BACKGROUND:Acute laparotomy for trauma or sepsis often prevents definitive closure due to need for relook laparotomy or to prevent abdominal compartment syndrome. Skin-only closure is widely used in our setting. In this study, we review the safety and effectiveness of this technique.METHODS:Patients presenting with intra-abdominal pathology undergoing acute laparotomy and then subsequent skinonly closure using 2-0 prolene were included in the study and followed postoperatively for a three-month period for adverse events stratified by Clavien-Dindo grading, and rate of definitive closure.RESULTS:During the study period, twenty-five patients underwent emergent laparotomy and skin-only closure. The median age of patients undergoing skin-only closure was 27 years (standard deviation 9.1). Six patients presented with major trauma and 19 presented with sepsis. Twenty-one patients underwent subsequent fascial closure. One patient was unable to undergo fascial closure and was managed as a planned ventral hernia. Fourteen patients developed a postoperative complication. There were no deaths and no readmissions to intensive care. Three further patients developed a ventral hernia.CONCLUSION:Skin-only closure, in carefully selected patients, is a feasible alternative to other temporary abdominal closure techniques in a resource-constrained setting.

BACKGROUND:Whilst access to cannabis-based medicinal products (CBMPs) has increased globally subject to relaxation of scheduling laws globally, one of the main barriers to appropriate patient access remains a paucity of high-quality evidence surrounding their clinical effects.DISCUSSION:Whilst randomised controlled trials (RCTs) remain the gold-standard for clinical evaluation, there are notable barriers to their implementation. Development of CBMPs requires novel approaches of evidence collection to address these challenges. Real world evidence (RWE) presents a solution to not only both provide immediate impact on clinical care, but also inform well-conducted RCTs. RWE is defined as evidence derived from health data sourced from non-interventional studies, registries, electronic health records and insurance data. Currently it is used mostly to monitor post-approval safety requirements allowing for long-term pharmacovigilance. However, RWE has the potential to be used in conjunction or as an extension to RCTs to both broaden and streamline the process of evidence generation.CONCLUSION:Novel approaches of data collection and analysis will be integral to improving clinical evidence on CBMPs. RWE can be used in conjunction or as an extension to RCTs to increase the speed of evidence generation, as well as reduce costs. Currently, there is an abundance of potential data however, whilst a number of platforms now exist to capture real world data it is important the right tools and analysis are utilised to unlock potential insights from these.

Background: Recent legislative change has allowed increased access to cannabis products in many jurisdictions. In some locations, this includes over-the-counter (OTC) and/or online access to products containing cannabidiol (CBD), a non-intoxicating cannabinoid with therapeutic properties. Here we compared the availability of CBD products and the associated legislative and regulatory background in nine selected countries. Methods: Accessibility of CBD products was examined in the USA, Canada, Germany, Ireland, United Kingdom, Switzerland, Japan, Australia, and New Zealand as of May 2020. Regulatory and other relevant documents were obtained from government agency websites and related sources. Relevant commercial websites and some physical retailers were visited to verify access to CBD-containing products and the nature of the products available. Results: A range of CBD products appeared to be accessible without prescription in seven out of nine countries reviewed. Australia and New Zealand were the exceptions where clinician prescription was required to access any CBD-containing product. CBD products commonly available without prescription included oils, gel capsules, purified crystal and topical products. The daily recommended doses with orally administered non-prescription products were typically well below 150 mg and substantially lower than the doses reported to have therapeutic effects in published clinical trials (e.g., 300-1500 mg). The legal foundations enabling access in several countries were often unclear, with marketed products sometimes failing to meet legal requirements for sale. There was an obvious disparity between federal directives and available products in both the USA and European countries examined. Conclusions: There are a variety of approaches in how countries manage access to CBD products. Many countries appear to permit OTC and online availability of CBD products but often without legislative clarity. As consumer demand for CBD escalates, improved legislation, guidelines and quality control of CBD products would seem prudent together with clinical trials exploring the therapeutic benefits of lower-dose CBD formulations.

Background and purpose: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion. Experimental approach: Caco-2 cells were grown on cell culture inserts to confluence. Trans-epithelial electrical resistance (TEER) was used to measure permeability. To generate hypoxia (0% O-2), a GasPak (TM) EZ anaerobe pouch system was used. Endocannabinoids were applied to the apical or basolateral membrane in the presence or absence of receptor antagonists. Key results: Complete hypoxia decreased TEER (increased permeability) by similar to 35% after 4 h (recoverable) and similar to 50% after 6 h (non-recoverable). When applied either pre- or post-hypoxia, apical application of N-arachidonoyl-dopamine (NADA, via TRPV1), oleamide (OA, via TRPV1) and oleoylethanolamine (OEA, via TRPV1) inhibited the increase in permeability. Apical administration of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) worsened the permeability effect of hypoxia (both via CB1). Basolateral application of NADA (via TRPV1), OA (via CB1 and TRPV1), noladin ether (NE, via PPAR alpha), and palmitoylethanolamine (PEA, via PPAR alpha) restored permeability after 4 h hypoxia, whereas OEA increased permeability (via PPAR alpha). After 6 h hypoxia, where permeability does not recover, only basolateral application PEA sustainably decreased permeability, and NE decreased permeability. Conclusions and implications: A variety of endocannabinoids and endocannabinoid-like compounds modulate Caco-2 permeability in hypoxia/reoxygenation, which involves multiple targets, depending on whether the compounds are applied to the basolateral or apical membrane. CB1 antagonism and TRPV1 or PPAR alpha agonism may represent novel therapeutic targets against several intestinal disorders associated with increased permeability.

BACKGROUND AND AIMS We aimed to examine, for the first time, the effect of cannabidiol (CBD) and palmitoylethanolamide (PEA) on the permeability of the human gastrointestinal tract in vitro, ex vivo, and in vivo. METHODS Flux measurements of fluorescein-labeled dextrans 10 (FD10) and fluorescein-labeled dextrans 4 (FD4) dextran across Caco-2 cultures treated for 24 hours with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα) (10 ng·mL-1) were measured, with or without the presence of CBD and PEA. Mechanisms were investigated using cannabinoid receptor 1 (CB1), cannabinoid receptor 2 (CB2), transient receptor potential vanilloid 1 (TRPV1), and proliferator activated receptors (PPAR) antagonists and protein kinase A (PKA), nitric oxide synthase, phosphoinositide 3-kinases, extracellular signal-regulated kinases (MEK/ERK), adenylyl cyclase, and protein kinase C (PKC) inhibitors. Human colonic mucosal samples collected from bowel resections were treated as previously stated. The receptors TRPV1, PPARα, PPARδ, PPARγ, CB1, CB2, G-coupled protein receptor 55 (GPR55), G-coupled protein receptor 119 (GPR119), and claudins-1, -2, -3, -4, -5, -7, and -8 mRNA were measured using multiplex. Aquaporin 3 and 4 were measured using enzyme-linked immunosorbent assay (ELISA). A randomized, double-blind, controlled-trial assessed the effect of PEA or CBD on the absorption of lactulose and mannitol in humans taking 600 mg of aspirin. Urinary concentrations of these sugars were measured using liquid chromatography mass spectrometry. RESULTS In vitro, PEA, and CBD decreased the inflammation-induced flux of dextrans (P < 0.0001), sensitive to PPARα and CB1 antagonism, respectively. Both PEA and CBD were prevented by PKA, MEK/ERK, and adenylyl cyclase inhibition (P < 0.001). In human mucosa, inflammation decreased claudin-5 mRNA, which was prevented by CBD (P < 0.05). Palmitoylethanolamide and cannabidiol prevented an inflammation-induced fall in TRPV1 and increase in PPARα transcription (P < 0.0001). In vivo, aspirin caused an increase in the absorption of lactulose and mannitol, which were reduced by PEA or CBD (P < 0.001). CONCLUSION Cannabidiol and palmitoylethanolamide reduce permeability in the human colon. These findings have implications in disorders associated with increased gut permeability, such as inflammatory bowel disease.

Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score. Results: From 2008 papers, 51 publications examining the effect of cannabinoid compounds on murine colitis and 2 clinical studies were identified. Twenty-four compounds were assessed across 71 endpoints. Cannabidiol, a phytocannabinoid, was the most investigated drug. Macroscopic colitis severity (disease activity index [DAI]) and myeloperoxidase activity (MPO) were assessed throughout publications and were meta-analyzed using random effects models. Cannabinoids reduced DAI in comparison with the vehicle (standard mean difference [SMD] -1.36; 95% CI, -1.62 to-1.09; I-2 = 61%). FAAH inhibitor URB597 had the largest effect size (SMD -4.43; 95% CI, -6.32 to -2.55), followed by the synthetic drug AM1241 (SMD -3.11; 95% CI, -5.01 to -1.22) and the endocannabinoid anandamide (SMD -3.03; 95% CI, -4.89 to -1.17; I-2 not assessed). Cannabinoids reduced MPO in rodents compared to the vehicle; SMD -1.26; 95% CI, -1.54 to -0.97; I-2 = 48.1%. Cannabigerol had the largest effect size (SMD -6.20; 95% CI, -9.90 to -2.50), followed by the synthetic CB1 agonist ACEA (SMD -3.15; 95% CI, -4.75 to -1.55) and synthetic CB1/2 agonist WIN55,212-2 (SMD -1.74; 95% CI, -2.81 to -0.67; I-2 = 57%). We found no evidence of reporting bias. No significant difference was found between the prophylactic and therapeutic use of cannabinoid drugs. Conclusions: There is abundant preclinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted.

OBJECTIVE:We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants.DESIGN:Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55.RESULTS:IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants.CONCLUSION:PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.

The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1-knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.

Aim The 2-week wait pathway was designed to decrease the time from presentation to primary care of patients with red flag' symptoms of suspected cancer for review by a specialist for the diagnosis or exclusion of cancer. In our tertiary referral centre we have found that 968 colonoscopies per year are required to satisfy the demand for the 2-week wait, leading to limited colonoscopy availability for other services. We sought to determine the yield of colorectal cancer found at colonoscopy referred via the 2-week wait and referenced to the original red flag symptoms. This was in order to select the most efficacious alternative primary investigation based upon presenting symptoms.Method Electronic records were retrospectively analysed. All patients who went through the 2-week wait for suspicion of colorectal cancer in 2013 and were found to have colorectal cancer on colonoscopy were included. Patients not undergoing colonoscopy as the first investigation were excluded. The splenic flexure was deemed to be within the range of a flexible sigmoidoscope.Results In all, 2950 referrals were made. 968 colonoscopies were performed as the primary investigation of which 35 were found to have colorectal cancer. No patients referred with rectal bleeding and another symptom had a tumour more proximal to the range of flexible sigmoidoscopy. 80% of tumours proximal to the splenic flexure were suitable for CT diagnosis alone.Conclusion Our data support the use of flexible sigmoidoscopy alone as an initial investigation for patients presenting with rectal bleeding with or without additional colorectal symptoms. Patients with anaemia (without bleeding) or change in bowel habit (without bleeding) may be investigated with CT colonography alone; colonoscopy may then be used selectively prior to surgery.

Introduction Emerging evidence has shown that using smaller more frequent sutures close to the fascial wound edge is associated with a lower incidence of incisional hernia, dehiscence and surgical site infection compared to conventional wound closure.1However in implementing this practice we have experienced difficulty due to concerns regarding sutures below 1–0 grade allowing increased rates of early dehiscence and incisional hernia. We sought to demonstrate the safety of this method of wound closure. Method Un-selected patients undergoing abdominal surgery (elective and emergency) were prospectively collected from within the practice of a single surgeon in a regional teaching hospital. All wounds greater than four centimetres (fascia defect length) were included. All patients underwent closure of abdominal fascial wounds using a suture to wound length ratio of at least 4:1. Suture material was 2–0 PDS. Risk of death from surgery was preoperatively calculated using the P-POSSUM score. Initial follow up period was 30 days from procedure. Study end points were length of stay, morbidity and mortality within 30 days, dehiscence and hernia formation rate. Results 34 patients underwent fascial closure as described above, 17 cases were patients undergoing emergency laparotomy. Average fascial defect length was 13.8 cm (median 14.5 cm); average length of suture used was 98.5 cm (median 82 cm). Average ratio of suture length to wound length was 7.5. Mean length of stay in this group was 5.4 days. Average BMI was 28.9; average calculated risk of death was 11.6%. A single patient died from overwhelming sepsis shortly after emergency laparotomy. Three patients developed chest sepsis post operatively (emergency group) and two elective patients were readmitted within 30 days with chest infection and hypocalcaemia respectively. Conclusion We have demonstrated that using a small, frequent suture does not give rise to increased rates of early dehiscence, incisional hernia or major wound complications in the early post operative period. Disclosure of interest None Declared. Reference Israelsson L, Millbourn D. Prevention of incisional hernias. How to close a midline incision. Surg Clin North Am. 2013;93:1027–1040

Introduction The 2-week wait pathway was designed to decrease the time from presentation to primary care with “red flag” symptoms of suspected cancer to review by a specialist for diagnosis or exclusion of cancer. Within our tertiary referral centre 968 colonoscopies per year are required to satisfy the demand for the 2-week wait at the expense of other services. We sought to determine yields of colorectal cancer found at colonoscopy in reference to original red flag symptoms in order to select the most efficacious primary investigation based upon presenting symptoms. Method Electronic records were retrospectively analysed. All patients who went through the 2-week wait system for suspicion of colorectal cancer in 2013 found to have colorectal cancer at colonoscopy were included. Patients not undergoing colonoscopy as first investigation were excluded. The splenic flexure was deemed within the range of a flexible sigmoidoscope. Results 2950 referrals were made. 968 colonoscopies were performed as the primary investigation. 35 patients were found to have colorectal cancer. No patients referred with rectal bleeding and another symptom had a tumour outside the range of a flexible sigmoidoscope. Eighty percent of tumours proximal to the splenic flexure were suitable for CT diagnosis alone. Conclusion Our data supports the use of flexible sigmoidoscopy alone as an initial investigation for patients presenting with rectal bleeding with or without additional colorectal symptoms within our local population. Patients with anaemia (without bleeding) or change in bowel habit (without bleeding) may be investigated with CT colonography alone; colonoscopy may then be used selectively prior to surgery. Disclosure of interest None Declared.

Colorectal DiseaseVolume 15, Issue 6 p. 758-758 Correspondence Response to Gash et al.: Enhanced recovery after laparoscopic colorectal resection with primary anastomosis: accelerated discharge is safe and does not give rise to increased readmission rates D. G. Couch, D. G. Couch couch27@gmail.com Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorA. Luther, A. Luther Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorS. Farid, S. Farid Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorP. Kang, P. Kang Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this author D. G. Couch, D. G. Couch couch27@gmail.com Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorA. Luther, A. Luther Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorS. Farid, S. Farid Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this authorP. Kang, P. Kang Northampton General Hospital NHS Trust, Cliftonville Road, Northampton, NN1 5BD UKSearch for more papers by this author First published: 23 May 2013 https://doi.org/10.1111/codi.12184Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume15, Issue6June 2013Pages 758-758 RelatedInformation

Aim Colonoscopic follow-up after colorectal cancer resection (CRC) is recommended to screen for anastomotic recurrence and metachronous neoplasia, although guidelines vary in the timings of the first investigation. We aimed to quantify current practice and yield of neoplasia at first colonoscopy in relation to time from original resection. Method We conducted a retrospective case note study of all CRCs treated with curative intent within our hospital between two time periods: 20012003 and 20062007. Variables collected were the extent of preoperative luminal imaging, tumour site, procedure, timing and findings of initial colonoscopy, postoperative CT findings and mortality. The first follow-up colonoscopy findings including neoplasia formation and recurrence rates were matched with rates of complete preoperative luminal imaging. Two-year and 5-year outcomes were sought. Results A total of 863 patients underwent CRC with curative intent within these two time periods (518 vs 345). Colonoscopic follow-up rates by 2years were 32.8%vs 54.1%. Within the first cohort 63.5% of patients underwent colonoscopy by 5years. Significant volumes of neoplasia and resectable recurrences were found before 2years within these groups. Earlier detection of recurrent malignancy was associated with an improved patient outcome. Complete preoperative screening of the bowel was not associated with a lower incidence of neoplasia at first postoperative colonoscopy. Conclusion Our study demonstrates significant colonoscopic detection rates of neoplasia within 2years of CRC. Patient outcomes were improved with earlier detection. We would therefore suggest an interval of no more than 2years between resection and first surveillance colonoscopy.