The Clinical Translation of α-humulene - A Scoping Review.

α-humulene, a sesquiterpene found in essential oils of various plant species, has garnered interest due to its potential therapeutic applications. This scoping review aims to consolidate α-humulene's evidence base, informing clinical translation, and guiding future research directions. A scoping review was conducted of EMBASE, MEDLINE, and PubMed databases up to 14th July 2023. All studies describing original research on α-humulene extraction, as well as pre-clinical and clinical research, were included for review. Three hundred and forty articles were analysed. α-humulene yields ranged from negligible to 60.90% across plant species. In vitro experiments demonstrated cytotoxicity against adenocarcinomas (such as colorectal, pulmonary, breast, prostatic, lung, and ovarian), with varying responses in other cell models. Mechanistic insights revealed its involvement in mitochondrial dysfunction, diminished intracellular glutathione levels, and the induction of oxidative stress. In rodent studies, oral administration of α-humulene at 50 mg/kg reduced inflammation markers in paw oedema and ovalbumin-induced airway inflammation. Intraperitoneal administration of α-humulene (50 - 200 mg/kg) exhibited cannabimimetic properties through cannabinoid 1 and adenosine A2a receptors. α-humulene also exhibited a multitude of properties with potential scope for therapeutic utilisation. However, there is a paucity of studies that have successfully translated this research into clinical populations with the associated disease. Potential barriers to clinical translation were identified, including yield variability, limited isolation studies, and challenges associated with terpene bioavailability. Consequently, rigorous pharmacokinetic studies and further mechanistic investigations are warranted to effectively uncover the potential of α-humulene.

Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy-Analysis from the UK Medical Cannabis Registry.

BACKGROUND: There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. METHODS: A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events. RESULTS: Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). CONCLUSION: The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine.

Cannabidiol (CBD) is the main pharmacologically active phytocannabinoid. CBD exerts an analgesic effect in several pain models, does not have side effects and has low toxicity. The data about CBD mechanisms of action in pain and its therapeutic potential in this area are limited. Here, we tested CBD effects in animal models specific for migraine. We assayed CBD distribution in plasma and in cranial areas related to migraine pain in male Sprague Dawley rats treated chronically (5 days). Successively, we tested CBD activity on the behavioral and biochemical effects induced in the acute and the chronic migraine animal models by nitroglycerin (NTG) administration. In the acute migraine model, rats received CBD (15 mg or 30 mg/kg, i.p) 3 h after NTG (10 mg/kg i.p.) or vehicle injection. In the chronic migraine model, rats were treated with CBD and NTG every other day over nine days with the following doses: CBD 30 mg/kg i.p., NTG 10 mg/kg i.p. We evaluated behavioral parameters with the open field and the orofacial formalin tests. We explored the fatty acid amide hydrolase gene expression, cytokines mRNA and protein levels in selected brain areas and CGRP serum level. CBD levels in the meninges, trigeminal ganglia, cervical spinal cord, medulla pons, and plasma were higher 1 h after the last treatment than after 24 h, suggesting that CBD penetrates but does not accumulate in these tissues. In the acute model, CBD significantly reduced NTG-induced trigeminal hyperalgesia and CGRP and cytokine mRNA levels in peripheral and central sites. In the chronic model, CBD caused a significant decrease in NTG-induced IL-6 protein levels in the medulla-pons, and trigeminal ganglion. It also reduced CGRP serum levels. By contrast, CBD did not modulate TNF-alpha protein levels and fatty acid amide hydrolase (FAAH) gene expression in any of investigated areas. In both experimental conditions, there was no modulation of anxiety, motor/exploratory behavior, or grooming. These findings show that CBD reaches brain areas involved in migraine pain after systemic administration. They also show for the first time that CBD modulates migraine-related nociceptive transmission, likely via a complex signaling mechanism involving different pathways.

Quality of life after pancreatic surgery - A systematic review.

BACKGROUND: Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to assess the impact of surgical resection on health-related quality of life (HRQOL) of pancreatic cancer patients. METHODS: A systematic review of the literature was performed according to the PRISMA guidelines. All studies assessing QOL using validated questionnaires in pancreatic cancer patients undergoing surgical resection were included. RESULTS: Twenty-two studies were assessed. Patients reported a decrease in physical, social and global scales within the first 3 months after surgery. These values showed improvement and were comparable to baseline values by 6 months. Recovery in emotional functioning towards baseline figures was demonstrated in the first 3 months post-operatively. Symptom scales including pain, fatigue and diarrhoea deteriorated after surgery, but reverted to baseline after 3-6 months. CONCLUSIONS: Surgical resection for pancreatic cancer has short-term negative impact on QOL. In the longer term, this will improve and eventually recover to baseline values after 6 months. Knowledge on the impact of surgery on QOL of pancreatic cancer patients is necessary to facilitate decision-making and tailoring of surgical techniques to the individual patient.

PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma.

BACKGROUND: After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209-040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3-4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. METHODS: The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. DISCUSSION: The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. TRIAL REGISTRATION: EudraCT Number: 2018-000987-27 Clinical trial registry & ID: ClinicalTrials.gov : NCT03682276 .

MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models.

The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.

Visual gaze patterns reveal surgeons' ability to identify risk of bile duct injury during laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury is a serious surgical complication of laparoscopic cholecystectomy. The aim of this study was to identify distinct visual gaze patterns associated with the prompt detection of bile duct injury risk during laparoscopic cholecystectomy. METHODS: Twenty-nine participants viewed a laparoscopic cholecystectomy that led to a serious bile duct injury ('BDI video') and an uneventful procedure ('control video') and reported when an error was perceived that could result in bile duct injury. Outcome parameters include fixation sequences on anatomical structures and eye tracking metrics. Surgeons were stratified into two groups based on performance and compared. RESULTS: The 'early detector' group displayed reduced common bile duct dwell time in the first half of the BDI video, as well as increased cystic duct dwell time and Calot's triangle glances count during Calot's triangle dissection in the control video. Machine learning based classification of fixation sequences demonstrated clear separability between early and late detector groups. CONCLUSION: There are discernible differences in gaze patterns associated with early recognition of impending bile duct injury. The results could be transitioned into real time and used as an intraoperative early warning system and in an educational setting to improve surgical safety and performance.

Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice.

Excessive or inappropriate inflammatory responses can cause serious and even fatal diseases. The CCAAT/enhancer-binding protein alpha (CEBPA) gene encodes C/EBPα, a transcription factor that plays a fundamental role in controlling maturation of the myeloid lineage and is also expressed during the late phase of inflammatory responses when signs of inflammation are decreasing. MTL-CEBPA, a small activating RNA targeting for upregulation of C/EBPα, is currently being evaluated in a phase 1b trial for treatment of hepatocellular carcinoma. After dosing, subjects had reduced levels of pro-inflammatory cytokines, and we therefore hypothesized that MTL-CEBPA has anti-inflammatory potential. The current study was conducted to determine the effects of C/EBPα saRNA - CEBPA-51 - on inflammation in vitro and in vivo after endotoxin challenge. CEBPA-51 led to increased expression of the C/EBPα gene and inhibition of pro-inflammatory cytokines in THP-1 monocytes previously stimulated by E. coli-derived lipopolysaccharide (LPS). Treatment with MTL-CEBPA in an LPS-challenged humanized mouse model upregulated C/EBPα mRNA, increased neutrophils, and attenuated production of several key pro-inflammatory cytokines, including TNF-α, IL-6, IL-1ß, and IFN-γ. In addition, a Luminex analysis of mouse serum revealed that MTL-CEBPA reduced pro-inflammatory cytokines and increased the anti-inflammatory cytokine IL-10. Collectively, the data support further investigation of MTL-CEBPA in acute and chronic inflammatory diseases where this mechanism has pathogenic importance.

No difference in mortality among ALPPS, two-staged hepatectomy, and portal vein embolization/ligation: A systematic review by updated traditional and network meta-analyses.

BACKGROUND: There is an ongoing debate on the feasibility, safety, and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique. The aim of this study was to compare ALPPS, two-staged hepatectomy (TSH), and portal vein embolization (PVE)/ligation (PVL) using updated traditional meta-analysis and network meta-analysis (NMA). DATA SOURCES: Electronic databases were used in a systematic literature search. Updated traditional meta-analysis and NMA were performed and compared. Mortality and major morbidity were selected as primary outcomes. RESULTS: Nineteen studies including 1200 patients were selected from the pool of 436 studies. Of these patients, 315 (31%) and 702 (69%) underwent ALPPS and portal vein occlusion (PVO), respectively. Ninety-day mortality based on updated traditional meta-analysis, subgroup analysis of the randomized controlled trials (RCTs), and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE, PVL, and TSH cohorts. Moreover, analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts. The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters, time to operation, definitive hepatectomy, and R0 margins rates compared with the PVO cohort. In contrast, 1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort. CONCLUSIONS: This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches. Furthermore, two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

Gaze patterns hold key to unlocking successful search strategies and increasing polyp detection rate in colonoscopy.

BACKGROUND: The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR. METHODS: 18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses - screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis. RESULTS: Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P = 0.02; anatomy: r = 0.62, P < 0.01). Fixation distribution to the "bottom U" of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P = 0.01). HMM demarcated the VGPs into three PDR groups. CONCLUSION: This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment.

Eye-tracking technology in medical education: A systematic review.

BACKGROUND: Eye-tracking technology is an established research tool within allied industries such as advertising, psychology and aerospace. This review aims to consolidate literature describing the evidence for use of eye-tracking as an adjunct to traditional teaching methods in medical education. METHODS: A systematic literature review was conducted in line with STORIES guidelines. A search of EMBASE, OVID MEDLINE, PsycINFO, TRIP database, and Science Direct was conducted until January 2017. Studies describing the use of eye-tracking in the training, assessment, and feedback of clinicians were included in the review. RESULTS: Thirty-three studies were included in the final qualitative synthesis. Three studies were based on the use of gaze training, three studies on the changes in gaze behavior during the learning curve, 17 studies on clinical assessment and six studies focused on the use of eye-tracking methodology as a feedback tool. The studies demonstrated feasibility and validity in the use of eye-tracking as a training and assessment method. CONCLUSIONS: Overall, eye-tracking methodology has contributed significantly to the training, assessment, and feedback practices used in the clinical setting. The technology provides reliable quantitative data, which can be interpreted to give an indication of clinical skill, provide training solutions and aid in feedback and reflection. This review provides a detailed summary of evidence relating to eye-tracking methodology and its uses as a training method, changes in visual gaze behavior during the learning curve, eye-tracking methodology for proficiency assessment and its uses as a feedback tool.

The role of technology in minimally invasive surgery: state of the art, recent developments and future directions.

The diffusion of minimally invasive surgery has thrived in recent years, providing substantial benefits over traditional techniques for a number of surgical interventions. This rapid growth has been possible due to significant advancements in medical technology, which partly solved some of the technical and clinical challenges associated with minimally invasive techniques. The issues that still limit its widespread adoption for some applications include the limited field of view; reduced manoeuvrability of the tools; lack of haptic feedback; loss of depth perception; extended learning curve; prolonged operative times and higher financial costs. The present review discusses some of the main recent technological advancements that fuelled the uptake of minimally invasive surgery, focussing especially on the areas of imaging, instrumentation, cameras and robotics. The current limitations of state-of-the-art technology are identified and addressed, proposing future research directions necessary to overcome them.

Validation of NOViSE.

The goal of this study was to establish face, content, and construct validity of NOViSE-the first force-feedback enabled virtual reality (VR) simulator for natural orifice transluminal endoscopic surgery (NOTES). Fourteen surgeons and surgical trainees performed 3 simulated hybrid transgastric cholecystectomies using a flexible endoscope on NOViSE. Four of them were classified as "NOTES experts" who had independently performed 10 or more simulated or human NOTES procedures. Seven participants were classified as "Novices" and 3 as "Gastroenterologists" with no or minimal NOTES experience. A standardized 5-point Likert-type scale questionnaire was administered to assess the face and content validity. NOViSE showed good overall face and content validity. In 14 out of 15 statements pertaining to face validity (graphical appearance, endoscope and tissue behavior, overall realism), ≥50% of responses were "agree" or "strongly agree." In terms of content validity, 85.7% of participants agreed or strongly agreed that NOViSE is a useful training tool for NOTES and 71.4% that they would recommend it to others. Construct validity was established by comparing a number of performance metrics such as task completion times, path lengths, applied forces, and so on. NOViSE demonstrated early signs of construct validity. Experts were faster and used a shorter endoscopic path length than novices in all but one task. The results indicate that NOViSE authentically recreates a transgastric hybrid cholecystectomy and sets promising foundations for the further development of a VR training curriculum for NOTES without compromising patient safety or requiring expensive animal facilities.

Looking towards objective quality evaluation in colonoscopy: Analysis of visual gaze patterns.

BACKGROUND AND AIM: There are currently limited training and assessment tools available to novice endoscopists. A potential tool for the objective assessment of endoscopist visual search strategy is eye-tracking technology. The aim of this study is to assess whether eye-tracking technology can be used to differentiate the visual gaze patterns (VGP) of experienced and novice endoscopists, and to characterize any differences arising between the two groups. METHOD: With the use of portable eye-tracking glasses, VGP of novice (n = 20) and experienced (n = 14) endoscopists were compared while viewing a colonoscopy withdrawal through the hepatic flexure. Analysis was performed by comparing the central versus peripheral distribution and the horizontal distribution of novice and experienced endoscopist fixations, along with comparison of basic eye-tracking metrics. RESULTS: This study found that experienced endoscopists had a significantly higher percentage of fixations within the periphery of the screen (13.4% vs 23.0%, P = 0.013). Experienced endoscopists also had a significantly greater percentage of fixations on the left side of the screen (18.6% vs 33.5%, P = 0.005) that displayed the poorly visualized "inside bend" of the hepatic flexure. CONCLUSION: This study has detailed specific VGP acquired through expertise, which can potentially explain why adenomas are regularly missed at the hepatic flexure during colonoscopy. These may be useful for the training of novice colonoscopists, and further validation may utilize VGP in the development of an objective proficiency based curriculum to improve the detection of pathology and overall quality in endoscopy.

Consumer demand for surgical innovation: a systematic review of public perception of NOTES.

BACKGROUND: The full scope of benefits offered by NOTES over traditional laparoscopy, if any, is not yet fully clear. Perceived patient demand for truly "scarless surgery" is often referenced one of the driving factors in the continued development of this relatively new technique. The true scale of patient preference and demand for NOTES as a surgical technique is unknown. This review aims to summarise currently available literature on the topic of patient perceptions of NOTES to guide future development of the technique. METHODS: A comprehensive search of PubMed and Web of Science electronic databases was performed on 1st Jan 2014. To be considered for inclusion, articles were required to assess and report the perception of NOTES in a sample of laypersons (patients or general public). The primary endpoint assessed was acceptance or preference rates expressed by patients for NOTES procedures. Reasons given for preference or rejection of NOTES were recorded, as well as preferred access routes and any predicting factors of NOTES acceptance. RESULTS: Initial search returned 1,334 results, resulting in 15 articles included in final data synthesis. These polled a total of 4,420 subjects. Acceptance of NOTES ranged between 41 and 84 %. Compared to a laparoscopic approach, preference rates for NOTES ranged from 0 to 78 %. Reasons for preferring NOTES were largely centred on potentially reduced recovery time, complications (particularly with reference to hernias) and postoperative pain. Improved cosmesis also played a role, but was secondary to the above issues. Overall, study quality was poor. CONCLUSIONS: This review suggests significant public interest in NOTES and scarless surgery in general. Further research and consideration of differences in public perceptions across regions, countries and cultures are required.

Differences in gaze behaviour of expert and junior surgeons performing open inguinal hernia repair.

INTRODUCTION: Various fields have used gaze behaviour to evaluate task proficiency. This may also apply to surgery for the assessment of technical skill, but has not previously been explored in live surgery. The aim was to assess differences in gaze behaviour between expert and junior surgeons during open inguinal hernia repair. METHODS: Gaze behaviour of expert and junior surgeons (defined by operative experience) performing the operation was recorded using eye-tracking glasses (SMI Eye Tracking Glasses 2.0, SensoMotoric Instruments, Germany). Primary endpoints were fixation frequency (steady eye gaze rate) and dwell time (fixation and saccades duration) and were analysed for designated areas of interest in the subject's visual field. Secondary endpoints were maximum pupil size, pupil rate of change (change frequency in pupil size) and pupil entropy (predictability of pupil change). NASA TLX scale measured perceived workload. Recorded metrics were compared between groups for the entire procedure and for comparable procedural segments. RESULTS: Twenty-five cases were recorded, with 13 operations analysed, from 9 surgeons giving 630 min of data, recorded at 30 Hz. Experts demonstrated higher fixation frequency (median[IQR] 1.86 [0.3] vs 0.96 [0.3]; P = 0.006) and dwell time on the operative site during application of mesh (792 [159] vs 469 [109] s; P = 0.028), closure of the external oblique (1.79 [0.2] vs 1.20 [0.6]; P = 0.003) (625 [154] vs 448 [147] s; P = 0.032) and dwelled more on the sterile field during cutting of mesh (716 [173] vs 268 [297] s; P = 0.019). NASA TLX scores indicated experts found the procedure less mentally demanding than juniors (3 [2] vs 12 [5.2]; P = 0.038). No subjects reported problems with wearing of the device, or obstruction of view. CONCLUSION: Use of portable eye-tracking technology in open surgery is feasible, without impinging surgical performance. Differences in gaze behaviour during open inguinal hernia repair can be seen between expert and junior surgeons and may have uses for assessment of surgical skill.

Safety of transvaginal hybrid NOTES cholecystectomy: a systematic review and meta-analysis.

BACKGROUND: Despite increasing data regarding clinical outcomes following transvaginal hybrid NOTES cholecystectomy (TVC), a consensus regarding safety based on comparative studies has yet to be reached. The aim of this systematic review and meta-analysis was to compare safety and clinical outcomes of TVC with conventional laparoscopic cholecystectomy (CLC) for the treatment of benign gallstone disease. METHODS: A comprehensive search for published studies comparing TVC and CLC was performed. Review of each study was conducted and data were extracted. All pooled outcome measures were determined using random-effects models. RESULTS: Data were retrieved from 14 studies describing 1,145 patients. There was no difference in total complications (POR = 0.68; 95 % CI 0.40-1.14; P = 0.14), incidence of bile duct injury (POR = 1.33; 95 % CI 0.31-5.66; P = 0.70), Clavien-Dindo Grade II (POR = 0.48; 95 % CI 0.14-1.60; P = 0.23) or Grade III (POR = 0.63; 95 % CI 0.24-1.65; P = 0.34) complications between TCV and CLC. Time of return to normal activities was significantly reduced in the TVC group (WMD = -4.86 days; 95 % CI -9.33 to -0.39; P = 0.03), and there was a non-significant reduction in postoperative pain on days 1 (WMD = -0.80; 95 % CI -1.60 to 0.01; P = 0.05) and 3 (WMD = -0.89; 95 % CI -1.77 to -0.01; P = 0.05). CONCLUSIONS: TVC is safe when performed by appropriately trained surgeons and may be associated with a faster return to normal activities and decreased postoperative pain.

A novel flexible hyper-redundant surgical robot: prototype evaluation using a single incision flexible access pelvic application as a clinical exemplar.

INTRODUCTION: The flexible endoscope is increasingly being considered as a surgical tool to enable innovative natural orifice or flexible access techniques. These experiences have exposed unique advantages but also significant challenges. Major current technical drawbacks in this setting relate to uncontrolled flexibility, inaccurate sustained target localization, unreliable navigation and overall platform instability. In striving to address existing technical limitations, this paper introduces a novel flexible hyper-redundant surgical robot and evaluates its clinical potential using a focused clinical application. METHOD: To assess utility of the device within tight confines of the human pelvis or peritoneal cavity, detailed laboratory workspace analysis experiments were undertaken using a computer-simulated model that incorporated anatomical data obtained via pelvic magnetic resonance images of eight women. Ten participants executed ninety usability and reliability trials on an ex vivo simulator, before the robot was repeatedly trialled in an in vivo porcine model. RESULTS: The robot demonstrated capability of targeting >90 % of the anatomic region of interest. All 90 user trials were successfully performed without interruption or malfunction. Significant improvements in performance, time and motion were observed between first and last sets of trials (p = 0.001). In vivo feasibility testing affirmed robustness of the device when deployed within the physiological demands of a live scale appropriate model. CONCLUSION: Technologically advanced flexible operative platforms are needed to fulfil aspirations for an introductory era of flexible access surgery. This prototype is proposed as a potential future platform for robot-assisted flexible endoscopic surgery. Encouraging pre-clinical feasibility results are demonstrated for diagnostic and therapeutic applications within the pelvis.

A Randomized Controlled Study to Evaluate the Impact of Instrument and Laparoscope Length on Performance and Learning Curve in Single-Incision Laparoscopic Surgery.

INTRODUCTION: The proximity of instrumentation in single-incision laparoscopic surgery (SILS) creates ergonomic challenges. An innovative method to reduce external collisions between instruments and handles is to use instruments of different lengths. This study evaluated the impact of instrument and laparoscope length on simulated SILS performance. METHODS: Performance was assessed using peg transfer (PEG) and pattern cutting (CUT) tasks from the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Following baseline testing, surgeons were randomized into 3 trial arms: Control--standard length instruments and standard length laparoscope; group 1--one long instrument, one standard length instrument and standard length laparoscope; and group 2--standard length instruments and long laparoscope. Two phases were undertaken using a validated SILS-modified FLS box trainer: phase 1--25 repetitions of PEG and phase 2--5 repetitions of CUT. FLS scoring parameters measured performance and the Imperial College Surgical Assessment Device (ICSAD) captured motion analysis of hands. RESULTS: Twenty-three surgeons were recruited--control (n = 7), group 1 (n = 9), and group 2 (n = 7). No significant differences were observed in operative experience or baseline skills performance. Phase 1: Peak FLS score was significantly higher in group 1 compared with control (P = .009). Comparison of learning curves revealed learning plateau was significantly higher in group 1 compared with control (P = .010). Phase 2: Group 1 revealed a trend toward higher peak FLS scores over the control (P = .067). No significant differences in motion analysis of hands were demonstrated using ICSAD. CONCLUSIONS: This study demonstrates that using instruments of different lengths can improve simulated SILS performance.