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1.
Planta Med ; 90(9): 664-674, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38626911

ABSTRACT

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.


Subject(s)
Monocyclic Sesquiterpenes , Oils, Volatile , Monocyclic Sesquiterpenes/pharmacology , Monocyclic Sesquiterpenes/chemistry , Humans , Animals , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry
2.
Neuropediatrics ; 54(3): 174-181, 2023 06.
Article in English | MEDLINE | ID: mdl-36539215

ABSTRACT

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.


Subject(s)
Cannabis , Drug Resistant Epilepsy , Epilepsy , Medical Marijuana , Child , Humans , Adolescent , Medical Marijuana/adverse effects , Dronabinol/therapeutic use , Drug Resistant Epilepsy/drug therapy , Epilepsy/drug therapy , Seizures/drug therapy , United Kingdom
3.
Int J Mol Sci ; 24(22)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38003528

ABSTRACT

Terpenes in Cannabis sativa exert analgesic effects, but the mechanisms are uncertain. We examined the effects of 10 terpenes on capsaicin responses in an established model of neuronal hypersensitivity. Adult rat DRG neurons cultured with neurotrophic factors NGF and GDNF were loaded with Fura2AM for calcium imaging, and treated with individual terpenes or vehicle for 5 min, followed by 1 µMol capsaicin. In vehicle treated control experiments, capsaicin elicited immediate and sustained calcium influx. Most neurons treated with terpenes responded to capsaicin after 6-8 min. Few neurons showed immediate capsaicin responses that were transient or normal. The delayed responses were found to be due to calcium released from the endoplasmic reticulum, as they were maintained in calcium/magnesium free media, but not after thapsigargin pre-treatment. Terpene inhibition of calcium influx was reversed after washout of medium, in the absence of terpenes, and in the presence of the Na+/K+ ATPase inhibitor ouabain, but not CB1 or CB2 receptor antagonists. Thus, terpenes inhibit capsaicin evoked calcium influx by Na+/K+ ATPase activation. Immunofluorescence showed TRPV1 co-expression with α1ß1 Na+/K+ ATPase in most neurons while others were either TRPV1 or α1ß1 Na+/K+ ATPase positive.


Subject(s)
Cannabis , Capsaicin , Rats , Animals , Capsaicin/pharmacology , Cannabis/metabolism , Adenosine Triphosphatases , Terpenes/pharmacology , Calcium/metabolism , Neurons/metabolism , TRPV Cation Channels , Ganglia, Spinal/metabolism , Cells, Cultured
4.
J Headache Pain ; 24(1): 48, 2023 May 03.
Article in English | MEDLINE | ID: mdl-37138206

ABSTRACT

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.


Subject(s)
Cannabidiol , Migraine Disorders , Rats , Male , Animals , Rats, Sprague-Dawley , Cannabidiol/adverse effects , Calcitonin Gene-Related Peptide/metabolism , Pain , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Hyperalgesia/metabolism , Nitroglycerin/adverse effects , Migraine Disorders/chemically induced , Migraine Disorders/drug therapy , Migraine Disorders/metabolism , Disease Models, Animal
5.
Scand J Gastroenterol ; 57(9): 1138-1146, 2022 09.
Article in English | MEDLINE | ID: mdl-35450506

ABSTRACT

BACKGROUND: Colonoscopy proficiency is significantly influenced by skills achieved during training. Although assessment scores exist, they do not evaluate the impact of visual search strategies and their use is time and labour intensive. Eye-tracking has shown significant differences in visual gaze patterns (VGPs) between expert endoscopists with varying polyp detection rates, so may provide a means of automated assessment and guidance for trainees. This study aimed to assess the feasibility of eye-tracking as a novel assessment method for trainee endoscopists. METHODS: Eye-tracking glasses were used to record 26 colonoscopies from 12 endoscopy trainees who were assessed with directly observed procedural scores (DOPS), devised by the Joint Advisory Group (JAG) on GI endoscopy, and a visual analogue score of overall competence. A 'total weighted procedure score' (TWPS) was calculated from 1 to 20. Primary outcomes of fixation duration (FixD) and fixation frequency (FixF) were analysed according to areas of interest (AOIs) with the bowel surface and lumen represented by three concentric rings. Correlation was assessed using Pearson's coefficient. Significance was set at p<.050. RESULTS: Trainees displayed a significant positive correlation between TWPS and FixD (R = 0.943, p<.0001) and FixF (R = 0.936, p<.0001) in the anatomical bowel mucosa peripheries. Conversely, they had significant negative correlations between TWPS and the anatomical bowel lumen (FixD: R= -0.546, p=.004; FixF: R= -0.568, p=.002). CONCLUSIONS: Higher objective performance scores were associated with VGPs focussing on bowel mucosa. This is consistent with prior analysis showing peripheral VGPs correspond with higher polyp detection rates. Analysis of VGPs, therefore, has potential for training and assessment in colonoscopy.


Subject(s)
Colonic Polyps , Colonoscopy , Gastroenterologists , Intestinal Mucosa , Clinical Competence , Colonic Polyps/diagnostic imaging , Colonoscopy/methods , Eye Movement Measurements , Gastroenterologists/education , Humans
6.
Curr Treat Options Oncol ; 23(7): 1014-1034, 2022 07.
Article in English | MEDLINE | ID: mdl-35511346

ABSTRACT

OPINION STATEMENT: Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) comprise a heterogeneous group of slow growing tumors arising from the neuroendocrine cells of the gastrointestinal (GI) tract. Although they are considered relatively rare, their incidence is rising and it is believed that the more frequent use of endoscopy and imaging studies have at least in part contributed to the increased diagnosis especially of localized neoplasms. The management of these neoplasms should be guided by a multidisciplinary NEN team following appropriate staging investigations. Localized neoplasms of the GI tract may be suitable for endoscopic therapy, while patients with pancreatic NENs, unsuitable for surgery, should be considered for endoscopic ultrasound (EUS)-guided ablation. In this review, we discuss the evidence regarding endoscopic resection of luminal NENs and EUS-guided therapy of pancreatic NENs. The efficacy, safety, and other longer-term outcomes of these techniques are summarized. In conclusion, this review of endoscopic therapies for localized NENs may be a useful guide for NEN clinicians and endoscopists who are considering these therapeutic options for the management of focal GEP NENs.


Subject(s)
Gastrointestinal Neoplasms , Intestinal Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Stomach Neoplasms , Endoscopy , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/surgery , Humans , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/surgery , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery
7.
HPB (Oxford) ; 24(8): 1223-1237, 2022 08.
Article in English | MEDLINE | ID: mdl-35304039

ABSTRACT

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.


Subject(s)
Pancreatic Neoplasms , Quality of Life , Humans , Pancreatic Neoplasms/psychology , Pancreatic Neoplasms/surgery , Prospective Studies , Surveys and Questionnaires , Pancreatic Neoplasms
8.
BMC Cancer ; 21(1): 301, 2021 Mar 23.
Article in English | MEDLINE | ID: mdl-33757459

ABSTRACT

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 .


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Hepatectomy , Immune Checkpoint Inhibitors/administration & dosage , Liver Neoplasms/drug therapy , Humans , Ipilimumab/administration & dosage , Ipilimumab/adverse effects , Neoadjuvant Therapy , Nivolumab/administration & dosage , Nivolumab/adverse effects , Outcome Assessment, Health Care
9.
Int J Mol Sci ; 22(17)2021 Aug 25.
Article in English | MEDLINE | ID: mdl-34502076

ABSTRACT

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.


Subject(s)
CCAAT-Enhancer-Binding Proteins/genetics , Carcinoma, Hepatocellular/drug therapy , Colonic Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/drug therapy , Lymphocytes, Tumor-Infiltrating/drug effects , RNA, Double-Stranded/therapeutic use , Animals , CCAAT-Enhancer-Binding Proteins/metabolism , Carcinoma, Hepatocellular/surgery , Cell Line, Tumor , Cells, Cultured , Colonic Neoplasms/surgery , Liver Neoplasms/immunology , Liver Neoplasms/radiotherapy , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Inbred BALB C , Radiofrequency Ablation , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
10.
HPB (Oxford) ; 23(5): 715-722, 2021 05.
Article in English | MEDLINE | ID: mdl-32988756

ABSTRACT

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.


Subject(s)
Bile Duct Diseases , Cholecystectomy, Laparoscopic , Surgeons , Bile Ducts/diagnostic imaging , Bile Ducts/surgery , Cholecystectomy, Laparoscopic/adverse effects , Common Bile Duct/diagnostic imaging , Common Bile Duct/surgery , Cystic Duct , Humans
11.
Mol Ther ; 27(5): 999-1016, 2019 05 08.
Article in English | MEDLINE | ID: mdl-30852139

ABSTRACT

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.


Subject(s)
CCAAT-Enhancer-Binding Proteins/genetics , Inflammation/therapy , Monocytes/drug effects , RNA/genetics , Animals , Anti-Inflammatory Agents/pharmacology , CCAAT-Enhancer-Binding Proteins/antagonists & inhibitors , Gene Expression Regulation/drug effects , Humans , Inflammation/chemically induced , Inflammation/genetics , Inflammation/pathology , Interleukin-10/genetics , Interleukin-1beta/genetics , Lipopolysaccharides/toxicity , Mice , Monocytes/metabolism , RNA/pharmacology , RNA, Messenger/genetics , Tumor Necrosis Factor-alpha/genetics
12.
Hepatobiliary Pancreat Dis Int ; 19(5): 411-419, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32753333

ABSTRACT

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.


Subject(s)
Embolization, Therapeutic , Hepatectomy , Liver Regeneration , Liver/surgery , Portal Vein/surgery , Adult , Aged , Aged, 80 and over , Bayes Theorem , Cell Proliferation , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/mortality , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Ligation , Liver/pathology , Liver/physiopathology , Male , Middle Aged , Network Meta-Analysis , Organ Size , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
Surg Endosc ; 33(8): 2710-2718, 2019 08.
Article in English | MEDLINE | ID: mdl-31227900

ABSTRACT

BACKGROUND: Ligation clips are used ubiquitously throughout minimally invasive surgery for apposition of tissues. Their size limits their application beyond ligation of small tubular structures. A novel clip and clip applicator that allows for broad-area clamping and rotation has been developed by our team. The primary aim of this study is to provide preliminary data assessing tensile strength of the clip across apposed segments of bowel. METHODS: A comparative study evaluating the maximum load (N) held across two apposed tissues by (a) our novel broad-area clip and (b) a conventional commercial clip was performed. Two sections of porcine bowel were clamped together and the maximum load (N) was measured using a tensile strength material testing machine. A preliminary experiment comparing staple line leak pressures in a porcine model ± clip enforcement of staple line was also conducted. p < 0.05 determined statistical significance. RESULTS: Twenty-four samples (intervention = 15; control = 9) of porcine bowel annealed by surgical clips were tested. The mean maximum force withheld by the bowel and staples was greater for our novel clip design (2.043 ± 0.831 N) than the control clip (1.080 ± 0.466 N, p = 0.004). Ten staple line (intervention = 5; control = 5) pressures of porcine bowel were measured. There was no statistically significant difference between the leak pressures with clip reinforcement (84.8 mmHg; range 71.8-109.8 mmHg), or without (54.1 mmHg; range 26.3-98.9 mmHg). CONCLUSION: These preliminary results suggest that our novel clip is able to withstand higher tensile force across tissues compared to a leading commercial clip. A small preliminary trial of effect on leak pressures demonstrated no statistical significance; however, increasing reliability of staple line deformation may be a clinically important finding. Whilst further iteration of product design and clinical testing is required, this product may occupy an important clinical niche through staple line reinforcement, enterotomy closure and other applications.


Subject(s)
Intestines/surgery , Ligation/instrumentation , Minimally Invasive Surgical Procedures/instrumentation , Surgical Stapling/instrumentation , Anastomosis, Surgical , Animals , Equipment Design , Intestines/physiology , Models, Animal , Pressure , Reproducibility of Results , Surgical Instruments , Surgical Stapling/methods , Swine , Tensile Strength
15.
Endoscopy ; 50(7): 701-707, 2018 07.
Article in English | MEDLINE | ID: mdl-29415286

ABSTRACT

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.


Subject(s)
Colonic Polyps/diagnostic imaging , Colonoscopy , Eye Movements , Fixation, Ocular , Adult , Humans , Middle Aged
16.
Med Teach ; 40(1): 62-69, 2018 01.
Article in English | MEDLINE | ID: mdl-29172823

ABSTRACT

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.


Subject(s)
Education, Medical/methods , Eye Movements , Teaching , Feedback , Humans , Learning , Qualitative Research
18.
Postgrad Med J ; 93(1097): 159-167, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27879411

ABSTRACT

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.


Subject(s)
Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/trends , Surgical Instruments/trends , Diffusion of Innovation , Forecasting , Humans
19.
Surg Innov ; 24(1): 55-65, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27671036

ABSTRACT

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.


Subject(s)
Cholecystectomy/education , Computer Simulation , Formative Feedback , Natural Orifice Endoscopic Surgery/education , Simulation Training , Adult , Clinical Competence , Female , Humans , Male , Middle Aged , Reproducibility of Results , User-Computer Interface
20.
J Gastroenterol Hepatol ; 31(3): 604-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26414929

ABSTRACT

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.


Subject(s)
Colonoscopy/education , Colonoscopy/methods , Professional Competence , Quality Assurance, Health Care , Adenoma/diagnosis , Adenoma/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Curriculum , Humans
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