Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

Post-operative pain after laparoscopic right hemicolectomy for Crohn's disease: a case control study.

AIM: Surgery for Crohn's disease (CD) is characterized by an enhanced inflammatory response. While inflammation can induce hyperalgesia, post-operative pain following surgery for CD has not been characterized. This retrospective study compared a consecutive series of patients undergoing laparoscopic right hemicolectomy for CD and neoplasia performed by a single surgeon. METHOD: Elective resections performed between Jan-2016 and Aug-2017 managed in an enhanced recovery pathway were eligible for inclusion. Patients were excluded if open surgery was performed, an ileostomy was fashioned, no patient-controlled analgesia (PCA) was used or data were incomplete. Results : 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. RESULTS: 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. CONCLUSIONS: CD patients experience increased post-operative pain, require more post-operative analgesia and have an enhanced post-operative inflammatory response. Further studies to elucidate the mechanism of this hyperalgesia and strategies to obviate it are required.

Botulinum toxin injection vs topical nitrates for chronic anal fissure: an updated systematic review and meta-analysis of randomized controlled trials.

AIM: Chronic anal fissures (CAFs) are frequently encountered in coloproctology clinics. Chemical sphincterotomy with pharmacological agents is recommended as first-line therapy. Topical nitrates (TN) heal CAF effectively but recurrences are common. An alternative treatment modality is injection of botulinum toxin (BT) into the anal sphincter. We aimed to perform an updated systematic review and meta-analysis to compare the effectiveness of BT and TN in the management of CAF. METHOD: PubMed, EMBASE and Cochrane databases were searched for relevant articles from inception until March 2017. All randomized controlled trials (RCTs) that reported direct comparisons of BT and TN were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. RESULTS: Six RCTs describing 393 patients (194 BT, 199 TN) were included. There was significant heterogeneity among the trials. On random effects analysis there were no significant differences in incomplete fissure healing (OR = 0.47, 95% CI 0.13-1.68, P = 0.24) or recurrence (OR = 0.70, 95% CI 0.39-1.25, P = 0.22) between BT and TN, respectively. BT was associated with a higher rate of transient anal incontinence (OR = 2.53, 95% CI 0.98-6.57, P = 0.06) but significantly fewer total side effects (OR = 0.12, 95% CI 0.02-0.63, P = 0.01) and headache (OR = 0.10, 95% CI 0.02-0.60, P = 0.01) compared with TN. CONCLUSION: BT is associated with fewer side effects than TN but there is no difference in fissure healing or recurrence. Patients need to be warned regarding the risk of transient anal incontinence associated with BT.

Regional Versus Local Anaesthesia for Haemodialysis Arteriovenous Fistula Formation: A Systematic Review and Meta-Analysis.

BACKGROUND: Arteriovenous fistula (AVF) formation is the most common vascular access procedure for patients requiring haemodialysis. However, it is associated with high failure rates, influenced by vessel diameter and arterial inflow. Mode of anaesthesia may affect these factors, and subsequently AVF maturation rates. OBJECTIVE: To perform a systematic review and meta-analysis to assess the effect of anaesthesia type for autologous primary radiocephalic or brachiocephalic AVF creation on subsequent fistula failure rates. METHODS: The online databases of Medline, EMBASE, CINAHL, The Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and Google Scholar as well as vascular and anaesthesiology conference abstracts were searched on August 1, 2016. Randomised control trials (RCTs) that reported the effect of anaesthesia type on subsequent failure rates during autologous AVF creation were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out. RESULTS: Four RCTs (286 patients) were identified with 286 autologous AVFs. There were 48 fistula failures. Most of the studies suffered from significant methodological flaws. There was a significantly lower failure rate among patients undergoing regional (12/143) compared with local (36/143) anaesthesia (OR 0.28, 95% CI 0.14-0.57). On sensitivity analysis, having excluded the most heavily weighted study, the results remained significant (OR 0.20, 95% CI 0.05-0.75). CONCLUSIONS: The use of regional anaesthesia is associated with lower AVF failure rates when compared with local anaesthesia in patients undergoing primary forearm AVF formation for haemodialysis.

Should patients with infrainguinal arterial bypasses using autologous vein conduit undergo follow-up surveillance with duplex ultrasound?

This best evidence topic was investigated according to a structured format. The question asked was: should duplex ultrasound (DUS) scanning be a routine component of surveillance following infrainguinal arterial bypass using vein conduit? We performed a systematic literature search and identified 4 studies (3 randomised controlled trials and 1 meta-analysis) that provided the best evidence. The highest quality study was a multi-centre randomised controlled trial (n = 594). At 18 months following surgery, it found no difference in patency rates, amputations, vascular mortality or mortality. However it achieved just over half of anticipated recruitment and thus was underpowered. The remaining two randomised controlled trials had smaller sample sizes and methodological weaknesses and found conflicting results. Lundell et al. (n = 106) found improved primary assisted and secondary patency rates and fewer graft occlusions with a routine DUS policy. Ihlberg et al. (n = 152) found no difference in primary assisted patency or amputations although secondary patency was improved. A meta-analysis of mostly observational data (n = 6649) found fewer occlusions with routine DUS surveillance and no effect on amputations or mortality. Results are conflicting. The strongest evidence comes from the single high quality multi-centre trial. It appears as though routine DUS surveillance does not yield benefits in patient important outcomes. Further studies are needed.

A randomized controlled trial comparing polyethylene glycol + ascorbic acid with sodium picosulphate + magnesium citrate solution for bowel cleansing prior to colonoscopy.

INTRODUCTION: Adequate bowel cleansing which is acceptable to the patient is a prerequisite for safe and effective colonoscopy. A 2-L polyethylene glycol solution containing ascorbic acid and electrolytes (PEG-Asc) is an alternative to sodium picosulphate + magnesium citrate (SPS-Mg) for bowel preparation. The aim of the current study is to compare PEG-Asc to SPS-Mg in terms of tolerability and efficacy. METHODS: This was a single blind, randomized controlled trial. A blinded assessment of bowel cleansing was made by the attending endoscopist. Patients completed a questionnaire on the acceptability of the preparation. RESULTS: One hundred and thirty (130) consecutive patients attending for day case colonoscopy were randomly allocated to bowel preparation with PEG-Asc (n = 66) or SPS-Mg (n = 64). More patients found PEG-Asc to taste unpleasant (37.9 vs. 10.9%, P < 0.001) and more patients found PEG-Asc to be a more distressing preparation than SPS-Mg (15.1 vs. 4.7%, P = 0.043). However, there was no difference in the proportion of patients being able to complete bowel preparation (PEG-Asc vs. SPS-Mg, 92.4 vs. 93.8%, P = 0.520). There was no detectable difference between PEG-Asc and SPS-Mg in the quality of cleansing with a good or very good preparation being reported by the endoscopist in 46.9 and 54.5% of cases, respectively (P = 0.242). CONCLUSIONS: More patients find PEG-Asc to taste unpleasant and to be a more distressing preparation than SPS-Mg. However, there was no detectable difference between PEG-Asc and SPS-Mg in bowel cleansing prior to colonoscopy.

Circulating fibrocytes and Crohn's disease.

BACKGROUND: Despite advances in medical therapy, there remains no effective preventive or non-surgical therapeutic option for fibrostenotic Crohn's disease (CD). Symptomatic recurrences are common, necessitating reintervention. Intestinal fibroblasts mediate stricture formation, but their exact source is unclear. Recent evidence indicates that circulating fibrocytes drive fibrosis through differentiation into fibroblasts and the production of extracellular matrix proteins. The aim of this review is to describe current understanding of the pathophysiology underlying fibrosis in CD, the cellular and molecular biology of fibrocytes and their role in CD. METHODS: The electronic literature (January 1972 to December 2012) on 'circulating fibrocytes' and 'Crohn's fibrosis' was reviewed. RESULTS: Circulating fibrocytes appear universally involved in organ fibrosis. A complex array of cytokines, chemokines and growth factors regulate fibrocyte biology, and these are associated with fibrogenesis in CD. The cytokines transforming growth factor ß1, connective tissue growth factor and interleukin 13, overexpressed in the strictured Crohn's intestine, promote fibrocyte generation and/or differentiation. CONCLUSION: Levels of circulating fibrocytes are raised in conditions marked by exaggerated fibrosis. These and other observations prompt a characterization of fibrocyte activity in CD with a view to investigating a pathogenic role.