparoscopic hysterectomy and a subsequent posterior vaginal wall incision (Colpo-V) to facilitate the intact extraction of the uterus through the vagina. Patients were seen in the clinic six weeks after the surgery for post-operative assessment and documentation of late complications. RESULTS Seventeen women underwent the procedure, and the intact extraction of the specimen was successful in 16 out of the 17 cases (94%). No major complications were encountered during or after the procedure. CONCLUSION Colpo-V incision is a simple and effective technique for the intact extraction of larger uterine specimens at hysterectomy.

A survey performed by the AAPS Drug Product Handling community revealed a general, mostly consensus, approach to the strategy for the selection of surfactant type and level for biopharmaceutical products. Discussing and building on the survey results, this article describes the common approach for surfactant selection and control strategy for protein-based therapeutics and focuses on key studies, common issues, mitigations, and rationale. Where relevant, each section is prefaced by survey responses from the 22 anonymized respondents. The article format consists of an overview of surfactant stabilization, followed by a strategy for the selection of surfactant level, and then discussions regarding risk identification, mitigation, and control strategy. Since surfactants that are commonly used in biologic formulations are known to undergo various forms of degradation, an effective control strategy for the chosen surfactant focuses on understanding and controlling the design space of the surfactant material attributes to ensure that the desired material quality is used consistently in DS/DP manufacturing. The material attributes of a surfactant added in the final DP formulation can influence DP performance (e.g., protein stability). Mitigation strategies are described that encompass risks from host cell proteins (HCP), DS/DP manufacturing processes, long-term storage, as well as during in-use conditions.

Background The negative media attention surrounding vaginal mesh procedures has seen a rise in demand for minimally invasive non-mesh options for the treatment of stress urinary incontinence (SUI). The laparoscopic Burch colposuspension (LBC) is a non-mesh alternative to synthetic midurethral slings (MUS) with similar short-term outcomes. However, long-term outcomes are not well established. Aims To evaluate the long-term outcomes of LBC for treatment of SUI in women. Material and methods One hundred and fifty-one cases of LBC were performed by a single surgeon over two private hospital settings between January 2010 and January 2016. Follow-up subjective outcomes were obtained in 137 cases (90.7%) utilising standardised questionnaires. Primary outcome was successful treatment of SUI, defined as subjective cure or significant improvement of stress incontinence symptoms. Secondary outcomes included new-onset or worsened symptoms of overactive bladder (OAB), voiding dysfunction, prolapse, and perioperative complications. Results One hundred and thirty-seven patients were analysed with a mean follow-up of 50.6 months (range: 13-89 months). Primary outcome of successful treatment was achieved in 90.5% of women. New-onset or worsened symptoms of OAB was reported in 10.2%, with a further 8.8% of women experiencing symptomatic voiding dysfunction. Sixteen patients (11.7%) reported new-onset or worsening symptoms of prolapse. There were no major surgical complications. Conclusions LBC is a safe and effective long-term treatment for SUI, with low failure rates and minimal adverse outcomes. It is a suitable alternative for women with contraindications to mesh or those having concomitant laparoscopic procedures.

Endometriosis is a common gynecological condition which affects 5-10% of women of reproductive age and up to 50% of women with pelvic pain and infertility. The most commonly affected areas are the pelvic peritoneum, ovaries and rectovaginal septum. Isolated endometriosis of the sciatic nerve is very rare. Our patient suffered from worsening right hip and buttock pain with severe exacerbation during menstruation. Several different imaging modalities (ultrasound of her pelvis and right hip, as well as X-rays and computed tomography scans of her right hip and lumbosacral spine) failed to identify any pathology. Magnetic resonance imaging scans of her pelvis revealed a 3.5 cm endometriotic lesion over the pelvic segment of her right sciatic nerve. Following a multidisciplinary discussion, the patient underwent laparoscopic excision of endometriosis. The patient recovered well from her surgery. She successfully conceived with in vitro fertilization 3 years after her surgery, following a failed course of Clomid (Clomiphene citrate) for ovulatory dysfunction.

Study Objective To demonstratefull-thickness excision of the affected muscularis along the submucosal plane. Design Stepwise demonstration of LRSD technique with narrated video footage. Setting LRSD takes advantage of the submucosal layer of the bowel wall and uses it as an easier line of excision for rectal endometriosis compared with the very difficult traditional line of excision of irregular disease-muscularis interface. The expansion of the submucosal layer by the injection separates the affected muscularis away from the mucosa, making it safer to excise the lesion with less chance of entering the bowel lumen. Excision of disease is more complete with LRSD because the full-thickness excision of the muscularis layer includes the healthy deep muscularis, which will form the disease-free deep excision margin. Intervention This video will highlight anatomic and technical aspects of LRSD including the following key steps: 1. Mobilization of diseased bowel segment 2. Submucosal injection 3. Circumferential incision of the muscularis 4. Submucosal dissection along the submucosal plane 5. Bowel wall integrity test 6. Muscularis defect repair Conclusion Rectal shaving by LRSD appears to be easier, safer, and more complete in excision of bowel endometriosis than the classical rectal shaving technique. This modification requires further evaluation to confirm its potential in the surgical management of rectosigmoid deep infiltrative endometriosis.

Objectives To examine the association between ovarian immobility and presence of endometriomas and assess the diagnostic accuracy of transvaginal sonographic (TVS) ovarian immobility in the detection of deep infiltrating endometriosis (DIE). Methods This was a multicenter prospective observational study of women presenting with chronic pelvic pain from January 2009 to March 2015. Women with or without history of endometriosis who were scheduled to undergo laparoscopic surgery for endometriosis gave a detailed history and underwent specialized TVS in a tertiary referral unit prior to laparoscopy. During TVS, ovarian mobility and the presence of endometriomas were assessed. The relationship between TVS ovarian mobility, with or without endometriomas, and DIE was correlated with the gold standard, diagnosis of endometriosis at laparoscopy. Results Included in the analysis were 265 women with preoperative TVS and laparoscopic outcomes. Ovarian immobility on TVS was significantly associated with presence of endometriomas at surgery, with a prevalence of 12.2%, 10.8% and 52.7% for fixation of the left ovary only, the right ovary only and bilateral ovaries, respectively, compared with 4.2%, 3.7% and 7.3% for normal ovaries. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive and negative likelihood ratios of TVS ovarian immobility for diagnosis at surgery of immobility of ovaries with endometriomas in the left ovary only were 44.4%, 92.3%, 44.4%, 92.3%, 5.8, 0.6, in the right ovary only were 50.0%, 98.5%, 80.0%, 94.2%, 33.0, 0.5 and bilaterally were 74.4%, 68.6%, 72.5%, 70.6%, 2.4, 0.4, while those for diagnosis of immobility of normal ovaries were 25.0%, 87.9%, 8.3%, 96.4%, 2.1, 0.9 for left ovary only, 14.3%, 92.9%, 7.1%, 96.6%, 2.0, 0.9 for right ovary only and 35.7%, 97.2%, 50.0%, 95.0%, 12.6, 0.7 bilaterally, respectively (P < 0.05 except for normal left and right ovaries with P = 0.2 and 0.4, respectively). The sensitivity, specificity, PPV and NPV for performance of ovarian immobility in the prediction of DIE for all women were 58.3%, 74.1%, 60.6%, 72.2% and in the prediction of need for bowel surgery were 78.2%, 71.1%, 41.3%, 92.6%, respectively. Conclusions There is a significant association between ovarian immobility and the presence of endometriomas. Ovarian immobility as a sonographic ‘soft marker’ of DIE performs better in the presence of endometriomas compared with in normal ovaries. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

We herein describe the operative approach of a postmenopausal woman with a history of surgically corrected congenital bladder exstrophy-epispadias who presented with long-standing complete procidentia. The patient was initially treated by laparoscopic sacral colpopexy in conjunction with a modified Elevate mesh kit anterior vaginal repair with and posterior vaginal wall repair in the form of native tissue suture plication repair. Her prolapse recurred 8 months' later due to a detachment of the mesh at the level of the promontorium. During the second-look laparoscopy, a resuspension of this mesh was deemed unsatisfactory; therefore, with patients' consent, a successful colpocleisis was performed. This case report emphasizes the complexity of pelvic organ prolapse (POP) in the context of a bladder exstrophy-epispadias complex. These women are more likely to fail the more conventional current surgical treatments for POP, coercing to revert to colpocleisis.

The improved cosmesis and recovery from minimally invasive techniques has seen a dramatic rise in its popularity. Unfortunately, the laparoscopic myomectomy for large fibroids presents a unique challenge to the surgeon. It is reputed to be difficult and time consuming, with a high risk of conversion to laparotomy. As laparoscopic techniques improve, the laparoscopic myomectomy for larger fibroids is becoming more feasible. This article outlines the case of laparoscopic removal of a 4.2 kg fibroid with the assistance of a minilaparotomy.

Study Objective To evaluate the diagnostic accuracy of transvaginal ultrasound in predicting a laparoscopic, surgically assigned, revised American Society of Reproductive Medicine (ASRM) endometriosis stage. Design A multicenter, retrospective, diagnostic accuracy study. Setting The patients visited 1 of 2 academic gynecologic ultrasound units and underwent laparoscopy led by 1 of 6 surgeons in metropolitan Sydney, Australia, between 2016 and 2018. Patients Patients with suspected endometriosis (n = 204). Interventions Ultrasound followed by laparoscopy. Measurements and Main Results Surgical cases were identified. The preoperative ultrasound report and surgical operative notes were each used to retrospectively assign an ASRM score and stage. The breakdown of surgical findings was as follows: ASRM 0 (i.e., no endometriosis), 24/204 (11.8%); ASRM 1, 110/204 (53.9%); ASRM 2, 22/204 (10.8%); ASRM 3, 16/204 (7.8%); ASRM 4, 32 204 (15.7%). The overall accuracy of ultrasound in predicting the surgical ASRM stage was as follows: ASRM 1, 53.4%; ASRM 2, 93.8%; ASRM 3, 89.7%; ASRM 4, 93.1%; grouped ASRM 0, 1, and 2, 94.6%; and grouped ASRM 3 and 4 of 94.6%. Ultrasound had better test performance in higher disease stages. When the ASRM stages were dichotomized, ultrasound had sensitivity and specificity of 94.9% and 93.8%, respectively, for ASRM 0, 1, and 2 and of 93.8% and 94.9%, respectively, for ASRM 3 and 4. Conclusion Ultrasound has high accuracy in predicting the mild, moderate, and severe ASRM stages of endometriosis and can accurately differentiate between stages when ASRM stages are dichotomized (nil/minimal/mild vs moderate/severe). This can have major positive implications on patient triaging at centers of excellence in minimally invasive gynecology for advanced-stage endometriosis.

To demonstrate laparoscopic shaving of deeply infiltrative endometriosis affecting the rectosigmoid colon, with particular emphasis on the anatomic and technical aspects of the procedure.Stepwise demonstration of the technique with narrated video footage.Intestinal involvement in deep endometriosis is estimated to occur in 8% to 12% of patients, with 90% of occurrences being located in the colorectal segment. Deep endometriosis of the rectosigmoid is defined as endometriosis involving the muscular layer of the bowel wall, usually5 mm deep, thus excluding superficial lesions that only affect the serosal layer. In cases in which medical therapy is unsatisfactory, rectosigmoid deep endometriosis can be surgically managed by 3 recognized surgical techniques: (1) rectal shaving, (2) disc excision, and (3) segmental resection. There are helpful recommendations for different approaches on the basis of the characteristics of the lesion, including the size, length, depth of invasion, involved rectal circumference, and number of lesions, among other factors [1]. Rectal shaving is well suited for smaller lesions, typically3 cm, and involves "shaving" the lesion in the affected muscular layer of the bowel wall off the mucosa, ideally without entering the bowel lumen. It is associated with lower rates of perioperative complications and lower probability of long-term postoperative bladder and bowel dysfunctions [2].This video demonstrates and highlights the anatomic and technical aspects of the following important steps of the rectal shaving procedure: (1) suspension of ovaries; (2) mobilization of the diseased segment of the rectum; (3) shaving of the lesions, with pertinent comments at different stages of nodule excision; (4) checking for the integrity of the bowel wall; and (5) suture of the muscularis defect after excision of the lesions from the muscularis layer of the bowel.Compared with other alternatives, shaving for bowel endometriosis is a more conservative procedure with lower rates of perioperative complications, and it is less likely to result in long-term bladder and bowel dysfunctions. Therefore, shaving is preferable and recommended for appropriate lesions.

Objective To use office gel sonovaginography (SVG) to predict posterior deep infiltrating endometriosis (DIE) in women undergoing laparoscopy. Methods This was a multicenter prospective observational study carried out between January 2009 and February 2013. All women were of reproductive age, had a history of chronic pelvic pain and underwent office gel SVG assessment for the prediction of posterior compartment DIE prior to laparoscopic endometriosis surgery. Gel SVG findings were compared with laparoscopic findings to determine the diagnostic accuracy of office gel SVG for the prediction of posterior compartment DIE. Results In total, 189 women underwent preoperative gel SVG and laparoscopy for endometriosis. At laparoscopy, 57 (30%) women had posterior DIE and 43 (23%) had rectosigmoid/anterior rectal DIE. For the prediction of rectosigmoid/anterior rectal (i.e. bowel) DIE, gel SVG had an accuracy of 92%, sensitivity of 88%, specificity of 93%, positive predictive value (PPV) of 79%, negative predictive value (NPV) of 97%, positive likelihood ratio (LR+) of 12.9 and negative likelihood ratio (LR–) of 0.12 (P = 3.98E–25); for posterior vaginal wall and rectovaginal septum (RVS) DIE, respectively, the accuracy was 95% and 95%, sensitivity was 18% and 18%, specificity was 99% and 100%, PPV was 67% and 100%, NPV was 95% and 95%, LR+ was 32.4 and infinity and LR– was 0.82 and 0.82 (P = 0.009 and P = 0.003). Conclusions Office gel SVG appears to be an effective outpatient imaging technique for the prediction of bowel DIE, with a higher accuracy for the prediction of rectosigmoid compared with anterior rectal DIE. Although the sensitivity for vaginal and RVS DIE was limited, gel SVG had a high specificity and NPV for all forms of posterior DIE, indicating that a negative gel SVG examination is highly suggestive of the absence of DIE at laparoscopy. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Objective To evaluate preoperative real-time dynamic transvaginal sonography (TVS) in the prediction of pouch of Douglas (POD) obliteration in women undergoing laparoscopy for suspected endometriosis. METHODS This was a multicenter prospective observational study undertaken from January 2009 to November 2011. All women with symptoms suggestive of endometriosis who were scheduled for laparoscopy underwent detailed preoperative TVS, in particular to ascertain whether the POD was obliterated. POD obliteration was assessed using a real-time TVS technique called the ‘sliding sign’. Preoperative TVS sliding sign findings were then compared to gold standard laparoscopic POD findings. Results One hundred consecutive women with preoperative TVS and laparoscopic outcomes were included in the final analysis. Mean age was 32.8 years and mean age at diagnosis of endometriosis was 27.4 years. At laparoscopy, 84/100 (84%) were found to have some form of endometriosis (73% peritoneal endometriosis, 35% ovarian endometrioma(s), 33% deep infiltrating endometriosis). At laparoscopy, 30/100 (30%) had an obliterated POD and 19/30 (63.3%) of these women also had evidence of bowel endometriosis. The sonographic sliding sign technique had an accuracy of 93.0%, sensitivity of 83.3%, specificity of 97.1%, positive predictive value of 92.6%, negative predictive value of 93.2%, positive likelihood ratio of 29.2 and negative likelihood ratio of 0.17 in the prediction of POD obliteration (P = 1.8E−16). Conclusions Preoperative real-time dynamic TVS evaluation using the sliding sign seems to establish with a high degree of certainty whether the POD is obliterated. Given the increased risk of deep infiltrating endometriosis in women with POD obliteration, the TVS sliding sign technique may also be useful in the identification of women who may be at a higher risk for bowel endometriosis. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.

Acute generalized exanthematous pustulosis We reviewed eight cases of acute generalized exanthematous pustulosis managed in a tertiary hospital in Singapore. Background Acute generalized exanthematous pustulosis (AGEP) is a pustular reaction characterized by a sudden eruption of widespread nonfollicular sterile pustules associated with systemic symptoms. AGEP is primarily believed to be an adverse reaction to drugs. Outside of Europe, few reports exist on the clinical presentation of AGEP. Methods A retrospective review of patients who presented with AGEP to a Singapore tertiary hospital was performed. Results Eight patients were diagnosed with AGEP in 2006–2007. All patients presented with a macular, maculopapular eruption prior to the onset of pustules. AGEP was characterized by nonfollicular, pinpoint pustules, which were generalized and accentuated in the flexural areas in seven of the patients. The remaining patient had erythematous patches, and scattered plaques studded with pustules. Other less common features included oral/genital mucositis, blisters and erosions. The mean duration from the cessation of medications to defervescence, resolution of pustules and normalization of leukocytosis was 5, 6, and 7 d, respectively. Despite the resolution of pustules, two patients had protracted clinical courses with evolution to generalized exfoliative dermatitis and Drug rash, eosinophilia, and systemic symptoms (DRESS), respectively. The implicated medications included antibiotics in six patients, morphine and phenytoin in one patient each. Conclusions Acute generalized exanthematous pustulosis is generally described as benign and self-limiting. However, in certain patients, the clinical course is prolonged and may exhibit features that overlap with other forms of cutaneous adverse drug reactions such as toxic epidermal necrolysis and DRESS.

We present an interesting case of a large anterior sacral meningocele. Despite its rarity, this anomaly can have serious complications and therefore should not be overlooked. A female presenting with a cystic presacral mass requires detailed imaging and a complete diagnostic workup prior to definitive treatment.

Study objective To identify the volume and type of laparoscopic surgery being performed. To review the incidence, nature of associated complications, and reasons for conversion to laparotomy. Design A multicenter, prospective case load analysis and chart review, identifying operations performed by 6 advanced laparoscopic surgeons over a 12-month period (1/1/05 to 12/31/05). Setting Surgical cases were performed in 5 hospitals in Sydney, New South Wales. Patients One thousand two hundred sixty-five women underwent a variety of major and advanced operative procedures. Measurements and main results A total of 1265 major and advanced laparoscopic procedures were performed. Laparoscopic hysterectomy accounted for 364 cases (28.8%), pelvic floor repair and Burch colposuspension 280 cases (22.2%), excisional endometriosis surgery 354 cases (28%), adnexal surgery 177 cases (13.9%), adhesiolysis 75 cases (5.9%), and miscellaneous cases 15 (1.2%). Overall major complications in terms of bowel, urologic, or major vessel injuries accounted for 8 cases (0.6%). There were 4 injuries of the bowel, 2 injuries to the bladder, and 2 injuries to ureters. There were no major vessel injuries. There were no injuries associated with primary trocar or Veres needle insertion. The most common perioperative morbidity reported was the requirement for blood transfusion (11 cases [0.9%]), and the second most common was venous thromboembolism (4 patients [0.3%]). Six (0.5%) cases were converted to laparotomy, 2 as a result of a complication and 4 for technical reasons. Six of the 8 complications were managed laparoscopically, and a multidisciplinary input was sought only in 4 of the 8 complications. Conclusions Despite the advanced nature of laparoscopic procedures performed by our group, the complication rate and conversion to laparotomy remain low. There is an increasing feasibility to perform traditional open operations laparoscopically. An increasing number of these complications are now being managed laparoscopically by the gynecologist.

Laparoscopic sacrocolpopexy is becoming an increasingly popular surgical approach for repair of apical vaginal prolapse. The aim of this study was to document the postoperative anterior mesh position after laparoscopic sacrocolpopexy and to investigate the relationship between mesh location and anterior compartment support.This was an external audit of patients who underwent laparoscopic sacrocolpopexy for apical prolapse ≥ Stage 2 or advanced prolapse ≥ Stage 3, between January 2005 and June 2012. All patients were assessed with a standardized interview, clinical assessment using the International Continence Society Pelvic Organ Prolapse quantification and four-dimensional transperineal ultrasound to evaluate pelvic organ support and mesh location. Mesh position was assessed with respect to the symphysis pubis whilst distal mesh mobility was assessed using the formula √[(XValsalva - Xrest )2 + (YValsalva - Yrest )2 ], where X is the horizontal distance and Y is the vertical distance between the mesh and the inferior symphyseal margin, measured at rest and on Valsalva.Ninety-seven women were assessed at a mean follow-up of 3.01 (range, 0.13-6.87) years after laparoscopic sacrocolpopexy, 88% (85/97) of whom considered themselves to be cured or improved, and none had required reoperation. On clinical examination, prolapse recurrence in the apical compartment was not diagnosed in any patient; however, 60 (62%) had recurrence in the anterior compartment and 43 (44%) in the posterior compartment. On ultrasound examination, mesh was visualized in the anterior compartment in 60 patients. Both mesh position and mobility on Valsalva were significantly associated with recurrent cystocele on clinical and on ultrasound assessment (all P < 0.01). For every mm that the mesh was located further from the bladder neck on Valsalva, the likelihood of cystocele recurrence increased by 6-7%.At an average follow-up of 3 years, laparoscopic sacrocolpopexy was highly effective for apical support; however, cystocele recurrence was common despite an emphasis on anterior mesh extension. Prolapse recurrence seemed to be related to mesh position and mobility, suggesting that the lower the mesh is from the bladder neck, the lower the likelihood of anterior compartment prolapse recurrence. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Gynecologists are increasingly adopting total laparoscopic hysterectomy as their preferred method for performing a hysterectomy. The laparoscopic approach offers a superior view of the anatomy, facilitates meticulous hemostasis, enables the surgeon to perform adnexal surgery and pelvic reconstructive surgery, and reduces morbidity associated with large abdominal incisions. During the last 10 years, the surgeons at the Sydney Women's Endosurgery Centre (SWEC) have developed a laparoscopic technique using the same well-known steps as in the open abdominal approach. The ovarian pedicles are ligated, the uterine pedicles and vaginal vault are sutured laparoscopically, and some novel time-saving maneuvers are adopted.

Solid tumor profiling assays need to deliver accurate and consistent results in the face of decreased quality and quantity of nucleic acids extracted from FFPE samples. Understanding the performance of a particular solid tumor profiling assay with FFPE tissue is critical, but with limited and non-renewable samples available to most assay-developers, the sample number used to understand this performance can be small. TruSight® Tumor 1701 is an Illumina-developed comprehensive solid tumor profiling panel targeting 170 genes using DNA and RNA from FFPE samples. In order to confirm the robustness of the assay with FFPE tissue, 2310 FFPE samples were brought in-house and evaluated. Quantity of both DNA and RNA extraction were determined by various methods, including AccuClear™, Qubit™ and Quantifluor® fluourometric assays. Overall, >95% of the samples achieved the minimum concentrations required for the TruSight® Tumor 170 assay. As a surrogate for DNA quality, we measured the amplification potential of the nucleic acid by assessing a ΔCq value using quantitative PCR after normalization to a fixed input mass. To assess RNA quality, we used the DV200 metric, which measures the percentage of RNA fragments >200 nucleotides in length. We examined ΔCq and DV200 values across different tissues and didn’t find a significant difference between tissues. Finally, we assessed the ability of samples to pass the sample quality control (QC) metrics in the TruSight® Tumor 170 assay. These QC metrics ensure accurate variant calling, with a sensitivity and specificity of ≥95%. We found that samples that had a ΔCq value of ≤5 and a DV200 value of ≥20 achieved a QC success rate above 95%. This data highlights the need for further investigation into the methods for extraction, quantification and quality assessment of nucleic acids for solid tumor profiling and underscores the robustness of TruSight® Tumor 170 with FFPE samples. 1 For Research Use Only. Not for use in diagnostic procedures. Citation Format: Jennifer S. LoCoco, Li Teng, Danny Chou, Xiao Chen, Byron Luo, Jennifer Sayne, Ashley Adams, Naseem Ajili, Cody Chivers, Beena Murthy, Laurel Ball, Allan Castaneda, Katie Clark, Brian Crain, Anthony Daulo, Manh Do, Tingting Du, Sarah Dumm, Yonmee Han, Michael Havern, Chia-Ling Hsieh, Tingting Jiang, Suzanne Johansen, Scott Lang, Rachel Liang, Jaime McLean, Yousef Nassiri, Austin Purdy, Jason Rostron, Jennifer Silhavy, June Snedecor, Natasha Talago, Li Teng, Kevin Wu, Chen Zhao, Clare Zlatkov, Ali Kuraishy, Karen Gutekunst, Sohela De Rozieres, Matthew Friedenberg, Han-Yu Chuang, Anne C. Jager. Evaluation of quantity, quality and performance with the TruSight® Tumor 170 solid tumor profiling assay of nucleic acids extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5354. doi:10.1158/1538-7445.AM2017-5354

Expanding the paradigm of solid tumor profiling from single-gene testing to comprehensive panels presents many challenges. One such challenges is the ability of these panels to detect genetic alterations from FFPE samples, where the DNA is of low abundance and often heavily compromised. Despite these challenges, next-generation sequencing (NGS) offers the ability to assess multiple variants simultaneously in an ever-expanding list of relevant tumor genes. To that end, Illumina developed a comprehensive, hybrid capture-based NGS assay targeting 170 key cancer genes that is FFPE optimized. The assay consists of a DNA workflow for the identification of single and multiple nucleotide variants (SNVs, MNVs), small insertions and deletions (indels), gene amplifications, as well as a RNA workflow for the identification of splice variants and gene fusions. Following sequencing on the NextSeq® or HiSeq® instruments, the analytical pipeline initiates variant calling. The DNA aligner and variant callers were first optimized against the simulated read data from >40,000 COSMIC[1] mutations reported in the exons of the 170 genes. To reduce false positive variant calling due to systematic errors, each variant call was evaluated against its locus specific background error distribution. This distribution was compiled from a panel of FFPE normal samples and was also used to normalize against systematic bias in read coverage to increase the accuracy of amplification calling. Furthermore, gene amplification calling was improved by the addition of enhancer probes to the hybrid capture pool. The analytical sensitivity and specificity of TruSight® Tumor 170* was assessed on a large collection of FFPE samples and reference material. A panel of 72 cancer samples, including multiple tissue types, reference standards, and cell line and FFPE mixes were used to evaluate the limit of detection. The samples contained 533 SNVs, 80 indels including deletions up to 30 base pairs and insertions up to 31 base pairs, 4 MNVs, and 31 gene amplifications, characterized by orthogonal testing methods. Using 40 ng DNA input, detection sensitivity of the >1000 variants (including replicates) tested at variant allele frequencies down to ~5% was at 99.6%, while detection sensitivity of gene amplifications as low as 1.45x to 2.2x was at 98%. For limit of blank samples, a panel of 24 normal samples was used. Again using 40 ng DNA input, we show >99% specificity for small variant calling and >95% specificity for gene amplification calling. These data demonstrates the TruSight® Tumor 170 is able to detect multiple variant types within a single sample at low nucleic acid input, while exhibiting high analytical sensitivity and specificity for low allele fraction detection. [1] Forbes, et al. (2015) *For Research Use Only. Not for use in diagnostic procedures. Citation Format: Danny Chou, Xiao Chen, Austin Purdy, Li Teng, Byron Luo, Chen Zhao, Laurel Ball, Allan Castaneda, Katie Clark, Brian Crain, Anthony Daulo, Manh Do, Tingting Du, Sarah Dumm, Yonmee Han, Michael Havern, Chia-Ling Hsieh, Tingting Jiang, Suzanne Johansen, Scott Lang, Rachel Liang, Jennifer S. LoCoco, Jaime McLean, Yousef Nassiri, Jason Rostron, Jennifer Silhavy, June Snedecor, Natasha Talago, Kevin Wu, Clare Zlatkov, Ali Kuraishy, Karen Gutekunst, Sohela De Rozieres, Matthew Friedenberg, Han-Yu Chuang, Anne C. Jager. Analytical performance of TruSight® Tumor 170 on small nucleotide variations and gene amplifications using DNA from formalin-fixed, paraffin-embedded (FFPE) solid tumor samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3732. doi:10.1158/1538-7445.AM2017-3732

Study Objective To demonstrate a new technique of contained in bag morcellation of a myoma after laparoscopic myomectomy. Design Step-by-step explanation of the technique in a narrated video. Intervention Contained In Bag Morcellation of myoma after laparoscopic myomectomy. Measurements and Main Results Recent controversy regarding the risk of disseminating occult leiomyosarcomatous tissue during morcellation means we need to revise our current approach to tissue extraction at laparoscopic myomectomy and morcellation in general. Herein we present a novel technique, conceived by Dr. Danny Chou, called the Sydney Contained In Bag Morcellation technique for laparoscopic myomectomy. In this technique an EndoCatch bag (EndoCatch II Auto Suture Specimen Retrieval Pouch; Covidien, Mansfield, MA) is introduced in the typical fashion, the myoma is retrieved, and the mouth of the bag is exteriorized onto the abdominal wall. A 12-mm trocar is then introduced within the bag, and pneumoperitoneum is created before introducing an optical balloon tip port (KII Balloon Blunt Tip System; Applied Medical, Rancho Santa Margarita, CA) and the power morcellator device. Morcellation is then performed within the bag, under direct vision. This technique may offer a safer approach to morcellation because the bowel is not within the morcellation field and there is lower risk of disseminating occult leiomyosarcomatous tissue during morcellation. Subsequent to the morcellation process, suctioning of the bag removes any aerosolized particles of myoma, further minimizing the risk of possible dissemination. Conclusion This technique may enable a minimally invasive approach to myomectomy to continue as a viable option in the era since the warning by the US Food and Drug Administration.

Study Objective To demonstrate a modification of the Shibley single-port technique suitable for morcellation of large myomatous uteri after total laparoscopic hysterectomy in a contained environment within the abdominal cavity [1]. Design Step-by-step explanation of the technique using descriptive text and an educational video. Setting In light of recent concern about the use of power morcellators and increasing the risk of disseminating occult leiomyosarcomatous myoma fragments throughout the abdominal cavity, we propose this new technique for management of morcellation of large myomatous uteri after total laparoscopic hysterectomy, to contain the morcellation process and minimize the risk. This technique, which we have coined "Sydney Contained in Bag Morcellation" involves introduction of a sterile plastic bag (Dual Drawstring Bag, 460 × 460 mm; Southern Cross Hospital Supplies, Northmead, NSW, Australia) before introducing an optical port and the power morcellator. Before insertion this bag is modified in several ways to facilitate bag opening and specimen retrieval. The dual drawstring is removed and replaced with a 150-cm length of PDS I (polydioxanone) suture material as the new drawstring, with its exit at the mouth of the bag in the 6 o'clock position. Five stay sutures are placed around the bag mouth, corresponding to the 12, 1, 5, 7, and 11 o'clock positions. This assists with opening the mouth of the bag intraabdominally and enables orientation to be maintained. The bag is then inserted in a McCartney tube (Gates Healthcare, Cheshire, UK). Corresponding slits are made in the tip of the tube to enable the end of the stay sutures to be securely held in place during tube insertion. These ends are then retrieved using atraumatic graspers and exteriorized and clipped alongside their corresponding port sites. After hysterectomy the uterus is placed in the bag, and the stay sutures maintain the mouth opening. The bag is closed and its mouth exteriorized onto the abdominal wall at the site of the umbilical trocar. The 12-mm umbilical trocar is then replaced within the bag, and pseudopneumoperitoneum is created. Once established, an optical trocar is introduced via one of the lower quadrant port sites using a balloon tip trocar (Kii; Applied Medical, Rancho Santa Margarita, CA). The insufflation tubing is attached to this trocar, and the umbilical trocar is replaced with the morcellator device. Morcellation is performed under direct vision in a contained environment. Once complete, all fragments are removed, and the bag is washed out. The original pneumoperitoneum is re-established. The bag is then removed during aspiration to encourage negative pressure relative to the re-established pneumoperitoneum, minimizing aerosolized fragment leakage. Intervention Contained in bag morcellation of a large myomatous uterus during total laparoscopic hysterectomy. This technique has been specifically developed to address the concerns of morcellating large myomatous uteri after hysterectomy. In the case of supracervical hysterectomy or myomectomy, in which there would be no vaginal conduit to exploit, we use an endocatch bag, inserted in the usual manner, with reintroduction of the umbilical trocar within the mouth of the bag to enable creation of pseudopneumoperitoneum. Again, an optical trocar would be introduced in a lower lateral port, and morcellation would be performed under direct vision. An article describing this technique has recently been published [2]. Conclusion The Sydney Contained in bag Morcellation technique offers a possible solution to the risk of dissemination of benign morcellated and potentially leiomyosarcomatous myoma fragments. Certain aspects of the procedure are key to its success. The stay sutures are essential to facilitate orientation and opening of the bag mouth. The McCartney tube enables easier insertion of the flaccid bag into the vagina, and the suture-retaining slits enable the mouth of the bag to be opened quickly and easily. We have used this technique in 5 cases with uteri ranging in weight from 350 to 978 g. Recently, similar techniques have been described for use in single-port surgery and conventional laparoscopy [1,2]. Our technique is suitable for use with large uteri after total laparoscopic hysterectomy because the large capacity of the bag enables containment of uteri that would exceed the capacity of manually deployed specimen retrieval bags. This technique offers an alternative to vaginal morcellation, with the advantage of improved vision during morcellation and the ability to morcellate large uteri using a familiar instrument and view.

Tensile strengths of extracorporeal slip knots tied with poliglecaprone and polydioxanone. Objective To compare the tensile strengths of commonly used extracorporeal slipknots when tied with poliglecaprone and polydioxanone. Design The tensile strength of seven extracorporeal slip knots and the flat square knot were tested using a tensiometer. Knots were tied in random order with 2/0 poliglecaprone and polydioxanone. The study was designed to demonstrate a 5-newton difference in knot strength with 95% confidence at 80% power. Five knots were studied in each arm of the experiment. Setting A laboratory experiment. Main outcome measures Force required to break or cause slippage of knots. Results Knots tied with polydioxanone had a marginal yet significantly stronger tensile strength of 2.3 N (95% CI 0.1- 0.75 N, P=0.0332). The Tayside, Blood, Hutchon and Western knots had lower tensile strengths than the flat square knot in both poliglecaprone and polydioxanone. The modified Roeder knot was also stronger than the other ligatures when tied in poliglecaprone and more secure than the Western and Tayside knots when tied in polydioxanone. Conclusions Slip knots tied in poliglecaprone are marginally less strong than those tied in polydioxanone. No extracorporeally tied slip knot is stronger than the modified Roeder knot.

Comparative mass of suture material involved in extracorporeal slip knots. Objective To compare the weights of commonly used extracorporeal slip knots. Design The weights of seven commonly used types of extracorporeal slip knots and an intracorporeally tied flat square knot were compared. In each arm of the study, 17 knots were tied around a 5-mm jig using a laparoscopic trainer. Knots were weighed using microscales. Setting A laboratory experiment. Main outcome measure Weight of knot loops in milligrams. Results The heaviest ligature was the modified Roeder knot. The Western knot utilized less suture material than all the other knots studied. The flat square knot utilized less suture material than all the slip knots with the exception of the Western ligature. Conclusion As other studies have correlated suture mass with the incidence of wound infection, a ligature with a low weight should be chosen in preference to the modified Roeder knot where possible.

The lower-limb venous return, assessed by the peak systolic venous velocities (PSVV) of the left common femoral vein, was recorded at different stages of operation for five patients undergoing major gynecologic operative laparoscopy. The average baseline PSVV was 23.1 cm/s. After positioning the patient in the Trendelenburg position, the PSVV increased to an average of 31.5 cm/s; this was a statistically significant increase. Creation of the pneumoperitoneum changed the waveform from a normal phasic pattern to a dampened, continuous, monophasic waveform. The average PSVV was reduced to 15.9 cm/s; this dampening was statistically significant. Further dampening was evident 1 hour intraoperatively, and the flow became intermittent, with cycles of dampened flow followed by periods of absent flow; these changes in PSVV were not statistically significant. Calf compressors did not increase the femoral PSVV at the beginning of operation, nor at I hour intraoperatively; the decrease was not statistically significant. After release of the pneumoperitoneum, the baseline waveform pattern and velocity returned. The Trendelenburg position used for gynecologic operative laparoscopy was associated with a statistically significant increase in the lower-limb PSVV. This increase did not fully counteract the dampening effect of a pneumoperitoneum on lower-limb PSVV. The authors' study did not support the benefit previously reported on the use of pneumatic calf compressors. The authors therefore recommend continuing the practice of antithrombotic measures for patients undergoing gynecologic operative laparoscopy.

We present a multidisciplinary approach to the management of a 41-year-old woman who presented with an acute on chronic history of pelvic pain and urinary tract symptoms. The underlying pathology was found to be infiltrative ureteric and vesical endometriosis. The extent of the disease had caused partial ureteric obstruction. The patient subsequently underwent laparoscopic excision of the endometriosis with a laparoscopic extravesical neoureterocystostomy and vesicopsoas hitch, performed by an advanced laparoscopic gynaecologist and a urologist.

Traditional phase-resolve Doppler method demonstrates great success for in-vivo imaging of blood flow and blood vessel. However, the phase-resolved methods always require high phase stability of the system. During phase instable situations, the performance of the phase-resolved methods will be degraded. We propose a modified Doppler variance algorithm that is based on the intensity or amplitude value. Performances of the proposed algorithm are compared with traditional phase-resolved Doppler variance and color Doppler methods for two phase instability systems. The proposed algorithm demonstrates good performances without phase instability induced artifacts.

Herein is described an anterior approach to uterine artery ligation during laparoscopic myomectomy and total laparoscopic hysterectomy. The anterior leaf of the broad ligament is opened and the uterine artery is clipped lateral to its crossing over the ureter. Outcome measures were completion of the procedure laparoscopically and the need for transfusion postoperatively. Thirty-eight myomectomies and 28 difficult total laparoscopic hysterectomies (primarily uteri with large myomas) were performed, with 1 conversion to laparotomy during myomectomy and 1 during hysterectomy, and 1 transfusion after total laparoscopic hysterectomy. The anterior approach to uterine artery ligation is an alternative method for treatment of uterine artery occlusion during laparoscopic myomectomy or hysterectomy performed to treat large myomas.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS: We reviewed eight cases of acute generalized exanthematous pustulosis managed in a tertiary hospital in Singapore.Acute generalized exanthematous pustulosis (AGEP) is a pustular reaction characterized by a sudden eruption of widespread nonfollicular sterile pustules associated with systemic symptoms. AGEP is primarily believed to be an adverse reaction to drugs. Outside of Europe, few reports exist on the clinical presentation of AGEP.A retrospective review of patients who presented with AGEP to a Singapore tertiary hospital was performed.Eight patients were diagnosed with AGEP in 2006-2007. All patients presented with a macular, maculopapular eruption prior to the onset of pustules. AGEP was characterized by nonfollicular, pinpoint pustules, which were generalized and accentuated in the flexural areas in seven of the patients. The remaining patient had erythematous patches, and scattered plaques studded with pustules. Other less common features included oral/genital mucositis, blisters and erosions. The mean duration from the cessation of medications to defervescence, resolution of pustules and normalization of leukocytosis was 5, 6, and 7 d, respectively. Despite the resolution of pustules, two patients had protracted clinical courses with evolution to generalized exfoliative dermatitis and Drug rash, eosinophilia, and systemic symptoms (DRESS), respectively. The implicated medications included antibiotics in six patients, morphine and phenytoin in one patient each.Acute generalized exanthematous pustulosis is generally described as benign and self-limiting. However, in certain patients, the clinical course is prolonged and may exhibit features that overlap with other forms of cutaneous adverse drug reactions such as toxic epidermal necrolysis and DRESS.

Laparoscopic clipping of uterine arteries facilitates laparoscopic myomectomy with minimal blood loss. This paper shows the return to normal myometrial perfusion following this procedure with literary evidence of the safety and efficacy of this technique.

Study Objective To evaluate whether the addition of hysterectomy to laparoscopic pelvic floor repair has any impact on the short-term (perioperative) or long-term (prolapse outcome) effects of the surgery. Design A controlled prospective trial (Canadian Task Force classification II–1). Setting Private and public hospitals affiliated with a single institution. Patients A total of 64 patients with uterovaginal prolapse pelvic organ prolapse quantification system stage 2 to 4 had consent for laparoscopic pelvic floor repair from January 2005 through January 2006 (32 patients in each treatment arm). Patients self-selected to undergo hysterectomy in addition to their surgery. Interventions Patients were divided into group A (laparoscopic pelvic floor repair with hysterectomy) or group B (laparoscopic pelvic floor repair alone). All patients had laparoscopic pelvic floor repair in at least 1 compartment, whereas 52 patients had global pelvic floor prolapse requiring multicompartment repair. Burch colposuspension and/or additional vaginal procedures were performed at the discretion of the surgeon in each case. Measurements and Main Results Symptoms of prolapse and pelvic organ prolapse quantification system assessments were collected preoperatively, perioperatively, and at 6 weeks, 12 months, and 24 months postoperatively. Validated mental and physical health questionnaires (Short-Form Health Survey) were also completed at baseline, 6 weeks, and 12 months. No demographic differences occurred between the groups. Time of surgery was greater in group A (+35 minutes), as was estimated blood loss and inpatient stay, although the latter 2 results had no clinically significant impact. No difference between groups was detected in the rate of de novo postoperative symptoms. At 12 months, 4 (12.9%) patients in group A had recurrent prolapse as did 6 (21.4%) patients in group B. At 24 months these figures were 6 (22.2%) and 6 (21.4%), respectively. These differences were not statistically significant (p = .500 at 12 months and .746 at 24 months). In the group not having hysterectomy, 4 (14.3%) of 28 patients had cervical elongation or level-1 prolapse by the 12-month assessment. Conclusion The addition of total laparoscopic hysterectomy to laparoscopic pelvic floor repair adds approximately 35 minutes to surgical time with no difference in the rate of perioperative or postoperative complications or prolapse outcome. Leaving the uterus in situ, however, is associated with a risk of cervical elongation potentially requiring further surgery. Laparoscopic pelvic floor repair is successful in 80% of patients at 2 years.