Operative blood loss adversely affects short and long-term outcomes after colorectal cancer surgery: results of a systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to assess the impact of operative blood loss on short and long-term outcomes following colorectal cancer surgery. METHODS: A systematic literature review and meta-analysis were performed, from inception to the 10th of August 2020. A comprehensive literature search was performed on the 10th of August 2020 of PubMed MEDLINE, Embase, Science Citation Index Expanded, and Cochrane Central Register of Controlled Trials. Only studies reporting on operative blood loss and postoperative short term or long-term outcomes in colorectal cancer surgery were considered for inclusion. RESULTS: Forty-three studies were included, reporting on 59,813 patients. Increased operative blood loss was associated with higher morbidity, for blood loss greater than 150-350 ml (odds ratio [OR] 2.09, p < 0.001) and > 500 ml (OR 2.29, p = 0.007). Anastomotic leak occurred more frequently for blood loss above a range of 50-100 ml (OR 1.14, p = 0.007), 250-300 ml (OR 2.06, p < 0.001), and 400-500 ml (OR 3.15, p < 0.001). Postoperative ileus rate was higher for blood loss > 100-200 ml (OR 1.90, p = 0.02). Surgical site infections were more frequent above 200-500 ml (OR 1.96, p = 0.04). Hospital stay was increased for blood loss > 150-200 ml (OR 1.63, p = 0.04). Operative blood loss was significantly higher in patients that suffered morbidity (mean difference [MD] 133.16 ml, p < 0.001) or anastomotic leak (MD 69.56 ml, p = 0.02). In the long term, increased operative blood loss was associated with worse overall survival above a range of 200-500 ml (hazard ratio [HR] 1.15, p < 0.001), and worse recurrence-free survival above 200-400 ml (HR 1.33, p = 0.01). Increased blood loss was associated with small bowel obstruction caused by colorectal cancer recurrence for blood loss higher than 400 ml (HR 1.97, p = 0.03) and 800 ml (HR 3.78, p = 0.02). CONCLUSIONS: Increased operative blood loss may adversely impact short term and long-term postoperative outcomes. Measures should be taken to minimize operative blood loss during colorectal cancer surgery. Due to the uncertainty of evidence identified, further research, with standardised methodology, is required on this important subject.

A systematic review and network meta-analysis comparing energy devices used in colorectal surgery.

BACKGROUND: The aim of this study was to compare energy devices used for intraoperative hemostasis during colorectal surgery. METHODS: A systematic literature review and Bayesian network meta-analysis performed. MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane were searched from inception to August 11th 2021. Intraoperative outcomes were operative blood loss, operative time, conversion to open, conversion to another energy source. Postoperative outcomes were mortality, overall complications, minor complications and major complications, wound complications, postoperative ileus, anastomotic leak, time to first defecation, day 1 and 3 drainage volume, duration of hospital stay. RESULTS: Seven randomized controlled trials (RCTs) were included, reporting on 680 participants, comparing conventional hemostasis, LigaSure™, Thunderbeat® and Harmonic®. Harmonic® had fewer overall complications compared to conventional hemostasis. Operative blood loss was less with LigaSure™ (mean difference [MD] = 24.1 ml; 95% confidence interval [CI] - 46.54 to - 1.58 ml) or Harmonic® (MD = 24.6 ml; 95% CI - 42.4 to - 6.7 ml) compared to conventional techniques. Conventional hemostasis ranked worst for operative blood loss with high probability (p = 0.98). LigaSure™, Harmonic® or Thunderbeat® resulted in a significantly shorter mean operative time by 42.8 min (95% CI - 53.9 to - 31.5 min), 28.3 min (95% CI - 33.6 to - 22.6 min) and 26.1 min (95% CI - 46 to - 6 min), respectively compared to conventional electrosurgery. LigaSure™ resulted in a significantly shorter mean operative time than Harmonic® by 14.5 min (95% CI 1.9-27 min) and ranked first for operative time with high probability (p = 0.97). LigaSure™ and Harmonic® resulted in a significantly shorter mean duration of hospital stay compared to conventional electrosurgery of 1.3 days (95% CI - 2.2 to - 0.4) and 0.5 days (95% CI - 1 to - 0.1), respectively. LigaSure™ ranked as best for hospital stay with high probability (p = 0.97). Conventional hemostasis was associated with more wound complications than Harmonic® (odds ratio [OR] = 0.27; CI 0.08-0.92). Harmonic® ranked best with highest probability (p = 0.99) for wound complications. No significant differences between energy devices were identified for the remaining outcomes. CONCLUSIONS: LigaSure™, Thunderbeat® and Harmonic® may be advantageous for reducing operative blood loss, operative time, overall complications, wound complications, and duration of hospital stay compared to conventional techniques. The energy devices result in comparable perioperative outcomes and no device is superior overall. However, included RCTs were limited in number and size, and data were not available to compare all energy devices for all outcomes of interest.

Right hemicolectomy with complete mesocolic excision is safe, leads to an increased lymph node yield and to increased survival: results of a systematic review and meta-analysis.

BACKGROUND: The introduction of complete mesocolic excision (CME) for right colon cancer has raised an important discussion in relation to the extent of colic and mesenteric resection, and the impact this may have on lymph node yield. As uncertainty remains regarding the usefulness of and indications for right hemicolectomy with CME and the benefits of CME compared with a traditional approach, the purpose of this meta-analysis is to compare the two procedures in terms of safety, lymph node yield and oncological outcome. METHODS: We performed a systematic review of the literature from 2009 up to March 15th, 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two hundred eighty-one publications were evaluated, and 17 met the inclusion criteria and were included. Primary endpoints analysed were anastomotic leak rate, blood loss, number of harvested lymph nodes, 3- and 5-year oncologic outcomes. Secondary outcomes were operating time, conversion, intraoperative complications, reoperation rate, overall and Clavien-Dindo grade 3-4 postoperative complications. RESULTS: In terms of safety, right hemicolectomy with CME is not inferior to the standard procedure when comparing rates of anastomotic leak (RR 0.82, 95% CI 0.38-1.79), blood loss (MD -32.48, 95% CI -98.54 to -33.58), overall postoperative complications (RR 0.82, 95% CI 0.67-1.00), Clavien-Dindo grade III-IV postoperative complications (RR 1.36, 95% CI 0.82-2.28) and reoperation rate (RR 0.65, 95% CI 0.26-1.75). Traditional surgery is associated with a shorter operating time (MD 16.43, 95% CI 4.27-28.60) and lower conversion from laparoscopic to open approach (RR 1.72, 95% CI 1.00-2.96). In terms of oncologic outcomes, right hemicolectomy with CME leads to a higher lymph node yield than traditional surgery (MD 7.05, 95% CI 4.06-10.04). Results of statistical analysis comparing 3-year overall survival and 5-year disease-free survival were better in the CME group, RR 0.42, 95% CI 0.27-0.66 and RR 0.36, 95% CI 0.17-0.56, respectively. CONCLUSIONS: Right hemicolectomy with CME is not inferior to traditional surgery in terms of safety and has a greater lymph node yield when compared with traditional surgery. Moreover, right-sided CME is associated with better overall and disease-free survival.

Sigmoid resection for diverticular disease - to ligate or to preserve the inferior mesenteric artery? Results of a systematic review and meta-analysis.

AIM: In colorectal cancer, ligation of the inferior mesenteric artery (IMA) is a standard surgical approach. In contrast, ligation of the IMA is not mandatory during treatment of diverticular disease. The object of this meta-analysis was to assess if preservation of the IMA reduces the risk of anastomotic leakage. METHOD: A search was performed up to August 2018 using the following electronic databases: MEDLINE/PubMed, ISI Web of Knowledge and Scopus. The measures of treatment effect utilized risk ratios for dichotomous variables with calculation of the 95% CI. Data analysis was performed using the meta-analysis software Review Manager 5.3. RESULTS: Eight studies met the inclusion criteria and were included in the meta-analysis: two randomized controlled trials (RCTs) and six non-RCTs with 2190 patients (IMA preservation 1353, ligation 837). The rate of anastomotic leakage was higher in the IMA ligation group (6%) than the IMA preservation group (2.4%), but this difference was not statistically significant [risk ratio (RR) 0.59, 95% CI 0.26-1.33, I2  = 55%]. The conversion to laparotomy was significantly lower in the IMA ligation group (5.1%) than in the IMA preservation group (9%) (RR 1.74, 95% CI 1.14-2.65, I2  = 0%). Regarding the other outcomes (anastomotic bleeding, bowel injury and splenic damage), no significant differences between the two techniques were observed. CONCLUSION: This meta-analysis failed to demonstrate a statistically significant difference in the anastomotic leakage rate when comparing IMA preservation with IMA ligation. Thus, to date there is insufficient evidence to recommend the IMA-preserving technique as mandatory in resection for left-sided colonic diverticular disease.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

The genomics of sporadic and hereditary colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Over the past three decades, extensive efforts have sought to elucidate the genomic landscape of CRC. These studies reveal that CRC is highly heterogeneous at the molecular level, with different subtypes characterised by distinct somatic mutational profiles, epigenetic aberrations and transcriptomic signatures. This review summarises our current understanding of the genomic and epigenomic alterations implicated in CRC development and progression. Particular focus is given to how characterisation of CRC genomes is leading to more personalised approaches to diagnosis and treatment.

Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis.

OBJECTIVE: The objective of this paper is to report the clinical outcome of B cell depletion therapy in 18 patients with refractory lupus nephritis (LN). METHODS: Eighteen patients received rituximab on an open-label basis with prospective evaluations. All patients had renal disease refractory to conventional immunosuppressive therapy, including intravenous cyclophosphamide (CyC). All patients fulfilled the revised ACR classification criteria for SLE. Rituximab was given as 2 × 1 g infusions with 500 mg iv CyC and 500 mg iv methylprednisolone, two weeks apart. Complete remission (CR) of nephritis at six months was defined as normal serum creatinine and serum albumin levels, inactive urine sediment, and proteinuria < 0.5 g/day; partial remission (PR) was defined as a ≥50% improvement in all renal parameters that were abnormal at baseline. Clinical response was assessed by the British Isles Lupus Assessment Group (BILAG) score pre- and post-rituximab treatment, and efficacy was recorded by extent and duration of B lymphocyte depletion (normal range 0.100-0.500 × 10(9)/l). Follow-up data were collected at six months, one year post-treatment and at the most recent clinic visit. RESULTS: At six months, 11/18 patients reached renal CR and two of 18 PR. The mean global BILAG scores for responders decreased from 15 (SD 10) to 5 (SD 3), and a total of ten A scores disappeared. Five patients failed to show complete or partial renal response despite peripheral B lymphocyte count depletion, and progressed to end-stage renal failure (ESRF) and dialysis. Four of these patients had severe proliferative, crescentic nephritis, of whom three had Class IV-G, one Class III and one late membranous glomerulonephritis. One patient died six years after rituximab therapy from overwhelming sepsis while on long-term haemodialysis. CONCLUSION: Rituximab therapy achieved a response in 13/18 patients with refractory LN. However, in patients with rapidly progressive crescentic LN, when there is already evidence of significant renal impairment, rituximab therapy may not prevent progression to ESRF and dialysis. Our data also suggest that severe Class IV-G LN may be associated with a poor response to therapy.

Weight loss and improvements in fatigue in systemic lupus erythematosus: a controlled trial of a low glycaemic index diet versus a calorie restricted diet in patients treated with corticosteroids.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) may require prolonged periods of corticosteroid therapy which lead to excessive weight gain and increased cardiovascular risk. OBJECTIVE: To assess the utility of a low glycaemic index diet in patients with corticosteroid dependent SLE in achieving weight loss and improving glycaemic control. DESIGN: A total of 23 women were enrolled in a 6 week study. All had mild, stable SLE, were receiving corticosteroids and had a body mass index > 25 kg/m(2). Subjects were randomly assigned to a low glycaemic index (Low GI) diet or a calorie restricted (Low Cal) diet. The primary end point was weight loss. Secondary end points included tolerability of diet, bio-markers of cardiovascular risk, disease activity, fatigue and sleep quality. RESULTS: Weight loss in both treatment groups was significant (mean ± SD: Low GI diet 3.9 ± 0.9 kg; Low Cal diet 2.4 ± 2.2 kg, p < 0.01 from baseline in each group). There were also significant improvements in waist and hip measurements. However, the difference in weight loss and waist and hip measurements between the two diet groups was not statistically significant. There was a statistically significant reduction in Fatigue Severity Scale in both diet groups, (p < 0.03). Both Low GI and Low Cal diets were well tolerated, resulting in no serious adverse effects or increase in disease activity. CONCLUSION: Significant weight loss is achievable over 6 weeks in a diet-specific trial in subjects with stable SLE, who are on low dose prednisolone. Both diets were equally tolerable, and did not cause flares in disease activity. Our results suggest that dietary manipulation may significantly improve fatigue in subjects with SLE.

Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target.

Stem cells are responsible for maintaining differentiated cell numbers during normal physiology and at times of tissue stress. They have the unique capabilities of proliferation, self-renewal, clonogenicity and multi-potentiality. It is a widely held belief that stem-like cells, known as cancer stem cells (CSCs), maintain tumours. The majority of currently identified intestinal stem cell populations appear to be rapidly cycling. However, quiescent stem cell populations have been suggested to exist in both normal intestinal crypts and tumours. Quiescent CSCs may have particular significance in the modern management of colorectal cancer making their identification and characterisation a priority. In this review, we discuss the current evidence surrounding the identification and microenvironmental control of stem cell populations in intestinal crypts and tumours as well as exploring the evidence supporting the existence of a quiescent stem and CSC population in the gut and other tissues.

A single centre evaluation of risk prediction models and imaging modalities in acute appendicitis.

INTRODUCTION: Patients with suspected appendicitis remain a diagnostic challenge. The aim of this study was to validate risk prediction models, and to investigate diagnostic accuracy of ultrasonography and computed tomography (CT) in adults undergoing appendicectomy. METHODS: A retrospective case review was performed of patients aged 16-45 years having an appendicectomy between January 2019 and January 2020 at a tertiary referral centre. Primary outcomes were the accuracy of a high risk appendicitis risk score and ultrasonography and CT imaging modalities compared with histological reports following appendicectomy. RESULTS: A total of 206 patients (52% female) were included in the study. Removal of a histologically normal appendix was equally likely in men and women (13.1% vs 11.2% respectively, relative risk: 1.17, 95% confidence interval: 0.56-2.44, p=0.674). A high risk appendicitis score correctly identified 84.0% (79/94) of cases in men and 85.9% (67/78) of cases in women. Ultrasonography was reported as equivocal in 85.7% (18/21) of low risk women and 59.0% (23/39) of high risk women. CT correctly detected or excluded appendicitis in 75.0% (6/8) of low risk women and 88.5% (23/26) of high risk women. CONCLUSIONS: This study suggests that risk prediction models may be useful in both women and men to identify appendicitis. Ultrasonography gave high rates of equivocal results and should not be relied on for the diagnosis of appendicitis. CT is a highly accurate diagnostic tool and could be considered in those at low risk where clinical suspicion remains to reduce negative appendicectomy rates.

Appraisal of the current guidelines for the management of diverticular disease using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument.

INTRODUCTION: Diverticular disease is one of the most frequent reasons for attending emergency departments and surgical causes of hospital admission. In the past decade, many surgical and gastroenterological societies have published guidelines for the management of diverticular disease. The aim of the present study was to appraise the methodological quality of these guidelines using the Appraisal of Guidelines Research and Evaluation II (AGREE II) tool. METHODS: PubMed, Embase, Cochrane Library and Google Scholar databases were searched systematically. The methodological quality of the guidelines was appraised independently by five appraisers using the AGREE II instrument. FINDINGS: A systematic search of the literature identified 12 guidelines. The median overall score of all guidelines was 68%. Across all guidelines, the highest score of 85% was demonstrated in the domain 'Scope and purpose'. The domains 'Clarity and presentation' and 'Editorial independence' both scored a median of 72%. The lowest scores were demonstrated in the domains 'Stakeholder involvement' and 'Applicability' at 46% and 40%, respectively. Overall, the National Institute for Health and Care Excellence (NICE) guidelines performed consistently well, scoring 100% in five of six domains; NICE was one of the few guidelines that specifically reported stakeholder involvement, scoring 97%. Generally, the domain of 'Stakeholder involvement' ranked poorly with seven of twelve guidelines scoring below 50%, with the worst score in this domain demonstrated by Danish guidelines at 25%. CONCLUSION: Six of twelve guidelines (NICE, American Society of Colon & Rectal Surgeons (ASCRS), European Society of Coloproctology (ESCP), American Gastroenterological Association, German Society of Gastroenterology/German Society for General and Visceral Surgery (German), Netherlands Society of Surgery) scored above 70%. Only three, NICE, ASCRS and ESCP, scored above 75% and were voted unanimously by the appraisers for use as they are. Therefore, use of AGREE II may help improve the methodological quality of guidelines and their future updates.

NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations.

The proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) has a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-kappaB inhibitor, IkappaB-alpha, associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IkappaB-zeta gene NFKBIZ in the development of invasive pneumococcal disease (IPD) has not been reported previously. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium (LD) block and all four polymorphisms within the equivalent, shorter Kenyan LD block displayed either a significant association with IPD or a trend towards association. For each polymorphism, heterozygosity was associated with protection from IPD when compared with the combined homozygous states (for example, for rs600718, Mantel-Haenszel 2 x 2 chi(2)=7.576, P=0.006, odds ratio (OR)=0.67, 95% confidence interval (95% CI) for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2 x 2 chi(2)=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to IPD in humans. The study of multiple populations may aid in fine mapping of associations within extensive regions of strong LD ('transethnic mapping').

Raster microdiffraction with synchrotron radiation of hydrated biopolymers with nanometre step-resolution: case study of starch granules.

X-ray radiation damage propagation is explored for hydrated starch granules in order to reduce the step resolution in raster-microdiffraction experiments to the nanometre range. Radiation damage was induced by synchrotron radiation microbeams of 5, 1 and 0.3 µm size with ∼0.1 nm wavelength in B-type potato, Canna edulis and Phajus grandifolius starch granules. A total loss of crystallinity of granules immersed in water was found at a dose of ∼1.3 photons nm(-3). The temperature dependence of radiation damage suggests that primary radiation damage prevails up to about 120 K while secondary radiation damage becomes effective at higher temperatures. Primary radiation damage remains confined to the beam track at 100 K. Propagation of radiation damage beyond the beam track at room temperature is assumed to be due to reactive species generated principally by water radiolysis induced by photoelectrons. By careful dose selection during data collection, raster scans with 500 nm step-resolution could be performed for granules immersed in water.

Systematic review and meta-analysis of preoperative antisepsis with chlorhexidine versus povidone-iodine in clean-contaminated surgery.

BACKGROUND: Surgical-site infection increases morbidity, mortality and financial burden. The preferred topical antiseptic agent (chlorhexidine or povidone-iodine) for preoperative skin cleansing is unclear. METHODS: A meta-analysis of clinical trials was conducted to determine whether preoperative antisepsis with chlorhexidine or povidone-iodine reduced surgical-site infection in clean-contaminated surgery. RESULTS: The systematic review identified six eligible studies, containing 5031 patients. Chlorhexidine reduced postoperative surgical-site infection compared with povidone-iodine (pooled odds ratio 0.68, 95 per cent confidence interval 0.50 to 0.94; P = 0.019) . CONCLUSION: Chlorhexidine should be used preferentially for preoperative antisepsis in clean-contaminated surgery.