Hypoxia-Inducible Factor-1 as a Therapeutic Target in Endometrial Cancer Management

In the Western world, endometrial cancer (EC) is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1α (HIF-1α) plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1α protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials

Ninety-day morbidity of robot-assisted redo surgery for recurrent rectal prolapse, mesh erosion and pelvic pain:lessons learned from 9 years' experience in a tertiary referral centre

Aim With increasing follow-up of patients treated with minimally invasive ventral mesh rectopexy (VMR) more redo surgery can be expected for recurrent rectal prolapse, mesh erosion and pelvic pain. The aim of this study is to evaluate the 90-day morbidity of robot-assisted redo interventions. Method All robot-assisted redo interventions after primary transabdominal repair of rectal prolapse between 2011 and 2019 were retrospectively analysed and compared with the results for patients after primary robot-assisted VMR during the same period. The redo interventions were divided into groups based on the indication for surgery (recurrent prolapse, mesh erosion, pelvic pain). Intraoperative complications and 90-day postoperative morbidity were evaluated. Results Three hundred and fifty nine patients were treated with primary VMR, with 73 for recurrent rectal prolapse, 12 for mesh erosion and 14 for pelvic pain. Complications of recurrent prolapse surgeries were comparable to those of primary VMR (p > 0.05). More intraoperative complications, minor and major complications were seen in redo surgery for erosion compared with primary VMR (23% vs. 3%, p = 0.01; 31% vs. 11%, p = 0.055; and 38% vs. 1%, p 0.05). Half of the patients with pelvic pain experienced relief of their symptoms. Conclusion Redo surgery for management of recurrent rectal prolapse is safe. Redo surgery for mesh erosion is associated with high morbidity rates. Redo surgery for pelvic pain can have major complications and is only effective in half of the cases

The learning curve of laparoscopic, robot-assisted and transanal total mesorectal excisions:a systematic review

Background The standard treatment of rectal carcinoma is surgical resection according to the total mesorectal excision principle, either by open, laparoscopic, robot-assisted or transanal technique. No clear consensus exists regarding the length of the learning curve for the minimal invasive techniques. This systematic review aims to provide an overview of the current literature regarding the learning curve of minimal invasive TME. Methods A systematic literature search was performed. PubMed, Embase and Cochrane Library were searched for studies with the primary or secondary aim to assess the learning curve of either laparoscopic, robot-assisted or transanal TME for rectal cancer. The primary outcome was length of the learning curve per minimal invasive technique. Descriptive statistics were used to present results and the MINORS tool was used to assess risk of bias. Results 45 studies, with 7562 patients, were included in this systematic review. Length of the learning curve based on intraoperative complications, postoperative complications, pathological outcomes, or a composite endpoint using a risk-adjusted CUSUM analysis was 50 procedures for the laparoscopic technique, 32-75 procedures for the robot-assisted technique and 36-54 procedures for the transanal technique. Due to the low quality of studies and a high level of heterogeneity a meta-analysis could not be performed. Heterogeneity was caused by patient-related factors, surgeon-related factors and differences in statistical methods. Conclusion Current high-quality literature regarding length of the learning curve of minimal invasive TME techniques is scarce. Available literature suggests equal lengths of the learning curves of laparoscopic, robot-assisted and transanal TME. Well-designed studies, using adequate statistical methods are required to properly assess the learning curve, while taking into account patient-related and surgeon-related factors

Long-term Anatomical and Functional Results of Robot-Assisted Pelvic Floor Surgery for the Management of Multicompartment Prolapse:A Prospective Study

BACKGROUND: Long-term data on robot-assisted sacrocolporectopexy for the treatment of multicompartment pelvic organ prolapse are scarce. With the rising prevalence of prolapse and increasing surgical repair, it is essential to evaluate long-term results. OBJECTIVE: This study aimed to evaluate long-term functional and anatomic outcomes after sacrocolporectopexy. DESIGN: This is a prospective, observational cohort study. SETTINGS: This study was conducted at a teaching hospital with tertiary referral function for patients with gynecological/rectal prolapse. PATIENTS: All patients undergoing robot-assisted sacrocolporectopexy from 2011 to 2012 were included. INTERVENTION: Robot-assisted sacrocolporectopexy was performed. MAIN OUTCOME MEASURES: The primary outcome was the anatomic cure rate after 1 and 4 years, defined as simplified pelvic organ prolapse quantification stage 1 vaginal apical prolapse and no external rectal prolapse or internal rectal prolapse present. Kaplan-Meier curves were used for determination of recurrence-free intervals. Secondary outcomes were functional pelvic floor symptoms (symptoms of bulge, obstructed defecation, fecal incontinence, urogenital distress inventory) and quality of life (Pelvic Floor Impact Questionnaire). RESULTS: Fifty-three patients were included. After 12 and 48 months, the recurrence-free intervals based on Kaplan-Meier estimates were 100% and 90%. In total, there were 10 recurrences: 2 apical and 8 internal rectal prolapses. Symptoms of bulge (94%-12%; p < 0.0005), fecal incontinence (62%-32%; p < 0.0005), obstructed defecation (59%-24%; p = 0.008), and median Pelvic Floor Impact Questionnaire scores (124-5; p = 0.022) improved significantly at final follow-up. Median urogenital distress inventory scores showed improvement after 1 year (30-13; p = 0.021). LIMITATIONS: This was an observational, single-center study with selective postoperative imaging. CONCLUSIONS: Ninety percent of patients were recurrence free 48 months after robot-assisted sacrocolporectopexy. Symptoms of vaginal bulge, quality of life, constipation, and fecal incontinence improved significantly. However, a subgroup of patients showed persistent bowel complaints that underlie the complexity of multicompartment prolapse. See Video Abstract at http://links.lww.com/DCR/B265

Long-term mesh erosion rate following abdominal robotic reconstructive pelvic floor surgery:a prospective study and overview of the literature

Introduction and hypothesis: The use of synthetic mesh in transvaginal pelvic floor surgery has been subject to debate internationally. Although mesh erosion appears to be less associated with an abdominal approach, the long-term outcome has not been studied intensively. This study was set up to determine the long-term mesh erosion rate following abdominal pelvic reconstructive surgery. Methods: A prospective, observational cohort study was conducted in a tertiary care setting. All consecutive female patients who underwent robot-assisted laparoscopic sacrocolpopexy and sacrocolporectopexy in 2011 and 2012 were included. Primary outcome was mesh erosion. Preoperative and postoperative evaluation (6 weeks, 1 year, 5 years) with a clinical examination and questionnaire regarding pelvic floor symptoms was performed. Mesh-related complications were assessed using a transparent vaginal speculum, proctoscopy, and digital vaginal and rectal examination. Kaplan–Meier estimates were calculated for mesh erosion. A review of the literature on mesh exposure after minimally invasive sacrocolpopexy was performed (≥12 months’ follow-up). Results: Ninety-six of the 130 patients included (73.8%) were clinically examined. Median follow-up time was 48.1 months (range 36.0–62.1). Three mesh erosions were diagnosed (3.1%; Kaplan–Meier 4.9%, 95% confidence interval 0–11.0): one bladder erosion for which mesh resection and an omental patch interposition were performed, and two asymptomatic vaginal erosions (at 42.7 and 42.3 months) treated with estrogen cream in one. Additionally, 22 patients responded solely by questionnaire and/or telephone; none reported mesh-related complaints. The literature, mostly based on retrospective studies, described a median mesh erosion rate of 1.9% (range 0–13.3%). Conclusions: The long-term rate of mesh erosion following an abdominally placed synthetic graft is low

Robot-Assisted Total Mesorectal Excision Versus Laparoscopic Total Mesorectal Excision:A Retrospective Propensity Score-Matched Cohort Analysis in Experienced Centers

BACKGROUND: The superiority of robot-assisted over laparoscopic total mesorectal excision has not been proven. Most studies do not consider the learning curve while comparing the surgical technique. OBJECTIVE: This study aims to compare laparoscopic with robot-assisted total mesorectal excision performed by surgeons who completed the learning curve of the technique. DESIGN: This is a multicenter retrospective propensity score-matched analysis. SETTINGS: The study was performed in 2 large, dedicated robot-assisted hospitals and 5 large, dedicated laparoscopic hospitals. PATIENTS: Patients were included if they underwent a robot-assisted or laparoscopic total mesorectal excision for rectal cancer with curative intent at a dedicated center for the minimally invasive technique between January 1, 2015, and December 31, 2017. INTERVENTIONS: We compared robot-assisted with laparoscopic total mesorectal excision. MAIN OUTCOME MEASURES: The main outcome was conversion to laparotomy during surgery. Secondary outcomes were postoperative morbidity and positive circumferential resection margin. RESULTS: A total of 884 patients were included and, after matching, 315 patients per treatment group remained. Conversion was similar between laparoscopic and robot-assisted total mesorectal excision (4.4% vs 2.5% (p = 0.20)). Positive circumferential resection margin was equal (3.2% vs 4.4% (p = 0.41)). Overall morbidity was comparable as well, although a lower rate of wound infections was observed in the robot-assisted group (5.7% vs 1.9% (p = 0.01)). More primary anastomoses were constructed in the robot-assisted group (50.8% vs 68.3% (p < 0.001)). Finally, more open procedures were performed in dedicated laparoscopic centers, with an overrepresentation of cT4N+ tumors in this group. LIMITATIONS: This is a retrospective multicenter cohort; however, propensity score matching was applied to control for confounding by indication. CONCLUSIONS: Robot-assisted and laparoscopic total mesorectal excision are equally safe in terms of short-term outcomes. However, with the robot-assisted approach, more primary anastomoses were constructed, and a lower wound infection rate was observed. See Video Abstract at http://links.lww.com/DCR/B677

Diffusive and Ballistic Transport in Ultra-thin InSb Nanowire Devices Using a Few-layer-Graphene-AlOx Gate

Quantum devices based on InSb nanowires (NWs) are a prime candidate system for realizing and exploring topologically-protected quantum states and for electrically-controlled spin-based qubits. The influence of disorder on achieving reliable topological regimes has been studied theoretically, highlighting the importance of optimizing both growth and nanofabrication. In this work we investigate both aspects. We developed InSb nanowires with ultra-thin diameters, as well as a new gating approach, involving few-layer graphene (FLG) and Atomic Layer Deposition (ALD)-grown AlOx. Low-temperature electronic transport measurements of these devices reveal conductance plateaus and Fabry-P\'erot interference, evidencing phase-coherent transport in the regime of few quantum modes. The approaches developed in this work could help mitigate the role of material and fabrication-induced disorder in semiconductor-based quantum devices.Comment: 14 pages, 5 figure

GASKAP -- The Galactic ASKAP Survey

A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (HI) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of HI emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b|< 10deg) at all declinations south of delta = +40deg, spanning longitudes 167deg through 360deg to 79deg at b=0deg, plus the entire area of the Magellanic Stream and Clouds, a total of 13,020 square degrees. The brightness temperature sensitivity will be very good, typically sigma_T ~ 1 K at resolution 30arcsec and 1 km/s. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.Comment: 45 pages, 8 figures, Pub. Astron. Soc. Australia (in press